[Evolution of the concept of sustainable development from "our common future" to "a new WHO"].
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Biomedical subjects
Publications and source records attributed to K Usuda.
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A 47-year-old male, a heavy smoker, was referred to our hospital after Class IV was detected by screening of sputum cytology. His chest X-ray film showed no abnormalities, but bronchoscopy revealed a small nodular lesion at the orifice of right B2. Squamous cell carcinoma was diagnosed by transbronchial biopsy. The clinical stage was I (T1N0M0), and S2 sleeve segmentectomy with lymph node dissection (R 2 b) was performed. The pathological stage was I (T1N0M0), and it was confirmed as early hilar lung cancer. There were no post operative complications and he is well without any evidence of recurrence 5 months after surgery. It may well be considered that this segmental bronchoplastic procedure is useful for cases with early stage squamous cell carcinoma of the segmental bronchus to preserve pulmonary function.
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BACKGROUND: Although a few reports indicated some benefit to survival, the effect of adjuvant therapy for the patients with resected lung cancer was still controversial. The aim of our study was to evaluate survival advantage of CDDP-based adjuvant therapy compared with short-term immunochemotherapy. METHODS EXPERIMENTAL DESIGN: prospective randomized trial. PATIENTS: from 1990 through 1994, 94 patients were registered. Forty-seven patients were randomly assigned to each group, i.e., CDDP-based therapy group (CB Group, CDDP+VDS+tegafur+OK-432 or CDDP+OK-432+mediastinal irradiation) or immunochemotherapy group (IC Group, tegafur+OK-432). PATIENTS in both groups were followed at 4-month intervals with the routine follow-up program of our department. RESULTS: No significant difference was observed between the patients' characteristics of two groups. Compliance of the regimen in each group was 79% in CB Group and 85% in IC Group. No treatment-related death was observed. Five-year survival rates of CB Group and IC Group were 49% and 51%, and 5-year disease-free survival rates were 46% and 44%, respectively. There were no statistical differences between the two groups. Furthermore, no survival differences could be found between CB Group and IC Group in any subgroup of patients. CONCLUSIONS: Both of these regimens were feasible. However, we have not observed any survival benefit in the CB Group in any subgroup, so far. Induction therapy, new chemotherapeutic agents, or anti-angiogenetic a agents may improve the survival of surgically treated lung cancer patients.
BACKGROUND: Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow-up periods. METHODS: Between 1981-1990, 178 patients with pN2 nonsmall cell lung carcinoma underwent complete resection with systemic lymph node dissection. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors were compared. RESULTS: Gender, the side that was operated on, location of the tumor, histologic type, or surgical procedure were not related to the ratio of 5-year survivors. However, T classification, skip metastasis, and the number of levels involved were associated with the ratio significantly. The authors also found that the location of the involved lymph node(s) affected the ratio. CONCLUSIONS: Even in the presence of pN2 disease, lung carcinoma patients with T1 tumors, skip metastasis, or single level mediastinal lymph node involvement, especially Level 4, Level 5, or Level 6 lymph nodes, had a relatively favorable prognosis and may be candidates for primary resection.
Serum KL-6 has been shown to be a useful marker of active interstitial pneumonitis in patients who have not undergone lobectomy. Considering that KL-6 is produced mainly in the distal airway epithelium, the present study was conducted to determine whether resected lung volume influenced the postoperative KL-6 levels, and also to evaluate whether it is a useful parameter in patients who have undergone lobectomy. The serum KL-6 levels decreased by 36% 1 week after lobectomy, but returned to the preoperative levels by 2 months postoperatively. Although the KL-6 levels increased by 100% 3 to 4 months after lobectomy, the levels were significantly lower than those in interstitial pneumonitis (P < 0.05). The decrease in the KL-6 levels correlated with the number of resected lung segments, but not with the changes in white blood cell count, lactate dehydrogenase level, or C-reactive protein level. In comparison with the lobectomy patients, the serum KL-6 levels decreased by half in patients who had undergone partial resection (P < 0.05). The results of this study suggest that the serum KL-6 level may be a useful indicator of interstitial pneumonitis after lobectomy. Serum KL-6 levels are influenced by the volume of the resected lung, and probably also by the upregulation of KL-6 production.
