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Background: The acute antiemetic effect was compared between oral azasetron and intravenous granisetron based on the 5-hydroxytryptamine(3) (5-HT(3)) receptor occupancy theory., Patients and Methods: Receptor occupancy was estimated from reported data on plasma concentrations and affinity constants to 5-HT(3) receptor. A randomized non-inferiority study comparing acute antiemetic effects between oral azasetron and intravenous granisetron was performed in 105 patients receiving the first course of carboplatin-based chemotherapy for lung cancer., Results: Azasetron exhibited the highest 5-HT(3) receptor occupancy among various first-generation 5-HT(3) antagonists. The complete response to oral azasetron was shown to be non-inferior to that of intravenous granisetron, in which the risk difference was 0.0004 (95% confidence interval: -0.0519-0.0527). The lower limit of the confidence intervals did not exceed the negative non-inferiority margin (-0.1). The complete response during the overall period was not different (68% versus 67%)., Conclusion: Oral azasetron was found to be non-inferior to intravenous granisetron in the acute antiemetic effect against moderately emetogenic chemotherapy.

Rationale, Aims and Objectives: Outpatient cancer chemotherapy is increasing with the development of anticancer agents, and roles of medical staff are becoming more and more important in cancer chemotherapy. We showed here roles of pharmacists with experience in oncology and evaluated outcomes of their activities in medical practices in cancer chemotherapy clinic., Methods: Two pharmacists were newly assigned to the outpatient cancer chemotherapy clinic, where they were in charge of verification of prescription orders, mixing of anticancer injections, monitoring adverse drug reactions, implementation of supportive care and provision of information about cancer chemotherapy to medical staff and patients. The number of patients, amounts of mixing of anticancer injections and hospital revenue were compared before and after assignment of pharmacists. Management of chemotherapy-induced nausea and vomiting in breast cancer patients receiving the combination chemotherapy with anthracycline and cyclophosphamide were also compared., Results: Pharmacists spent 75 hours per month in patient education and adverse drug reactions monitoring, which led to the reduction of the workload of physicians. As a consequence, the number of outpatients and the resultant hospital revenue markedly increased. In addition, facilitation of proper use of anti-emetic drugs led to the improved control of chemotherapy-induced nausea with reducing the cost for anti-emesis by 16%., Conclusions: Pharmacists contributed to the improved efficiency of medical practices., (© 2011 Blackwell Publishing Ltd.)

The efficacy and safety of generic and brand name levofolinate injectable drugs were evaluated in 42 chemotherapy-naïve patients with colorectal cancer who received the combination chemotherapy of levofolinate, 5-fluorouracil, and oxaliplatin with or without bevacizumab. The tumor response rate was similar between generic drug group and brand drug group, in which the efficacy rate (complete response plus partial response) was 50% for generic drug group and 42% for brand name drug (odds ratio: 1.400, 95% confidence intervals: 0.409-4.788, P = 0.756). The rates of the decrease in plasma tumor markers such as carcinoembryonic antigen and carbohydrate antigen 19-9 were not different between the two groups. The incidence of adverse drug reactions was not significantly different between the two groups, although the incidence rates of adverse events associated predominantly with 5-fluorouracil such as hand-and-foot syndrome, diarrhea, and oral mucositis were rather higher, though not significantly, in generic drug group than in brand drug group (16 vs. 4% for hand-and-foot syndrome; 33 vs. 25% for diarrhea; 33 vs. 25% for oral mucositis). These findings suggest that both the effectiveness and safety profiles of the generic name levofolinate are comparable to those of the brand name drug, when used in combination with 5-fluorouracil and oxaliplatin in patients with colorectal cancer.

Background: The significance of repeated treatment with the 5-HT(3) receptor antagonist for prophylaxis of chemotherapy-induced emesis remains to be clarified., Patients and Methods: A retrospective analysis was performed to compare the effects of single and repeated treatment with granisetron on anorexia, nausea and vomiting in patients with breast cancer who undertook anthracycline and cyclophosphamide-based cancer chemotherapy., Results: The control of anorexia was significantly better in the single treatment group than in the repeated treatment group (54% versus 73%; odds ratio (OR), 0.433; 95% confidence intervals (CI), 0.226-0.828; p=0.016), although the rate of complete response to any signs of the gastrointestinal side-effects was not different between the two groups (37% versus 39%; OR, 0.911; CI, 0.489-1.700; p=0.874). However, the incidence of constipation was more frequent in the repeated treatment group (60% versus 37%; OR, 2.586; CI, 1.388-4.818; p=0.003)., Conclusion: Repeated treatment with 5-HT(3) receptor antagonist is not likely to be beneficial to breast cancer patients who undertook anthracycline/cyclophosphamide combination chemotherapy.

