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The efficacy and safety of gatifloxacin (GFLX) was evaluated for elderly patients with respiratory infections. Each patient received one-half (100 mg b.i.d.) or one-quarter (100 mg q.d.) of the conventional dosage of 200 mg b.i.d., after a tentative clinical dosage for GFLX was estimated based on the patient's age and body weight. The subjects were 34 patients aged 65 years or older with mild to moderate acute bronchitis, pneumonia, or chronic respiratory tract infections. The serum concentration of GFLX was measured for each patient, and population and pharmacokinetic (PPK) analysis was performed, using the Bayesian method, to calculate the AUC and maximum drug concentration (Cmax). The overall efficacy rate of GFLX for 33 patients was 87.9% (29/33 patients). GFLX was effective for 75.0% (6/8 patients) in the 100-mg dosage group and 92.0% (23/25 patients) in the 200-mg dosage group. The clinical efficacy was 90.0% (9/10 patients) for acute bronchitis, 86.7% (13/15 patients) for pneumonia, and 87.5% (7/8 patients) for chronic respiratory tract infections. The bacterial eradication rate was 85.7% (12/14 patients). No adverse events or laboratory abnormalities were observed. The AUC values were 11.2-37.5 microg.h/ml and 12.7-111 microg.h/ml for the 100-mg and 200-mg dosage groups, respectively, and the Cmax values were 1.28-3.02 microg/ml and 0.72-6.35 microg/ml, respectively, for the two groups. These results suggest that the dosage of GFLX examined in this study is clinically useful in elderly patients aged 65 or older with acute bronchitis, pneumonia, or chronic respiratory tract infections. The results of PPK analysis with the dosage management also support the efficacy of GFLX.

A 61-year-old man with chronic renal failure caused by polycystic kidney disease requiring hemodialysis three times weekly developed small cell carcinoma of the lung. The patient received combination chemotherapy with nedaplatin (50 mg) and etoposide (50 mg). Blood levels were monitored, showing that nedaplatin was more dialyzable than cisplatin. The patient achieved a complete response. These results suggest that nedaplatin-etoposide combination chemotherapy may be safer than cisplatin-containing regimen for patients with chronic renal failure hemodialysis and that a satisfactory response can be expected.

We evaluated the role of very late antigen-4 (VLA-4) in asthmatic responses. Brown-Norway rats were sensitized with ovalbumin and then challenged with ovalbumin. Respiratory impedance, and the influx of eosinophils and of VLA-4-positive cells were measured. Eosinophils were stained with Giemsa's solution and VLA-4-positive cells were detected by an immunocytochemical method with a monoclonal antibody against rat VLA-4 (MR alpha 4-1). The numbers of eosinophils and of VLA-4-positive cells in sections of lung tissue from the rats were counted. The effect of MR alpha 4-1 and of a new anti-allergic drug, TYB-2285, on late asthmatic responses was also studied. Respiratory impedance had increased in all the rats by 6-7 hours after the challenge, which indicated that these animals had a late asthmatic response. These rats had more eosinophils and more VLA-4-positive cells than did sensitized animals that were not challenged. The rats given MR alpha 4-1 had significantly smaller increases in respiratory impedance and less eosinophil influx than did those given only phosphate-buffered saline. The rats given TYB-2285 had significantly smaller increases in impedance and less influx of eosinophils and of VLA-4-positive cells. These results show that infiltration of eosinophils and of VLA-4-positive cells corresponds closely with the late asthmatic response, and they suggest that the VLA-4/VCAM-1 pathway plays an important role in this response. These data also suggest that the infiltration of VLA-4-positive cells can be used to evaluate the effect of anti-allergic drugs on the late asthmatic response.

To investigate the involvement of oxygen radicals in the development of asthma, we examined the time course of changes in the expression of superoxide dismutases (SODs) both at mRNA and protein levels in the rat model of allergic asthma. We then examined the effects of recombinant-human SOD (r-hSOD) on these expressions and on the late asthmatic response (LAR). 1) In situ hybridization histochemistry and immunocytochemistry revealed that non-sensitized and sensitized rats before challenge had a very low level of manganese SOD (MnDOS) in the bronchial epithelial cells, although they showed a significant level of copper-zinc SOD (CuZnSOD). 2) All of the animals displayed LAR within 7 hours after the challenge, when they showed dramatic induction of MnSOD, but not of CuZnSOD, in the epithelial cells. 3) Treatment with r-hSOD almost completely suppressed LAR, with abolishment of MnSOD induction. This study suggests that the oxygen radical plays an important role in the inflammatory state of bronchial asthma, during which some cytokines induce the expression of MnSOD in the lung.

A 78-year-old man was admitted to hospital because of episodes of high grade fever and multiple nodular shadows on chest roentgenogram. He had a past history of percutaneous drainage and partial resection of the left lobe of the liver for liver abscess of unknown origin in 1987. The high grade fever was secondary to sepsis due to Citrobacter freundii. The sepsis improved with antibiotic therapy, but the abnormal shadows on chest roentgenogram did not improved. Immunoserological tests indicated a probable diagnosis of alveolar hydatid disease of the lung, which is very rare in the Kansai district of Japan. Open lung biopsy was performed and the diagnosis of alveolar hydatid disease of the lung was confirmed.

Taste sensitivity of preweanling mice was studied by examining responses of the chorda tympani (CT) and glossopharyngeal (GL) nerves to various taste stimuli, and was compared to that of adult mice. In mice of 7-10 days of age, comparing to that of the CT nerve, threshold of the GL nerve for monosodium l-glutamate (MSG) was low, but those for sucrose and NaCl were high. Sensitivities to HCl and quinine-HCl were similar between the CT and GL nerves, although that to quinine-HCl was larger in the GL nerve than in the CT nerve in adult mice. Enhancement of MSG responses by addition of GMP was observed in the CT nerve but not in the GL nerve in this age group. In mice of 8-16 weeks of age, threshold of the GL nerve for MSG became higher but that for NaCl became lower. Enhancement of MSG responses by addition of GMP appeared also in the GL nerve. Inhibition of NaCl responses by amiloride was observed in the CT nerve. These results suggest that, in mice, the GL nerve is important taste input for umami substances especially during the preweanling period, whereas the CT nerve is for sweet and salty substances. Properties of umami and salt receptor systems change during the postweanling period.