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For the periods ranging from the fifth gravid month to the sixth post partum week continuous examinations were conducted on the blood picture of 10 multiparas and 18 primipars who came to the Second Maternity Hospita, Okayama University Medical School, from December 1955 to December 1956, and all those who had no complications throughout pregnancy, delivery and puerperium. In addition observations were carried on the 245 subjects who had no complibation throught pregnancy, delivery and puerperium to see what influences the blood loss during delivery might exert on blood picture during puerperium, particularly the changes of hemoglobin concentration (Hb), and the author arrived at the following conclusions: 1) By the continuous examinations of pregnat women the existence has been recognized of physiological anemia which recovers close to the level of healthy non-pregnant women within one month after delivery. Namely, it has been found that already by the fifth month of pregnancy a considerable decrease both in erythrocyte counts and Hb values is recognized as compared with those of healthy non-pregnant women (the control), but starting around the eighth month the values of both keep on increasing month after month until reaching their maximum at delivery yet still a little below those of the control, and particularly Hb values as compared with those of the control show a significant fall. During puerperium erythrocyte counts and Hb values recover rapidly and by the sixth post partum week they reach close to the level of the control. 2) By the latter part of pregnancy both in multipara and primipara Hb values shew a marked decrease as compared with erythroyte count. Gradually presenting hypochromic-anemia picture, even in the sixth post partum week a delay in the recovery of Hb values can still be recognized, the delay being particularly striking in primipara. 3) It has been noticed that there is a greater tendency of delay in the recovery of Hb values along with increase in blood loss during delivery. Namely, though in the groups with blood loss of less than 10g./kg. at delivery the recovery of Hb values during puerperium is smooth and hematopoietic functions seem to be undisturbed. However, with increase in blood loss the recovery is proportionately delayed and in the groups with over 12.5 g./kg. loss a marked delay in the recovery of Hb has been recognized. 4) In primipara groups with under 7.5g./kg. blood loss and in multipara with under 12.5 g./kg. loss, the recovery of Hb values during puerperium is smooth; but in primipara with blood loss of over 10 g./kg. and in multipara with the loss of over 15 g./kg. the delay has been quite marked. In other words, in the groups with blood loss of over 7.5 g./kg. the rate of recovery in Hb values tends to be faster in multipara than in primipara. 5) Along with increase in the frequency of labor, the rates of increase have tended to increase by degrees.

Separation of the urinary ester-form bilirubin was attempted, and the results obtained may be summarized as follows: 1. A brown pigment was obtained from jaundiced urine by the following procedures; namely, salting out, methanol extraction, chloroform flocculation, and separation on cellulose column. The pigment has been found to be easily soluble in water, displaying the absorption maximum at 420 - 410 mμ at pH 7.0, and it also gave a positive reaction both to GMELIN's and EHRLICH's diazo reagents within a minute without the addition of alcohol. These characteristics agree well with those of the socalled ester-form bilirubin. 2. On the basis of the results of paper chromatography and paper electrophoresis, the pigment has been determined to contain no amino acid, steroid, nor reducing substance. Moreover, no glucuronic acid could be detected whether examined in vitro or by paper chromatography together with paper electrophoresis, either.

By prepariug over 100 thin slices from 77 cases of urinary calculi mainly consisted of vesical calculi and immersing them in various solvents, the solubility of these calculi has been examined by polarization microscopy from the standpoints of the composition and structure of urinary calculi. (1) MgNH4P04·6H20 (struvite) has been found to be most soluble and it is the best example in the dissolution of urinary calculi; and as for the solvents, Versene proved to be the best solvent. (2) The alkaline pH seems to have an intimate relationship with the dissolution of uric acid calculi. (3) Calcium oxalate proved to be insoluble in any solvent. In addition, no difference in its stability against solvents could be recognized in its monohydrate or dihydrate: (4) Cystine dissolved in the 10% Versene solution. (5) Amorphous-like substance apparently was dissolved slightly in 0.5% urease solution at 37°C, however, it is not possible to dissolve this substance completely, From these results calcium oxalate and amorphous-like substance seem to be the most difficult substances to dissolve, and therefore, the bearing they have on the dissolution of urinary calculi seems to most significant. In the present stage where little is known of real etiologic factors concerning the formation of urinary calculi, in the clinical application of the dissolution of stones further studies need to be carried on, but from the very nature of construction of urinary calculi, the local dissolution methods seem to be rather difficult at present, and rather somatic dissolution in connection with prophylaxis against recurrent stones seems to be the direction in which future studies need to be carried out.

