Some difficulties have remained to be overcome for the effective statistical evaluation of the clinical efficacy of the therapeutic agents for peptic ulcer; that is quantitative evaluation of sequential X-ray and gastroscopic films, collection of cases identical in many biological factors and so on. In this report, we attempted to investigate the validity of the method of paired comparison by double blind controlled study for the evaluation of clinical efficacy of one of the therapeutic agents for peptic ulcer, dehydrocorydaline. Followings are the conclusions to be obtained at the present time. 1) The method of paired comparison was considered valid to obtain satisfactory informations from X-ray and gastroscopic films for the statistical analysis. Concordance of judgements among judge doctors was quite satisfactory. 2) Although no difference of statistical significance was detected for any factors by Scheffe's analysis of variance, positive trend was demonstrated in dose-response in respect of difference of main effects (drug efficacy). It should be mentioned, however, that statistical difference of significance was detected (0.05 P 0.10) just in case comparison among dose levels by Kruskal-Wallis' H test was made during the first month period. 3) Other interesting informations obtained in this evaluation include; a tendency of greater effect in a group of decreasing dosage than in that of increasing dosage during the trial period, a tendency of positive dose-response effect only in cases with a single round gastric ulceration, a greater therapeutic effect of dehydrocorydaline during the first month period, a gradual decrease with passage of time in the rate of improvement of peptic ulcer. These informations are well in concordance with our daily clinical impressions. 4) As for side effects, dry mouth was complained of in only one case receiving 120mg per day, the degree of which was minimal. 5) Further investigations are necessary for comparison of this method with those which have hitherto been used for evaluation of drug efficacy of the therapeutic drugs of peptic ulcer.
The purpose of this report is to present the deconjugation of bile acids by numbers of strains of bacteria in the small intestine and feces. The small intestinal juice was aseptically aspirated by a double lumen tube with a rubber cover on the tip deviced by us ("Fukushima Type 1"). Bile acids were analyzed with thin layer chromatography. The results: 1) Among aerobic bacteria, species of which all of the strains split conjugated bile acids was enterococcus, and most of the strains split were Staphy. epidermidis and Lact. bifidus. Species of which none of the strains split were Esch. coli, Esch. communior, Esch. freundii, Lact. plantarum, Lact. acidophilus, Lact. buchneri, Lact. cellobiosus, Lact. bulgaricus, Staphy. aureus, Aerobacter aerogenes, Pseudomonas aeruginosa, candida, proteus, serratia, and almost none of the species split was Intermediate coliform bacilli. 2) Among anaerobic bacteria, species of which all of the strains split were Bact. vulgatus, Bact. thetaiothaomicron, Bact. uniformis, Coryne. granulosum, Coryne. avidum, Peptostrept. putridus, E. lentum, Pept. grigoroffii, Pept. anaerobius, V. orbiculus, and most of the strains split were Coryne. diphtheroides, E. parvum, Peptostrept. intermedius. Species of which none of the strains split were Coryne. parvum, Peptostrept. micros, V. alcalescens, V. parvula, Catena. catenaforme, and Catena. filamentosum. 3) All or none, or almost all or none, of the strains of each species tested split conjugated bile acids, and it seems probable that the presence or absence of this ability would be a proper character of each species.
The Pancreozymin-Secretin test seems to have some limitation for the diagnostic evaluation of the pancreatic exocrine function. Some basic experiments were performed to investigate the reaction mechanism of pancreatic cells to pancreozymin stimulation. 1) Pancreozymin stimulates and increases the secretion of amylase in rat pancreas slices. 2) 30 minutes are needed until the newly synthesized enzyme is transported and excreted from the cells with pancreatic stimulation. 3) The effect of pancreozymin on exocrine cells seems to accelerate the first step of the transportation of the newly synthesized ribosomal enzymes to the menbrane system. 4) The synthesis of RNA and of protein by pancreatic cells is stimulated by pancreozymin in vitro. 5) Amylase secretion is still stimulated by pancreozymin when synthesis of RNA or of protein is inhibitted. The activity of ATPase and of alkaline phosphatase in the cells is increased by pancreozymin, and the turnover rate of phospholipid fraction of the cell is stimulated by pancreozymin. From these results, it seems that the increase of enzyme secretion is initiated through the energy metabolism in the cell, but not through the stimulation of protein synthesis. 6) Both theophyllin and dibutyryl 3'5' cyclic AMP stimulate the secretion of amylase in rat pancreas slices. And they stimulate the transport of the newly synthesized ribosomal enzyme to the membrane system like pancreozymin. 7) Both theophyllin and dibutyryl 3'5' cyclic AMP do not stimulate the synthesis of the protein in vitro. 8) Perhaps there may be some differences in mechanisms between the energy metabolism by pancreozymin and by cyclic AMP.
Non-erythropoietic component of early labelled bilirubin was studied in 7 acute infectious hepatitis patients (in recovery stage), 18 cirrhotic patients and in 7 control subjects with plasma and bile, after injection of 2.5μc of [4-14C] δ-aminolaevulinic acid intravenouslly. All cases were examined in the nonicteric stage (total serum bilirubin below 1.5mg/dl). The mean cumulative radioactivities in 4 hours in the control subjects were 29.6±4.7×103 D.P.M./mg x hrs. in plasma, and 27.0±1.2×103D.P.M./mg x hrs. in bile. In acute hepatitis patients (in recovery stage), the mean cumulative radioactivities in 4 hours in both plasma and bile were approximately twice as large as that in control subjects. (P<0.001 and <0.005 respectively). In cirrhotic patients with large sized liver scintigrams, the mean cumulative radioactivities in both plasma and bile were approximately 1.4 times as large as that in control subjects. (P<0.001 both in plasma and bile). In cirrhotic patients with medium sized liver scintigrams, the mean cumulative radioactivities in both plasma and bile were approximately the same as large as that in control subjects. In cirrhotic patients with markedly small sized liver scintigrams, the mean cumulative radioactivities in both plasma and bile were approximately one half as large as that in cotrol subjects. (P<0.001 both in plasma and bile). In the cirrhotic patients, two peaks of bilirubin activities were observed in many cases in both plasma and bile. The more the cirrhosis advanced with the liver reduced in size, the more the cases showed two peaks.
One hundred-seventy five patients including 33 with pancreatic cancer, 45 with chronic calcifying pancreatitis, 23 with choledocholithiasis, and 45 with cholelithiasis were subjected to pancreozymin-secretin test for the purpose of providing more acceptable criteria for defining an abnormal function of the exocrine pancreas. The diagnosis was established by radiologically demonstrable calcification of the pancreas in chronic calcifying pancreatitis and all others were done at operation. Abnormal values of five parameters, total volume, maximal bicarbonate concentration, total bicarbonate output, maximal amylase concentration and total amylase output, were obtained from M.V.±2.S.D., calculated from 43 normal persons. To separate the pancreatic juice from the bile as our method, was most important thing to make an accurate criteria for this test. Diagnostic value was not enhanced by adding new parameters, maximal amylase concentration and total bicarbonate output, to classical three parameters. Among three parameters, maximal bicarbonate concentration was most sensitive index in chronic pancreatitis and total amylase output in pancreatic cancer. The 60-minute volume was the least reliable of three parameters.Therefore, the item of abnormal parameter should be employed instead of numbers of abnormal parameter. Abnormal low value as well as abnormal high response of blood amylase after pancreozymin secretin administration should be checked for detecting abnormal pancreatic function.