Dispersion of Filtered P Wave Duration by P Wave Signal-Averaged ECG Mapping System:

INTRODUCTION: Although it is desirable to know drug efficacy before initiating antiarrhythmic therapy, there have been no methods for this evaluation. P wave signal-averaged ECG (P-SAECG) is useful to detect subtle changes in disturbance of atrial conduction. The purpose of this present study was to test whether P-SAECG mapping system would give any information on the efficacy of disopyramide on the prevention of paroxysmal atrial fibrillation (PAF). METHODS AND RESULTS: P-SAECG was performed before disopyramide treatment, at 3 hours after a single dose of oral disopyramide (200 mg), and after 4 weeks of disopyramide treatment (300 mg/day). After measuring the filtered P wave duration by the vector magnitude and mapping methods, we calculated filtered P wave duration dispersion, difference between the maximal and minimal filtered P wave duration within 16 chest leads at these three time points. Filtered P wave duration and filtered P wave duration dispersion before treatment were longer in 32 patients with symptomatic PAF than in 31 healthy volunteers. Disopyramide was effective for suppression of PAF in 17 patients and ineffective in 15 patients after 4 weeks of treatment. Filtered P wave duration was similarly prolonged at 3 hours in the two groups, whereas filtered P wave duration dispersion at 3 hours after the disopyramide administration behaved differently; it decreased in all of the effective group and increased in all of the ineffective group. The effective patients were prospectively followed with the same treatment for 6 months. In 16 (94%) of these 17 effective patients, no PAF was documented and they remained to be asymptomatic. CONCLUSIONS: Thus, measuring filtered P wave duration dispersion with the P-SAECG mapping method after a single administration may predict the long-term efficacy of disopyramide in patients with PAF.     

Clinical Evaluation of an Immunoradiometric Assay for CA15-3 Antigen Associated With Human Mammary Carcinomas: Comparison With Carcinoembryonic Antigen

Serum levels of CA15-3, a mammary tumor associated antigen recognizedby two different murine monoclonal antibodies (115D8 and DF3),were investigated in patients with mammary carcinoma and otherbenign or malignant diseases. The reference value of the serumCA15-3 level was obtained as 24 units/ml at the 99% confidencelimit among healthy individuals (n = 462). Elevation of serumCA15-3 levels was observed in 24.3% of overall patients withmammary carcinoma. Serum CA15-3 levels in breast cancer patientscorrelated with the clinical stage; higher percentages of positivitywere observed in those with advanced breast cancer (stage IV,64.7%, recurrent, 52.4% and metastatic, 70.3%). Furthermore,elevated serum CA15-3 levels in breast cancer patients respondedwell to the effect of therapy. Although the serum CA15-3 testgave percentages of positivity of breast cancer similar to thosefound by the serum CEA test, the serum CA15-3 test revealedlower percentages of posi-tivity than the serum CEA test amongpatients with benign breast lesions, liver cirrhosis or othercarcinomas. These results suggest that the serum CA15-3 antigenlevel provides a very useful marker for diagnosis and clinicalmonitoring of patients with breast cancer.     

Diastolic Mitral Regurgitation in Patients with First-Degree Atrioventricular Block

Diastolic mitral regurgitation has been observed in patients with DDD pacemakers when the atrioventricular (AV) delay was prolonged. However, diastolic mitral regurgitation associated with first-degree AV block has not been fully studied. We examined transmitral blood flow in 24 patients with first-degree AV block and normal cardiac function (ages 35.3 ± 17.4 years), and in nine patients with DDD pacemakers and normal cardiac function (ages 73.1 ± 8.1 years), using pulsed Doppler echocardiography. Diastolic mitral regurgitation was observed in 19 of 24 patients with first-degree AV block. Although PQ interval was shortened from 0.32 ± 0.06 to 0.20 ± 0.05 seconds (P < 0.01) after 1 mg atropine sulfate IV, the interval between P wave (ECG) and the beginning of diastolic mitral regurgitation did not change, while the duration of diastolic mitral regurgitation was shortened from 0.15 ± 0.03 to 0.05 ± 0.03 seconds (P < 0.01). There was a significant correlation between changes in PQ interval and changes in the duration of diastolic mitral regurgifation (r = 0.92, P < 0.001). Although cardiac output (3.9 ± 0.05 L/min) and pulmonary capillary wedge pressure (5.1 ± 1.5 mmHg) were normal in all patients with pacemakers, diastolic mitral regurgitation was observed when the AV delay was prolonged. The critical PQ interval for the appearance of diastolic mitral regurgitation was 0.23 ± 0.01 seconds. In patients with prolonged PQ intervals, delayed ventricular contraction following atrial contraction may be associated with mitral regurgitation in the presence of a reversed AV pressure gradient. The results of this study suggest that diastolic mitral regurgitation occurs not only in patients with DDD pacemakers, but also with AAIR pacemakers when the PQ interval is prolonged. The occurrence of diastolic mitral regurgitation is associated with the pacing mode or the setting of AV delay.     

