The trihalomethane (THM) levels were examined in discharged water from a human waste treatment plant, in tap water and in the water of swimming pools. The amounts of residual free chlorine, consumed KMnO4 and coliform in the water of swimming pools were also determined. A significant increase in the THM content was found in the water of swimming pools, where the proportion of chloroform against total THM was remarkably high. The high proportion of THM may have resulted from THM formation due to repeated disinfection by chlorine. The trihalomethane content increases in accordance with residual free chlorine in the water of swimming pools. When chlorine was under the standard level (0.4mg/l), some pools had high levels of coliform, but few had high concentrations of THM. However, when chlorine was over the standard level no pools had unsatisfactory levels of coliform, although more pools had high concentrations of THM.
Fe(II)-induced lipid peroxidation was measured at 25°C by the TBA method in rat liver mitochondria 3 days after 800R of whole-body irradiation, and decrements in Fe(II) concentrations in the medium were measured by the Nitroso-PSAP method, simultaneously. An induction period (lag) was observed in the reaction curve of the Fe(II)-induced lipid peroxidation. The Fe(II) concentration decreased gradually during the lag period, but decreased rapidly thereafter. The oxidating velocity of Fe(II) in the presence of mitochondria was significant compared with the Fe(II) auto-oxidation in the mixture. At a given dose of Fe(II), a greater amount of mitochondrial protein allowed a shortened lag and accelerated the oxidating velocity of Fe(II). The relationship between MDA formation per unit protein and lag time showed the same tendency, so that MDA formation increased with a lengthened lag. With given doses of protein (0.5 mg/ml) and Fe(II), a shorter lag and greater MDA formation were found in irradiated rat liver mitochondria than in non-irradiated rat liver mitochondria. With the addition of Fe(II) (0.10 mM), the lag was lengthened and MDA formation increased the same in irradiated as in nonirradiated mitochondria, compared with Fe(II) (0.05 mM).
The effects of phosphate (Pi) and ascorbic acid on Fe(II)-induced lipid peroxidation were studied in rat liver mitochondria (RLM) at 25°C The examination was conducted with RLM at a concentration of 0.5mg protein/ml, 0.05mM Fe(II), 2mM Pi and 0.5mM ascorbic acid. Peroxidation was detected by the thiobarbituric acid reaction (TBA-value), and the concentration of Fe(II) in the reaction mixture was determined simultaneously by the Nitroso-PSAP method. Fe(II)-induced peroxidation had a lag period followed by a burst in the TBA-value and then held a moderate level. A slow decrease in Fe(II) content was observed during the lag period which was followed by a greater decrease that paralleled the burst in the TBA-value. The Fe(II) concentration at the initiation of the burst was one-third of the added Fe(II) concentration. The ascorbic acid-induced peroxidation had a lag period accompanied by a slow increase in the TBA-value. The Fe(II)·ascorbic acid-induced peroxidation had a longer lag period than the ascorbic acid-induced one. The TBA-value increased more slowly, and the Fe(II) concentration was not reduced in this case. Peroxidation induced by Fe(II)·Pi had a shorter lag period and a greater TBA value than that by Fe(II). The Fe(II) content was reduced more rapidly with Fe(II)·Pi than with Fe(II) only. Ascorbic acid·Pi-induced peroxidation showed an elongated lag period compared with ascorbic acid only, and the TBA-value increased more slowly. Fe(II)·Pi·ascorbic acid-induced peroxidation had a slightly longer lag period than the peroxidation induced by Fe(II)·Pi, and had the highest TBA-value. Fe(II) content was reduced during the lag period, and then increased. Other experiments under this condition indicated that the rate of Fe(II) content reached the optimum level needed for the initiation of burst peroxidation.
