Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 19 recordsLinked to original sources

PubMed2005

Experimental microdosimetric distributions of protons, from 19 to 65 MeV, using an A150-walled Low Pressure Proportional Counter.

Microdosimetric distributions of protons, from 19 to 65 MeV, were measured using an A150-walled Low Pressure Proportional Counter at the cyclotron facility in the National Institute of Radiological Sciences. The measured distributions were found to be very different from the spectra assumed by the Continuous Slowing Down Approximation. The measurements consisted of determining the energy deposition by direct incident protons, by secondary electrons produced in the wall of the detector and by scattered protons at the wall. The secondary electron and the scattered proton distributions were studied using analytical functions and the MCNPX Monte Carlo code, respectively.

Electrons↗

PubMed2005

Appropriate dosing of antiarrhythmic drugs in Japan requires therapeutic drug monitoring.

OBJECTIVE: In general, drugs are used in accordance with an approved dosage regimen in expectation of an appropriate balance between efficacy and toxicity. However, dose control of drugs with a narrow therapeutic range and marked intersubject variability in pharmacokinetics should be established through individualization of dosing based on therapeutic drug monitoring (TDM). The purpose of this study was to examine differences between the approved dosage regimen and the doses of antiarrhythmic drugs and digoxin used in clinical practice and to examine the influence of TDM on dosing. METHODS: Prescription research of antiarrhythmic drugs was performed at five national hospitals in Japan. Prescriptions for antiarrhythmic drugs (cibenzoline, disopyramide, pirmenol, mexiletine, aprindine, flecainide, pilsicainide, amiodarone and digoxin) were counted for the study period. The mean dose and dose distribution of the drugs were determined in each hospital. Comparisons were made of mean dose obtained in the study with the dosage approved by the authority. In addition, the percentage of patients that received TDM was determined. RESULTS: A difference was seen between the approved dosage and the actual dose. For all drugs except flecainide, the mean dose was smaller than the approved dosage. For all drugs except digoxin, remarkable variations were seen in the dose distribution among the hospitals. Digoxin showed a similar dose distribution among the five hospitals. Overall, the percentage of patients that received TDM was low except for Hospital A. However, TDM of digoxin was relatively common at four of the hospitals. CONCLUSIONS: It is concluded that, with the exception of digoxin, the appropriate dosing regimen for antiarrhythmic drugs is not yet established. The establishment of appropriate dosing regimens for antiarrhythmic drugs requires the more widespread adoption of TDM.

Anti-Arrhythmia Agents↗

PubMed2004

Comparative study of electrothermal bipolar vessel sealer and ultrasonic coagulating shears in laparoscopic colectomy.

BACKGROUND: As an alternative to suture ligatures of the vessels, an electrothermal bipolar vessel sealer (EBVS) was recently developed. Meanwhile, ultrasonic coagulating shears (UCS) have been widely used clinically to provide hemostatic cutting in laparoscopic procedures. We conducted a comparative study to investigate the relative advantages of these two instruments. METHODS: The study included 30 patients with colon cancer who underwent laparoscopic colectomy using either the EBVS or the UCS. We performed a comparative analysis of the instruments by viewing videotapes showing their application in laparoscopic transverse colectomy and sigmoidectomy. RESULTS: Average patient age was 71.6 +/- 1.4 years. Average hospital stay was 14.2 +/- 1.0 days. There were no statistical differences between the groups in age and hospital stay. The incidence of rebleeding was significantly lower in the EBVS group than in the UCS group for both surgical procedures (0.3 vs 1.2 in transverse colectomy, 0.3 vs 2.0 in sigmoidectomy, respectively). In addition, the required time for mesocolon dissection was also significantly shorter when the EBVS was used in both laparoscopic transverse colectomy and sigmoidectomy (7.9 vs 18.4, 15.0 vs 27.6, respectively). CONCLUSION: The use of the EBVS will enable surgeons to reduce the total operating time for laparoscopic colectomy.

Aged, 80 and over↗

PubMed2004

Modulation of thymidine phosphorylase by neoadjuvant chemotherapy in primary breast cancer.

