Influence of peripheral intravenous contrast injection on the QRS complex in healthy men.

The influence of acute plasma expansion induced by the administration of sodium containing hyperosmolar contrast medium on Frank lead electrocardiograms was investigated in 10 healthy male volunteers. The major electrocardiographic changes after injection of the contrast medium were a significant decrease in the amplitudes of Rx, Ry, and Qz and the maximal spatial QRS voltage, and a significant increase in the amplitude of Sx. The echocardiographic left ventricular end diastolic dimension tended to be larger after the injection, whereas no significant change occurred in the left ventricular systolic dimension. The electrocardiographic changes in this study were the opposite of those expected with the Brody effect. Although the precise mechanism underlying these findings is unclear, the increased intracardiac blood volume may have caused a decrease in the QRS voltage by a short circuiting effect. Alternatively if the activation in the left ventricle is assumed to be predominantly tangential the QRS voltage should have decreased with the Brody effect. The Brody effect may lead to an erroneous interpretation of electrocardiograms in certain clinical settings.

Effect of dipyridamole at the usual oral dose on exercise-induced myocardial ischemia in stable angina pectoris.

A randomized, double-blind, placebo-controlled study was performed to investigate the effect of dipyridamole at a usual oral dose of 150 mg/day on 18 patients with angina pectoris and positive treadmill exercise electrocardiography. After their angina pectoris was stabilized in phase 1, the patients were randomly assigned to sequence group A or B. Group A received a placebo 3 times daily in phase 2 and then 50 mg of dipyridamole 3 times daily in phase 3. Group B received the treatment in the reverse order. The degree of ST depression and the threshold for angina pectoris in treadmill exercise electrocardiography, which was performed on the last days of phases 2 and 3, were compared. The mean duration of exercise was 5 minutes and 23 seconds during dipyridamole and 5 minutes and 13 seconds during placebo administration, with no significant difference. Dipyridamole caused an aggravating effect on the ST change (earlier appearance of ST depression and/or deeper total sum of ST depression at the end of the exercise) in 3 patients, a salutary effect in 5 and no effect in 10. Dipyridamole decreased the threshold for angina pectoris in 5 patients, increased it in 6 and did not change it in 7. To summarize, dipyridamole showed adverse effects (aggravative effects on the ST change and/or on the threshold for angina pectoris) in 6 patients, beneficial effects in 8 and no effect in 4. A usual oral dose of dipyridamole induced myocardial ischemia during exercise in some patients while it improved it in a similar number of patients.

Limited-sampling models for estimation of the carboplatin area under the curve.

BACKGROUND: The area under the curve (AUC) of free carboplatin, is a major determinant of toxicity and response. A conventional pharmacokinetic study to determine AUC requires frequent blood sampling. One strategy for overcoming this problem is to apply a limited sampling model (LSM). MATERIALS AND METHODS: We developed LSMs by stepwise forward multiple regression analysis using 27 data series from 24 patients with lung cancer (training data set) who received carboplatin in combination with oral etoposide. The models were then validated using 24 data series from 18 patients (test data set). RESULTS: In the test data set, the single-sample model was confirmed to give excellent estimation of the AUC: AUC (mg/ml x min) = 0.93 x C3h + 0.47 (MPE% = 4.4%, RMSE% = 8.9%). Furthermore, the two-sample model was shown to improve both the bias and precision of AUC estimation: AUC = 0.16 x C1h + 2.26 x C8h + 0.75 (MPE% = 0.9%, RMSE% = 5.3%). CONCLUSIONS: Our models are useful for future trials to define the accurate relationships between the dose-intensity and effect of carboplatin.

Expression of lung-resistance protein gene is not associated with platinum drug exposure in lung cancer.

BACKGROUND: Platinum drug resistance is an important problem in lung cancer chemotherapy. In this study, we examined lung-resistance protein (LRP) gene expression in vivo and in vitro in relation to platinum drug exposure. MATERIALS AND METHODS: The expression levels of the LRP gene were assessed by the reverse transcription polymerase chain reaction, in 80 autopsy samples (40 lung tumors and 40 corresponding normal lung tissues), two lung cancer cell lines and in peripheral mononuclear cells collected from 8 lung cancer patients before and after platinum drug administration. RESULTS: The LRP gene expression levels of autopsy specimens exposed antemortem to platinum drugs were not significantly different to those of specimens without platinum drug exposure, for both lung tumors and normal lung tissues. Our results also demonstrate that LRP gene expression was not induced by platinum drugs either in vitro or in vivo. CONCLUSIONS: The present results indicate that LRP gene expression is not associated with platinum drug exposure in lung cancer.

