Significance of ICSA in the development of diabetes mellitus.
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Biomedical subjects
Publications and source records attributed to M Kondo.
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Naproxen has been administered for 22 febrile episodes of unknown etiology in 21 patients with malignant tumors. Ten patients had malignant lymphomas, and the others had solid tumors. The highest temperature was 38.5 degrees C or more in all but one of the patients. Out of the 22 episodes, 2 episodes were found to have been caused by an infection. The naproxen doses ranged from 300 to 600 mg per day. Of the 20 episodes of neoplastic fever, the temperature decreased 1.0 degree C or more in 16 patients, in 13 of whom the temperature decreased to 37.0 degrees C or less. There was some evidence that suggests the existence of a dose-response relation-ship. The initial use of 600 mg per day seemed to be appropriate. The antipyretic effect did not seem to be influenced by the type of the underlying tumors. Three patients continued to receive naproxen for one to to months. No side effect was observed, excepting for one patient who developed a mild nausea. We thus conclude that naproxen is an effective safe drug for the control of neoplastic fever.
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In 37 patients with seemingly localized non-Hodgkin's lymphoma of the Waldeyer's ring (WR-NHL), lymphangiography (LAG) and/or gallium-67 scans (Ga-67 scans) were done. Before these procedures, 20 patients were diagnosed as Stage I, and 17 as Stage II. LAG was done for 30, and Ga-67 scans for 32, 25 of whom had both. Five patients (16%) were upstaged to Stage III or IV by Ga-67 scans. Only one (3%) had abnormal LAG findings, in whom Ga-67 scans also showed abnormal accumulation in the para-aortic region. Because of this low positive rate, LAG is not recommended for staging of WR-NHL.
Eleven patients with invasive thymoma were treated with radiotherapy. All patients had gross anterior mediastinal tumors that invaded the adjacent structures, four of whom showed intrathoracic dissemination. Before radiotherapy, only one had macroscopic complete resection of the tumor, and another had partial resection; the other nine patients underwent biopsy only. All 11 patients achieved complete remission after radiotherapy, eight of whom have been free from relapse for 31 to 202 months. Three patients experienced recurrence within the thorax but outside the radiation fields. Even after whole mediastinal irradiation, recurrence could occur in the pleural cavity. Therefore, extended radiation fields including the entire hemithorax is recommended. Intensive combination chemotherapy was administered for two patients with recurrence and they achieved complete remission. A possible role of intensive chemotherapy in induction phase for invasive thymomas is discussed.
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Authors present the statistics of the diagnosis and treatment of infertile patients who visited the outpatient clinic of the Department of Obstetrics and Gynecology, School of Medicine, University of Occupational and Environmental Health, Japan throughout 1985. The number of primary infertility (78) was greater than that of secondary infertility (63). The average age and the duration of infertility were 30.5 y. old/3.86 y. (primary) and 31.6 y. old/3.59 y. (secondary), respectively. The most frequent cause of infertility was ovarian-endocrine factor both in primary and secondary infertilities. The second cause was the male factor in primary infertility in spite of the idiopathic factor in secondary infertility. Tubal disorder as a cause was relatively few in both infertilities. So-called open laparoscopy was performed on 11 patients, with little hope of cure. In eight of these patients, disorders of tubal patency and endometriosis, which were not found by hysterosalpingography and hydrotubation before laparoscopy, were discovered for the first time. In twenty pregnancies at the day of statistics, the number of secondary infertility (13) was greater than that of primary infertility (7). All pregnant cases were under 35 years of age and under 5-year of infertility duration at the initial visit to our outpatient clinic. The number 1 cause of infertility was ovarian-endocrine factor. In eight pregnant cases, hysterosalpingography was performed in the same or one cycle before the pregnant cycle. According to the summation of the questionnaire of 65 infertile patients, most of infertile patients were affirmative to in-vitro-fertilization and embryo transfer. Depressive and neurotic tendencies were not remarkable at that time by Self-Rating-Depression Scale (SDS) and Cornell Medical Index (CMI) in 42 infertile patients.
