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Biomedical subjects

Y Inamoto

Publications and source records attributed to Y Inamoto.

At least 19 recordsLinked to original sources

Significance of additional high-dose cytarabine in combination with cyclophosphamide plus total body irradiation regimen for allogeneic stem cell transplantation.

The combination of cyclophosphamide (CY) and total body irradiation (TBI) has been used as a standard conditioning regimen for allogeneic transplantation. Several studies showed an advantage of adding high-dose cytarabine (HDCA) to this regimen. To clarify the significance of additional HDCA, we conducted a retrospective multicenter study and compared the clinical results of these two regimens. From June 1985 to March 2003, 219 patients with hematological malignancies underwent allogeneic transplantation after conditioning with CY+TBI 12Gy (n=73) or CA+CY+TBI 12Gy (n=146). Engraftment, overall survival, transplant-related mortality (TRM), relapse rate and incidence of graft-versus-host disease (GVHD) were compared according to risks and donors. Addition of HDCA had no impact on the relapse rate in all subgroups, and it was associated with lower TRM among standard-risk patients after related transplantation, and with higher TRM and worse survival among standard-risk patients after unrelated transplantation. The incidence of acute GVHD was not significantly different between the two regimens, and HDCA resulted in a higher incidence of chronic GVHD among standard-risk patients after related transplantation. In summary, addition of HDCA is not beneficial for high-risk patients, and is not recommended for standard-risk patients receiving unrelated transplantation.

Adolescent↗

Reduced-intensity stem-cell transplantation for adult acute lymphoblastic leukemia: a retrospective study of 33 patients.

Efficacy of reduced-intensity stem-cell transplantation (RIST) for acute lymphoblastic leukemia (ALL) was investigated in 33 patients (median age, 55 years). RIST sources comprised 20 HLA-identical related donors, five HLA-mismatched related, and eight unrelated donors. Six patients had undergone previous transplantation. Disease status at RIST was first remission (n=13), second remission (n=6), and induction failure or relapse (n=14). All patients tolerated preparatory regimens and achieved neutrophil engraftment (median, day 12.5). Acute and chronic graft-versus-host disease (GVHD) developed in 45 and 64%, respectively. Six patients received donor lymphocyte infusion (DLI), for prophylaxis (n=1) or treatment of recurrent ALL (n=5). Nine patients died of transplant-related mortality, with six deaths due to GVHD. The median follow-up of surviving patients was 11.6 months (range, 3.5-37.3 months). The 1-year relapse-free and overall survival rates were 29.8 and 39.6%, respectively. Of the 14 patients transplanted in relapse, five remained relapse free for longer than 6 months. Cumulative rates of progression and progression-free mortality at 3 years were 50.9 and 30.4%, respectively. These findings suggest the presence of a graft-versus-leukemia effect for ALL. RIST for ALL is worth considering for further evaluation.

Adolescent↗

Stroke incidence and case fatality in Shiga, Japan 1989-1993.

BACKGROUND: This paper describes incidence rates and case-fatality for sub-types of stroke using data collected in Takashima, Shiga, Japan, from 1989 to 1993 and compares these with similar registers in other parts of Japan. METHODS: Registered patients included all residents of the county who experienced a first-ever stroke. Stroke was defined as sudden onset of neurological symptoms which continued for a minimum of 24 hours or led to death. Almost all such patients are hospitalized in this country. Early case fatality was defined as patients who died within 28 days of stroke onset. Diagnosis of stroke type was based on clinical symptoms as well as computed tomography (CT) scans. RESULTS: Age-adjusted incidence rates for stroke per 100,000 population aged 35 years and older were 268.7 for men and 167.5 for women. The age-specific incidence rate of both cerebral infarction and cerebral haemorrhage increased with advancing age. The occurrence of cerebral infarction in men was twice as high as in women. The 28-day case fatality for all sub-types of stroke was 16.1% in men and 15.8% in women. Case fatality for cerebral infarction, cerebral haemorrhage, and subarachnoid haemorrhage was 10.7%, 22.4% and 28.6% respectively. CONCLUSIONS: Takashima County has a moderately high stroke incidence rate and case fatality compared with other similar studies in Japan. The incidence rate of cerebral infarction in men is twice that in women, while other sub-types of stroke showed smaller differences. In order to decrease the incidence of stroke in Japan, greater efforts at primary prevention will be necessary, in particular, it is important to prevent cerebral infarction in men.

