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Biomedical subjects

K Shimokata

Publications and source records attributed to K Shimokata.

At least 145 records · Page 8Linked to original sources
PubMed1993

Phase II study of carboplatin, cisplatin, and vindesine in advanced non-small-cell lung cancer.

Cisplatin in combination with vindesine has been widely used for the treatment of advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 32%. We conducted a phase II study to examine whether the addition of carboplatin to the combination of cisplatin and vindesine would improve the antitumor activity of the two platinum agents in advanced NSCLC without increasing their toxicity. Carboplatin (240 mg/m2) and vindesine (3 mg/m2) were given intravenously on day 1 and cisplatin (60 mg/m2) and vindesine (3 mg/m2), on day 8. Of the 40 evaluable patients with advanced NSCLC, 12 showed a partial response, for an overall response rate of 30% (95% confidence interval, 17%-47%). The median duration of response was 12 weeks, and the median survival duration for all patients was 38 weeks. The major toxicity was hematologic: leukopenia (WHO grade > or = 3) was observed in 21 patients (53%) and anemia (WHO grade > or = 3), in 13 patients (33%). However, thrombocytopenia was mild and WHO grade 3 toxicity was observed in only 4 patients (10%). Nonhematologic toxicities consisted mainly of WHO grade > or = 2 nausea and vomiting in 16 patients (40%) and WHO grade > or = 2 alopecia in 11 patients (28%). No significant nephrotoxicity or neurotoxicity was seen. Our findings indicate that the addition of carboplatin to the combination of cisplatin and vindesine does not improve antitumor activity in patients with advanced NSCLC.

Adult↗
PubMed1993

Phase II study of a 72-h concurrent continuous infusion of cisplatin and etoposide in advanced non-small-cell lung cancer.

We conducted a phase II study to evaluate the antitumor activity and safety of concurrent continuous infusion of cisplatin and etoposide in advanced non-small-cell lung cancer (NSCLC). Cisplatin (30 mg/m2 daily) and etoposide (80 mg/m2 daily) were given as a 24-h continuous infusion for 72 h to 48 patients with previously untreated advanced NSCLC. Of the 46 evaluable patients, 9 achieved a partial response, for an overall response rate of 20% (95% confidence interval, 9.4%-33.9%). The median duration of response was 23 weeks. The median duration of survival for all patients was 34.4 weeks. The major toxicity was hematologic. Leukopenia (WHO grade > or = 3) was observed in 22 patients (48%) and thrombocytopenia (WHO grade > or = 3), in 13 patients (28%). In all, 20 patients (43%) experienced severe anemia (WHO grade > or = 3). Nonhematologic toxicity mainly consisted of moderate to severe alopecia in 33 patients (72%) and moderate to severe nausea and vomiting in 25 patients (54%). No significant nephrotoxicity was seen. We conclude that a 72-h concurrent continuous infusion of cisplatin and etoposide does not appear to be active against advanced NSCLC.

Adult↗
PubMed1993

Comparative study of a biphasic culture system (Roche MB Check system) with a conventional egg medium for recovery of mycobacteria. Aichi Mycobacteriosis Research Group.

OBJECTIVE: The clinical utility of a new biphasic culture system (Roche MB Check system) for the recovery of mycobacteria was evaluated in comparison with a conventional egg based medium. DESIGN: A total of 905 clinical specimens (mainly sputum samples) were tested in 9 clinical microbiology laboratories in Aichi Prefecture, Japan. The recovery rate and detection time of mycobacteria from the specimens were compared between the biphasic system and the egg medium. RESULTS AND CONCLUSION: Of the 905 samples, 311 were positive in the culture of mycobacteria. The recovery rate of the biphasic system was superior to that of the egg medium (99.0% versus 74.0%, P < 0.0001). In addition, the biphasic system showed a considerable decrease in the number of days required for isolation compared with the egg medium (18.8 days vs. 23.1 days for Mycobacterium tuberculosis, P < 0.0001; 13.4 days vs. 19.8 days for M. avium complex, P = 0.007). The biphasic system is therefore proposed as a feasible and practical method for the recovery of mycobacteria from clinical specimens.

