Effects of simvastatin, an HMG-CoA reductase inhibitor, on plasma lipids and steroid hormones.

Seven hyperlipidemic postmenopausal women received 2.5 mg of simvastatin daily for six months, 5 mg for four months, and 2.5 mg for two months. During treatment, there were significant decreases in the patients' levels of plasma total cholesterol, phospholipids, low-density lipoprotein cholesterol, apolipoprotein (apo) B, apo E, and in the ratios of low-density lipoprotein:high-density lipoprotein cholesterol and apo B:apo A-I. Levels of high-density triglycerides increased significantly. Blood pressures tended to decrease. No significant changes in the plasma levels of cortisol, adrenocorticotropic hormone, testosterone, progesterone, or plasma renin activity were noted. Plasma aldosterone levels decreased significantly after nine months of treatment, but remained within normal limits. No other treatment side effects were recorded.

An evaluation of serum high density lipoproteins-phospholipids.

Phospholipids in high density lipoproteins (HDL) is being used as a negative risk indicator of atherosclerosis. Phospholipids in HDL may not demonstrate the actual level of HDL-phospholipids when determined by the precipitation or ultracentrifugal methods, because HDL fractions contain very high density lipoproteins (VHDL) and albumin. In the present study, the true level of phospholipids in HDL was estimated using high performance liquid chromatography (HPLC), and it was compared with the level of phospholipids in HDL determined by the precipitation method. Sera from 18 healthy subjects were used as materials. In the HPLC method, the HDL fraction was extracted making sure that it contained no free albumin, which is albumin not bound to phospholipids. The HDL fraction was separated into subfractions. It was found that phospholipids in the VHDL fraction make a 20.2 +/- 7.3% (mean +/- S.D.) part of the total HDL-phospholipids. A large part of the VHDL fraction was constituted of albumin-bound phospholipids. A significant correlation was observed between HDL-phospholipids determined by the precipitation method, which contain albumin, and the actual HDL fraction phospholipids determined by HPLC, which do not contain VHDL (r = 0.903, p less than 0.01). These results suggest that HDL-phospholipids values determined by the precipitation method give useful clinical data.

[Effects of hydrostatic pressure on cardiac function in human].

Effects of hydrostatic pressure on cardiac function were measured by echocardiography and radiography. Seven normal subjects (three females and four males) aged from 21 to 45 years were performed echocardiography on long axis of the heart at standing position in air and in head-out water (36 degrees C) immersion. A same trials were done at long sitting position in four subjects (one female and three males). The measurement of cardiac functions was calculated by Pombo's method. A chest radiography of a normal male individual (45 years) was taken at the time of functional residual capacity of lung in air and in head-out water (36 degrees C) immersion. For taking the chest radiography in water and in air, a box made by wood was used. X-ray exposure was synchronized with R wave of electro-cardiogram. The end-diastolic left ventricular volume, end-systolic volume and cardiac output in water immersion were significantly increased to compare with that of in air. Mean +/- SD of these percent changes were 213 +/- 71% (p less than 0.005), 193 +/- 90% (p less than 0.05), 220 +/- 83% (p less than 0.005), respectively. A same results were obtained at long sitting position. There was no significant changes on the heart rate between in water and in air. The circumstance of the abdomen decreased significantly in water immersion in comparison to in air. The percent change was 94.4 +/- 3.1% (p less than 0.001). There was a significant correlation between percent changes of abdominal circumstance and percent changes of end-systolic left ventricular volume (r = 0.754, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy.

Seven men and four women with symptomatic diabetic neuropathy were treated with methylcobalamin (2,500 micrograms in 10 ml of saline) injected intrathecally. Treatment was begun when patients had good metabolic control, as determined by measurements of plasma glucose and hemoglobin, and was repeated several times with a one-month interval between injections. Three patients were re-treated one year after the last intrathecal injection. Symptoms in the legs, such as paresthesia, burning pains, and heaviness, dramatically improved. The effect appeared within a few hours to one week and lasted from several months to four years. The mean peroneal motor-nerve conduction velocity did not change significantly. The mean (+/- SD) concentration of methylcobalamin in spinal fluid was 114 +/- 32 pg/ml before intrathecal injection (n = 5) and 4,752 +/- 2,504 pg/ml one month after intrathecal methylcobalamin treatment (n = 11). Methylcobalamin caused no side effects with respect to subjective symptoms or characteristics of spinal fluid. These findings suggest that a high concentration of methylcobalamin in spinal fluid is highly effective and safe for treating the symptoms of diabetic neuropathy.

