Yoshito Nakagawa

Evaluation of the Bactericidal Activity of Povidone-Iodine and Commercially Available Gargle Preparations

Objective: Encouragement of gargling is important for the control of opportunistic and community-acquired infections. In hospitals, a povidone-iodine (PVP-I) gargle is used frequently. However, at pharmacies in the community a variety of gargles containing various ingredients are now available. In view of this, we conducted a study to compare the bactericidal activities of a PVP-I gargle with those of other commercially available gargles. In addition, we asked about the feeling after use by questionnaire. At middle schools in our city, we investigated whether the encouragement to use the PVP-I gargle had an effect on the absence rate from school due to common cold and influenza. Methods: In vitro, using 3 strains of gram-positive and 4 strains of gram-negative bacteria as the test strains, the bactericidal activities of the PVP-I, chlorhexidine gluconate (CHG) and cetylpiridium chloride gargles (CPC) were compared by the contact test method. In vivo, with subjects in groups of 6 each, the reduction rate in the oral bacterial count after gargling as compared to the baseline count before gargling was determined and compared among the 3 gargling agents used. In addition, a questionnaire study was conducted to compare the feeling after use of the 3 gargling agents. Whether the absence rate due to common cold and influenza changed by encouraging the use of the PVP-I gargle was determined by comparing a middle school where the PVP-I gargle was used and other middle schools where it was not. Results: (1) PVP-I killed all the test strains after 30 s of exposure. (2) The mean reduction rate in bacterial count immediately after gargling was 99.4% for PVP-I, 59.7% for CHG and 97.0% for CPC. (3) Findings of the questionnaire study revealed that the PVP-I gargle was evaluated highest in terms of taste, feeling after gargling and odor among all the gargles tested. (4) At the middle school where the use of the PVP-I gargle was encouraged, the absence rate due to common cold and influenza was significantly lower as compared to those at middle schools where another gargle was used. Conclusion: Of the 3 gargles tested, PVP-I showed the highest bactericidal rate and the highest reduction rate in oral bacterial count. Encouragement of the use of the PVP-I gargle contributed to the decrease in absence rates due to common cold and influenza, indicating that encouragement of gargling with PVP-I is useful for the prevention of common cold and influenza.

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.

Pharmaceutical and Bacteriological Study on Povidone-Iodine Sugar Ointment

Povidone-iodine sugar ointment is an excellent preparation for the treatment of decubitus. It has been used as an intrahospital preparation made according to the formula each hospital decided on from experience. Although commercial products have also been developed and used, they are too expensive. The efficacy of a povidone-iodine sugar ointment formulation which can be prepared by a single method and which has the stability and antibacterial activity equal to commercially available products was evaluated. As the test drugs, one commercially available product (UP), and three preparations with different formulas (P-1, P-2 and P-3) were used. All of these test drugs were stored at 20 and 40 degrees C. Specimens were sampled immediately after storage and after 20, 60, 90, 120 and 150 days and examined pharmaceutically (measurement of pH value and determinations of available iodine and sucrose levels). For the determination of bacteriological effects, 5 standard strains of 5 genera and 5 strains of methicillin-resistant Staphylococcus aureus (MRSA) were used and the time required to kill the bacteria was determined. For UP and P-3, no changes were seen pharmaceutically after 150 days of storage at 20 and 40 degrees C. However, MRSA could not be killed within 30 min. P-1 and P-2 showed remarkable changes pharmaceutically after 60 days of storage at 40 degrees C and could not be used any more. It became possible to make a preparation of povidone-iodine sugar ointment which has a stability almost similar to that of UP. Moreover, such a preparation can be made at low cost. However, since the bactericidal activity against MRSA was not higher than those of other drugs, the future task is to improve the bactericidal activity.

Organ distribution of thallium-201 during intravenous adenosine infusion: Comparison with exercise☆

