A new disc technique for drug sensitivity test of tubercle bacilli.
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Aminosalicylic Acids↗
Biomedical subjects
S Kudoh
Publications and source records attributed to S Kudoh.
Contribution of nitric oxide synthase to human neutrophil chemiluminescence.
A chemiluminescence (CL) assay has been used to measure the reactive oxygen species (ROS)-generating capacity of phagocytes. Primed neutrophils produce ROS and nitric oxide (NO) upon induction of nitric oxide synthase (NOS) activity. NO and superoxide (O(2)(-)) form peroxynitrite (ONOO(-)), and emit CL. We examined the involvement of NOS in the CL response of neutrophils using a method based on the modulation of enzyme activity of NOS by the substrate L-arginine and an inhibitor; L-NAME. We used lipopolysaccharide (LPS) as the neutrophil-priming agent. Addition of sodium azide (NaN(3)) with horseradish peroxidase (HRP) to luminol-dependent CL, gave a CL response that was significantly enhanced when 10 mmol/L L-arginine was present (p <0.05), suggesting that NOS activity contributed to the CL response of human neutrophils. LPS-primed luminol-dependent CL was significantly inhibited by L-NAME compared with D-NAME. The proportion of the difference between the two inhibitors in luminol-dependent CL was 12.3 +/- 15.0%. Therefore, approximately 12% of the LPS-primed luminol-dependent CL decrease induced by L-NAME indicated the contribution of NOS activity to the CL response.
Enzyme Inhibitors↗
Appearance of drug-resistant tumor cells in a maxillary cancer patient undergoing chemotherapy and chemoradiotherapy.
In this study, we examine drug resistance and sensitivity in tumor cell lines cultured from a patient undergoing prolonged chemotherapy. Four serially established primary tumor cell lines (KKM-A, -B, -C, and -D) were cultured from a case of maxillary sinus carcinoma: KKM-A from the nontreated primary tumor; KKM-B from the residual tumor after chemotherapy with cisplatin (CDDP) and 5-fluorouracil (5-FU); KKM-C from the local tumor that recurred following complete remission with chemoradiotherapy (combination of 5-FU, vitamin A, and radiation); and KKM-D from a metastatic lymph node tumor after further chemotherapy with CDDP and peplomycin. The sensitivity of the four cell lines to CDDP, 5-FU bleomycin (BLM), carboquone (CQ), and colchicine was assessed according to the reduction in colony formation. The KKM-A cell line was very sensitive to CDDP, BLM, CQ, and colchicine, whereas the posttreatment cell lines were resistant to these four drugs. The resistant cell lines were probably selected as a result of chemotherapy and radiotherapy. The nontreated KKM-A cell line was naturally somewhat resistant to 5-FU. The 5-FU-resistance of the KKM-B, -C, and -D cell lines was reduced in that order, corresponding to their relative degree of treatment. The KKM-D cell line from the metastatic lymph node showed a different sensitivity from the KKM-B and -C cell lines from the primary site, suggesting a heterogeneity in drug sensitivity between primary and metastatic tumor cells.
Adult↗
Distribution of antibody titres against phenolic glycolipids from Mycobacterium tuberculosis in the sera from tuberculosis patients and healthy controls.
Sera from tuberculosis (TB) patients and healthy controls were tested by ELISA for their antibody titres against the two major phenolic glycolipids (PGLs) of Mycobacterium tuberculosis, PGL-tbO (a 1:3 mixture of PGL-tb1 and its analogue whose phthiocerol moiety is phenolphthiotriol A) and PGL-tbK. Both PGL-tbs were shown to be specific to M. tuberculosis, and the profiles of serum anti-PGL-tbK titres revealed that PGL-tbK, like PGL-tb1, was fairly widely distributed among strains of M. tuberculosis. Even when these two PGL-tbs were used, however, the rate of ELISA-positives was not very high among TB patients, which is probably explained by the nature of the disease. Moreover, a considerable number of sera from healthy controls, especially from younger age groups, had high anti-PGL-tb titres, which implies that environmental exposure to M. tuberculosis is much higher than has been estimated from the actual TB cases. The ELISA system using these species-specific PGL-tb antigens may be useful for the survey of TB infection, since it gives more direct information on TB infection than the PPD skin test.
Antibodies, Bacterial↗
Phase I and pharmacologic study of oral (E)-2'-deoxy-2'-(fluoromethylene) cytidine: on a daily x 5-day schedule.