Adult↗

Liquid chromatography of guanidino compounds using a porous graphite carbon column and application to their analysis in serum.

The retention mechanism of guanidino compounds on a porous graphitic carbon seemed to be mainly hydrophobic interaction, according to the retention factors in buffer solutions and the results of an analysis by computational chemical calculation using molecular mechanics (MM2). The baseline separation of ten guanidino compounds was achieved by the addition of a hydrophobic counterion. The retention mechanism may be dynamic ion-exchange. The stable system was applied to the analysis of guanidino compounds in serum from nephritic patients. The effluent was monitored by a post-column labeling detection method using ninhydrin. The detection limit of guanidino compounds was a few picomoles; however, that of creatinine was one hundredth of those of the other compounds. The reproducibilities of the peak height and area of the ten guanidino compounds using gradient elution were quite high, and the standard deviations were within a few percent (n=5), except for creatinine. The recovery of the compounds from serum was more than 90% (n=5). The reproducibility of retention times was within 1% (n=5).

Buffers↗

Studies on 3'-quaternary ammonium cephalosporins--III. Synthesis and antibacterial activity of 3'-(3-aminopyrazolium) cephalosporins.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]cephalos porins bearing N-mono or dialkyl and carbamoyl aminopyrazolium, and five- or six-membered rings fused to the 3-aminopyrazolium methyl groups at the 3-position, are described. Aminopyrazolium methyl cephalosporins (23e, f, i), with fused saturated and unsaturated rings were especially effective against Staphylococcus strains compared to 3-amino-2-methylpyrazolium methyl cephalosporin (1). Among the cephalosporins prepared in this work, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(4,5, 6, 7-tetrahydro-1-pyrazolo[1,5-a]pyrimidinio)methyl-3-cephem-4-carbox ylate (23f) showed a good balance of antibacterial activity against both Gram-positive bacteria including Staphylococcus aureus and Gram-negative bacteria including P. aeruginosa. An imidazopyrazolium group at the 3-position in, for example, cephalosporin (23i) was particularly effective for improving antibacterial activity against MRSA.

Cephalosporins↗

Studies on 3'-quaternary ammonium cephalosporins--IV. Synthesis and antibacterial activity of 3'-(2-alkyl-3-aminopyrazolium) cephalosporins related to FK037.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

Anti-Bacterial Agents↗

Septal perfusion and wall thickening in patients with left bundle branch block assessed by technetium-99m-sestamibi gated tomography.

UNLABELLED: Septal hypoperfusion is often observed in patients with complete left bundle branch block (LBBB) in myocardial perfusion imaging. Abnormal wall motion in the septal region may potentially cause artifactual perfusion abnormalities. To assess the effect of abnormal wall thickening on myocardial perfusion images, ECG-gated sestamibi SPECT was performed on 12 patients with LBBB and 10 normal subjects used as controls. METHODS: After administration of 740 MBq 99mTc-sestamibi injection at rest, ECG-gated SPECT was obtained 60 min later with division of the cardiac cycle into eight frames. RESULTS: Septal hypoperfusion was noted in 10 patients on nongated images and 11 patients on end-systolic (ES) images, whereas only two patients showed abnormalities on end-diastolic (ED) images. The septal to lateral wall count ratio in the LBBB group was lower (0.72 +/- 0.09) than in the control group (0.84 +/- 0.09) (p < 0.01) at nongated images, while it was similar at ED images (0.84 +/- 0.11 versus 0.86 +/- 0.12; ns). In addition, the count increase from ED to ES during a cardiac cycle in the septal region was smaller compared with the lateral region in the LBBB patients (25% +/- 19% in the septal region, versus 48% +/- 14% in the lateral region; p < 0.01), indicating less wall thickening in the septal region. CONCLUSION: Smaller count increase due to reduced wall thickening in the septal region may mimic hypoperfusion in patients with LBBB. This artifact can be eliminated with ECG-gated 99mTc-sestamibi SPECT, particularly with ED images.

