Effects of desipramine on autonomic control of the heart.

Objective: To assess the effects of desipramine (DMI) on autonomic control of the heart.

Methods: Blood pressure, RR interval (the time between successive heart beats), and RR interval variability, a noninvasive measure of autonomic control of the heart, were assessed in 13 subjects younger than 30 years old.

Results: DMI treatment was associated with an increase in blood pressure, a decrease in RR interval, and a decline in low and high frequency RR interval variability.

Anti platelet property of anti-single-stranded DNA antibodies in type 1 (insulin-dependent) diabetes mellitus.

Nineteen of 50 sera from children with type 1 (insulin-dependent) diabetes mellitus showed anti-platelet reactivity. This reactivity was significantly associated with the presence of proteoglycan cross-reactive anti-ssDNA antibodies. As well as DNA-anti-DNA interaction, increasing salt concentration of the dilution buffer caused a decrease in the binding of positive sera to platelets.

Inhibition of Fc gamma receptors in the plasma of subjects with Down's syndrome.

Subjects with Down's syndrome have several immunological abnormalities. We examined the sera of 29 subjects with Down's syndrome for the presence of Fc gamma receptor blocking and for the presence of anti-ssDNA antibodies by EA rosette inhibition. Fifty-five percent of Down subjects had levels of inhibition above the upper limit of normality in comparison to 7% of normal controls.

Two-site ELISA for quantification of the terminal C5b-9 complement complex in plasma. Use of monoclonal and polyclonal antibodies against a neoantigen of the complex.

A quantitative ELISA procedure using monoclonal and polyclonal antibodies against neoantigens of the terminal C5b-9 complement complex has been developed. The ELISA was demonstrated to be both sensitive and reproducible. The normal range for C5b-9 determinations, defined as 2.

Is doxepin a safer tricyclic for the heart?

Background: Many clinicians believe that doxepin is the safest tricyclic with respect to cardiovascular effects. This belief has persisted for two decades despite the absence of rigorous prospective evaluation.

Method: To address this issue, the authors studied the cardiovascular effects of doxepin in 32 depressed patients with preexisting left ventricular impairment, ventricular arrhythmias, and/or conduction disease.

Time course of moricizine's effect on signal-averaged and 12 lead electrocardiograms: insights into mechanism of action.

The mechanism of action of moricizine, a new antiarrhythmic agent used in the Cardiac Arrhythmia Suppression Trial, is incompletely characterized. In addition, because moricizine is extensively metabolized, plasma moricizine concentration has an unknown relation to myocardial drug effect. Signal-averaged and standard electrocardiograms (ECGs) were used to monitor moricizine's myocardial effects in 16 patients with frequent ventricular premature complexes taking 600 to 900 mg daily.

Detection of the terminal fluid-phase complement complex, SC5b-9, in the plasma of patients with insulin-dependent (type I) diabetes mellitus. Relation to increased urinary albumin excretion and plasma von Willebrand factor.

An ELISA was used to measure the fluid-phase complement complex in the plasma of 54 patients with insulin-dependent (type I) diabetes mellitus. Sixty-seven per cent of the diabetic patients had increased levels of SC5b-9. In individual diabetic patients, increased SC5b-9 was found to be significantly associated with the occurrence of anti-heparan sulphate cross-reactive anti-ssDNA antibodies and in some cases with circulating immune complexes.

Cardiovascular effects of bupropion in depressed patients with heart disease.

Objective: The cardiovascular effects of therapeutic plasma levels of tricyclic antidepressants in depressed patients with and without preexisting cardiac disease have been well characterized and include orthostatic hypotension and conduction delay. Bupropion, structurally unrelated to tricyclic antidepressants, is relatively free of cardiac side effects in depressed patients without cardiac disease. However, it is unknown whether bupropion is safe for depressed patients with preexisting heart disease, so the authors studied the cardiovascular effects of bupropion in such patients.

IgG auto-anti-idiotype antibodies against antibody to insulin in insulin-dependent (type 1) diabetes mellitus. Detection by capture enzyme linked immunosorbent assay (ELISA) and relationship with anti-insulin antibody levels.

Antibody directed against insulin carries idiotypic determinants that may induce an auto-anti-idiotype (anti-Id) antibody response. We describe a solid-phase enzyme immunoassay which allows specific detection of IgG anti-Id directed against anti-insulin antibodies. Among 36 patients with type 1 diabetes, IgG anti-idiotype was detected in 21 (58%).

