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T Okawa

Publications and source records attributed to T Okawa.

At least 37 records · Page 2Linked to original sources

The role of cyclic nucleotides in the spontaneous contractility and responsiveness to nitric oxide of the rat uterus at midgestation and term.

OBJECTIVES: The aim of this investigation was to study the effects of pharmacologic manipulation of cyclic nucleotide levels on the uterine spontaneous contractile activity and responsiveness to nitric oxide in pregnant rats at midgestation and term. STUDY DESIGN: Uterine rings from pregnant rats at midgestation and term were placed in organ chambers for isometric tension recording. Concentration-response curves were obtained for phosphodiesterase and guanylate cyclase inhibitors, membrane-permeable cyclic nucleotide analogs, and forskolin. In addition, the effects of minimal inhibitory concentrations of these agents on the concentration-response relationships for diethylamine nitric oxide (a nitric oxide donor) were studied. RESULTS: Nonselective phosphodiesterase inhibitors induced more inhibition of contractions of uterine rings from pregnant rats at term than at midgestation and zaprinast induced less. Inhibitors of guanylate cyclase and membrane-permeable analogs of cyclic guanosine monophosphate were equally effective in tissues from pregnant rats at midgestation and term. All agents attenuated the inhibitory effect of diethylamine nitric oxide at midgestation; however, dibutyryl cyclic adenosine monophosphate and papaverine increased the inhibitory effect of diethylamine nitric oxide in tissues from pregnant animals at term. CONCLUSIONS: Cyclic nucleotides modulate both spontaneous and nitric oxide-induced changes in uterine contraction during pregnancy. Application of nonselective inhibitors of phosphodiesterase, as well as membrane-permeable analogs of cyclic adenosine monophosphate, may counteract refractoriness to nitric oxide at term.

1-Methyl-3-isobutylxanthine↗

Prospective study of external radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. JASTRO Study Group.

To improve the results of treatment of patients with esophageal cancer, it is important to achieve good local control. Since the esophagus is adjacent to highly radiation-sensitive organs such as the lungs, bone marrow, etc., it is difficult to irradiate tumors with high doses. Although irradiation techniques have improved as a result of advances in treatment-planning equipment and irradiation equipment, there are still some patients for whom radical radiation therapy within doses that the bone marrow and lungs can tolerate is difficult with external irradiation alone. On the other hand, intraluminal brachytherapy allows high-dose irradiation of esophageal cancer with little risk to adjacent organs. However, intraluminal brachytherapy, in which the dose sharply declines with the distance from the radiation source, is suggested to be a useful technique for tumors with relatively shallow invasion. With the aim of improving the results of esophageal cancer treatment, we designed this study to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy.

Adult↗

Multi-institutional randomized trial of external radiotherapy with and without intraluminal brachytherapy for esophageal cancer in Japan. Japanese Society of Therapeutic Radiology and Oncology (JASTRO) Study Group.

PURPOSE: With the aim of improving the results of treatment of esophageal cancer, we designed this multi-institutional, randomized trial to establish the optimal irradiation method in radical radiation therapy for esophageal cancer by clinically evaluating external irradiation alone and in combination with intraluminal brachytherapy. METHODS AND MATERIALS: The study population consisted of patients with squamous cell carcinoma who were expected to be successfully treated with radical radiation therapy. The patients who could be given intraluminal brachytherapy at the end of external irradiation of 60 Gy were stratified into 2 groups. Patients assigned to receive external irradiation alone received boost irradiation of 10 Gy/week on a schedule similar to the previous one, and with the same or smaller irradiation field. Intraluminal brachytherapy was performed, as a rule, with the reference dose point set at a depth of 5 mm of the esophageal submucosa, and a total of 10 Gy was irradiated at a daily dose of 5 Gy, on a once-weekly schedule with low-dose-rate or high-dose-rate brachytherapy equipment. RESULTS: A total of 103 patients were registered, 94 of whom were analyzable, with 8 ineligible, and 1 for whom complete information was unavailable. The overall cumulative survival rate was 20.3% at 5 years. The cause-specific survival rate was 31.8% at 5 years. The cause-specific survival rate at 5 years was 27% in the external irradiation alone group and 38% in intraluminal brachytherapy combined group. There was no significant difference between the 2 groups (p = 0.385). However, in the patients with 5 cm or less tumor length, the cause-specific survival rate was 64% at 5 years in the intraluminal brachytherapy combined group, which showed a significant improvement over 31.5% in the external irradiation alone group (p = 0.025). In the patients with Stage T1 and T2 disease, cause-specific survival rates tended to be better in the intraluminal brachytherapy combined group than in the external irradiation alone group (p = 0.088). In the patients with more than 5 cm tumor length or Stage T3-4 disease, there were no significant differences between the two groups by treatment methods (p = 0.290). The incidence of early and late complications did not differ according to whether intraluminal brachytherapy was used. CONCLUSION: For the purpose of establishing the usefulness of intraluminal brachytherapy, further prospective randomized studies are necessary to evaluate the efficacy in tumors with short length and those with shallow invasion, or to assess the usefulness of intraluminal brachytherapy, as additional irradiation in large advanced tumors have been shown to have disappeared by diagnostic imaging after chemoradiotherapy with 60 Gy/6w external irradiation.

