Biomedical subjects
Publications and source records attributed to H Kunitoh.
A 19 year old man presented with fever and left pleural effusion. Biopsy of a subcutaneous nodule and bone marrow led to the diagnosis of idiopathic lobular panniculitis (Weber-Christian disease). Thoracoscopically guided biopsy of the visceral pleura also revealed panniculitis change in the pleural adipose tissue.
PURPOSE: The primary objective of this study was to determine the pharmacodynamics of prolonged administration of low-dose etoposide by continuous infusion (CI). We investigated the hypothesis that maintenance of an etoposide concentration of 1 microgram/mL would be cytotoxic in non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Thirty patients with advanced NSCLC without prior chemotherapy or radiotherapy were treated with etoposide at 20, 25, or 30 mg/m2/d infused continuously for 14 days (336 hours), following a 10-mg/m2 bolus. They also received cisplatin 30 mg/m2 on chemotherapy days 1, 2, and 3. Plasma concentrations of etoposide were measured by high-performance liquid chromatography at 0, 2, 4, 24, 48, 120, 336, and 342 hours after initiation of CI etoposide. RESULTS: The maximum-tolerated dose (MTD) of etoposide was 25 mg/m2/d with leukocytopenia as the dose-limiting toxicity. Plasma concentrations of etoposide at steady-state (Css) showed approximately twofold interpatient variability at each dose level, and were greater than 1 microgram/mL in most patients at higher dose levels. The severity of neutropenia was dependent on performance status (PS), age, and the Css of etoposide. The overall response rate for the 29 assessable cases was 28%. Five of 11 patients with a Css greater than 1.2 micrograms/mL responded to the therapy, whereas only one of 10 patients with a Css less than 1 microgram/mL responded. CONCLUSION: With long-term CI of etoposide, a Css greater than 1 or 1.2 micrograms/mL appeared necessary, but not sufficient, to achieve a major response against NSCLC.
Arterial blood gas data were correlated with clinical variables including patients' perception of dyspnea and spirometry in 79 episodes of acute asthma attacks. Among several variables that showed univariate significance with severity, only subjective degree of dyspnea rated on a modified Borg scale (MBS) remained predictive to discriminate the presence or absence of hypoxia/hypercapnia in multivariate analyses. MBS alone could predict the arterial blood gas status with accuracy of approximately 75%. Therefore, patients' sensation of dyspnea seemed to be an important factor in the evaluation of acute asthma in an emergency room.
Many problems remain to the solved in the management of acute bronchial asthma. Acute fatal or near-fatal asthma can occur in apparently low-risk patients. Patients should be educated about the potential risk of the disease. Subjective degree of dyspnea perceived by the patients was useful in judging the severity of the attack and in predicting the outcome, i.e. need for hospitalization after the initial treatment. However, clinical status on arrival at the emergency room did not predict the out-come. In the treatment of acute attacks, the optimal dosage and timing of corticosteroids and the effectiveness of aminophylline remain controversial. Many patients with respiratory failure due to acute severe asthma can be successfully treated without mechanical ventilation. There have been very few clinical studies of acute asthma in Japan. Appropriately planned and performed clinical studies are clearly necessary to solve the problems encountered in the management of acute asthma, and such studies should be done in Japan.
Pulmonary function, arterial blood gases, and pulse rate were prospectively compared with dyspnea perceived by patients before and after emergency room treatment for acute asthma in 83 episodes. Subjective degree of dyspnea was rated on a modified Borg scale. Before treatment, all spirometry (FVC, FEV1, and peak expiratory flow rate) and arterial blood gas (PaO2, PaCO2, and bicarbonate) data as well as pulse rate were significantly correlated with modified Borg scale, but only PaCO2 showed significant correlation (P < .001) in a multivariate analysis. After treatment, only PaO2 was significantly correlated with modified Borg scale (P = .008) in a multivariate analysis, and pulse rate showed correlation of borderline significance (P = .06). In another 37 episodes of relapsed acute asthma, the correlations between laboratory data and modified Borg scale were very weak, especially after treatment. We conclude that dyspnea expressed by asthmatic patients in an emergency room might be reflecting different mechanisms as treatment is performed. Although it should be one useful guide in emergency evaluation, it must be recognized that dyspnea in the same patient could mean different abnormalities.
A case of pulmonary leiomyoma is presented. A 61-year-old asymptomatic woman underwent surgical resection of the lung for definite diagnosis of abnormal shadow on chest X-ray. Her history was hysterectomy and bilateral salpingo-oophorectomy performed 25 years previously because of uterine myoma. Histologic findings of pulmonary lesion was leiomyoma, and nuclear atypia and mitotic figures were not found. Pulmonary smooth muscle neoplasms are exceptionally rare. We review pulmonary leiomyoma reported in the Japanese literature, and also discuss the diagnostic problems in relation to metastasizing leiomyoma of the uterus.