Increased plasma levels of IgA-IgG immune complexes and anti-F(ab')2 antibodies in patients with type 2 (non insulin-dependent) diabetes mellitus and microangiopathy.

C3 fixing IgA immune complexes were found to be elevated in 25% of patients with type 2 (non insulin-dependent) diabetes mellitus as compared to healthy subjects (2%). Immune complexes containing both IgA and IgG were found in 42% of the diabetic population but not in controls. The presence of C3-IgA and/or IgA/IgG immune complexes correlated with the occurrence of antiglobulins antibodies of IgA class in particular with autoantibodies reactive with the Fab2 portion of IgG.

Effect of indecainide in patients with left ventricular dysfunction.

Indecainide, a new antiarrhythmic agent classified as type Ic was evaluated in 11 patients with heart disease who had greater than or equal to 30 ventricular premature complexes/hour, moderate-to-marked left ventricular dysfunction, and mean ejection fraction 34% +/- 8%. Patients received indecainide, 50 mg by mouth, every 6 hours and the dose was increased until greater than or equal to 80% suppression was noted, adverse effects occurred, or a maximum dose of 100 mg indecainide was given every 6 hours. Ventricular premature complexes were suppressed greater than or equal to 80% in nine patients (p less than 0.

Myocardial amiodarone and desethylamiodarone concentrations in patients undergoing cardiac transplantation.

Myocardial amiodarone and desethylamiodarone concentrations were measured at multiple sites in the explanted heart in four patients who underwent cardiac transplantation. Patients were taking amiodarone, 200 to 400 mg/day (mean 300 +/- 115), for 88 to 428 days (mean 229 +/- 148). The mean cumulative dose was 58 +/- 21.

Low dose quinidine-mexiletine combination therapy versus quinidine monotherapy for treatment of ventricular arrhythmias.

Low dose quinidine-mexiletine combination therapy was compared with quinidine monotherapy in 15 patients with frequent ventricular premature complexes and nonsustained ventricular tachycardia in a dose escalation cross-over study. Oral combination therapy was initiated with quinidine gluconate (165 mg) plus mexiletine (150 mg) every 8 h. If ventricular premature complexes were not suppressed greater than or equal to 80% and nonsustained ventricular tachycardia greater than or equal to 90%, the dose was increased to a maximum of 330 mg of quinidine plus 200 mg of mexiletine.

Cross-reactivity of anti-ssDNA antibodies with heparan sulfate in patients with type I diabetes mellitus.

Anti-single-stranded-DNA antibodies cross-reactive with heparan sulfate were detected in serums of patients with type I (insulin-dependent) diabetes mellitus. The results suggested that heparan sulfate, the major glycosaminoglycan constituent of the glomerular basement membrane, may serve as a target antigen in vivo for cross-reactive anti-DNA antibodies. These polyreactive antibodies, directed toward repeating negatively charged units, may neutralize the heparan sulfate-associated polyanionic sites in the glomerulus, leading to an abnormal permeability of anionic plasma proteins.

Detection of anti-phospholipid (cardiolipin, phosphatidylserine) antibodies in the serum of patients with non insulin-dependent (type 2) diabetes mellitus and macroangiopathy. Coexistence of anti-platelet reactivity.

IgA and IgG antibodies against cardiolipin and/or phosphatidylserine were detected in the sera of patients with non insulin-dependent (type 2) diabetes mellitus. The highest prevalence was observed in particular in patients with macrovascular complications (86%). A significant increase of platelet bound IgA and IgG was observed also in patients with sera positive for anti-phospholipid antibodies suggesting the coexistence of reactivity against phospholipid and platelets.

Serum levels of type III procollagen peptide in diabetes mellitus.

Serum levels of type III procollagen peptide (P-III-P) were investigated in 19 patients with type 1 (insulin-dependent) and in 48 (25 orally treated, 23 insulinized) patients with type 2 (non insulin-dependent) diabetes mellitus. Among patients with type 2 diabetes, 16 orally treated and 14 insulin-treated subjects had macrovascular complications. P-III-P levels were not correlated with the duration of diabetes and with glucose control, nor were there any significant sex and age differences in the levels.

[Velocity of nerve conduction in children and adolescents with type I diabetes mellitus: clinical, metabolic and immunologic correlations].