Aged↗

Lipid composition and fatty acid analysis of Helicobacter pylori.

Lipids extracted from Helicobacter pylori were separated into lipid classes by thin-layer chromatography. Simple H. pylori lipids consisted of cholesterol esters, triglycerides, free fatty acids, cholesterol, diacylglycerols, and monoacylglycerols. Fatty acids were released from each lipid class by acid methanolysis, and analyzed by gas liquid chromatography and mass spectrometry. Unique methoxy fatty acids, including 11-methoxy heptadecanoic and 11-methoxy nonadecanoic acids, were the major components of the cholesterol esters and triglycerides. The predominance of methoxy fatty acids in the cholesterol esters of H. pylori may contribute to the acid-resistant characteristic of this bacillus.

Chromatography, Gas↗

[Assessment of 201Tl myocardial SPECT reinjected at 24 hours after stress imaging].

To improve the quality of 24 hours delayed images (24 DL) of stress thallium-201 myocardial SPECT, reinjection was performed at 24 hours later (24 RI), and the results were compared with those of 24 DL. A total of 45 patients were studied, including 18 patients in 24 DL, 27 patients in 24 RI. All of them showed persistent defect or incomplete redistribution on the routine stress and 3 hours delayed SPECT scans. In 24 RI, 37 MBq of thallium-201 was reinjected at 24 hours later. Myocardial count of 24 DL was about 1/4 of stress image, while 24 RI was about 1/2. Quality of 24 RI image was nearly equal to 3 hours delayed image. Of regions without redistribution at 3 hours delayed image, 5 (36%) regions showed new redistribution at 24 RI. Of regions incomplete redistribution, 6 (25%) regions showed further redistribution. Compared with 24 DL, the frequency of redistribution tended to be higher in this protocol than that of the 24 DL (11%, 17% respectively). In conclusion, the reinjection at 24 hours delayed imaging was considered to be useful to evaluate viability of myocardium in patient with CAD.

Aged↗

[Value of stress-rest ECG gated SPECT one day protocol using 99mTc-MIBI].

A total of 110 patients suspected with CAD who had symptoms or ECG abnormalities were enrolled in the stress-rest ECG gated SPECT one day protocol using 99mTc-MIBI. All the patients underwent symptom-limited exercise testing and 250 MBq of MIBI was injected at peak exercise. Exercise perfusion SPECT images were reviewed by two trained doctors to classify into three groups; normal, equivocal and abnormal. Patients with normal stress image (n = 53) did not receive the resting study. On the other hand, those with equivocal (n = 20) and abnormal (n = 37) stress images performed resting study, including gated SPECT. Of 20 equivocal cases, 16 patients showed unchanged resting perfusion. All of these had normal wall motion. The remaining 4 patients showed improved resting perfusion, indicating presence of myocardial ischemia. Of 37 abnormal cases, 12 patients showed improved resting perfusion, whereas 25 patients showed unchanged resting perfusion. Cardiac events were more often observed in abnormal cases, especially those associated with myocardial ischemia, while good prognosis was obtained in normal cases. Values of this protocol are (1) Patients with normal stress images need no resting study. (2) All the procedure can be completed in one day. (3) Both cardiac function and perfusion can be obtained with gated SPECT. These data indicates that this protocol is valuable for screening patients suspected with CAD.

Coronary Circulation↗

Reliability of data obtained by radionuclide angiocardiography in follow-up studies with special reference to intra- and interobserver variations.