This study was performed on 17 hyperthyroid patients and 15 healthy controls. The patients were under propylthiouracil (PTU) therapy at a dosage of 3 x 100 mg/day for one month. Blood samples, taken at the beginning and on the 30th day of therapy, were analyzed for hormonal parameters (T3, T4, TSH), lipid peroxidation endproduct [thiobarbituric acid reactive substances (TBARS)] and antioxidant status parameters: glutathione (GSH), glutathione peroxidase (GSH-Px) and CuZn superoxide dismutase (CuZn SOD). Hyperthyroid patients were observed to have significantly higher TBARS, GSH and CuZn SOD levels than controls (P < 0.05, P < 0.001, P < 0.001, respectively). PTU therapy caused a relief in oxidative stress as reflected by significantly decreased TBARS levels (P < 0.001) and a selective modification in the antioxidant status parameters: significant decreases in GSH and CuZn SOD levels (P < 0.001) and a significant increase in GSH Px (P < 0.01) activity. Our findings suggest a selective modification of the antioxidative profile in hyperthyroidism. PTU should also be considered as an in vivo antioxidant, in addition to its antithyroid action.

Corticoids are well known for their immunosuppressive properties. Interleukin-10 (IL-10) is an intrinsic antiinflammatory peptide in immune diseases, originally identified as cytokine synthesis inhibitory factor. We examined the effect of hydrocortisone sodium succinate (HSS) on the production of IL-10 by human peripheral blood mononuclear cells (PBMCs). PBMCs from healthy volunteers and cancer-burden patients were preincubated separately with or without HSS for 1 h, then stimulated with 5 microg/ml lipopolysaccharide (LPS). Production of IL-10 by human PBMCs was detected with LPS stimulation and its production was higher in cancer-burden patients than in normal volunteers, although this was not statistically significant. HSS suppressed production of IL-10 by LPS-stimulated PBMCs in a dose-dependent manner both in normal volunteers and in cancer-burden patients. These results indicate that, in addition to their antiinflammatory properties, corticoids act to restore the immunosuppressive states even in cancer-burden states

Seventy-nine shoulders suspected of rotator cuff tears were examined by ultrasonography (US) and forty-three received surgery. Long and short axis scans were performed and findings of each were separately classified according to a five-grade system, and the results were correlated with the actual extent of tear observed during surgery. Internal echogenicity and subacromial impingement were analyzed before and after surgery. A accuracy of US in detecting rotator cuff tears was analyzed. In addition, the correlation between cuff shape observed by US before surgery and actual shape observed during surgery was assessed. It was noted that cuff thinning and abnormalities in shape did not recover to normal after surgery. However, in the cases of discontinuities observed by US before surgery, US findings indicated that the torn cuff was anchored to the greater tuberosity and functional during active motion. Although post-operative US findings were not normal, clinical results were good in most cases. Sensitivity of US for detecting rotator cuff tear was 100% and specificity 94%. US is non-invasive, cost effective and allows the physician to examine the joint while it is in motion. Therefore, at this time, we use US as a screening method for detecting rotator cuff tears. Furthermore, US allows us to check for re-tears while the joint is in motion, which is essential for accurate diagnosis.

To evaluate the efficacy and safety of additive triple disease modifying anti-rheumatic drug (DMARD) combination therapy of a low dose of sulfhydryl compounds inverted question markD-penicillamine, bucillamine or tiopronin inverted question mark, sulfasalazine (SSZ) and methotrexate (MTX) as a treatment for rheumatoid arthritis (RA) patients, we studied a total of 33 Japanese RA patients (6 males, 27 females). At 1 or 2 months after simultaneous administration of the 3 above-mentioned DMARDs was begun, significant improvements were seen in markers of joint inflammation, i.e., erythrocyte sedimentation rate and C-reactive protein in sera. At 6 months, clinical improvement judged by the physicians' overall assessment of joint symptoms and laboratory data was observed in 29 (88%) of the 33 RA patients. No marked effect was observed in the other 4 (12%) patients, however. We observed no significant adverse reaction to this therapy. This suggests that additive triple DMARD combination therapy of a low dose of sulfhydryl compounds, SSZ and MTX could be a useful drug therapy for the treatment of RA patients, even those who are refractory.

