Effects of hypertension and antihypertensive drugs on cardiovascular complications in the elderly

The role of hypertension and antihypertensive drugs in cardiovascular complications was evaluated in 380 elderly people living in the Tokyo Metropolitan Gerontology Center. The subjects were classified into four groups according to the presence or absence of hypertension and their antihypertensive treatment, and followed up prospectively for 5 years from 1979 to 1984. The average age of each group was 74 to 76 years. Cerebrovascular disease was observed in 19.3% of male hypertensives and 10.1% of male normotensives (p = 0.078). The drug treated group revealed no cerebral hemorrhage and less cerebral infarction. This tendency was not observed in females. Ischemic heart disease was prevalent in the drug treated group (10.9% vs 4.5%, p = 0.023) irrespective of blood pressure level. Risk factors such as body mass index, skinfold thickness, serum cholesterol, albumin, creatinine, blood urea nitrogen and uric acid at entry were elevated in the drug treated group. Diuretics were used in 92% of the drug treated group; in 53% as monotherapy and in 39% as combination therapy with other antihypertensive agents. The metabolic effect of diuretics may increase the incidence of ischemic heart disease in the elderly. We might conclude that hypertension in the aged accelerates cerebrovascular complications, and that antihypertensive treatment is effective even in this group. However, the wide use of diuretics could increase the incidence of ischemic heart disease. Careful selection of antihypertensive drugs as well as dose adjustment are needed in the treatment of elderly hypertensives.     

Beta2-glycoprotein I-dependent anticardiolipin antibody in early recurrent spontaneous abortion

The objective of this study was to assess the clinical significance of autoimmune anticardiolipin antibody that can react with cardiolipin only in the presence of beta2-glycoprotein I (beta2-glycoprotein I- dependent anticardiolipin antibody) in the pathogenesis of early recurrent abortion. A total of 72 early recurrent spontaneous aborters and 175 normal healthy women were analysed for the occurrence of beta2- glycoprotein I-dependent anticardiolipin antibody in serum samples by an enzyme-linked immunosorbent assay specific for the detection of beta2-glycoprotein I-dependent anticardiolipin antibody. The incidence of beta2-glycoprotein I-dependent anticardiolipin antibody in the early recurrent spontaneous aborters was essentially the same as that of normal women. Thus, the beta2-glycoprotein I-dependent anticardiolipin antibody seemed to have little, if any, implication in the pathogenesis of early recurrent spontaneous abortion.      

The use of the monoclonal antibody Ki-67 in the identification of proliferating cells: application to surgical neuropathology

In order to test its potential application to surgical neuropathology, the monoclonal antibody Ki-67 was used to demonstrate immunohistochemically the proliferating cells in 40 neoplasms of the nervous system. The antibody, which reacts with a nuclear protein expressed in the G1, G2, S, and M phases of the cell cycle, was demonstrated in frozen sections of all lesions. The highest incidence of stained nuclei was found in a metastatic carcinoma (57%). The percentage of stained cells in gliomas was in general agreement with the histologic grade and known biologic behavior of the lesions, ranging from 0.6% in a pilocytic astrocytoma to 12.4% in a glioblastoma multiforme. In the fibrillary astrocytic neoplasms of low cellularity, there were good correlations between the percentages of stained cells and the degrees of nuclear pleomorphism and chromatin density. In meningiomas, schwannomas, and a cerebellar hemangioblastoma, the fractions of labeled nuclei were less than 1%. The percentage of stained cells in pituitary adenomas showed considerable variation among the four cases (0.2-1.5%), the biologic significance of which is unknown. In four of the above cases, Ki-67 staining was performed on air-dried squash preparations with excellent visualization of immunoreactive nuclei. In one case, a hemangioblastoma, no stained nuclei were seen. The results confirm that Ki-67 staining is technically suitable as a diagnostic method, with good correlations between frozen sections and smear preparations. Determination of the replicating cell fraction could become an important additional criterion to predict the biologic behavior of nervous system neoplasms.     