The combination effect of docetaxel and capecitabine on tumour response rate and survival was demonstrated recently in metastatic breast cancer patients. This combination was based on an experimental hypothesis that taxane can increase tumour sensitivity to the effect of capecitabine through the upregulation of thymidine phosphorylase (TP), which is responsible for the metabolism of 5-fluorouracil (5-FU) and its derivatives, including capecitabine. To examine the alteration in TP expression before and after neoadjuvant chemotherapy, 92 patients with primary breast cancer (T2-4N0-1M0) were enrolled in this study; 14 were treated with adriamycin and cyclophosphamide (AC) or epirubicin and cyclophosphamide (EC); 58 with 5-FU, adriamycin, and cyclophosphamide (FAC) or 5-FU, epirubicin, and cyclophosphamide (FEC); and 20 with FEC followed by docetaxel/taxotere (TXT-containing regimen). Thymidine phosphorylase upregulation was seen in 54.4% and 32.6% of patients in tumour cells and stromal cells, respectively. Increases in TP expression were found only in the AC/EC and TXT-containing regimen groups. In conclusion, it was strongly suggested that unlike 5-FU-containing regimens, the taxane and AC combination therapies upregulate TP expression in primary breast cancer. Thymidine phosphorylase upregulation by several anticancer drugs implies the importance of individualised strategies for sensitisation of tumour tissues to 5-FU and its derivatives.

Adult↗

PubMed2004

Augmentation of interleukin-10 in pancreatic islets after brain death.

Clinical islet transplantation is now established as a treatment for patients with type I diabetes. Although organs from brain-dead (BD) donors are the main source for clinical transplantation, marginal status after BD produces deterioration of the organs followed by molecular activation. The effect of brain-death (BD) induction on the immunological status of donor islets was investigated using a rodent model of BD. BD animals showed decreased levels of peripheral white blood cells (WBC) compared to controls, indicating the extravasation of these cells (7270 +/- 500 vs 9570 +/- 370, respectively). In a densitometric study of RT-PCR products, the Th2 cytokine (IL-10) was significantly up-regulated in BD (2.91 +/- 0.26 vs 1.76 +/- 0.40), but a Th1 cytokine (IL-2) showed minimal change. Increased expression of IL-10 may inhibit macrophage function. As the marginal status after BD deteriorates, the islets of these donors may display early graft loss or poor long-term function. Integrative studies of immunomodulation might be necessary to eliminate islet infiltrates.

Animals↗

PubMed2004

Microdosimetry of neutron field for boron neutron capture therapy at Kyoto university reactor.

Microdosimetric single event spectrum in a human body simulated by an acrylic phantom has been measured for the clinical BNCT field at the Kyoto University Reactor (KUR). The recoil particles resulting from the initial reaction and subsequent interactions, namely protons, electrons, alpha particles and carbon nuclei are identified in the microdosimetric spectrum. The relative contributions to the neutron dose from proton, alpha particles and carbon are estimated to be about 0.9, 0.07 and 0.3, respectively, four depths between 5 and 41 mm. We estimate that the dose averaged lineal energy, yD decreased with depth from 64 to 46 keV microm(-1). Relative biological effectiveness (RBE) of this neutron field using a response function for the microdosimetric spectrum was estimated to decrease from 3.6 to 2.9 with increasing depth.

Academic Medical Centers↗

PubMed2004

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys.

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.

Animals↗

PubMed2004

Concomitant use of buffered and enteric-coated low-dose aspirin products and antisecretory drugs.

