Biomedical subjects

H Minami

Publications and source records attributed to H Minami.

At least 19 recordsLinked to original sources

PubMed2002

Expression of ABH/Lewis-related antigens as prognostic factors in patients with breast cancer.

PURPOSE: The prognostic value of altered blood group factor and Lewis-related carbohydrate antigen expression in breast cancers has not been fully determined. METHODS: To this end, breast carcinoma samples from 87 radical mastectomy patients with primary cancer were analyzed by immunohistochemistry for the ABH factors, Le(a), sialyl Le(a), Le(x), and sialyl Le(x). RESULTS: It was found that ABH, Le(a), sialyl Le(a), Le(x), and sialyl Le(x) antigens were expressed in 25 (21.8%), 26 (22.6%), 26 (22.6%), 36 (31.3%), and 37 specimens (32.2%), respectively. Tumors with lymph node metastasis expressed Le(x) or sialyl Le(x) antigens more frequently than those without lymph node metastasis ( P=0.0020 or P=0.039, respectively). The survival time of patient s after surgery was significantly shorter for those whose tumors expressed Le(x) or sialyl Le(x) than for those without Le(x)- or sialyl Le(x)-positive tumors ( P=0.0028 and P=0.0029, respectively). Cox's multiple regression analysis revealed that sialyl Le(x) expression was an independent prognostic factor for patient survival regardless of primary tumor (T factor) and lymph node (N factor) status (hazards ratio, 3.80). CONCLUSIONS: Thus, expression of sialyl Le(x) antigen in tumor cells is associated with poor prognosis in patients with breast cancer and must be considered in the design of future therapeutic trials.

ABO Blood-Group System↗

PubMed2002

[An elderly case of ruptured aortic arch aneurysm 3 years after coronary artery bypass grafting].

We reported a case of trans-aortic endovascular stent grafting (open stent method) for ruptured true aneurysm of the aortic arch. A 83-year-old female, who had suddenly complained back pain and been diagnosed as the ruptured aortic arch aneurysm by computer tomography, was admitted for an emergent surgery. We performed emergent trans-aortic endovascular stent grafting (open stent method). Postoperatively she had no complication and recovered uneventfully.

Aged↗

PubMed2002

[Cardiac surgery for chronic dialysis patients].

Chronic dialysis patients who received open heart surgery were examined, and main concern was perioperative management. There were 12 chronic dialysis patients and open heart surgeries were performed between October 1990 and June 2000. The patients were comprised of 7 men and 5 women with the average age being 64 with plus or minus 7.9. The operative procedure of 6 coronary artery bypass grafting (CABG) [on-pump], 1 CABG + mitral valve replacement (MVR), 3 aortic valve replacement (AVR), 1 mitral valvuloplasty (MVP) and 1 ascending aorta replacement were performed. All patients were discharged from the hospital with good conditions 27.1 days after operation. There were no hospital deaths. One postoperative complication of mediastinitis of the sternum has been found. A conventional dialysis was performed the day before the operation and an intra-operative hemodialysis (HD) was performed, placing a dialyzer into a cardiopulmonary system during the operation. For the perioperative management, HD was started the day or 2 days after the operation with no immediate postoperative hemocatharsis and returned to the normal HD 7 days after the operation. The result of the perioperative management has been good.

Aged↗

PubMed2001

Prognostic value of performance status assessed by patients themselves, nurses, and oncologists in advanced non-small cell lung cancer.

Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable, advanced non-small cell lung cancer were investigated prospectively. Weighted Kappa statistics for inter-observer agreement were 0.53 between oncologists and patients and 0.63 between oncologists and nurses. There was a significant difference among the assessments by the three groups (P < 0.001). Oncologists gave the healthiest performance status assessment, nurses an intermediate assessment, and patients the poorest. When included separately in the Cox model, the assessment by each group was significantly correlated with survival. However, the assessment by the patients themselves failed to distinguish survival of patients with performance status 1 and 2. Among the three models including patient-, nurse-, and oncologist-assessed PS, that including oncologist-assessed PS best fitted to the observed survival data. These results showed that the assessment by the patients themselves is different from those by the nurses and the oncologists and provided additional support for the use of the assessment by oncologists in clinical oncology.

