In vitro activity of pazufloxacin, tosufloxacin and other quinolones against Legionella species

OBJECTIVES: The activities of pazufloxacin and tosufloxacin against Legionella spp. were evaluated in vitro and compared with those of other quinolones, macrolides and azithromycin. METHODS: The conventional MICs were determined by the microbroth dilution method. Intracellular activities of drugs were evaluated by a cfu count. The minimal extracellular concentration inhibiting intracellular growth of bacteria (MIEC) was determined by a colorimetric cytopathic assay. RESULTS: MICs of pazuloxacin and tosufloxacin at which 90% (MIC90) of isolates are inhibited in 76 different Legionella spp. strains (38 ATCC strains and 38 clinical isolates) were 0.032 and 0.016 mg/L, whereas the MIC90s of levofloxacin, ciprofloxacin, garenoxacin, erythromycin, clarithromycin and azithromycin were 0.032, 0.032, 0.032, 2.0, 0.125 and 2.0 mg/L, respectively. Pazufloxacin and tosufloxacin at 4x MIC inhibited intracellular growth of Legionella pneumophila SG1 (80-045 strain), as did other quinolones, clarithromycin and azithromycin, whereas erythromycin at 4x MIC did not. MIECs of pazufloxacin, tosufloxacin, levofloxacin, ciprofloxacin and garenoxacin for the strain were 0.063, 0.004, 0.016, 0.032 and 0.008 mg/L respectively, which were superior to those of macrolides and azithromycin. Pazufloxacin showed potent activity against three additional clinical isolates of L. pneumophila SG1, one clinical isolate each of L. pneumophila SG3 and SG5, as well as Legionella micdadei, Legionella dumoffii and Legionella longbeachae SG1. CONCLUSIONS: Pazufloxacin and tosufloxacin, as well as other quinolones, were more potent than macrolides and an azalide. Present data warrant further study on the efficacy of these drugs in the treatment of Legionella infections.     

Simple self‐reported behavioral or psychological characteristics as risk factors for future type 2 diabetes in Japanese individuals: Toranomon Hospital Health Management Center Study 14

Aims/Introduction

Depression, anger, sleep disorders and cognitive impairment are regarded as presenting a high risk for diabetes. We investigated whether responses to single statements on a self-report questionnaire on the presence of each of these four factors were associated with the development of type 2 diabetes.

Materials and Methods

We investigated 3,211 Japanese individuals without diabetes. Cumulative incidence rate and hazard ratios (HRs) for future type 2 diabetes over 7–13 years were evaluated according to the presence of lack of perseverance, anger, memory loss or sleep disorders.

Results

Results of Cox regression analysis showed that lack of perseverance (age- and sex-adjusted HR 1.41, 95% confidence interval 1.07–1.84), anger, (HR 1.51, 95% confidence interval 1.07–2.12) or memory loss (HR 1.47, 95% confidence interval 1.14–1.90) was predictive of the development of diabetes. Even after adjustment for metabolic factors including glycemic measurements, anger was significantly associated with an increased risk of future diabetes. Individuals with both anger and memory loss had a 1.94-fold (95% confidence interval 1.19–3.15) increased risk of type 2 diabetes than those without those two symptoms.

Conclusions

Responses to a simple self-report questionnaire as to whether individuals were aware of anger or memory loss were associated with the development of type 2 diabetes independent of traditional risk factors for diabetes in this cohort of Japanese individuals.     

FDG PET for grading malignancy in thymic epithelial tumors: Significant differences in FDG uptake and expression of glucose transporter-1 and hexokinase II between low and high-risk tumors: Preliminary study

Purpose

To evaluate ¹⁸F-fluorodeoxyglucose (FDG) uptake to predict the malignant nature and analyze the correlation between FDG uptake and expression of glucose transporter 1 (Glut-1) and hexokinase II (HK-II) in thymic epithelial tumors.

Materials and methods

Eleven patients with a thymic epithelial tumor who underwent FDG PET/CT before therapy were reviewed. The thymic tumors were classified by the WHO histological classification and Masaoka clinical staging. Comparison of maximum standardized uptake value (SUV_max) of the lesion was made between the low-risk (Type A, AB and B1) and high-risk {Type B2, B3 and C (thymic cancer)} groups and among clinical stages. Expression of Glut-1 and HK-II was analyzed immunohistochemically.

Results

All 11 tumors showed FDG uptake visually. SUV_max was significantly higher in the high-risk group (n = 5, 5.24 ± 2.44) than the low-risk group (n = 6, 3.05 ± 0.55) (P = 0.008). Staining scores of both Glut-1 and HK-II were significantly higher in the high-risk group than in the low-risk group (Glut1: P = 0.034 and HK-II: P = 0.036). There were no significant differences in SUV_max (P = 0.11), Glut-1 (P = 0.35) and HK-II scores (P = 0.29) among clinical stages. SUV_max was significantly correlated to each of the staining scores of Glut-1 (ρ = 0.68, P = 0.031) and HK-II (ρ = 0.72, P = 0.024).

