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Biomedical subjects

S Akazawa

Publications and source records attributed to S Akazawa.

At least 109 records · Page 6Linked to original sources
PubMed1993

[Serum nitroglycerin concentrations during extracorporeal circulation with a membrane oxygenator incorporated with a cardiopulmonary bypass circuit].

The effect of a cardiopulmonary bypass circuit (CPB) on serum nitroglycerin (TNG) concentrations was studied in eight patients scheduled for cardiac surgery. The CPB consisted of polyvinyl chloride tubes and polypropyrene membrane oxygenator. TNG was administered intravenously at a rate of 1 microgram.kg-1.min-1 after induction of anesthesia. Blood samples were obtained from the radial artery, central vein, venous inlet of the CPB, and arterial outlet of the CPB. No significant difference in serum TNG concentration was found between the venous inlet of the CPB and arterial outlet of the CPB. Serum TNG concentration tended to increase during complete extracorporeal circulation. This suggests that the hypothermic inhibition of TNG metabolism may be greater than the adsorption of TNG by the CPB.

Adolescent↗
PubMed1993

[Atherosclerosis and endocrine disorders].

It has been demonstrated that high cholesterol levels are correlated with development of atherosclerosis, while high levels of high density lipoprotein (HDL) are associated with reduced cardiovascular mortality. Some endocrine disorders accelerate atherosclerosis in association with hypercholesterolemia, hypertension, low level of HDL and hypertriglyceridemia. In patients with acromegaly, hypertriglyceridemia is sometimes accompanied with and aggravated by the presence of impaired glucose tolerance. In patients with hypothyroidism, coronary atherosclerosis may develop in association with hypertension, hypercholesterolemia and moderate elevation of triglyceride which is often accumulation of intermediate lipoprotein. Cushing syndrome may accelerate atherosclerosis by the fact that corticosteroid may induce or exacerbate several known coronary risk factors including hypertension, hypercholesterolemia and impaired glucose tolerance. Estrogen has beneficial effects on the cardiovascular system for postmenopausal women by affecting lipid metabolism, decrease of LDL and increase of HDL.

Arteriosclerosis↗
PubMed1993

[Phase I study of 5-fluorouracil and l-leucovorin].

Leucovorin, given usually by i.v. injection or orally changes to 5, 10-methylene tetrahydrofolate in tumor as well as normal cells. And in normal FdUMP, an active metabolite of 5-FU, binds tightly to thymidylate synthase in the presence of cofactor, 5, 10-methylene tetrahydrofolate. This interaction leads to potentiate the cytotoxic effect of 5-FU by prolonged inhibition of thymidylate synthase. Phase I study using l-leucovorin (l-LV), an active form of leucovorin, combined with 5-FU, was conducted. In the weekly schedule, 5-FU was fixed to 600mg/m2, and l-LV dose was escalated from 125 mg/m2 to 250mg/m2, if toxicity was acceptable. On the other hand, in the five consecutive-day schedule, 5-FU was fixed to 370mg/m2 and l-LV was escalated from 25mg/m2 to 50mg/m2, 100mg/m2 and 200 mg/m2. l-LV 10mg/m2 was tested as reference. On weekly schedule of l-LV 250mg/m2, grade III diarrhea was seen in 2 cases and grade IV leucopenia was seen in one. In five consecutive-day schedule, at each dose of l-LV, stomatitis, nausea plus vomiting, anorexia, anemia and leucopenia were seen. However, the increase of toxicities were not seen by dose escalation of l-LV. Then, we have been conducted a randomized early phase II study using 250 mg/m2 of l-LV weekly (arm A) and 100mg/m2 (arm B) or 10mg/m2 (arm C) of l-LV for 5 consecutive days in gastric and colorectal cancer by multicenter cooperative study. Plasma concentrations of l-LV were maintained > 10(-5) mol/L for over 5 hrs. after 2 hrs. infusion of 250 mg/m2 of l-LV and for over one hr. after a rapid injection of 100mg/m2 of l-LV.

Adult↗
PubMed1993

[A new sequential chemotherapy of methotrexate with 5-fluorouracil against advanced colo-rectal cancer].

