Biomedical subjects

Yasuhiro Shimada

Publications and source records attributed to Yasuhiro Shimada.

15 recordsLinked to original sources

PubMed2003

Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan.

The prevention of post-chemotherapy symptoms such as delayed emesis, anorexia, and fatigue induced by irinotecan has not been studied. We compared the effects of dexamethasone (Dex) with those of a placebo on these symptoms in a randomized study. Seventy patients scheduled to receive irinotecan chemotherapy were enrolled in the study and randomly divided into a treatment or a placebo group. In the treatment group, 8 mg of Dex were administered on days 2-4 after the start of chemotherapy. All patients in both groups received Dex and granisetron for prophylaxis against acute emesis on day 1. We evaluated 68 patients (35 receiving Dex, 33 receiving the placebo). Although delayed emesis was completely prevented in most of patients in both groups (Dex, 82.9%; placebo, 78.8%), anorexia and fatigue were more completely prevented in those in the Dex group (Dex, 62.9% and 77.1%, placebo, 39.4% and 57.6%, respectively). The effect of Dex on improving simultaneous prophylaxis against all three symptoms was almost significant (Dex, 60.0%; placebo, 36.4%; P=0.058). The safety profiles of the two groups were not discernibly different. These results suggest that treatment with Dex may be beneficial to reduce post-chemotherapy symptoms induced by irinotecan, specifically anorexia and fatigue, with acceptable toxicities.

Adult↗

PubMed2003

Central projection of unmyelinated (C) primary afferent fibers from gastrocnemius muscle in the guinea pig.

We have demonstrated the central projections of muscle C or group IV afferent fibers in the guinea pig by tracing arborizations in the spinal cord. C afferent fibers from the gastrocnemius muscle (GCM) were electrophysiologically identified by conduction velocity (less than 1 m/second). A single neuron in the lumbar 5 dorsal root ganglion (L5 DRG) was intracellularly labeled with Phaseolus vulgaris leucoagglutinin (PHA-L). After iontophoretic injection of PHA-L, we processed the lumbar cord and L5 DRG for PHA-L immunohistochemistry. Six muscle C afferent fibers from 40 animals were labeled, and whole trajectories were recovered. Labeled fibers were reconstructed by tracing of the arbor in serial parasagittal sections. The GCM C afferents projected rostrocaudally for two or three segments and ran at the surface of the dorsal funiculus, giving off collaterals into laminae I and II and sometimes into parts of lamina III. We determined, based on the branching pattern and form of the terminal plexus, that the branching of muscle C afferent fibers showed an intermediate pattern that fell morphologically between the terminal patterns of somatic and visceral afferents. The numbers and sizes of fiber swellings and terminal swellings were measured on all collateral branches. We found that the area of distribution of the terminal swellings of muscle C afferent fibers is larger than that of somatic terminals but that the density of terminal swellings in the terminal area was lower than that of the somatic terminals.

Afferent Pathways↗

PubMed2003

Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205).

PURPOSE: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial. PATIENTS AND METHODS: A total of 280 patients with advanced gastric cancer were randomly allocated and analyzed for survival, response, and toxicity. The survival curves were compared between groups by log-rank test on an intent-to-treat basis. RESULTS: At the interim analysis, the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone, and the registration to UFTM was terminated. Both investigational regimens, FP and UFTM, had a significantly higher incidence of hematologic toxic effects than FU alone, although the effects were manageable. The overall response rates of the FU-alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and 2.4 months with UFTM, respectively. Although FP demonstrated a higher response rate (P <.001) and longer progression-free survival than did FU alone (P <.001), no differences in overall survival were observed between the arms. The median survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3 months and 29% with FP, and 6.0 months and 16% with UFTM, respectively. CONCLUSION: Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.

Adult↗

PubMed2003

Measurement and evaluation of the adhesive force between particles by the direct separation method.