[Experimental study of the mechanism of peritoneal dissemination--with special reference to scanning electron microscopic observations].

Most malignant ovarian tumors metastasize by peritoneal dissemination and have a poor prognosis. Few studies have been made to determine how free ovarian tumor cells act on the peritoneum and become lodged and proliferate therein and much still remains to be clarified concerning this issue. In the present study, we transplanted 2 X 10(6) cells of JOHYL-1 strain established from an atypical dysgerminoma into the peritoneal cavity of nude mice observed serially morphological changes in the peritoneum resulting from tumor cell dissemination both by light microscopy and SEM. The findings thus obtained may be summarized as follows: From 5 to 7 days after intraperitoneal transplantation of tumor cells, mesothelial cells of the peritoneum began to swell, with the intercellular boundaries becoming distinct. Microvilli of the mesothelial cells increased in number, forming a mesh-like structure, and in some places were found to be in direct contact with a tumor cell. From 10 days after tumor cell transplantation onwards the mesothelium showed enlarged intercellular spaces in some places, and at these sites tumor cells were seen to have adhered. On other sites mesothelial cells were being partially lost. From 11 days after being transplanted, the tumor cells started proliferating and infiltrating in the muscle layer. Concerning the site of tumor cell implantation, evidence was obtained showing that tumor cells adhered to intercellular spaces of mesothelial cells, and/or in defects formed on connective tissue by a loss of mesothelial cells. The study thus demonstrated a salient usefulness of the JOHYL-1 ascites type cell line, with a reliably great capacity for growth in vivo, as an experimental model for the study of peritoneal dissemination of tumor cells.

[Experimental chemotherapy of germ cell tumor heterotransplanted to nude mice].

While the treatment of ovarian cancer has made remarkable progress in recent years, the chemotherapy of ovarian germ cell tumor has not as yet been fully established and remains to be improved. We investigated the effectiveness of a single-agent therapy with Vincristine (VCR), Actinomycin D (ACD), and Cyclophosphamide (CPM) against a human undifferentiated dysgerminoma's cell line (JOHYL-1) with the following results. The ratio of the number of viable cells to the total cell population treated for JOHYL-1 cells of ascitic type was 70% with VCR, 58% with CPM and 25% with ACD; hence the efficacy on this malignant cell line was the greatest with ACD followed by VCR and CPM in that descending order. Notably with CPM, a striking antitumor effect was observed from 48 to 24 hours after treatment. The L.I. attained a peak at 24, 18 and 30 hours, respectively, after treatment with VCR, ACD and CPM. The M.I. was as high as a little more than 6% at 36 hours after treatment with VCR. There also was noted a shift in the cell cycle with any of the test drugs. Morphological changes observed in the cell were most obvious with ACD followed in order by VCR and CPM. LDH & isozyme pattern: In these respects there were no striking differences among the three drugs, even though the total enzyme activity was somewhat higher with VCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Stiff-man syndrome with spinal cord lesion.

An autopsy case of stiff-man syndrome is presented. The patient was a 54-year-old man who had suffered from fluctuating rigidity and tonic spasm of the trunk and leg muscles for three years. These symptoms were induced by emotional stress, strain at voiding and other external stimuli. Physical examination revealed stiffness of the neck, trunk and legs without obvious muscle weakness or atrophy. Deep tendon reflexes were hyperactive, while sensation was normal. EMG showed the stiffened muscles to have continuous motor unit activity which was decreased by myoneural block, spinal anesthesia, diazepam or sleep. Administration of diazepam (60 mg daily) gave some relief of the stiffness for several days. However, respiratory arrest suddenly occurred. Although the patient was resuscitated, he died nine days after this episode. Examination of the spinal cord revealed loss and degeneration of nerve cells with marked gliosis in the medial motor nuclei of the anterior horns. A symmetric degeneration in the bilateral anterior columns which has never been described as a spinal cord lesion in the stiff-man syndrome was also seen.

Characteristics of pulmonary function in patients with diabetes mellitus.