Multivariate autoregressive analysis of carotid artery blood flow waveform in an infant of a diabetic mother with cardiomyopathy

We analyzed the carotid artery blood flow waveform (CABFW) of an infant of a non-insulin dependent diabetic mother with hypertrophic cardiomyopathy (IDM cardiomyopathy) through multivariate autoregressive analysis and compared the developmental change of his CABFW with that of normal newborns. The total power was lower than normal newborns on the second and third day of life when his heart dysfunction was severe, and elevated on the fifth day of life when normal-heart function was recovered. The power of component 3 (C3), of which the damping frequency was 7–11 Hz, was slightly high on the second and third day of life and it decreased to the normal range on the fifth day of life by component analysis. In contrast, the power of C3 increased with decreasing resistance index of anterior cerebral artery (RI of ACA) which shows the cerebral vascular resistance of normal newborns. These results suggest that the carotid artery blood flow volume decreased by low cardiac output and the cerebral vascular resistance decreased to maintain the cerebral circulation, when the heart dysfunction was severe.     

Developmental change in carotid artery blood flow waveform by component analysis in children

The carotid artery blood flow waveform (CABFW) is regarded as a summation of cardiac impulse responses. These impulse responses are divided into several components through a two-dimensional autoregressive modelling approach. Using this approach, we determined the developmental change in CABFW in 94 normal subjects from the neonatal period to adolescence. Our analysis demonstrated that: (i) the total power of impulse response increased significantly with increasing age. The component of impulse response was divided into six groups according to the damping frequency: group I (0 Hz), group II (1–5 Hz), group III (5–8 Hz), group IV (8–13 Hz), group V (13–17 Hz) and group VI (> 17 Hz); (ii) the power-density and the damping time of group I and II impulse response increased significantly with increasing age; (iii) the power-density and percent power of group III impulse response and power-density of group IV impulse response increased significantly with increasing age. Our results indicated that CABFW contained some regular impulses and that group I, II, III and IV, which were influenced by several factors, including cardiac contraction and the compliance and frictional forces of the carotid artery, appeared to be important to the developmental change of CABFW in children.     

Frequency- and Time-Domain Analysis of P Wave in Patients with Paroxysmal Atrial Fibrillation

We investigated the usefulness of the time- and frequency-domain analysis of the P wave triggered signal-averaged ECG (P-SAECG) for detecting patients with paroxysmal atrial fibrillation (Paf). In previous studies, the usefulness of the time domain of the P-SAECG to detect patients with Paf was described but that of the frequency domain is unknown. We analyzed the P-SAECG in the time and frequency domain in 23 patients with Paf and 19 controls. The 32-unipolar chest lead ECGs and the standard bipolar limb lead ECGs were obtained. The time-domain analysis showed that the filtered P duration (fPd) was significantly longer (P < 0.01) in patients with Paf than controls: the predictive accuracy of Paf with fPd > 120 ms was 69%. The frequency domain analysis showed that the area ratio of power spectrum area of 0–20 Hz to 20–100 Hz (AR20) was significantly higher (P < 0.01) and the magnitude ratio at 30 Hz (%Mag.30) calculated by dividing the magnitude at 30 Hz by the maximal magnitude was significantly (P < 0.01) lower in patients with Paf than controls in the left lateral chest leads. The predictive accuracy of Paf with AR20 ≥ 1.5 and that with %Mag.30 < 40% was 83% and 73%, respectively. Our results indicate that the frequency-domain analysis of P waves in lateral leads is useful as is the time-domain analysis to detect patients with Paf. The AR20 ≥ 1.5 and %Mag.30 < 40% provides accurate predictability of Paf.     