(E)-2'-deoxy-2'-(fluoromethylene)cytidine (FMdC), one of the most potent inhibitors of ribonucleoside diphosphate reductase, was selected for clinical development because of its novel mechanisms of action, and strong antitumor activity against experimental tumor models. This study was designed to determine the toxicities, maximum-tolerated dose (MTD), and pharmacokinetic profile of FMdC. FMdC was given orally for 5 consecutive days every 3 or 4 weeks in patients with advanced solid tumors. The starting dose was 8 mg/m2/day. Pharmacokinetic studies were carried out on days 1 through 5 of the first cycle. Ten patients with non-small cell lung cancer received 15 courses of FMdC at doses which were de-escalated from 8 mg/m2/day to 2 mg/m2/day because of unexpected severe toxicities at the starting dose level. Neutropenia was the dose-limiting toxicity. Thrombocytopenia and anemia were mild. Flu-like symptoms and fever were the common non-hematologic toxicities. The MTD was 4 mg/m2/day, since four of six patients developed grade 3-4 neutropenia. At the 4 mg/m2/day dose level, the mean terminal half-life, maximum plasma concentration (Cmax), plasma clearance, and mean residence time on day 1 were 3.20 h, 15.8 ng/ml, 2.91 l/h/kg, and 4.03 h, respectively. The recommended dose for phase II studies with this schedule is also 4 mg/m2/day for 5 days. Further investigations are necessary to establish optimal dosing schedules and routes for the administration of FMdC.
Administration, Oral↗
Pulmonary rehabilitation program survey in North America, Europe, and Tokyo.
PURPOSE: To study a comparison of problems arising in pulmonary rehabilitation programs in North America, Europe, and Tokyo. METHODS: The survey instrument was a 13-item questionnaire sent in December 1994 to institutions in North America (n = 178), Europe (n = 179), and Tokyo (n = 399). RESULTS: Response rates were 51%, 40%, and 51% for North America, Europe, and Tokyo, respectively. Pulmonary rehabilitation programs were available at 56% of hospitals in North America and 74% in Europe, but at only 20% of hospitals in Tokyo. Most PRPs were conducted in an outpatient setting in North American (98%), whereas both outpatient (55%) and inpatient programs (65%) were adopted in Europe. Although the type of lung disease for which patients in both North America and Europe were referred to PRPs was mainly chronic obstructive pulmonary disease, this accounted for only 34% of referrals in Tokyo. However, referrals for primary tuberculosis sequelae (P = 0.028) and bronchiectasis (P = 0.021) were more common in Europe, similar to the situation in Tokyo. The following PRP items were available at significantly higher rates in North America than in Europe, and most were unavailable in Tokyo: family education, psychological support, nutritional instruction, treadmill, bicycle ergometer, walking training, and increasing the activity of daily living. CONCLUSION: Pulmonary rehabilitation programs in North America are more multidimensional. However, target diseases differ among North America, Europe, and Tokyo. Pulmonary rehabilitation programs in Tokyo differed from those in North America and Europe and were poorly programmed. Problems arising in PRPs in the three regions include lack of staff and insufficient reimbursement.
Canada↗
Calcitonin gene-related peptide antagonizes the protective effect of adrenomedullin on histamine-induced bronchoconstriction.
1. In the present study the possible relationship between adrenomedullin (AM) and calcitonin gene-related peptide (CGRP) in the regulation of airway functions in anaesthetized guinea-pigs was examined in vivo. 2. We found that AM significantly inhibited histamine-induced bronchoconstriction in a dose-dependent manner. CGRP or the CGRP receptor antagonist (CGRP [8-37]) alone did not affect pulmonary resistance and pretreatment with CGRP or CGRP [8-37] did not significantly affect histamine-induced bronchoconstriction. However, AM-induced bronchoprotection was significantly inhibited by pretreatment with CGRP or CGRP [8-37] in a dose-dependent manner. 3. It is therefore possible that CGRP may be competitive, at least in part, with binding sites of AM in the guinea-pig airway. Exogenous AM may be useful for the management of bronchial asthma, not only as a potent bronchodilator, but also as a functional antagonist of CGRP.
Adrenomedullin↗
Intrapleural administration of cisplatin and etoposide to treat malignant pleural effusions in patients with non-small cell lung cancer.
BACKGROUND: To determine the efficacy, toxicity and pharmacokinetics of intrapleural cisplatin (CDDP) and etoposide as a treatment for malignant pleural effusions (MPE) in patients with non-small cell lung cancer (NSCLC). METHODS: Seventy patients with MPE associated with NSCLC were enrolled in this study. In 68 patients, a catheter was inserted into the pleural cavity, within 24 h after complete drainage of the pleural effusion, CDDP (80 mg/m2) and etoposide (80 mg/m2) were simultaneously administered successfully via the catheter and the catheter was clamped. Seventy-two hours later, the catheter was unclamped to allow drainage. The catheter was removed when the accumulated intrapleural fluid decreased to 20 ml or less per day. RESULTS: The pharmacokinetic profiles showed high maximum concentrations of CDDP (free form, 88 microg/ml) and etoposide (182. 4 microg/ml) in intrapleural fluids. CDDP did not remain for a long period (free form, beta-phase half-life = 10.51 h) in the fluids, while etoposide persisted for a long period (beta-phase half-life = 62.53 h). The overall response rate was 46.2%, the median survival time 32.3 weeks, the 1-year survival rate 28.7% and the 2-year survival rate 12.8%. The most serious adverse reactions were WHO grade 3 anemia (3 patients), grade 3 nausea and vomiting (17 patients), grade 3 constipation (1 patient), grade 3 pulmonary toxicity (1 patient), grade 4 fever (1 patient), grade 3 infection (1 patient) and grade 3 mental disorder (1 patient). CONCLUSION: Intrapleural administration of CDDP and etoposide was an effective and acceptable regimen for patients with MPE due to NSCLC.