Pulmonary hypertension in progressive muscular dystrophy of the Duchenne type.

Right heart catheterization was performed in 8 patients with progressive muscular dystrophy of the Duchenne type (DMD) at the advanced stage. A mean pulmonary arterial pressure in excess of 20 mmHg was observed in all cases. Five of them showed severe pulmonary hypertension with a mean pressure above 40 mmHg. Since pulmonary hypertension was relieved by correction of hypoxemia, this represented a precapillary pulmonary hypertension caused by constriction of the pulmonary artery. Furthermore, elevation of the mean right atrial pressure above 5 mmHg was observed in 6 of the 8 cases, indicating the possible presence of right ventricular failure. Despite the presence of left ventricular dysfunction as assessed by echocardiogram, no manifestations of left ventricular failure, such as dyspnea and pulmonary rales, were noted in any of the patients. In conclusion, it can be said that even in the terminal stage of DMD, the left ventricular function may, in fact, still remain not markedly involved, and that respiratory failure, as well as right ventricular failure caused by precapillary pulmonary hypertension, will tend to occur frequently and may play a determinant role in prognosis of the advanced DMD patient.

A 10-year follow-up study by orthogonal Frank lead ECG on patients with progressive muscular dystrophy of the Duchenne type.

A 10-year follow-up study by orthogonal Frank lead electrocardiography was performed on 25 patients with progressive muscular dystrophy of the Duchenne type (DMD). With advancing age, no apparent changes were observed in the duration and amplitude of the P wave or in the PR interval, whereas the duration of the QRS complex tended to increase. The amplitudes of the R wave in lead X (Rx) and lead Y (Ry) tended to decrease from 1.75 +/- 0.90 and 1.96 +/- 0.59 mV to 0.80 +/- 0.63 and 1.39 +/- 0.62 mV (p < 0.01), whereas the amplitude of the S wave in lead X tended to increase from 0.24 +/- 0.23 mV to 0.53 +/- 0.36 mV in 10 years after initiation of the study (p < 0.01). It is noteworthy that the Ry amplitude began to decrease markedly from the seventh year after the initiation of this study, whereas the Rx amplitude showed a gradual and unceasing decline through the 10-year period. Observation of the sequential changes of the QRS loops in three planes clearly demonstrated that the electrical force tended to decrease in the leftward and inferior directions and increase in the rightward direction. It is of interest that the frequency of occurrence of the deep Q wave was found to be quite high even in the early stages of DMD and that it did not display a direct relation to the sequential evolution of this disease. It can be concluded that observation of the sequential changes in the QRS complex allows estimation of the extent and direction of myocardial involvement in DMD.

The prevalence and prognostic significance of arrhythmias in Duchenne type muscular dystrophy.

To investigate the prevalence and prognostic significance of cardiac arrhythmias in Duchenne type muscular dystrophy 24-hour ambulatory ECG was performed in 80 patients with Duchenne type muscular dystrophy, and they were followed up for 5 years. Various arrhythmias were observed in 63.8% (51 of 80) of the patients. Ventricular premature beats were found in 30% (24 of 80), and the incidence of ventricular premature beats increased as the clinical severity of skeletal muscle involvement advanced. Forty-seven patients survived for 5 years, but the incidence of arrhythmias increased from 38.3% (18 of 47) to 74.5% (35 of 47) (p < 0.001). During the 5-year period, four of 33 deaths were sudden. Malignant ventricular premature beats (ventricular couplets, ventricular tachycardia, and R-on-T-type ventricular premature beats) were observed in three of these four patients. It appears that cardiac arrhythmias are a common complication of Duchenne type muscular dystrophy and that the incidence of ventricular arrhythmias increases with the progression of myocardial involvement. There is an association between ventricular arrhythmias and sudden death, but the reduction of ventricular arrhythmias may not reduce the incidence of episodes of sudden death.

Inhibition of theophylline metabolism by aciclovir.

