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Biomedical subjects

K Ota

Publications and source records attributed to K Ota.

At least 235 records · Page 13Linked to original sources

Nation-wide randomized comparative study of doxorubicin, vincristine and prednisolone combination therapy with and without L-asparaginase for adult acute lymphoblastic leukemia.

A randomized clinical trial of combination chemotherapy for adult acute lymphoblastic leukemia (ALL) with doxorubicin, vincristine and prednisolone with and without L-asparaginase (AdVP vs L-AdVP) was conducted, involving 58 institutions throughout Japan. After reaching complete remission (CR), patients were treated with the same regimen for more than 2 years. Among 166 evaluable cases of the 198 cases enrolled, CR rates were 63.1% (53/84) with AdVP and 64.6% (53/82) with L-AdVP (P = 0.837). Median survival times and 7-year survival rates were 12.7 months and 21.2% with AdVP, and 16.0 months and 22.3% with L-AdVP (P = 0.955 by generalized Wilcoxon test [GW], P = 0.952 by log-rank test [LR]). Median disease-free survival times and 7-year survival rates were 13.5 months and 23.8% with AdVP and 17.0 months and 30.6% with L-AdVP, showing some increments for L-AdVP but no statistical significance (P = 0.141 by GW, P = 0.300 by LR). Among the cases of extramurally confirmed FAB subtypes, CR rates were 75.9% (63/83) for the L1 subtype and 51.3% (39/76) for the L2 subtype (P = 0.001). As to adverse effects, pancreatitis was complicated more frequently in L-AdVP than in AdVP (P = 0.039). Other side effects such as hyperbilirubinemia, diabetes mellitus, diarrhea and hypofibrinogenemia were observed more frequently with L-AdVP, but with no statistical significance. Thus, addition of a single course of L-asparaginase in the induction phase of combination chemotherapy with doxorubicin, vincristine and prednisolone did not significantly enhance the effect of antileukemic treatment of adult ALL.

Adolescent↗

Pharmacokinetics of doxorubicin and its active metabolite in patients with normal renal function and in patients on hemodialysis.

The comparative pharmacokinetics of doxorubicin (DOX) were investigated in five hemodialysis (HD) and eight non-hemodialysis (non-HD) patients who were infused with a 40- to 60-mg dose of DOX at a constant rate over 30 min. A significant difference was observed in the total body clearance (Cl tot) of DOX between HD and non-HD patients. The area under the curve (AUC) for both DOX and doxorubicinol (DOXol), an active metabolite, showed increases of approximately 1.5 and 3 times in HD patients as compared with non-HD patients. Although these differences were not statistically significant (P < 0.1), the mean residence time (MRT) of DOX and DOXol in HD patients showed a 2-fold increase in comparison with those in non-HD patients. Compartmental analysis indicated that the greater AUC values and longer MRT of DOX and DOXol in HD patients resulted from the lesser DOXol formation and disappearance of rate constants. As a consequence of the decrease in Cl tot for DOX and the marginal hemodialysis clearance of both DOX and DOXol, the present study suggests that the exposure to DOX and DOXol obtained in HD patients greater than achieved in non-HD patients. Careful attention should therefore be paid to HD patients receiving DOX.

Aged↗

Absence of right superior vena cava that was not detected by insertion of a pulmonary arterial catheter via the right internal jugular vein.

Pulmonary arterial catheter (PAC) placement under fluoroscopy is a useful and safe method to diagnose certain congenital cardiac anomalies [1]. However, when a PAC for intraoperative monitoring is placed without the aid of fluoroscopy, it may be inadvertently placed into anomalous veins. The following report presents a case of persistent left superior vena cava (PLSVC) with absence of right superior vena cava, which was not detected by a PAC inserted via the right internal jugular vein.

Aged↗

Effect of deoxyspergualin on vascular rejection in canine kidney transplantation.