In order to establish the performance reliability for the clinical use of the Pressurometer II (Del Mar Avionics, USA), I compared the blood pressure readings from the Pressurometer II with readings taken concurrently with a mercury sphygmomanometer in the supine, sitting, right lateral, left lateral and standing positions in 15 normotensive subjects. I also assessed the day to day reproducibility of the diurnal near-basal blood pressure in 9 normotensive subjects. Furthermore, diurnal variations of blood pressure and heart rate in 20 normotensive, hospitalized subjects were recorded in the absence of a physical activity limitation. Good correlations in systolic and diastolic blood pressure between the Pressurometer II and the mercury sphygmomanometer were obtained regardless of the position when taking on and off the Pressurometer II. Good reproducibility was demonstrated for whole-day blood pressure and heart rate measured with the Pressurometer II. Diastolic blood pressure in the right lateral position measured with the Pressurometer II was significantly but slightly higher than with the mercury sphygmomanometer. Second measurements indicated lower blood pressures at 9:00, 21:00 and 22:00 in comparison with the first measurements. A small diurnal variation in blood pressure with a lower level during sleep was observed in the subjects without physical activity limitation. These results indicate that the Pressurometer II is available for repeated evaluation of ambulatory blood pressure for periods of 24 hours.
The effect of cepharanthine on radiation- and Fe2+-induced lipid peroxidation was examined. Cepharanthine and α-tocopherol inhibited radiation-induced lipid peroxidation of liposomes and Fe2+-induced lipid peroxidation of mitochondria. Cepharanthine reduced the velocity of Fe2+oxidation in the presence of mitochondria but not in the absence. α-Tocopherol strongly inhibited radiation-induced peroxidation of lipid dissolved in MeOH/CHCl3/H2O (v/v, 2/1/0.8) and Fe2+-induced peroxidation of lipid dissolved in MeOH. Cepharanthine, on the other hand, only weakly inhibited lipid peroxidation in the MeOH/CHCl3/H2O system, and did not inhibit peroxidation in the MeOH system. The change in the absorption stectrum of α-tocopherol and cepharanthine by free radicals (X irradiation) was measured. The reagents were dissolved in 95% EtOH acidified with 20mM HCl and MeOH/CHCl3/H2O (v/v, 2/1/0.8). α-Tocopherol exhibited a change in its absorption spectrum in both systems and seemed to be oxidized at a higher rate by radicals. However, cepharanthine did not exhibit a change in its absorption spectrum in acidified 95% EtOH exposed to X irradiation, and slightly exhibited a chang in its absorption spectrum in MeOH/CHCl3/H2O exposed to X irradiation. From these observations, cepharanthine seemed not to exhibit a radical-trapping ability.
Twenty-nine patients with advanced non-Hodgkin's lymphoma (3 with follicular medium-sized cell type, 1 with follicular mixed cell type, 5 with diffuse small cell type, 17 with diffuse medium-sized cell type and 3 with lymphoblastic type) were treated with a four-drug combination chemotherapy consisting of adriamycin, vincristine, ifosfamide and prednisolone (AVIP). The objective response rate was 89% with a complete response rate of 55%. The median duration of complete response was 10 months ranging from 2 months to 6 years and 7 months. The median survival time calculated by the Kaplan-Meier method was 3 years and 9 months. As for the 17 patients with diffuse medium-sized cell type lymphoma, the complete response rate was 71%. Median survival time has not been reached, and 62% of the patients were alive after 5 years. Performance status, and presence or absence of systemic symptoms were important factors in predicting survival. The myelosuppressive toxicity of the regimen was well tolerated. No patients encountered life-threatening toxicity. This study demonstrated the efficacy of the AVIP regimen in patients with non-Hodgkin's lymphoma, and it appeared that patients with diffuse medium-sized cell type lymphoma were potentially curable.
