The renin-angiotensin system had been received a great deal of attention in references with the development of arterial hypertension. Although the measurement of the plasma renin activity (PRA) is very important for evaluating the patients with arterial hypertension, it may be difficult to decide whether the PRA measured is normal or abnormal since the rate of renin secretion from the kidney is said to be greatly determined by a variety of factors even under normotensive states. The recent introduction of radioimmunoassay has promoted studies in the dynamics of renin-angiotensin system. The purpose of this study is to evaluate the immunoassay method, to det ermine the normal dynamic ranges of PRA levels in the various conditions and to search for the factors influencing PRA. Radioimmunoassay of PRA was performed using the kits commercially distributed by Schwarz-Mann (SM), CEA-CEN-SORIN (CCS) and CEA-IRESORIN (CIS). For all of these kits PRA was given as an amount of angiotensin I generated in ng/ml/hr at 37°C and the range of the measurement was directed as from 0.05 to 0.80 ng. 1) PRA levels in the sample tubes increased lineally with the incubation time being elapsed from 0.5 to 6 hours. 2) The normal PRA levels under various conditions were measured in normotensive patients(patient controls). Under normal diet, PRA in mean at rest was 0.61±0.35(S. D. )ng/ml/hr by SM & CCS and 2.02±0.56ng/ml/hr (CIS), and after 4 hour-standing it increased to 1.67±0.55ng/ml/hr (SM & CCS) and 3.54 ±1.76ng/ml/hr (CIS). Under Na restricted diet (30mEq/day), PRA at rest was 1.46 ±O.62ng/ml/hr (SM & CCS),5.19±0.72 ng/ml/hr (CIS), and after 4 hour-standing under furosemide administration it was 6.96 ±2.19ng/ml/hr (SM & CCS),10.8 1±4.13ng/ml/hr (CIS). 3) Postural changes in PRA was investigated to prove that it was required one and a half, and two hours for PRA level to stabilize after taking recumbent, and standing position, respectively. 4) Diurnal change in PRA was studied in three healthy subjects and its level was found to be higher from the midnight to the morning and remained in the lower level in the afternoon. 5) The menstrual cycle was also found to affect PRA level in 4 normal females that it was higher in the luteinizing phase than in the follicular one. It was discussed that the measurement of PRA and its interpretation would be valid only when the factors and conditions of the patients such as diet, posture and so forth be clearly defined.
Zinc, a micronutrient essential to man, has been demonstrated to have a beneficial effect upon wound healing. In recent years, many investigators have documented that this element is essential for the function of a number of clinically important biologic enzymes, and that the activities of certain of these zinc-dependent enzymes are related during particular states of tissue destruction and repair. However, the mechanism by which zinc is involved in wound repair has not been determined. The aim of the present study was to obtain further information on this problem. In the first experiment, to clarify whether postoperative alterations of biologic zinc requirements and availabilities are affected by urinary loss of this ion, particulary in relation to tissue repair, the urinary zinc excretion and serum zinc level were measured. The results showed that urinary zinc excretion following surgical stress was significantly higher than before operation. On the other hand, the serum zinc level was not significantly affected. These experiments suggest that it is advisable to supply an adequate amount of zinc during the early postoperative period. Since it was disclosed that radio-z inc is preferentially concentrated in healing tissue, the author attempted to evaluate the effect of dietary zinc supplements (zinc sulfate) on the collagen elaboration in subcutaneously implanted polyvinyl hormal sponges (P. V. H. S. )in rats. The effect of dietary zinc sulfate on the tensile strength of sutured wounds in rats was also evaluated by tensimetric measurements. The results obtained from these experi ments disclosed that dietary supplementation of zinc sulfate resulted in an increased tissue ingrowth and collagen formation in the P. V. H. S. implants, and tensile strength was markedly increased as compared to controls.
Reported: A case of myasthenic gravis (Osserman group IV) of late onset with thymoma in a 45 year old female. Thymecctomy and subsepuent cobalt radiation therapy had yielded no significant effect. Three years after thymectomy, she was admitted to our department of the Kansai Medical University hospital because of a myasthenic crisis of the brittle type with an anti-choline-esterase resistance. After admission, tracheostomy was performed and an intermittent positive pressure respirator was applied. During course, however, a number of complications occurred, including cardiac shock, disturbed inflation of fhe left lung due to mediastinal pleural adhesion, severe infections (lung and urinary tract by pseudomonaus aeruginosa, klebsiella, and candida developing into candida sepsis in the prolonged cour se), drug allergies (sulpenicillin, ampicillin,, and amphotericine B), hepatomegaly with liver dysfunctions, and kidney involvement. Therefore, the patient was treated with intensitive chemotherapy, adrenal corticosteroid, ACTH, transfusion to maintain electrolyte balance, and nasal feeding of a high caloric diet. These treatments finally rescued the patient from the crisis, and eight months later, she was discharged. Discussed: The Management of a severe myasthenic crisis in due consideration of pathophysiological conditions.