OBJECTIVE: Buffered and enteric-coated formulations of low-dose aspirin therapy are although expected to avoid gastrointestinal complications, there are reports that these modified products are associated with such complications. One available option for preventing aspirin-induced gastrointestinal complications is the simultaneous use of the agents that inhibit acid secretion such as H(2)-receptor antagonists and proton pump inhibitors. We compared the frequency of prescriptions for antisecretory drugs between users of either buffered or enteric-coated low-dose aspirin. METHODS: Monthly prescriptions at the National Cardiovascular Center for aspirin products and antisecretory drugs were counted from January 1998 to December 2002. Counting was based on information from a prescription database file compiled from a computerized order entry system. Time-series analyses were performed to determine changes in the frequency of prescriptions for low-dose aspirin products and antisecretory drugs. In addition, the frequency of prescriptions for antisecretory drugs was compared in individuals using either buffered or enteric-coated low-dose aspirin. RESULTS: A significant reduction in the frequency of prescriptions for H(2)-receptor antagonists was observed during 2001 in users of enteric-coated low-dose aspirin compared with users of buffered low-dose aspirin users. In contrast, we observed a significant increase in the frequency of prescriptions for H(2)-receptor antagonists in users of enteric-coated low-dose aspirin during 2002. This change in prescribing H(2)-receptor antagonists in users of enteric-coated low-dose aspirin began in the latter half of 2001. Proton pump inhibitors accounted for 0.31% of prescriptions in users of buffered low-dose aspirin and 0.47% in users of enteric-coated low-dose aspirin, with this difference being statistically significant. CONCLUSION: The findings of the present study do not support the notion that enteric-coated low-dose aspirin reduces the risk of gastrointestinal complications and is safer than buffered low-dose aspirin products. However the usual caution about making inferences from observational retrospective data is appropriate.

Administration, Oral↗

PubMed2004

A malar granular cell tumor in a djungarian hamster.

'Granular cell' tumor observed in the malar subcutis of a Djungarian hamster was examined to determine its cellular origin. Histologically, the tumor consisted of a solid growth of oval or spindle-shaped large cells with abundant cytoplasm filled with eosinophilic granules that were periodic acid-Schiff-positive and diastase-resistant. Immunohistochemically, the tumor cells were positive to anti-vimentin and anti-desmin antibodies and a few cells showed positivity to anti-actin antibody as well. They did not react to myoglobin, S-100 protein, and glial fibrillary acidic protein (GFAP). Electron microscopic studies revealed that the tumor cells had pinocytotic vesicles, dense plaque and microfilaments. The first granular cell variant of myogenic tumor reported here in Djungarian hamsters was differentiated from granular cell tumor of Schwann cell origin.

Animals↗

PubMed2004

Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of neurons in the external pallidum in awake monkeys.

The neurons in the external segment of the pallidum (GPe) in awake animals maintain a high level of firing activity. The level and pattern of the activity change with the development of basal ganglia disorders including parkinsonism and hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus exploring the mechanisms controlling the firing activity is essential for understanding basal ganglia function in normal and pathological conditions. To explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe, unit recordings combined with local injections of receptor antagonists were performed in awake monkeys. Observations on the effects of local application of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide, the N-methyl-D-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing rate, firing patterns, and cortical stimulation induced responses in the GPe suggested the following: sustained glutamatergic and GABAergic inputs control the level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA receptors are activated by glutamatergic inputs; some GPe neurons receive glutamatergic inputs originating from areas other than the subthalamic nucleus; no GPe neurons became silent after a combined application of glutamate and GABA antagonists, suggesting that GPe neurons have intrinsic properties or nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing or a combination of a fast and a slow oscillatory firing in GPe neurons.

Animals↗

PubMed2003

Comparison of intestinal transit recovery between laparoscopic and open surgery using a rat model.

BACKGROUND: After laparoscopic surgery (LS), patients show faster recovery of intestinal transit than after conventional open surgery (OS). To prove the mechanism of this advantage, we compared the recovery of intestinal transit using steel carbon balls. METHODS: Rats underwent either open laparotomy or were insufflated with carbon dioxide followed by the administration of steel balls (0.6 mm). An abdominal radiograph was taken 12 h after the operation. Compliance of the intestinal walls was analyzed with a computer-driven barostat device. RESULTS: An abdominal radiograph of 12 h after administration of the steel carbon balls showed the balls scattered in the small and large intestine of the LS patients, whereas they remained mostly in the stomach of the OS patients. Compliance of the intestinal walls was sustained at approximately 100 microl/mmHg in the LS patients, whereas it dropped to 94 microl/mmHg in the OS patients with the increase in balloon pressure. Histologically, the extent of serosal edema was more severe in the OS than in the LS patients. In terms of intestinal transit and irritation LS has advantage over OS. CONCLUSIONS: Intestinal transit recovery, as measured by the migration of steel carbon balls, is faster in LS, and gastric emptying is slow in OS.

Animals↗

PubMed2003

Characterization of islet-infiltrating immunocytes after pancreas preservation by two-layer (UW/perfluorochemical) cold storage method.

