I tried several radiological experiments on the contrast medium and some other conditions of the radiography, and concluded that the most suitable substance for operative cholangiography to detect gall stones in biliary ducts was 30% Urografin diluted with physiological Saline after trying several kinds of reagents at various concentrations. According to the results cited above, 121 cases of biliary tract disorder were studied. Among 99 patients with cholelithiasis, stones were found in the biliary ducts in 20 cases (20.2%). One case (1.0% in cholelithiasis) turned to be residual stone and surgery was performed for it again. About operative cholangiograms upon 121 cases, analysis of the anatomic configurations of the bile ducts were performed. During operations, the base level of the biliary pressure and the resistence of the sphincter of Oddi were measured in 55 cases. The base level of the biliary pressure was found from 30mm to 310mm water, 128.5mm water on the average and the resistence of the sphincter of Oddi was showed from 60mm to 520mm water, 327.5mm water on the average. Choledocholithiasis apparently made them high. Difference of these two pressures, namely the base level of the biliary pressure and the resistence of the sphincter, was great in the cases with moderatly dilated biliary duct (1.1-2.0cm in diameter on X-ray image). No clear correlation was observed between X-ray picture of the terminal part of common bile duct and the biliary pressure.
Serum cholesterol-esterase activity was measured and discussed its siginificance in 200 patients with mainly surgical disease. The following results were obtained; 1. No decreased enzyme activity was observed in benign and non-inflammatory disease such as gall stone disease, gastric ulcer, Grave's disease and Banti's syndrome comparing with normal subject. But decreased enzyme activity was observed in hepatic parenchymal disease such as hepatitis and cirrhosis and in malignant tumor. 2. More thna one year after cholecystectomy slight depression of the enzyme activity was observed, but its significance is unknown. 3. There was a close correlation between serum cholinesterase and serum cholesterol-esterase in chronic hepatitis and cirrhosis. 4. There was a correlation between serum cholinesterase and serum cholesterolesterase in malignant tumor. 5. In a patient who had radical operation for malignant tumor of the digestive organ, decrease of the enzyme activity was observed 7 to 10 days after surgery. 6. Returning of the enzyme activity to the almost normal level was observed, within a month after the cause of the depression was taken away.
I have studied histochemical changes with eight different hydrolytic and oxidative enzymes in 31 gastric ulcers, 11 duodenal ulcers, 11 experimental gastric ulcers of rats and 70 gastric and duodenal mucosa with other various gastric diseases. 1) Increased activity of various enzyemes were observed in the granulation tissues under the ulcers of stomach and duodenum. Alkaline phosphatase (A.lP) showed marked activity, while Lactic dehydrogenase (LDH), DPN diaphorase (DPNd) showed moderate activity and Acid phosphatase (Ac. P), Adenosine triphosphatase (ATPase), Aminopeptidase (Amp) showed slight activity. Esterase (Est), Succinic dehydrogenase (SDH) showed very little activity. Experimental ulcers of rats showed the same results. 2) Fibfoblasts, collagen fibers and capillary walls in the granulation tissue under the ulcers showed marked activity of Al. P, especially in the young granulation tissue. Healing scar tissue showed little activity. The fact suggests that Al. P is related to the healing of ulcers. 3) The enzymes including Al. P, LDH, DPNd, Ac. P, ATPase and Amp showed increased activity in the granulation tissue, while they showed decreased activity in the scar tissue. I concluded that metabolism was very active in the healing granulation tissue. 4) Capillary walls in the granulation tissue showed marked activity of Al. P and ATPase. These enzymes may be related to the transport of the material through the capillary walls. 5) Histiocytes in and around the necrotic layer were plump and showed marked activity of Al. P and Est. They may be related to the cleaning of the base of ulcers. 6) Normal gastric mucosa did not show any activity of Al. P and Amp, while mucosa showing intestinal metaplasia showed marked activity of these enzymes. In addition to these enzymes, mucosa with intestinal metaplasia showed marked activity of the other enzymes and showed the same distribution of enzyme activity as in duodenal mucosa.
In comparative experimental and clinical studies with different doses of TRASYLOL for the treatment of acute pancreatitis the following results have been obtained: 1) Use of TRASYLOL from early after the onset of experimental pancreatitis in the dog was, even when the dosage was low, effective as compared with the control. The results of treatment were evidently much better in a group given high dosage than in the group given low dosage TRASYLOL. This effect was definitely better than those obtained from the conventional way only. 2) Clinically TRASYLOL in different dosages was given in addition to the conventional therapy. Taking the analgesic effect, the improvement of the abdominal findings, and the decrease of the serum amylase and catalase as a standard of evaluation, it turned out, that the high dosage TRASYLOL group of patients (1-200, 000 KIU per day) showed the most rapid improvement, followed by the low dosage group (1-50, 000 KIU per day). The conventional therapy alone showed less satisfactory results. 3) Examination of the correlation between the starting time of TRASYLOL treatment and its efficacy revealed that the drug is most potent when given at an early stage in the course of the development of acute pancreatitis. 4) Cases of acute pancreatitis with marked kidney function disturbances had the kidney function disturbances rapidly improved by TRASYLOL. 5) Even in high dosage treatment no side effect of the drug was observed. From the above reported experiments it was concluded that in the early stage of acute pancreatitis high dosage TRASYLOL treatment is of a significant therapeutical value. In addition, its beneficial effects are expectable against intoxication symptoms by pancreatitic toxin, such as kidney function disturbances in acute pancreatitis.
