Fractionated administration of carboplatin/paclitaxel reduces neurotoxicity in patients with advanced non-small cell lung cancer.

The combination of carboplatin/paclitaxel is commonly used as chemotherapy for advanced non-small cell lung cancer. However, the relatively high incidence of neurotoxicity remains a problem. This study was undertaken to determine whether the fractionated administration regimen can reduce the neurotoxicity. Patients with stage III or IV non-small cell lung cancer were randomized to the nonfractionated (NF) dose group, which received paclitaxel (200 mg/m(2)) and carboplatin (area under the concentration-time curve=6) on day 1, or the fractionated dose (F) group, which received paclitaxel (100 mg/m(2)) and carboplatin (area under the concentration-time curve=3) on days 1 and 8. The cycle was repeated every 3 weeks. Peripheral neuropathy was objectively evaluated by measuring the current perception threshold (CPT) in the median nerve using a neurometer. Fourteen and 13 patients were assigned to the NF and F groups, respectively. The incidence of subjective numbness was significantly lower in the F group (15.4%) than in the NF group (57.1%). The CPT value determined at 2000 Hz showed significant increases in the NF group compared with the pretreatment baseline, but no significant changes were observed in the F group. The response rate was comparable in both groups. The fractionated administration of carboplatin/paclitaxel combination therapy showed a significant reduction in neurotoxicity. Measurement of CPT by a neurometer is a useful tool to evaluate the neurotoxicity of anticancer drugs objectively.

Patients in whom active tuberculosis was diagnosed after admission to a Japanese university hospital from 2005 through 2007.

To identify problems in early diagnosis of tuberculosis and to design countermeasures against the disease, we examined the status of active tuberculosis among patients admitted to a university hospital that did not have an isolation ward for tuberculosis. Between 2005 and 2007, we analyzed demographic characteristics, disease type, chest radiologic findings, and the process leading to diagnosis. Active tuberculosis was diagnosed after admission in 55 patients (34 males and 21 females): pulmonary tuberculosis, 26; tuberculous pleuritis, 13; tuberculous meningitis, 6; miliary tuberculosis, 4; tuberculous pericarditis, 3; lymph-node tuberculosis, 2; and tracheal and bronchial tuberculosis, 1. Although radiographic examinations provided abundant information, chest radiography showed normal findings in 7 patients (12.7%). Computed tomographic scanning was useful for detailed evaluation of abnormalities. Twenty patients (36.4%) were given diagnoses at departments other than ours (Department of Pulmonary Medicine). Numbers of days between hospital admission and diagnosis of tuberculosis (50th percentile/80th percentile) were 8.0/37.8 for miliary tuberculosis, 8.0/8.0 for tracheal and bronchial tuberculosis, 7.5/17.8 for tuberculous pleuritis, 7.0/8.8 for tuberculous pericarditis, 6.0/15.6 for pulmonary tuberculosis, 3.5/4.4 for lymph-node tuberculosis, and 1/1 for tuberculous meningitis. Early diagnosis of tuberculosis requires adherence to the following precautions. Tuberculosis should be suspected in any patient with respiratory symptoms. Sputum tests for acid-fast bacteria should be performed at least three times initially. If findings on chest X-ray films are equivocal, high-resolution computed tomography should be performed to confirm details of shadows and to detect minimal pulmonary shadows or cavitary lesions. Physicians from all specialties should be repeatedly informed about the risk of tuberculosis and should include tuberculosis in the differential diagnosis in patients suspected to have pulmonary diseases.

Relation between the antimicrobial susceptibility of clinical isolates of Pseudomonas aeruginosa from respiratory specimens and antimicrobial use density (AUD) from 2005 through 2008.