Adult↗

Roles of potassium channels and nitric oxide in modulation of uterine contractions in rat pregnancy.

OBJECTIVE: We sought to study the involvement of potassium channels in the inhibition by nitric oxide of spontaneous contractions in isolated uterine rings from midterm and term pregnant rats. STUDY DESIGN: Uterine rings from Sprague-Dawley rats at midterm and term gestation were used for isometric tension recording. The inhibition of spontaneous contractile activity by potassium channel openers and nitric oxide was studied in the absence and presence of potassium channel inhibitors. RESULTS: The adenosine triphosphate-dependent potassium channel opener levcromakalim inhibited spontaneous contractions in rings from both midterm and term pregnant rats in a concentration-dependent manner, and the effects were significantly attenuated by pretreatment with selective inhibitor of the adenosine triphosphate-dependent potassium channel inhibitor glibenclamide. The opener of calcium-dependent potassium channel NS 1619 inhibited spontaneous contractions in rings from midterm but significantly less so in rings from term pregnant rats in a concentration-dependent manner, and the effect was significantly attenuated by pretreatment with potassium channel inhibitors tetraethylammonium and tetrabutylammonium but not with glibenclamide. Rings from midterm and term pregnant rats were more sensitive to the inhibitory effect of levcromakalim compared with NS 1619. Nitric oxide donor diethylamine-nitric oxide inhibited spontaneous contractions in rings from midterm but significantly less in rings from term pregnant rats in a concentration-dependent manner, and the effect was attenuated by tetraethylammonium and tetrabutylammonium but not by glibenclamide. CONCLUSIONS: There is gestational age-dependent refractoriness to calcium-dependent potassium but not adenosine triphosphate-dependent potassium channel opener-induced inhibition of spontaneous contractile activity of isolated rat uterine rings. Nitric oxide inhibits uterine contractions by opening of calcium-dependent potassium channels in pregnant rat myometrium. Refractoriness to nitric oxide toward term may result from decreased probability to open or number of calcium-dependent potassium channels.

Adenosine Triphosphate↗

Effect of placental tissue on inhibition of uterine contraction by nitric oxide donors.

OBJECTIVE: Our purpose was to test the hypothesis that placental tissue modulates the effect of nitric oxide on spontaneous uterine contractility in pregnant rats. STUDY DESIGN: Rings (approximately 4 mm) of uterus taken from rats on day 14 (midpregnancy, n = 6), day 18 (late pregnancy, n = 4), and day 22 (term, n = 4) of gestation were placed in organ chambers filled with Krebs-bicarbonate buffer bubbled with 5% carbon dioxide in air (37 degrees C, pH approximately 7.4) for isometric tension recording. In some rings a piece of placenta was left attached to the uterine wall. In the other rings the fetuses, placentas, and membranes were removed completely. Change of spontaneous contractions of the rings (percentage change of basal integral activity for 10 minutes) in response to cumulative concentrations of the nitric oxide donors diethylamine-nitric oxide and nitroglycerin (10(-6) mol/L to 10(-4) mol/L) were compared between rings with and without placenta. RESULTS: Diethylamine-nitric oxide and nitroglycerin inhibited spontaneous uterine contractions in rings from midpregnancy, in both the absence and the presence of placenta. In rings from midpregnancy, the maximal inhibition of contractions by diethylamine-nitric oxide but not by nitroglycerin was significantly (P <.05) higher in the presence (26.7% +/- 3.5% of basal activity) than in the absence (39. 6% +/- 3.3%) of placenta. Inhibition of contraction by nitric oxide donors in rings from late and term pregnancy was less than in midpregnancy, and the presence of placental tissue did not influence the responses. CONCLUSIONS: The presence of placental tissue enhances inhibition of uterine contractility by agents that spontaneously release nitric oxide, such as diethylamine-nitric oxide, but not by nitroglycerin, which requires metabolic transformation for nitric oxide to be released. Refractoriness to nitric oxide near or at term does not depend on the presence or absence of placental tissue.