BACKGROUND: The treatment of patients with multiple intrapulmonary lesions remains controversial. METHODS: Fifty-three patients with lung cancer, in whom preoperative evaluation disclosed intrapulmonary nodules distinct from the main tumor, were analyzed retrospectively to establish the optimal treatment in such cases. RESULTS: These sublesions proved to be intrapulmonary metastases (PM) in 16 cases (30%), multiple primary lung cancers in 7 cases (13%), and various nonmalignant lesions in the others. The survival of the 53 patients, and of patients with clinical Stage I/II disease in particular, compared favorably with that of all patients with resected lung cancer. Those with multiple sublesions had a poorer prognosis, irrespective of their nature. Although patients with PM as sublesions often had clinically advanced cancer, metastatic foci, per se, did not influence the survival data as calculated by a multivariate analysis. CONCLUSIONS: The authors conclude that the existence of a solitary intrapulmonary sublesion should not preclude surgical treatment, unless surgery is contraindicated because of other clinical and radiologic findings.
Despite the recent development of apparently effective asthma drugs, the number of deaths from asthma has not declined. The authors tried to establish an optimal strategy for the prevention of acute asthmatic death by analyzing the circumstances of acute fatal or near-fatal asthma. Data were collected from 51 adult patients admitted to Bokutoh Tertiary Emergency Center due to acute asthma between November 1985 and May 1990 and 38 asthmatic patients admitted to Yokohama City Hospital in 1990. Pre-admission data were obtained through interviews with the patients, their families, or doctors who had seen them. A total of 89 patients were classified into three subgroups: group 1 consisted of patients dead-on-arrival (DOA); group 2, non-DOA patients with disturbed consciousness; and group 3, patients with less severe episodes. Little background information was significantly different among groups, but symptomatic episodes in group 1 patients tended to occur more rapidly. The speed of onset of the episodes was also dependent on the asthma control status. Prehospital care of groups 1 and 2 patients was very poor despite severity of the symptoms. All patients in groups 2 and 3 were successfully treated and discharged, but five of the 26 patients in group 2 died during follow-up periods. Prognosis of patients after discharge appeared to be dependent upon asthma control status before the acute episodes. It was concluded that acute fatal or near fatal asthma could occur in apparently low-risk patients as well as high-risk ones. It was also suggested that the optimal strategy for preventing asthma deaths might be variable.
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This trial was initiated to evaluate the toxicity and activity of combination chemotherapy employing cisplatin (CDDP), docetaxel (DCT) and ifosfamide (IFX) in non-small cell lung cancer (NSCLC), and to determine the maximum tolerated dose (MTD) of IFX. Chemotherapy-naive patients with advanced or recurrent NSCLC received 60 mg/m(2) DCT followed after a 3-h interval by 60 mg/m(2) CDDP on chemotherapy day 1, and IFX at an escalating dose with mesna protection on days 2-4. The chemotherapy was repeated every 3 weeks. Granulocyte colony-stimulating factor (GCSF) was administered in the event of grade 3 leukopenia/neutropenia. The patients tolerated the treatment well up to level 4 of IFX dosing 1.5 g/day, but not the IFX dose at level 6 (2.0 g/day). Additional patients were enrolled in level 5 (IFX 1.7 g/day) to evaluate the toxicity of the drugs around the MTD. Level 5 was also judged as having exceeded the MTD, with febrile neutropenia and hepatic toxicity being observed as the dose-limiting toxicities. No toxicity-related deaths occurred. The majority of the chemotherapy courses were supported by GCSF administration. A total of 33 eligible patients were entered into the trial; the overall response rate was 10/33 or 30% among all eligible cases, and the rate for patients treated with the MTD or higher (levels 4-6) was 8/24, or 33% (90% confidence limit: 18-52%). The MTD of IFX was 1.5 g/m(2) administered for 3 days in this triplet combination. The clinical activity does not seem to justify the toxicity profile.
Genetic polymorphisms of UDP-glucuronosyltransferases (UGTs) are involved in individual and ethnic differences in drug metabolism. To reveal co-occurrence of the UGT1A polymorphisms, we first analyzed haplotype structures of the entire UGT1A gene complex using the polymorphisms from 196 Japanese subjects. Based on strong linkage disequilibrium between UGT1A8 and 1A10, among 1A9, 1A7, and 1A6, and between 1A3 and 1A1, the complex was divided into five blocks, Block 8/10, Block 9/6, Block 4, Block 3/1, and Block C, and the haplotypes for each block were subsequently determined/inferred. Second, using pyrosequencing or direct sequencing, additional 105 subjects were genotyped for 41 functionally tagged polymorphisms. The data from 301 subjects confirmed the robustness of block partitioning, but several linkages among the haplotypes with functional changes were found across the blocks. Thus, important haplotypes and their linkages were identified among the UGT1A gene blocks (and segments), which should be considered in pharmacogenetic studies.