The incidence of pulmonary diseases among diabetics in Japan has been found to be more than 50% at death. This suggests the existence of some pulmonary risk factors. We analyzed pulmonary functions in 50 diabetics (31 males and 19 females) without overt lung disease, compared to 21 healthy male subjects of the same age (around 50 years old). Forced vital capacity and timed vital capacity were lower in diabetics (P less than 0.005). Diffusing capacity was also decreased in male diabetics (P less than 0.05). Among diabetics, a decrease in the diffusing capacity was dominant in patients with diabetic retinopathy, which correlated with an increasing duration of their diabetes. Analysis by the partial correlation method which accounts for the smoking index showed that standardized indices for peripheral airflow in male diabetics decreased significantly as the patient's age increased (P less than 0.005); the rate of decrement was greater than that of the control subjects. Diabetic patients showed abnormal lung function in the peripheral airways which increased with age and gas transfer was also affected by diabetic microangiopathy as well as the duration of diabetes. These changes seemed to deteriorate progressively, possibly combining and contributing to respiratory insufficiency in critical pathological conditions.

[In vitro sensitivity test of a cultured human ovarian cancer cell line to anticancer agents].

In vitro tests were performed to assess the sensitivity to six anticancer agents-ACT-D, ADM, CDDP, CQ, 5-FU and MMC-of a JOHYL-1 (ascites type) cell line from human dysgerminoma which was used as challenge strain. For comparative assessment, anticancer sensitivity was expressed as the ratio of IC50 and IC90 to LD50 (i.v.) in mice. Drug dose-response and time-response curves were plotted, and the IC50 ratio was calculated, for each test compound in order to investigate the mechanism of anticancer action. The results obtained were as follows. CQ proved to be remarkably active and ADM fairly active against JOHYL-1 (ascites), but 5-FU, CDDP and MMC varied remarkably with the parameter of measurement employed. Analysis of IC50 ratio data and patterns of cell growth inhibition indicated the growth-inhibitory effect of CDDP to be concentration-and time-dependent. The results of the present study are in close accord with the pattern of action reported in the literature.

[Mechanisms of high hemoglobin A1 in alcohol drinkers].

Hemoglobin A1 (HbA1) levels were significantly higher in healthy alcohol drinkers (HbA1 = 7.50%, n = 11) than in normal non-drinkers (HbA1 = 6.62%, n = 13). Ethanol was not able to change HbA1 level when ethanol was added to human whole blood in vitro. Acetaldehyde (AcCHO), although, markedly increased it. Glucose utilization in erythrocytes was stimulated by AcCHO. While it was completely blocked by sodium fluoride in the presence of AcCHO in the incubation medium, but sodium fluoride did not affect the formation of HbA1. AcCHO formed HbA1 with human purified hemoglobin in vitro. The level of HbA1 formed by AcCHO was significantly low when purified human hemoglobin used as a substrate in comparison with the use of whole blood. AcCHO and dihydroxyacetone phosphate reacted in the presence of aldolase. The reacted product, 5-deoxy-D-xylulose-1-phosphate, increased HhA1 level of human purified hemoglobin. It is suggested, the high level of HbA1 in healthy drinkers was caused by AcCHO, the first metabolite of ethanol. AcCHO formed addicts with human hemoglobin directly, and there might be other mechanisms of HbA1 formation due to AcCHO, such as 5-deoxy-D-xylulose-1-phosphate, which is the reacted product of AcCHO.

[Alveolar septal changes in idiopathic pulmonary fibrosis (author's transl)].

To clarify the mechanism of the disturbance of alveolar gas exchange in idiopathic pulmonary fibrosis, various pulmonary function tests were performed on 7 patients with the disease, of which 5 were defined histo-pathologically and 2 clinically. On 4 of all patients, detailed comparative studies of histopathological findings to pulmonary functions were carried out additionally. As the results, marked decreases of total lung capacity, pulmonary diffusing capacity (DLco) and Pao2 were observed. On exercise, the improvement of DLco or physiologic dead space (VD/VT) was hardly seen, while AaDO2 increased markedly. Ventilation (VA), perfusion (Q), and VA/Q ratio examined by 133Xe scintigram distributed more evenly over the entire lung fields than controls. These may suggest that the disturbance of alveolar gas exchange is mainly due to the elongation of the distance for diffusion in the membrane.