E Matsuyama

Diltiazem, verapamil and nifedipine suppress sinoatrial (SA) nodal function in the excised rabbit heart. Clinically, however, their suppressive effect on the SA node is modified considerably by the reflex increase in sympathetic tone as a result of the fall in blood pressure caused by the vasodilating action of the calcium antagonists. Diltiazem, verapamil and nifedipine suppress atrioventricular (AV) nodal conduction and prolong refractory periods in the excised rabbit AV node. Clinically, diltiazem and verapamil exert a similar suppressive effect on the AV node and are useful for treating and preventing AV nodal reentrant tachycardia. Nifedipine, in clinically practical doses, has no antiarrhythmic properties, probably because of reflex activation of the sympathetic system secondary to its hypotensive effect, which is greater than that of the other two calcium antagonists. Diltiazem and verapamil may sometimes worsen AV conduction, especially in patients with conduction disturbances. Nifedipine, on the other hand, can be used as a coronary vasodilator with the least untoward effect on AV conduction.

Cumulative dose-dependent toxic effects, particularly cardiomyopathy, induced by doxorubicin and the possible prevention by coenzyme Q10 (CoQ10) were studied in rabbits. In rabbits given doxorubicin alone, there was considerable body weight loss, alopecia, pancytopenia, significant increase in serum creatine phosphokinase and LDH, and ECG changes characterized by tachycardia, flat and inverted T wave, the premature ventricular contractions. In rabbits given doxorubicin plus CoQ10, the only change was pancytopenia. In rabbits treated with doxorubicin alone, the most prominent histologic changes were observed in mitochondria of myocytes, and these changes were characterized by loss of outer membrane, disarrangement of cristae, and formation of numerous concentric lamellae. In addition to mitochondrial changes, there were numerous vacuolizations and extensive depositions of both electron-dense and membranous laminated bodies in the sarcoplasm and disarrangement of Z-band and filamentous changes of myofibrils. Numerous vacuolizations in the capillary endothelial cytoplasm in the myocardium were also conspicuous. On the other hand, few significant morphologic changes were seen in the nuclei of myocytes. There were few ECG and histopathologic changes in rabbits treated with both doxorubicin and CoQ10. These findings suggest that the cardiomyopathy of doxorubicin may be prevented or is at least inhibited by CoQ10. The mechanisms of both doxorubicin-induced cardiomyopathy and its prevention by CoQ10 are discussed.

A 62-year-old woman with chronic neutrophilic leukemia (CNL) is described. She presented in February 1988 for evaluation of leukocytosis of 3 years' duration with no complaint. Physical examination was normal. The leukocyte count was 20,100/microliters with 70% segmented neutrophils and 12% band forms. A myelogram showed marked myeloid hyperplasia and plasmacytosis (5.9%). Neutrophil alkaline phosphatase score, serum lysozyme and vitamin B12 levels were elevated. Cytogenetic analysis of the marrow aspirate showed normal karyotype, with no Philadelphia chromosome. Total serum protein (TP) was 7.5 g/dl with increased beta-globulin (23.5%), identified as monoclonal IgA kappa (3.3 g/dl) on immunoelectrophoresis. No activity of G-CSF was detected in the serum. A retrospective study revealed that the beta-globulin level was normal (6.3%, TP 6.9 g/dl) in 1980 and that it was slightly increased (11.6%, TP 7.0 g/dl) without leukocytosis (5,900/microliter) in 1981. In 1985, when leukocytosis obviously existed (9,900/microliter), the percentage of beta-globulin was increased to 17.5% (TP 7.2 g/dl). The possibility that monoclonal gammopathy preceded the leukocytosis must be admitted. On the basis of our observation, it is assumed that CNL and monoclonal gammopathy may be blood dyscrasias derived from a common precursor cell or that the immunological abnormality associated with monoclonal gammopathy may be implicated in the development of CNL.

In 1950, Japan's infant mortality rate was 60.1/1000 live births, its perinatal mortality rate was 46.6/1000 live births, and its maternal mortality rate 176.1/100,000 live births. In 1986, the infant mortality rate was 5.2, the perinatal mortality rate was 7.3/100,000 live births, and the maternal mortality rate was 11.7/100,000 live births. The infant mortality rate can be lowered further by reducing the incidence of hypoxia, asphyxia, and respiratory disorders through imoproved perinatal monitoring and a health care system. Factors which contribute to Japan's low infant mortality include 1) early prenatal care, 2) few unmarried mothers (In 1982, they were .9% of the total number of mothers.), 3) favorable age of mothers (Most are between ages 20 and 34.), 4) few adolescent mothers (In 1985, they constituted 1.3% of all mothers.), 5) competent medical attention (In 1985, 99.8% of all deliveries were in hospitals or private clinics.), 6) a week's stay in the hospital for the mother and child, and 7) use of the Maternal and Child Health handbook. The handbook is a detailed medical record of every child born in Japan, from the time it is conceived until it becomes 6 years old. 1st issued in 1942, the handbook has created a foundation for maternal and child health, stimulating and increasing pregnant women's awareness of the value of the health check-up.