Deoxyspergualin (DSG), an analogue of spergualin produced by Bacillus laterosporus, has a strong immunosuppressive effect in various transplantation models. In this study, we investigated the effect of DSG on vascular rejection in canine kidney transplantation. To enhance vascular rejection, donor-specific blood transfusion (DST) was carried out on days 28, 21 and 14 preceding kidney transplantation. After DST, the donor kidney was transplanted to the recipient iliac fossa. The recipient animals were divided into five groups: namely, Group 1 (n = 7), no treatment; Group 2 (n = 6), DST only; Group 3 (n = 5), DSG only (treated with DSG intravenously at 1.2 mg./kg./day for the first 3 days after transplantation, 1.0 mg./kg./day for the following 3 days and 0.8 mg./kg./day for the following 8 days); Group 4 (n = 6), DST and DSG treatment (same protocol as Group 3); and Group 5 (n = 5), DST and cyclosporine (CsA) (treated with CsA orally at 10 mg./kg./day for 14 days after transplantation). In Group 2, DST treatment significantly reduced kidney graft survival time (8.6 +/- 2.2 days) compared with Group 1 (14.1 +/- 5.5 days). Despite DST, DSG treatment (Group 4) significantly prolonged graft survival time (29.5 +/- 2.6 days), whereas treatment with CsA (Group 5) did not prolong survival time (14.1 +/- 5.5 days) (Group 4 versus 5, p < 0.01). The onset of rejection was significantly delayed in Group 4 (22.1 +/- 2.7 days) compared with Groups 2 (5.7 +/- 2.4 days) and 5 (13.0 +/- 5.7 days) (p < 0.01). In contrast, the interval between rejection onset and animal death was significantly reduced in Groups 2 (3.0 +/- 0.6 days) and 5 (2.4 +/- 1.0 days) compared with Group 4 (7.3 +/- 1.7 days) (p < 0.01). These findings suggest that DSG successfully prevented humoral-type (accelerated acute-type) rejections. Histologically, nonDST groups (Groups 1 and 3) showed minimum vascular rejection. In contrast, all recipients in Group 2 showed severe vascular rejection, as did 80% of CsA treated-animals (Group 5). Despite DST, however, 84% of DSG treated-animals (Group 4) showed minimal or mild vascular rejection and only 17% had severe rejection (Group 4 versus 5, p < 0.04). These data suggest that both clinically and histologically, DSG has more potent immunosuppressive effects against humoral and vascular rejection than CsA.

Animals↗

Treatment of adult T-cell leukaemia-lymphoma with irinotecan hydrochloride (CPT-11). CPT-11 Study Group on Hematological Malignancy.

A late phase II study of a new camptothecin analogue, irinotecan hydrochloride (CPT-11), was conducted to evaluate the anti-tumour effect and toxicity in patients with refractory leukaemia and lymphoma including adult T-cell leukaemia (ATL)-lymphoma, in a multi-institutional cooperative study. All the patients with ATL had been previously treated with various conventional combination chemotherapies and were refractory to these therapies or had relapsed. CPT-11 was administered at a dose of 40 mg m-2 day-1 for three consecutive days repeated weekly until evidence of disease progression. One complete remission and four partial remissions were achieved in 13 assessable patients with ATL. The median total dose to achieve remission was 240 mg m-2 and the median duration of response was 31 days. The major toxicities were leucopenia (83%), diarrhoea (62%) and nausea/vomiting (69%). These were relatively severe, but they were generally tolerable and reversible. However, one patient died probably as a result of this therapy. No effective chemotherapy for adult T-cell leukaemia-lymphoma has yet been established, and the prognosis for patients with this disease is very poor. Our results suggest that CPT-11 may be a promising agent for this disease. Further combination therapy with CPT-11 is needed to improve the therapy for ATL.

Adult↗

Complications in blood access for hemodialysis.