Aged↗

PubMed2001

2-Alkynyl-8-aryl-9-methyladenines as novel adenosine receptor antagonists: their synthesis and structure-activity relationships toward hepatic glucose production induced via agonism of the A(2B) receptor.

Novel adenosine antagonists, 2-alkynyl-8-aryl-9-methyladenine derivatives, were synthesized as candidate hypoglycemic agents. These analogues were evaluated for inhibitory activity on N-ethylcarboxamidoadenosine (NECA)-induced glucose production in primary cultured rat hepatocytes. In general, aromatic moieties at the 8-position and alkynyl groups at the 2-position had significantly increased activity compared to unsubstituted compounds. The preferred substituents at the 8-position of adenine were the 2-furyl and 3-fluorophenyl groups. In modifying the alkynyl side chain, change of the ring size, cleavage of the ring, and removal of the hydroxyl group were well tolerated. The order of the stimulatory effects of adenosine agonists on rat hepatocytes was NECA > CPA > CGS21680, which is consistent with involvement of the A(2B) receptor. In Chinese hamster ovary cells stably transfected with human A(2B) receptor cDNA, one of the compounds potent in hepatocytes, 15o (IC(50) = 0.42 microM), antagonized NECA-induced stimulation of cyclic AMP production (IC(50) = 0.063 microM). This inhibitory effect was much more potent than those of FK453, KF17837, and L249313 which have been reported to be respectively A(1), A(2A), and A(3) selective antagonists. These findings agree very well with the result that, compared to 15o, these selective antagonists for each receptor subtype showed only marginal effects in rat hepatocytes. These results suggest that adenosine agonist-induced glucose production in rat hepatocytes is mediated through the A(2B) receptor. Furthermore, 15o showed hypoglycemic activity in an animal model of noninsulin-dependent diabetes mellitus, the KK-A(y) mice. It is possible that inhibition of hepatic glucose production via the A(2B) receptor could be at least one of the mechanisms by which 15o exerts its in vivo effects. Further elaboration of this group of compounds may afford novel antidiabetic agents.

Adenine↗

PubMed2001

Impending rupture in an aortic arch aneurysm by Candida infection.

A 68-year-old man was hospitalized with the complaints of left back pain and fever. He had a history of using steroids to treat uveitis for about thirty years. Computed tomography on the chest demonstrated an impending rupture in an aortic arch aneurysm, which was consequently surgically excised. Candida albicans was identified in the wall of the aneurysm, so fluconazole and itraconazole were administered. The patient was discharged at 120 days after surgery without recrudescence of the candida. To our knowledge, this is the fifteenth case of a successfully treated aneurysm caused by candida infection.

Aged↗

PubMed2001

Preconcentration by coprecipitation of arsenic and tin in natural waters with a Ni-pyrrolidine dithiocarbamate complex and their direct determination by solid-sampling atomic-absorption spectrometry.

A method for the determination of trace amounts of arsenic and tin in natural waters is described. Trace amounts of arsenic and tin were preconcentrated by coprecipitation with a Ni-ammonium pyrrolidine dithiocarbamate (APDC) complex. The coprecipitates obtained were directly analyzed by graphite-furnace atomic-absorption spectrometry (GFAAS) using the Ni-APDC complex solid-sampling technique. The coprecipitation conditions used for the trace amounts of arsenic and tin in natural water were investigated in detail. It was found that arsenic and tin at sub-ng mL(-1) levels were both coprecipitated quantitatively by Ni(PDC)2 in the pH range 2-3. The concentration factors by coprecipitation reached approximately 40,000 when 2 mg nickel was added as a carrier element to 500 mL of the water sample. The proposed method has been applied to the determination of trace amounts of arsenic and tin in river water and seawater reference materials, and the detection limits for arsenic and tin, which were calculated from three times of the standard deviation of the procedural blanks, are 0.02 ng mL(-1) and 0.04 ng mL(-1), respectively, for 500-mL volumes of water sample.