In view of the central role of liver in the regulation of carbohydrate metabolism, deranged carbohydrate metabolism might be expected in both acute and chronic liver disease. The present study was performed in order to investigate carbohydrate metabolism in 112 patients with a variety of liver diseases, including acute hepatitis 14, active chronic hepatitis 19, inactive chronic hepatitis 25, fatty liver 4, hepatoma 12 and cirrhosis 38. Blood glucose changes were studied following glucose or tolbutamide loading and after administration of glucagon. The followings were administered: glucose, 50gm. by mouth; tolbutamide, 50mg. per kilogram of body weight by mouth; and glucagon, 1mg. intravenously. Venous blood samples were withdrawn in the fasting state and at appropriate intervals following glucose, tolbutamide or glucagon administration. Results are as follows: 1. Fasting blood glucose: Values below 59mg. per 100ml were found in 12 per cent of 17 determinations in 14 patients with acute hepatitis, in 14 per cent of 35 determinations in 19 patients with active chronic hepatitis (p<0.05), in 12 per cent of 33 determinations in 25 patients with inactive chronic hepatitis, in 3 per cent of 80 determinations in 38 patients with cirrhosis and in 5 per cent of 109 determinations in 109 controls. None of patients with fatty liver and hepatoma showed the values below 59mg. per 100ml. Hyperglycemia above 120mg per 100ml. was not obtained in patients with liver disease except for cirrhotics, which showed hyperglycemia in 11 per cent of 80 determinations in 38 patients. (p<0.01) 2. Oral glucose tolerance: Patients with liver disease were placed in one of three groups (i.e."mormal", "impaired"and"diabetic".) according to the result of the oral glucose tolerance test. The results were typically"diabetic"in 12 per cent of patients with acute hepatitis (p<0.05), in 7 per cent of patients with active chronic hepatitis (p<0.05), in 19 per cent of patients with inactive chronic hepatitis (p<0.01), in 39 per cent of patients with cirrhosis (p<0.01), in 43 per cent of patients with fatty liver (p<0.01), in 27 per cent of patients with hepatoma (p<0.01), and in 4 per cent of controls. Hypoglycemia below 59mg. per 100ml. at 3 hours blood sugar level in glucose tolerance test was significantly increased in frequency in patients with acute hepatisis and active chronic hepatitis. 3. Hyperglycemic response to glucagon: Glucagon was administered intravenously to 8 normal subjects, 49 patients with various liver diseases and 12 patients with diabetes mellitus. The decreased hyperglycemic response to glucagon was obtained in patients with acute hepatitis, active chronic hepatitis and cirrhosis of the liver. In contrast to the findings in the cirrhotic patients, the mean maximum hyperglycemic response to glucagon was significantly increased in patients with fatty liver. The hyperglycemic response in patients with diabetes mellitus without imparied liver function was similar to those of patients with fatty liver. 4. The maximum blood sugar decrease after the oral administration of tolbutamide was 56.8±9.0 per cent of fasting level in controls, 69.9±12.6 per cent of fasting level in cirrhotics with diabetic glucose tolerance(p<0.05), and 58.2±11.9 per cent of fasting level in cirrhotics without diabetic glucose tolerance. 5. Mechanism of impaired carbohydrate metabolism in liver disease was discussed.
The present study was undertaken to clearify the difference of metabolism between glucose, fructose, sorbital and xylitol in liver disease. Data were obtained from 5 normal subjects and 10 cirrhotic patients. 500ml. of a 5% solution of glucose, fructose, sorbitol or xylitol was administered intravenously in 60 minutes. Venous blood samples were withdrawn for the determination of glucose, lactate and pyruvate levels before, during and after the administration of carbohydrate solution. Blood glucose level did not change significantly after the, administration of sorbitol or xylitol both in controls and cirrhotics. Fructose loading caused the increase of blood sugar level in cirrhotics as well as in controls. In cirrhotic patients, glucose or fructose administration caused the marked increas of blood puruvate level more than that seen in controls, whereas sorbitol administration did not raise pyruvate level significantly. Pyruvate level did not changed following the administration of xylitol both in controls and cirrhotics. In cirrhotic patients, glucose or fructose administration raised blood lactate level markedly. In contrast to the rise in lactate level after glucose or fructose, there was no such increase after sorbitol or xylitol loading. The mean urinary excretion of sorbitol or xylitol in 24 hours following parenteral administration of sorbitol or xylitol was 12.95% and 11.76%, respectively in controls. In cirrhotic patients the urinary excretion of these carbohydrate increased slightly, but the difference between controls and cirrhotics was not statistically significant. The animal experiments demonstrated that in the acute stage of liver injury, glucose-u-C14, sorbitol-u-C14 and xylitol-u-C14 are inefficiently oxidized to C14O2 in the livers of rat treated with carbon tetrachloride. CO2 production from xylitol-u-C14 or sorbitol-u-C14 returned to the control level more quickly than that from glucose-u-C14. The in-vivo study revealed that sorbitol or xylitol is an efficient precursor of liver glycogen as well as glucose. Sorbitol or xylitol is expected to be used in patients with liver disease showing elevated blood lactate and pyruvate level, or in patients with chronic liver disease accompanied by diabetes mellitus.