Macrocytosis Resulting from Early Denucleation of Erythroid Precursors

In an attempt to elucidate the mechanism of production of macrocytosis inacute anemia, we studied changes in red cell volume and hemoglobin content, the RNA level of normoblasts and reticulocytes and RNA synthesis inreticulocytes of rabbits made anemic by blood loss or phenylhydrazine administration. The results were as follows:

(1) In severe phenylhydrazine anemia, red cell volume and hemoglobincontent per cell increased to twice the normal values.

(2) The RNA level of normoblasts decreases with the maturation of thecells and reaches a minimum at the orthochromatic stage. The decrease issimilar in the normal and anemic rabbits.

(3) The RNA level of reticulocytes in the bone marrow is higher in anemicthan in normal rabbits. In general, the RNA level of reticulocytes of anemicrabbits is comparable to that of the polychromatic normoblasts, while in normal rabbits this value is comparable to that of orthochromatic normoblasts.

(4) Autoradiographs of reticulocytes incubated with H³-uridine indicatethat the increased level of reticulocyte RNA of anemic rabbits is not due tonewly synthesized RNA.

From these results, we conclude that in an "emergency" situation of erythropoietic stimulation denucleation of normoblasts occurs at the polychromaticstage of red cell maturation, with skipping of the terminal cell division toorthochromatic cells and formation of macrocytic reticulocytes and red cells.

Submitted on August 28, 1963 Accepted on April 30, 1964     

Electrocoagulation Biopsy of Aberrant Pancreas of the Stomach A Case of Aberrant Gasthic Pancreas

Histopathological diagnosis of submucosal tumors of the stomach has been difficult by conventional examination, e.g. roentgenography, gastroscopy and/or routine biopsy procedure. When endoscopic diagnosis of submucosal tumor is made, surgery is generally performed for tissue biopsy. We have been attempting to avoid such exploratory laparotomy to determine the histologic nature of small asymptomatic submucosal tumors of the stomach by a technic of endoscopic biopsy followed by electrocoagulation. With such a procedure, we have been able to diagnose a case of aberrant pancreas of the stomach. Our experience suggests that this technic is a safe and useful diagnostic tool.     

Leukocyte Drumsticks in Chronic Granulocytic Leukemia and Related Disorders

1. The drumstick and other nuclear appendages of the nuclei of polymorphonuclear neutrophils from patients with chronic granulocytic leukemia(CGL), leukemoid reactions and inflammatory leukocytoses were studied.

2. The drumstick counts of the leukocytes of patients with CGL wereabnormally low. In contrast, the counts in the leukocytes from patients withthe other disorders were not reduced. The low counts increased rapidly inresponse to treatment and were maintained at normal levels during remission.

3. The normalization of drumstick counts in CGL paralleled the leukocytealkaline phosphatase and catalase concentrations.

4. The number of sessile nodules and small clubs in each of the disordersstudied was moderately reduced. Following treatment, the counts returnedto normal. This suggests a relationship between the development of theseappendages and hyperproliferation of neutrophils.

Submitted on July 10, 1961 Accepted on August 1, 1961     

In Vivo Localization of Heterologous Anti-Erythrocyte Antibodies in the Rat Bone Marrow and Their Effect on the Proliferative Capacity of Immature Erythroid Cells

The in vivo localization of heterologous anti-erythrocyte antibodies in therat bone marrow was determined by the I¹³¹-labeled antibody technic. I¹³¹-labeled anti-erythrocyte antibodies localized specifically in the bone marrowindicating the presence of localizing antibody. Both the localizing antibodyand the incomplete antibody were thermostable, whereas hemolysins andhemagglutinins were thermolabile. Following an intravenous injection of antierythrocyte antibodies in rats, hemolysins and hemagglutinins were clearedrapidly from the plasma. The incomplete antibodies became attached to circulating red cells within 6 hours and red cell sensitization persisted for 1 week.The localizing antibody localized in the bone marrow within 30 minutes, leaving no activity in plasma.

The anti-erythrocyte antibodies markedly reduced the uptake of tritiatedthymidine by erythroblasts in vitro, demonstrating their inhibitory effect onthe proliferative capacity of erythroblasts.

Submitted on February 3, 1964 Accepted on May 12, 1964