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Biomedical subjects

K Terakawa

Publications and source records attributed to K Terakawa.

At least 19 recordsLinked to original sources

Dose escalation study of irinotecan combined with carboplatin for advanced non-small-cell lung cancer.

From December 1994 to July 1997, we conducted a dose escalation study of irinotecan combined with carboplatin in 17 patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum tolerated dose and the dose-limiting toxicities. Irinotecan was administered intravenously over 90 min on days 1, 8 and 15, with carboplatin given at an area under the concentration-time curve dose of 5 mg/ml x min (calculated using Calvert's formula) on day 1. The starting dose of irinotecan was 30 mg/m2 and dose escalation was done in 10-mg/m2 increments. Treatment was repeated at 28-day intervals for at least two cycles. The dose-limiting toxicities were neutropenia and thrombocytopenia, since three out of five patients given 60 mg/m2 of irinotecan developed grade 4 neutropenia and thrombocytopenia. The overall response rate was 35.3%. The median survival time and the 1-year survival rate were 10.5 months and 35.3%, respectively. The maximum tolerated dose of irinotecan with this regimen was 60 mg/m2, while 50 mg/m2 can be recommended for future use. Further studies of this combination in advanced NSCLC are warranted.

Adult↗

Japanese experience with second-line chemotherapy with low-dose (60 mg/M2) docetaxel in patients with advanced non-small-cell lung cancer.

PURPOSE: To assess the efficacy and toxicity of relatively low-dose docetaxel (60 mg/m2) for previously treated advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced (clinical stage IIIA-IV) NSCLC who had previously undergone at least one series of chemotherapy were enrolled. Previous paclitaxel use was allowed, but docetaxel was not. Docetaxel was administered at an initial dose of 60 mg/m2 intravenously on day 1 over 90 min every 3 weeks. RESULTS: From June 1997 to November 1999, 22 patients were entered into this study. The total number of cycles delivered to 22 patients was 53, with a median per patient of 2. Four patients achieved a partial response (PR), and the overall response rate was 18.2% (95% confidence interval 5.1-40.3%). The median time to progression was 13.7 weeks. The median survival time was 7.8 months, and the 1-year survival rate was 25%. About 73% of patients experienced grade 3 or 4 neutropenia. Neutropenic fever was observed in four patients (18%). Non-hematologic toxicities were generally mild. No treatment-related deaths occurred. CONCLUSIONS: Although the validity of the results of this study is limited due to the small and monoracial study population examined, low-dose (60 mg/m2) docetaxel for previously treated advanced NSCLC appears to yield antitumor activity and survival benefit comparable to those obtained with the conventional dose (100 mg/m2).

Adult↗

[Thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope].

Thoracoscopy is indicated in patients with undiagnosed effusion after conventional methods. It has been usually performed under general anesthesia or using a thoracoscope with a thoracoscope with a diameter over 5 mm. However, it is an invasive diagnostic technique. We evaluated the feasibility of thoracoscopic pleural biopsy under local anesthesia using a 2 mm laparoscope. Six patients with a pleural effusion of unknown etiology after conventional methods, underwent thoracoscopy under local anesthesia. A 2 mm laparoscope and biopsy forceps (2 mm Minisite, United States Surgical Corp., USA) was used in all patients. Pleural fluid was removed, and the thoracic cavity was inspected. Thoracoscopic intercostal blocks were performed with 1% lidocaine, and then a biopsy was performed. The biopsy specimen was sent for histopathology. Three patients were shown to have carcinomatous pleurisy, two of them with localized lesions less than 10 mm. In the remaining three patients, non-specific diagnoses were made, but long-term follow-up revealed no malignant pleural disease. Although the pictures obtained using a 2 mm laparoscope were inferior in quality, they were adequate for the detection of malignant lesions in the pleural cavity. There were no procedure-related complications. These findings suggest that thoracoscopy using a 2 mm laparoscope is (1) a useful diagnostic tool in cases of pleural malignancy; (2) a minimally invasive method with the advantage of being easily performed under local anesthesia. Thus, thoracoscopic pleural biopsy using a 2 mm laparoscope appears to be useful for undiagnosed pleural effusion.

Anesthesia, Local↗

Nitric oxide metabolite concentrations in maternal plasma decrease during parturition: possible transient down-regulation of nitric oxide synthesis.

To elucidate the possible involvement of nitric oxide (NO) in parturition, we measured the maternal plasma concentrations of the NO metabolites, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and guanosine 3',5'-cyclic phosphate (cGMP) in pregnant women at various gestational ages including those at vaginal and elective Caesarean deliveries. The plasma cGMP and NO metabolite concentrations at vaginal delivery were significantly lower than those of the pregnant women in the third trimester of pregnancy. These concentrations remained low until 4 h after delivery but returned 24 h after delivery to values similar to those of the non-pregnant women. Such suppressions of plasma cGMP and NO metabolite concentrations were not observed in the women who underwent elective Caesarean section before the onset of labour. Moreover, no significant changes were observed in the plasma ANP and BNP concentrations at the time of vaginal and Caesarean deliveries, except that a slight but significant elevation of the plasma ANP concentration was observed 1 h after Caesarean delivery. In conclusion, the plasma concentrations of cGMP and NO metabolites significantly decreased at vaginal delivery but not at Caesarean delivery. These changes were independent of the plasma ANP and BNP concentrations, suggesting the possible down-regulation of maternal NO synthesis during parturition.

