Induced regression of bovine papillomas by intralesional immunotherapy.

It has long been assumed that papilloma regression is mediated by immunological mechanisms which are probably cellular in nature. The potentiation of these responses may alter the course of papilloma progression. Certain strains of the bacterium Corynebacterium parvum (Propionibacterium acnes) have been shown to augment cellular immune mechanisms by increasing both macrophage and natural killer cell activity. This study involves the use of naturally occurring bovine papillomas to investigate the immune mechanisms involved in induced papilloma regression. Papillomas were treated by intralesional injection of a C. parvum suspension. Treated papillomas were biopsied at various stages of regression. Tissue samples were subjected to immunohistochemical staining to identify specific infiltrating cells. Results showed that intralesional administration of C. parvum was capable of inducing regression of bovine papillomas in 8-15 weeks. Immunological staining revealed that regression was associated with an increased number of CD8+ and gamma delta+ cells in the dermis, as well as a marked infiltration of neutrophils.

Myocardial electrical propagation in patients with idiopathic dilated cardiomyopathy.

Myocardial propagation may contribute to fatal arrhythmias in patients with idiopathic dilated cardiomyopathy (IDC). We examined this property in 15 patients with IDC undergoing cardiac transplantation and in 14 control subjects. An 8 x 8 array with electrodes 2 mm apart was used to determine the electrical activation sequence over a small region of the left ventricular surface. Tissue from the area beneath the electrode array was examined in the patients with IDC. The patients with IDC could be divided into three groups. Group I (n = 7) had activation patterns and estimates of longitudinal (theta L = 0.84 +/- 0.09 m/s) and transverse (theta T = 0.23 +/- 0.05 m/s) conduction velocities that were no different from controls (theta L = 0.80 +/- 0.08 m/s, theta T = 0.23 +/- 0.03 m/s). Group II (n = 4) had fractionated electrograms and disturbed transverse conduction with normal longitudinal activation, features characteristic of nonuniform anisotropic properties. Two of the control patients also had this pattern. Group III (n = 4) had fractionated potentials and severely disturbed transverse and longitudinal propagation. The amount of myocardial fibrosis correlated with the severity of abnormal propagation. We conclude that (a) severe contractile dysfunction is not necessarily accompanied by changes in propagation, and (b) nonuniform anisotropic propagation is present in a large proportion of patients with IDC and could underlie ventricular arrhythmias in this disorder.

Rate-related electrophysiologic effects of long-term administration of amiodarone on canine ventricular myocardium in vivo.

The electrophysiologic effects of amiodarone were examined in 13 dogs that received 30 g amiodarone orally during 3 weeks and compared with 13 control dogs that did not receive amiodarone. Longitudinal and transverse epicardial conduction velocities were estimated with a square array of 64 closely spaced electrodes and a computer-assisted acquisition and analysis system. Amiodarone caused a rate-dependent decrease in conduction velocity with a slightly greater effect in the longitudinal direction of propagation. Rate-related depression of conduction velocity developed rapidly after abrupt shortening of the pacing cycle length; 67% of the change occurred between the first two beats of the rapid train, and little change occurred after the 10th beat. Recovery from use-dependent depression of conduction velocity was exponential with a mean time constant of 447 +/- 172 msec in the longitudinal direction and 452 +/- 265 msec in the transverse direction. Repolarization intervals, defined as the interval between the activation time and the repolarization time in the unipolar electrograms, correlated highly with refractory period determinations in the absence and presence of amiodarone at each cycle length tested. The increase in repolarization intervals and refractory periods resulting from amiodarone treatment did not vary with cycle length. Amiodarone treatment also resulted in a significant rate-related reduction in systolic blood pressure. The systolic blood pressure in the group that received amiodarone decreased by a mean of 50 +/- 23% between steady-state pacing cycle lengths of 1,000 and 200 msec, whereas the corresponding decrease in the control group was 21 +/- 32% (p less than 0.05). Plasma and myocardial amiodarone and desethylamiodarone levels were comparable to those observed clinically. We conclude that long-term amiodarone administration causes rate-dependent reductions in conduction velocity and blood pressure and causes rate-independent increases in repolarization intervals.