Bacteriological Techniques↗
PubMed1993

Polymerase chain reaction for the differentiation of Mycobacterium intracellulare and Mycobacterium avium.

Polymerase chain reaction (PCR) amplification was performed using DNA purified from 15 mycobacterial type strains and from 21 specimens isolated from patients suspected to have non-tuberculous mycobacterial diseases. Using a primer set of MTB1-MTB2, 11 specimens out of 21 were Mycobacterium avium and 8 were M. intracellulare, which were verified by the Gen Probe Rapid Diagnostic System for the M. avium complex (MAC). One of the remaining 2 specimens which did not hybridize with the probe for the MAC was identified as M. kansasii and the other was not specifically identified by the conventional culture method. PCR amplification, using a primer set of TB1-TB3, was also performed for the specific identification of M. tuberculosis complex.

Base Sequence↗
PubMed1993

Nonspecific crossreacting antigen (NCA) is a major member of the carcinoembryonic antigen (CEA)-related gene family expressed in lung cancer.

Carcinoembryonic antigen (CEA) is one of the most important tumour markers in the management of human carcinoma, including lung cancer. So far, however, because of the nonspecificity of anti-CEA antibodies, it remains unclear whether the experimental measurements of CEA expression really reflect genuine CEA. In normal lung, nonspecific cross reacting antigen (NCA) has been described as a major component of CEA-related antigens. Recently isolated CEA and NCA cDNA clones enabled us to analyse CEA and NCA expression of in vivo tumour specimens and tumour cell lines at mRNA levels. NCA-specific mRNA (but not CEA-specific mRNA) was detected in all normal lung tissues examined. Of 21 lung cancer tissue specimens, nine expressed both NCA and CEA and five expressed only NCA. Of 16 tumour cell lines, two expressed only NCA and one expressed both NCA and CEA, although its level of CEA mRNA was weaker than that of NCA mRNA. Therefore, CEA-related mRNA expression was always accompanied by NCA mRNA expression; there were no cases of CEA mRNA expression alone. These findings suggest that NCA is a major member of the CEA-related gene family expressed in lung cancer.

Animals↗
PubMed1993

Gene transfer of herpes simplex virus type I thymidine kinase gene as a drug sensitivity gene into human lung cancer cell lines using retroviral vectors.

One of the recent strategies for gene therapy as a cancer control is the targeted introduction of a drug-sensitivity gene into tumor cells. We investigated the gene transfer of herpes simplex virus type I thymidine kinase (HSV-TK) gene as a drug-sensitivity gene into human lung cancer cell lines. We used a recombinant retroviral vector derived from Moloney murine leukemia virus (MuLV) as one of potential vectors for gene therapy. The amphotropic retroviral vector consisted of the HSV-TK gene and the neomycin-resistant gene under Rous sarcoma virus (RSV) promoter control. The antiherpes drugs, acyclovir (ACV) and ganciclovir (GCV), were chosen for testing the activity of HSV-TK that was transferred into human lung cancer cell lines. ACV and GCV are nucleoside analogs specifically converted by HSV-TK to a toxic form capable of inhibiting DNA synthesis. The cytotoxicity was determined by using a tetrazolium-based colorimetric assay (MTT assay). The results obtained from our experiments demonstrated that the retroviral vector-mediated HSV-TK gene transfer leads to ACV- and GCV-dependent cytotoxicity in human lung cancer cell lines, which were both small cell carcinoma and non-small cell carcinoma established from human specimens. These findings suggest that the gene transfer of HSV-TK gene into tumor cells would be one of the models for the use of gene therapy to control lung cancer.

Drug Resistance, Microbial↗
PubMed1993

Phase I clinical and pharmacokinetic study of a 14-day infusion of etoposide in patients with lung cancer.