We retrospectively analyzed a total of 580 blood access complications that occurred at one institution from January 1991 to December 1992. Dysfunction and thrombosis of arteriovenous fistulas (AVFs) due to insufficient blood flow were the most frequent complications (451, 77.8%). Two hundred sixty-eight (71.5%) patients were treated by reconstructing the AVF at a proximal location in the ipsilateral arm. Sixty seven patients had prosthetic material. Their cumulative patency rates for 1 year were 74.6% with expanded polytetrafluoroethylene and 64.2% with polyurethane grafts. Twenty patients had blood access infections, 15 of whom had artificial grafts. Six patients with infections of artificial grafts were successfully treated by local resection with graft rerouting. Venous hypertension due to deep venous thrombosis developed in 23 patients. Fifteen (65.2%) had no previous trauma, and 18 (78.3%) required closure of AVFs. Aneurysm occurred in 40 patients, which included 13 at an anastomosis site in autogenous AVFs, 13 in repeatedly puncturing shunt veins, 11 in prosthetic grafts, and 3 in superficialized arteries. One patient died from septic shock associated with graft infection, and 1 suffered a fatal pulmonary embolism after replacement with a prosthetic graft. The other patients who received surgical treatment for their complications were successfully treated without life- or limb-threatening consequences. Operations developed to provide adequate blood access for hemodialysis have significant rates of complications. Surgeons performing such procedures need to be well-versed in techniques for creating blood access and for treating attendant complications.

Adolescent↗

Extraction of serum proteins adsorbed on the surface of dialysis membranes.

Extraction of adsorbed proteins from dialysis membranes that had been used during actual hemodialysis procedures was performed. The condition of extraction with SDS plus 2-mercaptoethanol at 95 degrees C is more efficient than with only PBS or with SDS solution without 2-mercaptoethanol at 37 degrees C.

Adsorption↗

Effects of acute salt loading on vasopressin mRNA level in the rat brain.

To assess the mutual relationship between acute osmotic stimulation and arginine vasopressin (AVP) gene expression, 2 ml/100 g body weight of 0.9 M NaCl was intraperitoneally administered into conscious rats. They were decapitated to collect blood and brain samples before and 15 min and 1, 3, 6, and 9 h after the injection. The total RNA from the hypothalamus or whole brain tissue was used to determine AVP mRNA by Northern blot analyses with a complementary DNA probe. Plasma AVP and osmolality increased rapidly and transiently 15 min and 1 and 3 h after the injection. AVP mRNA was detected in the hypothalamus but not in the brain tissue without hypothalamus under basal and stimulated conditions. Brain AVP mRNA increased 2.2-fold at 3 h and 1.7-fold at 6 h (P < 0.05-0.01). These increases appeared to be due to the appearance of AVP mRNA with the shorter migration in the gel. These results suggest that an acute osmotic challenge increases AVP mRNA with size heterogeneity within the hypothalamo-hypophyseal tract.

Actins↗

Effects of an acute water load on plasma ANP and AVP, and renal water handling in hypothyroidism: comparison of before and after L-thyroxine treatment.

To assess whether atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) participate in impaired water excretion in patients with hypothyroid states (HS), an oral acute water loading (WL) test (20 ml/kg.BW/45 min) was performed before and after L-thyroxine (T4) treatment in 5 hypothyroid patients. Plasma ANP, AVP, osmolality (Posm), total protein and renal water excretion were simultaneously determined, and these data were compared to the data from five normal subjects (NS). The impaired water excretion rate in HS was entirely improved in the euthyroid states (ES) after T4 therapy for at least 7 months. Plasma ANP in HS was lower than that in NS (5.9 +/- 0.9 vs. 16.5 +/- 3.6 pmol/L, P < 0.05), but increased after T4 treatment (21.2 +/- 5.7 pmol/L, P < 0.05). Plasma AVP in HS (1.6 +/- 0.5 pmol/L) showed a tendency to be lower than those in ES and NS (2.9 +/- 0.4 and 2.9 +/- 0.7 pmol/L), but did not respond to a fall in Posm after WL, unlike ES and NS. Significant positive correlations were noticed between Posm and plasma AVP in ES and NS, but not in HS. These results suggest that not only the impaired release and/or metabolisms of AVP and ANP, but also derangement of renal water and electrolytes handling might induce attenuation of CH2O formation in hypothyroid states.