Clinical, metabolic, neurophysiologic and immunological data were obtained in a group of 50 patients with type I diabetes mellitus Results were compared with those obtained in 30 healthy subjects of comparable age. M.N.

The relationship of insulin antibodies, platelet-fixing immune complexes and platelet-associated IgG to in vitro platelet aggregation and thromboxane B2 synthesis in childhood type 1 (insulin-dependent) diabetes mellitus.

The relationship of insulin antibodies, platelet-fixing soluble immune complexes and platelet associated IgG to in vitro platelet aggregation and thromboxane B2 synthesis was studied in a group of children with type 1 (insulin-dependent) diabetes mellitus. Insulin antibodies, through the formation of insulin anti-insulin platelet-fixing immune complexes, seem to increase the levels of platelet associated IgG and both insulin immunity and increased platelet associated IgG are associated with the highest degree of platelet aggregation and thromboxane synthesis. These data suggest a possible role of immune factors in the platelet disfunction of diabetic subjects.

Collagen binding activity in sera of patients with insulin-dependent (type 1) and non insulin-dependent (type 2) diabetes mellitus.

An increase in the capacity of serum IgG to bind to native type IV collagen was observed in patients with both insulin-dependent and non insulin-dependent diabetes mellitus. This increased binding seems to be due to circulating immune complexes in the majority of the cases and to autoantibodies in some. The increased collagen binding activity was associated in postpubertal patients with the presence of diabetic microangiopathy, suggesting a pathogenetic role.

Indecainide compared with quinidine for chronic stable ventricular arrhythmias secondary to coronary artery disease or to cardiomyopathy.

Indecainide, a new type Ic antiarrhythmic agent, and quinidine sulfate were compared in a randomized double-blind parallel study. Cardiac patients with greater than or equal to 30 ventricular premature complexes per hour hour received indecainide, 50 mg, or quinidine, 200 mg every 6 hours, and the doses were increased until more than 80% suppression was noted, adverse effects occurred or a maximal dose of 100 mg of indecainide or 400 mg of quinidine given every 6 hours. Efficacy was achieved in 8 of 10 taking indecainide (p less than 0.

Cardiovascular effects of imipramine and bupropion in depressed patients with congestive heart failure.

There has been a long-standing concern over the cardiovascular effects of tricyclic antidepressants, particularly in patients with preexisiting cardiac disease. Recent studies have demonstrated that imipramine causes no deleterious effect on ejection fraction as determined by radionuclide angiography in patients with impaired left ventricular function (LVF). However, the high rate of severe orthostatic hypotension induced by imipramine makes use of the drug problematic in these patients.

Cardiovascular effects of doxepin in cardiac patients with ventricular arrhythmias.

The effect of doxepin on ventricular arrhythmias, the ECG, and left ventricular function was evaluated in 10 cardiac patients with symptoms with frequent ventricular premature depolarizations in a dose-ranging protocol. Four patients (40%) had greater than or equal to 80% ventricular premature depolarization suppression; four of eight with pairs and four of six with ventricular tachycardia had greater than or equal to 90% suppression. The mean maximal doxepin dose was 115 +/- 41 mg/day; mean nadir total doxepin concentration was 61 +/- 48 ng/ml and mean nadir total desmethyldoxepin concentration was 51 +/- 42 ng/ml.

Antiarrhythmic effect of lorcainide in patients taking digoxin.

To assess the antiarrhythmic effect of lorcainide and determine whether there is a pharmacokinetic interaction between lorcainide and digoxin, 12 patients with frequent premature ventricular depolarizations (PVDs) who were taking digoxin were treated with lorcainide. During a placebo period, serum digoxin concentration was measured for three days; plasma lorcainide concentration, a 12-lead electrocardiogram (ECG), and a 24-hour continuous ECG were measured on the day before the patients began lorcainide and repeated on days 3, 7, and 14 of treatment. Lorcainide was given 100 mg bid or 100 mg tid.

Tricyclic antidepressants in depressed patients with cardiac conduction disease.

The observation that fatalities from tricyclic antidepressant (TCA) overdose are associated with heart block and/or arrhythmias has led to concern about the cardiovascular effects of TCAs. Contrary to expectations, studies have shown TCAs to be relatively safe in patients without heart disease. However, it is unclear whether these drugs are also safe in patients with heart disease.