Life expectancy, mortality and longevity data related to height and body size for various US and world population samples are reviewed. Research on energy restriction, smaller body size and longevity is also examined. Information sources include various medical and scientific journals, books and personal communications with researchers. Additional information is presented based on research involving eight populations of the world noted for their health, vigor and longevity. This information includes the findings of one of the authors who led research teams to study these populations. While conflicting findings exist on the cardiovascular death rates for shorter people, many examples of short populations with very little heart disease are described. Most cancer studies indicate that shorter people have significantly lower mortality risk. Considerable data suggest that shorter people generally have greater longevity than taller people, and extensive animal research supports human longevity findings. Tall populations with low mortality rates are also described. Shorter stature and smaller body weight appear to promote better health and longevity in the absence of malnutrition and infectious diseases. Several theoretical reasons for this greater longevity potential are covered. Also discussed, is the role of socioeconomic status, diet, relative weight, environment and other factors in increasing or decreasing the longevity of individuals, regardless of their heights and weights.

Three outbreaks and many isolated cases of enterohemorrhagic Escherichia coli O157:H7 occurred in 1996 and 1997 in Okayama Prefecture, Japan. In an attempt to investigate the route of these infections, the strains isolated from the 3 outbreaks (total 33 strains) and 15 isolated cases (total 15 strains) were investigated using random amplification of polymorphic DNA (RAPD) and pulsed-field gel electrophoresis (PFGE). In addition, 10 strains from an outbreak in Tojo Cho, Hiroshima Prefecture (June 1996), 2 strains from the particular types of meat in Kochi Prefecture, and 42 strains isolated from bovine feces in a farm in Okayama Prefecture were also investigated in the same manner. PFGE was much more useful than RAPD for molecular typing of the clinical isolates, in that it allowed us to classify them into 10 PFGE groups. We noted that the strains differed according to the time and place of the outbreaks (or isolated cases). This indicates that O157:H7 infections in Okayama Prefecture were caused by different strains (although some cases were aggravated by the same strains as were found in other areas). The isolates from bovine feces were classified into 5 groups by PFGE profiles, but none of them were identical to those of the clinical isolates.

In an attempt to elucidate the tumor properties relating to responsiveness to chemotherapy, we examined immunohistochemically the expression of P-glycoprotein (P-gp) and carcinoembryonic antigen (CEA) in small cell lung cancer (SCLC) tumors. Tumor specimens from 33 patients were obtained at the time of diagnosis and relapse. Four patients expressed P-gp in their initial tumors, and 7 others did in recurrent tumors. The overall response rate to chemotherapy of the initial tumors was 75% for P-gp-positive initial tumors and 86% for P-gp-negative tumors, whereas the disease-free and overall survival times were significantly shorter in the former than the latter. Three patients showed CEA in their initial tumors, and 5 others did in recurrent tumors. The patients with CEA-positive initial tumors tended to relapse earlier than those with CEA-negative tumors. In addition, recurrent tumors expressing CEA were resistant to salvage chemotherapy. A clear correlation between CEA expression by tumors and the CEA level in the serum was observed at diagnosis as well as at relapse. These findings indicate that P-gp and/or CEA expression by a tumor and elevated CEA level in the serum may predict refractoriness of the tumor to chemotherapy.

The aim of this study is to obtain data for improving a training program for patients with diabetes mellitus. One hundred eighty-seven patients with non-insulin dependent diabetes mellitus were tested with 20 questions about their knowledge for self-management of diabetes mellitus. Then to draw out factors in their personal backgrounds relating to their correct answers, multiple regression analyses were conducted. As a result, four factors showed significant differences in the following order: Educational careers > ages > duration of disease > socioeconomic strata. The results of the present study have shown for the first time, that these four factors closely concern patients to acquire the necessary knowledge for their self-management of the disease. In addition, this study has raised some fundamental problems regarding the training program for patients: how education should be given to patients.

Antitumor activities of five platinum analogs, including cisplatin, carboplatin, 254-S, DWA2114R, and NK121, were compared using five human lung cancer cell lines and 19 tumor specimens obtained from lung cancer patients. The antitumor activity was evaluated by determining the ratio of the maximum tolerated dose of each drug to the 70% tumor growth inhibitory concentration in a colony assay. Cisplatin was the most potent agent, followed by 254-S and carboplatin. DWA2114R and NK121 were less potent than cisplatin and 254-S. Cross-resistance to adriamycin was also investigated using an adriamycin-resistant small cell lung cancer subline, SBC -3/ADM30. SBC-3/ADM30 was 1.7- to 4.0-fold more resistant to cisplatin, carboplatin, NK121, and DWA2114R, than was the parent line, SBC-3, and the subline was 2.0-fold more sensitive to 254-S. Using SBC-3, in vitro combination effects of etoposide and cisplatin, carboplatin, or 254-S were evaluated by the median-effect principle. Synergism was noted when cisplatin and etoposide were combined at a fixed molar ratio of 1:1. Combination of carboplatin and etoposide showed an additive effect. The combination of 254-S and etoposide was antagonistic at low concentrations, but was markedly synergistic at higher concentrations. These data suggested the efficacy of 254-S in the treatment of lung cancer.