We developed a new apparatus to measure the adhesive force between particles with a high resolution of approximately 2 nN. The force was measured directly by applying a pulling force to the particles with a contact needle. In addition, the separation process was observed with a 3CCD camera during the measurement. The adhesive force of six kinds of pharmaceutical particles and glass beads was measured, and the effects of moisture, shape, and triboelectrification of the particles on the force were investigated. In the case of moisture-adsorptive particles, the force of adhesion increased rapidly with moisture content under high relative humidity. In the case of moisture-nonadsorptive particles, the force was affected by the particle shape and triboelectrification. The adhesive force of particles having sharp corners was greatly affected by triboelectrification at the corners of the particles.

Adhesives↗

PubMed2003

A Phase II study of irinotecan in combination with 120-h infusion of 5-fluorouracil in patients with metastatic colorectal carcinoma: Japan Clinical Oncology Group Study (JCOG9703).

PURPOSE: To evaluate the antitumor effect and feasibility of a combination of irinotecan (CPT-11) and 5-day infusional 5-fluorouracil (5-FU) in a sequential schedule based on our previous combination phase I studies in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty chemotherapy-naive patients with metastatic colorectal cancer received 90-min infusion of CPT-11 at a dose of 150 mg/m(2) on days 1 and 15 and 120-h protracted infusion of 5-FU at 600 mg/m(2)/day on days 3-7, which were repeated every 4 weeks. RESULTS: The median number of actually administered courses was five, ranging from one to 14. There were 16 (40%) patients who developed grade 3 or 4 neutropenia. Grade 3 or 4 nausea/vomiting and diarrhea were seen in three (8%) and seven (18%) patients, respectively. Only one early death not related to treatment occurred during the study. There was one complete response and 17 partial responses with a response rate of 45% (95% confidence interval: 29.3-61.5%). With a median follow-up period of 22.5 months for survivors, the median survival and median progression-free survival times were 15.9 and 7.0 months, respectively. CONCLUSIONS: Although the toxicities were modest, this sequentially combined regimen is active and feasible in patients with metastatic colorectal cancer.

Adult↗

PubMed2003

Weekly hepatic arterial infusion of 5-fluorouracil and subsequent systemic chemotherapy for liver metastases from colorectal cancer.

OBJECTIVE: To determine the antitumor activity and toxicity of weekly hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) for liver metastases from colorectal cancer. In addition, the present study also evaluated the efficacy of second-line chemotherapy after termination of HAI. METHODS: A retrospective study was designed to evaluate the clinical outcome in patients treated with HAI. Twenty-six patients with liver metastases from colorectal cancer were treated with 5-FU 1000 mg/m(2) over 5 h once per week on an outpatient basis. The treatment was continued until disease progression, unacceptable toxicity or the patient's refusal to continue treatment occurred. One of three kinds of second-line systemic chemotherapy, irinotecan alone, protracted venous infusion of 5-FU or methotrexate (MTX) and 5-FU, was chosen after termination of HAI. RESULTS: An objective tumor response to HAI was observed in 46% (95% confidence interval, 26.9-65.2%) of 26 patients. The most common adverse events were mild nausea and vomiting (35%) and occurrence of gastroduodenal ulcers (15%). Hematological toxicity was minimal. No responder was observed to improve following second-line chemotherapy after termination of HAI. CONCLUSION: Weekly HAI of 5-FU is both active and well tolerated. However, extrahepatic progression was observed in one-third of patients with termination of HAI and the efficacy of second-line chemotherapy was not demonstrated. Regional treatment with systemic chemotherapy should be conducted to achieve good results in terms of survival.

Adult↗

PubMed2002

Inhibition of fibrin-induced neurogenic pulmonary edema by previous unilateral left-vagotomy correlates with increased levels of brain nitric oxide synthase in the nucleus tractus solitarii of rats.

