Preclinical anticancer effects and toxicologic assessment of hepatic artery infusion of fine-powder cisplatin with lipiodol in vivo.

We conducted an in vivo study to evaluate the anticancer effect and toxicity of fine-powder cisplatin suspended in lipiodol (fCDDP/LPD suspension) after a single administration of three different doses to rats via the intrahepatic artery after transplantation of rat ascites hepatoma cells. The toxicity of the fCDDP/LPD suspension was also assessed in the same protocol in noncancer-bearing rats and the observed toxicologic changes were compared among groups administered saline (Sal), an aqueous solution of fCDDP (fCDDP/Sal solution), and LPD alone. In parallel with the toxicity test, plasma CDDP concentrations were compared between the fCDDP/LPD suspension and fCDDP/Sal solution. The mean weight of the tumors in the fCDDP/LPD suspension groups was significantly less than in the LPD-alone group. The pathologic changes in the liver observed in the fCDDP/LPD suspension group increased with dose, were more marked compared with those in the fCDDP/Sal solution and LPD-alone groups, and were reversible. No other toxicologic effects were observed. The concentration of CDDP in the plasma in the fCDDP/LPD suspension group was slightly lower than that in the fCDDP/Sal solution group. In conclusion, the results indicate that the fCDDP/LPD suspension has sufficient anticancer efficacy and tolerability for use in the clinical treatment of hepatocellular carcinoma.

Reduction of hypercholesterolemia and proteinuria in nephritic rats by low-meat-protein diets.

The effects of low-meat-protein diets on hypercholesterolemia and proteinuria were studied in rats with nephrotoxic serum nephritis. After an injection of nephrotoxic serum, rats were given either a 20% meat-protein diet (20M), an 8.5%-meat-protein diet (8.5M), or a valine-(0.05%)-supplemented 8.5%-meat-protein diet (8.5MV) for 12 days. Urinary protein excreted from the 20M-fed, nephritic control rats increased rapidly and linearly during the initial 3 days, and thereafter the high excretion rate was maintained for up to 12 days. Two low-meat-protein diets (8.5M, 8.5MV) commenced to suppress proteinuria 3 days after feeding and the suppression was preserved during the rest of the experimental periods. Compared with the 20M, both low-meat-protein diets significantly improved hypercholesterolemia induced in this nephritic model. These two diets significantly enhanced the fecal excretion of neutral sterols. They caused neither fatty liver nor severe growth retardation. These effects of 8.5MV were identical to those of 8.5M. The results suggest that low-meat-protein feeding, without amino acid supplementation, improves hypercholesterolemia and proteinuria in nephritis without severe protein malnutrition. The results also suggest that the hypocholesterolemic effect of the low-meat-protein diets may be, at least in part, attributed to increased fecal excretion of steroids.

[Risk factors for severe subarachnoid hemorrhage following aneurysmal rupture].

Major reduction in disability and death from severe subarachnoid hemorrhage (SAH) can probably be brought about more effectively by prevention than by better medical or surgical treatment. Identification of the major risk factors for severe SAH should facilitate the preventive efforts. As risk factors for severe SAH, a patient's age, sex, location and size of aneurysms, hypertension, rebleeding including minor leak, and cigarette smoking were selected. The relation between the incidence of severe SAH, a surgical results, and the risk factors was examined in 81 severe SAH cases. Hypertension, rebleeding from aneurysms, large aneurysm exceeding 1.0 cm/sec in size were closely connected to severe SAH. Treatment of hypertension, acute surgery for aneurysms and aggressive surgery for unruptured large aneurysms were the only hope for achieving substantial reduction in the incidence of severe SAH and for improving the surgical results.

[The surgical treatment of ruptured thoracic aortic aneurysm with use of permanent bypass].

Two surgical cases with ruptured thoracic aortic aneurysm were reviewed. Case 1 was a 74-year-old female, and Case 2 was a 77-year-old female. In both cases, chest X-ray examination revealed a mass like shadow in the left superior mediastinum, and aortography demonstrated a ruptured saccular aneurysm distal to the left subclavian artery. Midsternotomy and an incision over the third left intercostal space were made to approach the aneurysm. Since inflammatory adhesion was marked in the perianeurysmal area, a permanent bypass was placed between the ascending and descending aorta followed by exclusion of the aneurysm. One of the two cases was alive, but the other case was died due to bleeding from the area of permanent aortic clamp.

[Intramyocardial hemangioma of the right ventricle with successful resection--report of a case and review of the literature].