Forty patients underwent coronary revascularization using bilateral internal thoracic artery (ITA) grafts between 1988 and 1992. A total of 111 coronary grafts were performed, or an average of 2.8 grafts per patient. Each patient received bilateral ITA grafts, and in 20 patients an additional 29 grafts were constructed with 18 autologous veins and 11 gastroepiploic arteries. The right ITA was grafted as a free graft in 20 patients. The ITA graft patency rate was 96 per cent (67/70) at the time of hospital discharge. The operative morbidity included 3 reoperations for bleeding, 1 perioperative myocardial infarction, 1 renal failure, 2 postcardiotomy shock, and 1 colon perforation. Two hospital deaths occurred; one due to colon perforation and the other due to postcardiotomy cardiogenic shock. One patient died of cerebral infarction 6 month after the operation. Thirty-four patients were in New York Heart Association functional class I, 2 were in class II and 1 was in class III. Cardiac function evaluated by echocardiography and scintigraphy showed significant improvement postoperatively. These data suggest that the use of bilateral ITA grafts is associated with an acceptable mortality and increases the versatility of arterial grafting.

We investigated the antibody dependent cell-mediated cytotoxicity (ADCC) of lymphocytes and monocytes toward human O+ red cells coated with anti-D antibody using a 51Cr release assay. Lysis of sensitized red cells by lymphocytes occurred rapidly, but monocyte-mediated lysis occurred slowly. This difference might be due to postphagocytic 51Cr release by monocytes. ADCC of lymphocytes increased in proportion to the effector cell number, but large amounts of antibodies were required. In contrast, ADCC of monocytes was independent of the effector/target ratio and very small amounts of antibodies could produce red cell lysis. Large amounts of fluid phase IgG were required to inhibit the lymphocyte ADCC, whereas the monocyte ADCC was markedly inhibited by small amounts of IgG. Monocyte-mediated lysis was completely inhibited by the addition of 10% human AB serum, but lymphocyte-mediated lysis was only slightly inhibited. Purified IgG1 and IgG3 were much more inhibitory to the lysis by both effectors than IgG2 and IgG4 (IgG2 greater than IgG4). Erythrophagocytosis also was inhibited by IgG1 and IgG3. These studies demonstrate that lymphocytes as well as monocytes can cause the lysis of antibody sensitized red cells, and IgG1 and IgG3 subclasses are more important than IgG2 and IgG4 in causing lysis of anti-D coated red cells.

Twenty-five patients (30 hips) have had a total hip replacement using the cup supporter developed in our department. This report describes the follow-up findings on these patients. The mean period after hip replacement was 2 years and 8 months (range from 6 months to 6 years). The cup supporter was used in patients with rheumatoid arthritis with acetabular protrusions, central migration of the prosthesis after hemi-arthroplasty, revision operation for a defecting acetabular floor, primary acetabular protrusions (including osteoarthritis with acetabular protrusions) and traumatic fracture-dislocation of the hip. In five cases, autograft of bone was used in addition to the cup supporter for reinforcement of a thin acetabular floor. This combination appeared to provide good clinical results. The cup supporter was of value in revision operations due to loosening of the acetabular cup with severe acetabular protrusions.