A new sequential chemotherapy consisting of intravenous (IV) administration of methotrexate (MTX) 50 mg/m2 followed by 3 equal IV doses of 5-fluorouracil (5-FU) 500 mg/m2 at 1.4 and 21 hrs. and a leucovorin rescue (15 mg/body/8 hr) from 24 hrs. after MTX for 3 days was applied every two weeks for the patients with advanced colo-rectal cancer. The effectiveness of this MTX/3-dose 5-FU regimen was compared retrospectively with that of the standard sequential regimen consisting of the IV administration of MTX 100 mg/m2 followed by a single IV dose of 5-FU 800 mg/m2 one hr. later and a leucovorin rescue (21 mg/body/6 hr) 24 hrs. later given every week, namely MTX/1-dose 5-FU regimen. Partial response was achieved in 7 (46.7%) of 15 evaluable patients with the MTX/3-dose 5-FU regimen and in 3 (13.6%) of 22 evaluable patients with the MTX/1-dose 5-FU regimen (p < 0.05). The median survival times were 13 and 9 months, respectively. There were no significant difference in the patient characteristics between the two groups, and the toxic effects were much lower in the MTX/3-dose 5-FU than in the MTX/1-dose 5-FU regimen. It is therefore, concluded that the MTX/3-dose 5-FU regimen is superior to the standard MTX/1-dose 5-FU regimen.

Adult↗
PubMed1992

Immunoelectron microscopic localization of antigens which react with islet cell cytoplasmic antibodies within human pancreatic beta cells.

The presence of circulating autoantibody to islet cell cytoplasm is considered to be an important marker of Type 1 (insulin-dependent) diabetes mellitus. In the present study using islet cell cytoplasmic antibody positive patient sera as the first antibody, we studied the intracellular distribution of its antigen at the electron microscopic level using the pre-embedding immunoperoxidase method. Specific immunoreactivity was found in the membranes of beta cell-secretory granules and cytoplasmic membranes. This result is compatible with the interpretation that the antigen(s) on the membranes of beta cell secretory granules is (are) the target of islet cell cytoplasmic antibody.

Autoantibodies↗
PubMed1992

Autoantibodies to 64,000-M(r) islet cell protein in long-term type 1 (insulin-dependent) diabetic patients.

Autoantibodies to the 64,000-M(r) (64K) islet cell protein, identified as glutamic acid decarboxylase, were assayed in 46 Type 1 (insulin-dependent) diabetic patients with a disease duration of more than 5 years. Of 46 Type 1 diabetic patients, 18 (39.1%) were found to be positive for 64K antibodies and 12 of these patients had been diagnosed with autoimmune thyroid disease. Serum C-peptide levels were not detectable in 15 of 18 patients positive for 64K antibodies. The samples were also tested for titres of islet cell antibodies. Islet cell antibodies were detected in 15 (32.6%) of the 46 patients and all the islet cell antibody positive patients were also found to be positive for 64K antibodies. Furthermore, of these 15 patients 12 had previously been diagnosed with autoimmune thyroid disease. A correlation between levels of 64K antibodies and islet cell antibody titre revealed that higher levels of 64K antibodies were observed in patients who had higher islet cell antibody titre. These results demonstrate that most long-term Type 1 diabetic patients with 64K antibodies were also positive for islet cell antibodies complicated by autoimmune thyroid disease.

Adult↗
PubMed1992

Regional differences in insulin receptor function in Werner's syndrome.

Werner's syndrome is a genetic disease characterized by premature aging and is often associated with glucose intolerance due to insulin resistance. The clinical manifestations in this syndrome are preferentially expressed in the face and acral regions without apparent involvement of the trunk. We compared insulin receptor binding and amino acid uptake of fibroblasts derived from the forearm that had sclerodermoid features, and from the abdomen that was apparently normal in a patient with Werner's syndrome. In normal controls, specific insulin binding was not different in forearm and abdomen-derived fibroblasts (10.72 +/- 2.11%, 10.40 +/- 1.27%, respectively). In the patient, however, specific insulin binding was reduced in the fibroblasts derived from the forearm compared with those derived from the abdomen (3.55%, 8.16%, respectively). Scatchard analysis revealed that the reduction in insulin binding of the forearm fibroblasts from the patient was due to a reduction in receptor number with no change in receptor affinity. The dose-response curve for insulin of alpha-aminoisobutyric acid (AIB) uptake is shifted to the right in the fibroblasts derived from the acral area. The results show that in a patient with Werner's syndrome, regional differences occur in fibroblast insulin receptor binding and function. This suggests early phenotypic expression of the genetic abnormality of insulin receptor function in these patients.

Abdomen↗
PubMed1992

Type 1 (insulin-dependent) diabetes mellitus with coexisting autoimmune thyroid disease in Japan.