Comparative recognition of left ventricular thrombi by echocardiography and cineangiography.

Studies performed in 47 patients, 11 of whom underwent surgery for aneurysmectomy and 36 of whom underwent cardiac transplantation, were reviewed to assess the diagnostic accuracies of cross sectional echocardiography and cineangiography in detecting left ventricular mural thrombi and the effect of anticoagulation treatment on the incidence of such thrombi. Cross sectional echocardiography in 37 patients and cineangiography in 26 (16 patients were examined by both methods) were analysed independently by sets of two observers experienced in the respective methods. All four observers were blinded to the pathological or surgical findings regarding mural thrombus. Mural thrombus was confirmed by pathological investigation in 14 of 47 (30%) cases; 11 of these 14 patients had intra-aneurysmal thrombi. The negative predictive value was quite good for both methods, but cross sectional echocardiography had a superior positive predictive value. This was due both to detailed soft tissue resolution by cross sectional echocardiography and to overdetection of mural thrombi by cineangiography in cases of aneurysms without mural thrombi. Mural thrombi were present in three of 20 patients with preceding anticoagulation and in 10 of 19 patients without anticoagulation. The results emphasise that cross sectional echocardiography is more reliable than cineangiography in recognising thrombi.

Variability of the body surface distributions of QRS, ST-T and QRST deflection areas with varied activation sequence in dogs.

Distributions of QRS, ST-T and QRST areas of 192 lead body surface ECG's were measured in dogs for multiple activation orders. Qualitatively, the distributions of QRST area were found to be strikingly similar over all activation orders in contrast to the distributions of QRS or ST-T areas. Quantitative results showed that variability of the QRST areas over all activation orders was consistently less than those of either QRS or ST-T. The factor responsible for the QRS deflection is ventricular activation sequence while those responsible for the ST-T deflection are both activation sequence and ventricular recovery properties. Since the total QRST deflection area was largely independent of activation sequence it is likely the quantity is an index of ventricular recovery properties. The significance of this relation is that QRST deflection area may permit evaluation of intrinsic ventricular recovery properties in the presence of abnormal ventricular activation as occurs with intraventricular conduction disorders and ectopic origin of excitation. Evaluation of intrinsic ventricular recovery properties may also permit recognition of states at risk of ventricular arrhythmias due to increased disparity of these properties.

The characteristic sequence for the onset of contraction in the normal human left ventricle.

The sequence for the onset of segmental contraction of the left ventricle was studied in 25 normal patients by analyzing sequential frames obtained at 16.7-msec intervals of right anterior oblique (RAO) ventriculograms by two independent methods. In the first method, we compared the times of onset of contraction of the hemidiameters associated with each of 54 segments with time of onset of contraction of the average of all the hemidiameters for the ventricular contour. In the second method we used a radial coordinate system and determined relative phase relationships by plotting the motion of each of 54 segments against the average motion of all segments. The resulting pattern showed that, on the average, the midregion of the inferior wall began to contract 25 msec before the apex and the midregion of the anterior wall began contraction 18 msec before the apex. In 12 of 25 patients the interior and anterior walls both began to contrast before the apex. In only one of 25 patients did the apex begin to contract first. This sequences of contraction corresponds to the reported sequence of electrical activation for normal human left ventricles.

Assessment of ventricular function in coronary artery disease using nitroglycerin and computerized analysis of left ventriculograms.

The ability to predict if abnormalities in regional wall motion are reversible would assist in selecting patients for aortocoronary bypass operation. This study shows that asynergic areas of the ventricle may be reversed by nitroglycerin. Thirty-four asynergic areas in 30 patients with coronary artery disease were studied before and after administration of nitroglycerin. Nineteen patients with previous infarction, diagnostic Q waves in their electrocardiogram, and akinetic areas in the left ventricle had no change in their akinetic areas after nitroglycerin administration. Nine of these patients did show increased motion in other hypokinetic areas of the myocardium. Five of 11 patients with no evidence of previous infarction showed a dramatic improvement in akinetic areas after nitroglycerin, while of the remaining 6, 5 showed mild improvement. This illustrates that recoverable asynergic areas may be recognized by nitroglycerin.