161 cases of liver cirrhosis were selected for studying the correlation between their abnormality of glucose tolerance and the pathologic stage or clinical course of them. The cases were divided into two groups; a group of 42 cases were clinically considered to have combinated with primary diábetes and the remaining 119 cases were not. Besides, the latter were classified more small groups according to the results of GTT. These groups of cases with liver cirrhosis were compared with the groups of probable diabetics, chemical diabetics and the clinical diabetics without liver disease upon some clinical features or the results of examination, and the results were as follows: 1. Of 119 cases of liver cirrhosis without primary diabetes 51 cases (42.9%) showed diabetic pattern in GTT, 36 cases (30.2%) probable diabetic, 7 cases (5.9%) oxyhyperglycemic, and 25 cases (21.0%) non diabetic. 2. No incidence was found in the time of development or age distribution between the cases of liver cirrhosis with diabetic glucose tolerance and that combinated with primary diabetes or diabetic without liver disease. 3. Incidence of the abnormal glucose tolerance in the cases with liver cirrhosis did not correlate with the duration of the disease. 4. The abnormality of GTT showed high incidence in accordance with severity of liver injury in both of liver cirrhosis and hepatitis, however, it was impossible to find any significant correlation between the grade of abnormal glucose tolerance and the data of liver function test or the histological changes of the liver. 5. The glucose tolerance was not always aggravated inspite of progression from hepatitis to liver cirrhosis. The shift of the GTT and that of liver function disturbance were not always correlate with each other in both liver cirrhosis with abnormal glucose tolerance and that combinated with primary diabetes. 6. The grade or incidence of various abnormalities from such points of view was high in accordance with the grade of abnormal glucose tolerance in cases with liver cirrhosis and no significant difference was seen as compared to the primary diabetics that the cases showing more than 100 mg/dl of maximum fasting blood sugar in its duration, the cases with glycosuria before administration, or during GTT, occurance of the cases excreting more than 5 grams of glucose in whole day urine, influence of treatment with glucocorticoids, vacuolated nuclei occured in the liver cells, or development of complications related to the primary diabetes. It revealed that the stronger the abnormality of GTT in liver cirrhosis was, the more diabetic results. 7. The rate of abnormality of the results of prednisolonefrimed GTT was found to be higher in the cases of liver cirrhosis as compared to that of diabetes alone. 8. The incidence of occurence of vacuolated nuclei on the liver cells and of having complications related to primary diabetes was not different in the cases of liver cirrhosis with abnormal glucose tolerance or combinated with primary diabetes from that of chemical diabetes or clinical diabetes. 9. It might be possible to conclude from these results that the characteristics of abnormal glucose tolerance found in liver cirrhosis is similar to that found in primary diabetes and that the cases of liver cirrhosis with abnormal glucose tolerance might include primary diabetes or pancreas injury.
80 subjects with liver cirrhosis selected for this study were divided into 2 groups, 24 cases were considered to have combinated with primary diabetes and the remaining 56 cases were not. The latter was classified into groups of probable diabetics, chemical diabetics, clinical diabetics, and non-diabetics according to the diagnosis from GTT. The results of tolbutamide test obtained were compared not only with each group with and without primary diabetes, but also with pathologic stage of the liver. The results were as tfollow: 1. Of 56 cases of liver cirrhosis wihout primary diabetes, 12 cases (21.5%) revealed the diabetic curve in the tolbutamide test, and remaining 33 cases (58.9%) were normal, on the other hand, of 24 cases combinated with primary diabetes, 21 cases (87.5%), 3 cases (12.5%), and no cases, respectively. 2. Observing the incidence of the abnormality of TTT in the subjects with liver cirrhosis from the view of the diagnosis of GTT, 11.8% of 18 cases with non-diabetic GTT, 47.0% of 17 cases with probable GTT, 61.9% of 21 cases with diabetic GTT, showed no abnormality, while, 24 cases combinated with primary diabetes were all found to be abnormal. Although the incidences described were high by about 10% than that found in each group of primary diabetics without liver cirrhosis, the frequency of the cases with delayed recovery in each group of liver cirrhosis was high by about 10% than those of primary diabetics. 3. Although the mean blood glucose curve following tolbutamide infusion in the subjects with liver cirrhosis without combination of primary diabetes situated between those of normal controls and of clinical diabetics, however, no significant difference could be observed in the mean blood glucose curve comparing the groups of liver cirrhosis with non-diabetic, probable, chemical diabetic GTT, and of combination with primary diabetes with those without liver cirrhosis. 4. Not only initial fall and subsequent rise in the blood glucose level, but also the duration requiring for reaching the minimum value following tolbutamide infusion were similarly delayed in both subjects with liver cirrhosis and primary diabetics without liver cirrhosis, and these delays became greater proportional to the grade of the impairment of their GTT. 5. It was impossible to find any significant correlation between the results of TTT and the duration of liver disease, the results of liver function test, or the histological changes in the liver, however, the frequency of impairment of TTT was greater in the subjects with ascites as compaired to that without it. 6. The incidence of abnormality of tolbutamide test (TTT) in the subjects with impaired prednisolone-primed glucose tolerance was significantly greater than that of the cases without impairment of the test. 7. No significant correlation was observed between the results of TTT and of secretin test. 8. The response of immunoreactive insulin following tolbutamide infusion in the subjects with liver cirrhosis was higher than those of diabetics or normal subjects. 9. It was concluded from these results that the abnormal glucose tolerance found in the subjects with liver cirrhosis could not be distinguished by using the TTT from that derived from pancreatic factors.
In recent years, new theory concerned upon the estriol biosynthesis in the pregnant was developed remarkably. Diczfalusy and others demonstrated that DHA from foetal adrenal was the main precurssor of estriol in the pregnant. Their approaches for this problem were tried mainly with in vitro incubation and circulation studies. In this study, the approach was tried with the determination of steroids in cord blood, maternalblood, maternal urine and urine of newborn. Androstanedion, Δ4-androstenedione, DHA, androsterone and etiocholanolone in cord blood were deter minated by new method, which was cosisted of following procedure. 1) 3s Hydrolysis (free steroid extraction, hydrolysis with β-glucuronidase in phosphatete buffer and transesterification with methyl-green and acetic acid. 2) Florisil column chromatography. 3) Thin layer chromatography. 4) Colorimetry following Lieberman, colour development with modified zimmerman reaction. The results of this determination were as following. In two cases, five androgens in cord blood and maternal peripheral blood, eight fractions of estrogens and nine fractions of 17-Ketosteroids in maternal urine, were determined. Also nine fractions of 17-Ketosteroids and four fractions of estrogens were determined in pooled urine of newborn. The results of these determination were as followings. 1) DHA level in cord blood was higher than that in maternal blood. But DHA level in maternal blood was cosiderably high. DHA in cord blood: 88.4μg/100ml, DHA in maternal blood: 37.3μg/100 ml It should be indicated that, thinking of maternal blood volume, maternal DHA is important for estriol biosynthesis. 2) Although DHA level in maternal urine was high, but DHA level in urine of newborn was low. Urinary DHA in mother: 1111.3μg/day, Urinary DHA in newborn: 10.050.0μg/day By this results, it is difficult to think that all estriol should be the product of foetal DHA. 3) Urinary estriol in early post-natal days was relatively high and then decreased to 10 and less μg in seven days of newborn. This indicates that the stored estriol was excreted in post-natal days. By these results, it should be clear that estriol biosynthesis is done not only in foetoplacentar unit, but also in maternalplacentar unit. It is claimed that steroids metabolism in pregnancy, as was seen in estriol biosynthesis, must be examined not as foeto-placentar unit but as foeto-placentar-maternal relation.