The major toxicities associated with paclitaxel(PTX)-based chemotherapy are myelosuppression, peripheral neuropathy and myalgia/arthralgia. In the present study, a retrospective study was carried out to compare the incidence of adverse events during PTX-based chemotherapy between 58 cases treated every 3 weeks(tri-weekly regimen)for breast cancer and non-small cell lung cancer and 47 cases with weekly regimen for breast cancer and gastric cancer. Hematological toxicity such as neutropenia and thrombocytopenia, peripheral neuropathy and myalgia/arthralgia occurred more frequently in patients with a tri-weekly regimen than in those with a weekly regimen(grade 3/4 neutropenia: 65.5% versus 12.8%, odds ratio; 12.98, grade 2/3 peripheral neuropathy: 24.1% versus 6.4%, odds ratio; 4.67, and grade 2/3 myalgia/arthralgia: 43.1% versus 4.3%, odds ratio; 17.05). The development of peripheral neuropathy and myalgia/arthralgia was dependent on the dose per injection, but not on the cumulative dose of PTX. The initial onset of peripheral neuropathy and myalgia/arthralgia was observed in more than 80% of patients during the first course of the tri-weekly regimen, while it was seen in any course of the weekly regimen. The incidence of other nonhematological adverse events was not different between the two regimens except for nausea. Our present findings suggest that the peripheral neuropathy and myalgia/arthralgia are highly frequent adverse events that depend on the dose per injection of PTX, in which the incidence was more frequent in the tri-weekly than in the weekly regimen.

We report two cases of suture-related keratitis following penetrating keratoplasty. In both cases, Corynebacterium macginleyi was isolated from corneal specimens. Scanning electron microscopy revealed that corynebacteria could aggregate and form a biofilm. The MICs of sulbenicillin and fluoroquinolones were high for both isolates. Our findings show that C. macginleyi can cause keratitis with biofilm formation.

An indirect immunofluorescent assay to detect antibodies against the lipopolysaccharide (LPS) of Burkholderia pseudomallei and taxonomically closely related species was developed with the Luminex system. LPSs of Pseudomonas aeruginosa, Burkholderia cepacia, Burkholderia thailandensis, Burkholderia vietnamiensis, B. pseudomallei, and Burkholderia mallei were successfully conjugated to Luminex microspheres. Antibodies measured against the LPS of B. pseudomallei-conjugated Luminex beads only cross-reacted with those of two genetically closely related species, B. mallei and B. thailandensis (previously classified as non-pathogenic arabinose-negative B. pseudomallei). However, this system could distinguish other closely related species from B. pseudomallei. This assay is able to detect significantly high levels of anti-LPS antibodies of B. pseudomallei in serum from patients with culture-proven melioidosis.

In this study, we tried to isolate legionellae from nine Legionella DNA-positive soil samples collected from four different sites contaminated with industrial wastes in Japan. Using culture methods with or without Acanthamoeba culbertsoni, a total of 22 isolates of legionellae were obtained from five of the nine samples. Identification of species and/or serogroups (SGs), performed by DNA-DNA hybridization and agglutination tests, revealed that the 22 isolates consisted of ten isolates of Legionella pneumophila including five SGs, five Legionella feeleii, and one each of Legionella dumoffii, Legionella longbeachae, and Legionella jamestownensis. The species of the remaining four isolates (strains OA1-1, -2, -3, and -4) could not be determined, suggesting that these isolates may belong to new species. The 16S rDNA sequences (1476-1488bp) of the isolates had similarities of less than 95.0% compared to other Legionella species. A phylogenetic tree created by analysis of the 16S rRNA (1270bp) genes demonstrated that the isolates formed distinct clusters within the genus Legionella. Quantitative DNA-DNA hybridization tests on the OA1 strains indicated that OA1-1 should be categorized as a new taxon, whereas OA1-2, -3, and -4 were also genetically independent in another taxon. Based on the evaluated phenotypic and phylogenetic characteristics, it is proposed that one of these isolates from the soils, OA1-1, be classified as a novel species, Legionella impletisoli sp. nov.; the type strain is strain OA1-1(T) (=JCM 13919(T)=DSMZ 18493(T)). The remaining three isolates belong to another novel Legionella species, Legionella yabuuchiae sp. nov.; the type strain is strain OA1-2(T) (=JCM 14148(T)=DSMZ 18492(T)). This is the first report on the isolation of legionellae from soils contaminated with industrial wastes.