OBJECTIVE: To examine the relation between annual trends in the antimicrobial susceptibility of Pseudomonas aeruginosa and drug usage, we compared annual changes in the susceptibility rates of P. aeruginosa clinical isolates during a 4-year period and annual trends in the overall usage of antimicrobials during the same period. METHODS: We studied annual trends in MIC(90)/MIC(50), antimicrobial use density (AUD), and antimicrobial susceptibility rates based on clinical breakpoints for 150 strains of P. aeruginosa isolated from respiratory specimens at Dokkyo Medical University Hospital from 2005 through 2008. RESULTS: The MIC(90)/MIC(50) of antimicrobials effective against P. aeruginosa in years 2005, 2006, 2007, and 2008 were as follows: imipenem, 32/2, 32/1, 8/2, and 16/1 microg/mL; meropenem, 8/1, 8/1, 4/0.5, and 4/0.5 microg/mL; and biapenem, 16/1, 32/0.5, 4/0.5, and 8/0.5 microg/mL, indicating that susceptibility to carbapenems increased slightly. The MIC(90)/MIC(50) was 4/0.25, 2/0.125, 1/0.125, and 2/0.25 microg/mL for ciprofloxacin, 8/4, 8/4, 4/4, and 8/4 microg/mL for amikacin, 64/16, 64/16, 64/16, and 64/16 microg/mL for sulbactam/cefoperazone, 8/2, 16/2, 32/2, and 8/2 microg/mL for ceftazidime, indicating little change. The AUDs of fourth-generation cephalosporins increased from 2005 to 2008 (16.2, 18.4, 28.0, and 23.0), while the AUDs of carbapenems decreased (25.7, 23.7, 10.9, and 12.5). CONCLUSION: The decrease in the AUDs of carbapenems was associated with increased susceptibility rates of P. aeruginosa to carbapenem derivatives. A continuous understanding of trends in the resistance of P. aeruginosa and various other pathogens is essential for designing countermeasures against nosocomial infections, including the proper and effective use of antimicrobials.

An analysis of characteristics of patients with exacerbation of asthma in a large university hospital in Japan.

BACKGROUND: Considerable progress has been made in the management of asthma with the increasing use of inhaled corticosteroids. However, asthma exacerbation remains a problem. To analyze the characteristics of patients with exacerbation of asthma who visited our hospital in order to better understand the risk factors for fatal asthma. OBJECTIVES: We studied 100 patients who presented at Dokkyo Medical University Hospital (DMUH) with asthma exacerbation. METHODS: Entry sheets were completed by physicians and questionnaires by patients. RESULTS: Before the exacerbation, the severity was assessed as Step 1 in 46% of patients, Step 2 in 15%, Step 3 in 11%, and Step 4 in 18%. With regard to primary care physicians, 45% were treated at DMUH and 36% had no primary care physicians. Among the DMUH group, the largest proportion was aged 60-69 years and was in Step 4 category. According to asthma control test (ACT) scores, disease was poorly controlled in 83%. Patients with no primary care physician were most often aged 20-39 years (p < 0.01), and severity was assessed as Step 1 in 86% (p < 0.01). However, 44% were poorly controlled according to ACT (p < 0.05). CONCLUSION: Patients could be classified into two groups: older patients with severe intractable asthma, treated by a specialist and younger patients considered to have mild asthma, half of whom had poorly controlled asthma and no primary care physician. Systems are needed that allow the emergency physicians to evaluate the need for regular treatment in patients with exacerbation because such patients often visit the hospital at night or on a non-working day.

[A case of group G Streptococcus sepsis, chest wall abscess, and vertebral osteomyelitis mimicking a primary lung cancer with bone metastasis].

A 73-year-old woman who had been followed in our department of gynecology because of ovarian cancer since 2002, was admitted with liver dysfunction and complaining of back pain and light precordial chest pain. The chest radiograph on admission revealed a tumor in her left upper lung field, and chest CT revealed a tumor adjacent to the chest wall and mediastinum. FDG-positron emission tomography (PET) showed abnormal uptake in the tumor and Th6/7, and the subaortic lymph nodes. On the basis of these findings, primary lung cancer with bone metastasis was suspected. She had a high grade fever on admission, and blood cultures were positive for group G streptococcus. The treatment with intravenous penicillin was started. Percutaneous biopsy of the tumor in her left chest showed an abscess wall in the chest wall, but no evidence of malignancy. Transbronchial lung biopsy and CT-guided biopsy also showed no malignant cells. Since the tumor decreased in size and back pain improved gradually by only antibiotic treatment, a diagnosis of sepsis of group G streptococcus, chest wall abscess, and vertebral osteomyelitis was made. She was treated with intravenous penicillin for 4 weeks and oral amoxicillin for another 4 weeks. After 60 days of antibiotic treatment, the tumor vanished.

[Legionnaires' disease with acute renal failure caused by Legionella pneumophilla serogroup 4].

A 77-year-old man who had fever and chest pain was admitted to a neighboring hospital on a diagnosis of pneumonia. Chest X-ray film finding deteriorated despite treatment with 2 g cefotaxime per day. Because of accompanying acute renal failure, he was transferred to our hospital. Hemodialysis with intravenous administration of erythromycin and meropenem resulted in recovery from acute renal failure, and his general condition improved. Because of liver dysfunction, erythromycin was changed to pazufloxacin. Although he was negative for Legionella urinary antigen determined with a rapid assay kit, Binax NOW, his serum titer for Legionella pneumophila serogroup 4 was elevated. Finally, a diagnosis of Legionnaires' disease caused by Legionella pneumophila serogroup 4 was established.