There is a great need for prevention against parasitosis in the field of community health, though in actual practice, the mass examination for parasite carriers has not succeeded to get enough rate of receiving the examination. Because of this problem the author has investigated the conditions the performance of health practice against parasitosis, systematically. In order to get some criteria for the evaluation of the parasite control in communities, the author has investigated statistically the results of parasitic egg examination among general residents comparing to those of the school children at the same communities on O-prefecture. The objects were selected among the areas in this prefecture officially designed for “the promotion of preventive practice against ancylostomiasis”. The studies have been carried out statistically and the results checked by the field surveys to learn the social factors influencing the receiving rate of examination and the efficiency of the practice. The results of the studies have been as follows: 1) By examining annual change of correlation between the rates of general residents and those of the school children in the same communities, there have been observed differences among the kinds of parasites. 2) Concerning “the special areas for preventive practice against ancylostomiasis” the parasite carries among the children has showed high correlation with those among general residents at the beginning of the designation as the special areas. This correlation has changed as the preventive practice proceeded. About ascariasis and other parasitoses, the correlation between the children and general residents have maintained relatively unchanged in high value. The differences of the elapse between the numbers of ancylostomiasis and the others could be derived from the ecological specialities and the mode of infection. 3) Correlation between the residents and children was high in ancylostomiasis when the receiving rate was over 80% and the same could be said in ascariasis when it was over 60%. 4) Also high correlation were observed between 1 to 3% of ancylostomiasis among school children, and under 15% of ascariasis among them. 5) These statistical results have been investigated expecting to get some criteria for evaluation of preventive practice. 6) The results of field survey about factors influencing on these data have been described.
On 237 cases of acute leukemia admitted to our clinic from 1953 to 1965, the main symptoms and hematological findings in the initial stage were statistically evaluated. The observation time was devided into 3 periods; I (19531957), II (19581961)and III (19621965). 1) Peripheral blood picture: Severe cases with hemoglobin below 40% (Sahli) were 57.0% during the Ist period and were 28.2% during the IIIrd period. On the other hand mild cases with hemoglobin above 70% were 9.2% during the Ist period and increased to 17.2% during the IIIrd period. Similar tendency was observed on red blood cell count (R. B. C.). Severe cases with R. B. C. below 2×106 were found in 66.2% during the Ist period and decreased to 31.0% during the IIIrd period. Mild cases with white blood cell count below 1×104 were found in 33.9% during the Ist period and increased to 40.7% in the IIIrd period. Mild cases with leukemic blasts below 10% showed an increase from 22.6% in the Ist period up to 34.9% in the IIIrd period. Mild cases with thrombocytes above 1×105 increased from 13.1% in the Ist period up to 17.6% in the IIIrd period. 2) Myelogram: Mild cases with leukemic blasts below 20% increased from 33.9% in the Ist period up to 38.0% in the IIIrd period. Severe cases with erythroblastic cells below 5% gradually decreased from 75.4% in the Ist period up to 64.9% in the IIIrd period. Mild cases in which we maintained erythroblastic cells above 15% increased from 8.8% inthe Ist period up to 22.1%in the IIIrd period. 3) Clinical symptoms: Mild cases without hemorrhagic diathesis increased from 29.2% in the Ist period up to 42.0% in the IIIrd period. While severe cases with remarkable hemorrhagic diathesis gradually decreased from 34.6% in the Ist period up to 19.6% in the IIIrd period. Cases with hepatomegaly of more than 2 finger breath showed a slight decrease from 27.4% in the Ist period up to 20.5% in the IIIrd period. No conclusive tendency was observed on splenomegaly. Cases without palpable lymphnodes were increased from 35.0% in the Ist period to 41.7% in the IIIrd period, while cases with remarkable lymphadenopathy decreased from 18.3% in the Ist period to 13.1% in the IIIrd period. Cases with high grade fever decreased from 29.0% in the Ist period up to 13.3% in the IIIrd period. From these results the author confirmed that relatively mild cases of acute leukemia on admission have gradually increased recently. In addition the tendency of decrease of monocytic leukemia and increase of acute lymphocytic leukemia was observed.
The development of major side effects observed during steroid therapy was statistically evaluated on 266 leukemic patients admitted to Hiraki clinic from 1954 to 1964. These patients were devided into 2 groups, one treated with stercid, the other treated without steroid. 1) The incidence of infection was 27.7% in the steroid group, while it was 15.0% in the non steroid group. The incidence of mycosis was 7.3% in the steroid group, being 4.3 times that of non-steroid group. 2) The incidence of gastrointestinal ulcer was 7.3% in the steroid group, while it was 1.7% in the non steroid group. 3) The incidence of diabetes mellitus and psychiatric disturbances was observed only in the steroid group. These results indicated that infection, especially mycosis, gastrointestinal ulcer, diabetes mellitus and psychiatric disorders were to be regarded as iatrogenic diseases during the steroid therapy of leukemia.