Arsenic↗

PubMed2001

Direct determination of silicon in powdered aluminium oxide by use of slurry sampling with in situ fusion graphite-furnace atomic-absorption spectrometry.

A direct method for determination of silicon in powdered high-purity aluminium oxide samples, by slurry sampling with in situ fusion graphite-furnace atomic-absorption spectrometry (GF-AAS), has been established. A slurry sample was prepared by 10-min ultrasonication of a powdered sample in an aqueous solution containing both sodium carbonate and boric acid as a mixed flux. An appropriate portion of the slurry was introduced into a pyrolytic graphite furnace equipped with a platform. Silicon compounds to be determined and aluminium oxide were fused by the in situ fusion process with the flux in the furnace under optimized heating conditions, and the silicon absorbance was then measured directly. The calibration curve was prepared by use of a silicon standard solution containing the same concentration of the flux as the slurry sample. The accuracy of the proposed method was confirmed by analysis of certified reference materials. The proposed method gave statistically accurate values at the 95% confidence level. The detection limit was 3.3 microg g(-1) in solid samples, when 300 mg/20 mL slurry was prepared and a 10 microL portion of the slurry was measured. The precision of the determination (RSD for more than four separate determinations) was 14% and 2%, respectively, for levels of 10 and 100 microg g(-1) silicon in aluminium oxide.

Aluminum Oxide↗

PubMed2001

Phase I/II and pharmacologic study of irinotecan and carboplatin for patients with lung cancer.

PURPOSE: To determine the maximum tolerated dose (MTD) of irinotecan combined with carboplatin, to evaluate its efficacy and toxicity for patients with lung cancer, and to examine its pharmacokinetics and pharmacodynamics. METHODS: The dose of irinotecan was escalated from 40 mg/m2 per week in increments of 10 mg/m2. Carboplatin was fixed at 300 mg/m2. Multivariate regression models with an interaction term were used to evaluate synergistic pharmacodynamic interactions. RESULTS: The MTD and recommended dose of irinotecan were 60 and 50 mg/m2, respectively. Dose-limiting toxicities were grade 4 neutropenia and grade 3 or 4 diarrhea. In phase II studies, response rates were 81.3% (95% confidence interval 61.8-100%) in 16 patients with small-cell lung cancer and 22.2% (2.7-41.8%) in 18 patients with non-small-cell lung cancer. Two patients (6%) experienced grade 4 neutropenia, thrombocytopenia, and grade 3 diarrhea. The area under the plasma concentration versus time curve (AUC) of carboplatin ranged from 2.87 to 9.31 mg x min/ml, with a median of 4.66 mg x min/ml. In pharmacodynamic analyses, the log-transformed surviving fraction in platelet count (SFp) showed a significant association with the AUC of carboplatin (P=0.010), while that in neutrophil count (SFn) was not significantly correlated with any pharmacokinetic parameter. The interaction term was not significant in either case. CONCLUSIONS: These results indicate that AUC-based dosing of carboplatin is still rational in combination chemotherapy. A more sensitive method for predicting life-threatening toxicities is needed, however, because traditional pharmacokinetic parameters were not adequate tools for identifying patients at high risk of severe neutropenia and diarrhea. This combination regimen has only modest activity, and further studies are necessary to evaluate a different dose schedule.

Adult↗

PubMed2001

Triterpene and flavanone glycoside from Rhododendron simsii.

Antioxidative substances were isolated from the leaves of Rhododendron simsii. These were a triterpene and flavanone glycoside, together with the known matteucinol and two known benzoic acid derivatives. Their structures were characterized as 19,24-dihydroxyurs-12-en-3-one-28-oic acid and 7-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranosylmatteucinol by spectroscopic analysis.