The widespread clinical use of hemodialysis has prolonged the survival of a vast number of uremic patients, but it has also yielded some problems including renal osteodystrophy. Recently, it has become well known that the clinical use of active vitamin D metabolites is effective in many patients with renal osteodystrophy. However, there are many patients with bone diseases resistant to such treatment. Several lines of evidences implicate aluminum as one of the causal factors in the production of such diseases. We recently found 20 patients with bone diseases associated with the deposition of aluminum in front of active calcification in the bone. All of them were undergoing maintenance hemodialysis with softened water thrice weekly and taking aluminum containing antacids and 1 alpha-(OH)D3. The age of the patients ranged between 30 y.o. and 62 y.o. (46.5 +/- 9.0, mean +/- s.d.). All of them had severe bone pain and 8 of them had bone fractures. Bone X-ray, bone scintigraphy, serum Ca, P, ALP, serum aluminum and bone histology were examined. Based on the bone histology, they were classified into four types; inactive type (9), osteomalacia type (6), mild type (4) and mixed type (1). There were no significant differences among each group concerning serum values of Ca, P and aluminum. Serum value of ALP tended to be high in the osteomalacia type, and that of c-PTH was significantly low in the inactive type compared with the other types. Our finding suggest that aluminum associated bone disease is not so rare in Japan and show that the diagnosis of this disease should be made histologically and that clinical and blood chemical features are not reliable for the diagnosis of aluminum associated bone disease in hemodialysis patients.
Human plasma low molecular weight kininogen was purified with ammonium sulfate fractionation, DEAE-cellulose, CM-Sephadex C-50 and aprotinin-agarose affinity column chromatography, after which this was further purified with Sephadex G-150 and DEAE-Sephadex A-50 column chromatographies. Kallikrein activity was measured as the kininogenase activity reflecting the kinin-producing capacity from kininogen. The purification factor from crude plasma to purified substrate was 44-fold, and the recovery was 18%. The purified human substrate did not contain kinin-generating or destroying enzymes which would interfere with kininogenase activity, and showed a cross-reactivity of less than 0.1% against kinin antiserum. In the kininogenase assay, all kininogen was removed by adding ethanol to terminate the enzyme reaction. Because of the high sensitivity of kinin radioimmunoassay, the kinin levels in urine could be determined in very small amounts of samples (0.5 to 2.0 nl of the original urine). These findings indicated that kinin levels in incubation solution could be measured directly, and the control tubes are unnecessary in this assay procedure. In a comparison among human, dog and bovine low molecular weight kininogen as the substrate for human urinary kallikrein, the enzyme activity was 5 and 80 fold higher in the human low molecular weight kininogen, respectively, suggesting that a human substrate is the best for human enzymes. This simple, specific, sensitive and homologous kininogenase assay system seems to be very useful investigating the physiological or pathophysiological role of the renal kallikrein-kinin system in hypertensive and renal diseases.
To determine if clinically observed disorders in heme biosynthetic enzymes, known as sporadic porphyria cutanea tarda (PCT), could be reproduced in experimental animals, male Fischer rats were treated with ethanol, estrogen and hexachlorobenzene (HCB). A series of heme biosynthetic enzymes were assayed. In the rats given free access to 8% ethanol-drinking water for 15 weeks, delta-aminolevulinate (ALA) dehydratase was significantly reduced in erythrocytes. In the liver, ALA synthetase and uroporphyrinogen (UROgen) decarboxylase activities remained unchanged. In bone marrow cells, these activities did not change markedly. In the rats treated with estrogen (1 mg estrioltripropionate/rat/week, IM), no body weight gain was observed during the treatment for 15 weeks and urinary ALA excretion increased to 1.7 fold over normal level. In the liver, a significant increase was observed in the activity of ALA dehydratase, but other enzymes remained within the normal level. In bone marrow cells and erythrocytes, ALA dehydratase was also increased. ALA synthetase increased only in bone marrow cells to 2.1 times higher than the control level. In rats fed 0.3% HCB-diet for 8 weeks, urinary excretion of ALA, coproporphyrin and uroporphyrin increased to 2.4, 3.3 and 3.8 times higher than the controls, respectively. In the liver, an increase was observed in ALA synthetase, while a decrease was observed in ALA dehydratase and UROgen decarboxylase. In bone marrow cells and erythrocytes, ALA dehydratase was reduced and activities of other enzymes did not show any changes. These results indicate that alcohol, estrogen and HCB do not produce phenomena similar to those observed clinically in PCT.