PURPOSE: A phase I study was conducted to determine the maximum-tolerated dose (MTD) of a 14-day continuous infusion of etoposide, and to evaluate the pharmacokinetics in patients with lung cancer. PATIENTS AND METHODS: Etoposide was administered continuously through a central venous catheter using a pump. The starting dose level was 300 mg/m2 over 14 days, with dose escalations of 100 mg/m2 over 14 days until unacceptable toxicities occurred. Pharmacokinetic studies were performed in all patients. RESULTS: Twenty-one patients, 20 with non-small-cell lung cancer and one with refractory small-cell lung cancer, received 37 courses. No World Health Organization (WHO) grade III or greater toxicity occurred at doses up to 400 mg/m2 over 14 days. At 700 mg/m2 over 14 days, all four patients experienced grade III or IV leukocytopenia, and two developed grade III stomatitis. No cumulative toxicity was observed. A steady concentration of etoposide was achieved 24 hours after the start of chemotherapy, and it was significantly correlated with surviving fractions of leukocytes (r = -.64, P = .001) and platelets (r = -.68, P < .001). The leukocyte count at the termination of chemotherapy predicted the nadir count (r = .93, P < .001). CONCLUSION: Steady blood levels of etoposide were maintained for prolonged periods, during 14-day continuous infusions. Leukocytopenia and stomatitis were dose-limiting. Nadir counts and surviving fractions of leukocytes were predicted by the leukocyte count at the end of chemotherapy and the concentration of etoposide, respectively. The recommended dose for phase II trials is 600 mg/m2 over 14 days.

Adult↗
PubMed1993

Postoperative pneumonia in elderly patients: incidence and mortality in comparison with younger patients.

To determine whether elderly patients have an increased incidence of postoperative pneumonia and/or an increased mortality, we conducted a retrospective study of 4,380 patients who underwent thoracic, abdominal or neurosurgery under general anesthesia. Thirty of these patients developed postoperative pneumonia (incidence, 0.68%). The elderly patients aged 65 years or older who underwent thoracic surgery had the highest incidence of pneumonia. Nine of the 30 patients with pneumonia died (mortality, 30%). Elderly patients did not show a higher mortality than the younger patients. The extent of pulmonary infiltrates on chest roentgenogram and the serum bilirubin level, both of which were determined at the onset of pneumonia, independently had a significant association with mortality. Our study suggests that advanced age is a risk factor for postoperative pneumonia in patients who undergo thoracic surgery.

Adult↗
PubMed1993

Cisplatin, etoposide, and vincristine combination chemotherapy in the treatment of non-small cell lung cancer.

Thirty patients with previously untreated, inoperable non-small cell lung cancer (NSCLC) were treated with cisplatin, etoposide and vincristine. Among twenty-nine evaluable patients, eight patients achieved partial response and the overall response rate was 28%. No patient achieved a complete response. The median survival time was 51 weeks. Myelosuppression was the dose-limiting toxicity. Four patients had a leukocyte nadir of less than 1000/mm3, and one died from severe myelosuppression and sepsis. The other toxicities were nausea/vomiting, peripheral neuropathy, and alopecia. We conclude that cisplatin, etoposide, and vincristine combination chemotherapy offers moderate activity for inoperable non-small cell lung cancer.

Adult↗
PubMed1993

[A case of systemic primary amyloidosis with BHL and M-protein in pleural effusion].

A 76-year-old man was admitted to our hospital because of productive cough and dyspnea. Chest X-ray revealed cardiomegaly, bilateral pleural effusion, mediastinal lymphadenopathy, and marked bilateral hilar lymphadenopathy (BHL). His symptoms improved after therapy including diuretic for heart failure, but BHL was unchanged. M-protein in both serum and pleural effusion, and B-J protein in urine were detected. Protein immunoelectrophoresis demonstrated a heterogeneous increase in IgA with lambda light chain predominance. Bronchoscopy disclosed some prominent mucosal lesions of the bilateral bronchi, of which biopsies demonstrated amyloid deposition. Gastric mucosal biopsy also demonstrated amyloid deposition. Therefore this case was diagnosed as systemic primary amyloidosis due to AL-protein. In systemic amyloidosis, there are only a few reports of lymph node enlargement due to amyloid deposition, and it is particularly rare with BHL. From the presence of M-protein in pleural effusion, it is suggested that not only congestive heart failure due to cardiac amyloidosis but also amyloid deposition in the pleura would be related to the fluid production.