For the assessment of adriamycin (ADM)-induced cardio-toxicity, myocardial scintigraphy using technetium-99m pyrophosphate; electrocardiography, measuring the QRS voltage and QTc; mechanocardiography, measuring the systolic time interval (STI) and echocardiography, measuring the ejection fraction (EF) were performed in patients with malignant disease, mainly in those with malignant lymphoma. In a retrospective study, 17 patients who had received ADM therapy underwent cardiac evaluation after completion of the therapy. Out of these patients, 3 who had been given a total dose of ADM of 493 mg/m2, 545 mg/m2 and 705 mg/m2 developed congestive heart failure. Myocardial scintigrams showed the best correlation with the cumulative dose of ADM and congestive heart failure. Based on the results from the retrospective study, a prospective study was performed in 29 patients. Cardio-toxicity was evaluated at a cumulative ADM dose of 400 mg/m2 and 500 mg/m2 using the same means as in the retrospective study. ADM therapy was discontinued when a cumulative ADM dose of 500 mg/m2 was reached or a positive myocardial scintigram was observed. No patients developed congestive heart failure. Myocardial scintigrams were affected by the age of the patient. Among the QRS voltage, QTc, STI and EF, the QRS voltage correlated best with myocardial scintigrams; however, the QRS voltage seemed to be less sensitive than myocardial scintigrams for the early detection of ADM-induced cardiomyopathy. It is concluded that discontinuation of ADM at the time of a positive myocardial scintigram is a good way to avoid ADM-induced cardiomyopathy.
The streptococcal preparation, OK-432, has been found to be a biological response modifier. The effects of OK-432 on autologous CFUs in mice and hematopoietic disorders induced by anti-leukemic agents (DNR: daunorubicin, ara-C: cytosine arabinoside, NCS: neocarzinostatin) were investigated in order to obtain information as to the possibility of its clinical application in induction chemotherapy for acute leukemia. OK-432 increased autologous CFUs in irradiated mice, suggesting that it acted hematopoietically on multipotent stem cells. In mice treated with DNR, OK-432 reduced neutropenia when it was given before and simultaneously with DNR. In mice pretreated with OK-432, the duration of neutropenia caused by ara-C tended to be prolonged. On the other hand, simultaneous administration of OK-432 with ara-C showed no significant differences as compared to ara-C alone. These results suggested that the simultaneous administration of OK-432 with chemotherapeutic agents might protect normal hematopoiesis during induction chemotherapy for acute leukemia in man.
In this study NCMP (neocarzinostatin, cytosine arabinoside, 6-mercaptopurine and prednisolone) two-step regimen with OK-432 was applied to patients with ANLL in order to evaluate the clinical effects of the streptococcal preparation, OK-432. A total of 33 cases were randomized into two groups. Group A and group B were treated with NCMP two-step and NCMP two-step with OK-432, respectively. Group A consisted of 19 patients (16 AML and 3 AMoL) and group B consisted of 14 patients (13 AML and one AMMoL). All patients were previously untreated. The complete remission (CR) rate was 66.7% in group A and 64.3% in group B. However, patients in group B attained M1 marrow and CR earlier than those in group A. Cytoreduction in peripheral blood and bone marrow was more rapidly obtained in group B than in group A. Normal hematopoiesis recovered more rapidly in group B than in group A. Cellular immunity (PPD) in group B tended to be maintained more than in group A. The CR rate in relapsed cases was higher in group B than in group A (44% vs 14%). Fever related to OK-432 was recognized in group B, but it was tolerable. OK-432 showed no prophylactic effects on infection. The simultaneous combination of OK-432 with chemotherapeutic agents might be expected to rapidly reduce leukemic cells, accelerate recovery of normal hematopoiesis and maintain cellular immunity during induction chemotherapy for ANLL.