The dd-strain mice, in which the intraperitoneal injection of 0.15mg of MNU were repeatedly performed, were observed for 28 to 32 weeks. In both sexes, the high frequency of development of vascular tumor was observed in spleen. Moreover, in the female mice, the vascular tumor was demonstrated in uterus or ovary, and, in the male mice, it was demonstrated in seminal vesicle or epididymis. In the mice, in whieh MNU was administerd less than 2 weeks (and total dosage of MNU was below O.6mg)the development of vascular tumor was not observed, but, in the mice, in which MNU was injected more than 4 weeks (and total dosage of MNU was over 1.2 mg), the development of hemangioma or hemangioendothelioma was demonstrated. In the mice, in which MNU was administered more than 12 weeks (and total dosage of MNU was over 3.6mg), the development of hemangioendothelial sarcoma was detected.
The“mercury-affinity reaction”which is thought to demonstrate unsaturated C-C bonds of ceroid on formalin-fixed paraffin sections has been found to react heavily with the zymogen granules of the pancreatic exocrine portion, the striate portion as well as the serous cells of the parotid gland, the stratum corneum of the skin, the external root sheath of the hair cortex, nucleus of the hypothalamus, neurosecretory substances of the infundibulum hypothalamium and α cells (partially βcells) of the anterior pituitary. On the other hands, these tissue elements reveal a positive finding with the Maeda et al. colloidal iron hydroxide method for sulfhydryl and disulfide groups with or without the pretreatment of thioglycollic acid. Thereupon, the authors examined whether or not divalent mercury used in the“mercuryaffinity reaction”, would combine with sulfhydryl group, besides unsaturated C-C bonds, because there are a few test methods principle of which is based on a mercaptide formation of sulfhydryl group. Consequently, it was found that the degree of a positive coloring of the“mercury-affinity reaction”was considerably lowered by the pretreatment with thioglycollic acid and was not influenced by N-ethylmaleimide blocking for sulfhydryl group, these findings being contrary to those obtained by the colloidal iron hydroxide method. In view of the above results, it is concluded that the“mercury-affinity reaction”does not react with sulfhydryl or disulfide groups, its specificity for unsaturated C-C bonds being approved enough.
Although corticosteroid and ACTH are frequently used for the treatment of various diseases, including hematologic disorders such as aplastic anemia, the opinions concerning the effects of these hormones on hematopoietic function remain divided. With a view to contributing towards the rational use of these hormone s, the author attempted to investigate their effects on the blood and bone marrow pictures both in normal rabbits and in those with impaired bone marrow. Short-term administration: β-methasone (βM) (2 mg/kg/day) or ACTH (8.3 units/kg/day), was administered to normal rabbits five days, and their blood and bone marrow pictures were examined. Long-term administration: β-methasone was given for 77 days (1 mg/kg/day for 36 days followed by 2 mg/kg/day for 41 days) prior to examination. The results obtained are as follows: I. Short-term administration 1) The periph eral blood picture The red cell count (R C C) was decreased by,βM, but slightly increased by ACTH. The color index (CI) and the mean red cell diameter (MCD) was increased by βM, and decreased by ACTH. The white cell count (WCC) temporarily rose by treatment with either hormone, and thereafter went down. The neutrophil coun t (NC) generally went parallel with the WCC. The average segmentation r a te (SUGIYAMA) of the neutrophils increased during treatment with βM, while ACTH caused the appearance of metamyelocytes with a left shift of the segmentation rate after a transient shift to right. The lymphocyte count (LC) was decreased by W, while the changes caused by ACTH were inconsistent. 2) The bone marrow picture The bone marrow p i c ture showed an increase in erythroblasts after the administration of either hormone. On the other hand, the myeloid cells showed a d e crease which recovered to exceed the former count ten days after cessation of the hor mone dosage. II. Long -term administration The long-term βM administration yielded no recovery of the blood picture, except for a transient ascent of the WCC and NC when the daily dosage was increased. T he erythroblasts in the bone marrow decreased after the long-term administration.