Antioxidants↗

PubMed2001

Factors affecting the pharmacokinetics of CPT-11: the body mass index, age and sex are independent predictors of pharmacokinetic parameters of CPT-11.

This study was conducted to describe the relationship between pharmacokinetics of CPT-11 and its active metabolite SN-38, and clinical values with special emphasis on the influence of relative weight referring to the appropriateness of a conventional dose adjustment method by body surface area (BSA). Thirty-six patients received 100 mg/m2 of CPT-11 intravenously over 90 min. Body Mass Index (BMI) was used as a measure of relative weight which is calculated from the equation: BMI=weight(kg)/[height(m)]2. The area under the concentration-time curve (AUC) of CPT-11 was significantly correlated with sex, age, poorer creatinine clearance and indocyanine green retention test (ICG). The peak plasma concentration (Cmax) of CPT-11 was significantly correlated with sex a larger BMI, BSA and age. The AUC of SN-38 was significantly correlated with ICG. The volume of distribution at steady state of CPT-11 inversely correlated with BMI. Multiple regression analysis revealed that the best fitting model with significant independent predictors for AUC of CPT-11 included age and sex (F=6.93, R2=0.29). That of Cmax of CPT-11 included sex and BMI (F=8.96, R2=0.35). The only independent predictor of AUC of SN-38 was ICG (F=7.75, R2=0.19). These results indicated that several factors affect pharmacological behaviors of CPT-11 even in patients with normal organ functions. The dose modification method based solely on BSA is not sufficient to reduce interpatient variability of cancer chemotherapy. The influence of relative weight, sex and age on pharmacokinetics/pharmacodynamics should be taken into consideration in every pharmacological approach to establish the ideal dose modification method.

Adult↗

PubMed2001

Influence of the CYP2D6*10 allele on the metabolism of mexiletine by human liver microsomes.

AIMS: To study the influence of CYP2D6*10 on the formation of p-hydroxymexiletine (PHM) and hydroxymethylmexiletine (HMM) using microsomes from human liver of known genotypes. METHODS: Microsomes from human livers of genotype CYP2D6*1/*1 (n = 5), *1/*10 (n = 6) and *10/*10 (n = 6) were used in this study. The formation of PHM and HMM was determined by high-performance liquid chromatography. RESULTS: The formation rates of PHM and HMM were decreased by more than 50% and 85% in CYP2D6*1/*10 and *10/*10 microsomes, respectively, compared with *1/*1 microsomes. CONCLUSIONS: The metabolism of mexiletine to form PHM and HMM appears to be impaired to a significant extent in human liver microsomes from hetero- and homozygotes of CYP2D6*10.

Alleles↗

PubMed2001

Clinical effect of irinotecan in advanced and metastatic breast cancer patients previously treated with doxorubicin- and docetaxel-containing regimens.

BACKGROUND: Previous phase II trials in Japan suggested that irinotecan was a promising agent for advanced or metastatic breast cancer pretreated with anthracycline. However, irinotecan has not yet been evaluated in the salvage setting for breast cancer pretreated with both anthracycline and taxane, which are two active agents for breast cancer. METHODS: The efficacy and safety of irinotecan were retrospectively evaluated in patients with breast cancer who had previously been treated with both doxorubicin and docetaxel. From 1996 to 1999, irinotecan was administered to 20 patients, all with a performance status of <2. Irinotecan treatment was repeated in approximately 6 week cycles consisting of the administration of irinotecan once weekly for 4 weeks followed by a 2 week rest. The median dose of irinotecan administered was 100 mg/m(2) weekly. The median number of irinotecan cycles given was 1 (range: 1-8 cycles). The median total dose was 388 mg/m(2) (range: 50-2400 mg/m(2)). RESULTS: Performance status declined to >3 after treatment with irinotecan in four patients. Two patients had grade 3 leukopenia; three had grade 3 anemia and one had a creatinine elevation of grade 4. The objective response rate for all patients was 5.0% (95% CI: 0-15.5%). The median time to progression and overall survival were 35 days (range: 17-285 days) and 124 days (range: 17-667 days), respectively, since the start of the administration of irinotecan. CONCLUSIONS: Salvage chemotherapy with irinotecan may be inactive against advanced and metastatic breast cancer pretreated with doxorubicin and docetaxel. We will evaluate irinotecan for advanced and metastatic breast cancer patients as first- or second-line chemotherapy combined with anthracycline or taxane.

