Since the introduction of various hypotensive drugs into the clinical use for treatment of essential hypertension, many advantages have been expected for the prognosis in hypertensive patients. At present, however, very few reports are found about long-term observation on the effects of continuous therapy. No systematic investigation has been reported on changes in RBF, retinal findings and ECG in numbers of patients, which were resulted from the prolonged blood pressure reduction. In this study, 165 patients with moderate or severe essential hypertension were treated with various hypotensive drugs over the periods of 6 to 46 months continuously, and the hypotensive responses, changes in maintenance dosage of drugs, and effects on RBF, retinal findings and ECG were observed and following results were obtained. The percentages of effective cases, in which the continued blood pressure reduction exceeding 20/10 mmHg below pretreatment control levels was achieved by the single therapy, were 30% with Rauwolfia alkaloids, 29% with Veratrum alkaloids, 50% with hydralazine, 38% with hexamethonium and 50% with pentolinium. In the combined therapy, the above described hypotensive effects of Rauwolfia plus Veratrum alkaloids, Rauwolfia plus hydralazine, Rauwolfia plus hexamethonium, Rauwolfia plus pentolinium, and Rauwolfia plus hexamethonium or pentolinium plus hydralazine were observed in 40%, 55%, 76%, 81% and 91% of patients respectively. The combined therapy seems in general more effective than the single therapy so far as the hypotensive effects are concerned. Maintenance dosages of hypotensive agents were observed to have a tendency to decrease with duration of treatment when sufficient reduction of blood pressure was maintained. Daily requirements of drugs in summer were about 50 to 80% of those in winter. Of 79 treated patients, 31 cases (39%) showed significant increase in RBF measured by PAH clearance method, and 10 cases (13%) showed decrease in RBF after treatment. It was observed that the longer the duration of treatment the larger the percentage of cases whose RBF increased by the therapy. This percentage was also found to be larger in cases which maintained sufficient blood pressure reduction. In 22 cases (18%) of 124 treated patients, retinal findings showed improvement in grade of Keith-Wagener classification, while their aggravation was seen in 4 cases (3%). The rate of improvement increased with duration of treatment, and was larger in cases with good hypotensive response. ECG findings were improved in 28 cases (44%) of 63 treated patients and worsend in 5 cases (8%). The rate of improvement was larger in cases which maintained sufficient hypotensive response and it increased with duration of therapy. Improvement of ECG findings appeared relatively earlier comparing with that of RBF or retinal findings. It is concluded that adequate and prolonged treatment with hypotensive agents results in significant improvements of objective manifestations of various organs including the kidney, fundi and the heart in patients with essential hypertension.
Many reports on Giardia lamblia have been published since it was discovered by Lambl in 1859. However the pathogenesis of this disease has not been made clear because the pure culture of lamblia is not possible. The vegetative form of this protozoa was found in the duodenal contents of two patients who were initially diagnosed as having cholecystitis. Clinical considerations of the pathogenesis were carried out in this case. In the lst case, therapy consisted of oral administration of “Resochin” (Chloroquine-diphosphate) which showed good results. In an effort to investigate the pathogenesis of this disease, an attempt at pure culture was made using the vegetative form obtained from these patients. Five culture mediums tried were the modified V-Bouillon which I called L1-5 Bouillon. Following results were obtained: 1) The optimum pH of the medium for culture was found to be at 6.4. 2) Bouillons containing various concentrations of pig liver were tried and it was found that L4-Bouillon which contained 15 grams of pig liver per 100ml of water was the most suitable for culture. Distinct movement of the lamblia was observed for 12 days and on the second to the fourth day reproduction and multiplication-binary longitudinal fusion-of the vegetative form of the lamblia were seen. 3) As for the effect of antibiotics used in the culture solution to inhibit the growth of bacteria colimycin proved better than streptomycin. 4) Reproduction and multiplication of the lamblia were observed and its mode of reproduction was described. As noted above, I succeeded in culturing the lamblia for 12 days. However, the pure and continuous culture of this protozoa has not yet been accomplished. Further efforts are being made to study the pathogenesis of this disease.