Rabbits with bone marrow depression caused by Mitomycin C (MMC) (2 mg i. v., twice at a 2 week interval) were treated intramuscularly for five days with β-Methasone (βM) (2 mg/kg/day) or ACTH (8.3 units/kg/day). The treatment began from the fourth day after the second injection of MMC. The hemoglobin content are the red cell, leucocyte, neutrophil, and lymphocyte counts all decreased after the second MMC injection. The blood and bone marrow pictures of these rabbits (M group) during or after the hormone treatment were serially examined and compared with the findings in normal rabbits (N group) treated with the hormones. The results obtained were as follows 1) In both groups, the RCC decreased during treatment and increased after discontinuance: The increased counts recovered their normal levels quicker in the M group than in the N group. In both groups, the CI and MCD were similarly increased by,βM and decreased by ACTH. 2) In both groups, the WCC and NC temporarily rose followed by a descent with either hormone, the grade of the descent being more remarkable in the M group th a n in the N group. 3) Concerning the bone marrow picture, the erythroid cell count increased in the N group and the ACTH-treated M group. After the discontinuance of treatment, thi s cell count returned to normal in the N group, but in the ACTH-treated M group, t he count remained elevated. In both groups, the myeloid cell count was decreased by either hormone; the N group returned to normal after discontinuance, but the M group still maintained its low myeloid cell count.
The relation between corticosteroid administration and blood picture was investigated in forty-six patients with various diseases other than blood disorders (16 cases of liver diseases (LV),8 cases of nephrotic syndrome (NP),9 cases of bronchial asthma (AS),3 cases of pleurisy (FL), and 10 cases of SLE (SL)). The results obtained were as follows: The RCC became slightly increased in LV and PL, but decreased or showed no change in NP, AS, and SL Marked increases in the NC was observed in LV and NP, which were afterwards replaced by increases in the LC. No remarkable changes were observed in the NC of AS and PL. SL showed quite different changes: the NC increased immediately after the beginning of treatment, while the LC increase was delayed though it finally reached a high level in concomitance with the RCC and the NC after treatment for more than eighty days. This finding in SL seemed to be due to the recovery of hematopoietic function caused by improvement of the disease. Younger neutrophils appeared to accompany these neutrophil increases. As seen above, the blood reac tions to corticosteroid administration differed according to the disease; this finding could be attributed to the different pathophysiological states, especially the endocrinological and hematological ones.
The present investigation was undertaken to compare embryopathic, or teratogenic activities in mice of methylxanthines such as caffeine, theophylline and theobromine and of adenine. Sublethal dosages of these compounds were intraperitoneally administered to JCL: ICR mice on day 9 or day 12 of gestation. Fetuses were grossly and skeletally examined on day 18 of gestation. Main results were as follows. 1. Caffeine, theophylline, theobromine and adenin e induced significantly high frequencies of malformed fetuses mainly with axial skeletal defects when they were administered on day 9 of gestation. In addition, adenine caused various types of gross malformations. 2. When these chemicals were injected on day 12 of gestation, they also produced significantly high frequencies of abnormal fetuses mostly with cleft palate and/or subcutaneous hematoma. However, each incidence of abnormality varied with the cornpound injected. 3. A s each type of embryopathic effects caused by these compounds is compared, the effects of caffeine, theophylline and theobromine on the developing embryos resembled each other. However, the effects of adenine differed from them in terms of low maternal toxicity and high embryopathic activities. The mechanism of embryopathic activities of adenine may be different from that of methylxanthines.
The development of the outer segment of the rod of the retina of the albino rat has been studied with electron microscope on the eyes from the 13th day of gestation until the 14th day after birth. At the early sta g e (from the 13th day of gestation to the 17th day of gestation) of the development of the optic cup, one of the diplosomes in the cells at the outer most portion of the neuroblastic layer extended the cilium which contained ciliary tubules. The bulge of cytoplasma of the primitive inner segment could not be found in this stage. The protruding processes were directed toward outwards and kept close contact with the pigment epithelial cells. At the following sta ge (from the 18th day of gestation to the 5th day after birth), this primitive outer segment elongated its length and enlarged like cudgel. The plasma membrane showed an expansion in the tip of the cilium. The gradual enlargement of the cytoplasma at the tip of the cilium continued on opposite sides of the ciliary tubule. On the 6th or 7th day after birth, several large vesicles could be found s uddenly in the distal portion of the cilium. These large vesicles seemed to be associated with protein synthesis in the inner segment and the processes of the pigment epithelial cells. Namely, these may be a precursor material for the membrane formation and may induce the plasma membrane invagination. On the 8th day after birth, the plasma membrane invagination originating from the tip and all sides of the primitive outer segment appeared and were observed for one or two days. Thus, the lamellar membranous structure appeared suddenly on the 8th day after birth. Most of the invaginated disks were finally pinched off from the plasma membrane, however, only a few were continuous with it. Thereafter, these primitive rod sacs were arranged from inwards to outwards in a position perpendicular to the long axis of the outer segment seen in mature animal.