A single oral dose of sodium fluoride (NaF) in aqueous solution was given to male Wistar rats. Twenty-four-hour urine samples were collected and examined to evaluate fluoride-induced acute renal damage. The following parameters were measured in 24-h urine: urine volume and urinary excretion of fluoride, N-acetyl-beta-d-glucosaminidase (NAG), alpha-glutathione-S-transferase (alpha-GST), and creatinine (CR). Fluoride exposure produced specific, dose-dependent changes of these parameters. Significant increases of fluoride and fluoride-induced polyuria were observed. NAG as specific marker of proximal convoluted tubule (PCT) function showed a significant increase when the lowest dose of fluoride was administered. At this minimal dose, alpha-GST, a specific marker for the S3 segment, did not show a significant increase but presented the strongest relationship (r = 0. 83) to fluoride dose. No significant changes were measured for CR excretion, which showed a low correlation coefficient (r = 0.36) to administered fluoride. The specific differences in the increase pattern of these parameters show that the PCT is more susceptible to damage by low-dose fluoride than the S3 segment or the glomerulus. We concluded that both NAG and alpha-GST are useful for the diagnosis of fluoride-induced acute nephrotoxicity. Proper evaluation of these urinary indices may be of help to establish the site and extent of kidney injury in acute fluoride toxicity.
A pinealoma (benign) was found in a 61-week-old male Crj:CD (SD) IGS rat. The neoplasm was located between the cerebral hemispheres and the cerebellum. Histologically, the tumor cells consisted of two cell types: large, pale-staining cells and small dark-staining cells. A fibrovascular stroma divided the tumor cells into incomplete lobules or nest structures. Relatively numerous mitoses were noted in the tumor cells. Ultrastructurally, the tumor cells contained dense-cored vesicles, approximately 120 nm in diameter.
A 65-year-old female was admitted into our department with complaint of bloody sputum. An upper G-I series examinations and thoracic CT demonstrated an esophago-bronchial fistula with diverticulum located between the mid-esophagus and right B6. Following postero-lateral thoracostomy, the fistula was surgically removed and right lower lobectomy was carried out. No inflammatory changes were found in the surrounding tissues of the fistula and the diverticulum. Histological examination revealed that the fistula wall contained squamous epithelium and muscularis mucosa. These results suggested that this case was congenital esophago-bronchial fistula categorized as Braimbridge type I.
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A 66-year-old man admitted to our hospital as a roentgenographically occult lung cancer (ROLC) detected by sputum cytology of class IV. A differential brushing of all branches of the bronchi was performed and squamous cell carcinoma was detected only from the right B8 segmental bronchus. Right lower lobectomy was performed and the microscopic findings of surgical specimen revealed the squamous cell carcinomas were seen at not only B8 bronchus but also B7 bronchus. The frequency of multicentricity of ROLC is reported to be high, and a differential bronchial brushing of all bronchi is a very powerful method to diagnose synchronous multiple lung cancer. However, we failed to detect a cancer lesion of B7 segmental bronchus in this case. Since, the outcomes of surgical treatments for either synchronous or metachronous multiple primary lung cancer are satisfactory, limited surgical treatments might be appropriate as an initial treatment for a ROLC.
To clarify the pathway of the metastases from each pulmonary lobe to mediastinal nodes, we examined the pattern of mediastinal nodal involvement in 462 resected pN2 non-small cell lung cancer. Carcinomas of the right upper lobe frequently involved #3 (78/133) and #4 (70/133) nodes, whereas those of the right middle or lower lobe frequently metastasized to #7 nodes (18/23 and 86/113, respectively). On the other hand, carcinoma of left upper lobe frequently involved #5 nodes (81/118), whereas those of the left lower lobe most frequently metastasized to #7 nodes (50/75). Of 462 pN2 patients, 95 (20.6%) had skip metastases to the mediastinal nodes. Skip metastasis was observed more frequently in carcinomas of right upper and middle lobe. One of the reasons of skip metastasis may be the direct lymph drainage through subpleural space to mediastinum.
A simple and rapid method for the determination of urine boron by inductively-coupled plasma argon emission spectrometry (ICPAES) has been developed to establish boron exposure guidelines. After 11-fold dilution in 18.25 M omega cm ultra-pure water and vigorous shaking, urine may be directly injected into the spectrometer, providing accurate and reproducible results. We report the results obtained with urine samples obtained from a group of male Japanese electronic workers (n = 102) who had not been exposed to boron; boron concentrations were corrected with use of a specific gravity of 1.024 g/ml. The frequency distribution resulted in a log-normal distribution diagram for anatomical spread. The geometric mean values for urine boron in the non-exposed workers was 798.0 micrograms/l, while the confidence interval (C.I.) was between 398.1 and 1599.6 micrograms/l. Taking into consideration the short biological half-life of boron and its major excretion route via urine, urine was considered to be a suitable means for monitoring of exposure to this element. We conclude that the guidelines established by determining boron reference values are useful for the protection of individuals exposed to boron in their working environments.
The imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy and the effects of the neutrophil elastase inhibitors, sodium N-[2-[4-(2,2-Dimethylpropionyloxy)phenyl-sulfonylamino]benzo yl]aminoacetic acid (ONO-5046) and purified alpha1-antitrypsin, on neutrophil elastase activity were determined. The amount of neutrophil elastase complexed to alpha1-antitrypsin, measured by an enzyme-linked immunosorbent assay, was 170 times higher in pleural effusion than in blood 3 h after lobectomy. The alpha1-antitrypsin levels measured by laser nephelometry did not increase in either blood or pleural effusion. Although neutrophil elastase activity, measured by the hydrolysis of succinyl-(Ala)3-p-nitroanilide, was not detected in blood, it was increased in pleural effusion 3 h and 24 h after lobectomy. ONO-5046, but not alpha1-antitrypsin, reduced the neutrophil elastase activity in pleural effusion. There is an imbalance of neutrophil elastase and alpha1-antitrypsin in pleural effusion after lobectomy. ONO-5046 is a potent inhibitor of neutrophil elastase activity in human pleural effusion.
We have devised a new method for right ventricular endomyocardial biopsy, in which the use of a right ventriculography catheter (Nishiya Type) allows us to ensure the introduction of a guiding sheath (Cordis, right-angled long sheath) to the apical portion of the right ventricle by way of the femoral vein. With this method, we have biopsied the endomyocardium in 52 patients during the last 4 years. In each case, it only took us several minutes to complete the biopsy procedure. Neither failed applications nor significant complications were seen. We believe that this technique provides a clinically beneficial means as it enables us to readily and safely achieve right ventricular endomyocardial biopsy.
An excess of sodium fluoride (135 mg F/kg body weight) was given in a single oral dose to male Wistar rats. Effects were investigated of fluoride-induced acute kidney intoxication on the time-dependent variations of urine volume. Also, of urinary fluoride ion (F-), alpha-glutathione-S-transferase (alpha-GST), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine (CR) concentrations. Fluoride administration strongly affects these urinary biochemical indices. Of the several biomarkers studied, alpha-GST is particularly useful as marker of S3 proximal tubule damage. We found that alpha-GST shows the strongest and more durable changes as a result of the large dose of F- given to the experimental animals. Our results suggest that the toxic effect of F- on the kidney may be more pronounced in the proximal tubule than the glomeruli region, and that the disorder of the proximal tubule is more serious in the S3 segment than S1 or S2 segment. Alpha-GST proved to be a useful marker for the early detection and long-term observation of proximal renal tubular injury resulting from F- intoxication. The animal model should help to establish guidelines for the treatment of industrial workers suffering from acute renal failure resulting from accidental exposure to fluoride.
OBJECTIVE: The TNM staging system of lung cancer is widely used as a guide for estimating prognosis and selecting treatment modality. In 1997, the International Union Against Cancer and the American Joint Committee on Cancer have adopted a revised stage grouping for lung cancer. However, the validity of the new stage grouping has not been fully established. We investigated the prognoses of patients who had resection of non-small-cell lung cancer to confirm the validity of the revised classification. METHODS: A total of 1310 patients with non-small-cell lung cancer underwent complete resection and pathologic staging of the disease in our hospitals from 1980 through 1993. A pulmonary resection was performed with a systematic nodal dissection. The survivals were calculated with the Kaplan-Meier method on the basis of overall deaths, and the survival curves were compared by log rank test. RESULTS: There were significant differences in survival between patients with T1 N0 M0 and T2 N0 M0 disease and between those with T1 N1 M0 and T2 N1 M0 disease. However, there was no significant difference between patients with T2 NO M0 disease and those with T1 N1 M0 disease. No significant difference in survival was observed among patients with T2 N1 M0, T3 NO M0, and T3 N1 M0 cancer. Patients with different invaded organs of T3 subdivision (pleura, chest wall, pericardium, or diaphragm) had a different prognosis. There was no significant difference between patients with T3 N2 M0 disease and those with stage IIIB disease. CONCLUSIONS: We supported most of the revision, such as dividing stage I, dividing stage II, and putting T3 N0 M0 to stage IIB. Furthermore, we found some candidates for a subsequent revision, such as putting T3 N1 M0 to stage IIB, putting T2 N0 M0 and T1 N1 M0 together, regarding diaphragm invasion as T4, and putting T3 N2 M0 to stage IIIB.
Sputum cytology is useful for screening and diagnosis of centrally located lung cancer in Japan. On the other hand, cancer beyond the range of bronchoscopic visibility in X-ray negative patients can be detected only with difficulty. Of 265 patients detected by sputum cytology in mass screening, 85 had an abnormal chest roentgenogram and the remaining 180 were roentgenographically occult. A total of 200 roentgenographically occult squamous cell carcinoma lesions were detected in the above 180 patients. A total of 45 of the 200 lesions were bronchoscopically occult. Twenty-two of the above 45 lesions were beyond the range of bronchoscopic visibility with a standard bronchoscope. The data obtained show that a sputum cytology positive, X-ray negative squamous cell carcinoma may lie outside the reach of a flexible bronchoscope. Thus, when it is difficult to localize a cancer, brushing of the peripheral bronchi beyond bronchoscopic visibility and chest computed tomography should be performed.