By using right heart catheterization, electrolytes concentrations in arterial and mixed venous plasma were measured on 43 cases in steady state. Bicarbonate ion concentration in mixed venous plasma was slightly higher than in arterial, but in other electrolytes no significant difference was found between arterial and mixed venous plasma. In groups with markedly larger Pco2 or pH difference between arterial and mixed venous blood (ΔPco2 or ΔpH) than normal, sodium concentration in mixed venous plasma was statistically higher than in arterial. When the venous blood was saturated with O2 in vitro, decrease in Pco2 and increase in pH were so great, but in electrolytes concentrations no significant change except chloride shift was noticed. In 10 cases with ch onic pulmonary emphysema, when hyperventilated with IPPB/I artificially, ΔPco2 and ΔpH increased markedly, and sodium concentration in arterial plasma became lower than mixed venous. From these results concerning ΔPco2 or ΔpH and sodium concentration difference, I have presented a hypothesis stating buffer action of erythrocyte when pulmonary circulation is in abnormal state.
0.1cc of 1‰ Adrenaline in saline (containing 100μg of adrenaline hydrochloride) was injected indradermally on 241 cases with various diseases and 26 cases of healthy adults and children. 24 hours and 48 hours thereafter the local skin was explored on the existence of local hemorrhagic-necrotic response and the diameter of the lesion was measured when the response was found. The appearance of the dermal hemorrhagic-necrotic area larger than 2×2mm2 in its size was recorded as positive adrenaline cutireaction. The reaction was observed in 3 of 26 healthy subjects and in 6 of 57 ambulant patients with the minimal surgical injuries or malformation. The incidence of the reaction was low amounting 11% in those groups. In the patients with several acute infectious diseases, the incidence of the reaction was significantly high. 30 of 43 patients (70%) of fulminant type of bacillary dysentery (Ekiri) in its acute stage and 17 of 20 patients (85%) of colitis type of bacillary dysentery showed the reaction. In the stage of recovery the reaction decreased i.e., 4 of 16 patients (25%) of fulminant type and 9 of 22 (41%) patients of colitis-type showed the reaction. Patients with diphtheria showed also high incidence of the reaction, i.e. 8 of 13 cases showed positive reaction and especially the patients with the large destructive foci showed higher incidence. 15 in 20 cases suffering several types of ileus showed also the positive response and some of them showed somewhat larger hemorrhagic necrosis as compared with the other diseases. Such evidences suggest the significance of bacterial polysaccharides in the positive cutireaction in the patients with bacillary dysentery, ileus and diphtheria, and of tissue polysaccharides in the patients of diphtheria, especially with the severe destruction of the tissues, because in the other experiment of the authors similar positive adrenaline cutireaction was found on several animals treated with the intravenous administration of several bacterial and tissue polysaccharides capable of eliciting the host response of Landy and Shear. So that some of the positive adrenaline cutireaction, which was found on those patients, may be considered as a representation of the host response which indicates the generalized injury of the endothelial cells of the blood vessels or the intravascular blood coagulation due to the invasion by some high molecular weights substances. Patients suffering from hypertension, (4 of 4, positive) and nephritis, (4 of 7, positive) showed somewhat higher incidence of the reaction. The mechanism involved in those cases is not clear and the exploration is now under way.
In order to elucidate the mechanism and physiological significance of biliary excretion, three radioactive substances, Na2 HP32 O4, Co60 C12 and Co60-vitamin B12, were given to rabbits and the biliary excretion was compared with blood concentration and urinary excretion. These substances were chosen because of their differences in ionization and nutritional value. 1) P32 excretion: Biliary excretion of P32 following the intramuscular administration of Na2 HP32 O4 reached a maximum two hours after the injection, whereas the peak of radioactivity in the blood and urine came within 30 minutes and 1 hour, respectively. When administered intraperitoneally, the biliary radioactivity peak was lower and delayed, appering at 3 to 4 hours. The radioactivity in the blood was highest at 30 minutes and that in the urine reached a maximum at 2 hours following the intraperitoneal injection. The biliary excretion curve showed a gradual decline from the peak in both cases. The concentrations of P32 following oral administration were low both in blood and bile at one hour, but the biliary concentration exceeded that of blood at 6 hours when it was maximum. 2) Co60 C12 excretion: The biliary excretion of Co60 after intramuscular injection of its chloride was much smaller and delayed, with a peak at 3 to 4 hours, than in the case of P32. The greater portion of the injected amount was excreted into the urine in 2 hours, making 6 hours excretion 95% of the total dose. This figure is in a marked contrast with 18% in the case of P32. The biliary excretion rate was maintained for 24 hours. Following intraperitoneal injection the radioactivity in bile reached a maximum within 3 to 5 hours with little excretion in early hours. The blood concentration were low and gradually increased to reach the peak in 4 hours. The urinary excretion pattern resembled that of intramuscular administration. 3) Co60-vitamin B12: The appearance in bile of Co60 B12 administered intravenously was gradual with low concentrations at the beginning to reach the peak in 3 to 4 hours, although the blood concentrations were highest immediately after injection. There was a corresponding time lag in biliary excretion. The concentrations in blood and bile decreased gradually. The urinary excretion increased sharply in 2 hours and then decreased rapidly again. The excretion pattern in bile following both subcutaneous and intramuscular administrations was the same as that of intravenous injection for lower radioactivity in bile. The data seem to indicate that the biliary excretion reflects the metabolic behavior of administered substances and constitutes an extrarenal excretion route.