Clinical islet transplantation offers the prospect of good blood glycemic control without major surgical risks. Nevertheless, long-term function of the transplanted islets is seldom appreciated because rejection is followed by the graft failure. Although it has been implicated that islets have high immunogenicity, characterization of the islet-infiltrating immunocytes, such as leukocytes and macrophages, has not been extensively studied. Rat islets were isolated by the collagenase digestion method and separated by handpicking under the microscope. The islets were further dispersed into individual cells for flow cytometric analysis. Monoclonal antibodies directed toward T cells, B cells, and macrophages as well as ICAM-1, and MHC class I and II were used to enumerate cells. Pancreatic islets contained 6.3 +/- 2.9% immunocytes; T cells (39.6 +/- 4.2%), B cells (44.7 +/- 5.8%), and macrophages (1.7 +/- 0.6%). MHC class I was expressed on 85.6 +/- 2.8%, MHC class II on 36.8 +/- 2.9%, and ICAM-1 on 39.9 +/- 7.0%. The results of islets from preserved pancreas also showed the same tendency. As these islet-infiltrating immunocytes within the grafts may contribute to the rejection, one potential strategy to prevent early graft loss might start to eliminate or inactivate the islet-infiltrating immunocytes.

Adenosine↗

PubMed2003

Excitatory GABA input directly drives seizure-like rhythmic synchronization in mature hippocampal CA1 pyramidal cells.

GABA, which generally mediates inhibitory synaptic transmissions, occasionally acts as an excitatory transmitter through intense GABA(A) receptor activation even in adult animals. The excitatory effect results from alterations in the gradients of chloride, bicarbonate, and potassium ions, but its functional role still remains a mystery. Here we show that such GABAergic excitation participates in the expression of seizure-like rhythmic synchronization (afterdischarge) in the mature hippocampal CA1 region. Seizure-like afterdischarge was induced by high-frequency synaptic stimulation in the rat hippocampal CA1-isolated slice preparations. The hippocampal afterdischarge was completely blocked by selective antagonists of ionotropic glutamate receptors or of GABA(A) receptor, and also by gap-junction inhibitors. In the CA1 pyramidal cells, oscillatory depolarizing responses during the afterdischarge were largely dependent on chloride conductance, and their reversal potentials (average -38 mV) were very close to those of exogenously applied GABAergic responses. Moreover, intracellular loading of the GABA(A) receptor blocker fluoride abolished the oscillatory responses in the pyramidal cells. Finally, the GABAergic excitation-driven afterdischarge has not been inducible until the second postnatal week. Thus, excitatory GABAergic transmission seems to play an active functional role in the generation of adult hippocampal afterdischarge, in cooperation with glutamatergic transmissions and possible gap junctional communications. Our findings may elucidate the cellular mechanism of neuronal synchronization during seizure activity in temporal lobe epilepsy.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2003

Phaeohyphomycosis caused by Chaetomium globosum in an allogeneic bone marrow transplant recipient.

Bone marrow transplant recipients are highly susceptible to opportunistic fungal infections. This is the report, of the first case of a Chaetomium systemic infection described in Brazil. A 34 year-old patient with chronic myeloid leukemia underwent an allogeneic sibling matched bone marrow transplant. Seven months later, he developed systemic infection with enlargement of the axillary and cervical lymph nodes. Culture of the aspirates from both lymph nodes yielded Chaetomium globosum. The infection was successfully treated with amphotericin B. The increasing population of immunosupressed patients requires a careful microbiologic investigation for uncommon fungal infections.

Adult↗

PubMed2003

Involvement of the entorhinal cortex in the stress response to immobilization, but not to insulin-induced hypoglycaemia.