Animals↗

Comparison of parameters of 123I-MIBG scintigraphy for predicting prognosis in patients with dilated cardiomyopathy.

123I-metaiodobenzylguanidine (MIBG) scintigraphy has been used to predict prognosis of patients with dilated cardiomyopathy (DCM), although it is unknown which parameter of MIBG is the most useful clinically. We studied MIBG in 59 patients with DCM, and followed them up to evaluate the prognosis of DCM. Single photon emission tomography (SPET) and planar imaging were performed, both early (e) and 4 h (delayed, d) post-injection. 201Tl (TL) SPET and radionuclide-ventriculography were also investigated. The total defect score of early and delayed MIBG and 201 Tl (MIBGeDS, MIBGdDS, TLDS) was analysed visually for each SPET image. The heart to mediastinum ratio (H/M) for both the early and delayed MIBG planar images and myocardial washout rate at 4 h were analysed quantitatively. Sixteen patients died during follow-up. Cox Hazards univariate analysis selected washout rate (P < 0.0001), H/Me (P = 0.0012), H/Md (P = 0.0001) and left ventricular ejection fraction (P = 0.0004) as indices for the prediction of cardiac death. Multivariate analysis selected washout rate as the most powerful independent predictor of prognosis (P < 0.0001). Survival curves with a threshold value of 52% for washout rate were able to differentiate a negative outcome from survival (P < 0.0001). TLDS, MIBGeDS and MIBGdDS were not useful in the prediction of prognosis. The washout rate of MIBG is the most potent predictor of cardiac death and is considered clinically useful.

3-Iodobenzylguanidine↗

[History of radiotherapy for cancer].

The basic principle of radiotherapy for cancer patients is to establish a course of therapy which offers good prospects for a cure, has tolerable adverse effects, and promises a comfortable life for the patient thereafter. There have been two paths in the development of radiotherapy. One is physical, in which efforts have been made to improve the dose concentration on the tumor while avoiding healthy tissue, and the order is biological efforts to increase radiation susceptibility of tumors. Recently, computer medicine has improved radiation planning and made high quality radiotherapy possible. Elderly patients with cancer need to be treated with minimally invasive organ-preserving therapy techniques. Radiotherapy is an important tool for cancer treatment in the past, present and future.

Brachytherapy↗

[Development of radiotherapy--history and future prospects].

There have been two ways in the development of radiotherapy. One is physical development, in which efforts have been made to improve the dose concentration on the tumor while avoiding normal tissue, and the other is biological efforts to increase the radiation sensitivity of tumors. Computer medicine has improved oncological diagnoses and radiation planning, which in turn has made high quality radiotherapy possible. Radiotherapy is superior with regard to organ preservation in the treatment cancer. Elderly patients with cancer should be treated with minimally invasive organ-preserving therapy, and thus radiotherapy has been and will be an important tool for cancer treatment in the past, present and into the next century.

Brachytherapy↗

[Effectiveness of 3 ways method in intra-arterial infusion chemotherapy for advanced or recurrent cervical cancer with or without radiotherapy].

We analyzed 58 cases of advanced or recurrent cervical cancer treated with intra-arterial infusion chemotherapy (IAIC) with or without radiotherapy. Two separate IAIC regimens were administered since 1985: group I consisted of 5-FU + MMC +/- ADR (30 patients) and group II consisted of CDDP + MMC +/- 5-FU (28 patients). The tip of a catheter was placed in the bifurcation of the abdominal aorta (1 way method: 45 patients regimen II: 15) between 1977-1984. We have used selective catheterization (2 ways method: 9) since 1995 in order to get good drug distribution. However we experienced grade 4 toxic effect of cutaneous and pain with this method, so we have used a 3 ways method (4 patients) since 1998. The two-year survival rete was 60% with the 1 way method, and 67% with the 2 ways method and regimen II. Severe adverse effects (grade 3 + 4) were found in 53, 56, 0%, respectively, by each of the three methods (1, 2, 3 ways) hematologically, 13, 22, 0% in gastrointestinally, 0, 44, 0% in cutaneously and 0, 56, 0% in pain or neurotoxicity. These data suggest that IAIC by the 3 ways method is a useful treatment for advanced or recurrent cervical cancer. However, one should check the blood flow distribution periodically, and control concentration of drugs.

Adult↗

The effects of nitric oxide on the contractility of isolated uterine and aortic rings from pregnant rats.