Pathohistological study on the pulmonary edema was performed in 248 cases. Pulmonary edema was divided into two forms, i.e. intraalveolar and interstitial. Of 248 cases pulmonary edema in alveolar cavity was found in 106 (42.7%), in connective tissue 64 (25.8%), and combined 58, only in alveolar cavity 23, and in connective tissue 5. Some discussion has been made on the pathogenesis of interstitial edema, especially on the fact that both intraalveolar and interstitial edema were not found concurrently. In contrast to the inflammatory type, derangement of nervous control is thought to contribute some part in producing the pulmonary edema in congestive type usually seen in the nervous, cardiovascular, and renal diseases.
The lst Department of Internal Medicine, Kumamoto University, Medical School The sputum levels of isoniazid after oral administrations were estimated by the modified one of Dr. Mandel's bioassay after the homogenization of samples with papain digestion and decontamination with heating. The sputum INH levels were in most cases lower than the serum levels of the same cases, that is, the formers were half or quarter of the latters showing 0.2mcg/ml 2 to 6 hours after administration of 200mg. After giving 200mg of INH in three divided dosages the sputum levels were 0.1mcg/ml or less in more than 80% of cases. No remarkable rise of the sputum levels was obtained by the increased dosage of INH in 300mg or 600mg. The maximal INH levels in sputum were slightly later than those in serum, disappearing after 8 to 10 hours. The higher INH sputum levels were observed in the cases with recent origin, especially with cavities with non-sclerotic wall. As sputum, the softend caseous or purulent substances in the resected pulmonary or renal tuberculous lesions showed the lower INH levels than the serum. The increases of sputum INH levels were obtained by the combined use of Depot Kallikrein, Antigene methylique or old tuberculin in most cases. Indeed, the improvements of X-grams or the conversions of tubercle bacilli in the sputum were observed in the most cases treated combined with old tuberculin or Antigene methylique.
The establishment of the excellent leukocyte separation method is at first required in biochemical studies of leukocyte enzymes. The leukocyte separation method with highmolecular dextran (average M.W. 228, 000) was examined following the studies of phytohemagglutinin and Gam Acasia methods formerly reported. Several kinds of concentrations of dextran solution, mixing ratios of dextran solution and blood, and influence of temperature were investigated in order to establish optimal conditions i.e. comparative leukocyte yields, convenience, and minimal erythrocyte contaminations. It was found that the condition of mixing blood and six per cent dextran solution in the following volume ratio (B: D) 6: 1 was most suitable. The mean of leukocyte yields was 68.3±0.55 and erythrocyte contaminations were below 94 per cent of leukocytes. The nature of separated leukocytes showed no significant changes comparing with that of fresh capillar blood, by Giemsa staining, supravital staining, phagocytosis-test of indian ink and differentials. These indicate that leukocyte injuries with dextran method are minimal and separated leukocytes are usable for biochemical studies. The dextran method is better than the phytohemagglutinin and Gam Acasia methods in regard to leukocyte yields and convenience.
The influence of methionine on the excretion of the ether sulphuric acid in the urine was studied, and the following results were revealed. 1) In normal persons, the daily excretion of ether sulphuric acid in the urine is from 61 to 291mg. 2) Most of the patients of the liver diseases excretes the more ether sulphuric acid in the urine. 3) Enteral and parenteral administration of methionine often increases the excretion of ether sulphuric acid in the urine in normals and patients of the liver diseases. 4) In normal rabbits, the daily excretion of ether sulphuric acid is within 23 to 36mg. 5) It decreases markedly in the rabbits of damaged liver by CCl4 or CHCl3. 6) Increased excretion of ether sulphuric acid in the urine is often seen by the administration of methionine to normal or liver damaged rabbits.