Adult↗

Effects of interleukin-1 beta on blood pressure, thermoregulation, and the release of vasopressin, ACTH and atrial natriuretic hormone.

To assess how interleukins (IL) affect the release of vasopressin (AVP), atrial natriuretic hormone (ANH), and ACTH and the regulation of blood pressure (BP), heart rate (HR) and rectal temperature (RT), the 3 doses of 1.73 (low dose, LD), 8.63 (medium dose, MD), and 43.16 pmol/100 gBW (high dose, HD) of human recombinant IL-1 beta were intravenously (iv) administered in conscious rats, and plasma AVP, ANH, and ACTH, BP, HR and RT were determined simultaneously. In the control group (CON), the drug was omitted. Circulatory IL-1 beta levels were determined in each dose, and indomethacin (1 mg/rat, IM) was administered iv in the HD and CON groups. Plasma IL-1 beta increased transiently following IL-1 beta administration in each group. Plasma AVP, ANH, and ACTH increased in the LD, MD, and HD groups, respectively. Mean arterial BP (MABP) and RT increased in the LD group, but HR did not change. In the MD and HD groups, MABP decreased at 30 min followed by its increase at 120 min, but RT in both groups decreased. In the CON group, these parameters did not change. IM attenuated plasma AVP and ACTH responses to HD and also inhibited decreases in MABP and RT. These results suggest that IL-1 beta affects the release of AVP and ACTH, blood pressure and thermogenesis via prostaglandins (PGs), but ANH release related to IL-1 beta may not be mediated by PGs.

Adrenocorticotropic Hormone↗

Effects of a nitric oxide synthase inhibitor on vasopressin and atrial natriuretic hormone release, thermogenesis and cardiovascular functions in response to interleukin-1 beta in rats.

To assess whether nitric oxide (NO) formed by IL-1 beta affects vasopressin (AVP) and atrial natriuretic hormone (ANH) release and the regulation of blood pressure and body temperature, intravenous infusion of either N omega-nitro-L-arginine methyl ester (L-NAME) alone (50 micrograms/kg.body weight.min for 135 min), human recombinant interleukin 1 beta (IL-1 beta) alone (750 ng/kg.body weight.min for 120 min), or L-NAME (50 micrograms/kg.body weight.min for 135 min) with IL-1 beta (750 ng/kg.body weight.min for 120 min), was performed following priming doses of L-NAME (2 mg/kg.body weight) and IL-1 beta (7.5 micrograms/kg.body weight) into conscious rats (n = 6 each). In the control group, saline alone was administered. Plasma AVP and ANH, mean arterial blood pressure (MABP), heart rate (HR) and rectal temperature (RT) were determined. In response to L-NAME, plasma AVP significantly increased, but plasma ANH did not change, despite increases in MABP and decreases in HR. In response to IL-1 beta, both plasma AVP and ANH increased with decreases in MABP and RT without any changes in HR. With L-NAME and IL-1 beta, both plasma AVP and ANH increased, and depressor response to IL-1 beta was partly attenuated by L-NAME, without any changes in RT. With saline alone, none of these parameters changed during the study. These results suggest that NO may directly affect the release of AVP and ANH and the regulation of body temperature and blood pressure, but NO formed by IL-1 beta may not have direct effects on the release of these hormones, and the regulation of blood pressure and temperature.

Amino Acid Oxidoreductases↗

Nephrotic tunnels in glomerular basement membrane as revealed by a new electron microscopic method.