We report a case of side effects caused by the increase in plasma theophylline concentration after coadministration of aciclovir had been started during theophylline therapy. Interaction between theophylline and aciclovir has not previously been reported. Therefore, a study of the pharmacokinetic and metabolic interactions between theophylline and aciclovir was carried out in five healthy male volunteers. All subjects received a single oral dose of 320 mg theophylline (aminophylline, 400 mg) after they had taken oral aciclovir 800 mg five times daily for two consecutive days. The area under the curve from 0 to infinity of theophylline (AUC0-infinity) after coadministration of aciclovir was increased from 189.9 +/- 18.2 to 274.9 +/- 34.3 micrograms.h/ml (p < 0.01), and total body clearance was decreased from 28.4 +/- 2.9 to 19.8 +/- 2.5 ml/h/kg (p < 0.01). Further, there was a significant increase in urinary theophylline and decreases in urinary 1,3-dimethyluric acid and 1-methyluric acid after coadministration of aciclovir. The decrease in total body clearance is likely to have resulted from inhibition of metabolism via the oxidation pathway. The results indicated that with aciclovir therapy lower doses of theophylline might be necessary and careful monitoring of plasma concentrations was essential.

Primary hemangiopericytoma of the heart. A case report.

Hemangiopericytoma (HP) represents a rare cellular vascular tumor. The present report of primary HP of the heart in a 53-year-old Japanese male is the first of its kind. Most of the tumor masses were removed, but masses tightly adhering to both the pericardium and the epicardium were not excised because of profuse bleeding. The patient has remained free of complaints for 10 months post-operatively. Non-invasive methods including a chest X-ray, echocardiogram, and thallium-201 myocardial imaging were found to be useful adjuncts of the diagnosis of cardiac tumor.

[Non-invasive estimates of hemodynamics in normal pregnancy].

Pregnancy provides excellent opportunities for observing the hemodynamic alterations in cardiac function occurring during the physiologic stress imposed on the normal myocardium. Hemodynamically, the most important change in the maternal circulation during pregnancy is an increase in the circulating blood volume and cardiac output. In the average woman, the cardiac output at rest rises 30-50% above the normal non-gestational resting value. Echocardiography was performed for 25 normal pregnant women, ranging in age from 21 to 36 years (mean age of 28.7 years). Echocardiography was performed periodically through out pregnancy, at the gestational ages of the 10th, 24th, 32nd, 36th, and the 3rd postpartal weeks. Tracings were obtained in the left lateral and supine positions. All pregnancies were uncomplicated, and there was no twin pregnancy. The heart rate increased throughout gestation. However, the systolic and diastolic blood pressures did not change significantly throughout pregnancy. End-diastolic left ventricular dimension (LVDd) increased throughout gestation, with the peak at the 36th week of gestation. Left atrial dimension (LAD) and mVCF increased at the 36th week of gestation. Throughout gestation, the ejection fraction (EF) showed no significant change. There were no measurable differences in the cardiac size and function in the left lateral and supine positions. Increased LVDd and LAD throughout gestation were thought the reflexion of the increased blood volume and venous return which had its peak in the 36th week of gestation. The slightly larger cardiac size and end-diastolic volume seemed to induce the increased myocardial fiber stretch and, in turn, the increased mVCF. Our results indicated that chronic volume overload with increased circulating blood volume occurs in normal pregnancy, resulting in the large cardiac size and increased contractility of myocardial fiber.

Hepatocellular tumorigenicity of butylated hydroxytoluene administered orally to B6C3F1 mice.

Butylated hydroxytoluene (BHT), a preservative widely found in food as a food additive, was orally administered at concentrations of 1% and 2% of the diet to B6C3F1 mice for 104 consecutive weeks. Treated animals underwent a 16-week recovery period prior to pathological examination. In male mice administered BHT, the incidence of mice with either a hepatocellular adenoma or a focus of cellular alteration in the liver was increased in a clear dose-response relationship. The incidences of male mice with other tumors and the incidences of female mice with any tumor were not significantly increased as a consequence of BHT administration. The results of this study indicate BHT to be tumorigenic to the liver of the B6C3F1 male mouse.

Lack of tumorigenicity of aminopyrine orally administered to B6C3F1 mice.

To test the tumorigenic potential of aminopyrine, an antipyretic analgesic, it was administered in drinking water at levels of 0 (control), 0.04 and 0.08% to 50 male and 50 female B6C3F1 mice for 100 weeks, and the mice were subsequently maintained without aminopyrine for a further 4 weeks. The most frequent types of tumor, in both treated and control groups, were hepatocellular tumor in male mice and malignant lymphoma/lymphoid leukemia in female mice. No statistically significant differences were observed in the incidences of these tumors between treated and control groups. The incidences of several other tumors in male and female mice also showed no statistically significant differences between treated and control groups. Therefore, no tumorigenic effect of orally administered aminopyrine in B6C3F1 mice was apparent in the present study.