In the course of investigations on mechanisms underlying development of neurogenic pulmonary edema (NPE), we have evaluated effects of nitric oxide (NO) in the central nervous system on incidence and severity in the fibrin-induced pulmonary edema model. Rats left-unilaterally vagotomized 1, 2 and 4 weeks before injections of fibrinogen and thrombin into the cisterna magna, after cutting the right vagus nerve, grouped as LVIW, LV2W or LV4W, respectively. The brain NO synthase (NOS) mRNA level in the left medulla oblongata was elevated in the LV2W group, compared to the control, but decreased in the LV4W rats. Incidences of pulmonary edema were 100% in the control group, decreasing to 78% in LV1W group, 17% in LV2W group, and back to 72% in LV4W group. The lung water ratio, a parameter of severity, demonstrated a similar pattern of change as the incidence. The lowered incidence and severity obtained in the LV2W group were reversed by intracisternal injection of N-nitro-L-arginine methyl ester (L-NAME). From these results, we propose that an increase in nitric oxide, possibly in the nucleus tractus solitarius 2 weeks after left vagotomy, may have an inhibitory action on the development of neurogenic pulmonary edema in rats.

Animals↗

PubMed2002

Effect of a 3-hour interval between methotrexate and 5-fluorouracil in the treatment of metastatic colorectal cancer.

OBJECTIVE: This phase II study was designed to evaluate the efficacy and toxicity of 3-h interval sequential methotrexate (MTX) and 5-fluorouracil (5-FU) with leucovorin (LV) rescue in the treatment of patients with metastatic colorectal cancer. METHODS: Forty-two patients with histologically confirmed metastatic colorectal cancer and at least one two-dimensionally measurable lesion, aged 30-74 years old, with performance status < or =2 and no or one prior chemotherapy were selected. Patients received sequential MTX 100 mg/m2 by bolus injection and 5-FU 600 mg/m2 at 3 h followed by LV rescue initiated after 24 h (15 mg per body every 6 h for six doses). The treatment was repeated every week or every 2 weeks until disease progression. All patients were treated as out-patients unless complications arose. RESULTS: All 42 patients entered in this study were assessable both for response and toxicity. Fifteen patients achieved objective responses (one complete and 14 partial), for an overall response rate of 36% (95% CI: 11-51%). Response rates in pretreated patients and patients with naive chemotherapy were 27 and 42%, respectively. Sixteen patients had stable disease and 11 progressed with therapy. The median survival for all patients was 378 days. The hematological toxicity was mild with no grade 3/4 leukopenia. The major non-hematological toxicity was diarrhea (one grade 4, four grade 3). CONCLUSIONS: This 3-h interval sequential MTX and 5-FU with LV rescue is an active regimen in patients with metastatic colorectal cancer. The treatment showed mild toxicity and was administered on an out-patient basis. The present findings suggest that this regimen warrants further investigation in patients with metastatic colorectal cancer.

Adult↗

PubMed2002

A phase II study of doxifluridine in elderly patients with advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG 9410).

BACKGROUND: A previous phase II study of doxifluridine in non-elderly patients with advanced gastric cancer demonstrated a favorable survival with mild toxicity, despite a low response rate. The objectives of this study were to evaluate efficacy and feasibility of this agent for elderly patients. METHODS: This study protocol required elderly patients, aged 76-80 years, with advanced gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400 mg/m(2)/day, was administered for four consecutive days followed by a 10-day rest. RESULTS: Between October 1994 and March 1998, 18 patients were registered. The study was then closed because of poor accrual. Toxicity was moderate; three patients suffered from grade 3 anemia and one patient each had grade 3 thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial response, seven with no change and 10 with progressive disease, yielding a response rate of 5.6%. The median progression-free survival and median survival time for the 18 patients were 55 and 164 days, respectively, with a 1-year survival rate of 5.6%. CONCLUSIONS: Although the number of patients was too small to draw any definitive conclusions, this study failed to demonstrate the survival advantage of doxifluridine.