Thallium-201 (Tl-201) distribution during adenosine infusion was assessed quantitatively and compared with that of exercise imaging. Adenosine and exercise Tl-201 single-photon emission computed tomography (SPECT) were performed in 40 patients with suspected coronary artery disease. In the whole-body images (n = 5) and the unprocessed anterior projection images acquired as part of the initial imaging (n = 35), Tl-201 counts in the myocardium were normalized for the injected dose. Total heart counts were higher during adenosine infusion than during exercise (190 +/- 43 counts/MBq vs 145 +/- 31 counts/MBq, p < 0.01). A heart-to-lung count ratio between adenosine infusion and exercise was not different. A heart-to-liver count ratio was lower during adenosine infusion than during exercise (1.3 +/- 0.3 vs 2.3 +/- 0.5, p < 0.01). Regional Tl-201 uptakes at the inferior wall of the left ventricle during adenosine infusion were closely correlated with those uptakes during exercise (r = 0.94, p < 0.01, slope = 0.96). The sensitivity, specificity, and accuracy of adenosine Tl-201 SPECT for the detection of right coronary artery stenosis were comparable with those of exercise imaging. These results indicated that higher Tl-201 uptake in the liver during adenosine than during exercise did not interfere with the interpretation of myocardial images. Tl-201 counts in the myocardium that were larger during adenosine infusion than during exercise reflected a larger increase in coronary blood flow and thus resulted in better image quality.

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.

A survey of the appropriate use of antiseptic agents in the operating room of several key health care facilities. A comparison between surveys in 2000 and 2004.

Since 2000, new hand and environmental hygiene guidelines have been published by the Center for Disease Control and Prevention (CDC) based on scientific evidence. Accordingly, we expected that the use of disinfectants in clinical settings had been changed. To compare the use and amount of disinfectants before and after the publication of these guidelines, we conducted a questionnaire-based survey on the use of antiseptic agents in operating rooms (ORs) in 6 key hospitals over a period of a month in 2000 and 2004. As a result, the amount of disinfectants used in ORs was reduced in all hospitals in 2004. Especially, amphoteric detergents and glutaral products showed significant reductions in the total amount used in the 6 hospitals, by 94.8 and 96.8%, respectively. The use of povidone-iodine (PVP-I) was decreased by 23.4% overall, although it was increased in 3 hospitals by 11.0–58.6%. The number of applications of PVP-I on the surgical site did not change; however, the site was left to dry without wiping after PVP-I application more frequently in 2004 than in 2000. The time for surgical scrubbing was shortened in 2004, but brush scrubbing was still used as often as in 2000. Many of the hospitals used brush scrubbing in conjunction with alcohol-based rubs. These results indicated changes in infection control measures in hospital settings after publication of the new CDC guidelines; environmental disinfection had been limited and excessive use of disinfectants reevaluated.

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.

A Comparison of the Stability and the Antibacterial Activities of Povidone-Iodine Sugar Ointments which were Prepared in Our Hospital and Manufactured in a Company.

This study was designed to estimate the difference in the stability and the antibacterial activity between PVP-ISU and U-pasta®, (UP) of Povidone-iodine sugar ointments which were prepared in our hospital and manufactured in a company. Observed were the changes in these two preparations which were preserved throughout the experimental period of 7, 30 and 60 days and at the temperatures of 20 and 40°C. The stability of each sample was investigated on pH value, available iodine, and sugar quantity. The bacteria tested were six strains of two strains each of MRSA, P. aeruginosa and P. mirabilis isolated from the decubitus of patients.In PVP-ISU maintained for 30 days at 40°C, the findings revealed that pH value dropped from 4.0 to 2.9 and the concentrations of available iodine and sugar decreased to 74.7% and 41.1% respectively. When storing up to 60 days at 40°C, the pH value lowered to 2.7, the dissolution of sugar was remarkably witnessed, and the concentration of available iodine was recognized as being only 11%. However, all of the strains tested were killed within 10 min. On the other hand, in UP sustained for 60 days at 40°C, no remarkable changes were observed except for a slight change in the pH value (4.7→4.0).These results suggest that PVP-ISU, in which the stabilizing agents are not contained, cannot be used for an extended time because it cannot maintain the proper stability of pH, sugar and available iodine at a high temperature (40°C). However, UP may possibly be used safely longer than 60 days even if it were stored at a high temperature (40°C).

Pharmacokinetics of High Dose Methotrexate : 1 : In Acute Renal Failure

Acute renal failure developed in a 5 year-old girl during the fifth course of high dose methotrexate (MTX) treatment for osteosarcoma. She showed oliguria, and the serum MTX concentration, BUN and Scr were 461 μmoles/1, 50 mg/dl and 2.6 mg/dl, respectively, at 27 hr after infusion.Massive leucovorin calcium rescure, direct hemoperfusion, hemodialysis and plasma exchange therapies were successfully treated and she recovered gradually.Neither toxic bone marrow suppression nor side effect of massive leucovorin calcium appeared.The pharmacokinetic analysis of MTX during the renal failure and the dialysis treatment was investigated.