Effect of chloroquine on the motor activity of rabbit stomach were studied with or without combination of ATP-2Na by the balloon technique. 1) Four different doses of chloroquine 1, 3, 5 and 10 mg/kg were injected intravenously. At the doses of 1 and 3mg/kg the drug showed no effect on the gastric motility while at the doses of 5 and 10 mg/kg it showed a marked inhibitory action on the motility and tonus lasting for 48minutes. 2) ATP-2Na was administrated also intravenously in the doses of 3.1 and 6.2 mg/kg. At both doses the drug stimulated the gastric motor activity and tonus after a transient inhibition lasting for an average of 10 minutes. 3) When the motor activity of the stomach was accelerated by ATP-2Na, the addition of chloroquine showed either no effect or proved to be less inhibitory than when the latter was apllied alone. 4) Thus it is clear that chloroquine inhibits the gastric motility in rabbits and that ATP-2Na is antagonistic against chloroquine in this respect.
Effects of chloroquine on the autonomic peristalsis and tonus of the isolated rabbit ileum were studied by the Magnus' method, and the mechanisms of the drug action were investigated with combination of sympathicomimetic and parasympathicomimetic drugs and with some other drugs. 1) Chloroquine in the concentration of 20200γ/cc caused a diminution of autonomic peristalsis and tonus of the isolated ileum, and was noted to possess antagonistic actions against the intestinal contration induced by histamine, acetylcholine and BaCl2. 2) Chloroquine was found to possess a direct relaxant action on the gut smooth muscle rather than to act through the autonomic nervous system and also to possess antihistaminic and antiacetylcholinic actions.
Effects of chloroquine on gastric and bile secretion in rabbits were studied by intravenous injection of the drug. Furthermore the excretion rate of the drug into gastric juice and bile was determined. 1) Using the continuous collection technique, the basal secretory rate of gastric juice was found to decrease gradually with the lapse of time. However doses of 5 and 10 mg/kg of chloroquine, when injected intravenously, showed down the basal secretory rate. 2) On the other hand, these doses of the drug caused an elevation of gastric free acidity, and this stimulant effect on the acid secretion was more notable in the dose of 10 mg/kg, lasting for 3 hours after the intravenous injection. 3) Following intravenous injection of 10 mg/kg of chloroquine the drug was found to be excreted into gastric juice, yielding the concentration of 32.481.0γ/l after 20 minutes and reaching the maximum of 659.8792.0γ/l after 3 hours. This concentration tended decrease after 4 hours. 4) Intravenous injection of chloroquine showed no effect on bile secretion by the same continuous collection technique. 5) The dose of 10 mg/kg of the drug was injected intravenously and it was shown that the drug was excreted also into bile. The concentration curves rose rapidly to the maximum of 531.1γ/l 1 hour after the injection and slowly returned to the level of about 40% of the maximum after 4 hours. 6) These results show chloroquine has a stimulant action on gastric secretion, particularly on gastric acid secretion, but has no significant effect on bile secretion in the doses administered.
Experimental studies on viability of the kidney preserved under hyperbaric and hypothermic condition were performed on dogs. The left kidney was removed and perfused with refrigerated (4°C.)low molecular weight dextran in electrolytic solution containing heparin. Immediately after perfusion, the kidney was immersed in a same solution as used for perfusion and stored in a hyperbaric chamber for 6, 12 and 24 hours, respectively under 3 atmospheres of oxygen pressure and 4°C. Following the storage, the kidney was reimplanted in the left iliac fossa of the original donor. The contralateral kidney was removed 3 weeks after the renal autotransplantation. Following results were obtained. 1) Perfusion of the kidney with low molecular weight dextran in electrolytic solution resulted in no significant increas of the kidney weight and in no development of interstitial edema. 2) There was no correlation between the histologic appearance of the preserved kidney and its viability. 3) After the contralateral nephrectomy all two kidneys preserved for 6 hours and two out of three kidneys preserved for 12 hours were able to sustain life but all 9 kidneys preserved for 24 hours were unable. 4) The precise role played by hyperbaric oxygenation in these experiments was difficult to asses but hyperbaric oxygenation has beneficial effect on renal preservation and limitation of preservation time was considered between 12 and 24 hours.