The utility of the dnaJ gene for identifying Vibrio species was investigated by analyzing dnaJ sequences of 57 type strains and 22 clinical strains and comparing sequence homologies with those of the 16S rDNA gene and other housekeeping genes (recA, rpoA, hsp60). Among the 57 Vibrio species, the mean sequence similarity of the dnaJ gene (77.9%) was significantly less than that of the 16S rDNA gene (97.2%), indicating a high discriminatory power of the dnaJ gene. Most Vibrio species were, therefore, differentiated well by dnaJ sequence analysis. Compared to other housekeeping genes, the dnaJ gene showed better resolution than recA or rpoA for differentiating Vibrio coralliilyticus from Vibrio neptunius and Vibrio harveyi from Vibrio rotiferianus. Among the clinical strains, all 22 human pathogenic strains, including an atypical strain, were correctly identified by the dnaJ sequence. Our findings suggest that analysis of the dnaJ gene sequence can be used as a new tool for the identification of Vibrio species.

In the last few years, many attempts have been made to use conserved gene sequences for identification and for phylogenetic studies of Staphylococcus species. In an effort to identify a more reliable approach, a dnaJ gene sequence-based database was created. In this study, an approximately 883 bp portion of the dnaJ gene sequence from 45 staphylococcal type strains was compared with 16S rRNA and other conserved gene (hsp60, sodA and rpoB) sequences available in public databases. Nucleotide sequence comparisons revealed that the staphylococcal dnaJ gene showed higher discrimination (mean similarity 77.6 %) than the 16S rRNA (mean similarity 97.4 %), rpoB (mean similarity 86 %), hsp60 (mean similarity 82 %) and sodA (mean similarity 81.5 %) genes. Analysis of the dnaJ gene sequence from 20 Staphylococcus isolates representing two clinically important species showed <1 % sequence divergence. Phylogenetic data obtained from the dnaJ gene sequence were in general agreement with those of 16S rRNA gene sequence analysis and DNA-DNA reassociation studies. In conclusion, the dnaJ gene sequence-based assay is an effective alternative to currently used methods, including 16S rRNA gene sequencing, for identification and taxonomical analysis of Staphylococcus species.

We investigated the prevalence of mutations in the gyrA, gyrB, grlA, and grlB genes in 21 clinical isolates of methicillin-resistant Staphylococcus aureus recovered from ocular infections. These isolates were classified into 16 groups on the basis of pulsed-field gel electrophoresis (PFGE) patterns. Among these nonidentical strains, 9 different combinations of mutations were observed. We observed an unusually high frequency of mutations: 10 (62.5%) of the isolates had four or five mutations, 5 (31.3%) of the isolates had double mutations, and 1 isolate had a single mutation. Different mutations were detected in strains of the same PFGE type, and this is consistent with the independent acquisition of mutations. The minimun inhibitory concentrations values ranged from 0.5 to 512 microg/mL for levofloxacin and 0.125 to 128 microg/mL for gatifloxacin. Only 1 isolate was found to be susceptible to both agents. These results suggest that application of high concentration fluoroquinolone ophthalmic solutions selects for isolates presenting such mutations that may result in a high level of resistance to fluoroquinolones.

Three mycobacterium strains isolated from clinical specimens in Japan were provisionally assigned to the genus Mycobacterium based on their phenotypical characteristics. These isolates were further investigated to determine their specific taxonomic statuses. Mycolic acid analysis and 16S rRNA gene, rpoB, and hsp65 sequence data for the isolates showed that they are most similar to M. terrae complex. DNA-DNA hybridization studies indicated that the three strains were of two species and were distinguishable from M. terrae, M. nonchromogenicum, and M. hiberniae. Therefore, these strains represent two novel species within the genus Mycobacterium. However, one potential new species should have been considered as M. arupense with the 16S rRNA gene and hsp65 sequences similarities of 99.8% and 100% respectively; it was isolated from human specimens in the United States and was proposed in June 2006 as a new species. This report describes the first isolation of M. arupense in Japan, suggesting that the organism is clinically relevant. In addition, we propose the novel species designation Mycobacterium kumamotonense sp. nov. The type strain is CST 7247(T) (=GTC 2729(T), =JCM 13453(T), =CCUG 51961(T)).

Five strains of an unknown, multidrug-resistant coryneform, gram-positive rod were isolated from blood, bronchial aspirate, and abscess specimens. Four of the five strains isolated were highly resistant to antimicrobial agents, including beta-lactams, aminoglycosides, macrolides, quinolones, and tetracyclines, except for glycopeptides. In immunocompromised patients, bacteremia associated with this organism was rapidly fatal. This coryneform bacterium was nonmotile, lipophilic, and nonsaccharolytic. Lack of pyrazinamidase activity differentiated this organism from other lipophilic corynebacteria. Chemotaxonomic studies indicated that this multidrug-resistant coryneform bacterium belongs to the genus Corynebacterium. Comparative 16S rRNA gene sequencing and DNA-DNA hybridization analyses revealed that the five isolates were genetically identical and that they represent a new subline within the genus Corynebacterium, for which we propose the designation Corynebacterium resistens sp. nov. The type strain of Corynebacterium resistens is GTC 2026T (SICGH 158T, JCM 12819T, CCUG 50093T).