An experimental animal model of human ulcerative colitis using lipopolysaccharide (LPS) was studied. Rabbits were skin-sensitized by LPS and challenged with intrarectal instillation of LPS after 1% formalin enema. The course of experimental colitis was followed by performing serial colonofiberscopic examinations and biopsy. Petechiae appeared from the 8th hour, and ulcers and bleeding on the 3rd day. Mild macroscopic changes continued for about 2 weeks. By repeating the LPS enema after the initial treatment, the colitis was maintained for over 1 month. Control groups without formalin enema revealed no macroscopic changes, and the groups with only formalin enema showed mild transient changes. The endotoxin level in the blood during the experiment increased (36 pg/ml) at 24 h after the treatment in the LPS-sensitized group, while non-sensitized control rabbits had higher levels of endotoxin. Though fibrinogen and PTT levels had increased at 24 and 72 h, these levels were marked in the control rabbits. The direct reaction of LPS was minimal, and local immune reaction by LPS seems to play an important role in the perpetuation of experimental colitis. Tissue fibrinolysis of the colon increased significantly as the mucosal damage appeared. This experimental colitis with LPS may be useful as a model of human ulcerative colitis.
In order to compare the functional state of sympathetic ganglia in spontaneously hypertensive (SHR) with those in normotensive Wistar Kyoto rats (WKY), protein synthetic activity was examined by light microscopic autoradiography with 3H-lysine. The number of silver grains over the cytoplasm of ganglion cells in the superior cervical and stellate ganglia of newborn and 30-day-old animals were counted on photographic enlargements. In both sympathetic ganglia there were significantly more silver grains over ganglion cells in SHR compared with age-matched WKY at 15, 60, and 120 min after injection of 3H-lysine. The increased incorporation of the label by both sympathetic ganglia was more marked in newborn than in 30-day-old animals. This result shows that protein synthetic activity in these ganglion cells is increased in SHR from the newborn stage. It is suggested that a congenital hyperfunction of sympathetic ganglia occurs in SHR.
The clinical usefulness of calcium antagonists was studied in four patients with reactive hypoglycemia including two with alimentary and two with idiopathic. All patients had hyperresponses of plasma insulin (IRI) and C-peptide (CPR) during an oral glucose tolerance test (OGTT). A calcium antagonist (diltiazem 90 mg/d, or nifedipine 30 mg/d, or nicardipine 60 mg/d) was administered orally for about two months. After two months of treatment, plasma IRI and CPR responses during the OGTT were clearly suppressed in all patients and symptomatic reactive hypoglycemia disappeared. One month after the discontinuation of the treatment in two patients, plasma IRI and CPR responses during the OGTT became higher again and symptomatic reactive hypoglycemia recurred. In addition, an intravenous glucose tolerance test was performed before and after two months of the treatment with calcium antagonists in the two patients with reactive hypoglycemia and seven patients with hypertension, who were free from glucose intolerance and were also treated with a calcium antagonist. In these patients, plasma IRI and CPR responses were also reduced after the treatment compared with those before the treatment. These results suggest that calcium antagonists are useful as therapeutic agents for the treatment of reactive hypoglycemia associated with hyperinsulinemia, and that one of the main mechanisms of action of calcium antagonists is a direct action on the pancreatic B-cell to inhibit glucose-induced insulin release.
The role of complement in the polymorphonuclear leukocyte (PMN)-mediated tumor cell destruction in cancer ascites was investigated in relation to a streptococcal preparation OK-432, a so-called biological response modifier. Incubation of OK-432 with fresh human serum at 37 degrees C for 60 min resulted in the generation of C3a and C5a chemotactic factors. Intraperitoneal (i.p.) injection of the mixture to a patient with cancer ascites revealed an accumulation of PMNs in the ascitic fluid for a longer period with a rapid reduction of the ascitic fluid, than an intraperitoneal injection of OK-432 alone examined in the same patient. PMNs were found to invade clusters of the tumor cells and then form rosettes followed by the destruction of tumor cells. These findings induced by OK-432 continued over 10 days in the presence of fresh serum, while diminished within 3-4 days when OK-432 alone was injected. When fresh human plasma or fresh frozen plasma was used instead of serum and i.p. injected with OK-432 avoiding preincubation, the same cytological and clinical changes were observed in other patients. These data strongly indicate that OK-432 activates human complement either in vitro or in the peritoneal cavity, and induces PMNs to accumulate in the ascitic fluid. Although the mechanism of killing of tumor cells by PMNs is obscure, addition of human serum or plasma to i.p. use of OK-432 seems to be valuable for the management of patients with malignant ascites.