Aged↗

PubMed2002

Prognostic factors for patients with metastatic colorectal cancer receiving protracted venous infusion of 5-FU.

The objective of this study was to investigate the possible prognostic factors in patients with metastatic colorectal cancer (CRC) treated with protracted venous infusion (PVI) of 5-fluorouracil (5-FU). PVI of 5-FU is considered to be one of the standard therapies for patients with CRC because of its high efficacy and low toxicity, but possible prognostic factors in patients with CRC treated with PVI of 5-FU have not been reported until now. One hundred two consecutive patients with metastatic CRC, treated with PVI of 250 mg/m(2) /d of 5-FU at the National Cancer Center Hospital between January 1991 and December 1998, were investigated retrospectively. The data were evaluated for possible correlations with clinicopathologic indices or prognosis. In this study, grade III nausea, stomatitis, diarrhea, and hand-foot syndrome occurred in only 3%, 5%, 5%, and 6% of cases, respectively. No grade III or more hematologic toxicities were observed. The overall response (complete response + partial response) rate for all 102 cases was 26%, with a 95% CI of 18% to 35%. Overall median survival time for the 102 cases was 303 days. In multivariate analysis, the favorable prognostic factors were normal albumin level (<or=3.7 g/dl), histologic grades I, II, and low carcinoembryonic antigen level (<100 ng/ml).

Aged↗

PubMed2002

Heart rate variability and arterial blood pressure variability show different characteristic changes during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs.

UNLABELLED: We assessed the changes in heart rate variability (HRV) and blood pressure variability (BPV) as indices of autonomic nervous system and volume status during hemorrhage in isoflurane-anesthetized, mechanically ventilated dogs. Nine dogs were used. They were sequentially subjected to withdrawal of 30% estimated blood volume and graded isoflurane inhalation of 1% and 2% followed by discontinuation of isoflurane and retransfusion. The power spectra of HRV and BPV were computed using the fast Fourier transformation, and were quantified by determining the areas of the spectrum in two component widths: low-frequency component (LF) (0.04-0.15 Hz) and high-frequency component (HF) (0.15-0.4 Hz). During hemorrhage and isoflurane anesthesia, both HRV-LF and HRV-HF were decreased and plateaued at the smaller concentration of isoflurane, whereas BPV-LF decreased concentration-dependently. BPV-HF showed a completely different response and increased significantly during 2% isoflurane. We speculate that HRV and BPV-LF would be affected by the autonomic nervous activity, whereas BPV-HF would depend on relative/absolute change in circulating blood volume. IMPLICATIONS: Power spectra of heart rate variability (HRV) and blood pressure variability (BPV) were computed using the fast Fourier transformation. The HRV and BPV showed their differential characteristics during hemorrhage, isoflurane anesthesia, and retransfusion, and would help to assess changes in autonomic nervous system and preload under mechanical ventilation.

Anesthesia, Inhalation↗

PubMed2002

[4D-MRI using the synchronized sampling method (SSM)].

A synchronized sampling method (SSM) was developed for the study of voluntary movements by combining the electrocardiographic (ECG) gating method with an external triggering device, and four-dimensional magnetic resonance imaging (4D-MRI) at a rate of 30 frames per second was accomplished by volumetric imaging with the SSM. This method was first applied to the motion imaging of articulatory organs during repetitions of a Japanese five-vowel sequence, and the dynamic change in vocal tract area function was demonstrated with sufficient temporal resolution. This paper describes the methodology, applicability, and limitations of 4D-MRI with the SSM.

Electrocardiography↗

PubMed2002

[Post launch studies].