Adult↗

PubMed2001

Phase I study of intravenous PSC-833 and doxorubicin: reversal of multidrug resistance.

PSC-833 reverses multidrug resistance by P-glycoprotein at concentrations < or = 1000 ng / ml. A phase I study of PSC-833 and doxorubicin was conducted to determine the maximum tolerated dose and to investigate pharmacokinetics. PSC-833 was intravenously infused as a 2-h loading dose (LD) and a subsequent 24-h continuous dose (CD). Doxorubicin was infused over 5 min, 1 h after the LD. The starting dose was 1 mg / kg for both LD and CD with 30 mg / m(2) doxorubicin; these dosages were increased to 2 and 10 mg / kg and 50 mg / m(2), respectively. Thirty-one patients were treated. Nausea / vomiting was controllable with granisetron and dexamethasone. Neutropenia and ataxia were dose limiting. Steady-state concentrations of PSC-833 > 1000 ng / ml were achieved at a 2 mg / kg LD and a 10 mg / kg CD. Ex-vivo bioassay revealed that activity in serum for reversing multidrug resistance was achieved in all patients; IC(50) of P-glycoprotein expressing 8226 / Dox(6) in patients' serum was decreased from 5.9 to 1.3 microg / ml (P < 0.0001) by PSC-833 administration. Doxorubicin clearance was 24.3 +/- 13.7 (mean +/- SD) liter / h/m(2), which was lower than the 49.0 +/- 16.9 liter / h/m(2) without PSC-833 (P < 0.0001). The relationship between doxorubicin exposure and neutropenia did not differ between patients treated and not treated with PSC-833. The recommended phase II dose of PSC-833 was 2 and 10 mg / kg for LD and CD, respectively, which achieved a sufficient concentration in serum to reverse drug resistance, as confirmed by bioassay. The dose of doxorubicin should be reduced to 40 mg / m(2), not because of the pharmacodynamic interaction between PSC-833 and doxorubicin affecting hematopoiesis, but because of pharmacokinetic interaction.

Adult↗

PubMed2001

Pharmacodynamic modeling of the entire time course of leukopenia after a 3-hour infusion of paclitaxel.

The entire time course of leukopenia after anticancer treatment is clinically more relevant than a singly measured nadir count. In order to identify factors associated with neutropenic fever, a mechanistic pharmacodynamic model with two compartments corresponding to leukocytes in bone marrow and peripheral blood was applied to describe the time course of leukopenia. Seventeen patients with breast cancer were treated with 210 mg / m(2) of paclitaxel infused over 3 h as a single agent in a phase II study. Adequate fitting of the time course of leukopenia was achieved in all patients, and time-dependent parameters, including the time period during which leukocyte counts remained below 2000 / microl and the area between the curve for time versus leukocyte counts and the line of a leukocyte count of 2000 / microl (A < 2000), were calculated in each patient. Leukopenia was not significantly correlated with pharmacokinetic parameters, including time above a threshold concentration or the area under the time-concentration curve. A negative correlation between age and the sensitivity parameter of the pharmacodynamic model was observed (r (2) = 0.21, P = 0.07). Patients who experienced neutropenic fever had a larger A < 2000 than patients who did not experience fever (4512 vs. 6 days / microl, P = 0.05), but fever was not significantly related to any pharmacokinetic parameter or the leukocyte nadir count. Febrile episodes were better associated with the time course of leukopenia than the singly measured nadir count, and the pharmacodynamic model presents a novel platform to analyze the entire time course of leukopenia.