Aged↗
PubMed1993

[A clinical study on lomefloxacin to find appropriate dose levels in the treatment of respiratory tract infections].

A comparative clinical study of lomefloxacin hydrochloride (LFLX) was performed to confirm the optimal dose of LFLX for treatment of respiratory tract infections. Daily dosages of LFLX, 400 mg (200 mg b.i.d.) and 600 mg (200 mg t.i.d.) were allocated by the randomization method. Treatment period was 7-14 days. Of a total of 136 cases, 14 cases were excluded from evaluation of clinical efficacy and 4 cases from evaluation of safety. There were no differences in the background factors of the patients between the 2 dosage groups. The clinical efficacy rates, judged by a committee, were 76.4% (42/55) for the 400 mg group and 74.6% (50/67) for the 600 mg group. No significant difference was observed between the 2 groups (P = 1.000). Incidences of adverse effects were 1.6% (1/64) for the 400 mg group and 2.9% (2/68) for the 600 mg group. Incidences of abnormal laboratory test values were 3.4% (2/58) for the 400 mg group and 1.6% (1/63) for the 600 mg group. No significant differences were found between the 2 groups. These adverse effects and abnormal laboratory test values improved with the cessation of the administration of the drug. From these results, a dose of 400 mg (200 mg b.i.d.) LFLX seems to be better than that of 600 mg (200 mg t.i.d.) LFLX in the treatment of respiratory tract infections.

Adolescent↗
PubMed1992

Expression of factor X and its significance for the determination of paramyxovirus tropism in the chick embryo.

Enveloped animal viruses usually possess a surface glycoprotein which mediates fusion between the viral envelope and host cell membrane, hence enabling the initiation of infection, and its biosynthesis often involves post-translational endoproteolytic activation of the inactive precursor by a host cell protease(s). Therefore, the protease distribution in the host must be critical for determining the viral tropism. We previously isolated from chick embryo a cogent candidate endoprotease of this kind for paramyxovirus infection, and demonstrated its identity with factor X (FX), a vitamin K-dependent serine protease in the prothrombin family which, in general, is synthesized in the liver and circulates as one of the plasma proteases essential for blood clotting. Here, we examined FX expression with specific cDNA and antibody probes in a series of embryonic tissues. Many tissues other than the liver expressed the specific mRNA but, in most instances, the translation products remained inactive zymogen forms. The enzymatically active FXa was detectable only in the allantoic fluid and amniotic fluid, and virus spreading was strictly confined to the tissues in direct contact with these FXa-containing fluids. Thus, the ectopically expressed FXa is probably the major host determinant of paramyxovirus tropism in ovo.

Animals↗
PubMed1992

Pathogenesis of cytomegalovirus-associated pneumonitis in ICR mice: possible involvement of superoxide radicals.

We have studied the pathogenesis of murine cytomegalovirus (MCMV) pneumonitis in immunocompetent ICR mice and in mice treated with cyclophosphamide (CP). Intranasal infection of immunocompetent mice with MCMV resulted in transient and self-limited pulmonary lesions. When mice were given 200 mg/kg of CP one day before virus infection, transient splenic atrophy and subsequent splenic hypertrophy were induced, and the lesions in the lung were markedly augmented in their number and size although there was no significant enhancement of the virus growth. The augmentation coincided with the period of splenic hypertrophy. A marked increase in the number of pulmonary lesions was also induced in mice given 100 mg/kg of CP every 4 days following the initial dose of 200 mg/kg. In these mice, however, continuous splenic atrophy and augmented replication of MCMV in the lung were observed. When the activity of xanthine oxidase (XO) in lung tissue homogenates was measured, the activity was found to significantly increase after intranasal infection with MCMV irrespective of CP administration and there was a good correlation between the elevation of XO activity and the degree of pathological changes in the lung. In addition, we found that the administration of allopurinol, a specific inhibitor of XO and superoxide dismutase, a superoxide radical scavenger, reduced the number of the pulmonary lesions. These results suggest that superoxide radicals are involved in the pathogenesis of MCMV-associated pneumonitis in ICR mice.