Although the involvement of the limbic system in the neuroendocrine responses to some stressors has been documented, the specific role of the entorhinal cortex has not been elucidated. In this study, we investigated the involvement of the entorhinal cortex in stress responses. Fos immunoreactivity, a widely used marker for neuronal activation, was detected in the entorhinal cortex of rats subjected to immobilization stress, whereas no marked staining was observed in the entorhinal cortex of the control and insulin-induced hypoglycaemia groups. Lesion of the entorhinal cortex produced by ibotenic acid significantly attenuated the adrenocorticotropic hormone (ACTH) release evoked by immobilization; however, no significant change in ACTH release was observed in insulin-induced hypoglycaemia. No significant difference between entorhinal-lesioned rats and control rats was observed in blood glucose concentrations when subjected to either immobilization or to insulin-induced hypoglycaemia. Together, these results indicate that the entorhinal cortex is closely involved in the stress response to immobilization but not to insulin-induced hypoglycaemia.

Adrenocorticotropic Hormone↗

PubMed2003

Shielding experiment of heavy-ion produced neutrons using a tissue-equivalent proportional counter.

A shielding experiment was performed at the HIMAC (Heavy Ion Medical Accelerator in Chiba), of National Institute of Radiological Sciences (NIRS), to measure neutron dose using a spherical TEPC (tissue-equivalent proportional counter) of 12.55 cm inner diameter. Neutrons are produced from a 5 cm thick stopping length Cu target bombarded by 400 MeV/nucleon C6+ ions and penetrate concrete or iron shields of various thicknesses at 0 degree to the beam direction. From this shielding experiment. y-distribution, mean lineal energy, absorbed dose, dose equivalent and mean-quality factor were obtained behind the shield as a function of shield thickness. The neutron dose attenuation lengths were also obtained as 126 g cm(-2) for concrete and 211 g cm(-2) for iron. The measured results were compared with the calculated results using the MARS Monte Carlo code.

Calibration↗

PubMed2003

Physicians' prescribing attitudes to combined therapy with statins and fibrates.

OBJECTIVE: To assess the impact of a package insert revision and a drug-drug interaction warning embedded in a computerized prescription ordering system, on physicians' prescribing of concomitant statins and fibrates. METHODS: Data were obtained using a computerized prescription order entry system before and after administrative intervention advising of potentially adverse effects of this combined therapy. The number of prescriptions for statins and fibrates were counted monthly from January 1998 to June 2002 at the National Cardiovascular Center (NCVC). Counting was based on information from a prescription database file compiled from a computerized order entry system. The total number of prescriptions and frequency of requests for statins and fibrates were compared with the timing of either package insert revision or introduction of the warning on a computerized prescription ordering system. In addition, laboratory testing of renal function using serum creatinine (Scr) assays in patients treated with combined statins and fibrates was obtained from medical records at two stages during the study period (stage 1, January 1998 to June 1998; stage 2, January 2002 to June 2002). RESULTS: There were 204 prescriptions for concomitant statins and fibrates at the beginning and 50 prescriptions at end of the study period. The number of prescriptions began to decrease in the latter half of 1999 with the percentage of concomitant use of statins and fibrates showing an evident downward trend from January 2001. This acceleration in the downward trend coincided with the introduction of the computerized warning message. Scr levels were measured in 43.8% of patients in stage 1 and in 48.3% of patients in stage 2 in the past month. The percentage of patients having Scr levels measured in the past 6 months was 85.3% in stage 1 and 84.5% in stage 2. There was no significant difference in the percentages of patients whose Scr levels had been measured between the two stages. CONCLUSION: Revision of package inserts concerning combined therapy of statins and fibrates led to physicians' prescribing fewer of these combinations. A warning message displayed on a computerized prescription order entry system accentuated this effect.

Anticholesteremic Agents↗

PubMed2003

[Lung cancer with both sarcoid reaction and metastasis in the mediastinal lymph nodes; report of a case].

A 66-year-old man was admitted to our hospital for detailed investigation of an abnormal shadow on his chest X-ray. Chest radiography and computed tomography(CT) of the chest showed mediastinal lymphadenopathy and a tumor shadow in the left upper lobe. Biopsy of the mediastinal lymph nodes by mediastinoscopy showed that sarcoid nodules existed in all the biopsies nodes. Therefore, the lymphadenopathy was thought to be sarcoidosis or sarcoid reaction accompanied with lung cancer. Left upper lobectomy and dissection of hilar and mediastinal lymph nodes were performed. Although sarcoid nodules were seen in all the dissected lymph nodes, the cancer involved #5 and #14 lymph nodes. He died of brain metastasis 10 months after surgery.

Adenocarcinoma↗