Peripheral analgesic actions of opioid peptides and morphine analogues

Opiates and opioid peptides were administered in the order of 10(-9)-10(-6) mol peripherally, and their action on pain sensitivity was investigated by the modified formalin test which has two characteristic pain responses (the first and the second phase) in the mouse hindpaw. Opioid peptides (20-500 pmol) had dose-dependent analgesia against both first and second phases, and their action ranked dynorphin greater than [D-Ala2, Met5]-enkephalinamide greater than [Met5]-enkephalin. EKC and morphine (0.4-2.5 nmol) inhibited pain response of the first phase, but produced hyperalgesia in the second phase dose-dependently. Lidocaine hydrochloride had peripheral analgesic action, but was about 500-10000 times weaker than these substances. So, these peripheral analgesic actions have a different mechanism from that of local anesthetic action. N-methyl levallorphan which is thought to be a peripherally selective narcotic antagonist reversed these peripheral analgesic actions at the first and second phases and also prevented the hyperalgesic effects of EKC and morphine at the second phase. Naloxone reversed analgesia at only the first phase. These results suggest that an analgesic mechanism by opioids may exist at the peripheral site as well. Furthermore, it is estimated that a receptor exists which is antagonized by N-methyl levallorphan but not by naloxone and that there is a system of hyperalgesia by EKC and morphine in pain modulation.     

Sustained ventricular tachycardia responsive to verapamil in patients with hypertrophic cardiomyopathy. Clinical and electrophysiological assessment of drug efficacy

Recently, we examined 2 cases of hypertrophic cardiomyopathy (HCM) presenting with sustained ventricular tachycardia (VT). One case was a 62 year old male with midventricular hypertrophy and monomorphic sustained VT. After admission, the efficacies of procainamide, disopyramide, aprindin, flecainide, mexiletine and verapamil were evaluated by means of continuous electrocardiographic monitoring. Verapamil prevented the recurrence of sustained VT and markedly reduced the frequency and number of runs of nonsustained VT. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular apex. Intravenous verapamil at a dose of 10 mg prevented the induction of VT. The patient was discharged on verapamil and remains asymptomatic after 3 months of follow up. The other case was a 34 year old female who was a survivor of cardiac arrest. Monomorphic VT was observed on emergency admission and was converted to sinus rhythm by direct current cardioversion after resuscitation. In the electrophysiologic study, rapid VT was induced by double extrastimuli at the right ventricular outflow tract. Verapamil at a dose of 10 mg prevented the induction of VT. These 2 cases of HCM are rare in that they presented with sustained VT. It is also of interest that verapamil, which has been used conventionally in HCM, prevented VT.     

Hepatic Disposition Characteristics of Electrically Charged Macromolecules in Rat in Vivo and in the Perfused Liver

The effect of electric charge on the hepatic disposition of macromolecules was studied in the rat. Charged derivatives of dextran (T-70) and bovine serum albumin (BSA), mitomycin C–dextran conjugates (MMC-D), and lactosaminated BSA (Lac-BSA) were employed as model macromolecules. After intravenous injection, cationic macromolecules were rapidly eliminated from plasma because of their extensive hepatic uptake, while anionic and neutral macromolecules were slowly eliminated. Cationic macromolecules were recovered from parenchymal and nonparenchymal hepatic cells at a cellular uptake (per unit cell number) ratio of 1.4–3.2, while that of Lac-BSA was 14. During liver perfusion using a single-pass constant infusion mode, cationic macromolecules were continuously extracted by the liver, with extraction ratios at steady-state (E _ss) ranging between 0.03 and 0.54, whereas anionic and neutral macromolecules were almost completely recovered in the outflow at steady state. The E _ss for cationized BSA (Cat-BSA) and cationic MMC-Dcat were concentration dependent and decreased at low temperatures and in the presence of colchicine and cytochalasin B. The possible participation of the internalization process in the uptake of cationic macromolecules by hepatocytes was suggested.