Allopurinol↗
PubMed1992

On the association of human beta 2 microglobulin with cell culture-grown human cytomegalovirus (HCMV).

We studied the production of human beta 2 microglobulin (beta 2m) in mock-infected or human cytomegalovirus (HCMV) infected human embryonic lung fibroblasts (HEL) and the association of human beta 2m with HCMV virions. Titration of beta 2m by two-step sandwich enzyme immunoassay revealed that HEL released considerable amounts of human beta 2m into the culture medium and that the production of beta 2m was significantly enhanced by HCMV infection. The concentration of human beta 2m in the culture medium of HCMV-infected HEL reached 500 to 600 ng/ml, which corresponded to 7- to 12-fold of levels found in healthy adult urine. Immunoprecipitation assays showed that HEL-grown HCMV bound a significant amount of endogenous beta 2m, but the viruses were efficiently neutralized by either human hyperimmune anti-HCMV globulin or anti-HCMV monoclonal antibody even when treated with a large amount of human beta 2m or with dialysed urine. Thus it seems unlikely that the binding of beta 2m by HCMV is involved in masking the viral antigenic site necessary for neutralization.

Cells, Cultured↗
PubMed1992

Small caliber catheter drainage for spontaneous pneumothorax.

Excellent results have been reported after small caliber catheters were used for iatrogenic pneumothoraces. However, the value of using such catheters for spontaneous pneumothoraces is not clear. The purpose of this study, therefore, is to examine the efficacy of small caliber catheters in managing spontaneous pneumothoraces. Seventy six episodes of spontaneous pneumothorax were treated using a small caliber catheter (No. 5.5 or 7.0 French) connected to a Heimlich valve. All catheters were inserted by physicians. The treatment was considered successful when there was no air leakage and little or no residual pneumothorax. Before the lungs were fully expanded, four patients had died and one had refused to comply with further treatment. The remaining 71 episodes of pneumothoraces were evaluated for efficacy. The treatment was successful in 60 patients (84.5%) and ineffective in the remaining 11. The conventional large caliber tube was inserted in 10 of the 11 failures, but they were successful in only six. No major complications resulting from catheter insertion occurred, and no catheters became occluded. The catheter was easy to insert, and the scar that remained after removal of the catheter was very small. Not only are small caliber catheters effective for managing spontaneous pneumothoraces, they are the initial treatment of choice.

Catheterization↗
PubMed1992

Bacteriostatic and bactericidal activity of antituberculosis drugs against Mycobacterium tuberculosis, Mycobacterium avium-Mycobacterium intracellulare complex and Mycobacterium kansasii in different growth phases.

Bacteriostatic and bactericidal activities of rifampicin, isoniazid, streptomycin, enviomycin and ethambutol against Mycobacterium tuberculosis, Mycobacterium avium--M. intracellulare complex and Mycobacterium kansasii were studied in different growth phases. Bacteriostatic activities of the drugs were similar in different growth phases, except isoniazid. M. tuberculosis was much less susceptible to isoniazid in the lag phase than in the log and the stationary phases. In contrast, bactericidal activity was influenced by the growth phase. M. tuberculosis was killed by isoniazid, streptomycin and rifampicin. The bactericidal activity of isoniazid was strongest. The bactericidal activity of isoniazid and streptomycin was most marked in the log phase. M. avium complex and M. kansasii resisted the bactericidal activity, but some strains of M. avium complex were killed by streptomycin and enviomycin, and the activities of these two drugs were most marked in the lag phase.

Antitubercular Agents↗