OBJECTIVE: The object was to compare the effects of nitric oxide on isolated uterus and aorta of pregnant rats. STUDY DESIGN: Rings of uterus and thoracic aorta without endothelium from Sprague-Dawley rats at mid and late gestation were used for isometric tension recording. The concentration-response curve for diethylamine/nitric oxide was studied in the presence or absence of oxyhemoglobin (10(-5) mol/L), or oxyhemoglobin was added after the response to diethylamine/nitric oxide. RESULTS: Diethylamine/nitric oxide concentration dependently inhibited uterine contractions, and the effect was attenuated by previous treatment with oxyhemoglobin at mid gestation (n = 8). The effects were negligible at late gestation (n = 8). The relaxation of aortic rings by diethylamine/nitric oxide and its attenuation by previous treatment with oxyhemoglobin were similar at mid (n = 6) and late (n = 6) gestation. The sensitivity of aortic rings to diethylamine/nitric oxide is significantly higher than that of uterine rings. Oxyhemoglobin partly restored inhibited diethylamine/nitric oxide phenylephrine tension in aortic rings and had no effect on diethylamine/nitric oxide-inhibited uterine rings. CONCLUSIONS: Uterine smooth muscle is less sensitive to nitric oxide than is aortic smooth muscle. Nitric oxide sensitivity of rat uterus but not aorta decreases toward term.

Animals↗

Phase II study of paclitaxel (BMS-181339) intravenously infused over 3 hours for advanced or metastatic breast cancer in Japan. BMS-181339 Breast Cancer Study Group.

A Phase II study of paclitaxel in patients with primary advanced or metastatic breast cancer was conducted by a cooperative study group consisting of 16 institutions in Japan. Paclitaxel at a dose of 210 mg/m2 was intravenously infused over 3 hours, along with premedication to prevent hypersensitivity reactions. The course was repeated at 21-day intervals. Of 62 eligible patients, 60 were evaluable for toxicity and 59 were evaluable for efficacy. Forty-five patients were previously treated with anthracyclines. Twenty-one of 59 patients (35.6%) had a major objective response including 2 CRs and 19 PRs (95% confidence interval, 23.6-49.1%). A response rate of 35.5% (CR1, PR10) was observed in 31 patients refractory to the anthracyclines containing prior metastatic chemotherapy. Median (range) time was 41 (6-100) days to onset of and median duration of response was 125 (36-305) days. Toxicities included leukopenia (grade 3, 4: 67%), anemia (grade 1-3: 80%), thrombocytopenia (grade 1: 8%), alopecia (grade 3: 43%), peripheral neuropathy (grade 1-3: 93%), arthralgia (59%), myalgia (46%), nausea and vomiting (40%), fever (33%), allergic reaction (grade 3: 2%) and hypotension (grade 3: 5%). All toxicities were tolerable and manageable. Paclitaxel intravenously infused over 3 hours demonstrated a significant antitumor activity for metastatic breast cancer. Furthermore, paclitaxel exhibited non-cross resistance to anthracycline. Paclitaxel administered as a convenient 3-hour infusion is effective for patients with metastatic breast cancer and has an acceptable toxicity profile.

Adult↗

Evaluation of regional cardiac sympathetic innervation in congenital long QT syndrome using 123I-MIBG scintigraphy.

The aim of this study was to determine whether sympathetic imbalance in congenital long QT syndrome (LQTS) can be identified by cardiac sympathetic neuronal dysinnervation. 123I-metaiodobenzylguanidine (MIBG) is a tracer of the norepinephrine analogue which reflects the regional innervation and norepinephrine kinetics in cardiac sympathetic nerves. Sixteen patients with LQTS, who were members of 12 families, and 7 normal controls underwent MIBG scintigraphy. Myocardial SPET and planar images were obtained 15 min and 4 h after the injection of MIBG in each patient. The relative regional uptake (RRU) and regional washout rate (rWR) of MIBG at 4 h in each of nine regions were compared with those in the control group. The heat-to-mediastinum ratio (H/M) and global washout rate (GWR) were also calculated. The RRU, rWR, H/M and GWR showed no significant difference between LQTS patients and normal controls. Furthermore, the RRU in 96% of all regions in LQTS was within the mean +/- 2 standard deviations of that in the control group. Patients with LQTS have normal cardiac sympathetic innervation, as assessed by MIBG. The sympathetic imbalance hypothesis is unlikely to be attributed to an abnormal distribution and different regional norepinephrine kinetics of cardiac sympathetic nerves.

3-Iodobenzylguanidine↗

Relation between radiographic mottle for double and single emulsions.