There are many factors pointed out theoretically as influencing the progression of acute aortic dissection, but few factors have been proved experimentally. In this study, hemodynamic factors were evaluated experimentally as to how they related to the progression of aortic dissection. DeBaKey type IIIb aortic dissections were made by Blanton's method in the descending thoracic aorta of dogs. At the initiation of progression of aortic dissection, blood pressure, LV dp/dt, aorta dp/dt, flow volume, flow velocity and blood viscosity were measured. Each factor was also evaluated by Prokopf's method in which aorta was inserted in the closed circuit with pump. As to hemodynamic factors affecting the progression of acute aortic dissections; 1) Hypertension was the most important factor. 2) LV dp/dt was not so important, as mentioned by Wheat. 3) The flow volume, velocity and viscosity were thought to be important theoretically, but these factors did not prove to be significant in this study. Retrograde dissections progressed after making the intimal tear wider and longer, and by increasing peripheral resistances. The dissected layers in the media were variable, but most of the specimens were dissected at the outer layer in the proximal area and at the inner layer in the distal area.
Chlordane is widely used as an anti-termite pesticide for wooden houses. Pest control operators as well as the residents of chlordane treated houses might become sick through the exposure to the chemical. The chlordane concentration in the air and soil after the treatment was examined. The Chlordane concentration in the blood of pest control operators was also examined. A 40% emulsion of chlordane was used together wigh a 2% pestrolum emulsion as a sprinkling pesticide. Its constituents as determined by GC-ECD were in the descending order of trans-chloirdane, trans-nonachlor, cis-chlordane, γ-chlordene, heptachlor and cis-nonachlor. The Chlordane concentration in the air was the highest immediately after the treatment, and decreased gradually with the lapse of time. Heptachlor was the largest, and cis-nonachlor the smallest constituent of chlordane detected in the air. On the contrary, cis-nonachlor was the largest, and heptachlor the smallest contituent in the soil. This suggests that the exposure dose of heptachlor may be extreme. Heptachlorepoxide and oxychlordane as metabolites, and trans-nonachlor and cis-nonachlor were detected in the blood of pest control operators. The C. P. K. value increased in their blood.
I exposed rats to chlordane (industrial product) and measured the concentration of chlordane in various tissues of rats over time. Exposure to chlordane for 3.5 hours appoximated the exposure to chlordane in a house a hundred days after treatment for termites. However, chlordane and metabolites were detected in all the tissues of rats. The concentration of chlordane in various tissues showed highest level one hour after exposure. After that, heptachlor, γ-chlordane, trans-chlordane and cis-chlordane were excreted fast, while trans-noachlor and cis-nonachlor were excreted extremely slowly. The metabolites of chlordane (heptachlorepoxide and oxichlordane) showed the highest level one after exposure in the various tissues, and after that they were excreted slowly. Chlordane had the highest level in the adipose tissue and the second highest level in the liver, kidney, lung, pectoral muscle and heart. In the spleen and brain it showed a relatively low level. The lowest level was in the blood. As for Biological Harf Life (B. H. L.), the number of days in the secondary excretion in the adipose tissue of chlordane excreted late was as follows: trans-nonachlor 38.5 days, cis-nonachlor 16.5 days, and metabolites 16.9 days. It is suggested that the chronic toxicity of trans-nonachlor, cis-nonachlor and metabolites should be investigated in future.
In order to clarify the cytotoxicity of chlordane (industrial product as insecticide), the effect on oxidative phosphorylation in rat liver mitochondria was studied. The respiration rate. RCI and ADP/O ratio were inhibited by chlordane related compounds, and the degree of inhibition was in the descending order of trans-chlordane, cis-chlordane, heptachlor and heptachlor epoxide. Of the indexes indicating various respiratory activities, state 3 respiration was the most sensitively inhibited by these compounds, suggesting their energy transfer inhibition. However, electron transport was also inhibited by high concentrations of chlordane constituents. The inhibitory effect of the chlordane constituents on respiratory activity varied depending on the species of respiratory substrate, suggesting site specificity of these compounds. Trans-chlordane, cis-chlordane and heptachlor stimulated Mg2+ ATPase activity and inhibited DNP-stimulated ATPase activity. Heptachlorepoxide, a metabolic product of heptachlor, has less effect on mitochondria than heptachlor.