The reproducibility of the data obtained by radionuclide angiocardiography was studied in terms of the intra- and intervariations of three technicians. Three parameters were chosen: the left ventricular ejection fraction (LVEF), the 1/3 filling fraction (1/3FF), and the ratio of the time from end systole to the point of peak filling rate against the entire diastolic period (TRPFR). First, each technician studied an independent consecutive series of 40 patients for the initial analysis. The original data of each patient, composed of 26 frames for one beat, were stored on an optical disc for the intra- and intervariation studies. In this study, analysis of the volume curve was performed by using both 3rd order and 4th order Fourier series. The region of interest (ROI) for the left ventricle, which was set for the initial analysis, was recorded by Polaroid photography to be used as a reference for the later analyses for the variation studies. The least variation was noted in the LVEF not only for the intravariation study but also for the intervariation study, no matter which order of the Fourier series was used. However, the 3rd order Fourier series seemed to give better curve fitting to avoid fluctuation of the diastolic parameters. The results indicate that we can expect more steady and reliable information from LVEF than from the diastolic parameters, even when various technicians perform the follow-up study of a particular patient.

Angiocardiography↗

[Assessment of left ventricular count increase with ECG-gated 99mTc-MIBI SPECT using a single-head rotating gamma-camera].

ECG-gated 99mTc-MIBI SPECT was performed in 33 patients, including 17 normal subjects and 16 patients with old myocardial infarction. To compare the findings by echocardiography (UCG), regional wall motion was qualitatively assessed by cine-mode display and quantitatively measured as an increase in regional count from end-diastole to end-systole. The percent count increase and relative count increase was measured to display on the Bull's eye polar map. In the study of normal subjects, the count increase was greater in apical regions and smaller in septal regions. Regional wall motion by this method correlated well with UCG findings (agreement: 97%, complete agreement: 60%). A mild but significant correlation was observed between the count increase by this method and the percent wall thickening by UCG. We conclude that regional wall motion can be accurately evaluated with ECG-gated 99mTc-MIBI SPECT, which thus permits simultaneous assessment of regional wall motion and myocardial perfusion.

Aged↗

[Phase I study of paclitaxel].

Paclitaxel, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered as a 24-hour infusion in a phase I study. Twelve patients received 32 courses at 50, 100, 150, and 200 mg/m2. A premedication regimen of dexamethasone, diphenhydramine, and ranitidine was used to prevent the acute hypersensitivity reactions (HSRs). The dose-limiting factor was leukopenia (granulocytopenia) associated with Grade 4 infection. The maximum tolerated dose was 200 mg/m2. Other non-hematological effects included peripheral neuropathy, myalgia, alopecia, and elevations of transaminase and alkaline phosphatase. Severe HSRs were not observed. The paclitaxel plasma concentration declined with a half-life of 10.0 to 24.9 hours. Excretion into urine within 72 hours was in the range of 7.28 to 11.34% of paclitaxel dosage. Two patients with breast cancer at the 200 mg/m2 dose level had partial responses. The recommended dose of paclitaxel for phase II study, when administered as a 24-hour infusion, is considered to be 150 mg/m2 every 3 weeks.

Adolescent↗

Lipid analysis of Helicobacter pylori.

Lipids from Helicobacter pylori were extracted, isolated by conventional DEAE-Sephadex and silica gel column chromatography, and then purified by preparative thin-layer chromatography. Simple and phospholipids were analyzed by HPTLC and quantitatively determined by densitometry scanning. The fatty acid compositions of simple lipids were estimated by gas-liquid chromatography. The simple lipid composition of H. pylori consisted of wax ester (2.5%), triglycerides (4.9%), free fatty acids (30.0%), cholesterol (6.9%), diacylglycerol (29.1%), and monoacylglycerol (2.6%). The neutral phospholipid composition consisted of phosphatidyl ethanolamine (79.1%), lysophosphatidyl ethanolamine (16%), and phosphatidyl choline (1.9%). That of acidic phospholipids consisted of phosphatidic acid (52.7%) and phosphatidyl serine (47.3%). The major fatty acids of crude lipid, wax, free fatty acids, triglycerides, diacylglycerides, and monoacyl glycerides were C19:1 (cyclo), C18:2, C16:0, C19:1 (cyclo), C22h:0, and C18:0, respectively. These results are new findings and suggest significant characteristics from the metabolic, physiologic, and chemotaxonomic point of view.

