Fumiyoshi Ojima

Histamine Release Induced by Antimicrobial Agents and Effects of Antimicrobial Agents on Vancomycin‐induced Histamine Release from Rat Peritoneal Mast Cells

Vancomycin and certain fungicides may cause anaphylactoid reactions. We investigated the effects of vancomycin, miconazole and fluconazole on histamine release in rat peritoneal mast cells. Vancomycin and miconazole provoked histamine release in a dose‐dependent manner. In contrast, fluconazole did not provoke histamine release at concentrations of 3 times 10−6 ‐ 3 times 10 −3 m.

Development of a new method for simultaneously evaluating mucociliary clearance and pulmonary epithelial permeability in rabbit experiments by means of18FDG, three-dimensional positron emission tomography and rectilinear scan

We tried to simultaneously obtain the elimination constant of mucociliary clearance and the pulmonary epithelial permeability constant after inhalation of 2-[18F]fiuoro-2-deoxy-d-glucose (18FDG) solution by carrying out whole lung positron emission tomography and a rectilinear scan in rabbit experiments. The elimination constant of pulmonary epithelial permeability was obtained from the decrease in the amount of the radioactivity with time in the region of interest (ROI) confined to the lungs, trachea and tracheal cannula in the rectilinear scan. The total elimination constant of the radioactivity in the lungs was obtained from the ROI confined to the lungs in the tomography. The mucociliary clearance rate constant in the lungs was then obtained after subtracting the elimination constant of the pulmonary epithelial permeability from the total elimination constant of the18FDG in the lungs. The mucociliary clearance constant in the trachea was calculated from the residual radioactivity in the trachea and the mucociliary clearance constant in the lungs. The mean pulmonary epithelial permeability constant was 0.0020% min−1 obtained from the rectilinear scan. The mean mucociliary clearance constants of the lungs and the trachea were 0.0006 and 0.025% min−1, respectively. These results indicated that the pulmonary epithelial permeability and mucociliary clearance could be evaluated simultaneously with18FDG by using three-dimensional positron emission tomography and a rectilinear scan.

Study of Child-resistant Packaging Technologies to Prevent Children from Accidental Ingestion of Drugs in Japan

 When handling high risk medications, such as anticancer agents, at home, it is necessary to take measures to prevent children from accidentally ingesting these drugs. In this study, we investigated pediatric characteristics such as literacy ability and finger function in Japanese subjects and examined the usefulness of child-resistant (CR) packaging technologies used in the U.S. when given to children in Japan. The survey covered 104 Japanese children aged 37-84 months. The results of the survey revealed that of the five types of CR packaging technologies, that which leveraged the differences in hand size and muscle mass between children and adults was effective against children aged 3-6 years. However, the CR packaging styles that rely on literacy, the ability to use tools, and the ability to perform complex operations are only applicable to children of a certain age. This suggests that the differences in the language, culture, and preschool education between Japan and the U.S. have a significant influence on pediatric characteristics. Based on the results of this study, it is possible to adopt CR packaging for Japanese children, which is expected to decrease the number of cases of accidental drug ingestion by children in Japan.

Occurrence Rates of Gram-negative Bacteria after Treatment with Anti Methicillin-resistant Staphylococcm Aureus Agents

Methicillin-resistant Staphylococcus aureus (MRSA) is a gram-positive bacterium, and the treatment of patients with MRSA has induced microbial substitution. Regarding antibiotics used for treatment, vancomycin (VCM) has an antibacterial action only against gram-positive bacteria, while arbekacin (ABK) has an antibacterial action against both gram-positive and gram-negative bacteria. In view of this, we supposed that there would be a difference in gram-negative bacteria occurrence rates between patients administered VCM and those administered ABK and tested this supposition by comparing the appearance of gram-negative bacteria in these two patient groups. While gram-negative bacteria were newly detected in 45% of patients after receiving VCM, no patients receiving ABK showed any new gram-negative bacteria. On the other hand, gram-negative bacteria were still detected after administering ABK in patients who had gram-negative bacteria beforehand. This finding suggests that ABK may not be a superior agent when gram-negative bacteria are already present.

Retrospective Investigation of the Drug Interaction between Warfarin Potassium and Bucolome, and Pharmaceutical Advisory

Because of its drug interaction with warfarin K, bucolome is used to reduce the dose of warfarin K. We retrospectively investigated the prescription of warfarin K and bucolome in our hospital from January 2000 to June 2002, based on data from the thrombo test as an indicator of the effects. The total number of patients who were prescribed warfarin K was 654 (mean age, 62.7), and 55 (mean age, 62.8) of those were prescribed both warfarin K and bucolome during the period under investigation. All patients given bucolome were administered warfarin K. Bucolome was discontinued in nine patients, while it was added in five patients. The dose of warfarin K was changed when the bucolome therapy started or stopped in 11 patients, and the same dose of warfarin K was prescribed in three patients upon the discontinuation of bucolome. The doses of warfarin K in the 11 patients who started or stopped bucolome were reduced by more than 50% without any significant change in the thrombo test findings. However, the thrombo level increased in the other three patients and several thrombo tests were subsequently necessary to determine the proper dosage of warfarin K. Pharmacists must therefore monitor not only the dose of warfarin K but also that of any concurrently administered drugs interacting with warfarin K, as well as any previously prescribed medications. Pharmaceutical instruction to the patients, especially in clinical departments unfamiliar with warfarin use, is also essential.