Adenocarcinoma↗
Prognostic factors in elderly patients with unresectable non-small cell lung cancer.
BACKGROUND: The number of elderly patients with lung cancer is rapidly increasing and their management is an important issue. PATIENTS AND METHODS: 109 patients aged over 75 years with unresectable non-small cell lung cancer were assessed to define the prognostic factors. The median age was 80 years in a range of 76 to 95. The overall median survival time was 6.3 months. Fifty-one patients underwent chemotherapy and/or thoracic radiotherapy whilst the others received best supportive care. RESULTS: Multivariate Cox regression model showed performance status (PS) (p = 0.0063) and stage of disease (p = 0.0158) to be independent prognostic factors for survival. In seventy-six patients with a good PS of 0-1, choice of treatment (p = 0.0225) and hyponatremia (p = 0.0302) were the predictors for survival. CONCLUSIONS: PS, treatment and serum sodium level were important factors for survival, and most patients with good PS were able to undergo the treatment and have a good outcome.
Aged↗
Femoral arterial thrombosis in nephrotic syndrome. Steroid and long term heparin therapy.
Thrombosis due to increased coagulability of the blood is a common complication in patients with nephrotic syndrome. Thrombosis has a tendency to recur in these patients. We recommend steroid and long term heparin therapy after thrombectomy for the prevention of the recurrence of thrombosis in nephrotic patients and for the control of nephrotic syndrome. This report deals with two cases of femoral arterial thrombosis complicated by nephrotic syndrome. In one case the result was not satisfactory despite usual postoperative treatment, while the other case was successfully treated by long term heparin infusion in combination with oral administration of steroid.
Adult↗
Pilot trial of a combination comprising of consecutive oral administration of UFT, and two-divided administration of CDDP in non-small cell lung cancer.
A pilot study of a combination therapy comprising of consecutive oral administration of UFT, and two-part divided administration of CDDP was undertaken in patients with inoperative non-small cell lung cancer, based on the synergistic effects of CDDP and 5FU. UFT was administered orally at a dosage of 400 mg/m2 for two consecutive weeks (Day 1-Day 14) and CDDP was administered twice by intravenous infusion, once on Day 4 and again on Day 8. The unit dose of CDDP was increased sequentially, from 40 mg/m2 in step 1, to 50 mg/m2 in step 2, and then to 60 mg/m2 in step 3, with safety being confirmed during the process. The numbers of patients registered for each dose level were 3, 3, and 20, respectively. Evaluation of toxicities could be conducted for all the patients except one. No toxicities of grade 3 or higher were observed in step 1 or 2. There was no problem with continuous administration of UFT. The following toxicities of grade 3 or higher were observed in step 3: leukocytopenia in 2 patients; reduction of the hemoglobin count in 1; decrease in creatinine clearance in 2; anorexia in 3; and nausea and vomiting in 3. Bone marrow suppression was mild and transient. Renal failure and digestive symptoms, which were proved to be transient and treatable by symptomatic treatment, were also observed. The step 3 administration was effective in 8 (47.1%) of the 17 patients with measurable lesions (95% CI: 23-71%). In conclusion, since it was determined that the dose employed in step 3 should be recommended and that it could be expected to exhibit antitumour effects with mild bone-marrow suppression, a large scale phase II study should be conducted in no prior treatment non-small cell lung cancer.
Adenocarcinoma↗
Tumor angiogenesis as a major prognostic factor in stage I lung adenocarcinoma.
UNLABELLED: We investigated the correlation between tumor angiogenesis and prognosis of T1N0M0 lung adenocarcinoma. MATERIALS AND METHODS: Forty two specimens resected from patients with T1NOM0 lung adenocarcinoma were investigated by immunohistochemical staining with a monoclonal antibody to CD31. The relationship between microvessel count, clinicopathologic factors and prognosis was studied. RESULTS: The microvessel count was significantly higher in cases with vessel invasions than in those without. Univariate analysis showed that microvessel count was related to poorer prognosis. In patients with a high microvessel count (> or = 38), prognosis was significantly poorer than in those with a low count (< 38). Multivariate analysis indicated that the microvessel count and mitosis are prognostic factors in patients with lung cancer, and that the microvessel count is a more important factor than mitosis. CONCLUSIONS: Microvessel count may be a major prognostic factor and a useful tool to predict recurrence in patients with T1N0M0 lung adenocarcinoma.
Adenocarcinoma↗