Study on the frequency of hypocatalasemia, heterozygote of acatalasemia, has an extremely important bearing on acatalasemic gene distribution. For the identification of hypocatalasemia or for its screening, it is essential to study the methods of quantitative analysis of blood catalase. For such a quantitative analysis as well as for the screening test, a modified form of Euler-Josephson's method has been used by Okayama University Medical School and by Hiroshima and Nagasaki ABCC groups (Atomic Bomb Casuality Commission). This method is based on titration with potassium permanganate (KMnO4) to determine decrease of hydrogen peroxide (H2O2) by blood catalase. On the other hand, Beers et al. described a method of liver catalase assay for measuring the breakdown of hydrogen peroxide by estimating the decrease in the optical density at the wave length of 240mμ. As it is possible to check directly the decrease of H2O2 with this method, it seems to be the most simple and highly reliable method with little error. The purpose of this paper is an attempt to determine the catalase activity of human blood and to apply the identification of hypocatalasemia and normal individuals and, if possible, to employ as an assay method for investigating hypocatalasemic blood catalase from the aspect of enzyme kinetics by spectrophotometry (ultraviolet method). In this part an attempt was made to determine the catalase values of some blood samples. The results of this determination were compared with those obtained by the titration (modified Euler-Josephson's method) with the same samples under approximately the same condition. It was observed that the catalase values as estimated by the ultraviolet method (UV method) were about 70 to 80 per cent lower than those by the titration.
For the spectrophotometry a Hitachi Perkin-Elmer 139 type spectrophotometer with a constant temperature cell chamber and autorecorder was used. The measurements were conducted under the following conditions (final concentration of H2O2 0.0125 Mol in 0.01 Mol phosphate buffer, pH 6.8), which showed the identical conditions with a exception of H2O2 being 2.5 times the concentration employed in the titration method. Both assays were carried out at 37°C. The results by ultraviolet spectrophotometric method (UV method) were compared with those obtained by titration; the values obtained by UV method were about 90% of those by titration, and proved that each values showed a good correlation. Therefore this method will sufficiently serve for the measurement of human blood catalase activity or for the screening of hypocatalasemia.
The present communication deals with the principle of measuring and calculating the catalase activity of human blood by UV method. Under the conditions previously described, it has been clarified that the reaction of catalase-hydrogen peroxide practically follows the first order kinetics within 30-120 seconds. The velocity constant, k, seems to have no concern with the substrate concentration within the range of 0.005-0.025 mole. Catalase values, Kcat, measured under room temperature, are about 10% lower than those taken at 37°C. It has been found that measurements of the catalase activity have to be taken within 5 minutes after hemolysis
It is generally accepted that modified Euler-Josephson's method of titration gives the value of catalase activity, “Kcat” as the standard value. Whereas by the author's method taking the value of catalase activity as “k” measured, for example, at room temperature, recorded on an autorecording apparatus, it will be seen that we get the formula, Kcat=1/1.035 (100/90K+0.513) The present study has led to the following conclusions: This method is characterized by the fact that it is useful for the screening test for hypocatalasemia as well as for simultaneous measurement of the catalase activity in human blood. It is suggested that the level of the screening be fixed more appropriately at 2.4. Attempts have been made to use a portable UV-colorimeter to the screening but it seemed that this apparatus is not suitable for the purpose. This method can measure not only the activity of purified catalase but also that of a partially purified catalase. It can also be applied for the measurement of catalase activity in tissues other than blood. It is anticipated that this method can also be useful for the investigation of hypocatalasemic blood catalase from the aspect of enzyme kinetics.
A case of recurrent spontaneous pneumothorax was reported. Patient, a 18-year-old male, had recurring episodes of the chest pain and dyspnea for the last two years. Abnormal shadow, partially collapsed lung with emphysematous bullae, was found in the left upper lobe on a chest roentgenogram during the course. On thoracotomy, two bullae with air leakage, each being over tip-of-thumb sized, were recognized in the left upper lobe. Extirpation of the bullae was performed without difficulty. Histological appearance was characteristic of organized scar tissue.