Evidence Based Medicine (EBM) is a growing concept in Japan as it is elsewhere. Central to improving the use of EBM is generation of data through well conducted controlled clinical studies. There are many problems associated with conduct of clinical studies after launch in Japan, and many initiatives are ongoing to improve the situation. Development of Clinical Research Coordinators (CRO) and central Data Management centers are key to improving the quality of clinical research in Japan. Currently Japan has an undeveloped legal system with regard to post-launch trials and off-label use of registered drugs. There is no reimbursement for off-label and various restrictions imposed on the recipients of the Ministry of Health, Labour and Welfare's (MHLW) funds. Maybe the biggest problem is the high cost of post-marketing studies sponsored by pharmaceutical manufacturers. A high quality system to support post launch clinical studies need a solid financial base. There is a need for a suitable review system for investigator initiated multi-centre studies, as the current IRB system is not sufficient. There are also challenges regarding the differences, perceived or real, in treatment practice and available registrations in Japan and in the West, causing problems in choosing suitable comparators and study designs. At the present time it is not clear whether investigator initiated trials will be acceptable for registration purposes in Japan. The agreed first priority is to build a suitable and strong infrastructure within the academic community to support researchers to investigate important questions with or without pharmaceutical company support. Despite all these issues, several groundbreaking projects are under way throughout Japan, in many different areas and by different collaborative groups, some with government support. In fact, researcher-initiated clinical trials achieved a rapid growth in Japan in the past year.

Clinical Trials as Topic↗

PubMed2000

Significance of and problems in adopting response evaluation criteria in solid tumor RECIST for assessing anticancer effects of advanced gastric cancer.

BACKGROUND: The response evaluation criteria in solid tumor (RECIST) exclude the use of barium meal studies. This will deeply affect the Japanese criteria for evaluating the response in the primary lesion of gastric cancer.METHODS: Of 280 patients with gastric cancer enrolled in a Japan Clinical Oncology Group (JCOG) phase III study, 255 had been assessed for response by the WHO and/or Japanese criteria. We selected these 255 patients as our subjects and reassessed their response outcomes by RECIST.RESULTS: Of the 255 patients, 32 (13%) had no evaluable lesion other than the primary site, and 171 (67%) had some measurable lesion defined by the WHO criteria. Because the lesions in 129 of these 171 patients were 20 mm or more in size, only 51% of the 255 subjects were eligible for assessment of the target lesion by RECIST. In 162 of the 171 patients who had a lesion of 10 mm or more, response rates by the old and new criteria were nearly equal, in spite of the different methods of measurement. The response rate in the primary lesions assessed by the Japanese criteria was lowest among all the groups examined.CONCLUSION: The RECIST is simple and good for clinical practice. Nevertheless, the recommendation of 20 mm or more for target lesions, which may restrict the number of eligible patients, could be replaced by a size of 10 mm or more. Because the Japanese evaluation criteria are rigid and do not inflate the response rate, they can be used, as additional criteria for assessing the quality of response, when the RECIST is used.

Journal Article↗

PubMed2000

Long-term results for patients with unresectable gastric cancer who received chemotherapy in the Japan Clinical Oncology Group (JCOG) trials.

BACKGROUND: Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer.METHODS: Between 1985 and 1991, a total of 363 patients with gastric cancer were enrolled into a single randomized phase II study and into three series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C (UFTM), 5'deoxy-flurorouridine + cisplatin (5'P), etoposide + doxorubicin + cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363 patients' case records, 226 patients who fulfilled the criteria of having "unresectable" factors prior to chemotherapy became the subjects for this analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM; 49, in the 5'P; 42, in the EAP; and 46, in the FP group. Survival was updated continually.RESULTS: Of the 226 patients, 22 (10%) survived longer than 2 years, and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of 6 patients who had para-aortic node metastases alone as an "unresectable factor", 1 who had para-aortic and cervical node metastases, and the remaining patient who had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis alone had a significantly longer survival than the other 197 patients ( P < 0.001).CONCLUSION: Systemic chemotherapy may offer some hope of achieving long-term survival in patients with unresectable gastric cancer, particularly when the patient has metastasis only to para-aortic nodes.

Journal Article↗