To clarify the ultrastructure in situ of the normal human glomerular basement membrane and ultrastructural changes of the glomerular basement membrane in patients with nephrotic syndrome, specimens of normal renal tissue and specimens from patients with membranous nephropathy, lupus nephritis, minimal change nephrotic syndrome, diabetic nephropathy, and Alport's syndrome were obtained. Specimens were examined by transmission electron microscopy by the newly devised "tissue negative staining method." Normal glomerular basement membrane showed a three-dimensional lattice-like meshwork of fibrils measuring 1.9 +/- 0.4 nm in diameter that formed numerous uniform, round, oval, or polygonal pores 2.5 +/- 0.4 nm in short diameter and 2.8 +/- 0.5 nm in long dimension. The nephrotic glomerular basement membrane revealed varying degrees of ultrastructural defects, the most prominent being tunnels and cavities. Tortuous tunnels measuring approximately 15 to 50 nm in diameter penetrated the entire glomerular basement membrane. Cavities of various shapes measuring 15 to 200 nm in diameter were diffusely scattered in the glomerular basement membrane and occasionally aggregated to form a honeycomb structure that occupied the whole thickness of the glomerular basement membrane. These defects appeared to be the pathway for protein leakage.

Diabetic Nephropathies↗

The effects of chronic endoscopic variceal sclerotherapy on systemic and splanchnic hemodynamics in patients with cirrhosis.

The aim of this study was to determine whether endoscopic variceal sclerotherapy affects systemic or splanchnic hemodynamics. We measured hemodynamic parameters before and after the first course of sclerotherapy in 35 patients with cirrhosis. Following sclerotherapy, there was a significant decrease in cardiac index and a significant increase in systemic vascular resistance. Changes in hepatic venous pressure gradient varied from patient to patient with no statistically significant change in the group overall. However, all 20 patients with a decline in the hepatic venous pressure gradient had a concomitant decrease in cardiac index and/or a large extravariceal shunt. The multivariate analysis disclosed that the decrease in cardiac index was a statistically significant contributor for the decline in hepatic venous pressure gradient. We conclude that the obliteration of esophageal varices by sclerotherapy significantly reverses the hyperdynamic circulatory state in patients with cirrhosis. Spontaneous changes in systemic hemodynamics and the interaction with hepatic hemodynamics must be taken into account when evaluating hepatic hemodynamics in patients undergoing variceal sclerotherapy.

Endoscopy↗

Significant prolongation of guinea pig heart contraction transplanted in rat after removal of anti-xeno-antibodies by whole body rinse-out (WBRO) with hemoglobin solution.

PURPOSE: In order to investigate effectiveness of removal of the anti-xeno- antibodies in xenotransplantation (xeno Tx), WBRO using pyridoxalated-human hemoglobin-polyethyleneglycol conjugate (PHP solution) was performed prior to transplantation (Tx) of a guinea pig heart in a rat. MATERIALS & METHOD: Experiment I. Removal of the immunoglobulins and the anti-guinea pig lymphocytotoxic antibody (ALA) by WBRO. Exchange transfusion with the PHP solution was done in the Tx-expected rats until a hematocrit lowered below 5% (n = 11). Experiment II. Xeno heart Txs. Guinea pig hearts were transplanted into rats without immunosuppressants 1) without (n = 8) or 2) with the WBRO (n = 8). RESULTS: Experiment I. Levels lowered to 14% in IgG, 17% in IgA and 6% in IgM, respectively, to initial values after the WBRO. An ALA titer lowered from 4 X (+) to 1 X (-) after the WBRO. Experiment II. An average heart contraction period was 10.4 +/- 1.8 minutes 1) without the WBRO in contrast to 472.5 +/- 4.8 minutes with the WBRO (p < 0.01). CONCLUSION: WBRO using PHP solution is effective in removal of the anti-xeno-antibodies and consequent prolongation of survival of the xenograft.

Animals↗