Reported here is the autopsy of a 65 year old female who had succumbed to a severe cerebellar hemorrhage suddenly occurring during treatment for hypertension, diabetes mellitus, and arterio-sclerotic parkinsonism. Collation of the autopsy findin gs with the clinical symptoms disclosed, as the prodrome of the cerebellar hemorrhage, the appearance of signs of insufficiency of the vertebrobasillar and cerebellar arteries (such as persistence of drug-resistant hypertension, orthostatic hypotension, syncope and carotic artery's loss of reflex) and signs of parasympathicotonia, vertige, vomiting, nystagmus, oculogyric crisis and desequilibration. It is emphasized that if these symptoms or signs are found in old patients, the cerebellar ataxia should be examined and the general condition, especially the blood pressure, should be controlled.
The present experiment was performed to elucidate the problem whether N-ethylmaleimide (NEM) and trimetazidine react chemically in water solution or not as these drugs have shown the mutual antagonistic effects on isolated rat atrial tissue. Experiments were carried by means of the UV-spectrophotometer and the high speed liquid chromatography. (1) The UV-absorbance by NEM at 302mμwas reduced by the coexistence of L-cysteine in the solution at soonafter their mixing, while was little influenced by the coexistence of trimetazidine when these drugs were mixed at the same molars. And, the absorbance by trimetazidine at 268mμ was little influenced by the coexistence of L-Cysteine in the solution. (2) When NEM, L-cysteine and trimetazidine were coexisted in the solution, the appearance of NEM absorbance decrease induced by L-cysteine was delayed. In the experiment, in which rat erythrocytes were used as sulfhydryl preparation, the amount of NEM combined with erythrocytes might be reduced by the coexistence of trimetazidine. (3) The reaction between NEM and trimetazidine in the solution was little proved by means of the high speed liquid chromatography, and that between NEW and propranolol was similar. From these results, it was assumed that trimetazidine can influence the chemical reaction between NEM and SH radical, though the chemical reaction of trimetazidine with either NEM or L-cysteine is scarce.
The author studied the intermediate follow up results of open reduction for C. D. H. in infants in the orthopaedic clinic of Kansai Med. University. The surgical series consists of 36 hips of 31 infants. A surgical technique that we call“circular limbectomy”was used. This technique has several technical procedures and was first introduced about 8 years ago, These procedures are as follows: 1. A transverse skin incision is placed alongside the femoral crease. 2. The way of dissecting down to the hip joint is similar to the approach described by O. Aufranc, in Boston, in 1962. 3. After widely exposing the anterior surface of the hip joint, the capsule is opened by a J-shaped arthrotomy incision (in the right hip). The horizontal ramus of th i s incision is placed parallel to, and 0.5∼1 cm below, the acetabular margin. 4. After removing both ligamentum teres femoris and fibro-fatty tissue, thickened and often inverted limbus is cut in a circular fashion in the middle between its in n er and outer margins. In this way the limbus is divided into inner and outer layers and the inner layer is removed and the outer one is left behind. The lig. transversu s acetabuli is severed in order to have the medial inferior quadrant of the jo int capsule fully released so that, as a result, satisfactory space may be created for the f e moral head to be stably and concentrically held into place. 5. Before opening the capsule, the iliopsoas tendon is cut close to its insertion to the lesser trochanter. After closing the capsule, the severed end of the tendon is transplanted to the anterior inferior part of the closed capsule. The cases followed up in the surgical series involve 31 patients, (3 males and 28females), and 36 hips among which unilateral hip involvement involves 26 hips (8 right hips and 18 left hips). The average age of the infants at the time of surgery is 1 year and 3 months. The youngest is 3 months and the oldest is 2 years and 7 months. Surgery is indicated from clinical and radiological points of view in which a plain X-ray examination as well as an arthrographic examination are used. Radiologically, with the exception of one inreduceable hip joint, all the 35 hips show eccentric positions of the femoral head which, by our circular limbectomy performance, could be reduced more accurately into the anatomical position. Detorsion osteotomy was performed only secondarily in 8 hips. The postoperative results followed up are briefly summarized as follows. Out of 31 patients, normal gait with no limping is seen in 30 patients. Sight occasional limping with intermittent pain in walking is seen in only one. R. O. M. is almost normal in 27 patients and it is also fairly good in the rest of the 4 patients.