The radiographic density fluctuations produced by using dual screen-film systems are designated as the radiographic mottle. The density fluctuation of the radiographic mottle for the double emulsions at a density of the double emulsions consists of those for the front and back emulsions on a radiograph. However, the relation between the Wiener spectra of the radiographic mottle for the double and single emulsions had not been studied. Hence we compared the Wiener spectra of the radiographic mottle for the double emulsions with the sum of those for the front and back emulsions on the same radiographs and with the sum of those for the emulsions at the same densities. At all densities of more than 0.62 for lower spatial frequencies (< or = 1 mm-1), the Wiener spectral values of the radiographic mottle for the double emulsions were greater than the sum of those for the front and back emulsions for both comparisons on the same radiographs and at the same densities. In order to investigate the reason of the above phenomena, we separated the Wiener spectral values of the radiographic mottle for various densities into those of the three factors, i.e., quantum mottle, structure mottle, and film granularity, and performed the same comparisons as the radiographic mottle. Also, to explain the results for the three factors, we obtained the Wiener spectral values of the spatial fluctuations of the light exposure or the fluorescence intensity and the gradients of the characteristic curves of the film for the double and single emulsions of the x-ray film. As a result of the investigation, we found that the phenomena on the radiographic mottle were caused by that (1) on the same radiographs the squares of the gradients of the characteristic curves for the double emulsions were about 5.3 times as great as those for the single emulsion at densities of more than 0.62 of the double emulsions, and (2) at the same density of more than 0.62 those were more than about 2.2 times as great as those for the single emulsion.

Biophysical Phenomena↗

[Radiotherapy for elderly patients].

Radiotherapy is of particular benefit to elderly patients as alternative surgery, and it is widely used with curative and palliative intent. Patients aged 75 and older accounted for 5-10% of all cases, and half of them had some complications. Radical radiotherapy was performed in 63-73% of the elderly patients and 88-100% were able to complete the planned course. Several authors reported that the elderly patients adequately staged, can tolerate radical radiotherapy and have survival comparable to that of younger patients. But careful management is needed.

Age Distribution↗

[A trial to reduce cardiac motion artifact on HR-CT images of the lung with the use of subsecond scan and special cine reconstruction algorithm].

We describe our trial to reduce cardiac motion artifacts on HR-CT images caused by cardiac pulsation by combining use of subsecond CT (scan time 0.8 s) and a special cine reconstruction algorithm (cine reconstruction algorithm with 180-degree helical interpolation). Eleven to 51 HR-CT images were reconstructed with the special cine reconstruction algorithm at the pitch of 0.1 (0.08 s) from the data obtained by two to six contagious rotation scans at the same level. Images with the fewest cardiac motion artifacts were selected for evaluation. These images were compared with those reconstructed with a conventional cine reconstruction algorithm and step-by-step scan. In spite of its increased radiation exposure, technical complexity and slight degradation of spatial resolution, our method was useful in reducing cardiac motion artifacts on HR-CT images in regions adjacent to the heart.

Algorithms↗

Evaluation of myocardial perfusion and fatty acid uptake using a single injection of iodine-123-BMIPP in patients with acute coronary syndromes.

UNLABELLED: The purpose of this study was to clarify the possibility of simultaneous evaluation of myocardial perfusion and fatty acid metabolism using a single injection of 123I-beta-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) in patients with acute coronary syndromes. METHODS: Thirty patients with unstable angina pectoris (UAP group) and 15 patients with acute myocardial infarction (MI group) were studied. BMIPP dynamic SPECT was performed 2 min after the injection of BMIPP (185 MBq), and images were obtained every 3 min for 15 min with a three-head gamma camera. Conventional BMIPP SPECT was also performed 30 min after the injection. Serial BMIPP and resting 201TI images were compared. RESULTS: A 201TI-BMIPP mismatch between 30-min BMIPP and resting 201TI images was observed in 27 of 30 patients in the UAP group and 8 of 15 patients in the MI group, respectively. However, a 201TI-BMIPP mismatch between early (2-5-min) BMIPP and resting 201TI images was observed in only 2 of 30 patients in the UAP group and in only 2 of 15 patients in the MI group, respectively. The kappa statistics of tracer uptake between early BMIPP and resting 201TI images showed good concordance in UAP (kappa = 0.823) and MI (kappa = 0.765) groups, respectively. These results indicated that initial distribution of BMIPP reflects myocardial perfusion in patients with acute coronary syndromes. CONCLUSION: Myocardial perfusion and fatty acid metabolism can be evaluated simultaneously using a single injection of BMIPP, when images are taken soon (2-5 min) and long after the injection in patients with acute coronary syndromes.

Angina, Unstable↗