Type 1 diabetes mellitus is known to be a heterogenous disease which is frequently complicated with other autoimmune thyroid diseases (AITD). The present study was designed to investigate the clinical characteristics and HLA antigens in Japanese Type 1 diabetic patients with AITD. Subjects were 25 Type 1 diabetic patients with AITD (13 Graves' disease and 12 Hashimoto's thyroiditis) and 32 Type 1 diabetic patients without AITD. Compared with Type 1 diabetic patients without AITD, age at onset of diabetes was later and positive ICA persisted much longer in the diabetic patients with AITD. Compared with normal controls, DR9 was increased in the patients with AITD, while DR4 was increased in those without AITD. Type 1 diabetic patients with AITD were characterized by the late onset of diabetes, persistent ICA and increased association with DR9. These results suggest that immunological and genetic heterogeneity may exist within Japanese Type 1 diabetic patients.

Adolescent↗
PubMed1992

[Postoperative pain relief by continuous epidural infusion of bupivacaine and buprenorphine].

Continuous postoperative pain relief produced by epidural block with bupivacaine and buprenorphine was evaluated in 12 patients after thoracotomy, 19 patients after upper abdominal surgery, and 14 patients after lower abdominal surgery. Patients initially received 8 ml of 0.25% bupivacaine and 0.1 mg of buprenorphine at recovery room in operating theater and continuously received the mixture of 0.25% bupivacaine and 5 micrograms.ml-1 buprenorphine at a rate of 1 ml.h-1 using a portable pump. About fifty percent of the patients did not need additional narcotics during 48 postoperative hours. About ninety percent of the patients needed one additional narcotics during 48 postoperative hours. The authors conclude that epidural analgesia with the mixture of bupivacaine and buprenorphine produces satisfactory postoperative pain relief.

Abdomen↗
PubMed1992

[Biochemical modulation of 5-FU with interferon].

A phase II clinical trials of the combination of 5-FU and interferon (IFN) were reviewed. The treatment regimen was based on the method reported by Scott Wadler, et al: 5-FU was administrated as continuous infusion at 750 mg/m2/day for 5 consecutive days and as intravenous bolus at 750 mg/m2 weekly for 7 weeks beginning on day 12. IFN was administrated subcutaneously at 9 x 10(6) I.U three times a week during weeks 1 to 8. Although the mechanism of action remains to be elucidated, some studies in immunological, pharmacokinetics, or biochemical viewpoint were reported. In this paper, the mechanisms of action related to TS and TK were introduced in biochemical viewpoint. Furthermore, side effects of IFN/5-FU combination and dual modulation of 5-FU with IFN and LV were referred.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Production of islet cell antibodies from Epstein-Barr virus-transformed peripheral blood lymphocytes in type 1 (insulin-dependent) diabetic patients.

Islet cell antibodies are usually detected in the sera of almost all Type 1 (insulin-dependent) diabetic patients within several months after onset of the disease. The antibodies then disappeared quite early during the course of the disease. The present study was undertaken to detect islet cell antibody-producing clones in peripheral blood lymphocytes of Type 1 diabetic patients whose islet cell antibodies could not be detected in sera. Epstein-Barr virus-transformed lymphocytes were employed to enhance the production of antibodies and to detect the clones from peripheral blood lymphocytes. Peripheral blood lymphocytes were obtained from 40 islet cell antibody-negative Type 1 diabetic patients, 10 antibody-positive Type 1 diabetic patients, 30 Type 2 (non-insulin-dependent) diabetic patients and 40 normal control subjects. Epstein-Barr virus-transformed lymphocytes were cultured for 4 weeks and the culture supernatants were used for assay of islet cell antibodies. Islet cell antibody assays were performed by immunohistochemical methods using peroxidase-labelled protein A for IgG antibodies, peroxidase-labelled anti-human IgM antibodies for IgM antibodies and fresh frozen human pancreatic tissue. IgG-islet cell antibodies were detected in 26 islet cell antibody-negative patients (65%), eight antibody-positive patients (80%) and one Type 2 diabetic patient (3%) in the culture supernatants. Islet cell antibodies in the supernatants could not be detected in any of the control subjects. IgM-islet cell antibodies could not be detected in any of the patients or control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1991

Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats.

We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P less than 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 +/- 0.04 vs. 3.87 +/- 0.03 mm, P less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 +/- 0.06 vs. 3.37 +/- 0.04 mm, P less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Islet cell antibodies in patients with autoimmune thyroid disease.