The anti-tumor effect of immunization with heat-killed Mycobacterium tuberculosis (Tbc) and Tuberculin (PPD)-coupled syngeneic tumor cells was examined in vivo. Three tumor cell lines were employed. Immunization of Tbc-primed BALB/c mice with PPD-coupled syngeneic Meth-A tumor cells displayed a potent anti-tumor effect on viable Meth-A cells inoculated subcutaneously. Neither PPD-coupled LLC (Lewis Lung Carcinoma) cells nor sonicated PPD-coupled Meth-A cells were capable of immunizing these mice. PPD-coupled syngeneic whole tumor cells were indispensable for induction of this tumor-specific resistance. Immunization of Tbc-primed C3H/He mice with PPD-coupled syngeneic MH134 tumor cells did not elicit anti-tumor activity against MH134, but additional pretreatment of mice with cyclophosphamide brought on an anti-tumor effect. Antimetastatic reactivity was investigated in C57BL/6 mice bearing LLC, with a reduction in metastases noted. This antimetastatic effect was observed even when the mice were immunized with PPD-coupled LLC cells three days after removal of the initial tumor. Immunization with Tbc and PPD-coupled Meth-A cells together with intraperitoneal administration of murine or rat interleukin 2 (IL 2) further augmented anti-Meth-A resistance. Murine IL 2 further inhibited tumor growth during the early stage, while rat IL 2 showed an anti-tumor effect throughout the course of tumor growth.

Polyamines are polycationic substances which are widely distributed in living organisms and have a close relation to rapid growth phenomena. We examined ornithine decarboxylase (ODC), which is the rate limiting enzyme of polyamine biosynthesis, and polyamine induction in primary cultured rat hepatocytes by various hormones which increase during pregnancy, and revealed differences in hormonal responses between adult and fetal rat hepatocytes. Thirteen hormones, including estrone, estradiol, progesterone, testosterone, human chorionic gonadotropin (HCG), cortisol, dexamethasone, insulin, glucagon, epinephrine and epidermal growth factor (EGF), were tested. Among these hormones, only insulin, dexamethasone and EGF induced ODC activity and polyamine biosynthesis, especially that of putrescine, in both adult and fetal hepatocytes. The effects of EGF were the most significant. The combined effect of insulin and dexamethasone was additive, while that of insulin and EGF was synergistic. The rate of ODC induction was higher in adult hepatocytes than in fetal hepatocytes, however, the reaction was earlier in fetal hepatocytes. These observations suggest that ODC and polyamines in the fetal stage of development are regulated by a mechanism different from that in the adult liver.

Red blood cell and plasma polyamines in umbilical and maternal blood at delivery were measured using high performance liquid chromatography. The concentration of each polyamine in red blood cells and plasma of umbilical blood was significantly higher than in maternal blood. Spermidine and spermine concentrations in fetal red blood cells decreased markedly with the progress of pregnancy. In addition, younger red blood cells contained more polyamines than older cells. Red blood cell polyamines are closely associated with the cell membrane. Plasma polyamine in umbilical blood reflect active fetal metabolism, whereas red blood cell polyamines mainly reflect alterations in erythropoiesis in bone marrow and may indicate the proliferation of the bone marrow.

Thalamic neurons projecting to both the head of the caudate nucleus and the premotor cortex in the cat were studied by the retrograde fluorescent double labeling technique. After injections of Evans blue into the caudate nucleus, and diamidino-phenylindol into the premotor cortex, a small number of double labeled neurons appeared in the ventral anterior, ventral lateral, anteromedial, rhomboid, central dorsal, central lateral, central medial, paracentral and parafascicular nuclei, in addition to numerous single-labeled neurons. This indicates that some neurons in the thalamic nuclei send bifurcating axons to both the head of the caudate nucleus and the premotor cortex. The caudatal projections of these thalamic neurons are organized in a topical manner.

An anomalous zymogram of lactate dehydrogenase (LDH) in the serum from a patient with liver cirrhosis was reported. Agar-gel electrophoresis of serum showed an extra LDH band close to the anodic side of LDH5 and a wide band of LDH5. Gel filtration of patient's serum in Sephadex G-200 demonstrated an abnormal LDH fraction eluted between immunoglobulin G (IgG) and macroglobulin in addition to a normal LDH component. Chromatographically abnormal LDH was demonstrated on agar gel as extra and wide LDH5 bands and resembled closely human hepatic LDH in various physico-chemical properties such as inhibition by urea or substrate, stability against heat, and Michaelis-Menten's constant. Immunological analyses demonstrated that abnormal LDH could be in the state combined with IgG. Molecular weight of the complex estimated by gel filtration was approximately 300,000. Mixtures of the heated patient's serum with normal or patient's hepatic LDH showed abnormal LDH fraction by gel filtration, whereas abnormal fraction was not demonstrated when heated normal serum was mixed with normal or the patient's hepatic LDH. These results strongly suggest that the occurrence of anomalous LDH zymogram in patient's serum is due to a formation of LDH-IgG complex, which is based on the binding of essentially normal hepatic LDH and abnormal IgG.