Chromatography, Gas↗

[Research and development of new oral cephems, cefixime and cefdinir].

This article reviews the structure-activity relationships, biological properties and synthesis of two new oral cephalosporin antibiotics, cefixime (CFIX) and cefdinir (CFDN). Our research into new oral cephalosporin antibiotics began in the late 1970's. The first goal of our research was to discover a new oral cephem possessing similar antibacterial activity and resistance to beta-lactamase as the 3rd generation injectable cephalosporins. We focused our attention on searching for a non-prodrug type cephem, that is, a new parent structure with high intrinsic absorption. We selected ceftizoxime (CZX) as a seed compound due to its relatively high excretion rate (8.5%) in the urine after oral administration to rats. We concentrated our research on the chemical modification of the oxime moiety in CZX based on our hypothesis for oral absorption, and discovered a lead compound with a carboxymethoxyimino group which displayed better urinary excretion (41.0%). Optimization studies led to a new oral cephem, CFIX. However, CFIX shows only low to moderate antibacterial activity against gram-positive bacteria such as S. aureus. Hence, the second goal of our research was to discover a new oral cephem with enhanced activity against gram-positive bacteria. From a consideration of structure-absorption relationships, we studied the activity and absorbability of cephems bearing other acidic functional groups at the oxime moiety of CFIX. As a result, we found a new oral cephem, CFDN with a hydroxyimino group at the 7-position. CFIX has excellent biological properties, displaying potent antibacterial activity against a wide range of gram-positive bacteria except S. aureus and gram-negative bacteria including opportunistic pathogens, high stability towards beta-lactamases and long acting efficacy. CFDN exhibits excellent and well balanced antibacterial activities against gram-positive and gram-negative bacteria. The pharmacokinetic of CFDN in healthy volunteers showed that serum levels were high enough to make CFDN as an effective antibacterial agent. The proposed mechanisms of intestinal absorption of CFIX and CFDN are briefly described. The efficient synthetic methods to CFIX and CFDN were achieved via a common intermediate, 7-amino-3-vinylcephalosporanic acid diphenylmethyl ester from 7-ACA.

Administration, Oral↗

[Myocardial hemorrhage due to high-dose cyclophosphamide treatment in a case of non-Hodgkin's lymphoma].

43-year-old male with non-Hodgkin's lymphoma which was resistant to standard treatment received high-dose chemotherapy followed by autologous stem cell transplantation. He had a past history of nephrectomy due to renal cell carcinoma. He had received adriamycin at a total dose of 280mg/m2, but had no episode of heart disease. His chest radiograph, electrocardiogram and serum creatinine were within normal ranges at the start of high-dose chemotherapy. He was given 120 mg/kg of cyclophosphamide (CPM) over two days. Serum creatinine levels elevated two days before transplantation, and he felt discomfort of the chest followed by severe arrhythmia. He died of heart failure one day after the transplantation. Postmortem examination revealed diffuse myocardial hemorrhage with degeneration and necrosis of the heart muscle. CPM is one of the useful antitumor alkylating agents for the treatment of malignant neoplasms. Although conventional doses of CPM can be used without adverse cardiac effects, high-dose CPM has been reported to induce cardiotoxicity in a few cases. Patients often develop fatal acute heart failure. For the safe use of high-dose CPM, we must consider about the dosing schedule, early detection of adverse cardiac effects, and patient risk factors.

Adult↗