Islet cell antibodies (ICAs) were assayed in 316 patients with autoimmune thyroid disease (AITD; 190 with Graves' disease, 126 with Hashimoto's thyroiditis), 53 patients with insulin-dependent diabetes mellitus (IDDM), and 144 healthy control subjects. ICAs were measured by an immunohistochemical method with peroxidase-labeled protein A and human pancreatic tissues. The prevalence of ICAs in patients with AITD was 7.6% (24 of 316), whereas the prevalence in control subjects was 0.7% (1 of 144). Among 24 ICA+ patients, 20 (83%) had IDDM. In these 20 patients, the duration of diabetes from clinical onset was 5.4 +/- 5.1 yr. ICAs in patients with IDDM alone were positive in 90.9% at 1 yr and 7.7% at 5 yr after the onset of diabetes. These data have shown that most ICA+ patients with AITD have IDDM and that the prevalence of ICAs in patients with AITD in Japanese is as high as that found among whites, whereas the incidence of IDDM in Japanese is approximately one-thirtieth or one-fiftieth of that in whites.

Adolescent↗
PubMed1991

Effects of cyclosporin A and low dosages of steroid on posttransplantation diabetes in kidney transplant recipients.

OBJECTIVE: To investigate the adverse effects of cyclosporin A (CsA) on pancreatic beta-cell function in kidney transplant recipients. RESEARCH DESIGN AND METHODS: The study consisted of 73 patients without a history of diabetes mellitus who had undergone kidney transplantation in our clinic. RESULTS: We experienced a higher incidence of posttransplantation diabetes mellitus (PTDM) in patients receiving CsA and low dosages of methylprednisolone (6/20, 30%, P less than 0.05) than in patients receiving conventional therapy of azathioprine methylprednisolone (4/53, 7.5%) since the introduction of CsA. In all 6 patients in the CsA-treated group, PTDM occurred within 3 mo after transplantation. The CsA level during the initial 3 mo posttransplant was significantly higher in diabetic than nondiabetic subjects, and the highest CsA level was observed shortly (1 mo) before the development of PTDM. After an average of 71 days of insulin therapy, there was complete remission of PTDM in 5 of 6 diabetic patients, with a corresponding decrease in CsA level. For the patients who were in remission for greater than 1 yr, a significant improvement of glucose intolerance was observed in association with a significantly higher insulin response to oral glucose load; however, their glycemic profile still showed a significantly higher plasma glucose concentration and a prolonged continuous elevation without initial peak of the insulin-response curve in contrast to the normal pattern found in nondiabetic subjects in the CsA-treated group. CONCLUSIONS: This study suggests that CsA in combination with low dosages of steroid may have adverse effects on glucose metabolism, which may lead to effects similar to those in non-insulin-dependent diabetes mellitus.

Azathioprine↗
PubMed1990

Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myo-inositol supplementation.

To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p less than 0.05) and 64.6% (p less than 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p less than 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldehyde Reductase↗
PubMed1990

The echocardiographic assessment of left ventricular performance during sevoflurane and halothane anesthesia.

The cardiovascular effects of sevoflurane were studied and compared with those of halothane in 30 healthy patients. The patients were assigned to receive 1 MAC sevoflurane (n = 10), 2 MAC sevoflurane (n = 10) or 1 MAC halothane (n = 10) in N(2)O 2 l.min(-1) and O(2) 4 l.min(-1). The changes in left ventricular diastolic and systolic dimension (Dd and Ds), fractional shortening (FS), mean velocity of circumferential fiber shortening (mVcf), left ventricular diastolic and systolic volume (Vd and Vs), stroke volume (SV), ejection fraction (EF) and cardiac index (CI) were evaluated by echocardiography. Sevoflurane produced significant dose-dependent decreases in FS, mVcf, EF and SV, but no significant changes in Dd and Vd. Therefore, the decrease in SV was due mainly to the increase in left ventricular residual volume (Vs). One MAC halothane produced a more significant decrease in FS, mVcf, EF and SV, when compared to values obtained at 1 MAC sevoflourane ( P < 0.01). CI was more significantly decreased with 1 MAC halothane than with 1 MAC and 2 MAC sevoflurane ( P < 0.01). This was brought about by a slight decrease in HR with halothane and a slight increase in HR with sevoflurane, in addition to a smaller decrease in SV with sevoflurane than with halothane. This study suggests that sevoflurane may better preserve cardiac function as a pump in healthy patients, when compared to halothane.

Journal Article↗