Adult↗

PubMed2001

Treatable subsets in cancer of unknown primary origin.

The purpose of this study was to investigate the treatable subsets in cancer of unknown primary origin (CUP). Fifty patients (27 males and 23 females; median age, 53 years) with CUP diagnosed between April 1992 and June 1999 were analyzed retrospectively. Of the 50 patients, 39 received chemotherapy: platinum-based in 31, non-platinum-based in 4, and clinical trials of new agents in 4. Of the 39 patients, 13 (33.3%; 95% confidence interval: 19.1 - 50.2%) showed objective responses, with 4 complete responders. Patients with poorly differentiated carcinomas in whom beta-subunit of human chorionic gonadotropin (beta-HCG) was elevated more than 10 mIU / ml and female patients with peritoneal adenocarcinomatosis achieved high response rates (83.3% and 80%, respectively) with platinum-based chemotherapy, as compared with only a 15.3% response rate in the remaining patients. Platinum-based chemotherapy provided promising results in patients with poorly differentiated carcinomas and in female patients with peritoneal adenocarcinomatosis. Significantly elevated serum levels of beta-HCG in patients with poorly differentiated carcinoma might predict a better response to platinum-based chemotherapy. However, the investigation of novel chemotherapeutic approaches is warranted for other groups of patients with CUP.

Adenocarcinoma↗

PubMed2001

Coupling interval from slow to tachycardiac pacing decides sustained alternans pattern.

We discovered that the coupling beat interval from a slow to a tachycardiac pacing period considerably affected the pattern of the beat-to-beat alternation of the tachycardia-induced sustained contractile alternans. We analyzed the relationship between the coupling interval and the pattern and amplitude of the alternans in the isovolumic left ventricle of canine blood-perfused hearts. The alternans pattern and amplitude varied transiently over the first 30-50 beats and became gradually stable over the first minute in all 12 hearts. We discovered that stable alternans, even under the same tachycardiac pacing, had three different strong-weak beat patterns depending on the coupling interval. A relatively short coupling interval produced a representative sustained alternans of the strong and weak beats. A relatively long coupling interval produced a similar sustained alternans but in a reversed order of even- and odd-numbered beats counted from the coupling interval. However, sustained alternans disappeared after 1-3 specific coupling intervals. We conclude that ventricular pacing rate does not solely determine the pattern and amplitude of sustained contractile alternans induced by tachycardia.

Action Potentials↗

PubMed2001

Lung cancer treated surgically in patients <50 years of age.

STUDY OBJECTIVES: Some investigators have suggested that lung cancer in young patients has a more aggressive course and a poorer prognosis than lung cancer in older patients. The aim of this study was to determine if the basal characteristics and survival in younger patients with lung cancer undergoing surgical resection differ from those of older patients. DESIGN: Retrospective clinical study. PATIENTS: Of 1,208 consecutive patients who underwent surgery for primary lung cancer between June 1984 and March 2000, we reviewed the medical records of 110 younger patients who were < 50 years of age at the time of surgery and compared them with 1,098 older patients (> or = 50 years of age). All deaths were included. RESULTS: In the younger patient group, asymptomatic disease and adenocarcinoma was significantly more frequent, the rate of smoking was significantly higher, and the amount of smoking (Brinkman index) was significantly larger. For the 94 younger patients with complete resection, the 5-year survival rate was 61.0%, which was not significantly higher than that for the 923 older patients (57.7%). However, the 53 younger patients with stage I disease (5-year survival of 84.3%) had significantly better survival than older patients with the same condition (71.6%). Survival of patients in stage II or stage III disease was not significantly different. CONCLUSION: The younger patients had significantly better prognoses, and a statistical difference was shown especially in the early stage, while in the advanced stage the malignancy of the lung cancer itself surpassed the difference in survival.

Adenocarcinoma↗