Adult↗

Hyporesponsiveness to inhibitory agents of alveolar macrophages and polymorphonuclear leukocytes primed by platelet activating factor.

In this study, it was presented that PAF and LTB4 exert a priming effect on PMNs to promote their superoxide anion production. PMNs preincubated with PAF of normal controls or PMNs from asthmatic patients are activated and their responsiveness to inhibitory stimuli such as antiallergic drugs and corticosteroid are attenuated. In conclusions, inflammatory cells of asthmatics may be activated by various mediators and play an important role in the progress of airway damage.

Adult↗

The effect of thyroid hormone on generation of free radicals by neutrophils and alveolar macrophages.

We have sometimes observed the case of bronchial asthma accompanied by hyperthyroidism. But the pathophysiological mechanisms of both diseases remain obscure. In this study, we have shown that thyroid hormone directly stimulated the generation of superoxide anion by neutrophils and alveolar macrophages. In addition, neutrophils incubated with thyroid hormone became activated and generated greater amount of superoxide anion in response to f-met-leu-phe (fMLP) and phorbol myristate acetate (PMA). Our study suggests, for the first time, that reactive oxygen species may play one of the most important roles in exacerbating asthma in hyperthyroid patients.

Adult↗

Exercise performance and limiting factors in patients with chronic lung diseases.

To demonstrate the clinical usefulness of the treadmill exercise test in patients with chronic lung diseases (CLD), 272 consecutive tests done from Jan. 1986 to Dec. 1988 were analyzed. The subjects mainly consisted of patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). With the present incremental treadmill protocol the maximal stage attained by a patient or distance walked were closely related to the patient's maximal oxygen uptake. Comparing symptoms and cardio-pulmonary response, and exercise performance between patients with COPD and those with ILD, there was an evident difference in the exercise limiting factor (s): in the former ventilatory limitation was the most important whereas in the latter gas exchange and oxygen transport was critical. Assessment of breathlessness during the exercise test using the Borg scale was useful in evaluating various therapeutic modalities such as oxygen supplementation. In conclusion, the exercise performance in patients with CLD was properly assessed with the present treadmill protocol and the information derived thereby was of great clinical significance.

Exercise Test↗

Prediction of PaO2 during treadmill walking in patients with COPD.

We studied the possibility of predicting PaO2 during exercise of a given oxygen uptake (VO2) from resting pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD). The three-minute incremental treadmill exercise was performed with serial measurements of PaO2 via intra-arterial catheter in 46 patients (mean FEV1 = 1.09 +/- 0.49L, mean FEV1/FVC = 44 +/- 15 percent). In most of the patients, the changes of PaO2 were quite linear in relation to the oxygen uptake, so a slope (PaO2/VO2) could be obtained from the regression equation in each patient. The mean value of the slope (SL) was -23.0 +/- 16.6 mm Hg/L VO2/min. Correlation between SL and all parameters of resting PFTs were computed. Because of the high correlation coefficient between SL and %DCO (SL = -59.3 + 0.501 X %DCO, r = 0.851, p less than 0.001), it was possible to predict PaO2 at a given VO2 using the following equation: PaO2 predicted = PaO2 rest + SL X (VO2 -0.25), where SL was derived from measured %DCO and resting VO2 was assumed 0.25 L/min. There was a high correlation between the predicted PaO2 at VO2 of 1.0 L/min and the estimated PaO2 obtained from individual PaO2 regression with an r value = 0.898 and SEE = +/- 5.8 mm Hg. A prospective study in 12 patients with COPD was then carried out. There was a high correlation (r = 0.857) between the predicted PaO2 obtained from the present equation and the estimated PaO2 at VO2 = 1.0 L/min. It was concluded that PaO2 during treadmill walking with a given oxygen uptake is predictable from a resting PaO2 and a diffusing capacity. This predicted value may be useful in the management of patients with COPD.

Aged↗

Propylthiouracil-induced diffuse interstitial pneumonitis.

Cough productive of sputum, exertional dyspnea, and hypoxemia developed in two patients with Graves' disease after six months (patient 1) or three weeks (patient 2) of treatment with propylthiouracil, 300 mg/day. Chest roentgenograms and transbronchial lung biopsy specimens revealed diffuse interstitial pneumonitis. Lymphocyte transformation by phytohemagglutinin was highly stimulated by propylthiouracil. Symptoms and signs improved after cessation of the drug therapy and administration of prednisolone acetate. These cases represent the first report of a complication of diffuse interstitial pneumonitis induced by propylthiouracil.

Aged↗