A 62-year-old man developed symptoms of heart failure. Echocardiography showed a dense mass arising from the free wall of the right ventricle and occupying about 75% of the right ventricular cavity. Selective coronary angiography demonstrated intense neovascularization of a cardiac neoplasm arising in the distribution of the right coronary artery. Under cardiopulmonary bypass the tumor was resected completely and the defect of the ventricular wall was repaired with Gore-tex (EPTFE) patch (area 7.5 X 5.0 cm). The size of the resected tumor was 10.0 X 9.5 X 3.4 cm and weighed 170 g. Histological examination of the tumor disclosed cavernous hemangioma. The post operative course was uneventful and the patient has remained asymptomatic after the surgery. To our knowledge, only 23 cases of intramyocardial or intracavital hemangioma were reported in the world literature and this may be the first report in Japan.

Interacting effects of zinc and cadmium on the cadmium distribution in the mouse.

Effects of zinc (Zn) on cadmium (Cd) distribution in the mouse body were investigated after intranasal administration. The amounts of Cd (2 x 10(-6) M/0.02 ml) reaching respiratory organs increased as the ip dose of pentobarbital increased. Administration of Zn with Cd (2 x 10(-6) M Zn + 2 x 10(-6) M Cd /0.02 ml) further increased the Cd amounts reaching respiratory organs and increased mouse mortality. A single administration of Cd increased Cd levels in blood, liver, kidney and respiratory organs. High levels of Cd were maintained for at least 90 days in these organs after single administrations of Cd. The administration of Cd plus Zn further increased the Cd content in these organs during 0-60 min after administration. However, simultaneous administration of Zn with Cd inhibited prolonged Cd accumulation in kidney and liver. These results suggest that intranasally administered Zn (2 x 10(-6) M) has dual effects on Cd movement. Zn further increases the Cd levels in the lung and mouse mortality increases. On the contrary, Zn inhibits prolonged Cd accumulation in mice and decreases the chronic toxicity in mice that survive the acute phase.

Characteristics of chronically paced cardiac functions in the congenital complete atrioventricular block.

Characteristics of morphology, cardiac function, and cardiac reserve at late state were evaluated at rest, by changing the pacing rates, and after exercise in patients with ventricular pacemakers for isolated congenital complete atrioventricular block. Heart size was reduced statistically after pacemaker implantation, and concentric myocardial hypertrophy was observed. Cardiac pump functions at rest seemed fairly well compensated by increased ejection fraction, but the cardiac index was still lower than that of the normal heart. Responses of cardiac function towards the changing rates were considered satisfactory, and those variables had statistic correlations with the pacing rates. After exercise, significant increase of cardiac pump function and also statistic acceleration of myocardial function were observed. This fact proved that cardiac reserve was good, although the increased cardiac output after exercise was still insufficient without an increase in heart rate. More physiological pacing modes would be required as currently recommended.

Vapor compression distiller and membrane technology for water revitalization.

Water revitalization for a space station can consist of membrane filtration processes and a distillation process. Water recycling equipment using membrane filtration processes was manufactured for ground testing. It was assembled using commercially available components. Two systems for the distillation are studied; one is an absorption type thermopervaporation cell and the other is a vapor compression distiller. Absorption type thermopervaporation able to easily produce condensed water under zero gravity was investigated experimentally and through simulated calculation. The vapor compression distiller was studied experimentally and it offers significant energy savings for evaporation of water.

[Clinical study of ventriculo-lumbar perfusion in the patients of so-called normal pressure hydrocephalus (author's transl)].

The cerebrospinal fluid dynamics were studied in the ten patients between 33 and 67 years old with signs of so-called normal pressure hydrocephalus by the technique of ventriculo-lumbar perfusion. The perfusion fluid with Ringer's solution or Hartmann's solution containing tracer amounts (25 mg/dl) of insulin. The inflow fluid warmed up to the body temperature was introduced by the infusion pump to the trigone of the lateral ventricle through the ventricular tube. The outflow fluid was collected from the lumbar subarachnoid space through the spinal needle inserted into the L4-5 interspace. The perfusion pressure was adjusted by raising and lowering the height of the outflow manometric pressure relative to the spinous process. The distribution volume of the perfusion system was the range of 94 - 209 ml (average 136 ml) and exceeded the normal range. The formation rate of cerebrospinal fluid was the range of 0.21 - 0.69 ml/min (average 0.39 ml/min) at the opening pressure, and nearly equal to the bulk absorption rate. There was the relationship between the bulk absorption rate and the perfusion pressure, and the regression coefficients in nine cases were lower than reported in normals. The clinical condition of seven of the nine patients demonstrating this absorptive deficit improved after cerebrospinal fluid shunting. The perfusion test was useful to recognize the cerebrospinal fluid dynamics and also to determine the indication of cerebrospinal fluid shunt in the patients of so-called normal pressure hydrocephalus.