Conclusion

These preliminary results support the previously published view that SUV_max may be useful to predict the malignant nature of thymic epitherial tumors and suggest that the degree of FDG uptake in the thymic epitherial tumors is closely related to the amount of Glut-1 and HK-II in the tumor.     

The side‐effects and efficacy of leflunomide in Japanese patients with rheumatoid arthritis

Aims: To investigate the efficacy and safety of leflunomide, including the side‐effects, we assessed 84 rheumatoid arthritis (RA) patients who received leflunomide treatment. Methods: We analyzed the C‐reactive protein (CRP), white blood cell count (WBC), KL‐6, and visual analogue scale (VAS) scores, modified Stanford Health Assessment Questionnaire (MHAQ) score, American Rheumatism Association score (ACR20 and ACR50) within a time course after treatment with leflunomide. We treated 84 RA patients, 12 male and 72 female from 28 to 81‐years‐old, with an average age of 63.5 years. The patients were divided into three groups: a group consisting of 38 patients who received 100 mg/day of leflunomide for 3 days followed by 20 mg/day thereafter; a second group of 11 patients who received a no‐loading dose of 10 mg/day; and a third group of 35 patients who received a no loading dose of 20 mg/day. Results: The 50% decrease of CRP seen in 2 weeks was 52% of the total of 84 patients. The WBC score did not change significantly after the medication was given. The KL‐6 score did not change significantly, either. The VAS pain score improved 4 weeks later, and then further improved 8 weeks later. Therefore, RA patients using leflunomide obtained pain relief 4 weeks after commencing medication. The MHAQ score did not change significantly until 8 weeks after the patients started the medication. ACR20 was 62% and ACR50 was 38% at 8 weeks after treatment. The side‐effects of leflunomide observed in our patients were rash, respiratory infection, diarrhea, nausea, alopecia, muscle pain, headache, dizziness and general fatigue. Twenty‐three out of 84 patients experienced side‐effects (27%), and 48/84 (57%) experienced withdrawal. In our hospital, there were no patients who developed severe interstitial pneumonia (IP) or who died after taking leflunomide; however, the incidence of side‐effects of the 100 mg/day loading dose (42.1%) was 2.5 times higher than in the patients who received 20 mg/day (17.1%) of a no‐loading dose. Conclusion: Because of this, it is possible that a 100 mg/day loading dose is a relatively high risk dose in terms of causing side‐effects, especially for severely ill RA patients with a high CRP level.     

Clinical significance of iodine-123-15-(p-iodophenyl)-3-R, S-methylpentadecanoic acid myocardial scintigraphy in patients with aortic valve disease.

The present study sought to determine whether myocardial fatty acid metabolism as assessed with iodine-123-labeled 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) scintigraphy is impaired in patients with aortic valve disease (AVD) and whether the degree of the metabolic abnormality reflects the severity of AVD. BMIPP scintigraphy was performed in 12 patients with aortic stenosis (AS), 14 patients with aortic regurgitation (AR), and 9 healthy volunteers, and from that the heart-mediastinum uptake ratio (H/M ratio) corrected by the left ventricular (LV) mass (U/Mass ratio) and the myocardial washout rate (WR) were obtained. The H/M ratio tended to be higher in patients than in healthy volunteers (3.3 +/- 0.7 for AS, 3.5 +/- 0.5 for AR, 3.0 +/- 0.3 for healthy volunteers), and the WR was significantly higher in patients than in healthy volunteers (42.8 +/- 9.1% for AS, 35.7 +/- 6.5% for AR, 19.6 +/- 9.1% for healthy volunteers, p<0.01). In the AS patients, the U/Mass ratio showed significant negative correlations (r=-0.79 to -0.90, all p<0.01) and the WR showed significant positive correlations (r=0.61 to 0.82, all p<0.01) with transaortic pressure gradient, LV wall thickness, and LV mass. Similarly, in AR patients these BMIPP parameters showed proportional changes to the LV volumes and LV mass (r=-0.79 to -0.83, all p<0.01 for U/Mass ratio, r=0.55 to 0.70, p<0.05 to <0.01 for WR). In the 9 patients who underwent aortic valve replacement, the BMIPP parameters tended to normalize with increasing U/Mass ratio (0.90 +/- 0.41 x 10(-2)/g to 1.34 +/- 0.59 x 10(-2)/g, p<0.05) and decreasing WR (41.9 +/- 8.8% to 35.4 +/- 9.2%, p<0.01) after surgery. Myocardial fatty acid metabolism as assessed with BMIPP scintigraphy was impaired in patients with aortic valve disease and the U/Mass ratio and WR reflect the severity. These parameters may be useful for the noninvasive assessment of the myocardial metabolic abnormalities caused by hemodynamic overload.     

Decreased serum thyroglobulin levels in the late stage of pregnancy

Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH. Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P less than 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy.