As drug allergies are specific,dose independent,and unpredictable,they are difficult to prevent and manage in the clinical setting.The objectives of this study were to analyze drug allergies and elucidate their pathogenesis from the viewpoints of detection of the causative drug,the allergen (drug),the patient (organism) and the mechanism of manifestation of drug hypersensitivity.As for detection of the causative drug,our findings suggest that the leukocyte migration test (LMT) may be more effective than other tests,i.e.the intradermal test,patch test,sensitized hemagglutination test,enzyme-linked immunosorbent assay and drug-induced lymphocyte stimulation test.In addition,the LMT-chamber method appeared to be more sensitive than the LMT-agarose method
From the allergen viewpoint,our findings suggest that β-lactam antibiotics and X-ray contrast media have very high allergenicity,and macrolide antibiotics have the lowest allergenicity among antibacterial drugs.In addition,cross-allergic reactions arising among β-lactam antibiotics may be induced by drugs having similar structures in terms of parent skeleton and side chain.
From the organism viewpoint,our findings suggest that skin eruption may be the most common drug-induced hypersensitivity symptom,fever alone may be strongly related to allergic reactions,itching may be closely connected with allergic drug eruptions and concomitant symptoms strongly related to drug-induced allergic hepatic injuries.Also,drug-induced blood disorders with short latent periods may be serious and closely related to allergic reactions and patients with previous medical histories of drug allergy may have a very high risk of drug-induced hypersensitivity.Furthermore,drug allergies in elderly persons have a low incidence and a long latent period,and women a high incidence of drug eruption and a low incidence of drug-induced hepatic injury.
As regards the mechanism of manifestation of drug hypersensitivity,our findings suggest that IL-1,IL-2 and TNF-α play a part in drug allergies detected by means of the leukocyte migration activating factor and IL-8 in β-lactam antibioticinduced allergies detected by means of the leukocyte migration inhibitory factor.In addition,Shosaiko-to,a traditional Chinese medicine,may have a phytohemagglutinin-like immunologic activity (pseudoallergic effect).Pseudoallergic effects may also be involved in shock in response to lidocaines,iodinated contrast media and NSAIDs.

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The basic inhalation procedures for the Dry Powder Inhaler (DPI) and the pressurized Metered-dose Inhaler (MDI) in the control of bronchial asthma are very different.Effective methods of instructing patients in the use of the MDI have already been reported and we considered effective ways of instructing patients on inhalation with the DPI since none had really been established,for instance with regard to the basic inhalation procedure and inhalation persistence time.First,we considered it necessary to establish standards for selecting inhalation devices and with this in mind,investigated a relationship between the inspiratory flow rate and device,and applied our findings to the selection of inhalation devices.The inspiratory flow rate was measured using an Incheck instrument and the suitability of devices was examined using an inhalation tester.We also created an inhalation instruction sheet with the aim of standardizing instruction on inhalation.
It was considered that the inhalation persistence time for the DPI should be 1 second or more.Further,in instructing patients on inhalation using it,we found that it was effective to use the instruction sheet,a practice device,and an inhalation circuit tester.We felt that patients should be made aware of the importance of a persistence time of at least 1 second,their attention should be drawn to the inhalation velocity,and any method of instructing them on inhalation procedures should be easy to understand.Also,changing devices based on the results of an examination of their suitability was found to be effective.
In view of the above findings,we felt it necessary to develop a system under which doctors prescribe inhalation devices after pharmacists have evaluated their suitability using the Incheck instrument and an inhalation tester.Further,the introduction of the inhalation instruction sheet we made was successful in standardizing instruction on inhalation.In this paper,we describe the overall system based on our findings that was created in our institution.

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A total of 462 Escherichia coli , and 1,305 Staphylococcus aureus strains were collected in clinical isolates during a 32month period (February 2007 to September 2009) at Kizawa Memorial Hospital. One hundred twenty isolates of E. coli produced extended-spectrum Β-lactamase (ESBL), and 612 isolates of S. aureus were methicillin-resistant, suggesting that antibiotic resistant-bacteria were spreading in our hospital. The investigation we carried out resulted in clarifying the frequencies of occurrence and realities of ESBL-producing E. coli as well as the extent of MRSA, and infection control measures were improved. In addition to providing the opportunity to review the infection control measures in our hospital, it underlined the importance of monitoring antibiotic-resistant bacteria.
The administration of antimicrobial agents to 17,128 patients from January 2007 to June 2009 was analyzed through multivariate analysis using logistic regression. Significant risk factors influencing the occurrence of ESBL-producing E. coli were : age (Odds rate (OR) 1.022, 95% confidence interval (CI) 1.016∼1.028), history of hospital stay (OR 2.742, CI 1.400∼5.373), and number of times antimicrobials used (OR 1.026, CI 1.019∼1.032). Those for MRSA were : male sex (OR 1.279, CI 1.137∼1.438), age (OR 1.021, CI 1.018∼1.024), history of hospital stay (OR 1.698, CI 1.298∼2.221), and antimicrobial usage period (OR 1.056, CI 1.049∼1.063).
In conclusion, antimicrobial use may be creating a favorable environment for colonization by antibiotic-resistant bacteria.

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In order to clarify the status of clinical skills education in the faculties of pharmaceutical sciences at pharmacy schools in Japan,we carried out a questionnaire survey of such faculties at 74 schools in Japan.The results revealed that 67.9% of the pharmacy schools were providing clinical skills education such as that regarding physical assessment and assessment of vital signs.As for the amount of time spent in education on clinical skills,the median lecture time was 225 minutes and the median practical training time was 540 minutes.The ranking of lecture content was :[1]basic knowledge related to vital signs,[2]basic knowledge related to electrocardiography,[3]basic knowledge related to clinical laboratory test results,[4]pathophysiology and symptomatology and[5]Procedures for using assessment equipment,and the ranking of practical training :[1]primary or secondary emergency medical care,[2] assessment of vital signs,[3]electrocardiography measurements and analysis,[4]auscultation,[5]nursing and patient care.The ranking for equipment available at pharmacy schools was :[1]stethoscope (availability rate 50.9%),[2]mercury sphygmomanometer (41.5%),[3]AED trainer (24.5 %),[4]electrocardiograph (22.6%),[5]pulse oxymeter (20.8%).
Based on the results of our survey,it is felt that clinical skills education in pharmaceutical science courses will enhance the professional capabilities of pharmacists,and enable them to make greater contributions in various fields including emergency medical care and home medical care.

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There are currently many on-going discussions on expanding the professional skills of pharmacists and in the future,pharmacists will need to be able to check the condition of patients.In view of this,we conducted a survey of the attitudes of community pharmacists towards further developing their professional skills and sent a questionnaire to 333 randomly selected community pharmacists in Japan.The questionnaire investigated attitudes toward checking vital signs,performing emergency medical procedures and expanding professional skills.
The recovery rate was 26%.Analysis of the responses showed that there was a high level of interest in medical emergency education and expanding professional skills.However,it seemed that community pharmacists were experiencing difficulties in the current conduct of their duties and there was a general feeling that their profession was in a period of transition.There is therefore a need for innovative changes to be made in future pharmaceutical education and pharmacy practice programs and we feel that pharmacy schools need to devote energy to enhancing lifelong education for pharmacists designed to further develop their professional skills.

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In critical care,many different medicines are administered to patients with various types of complicated organ damage and dysfunction.In this regard,pharmacists started working in the ICU/CCU at the Fukuoka Tokushu-kai Medical Center in September,2005.To evaluate the importance of the role played by them in critical care,we carried out a retrospective analysis of the pharmaceutical care they provided in the ICU/CCU from October 2008 to June 2009.
During the 8-month period,there were 137 pharmacist interventions (11 interventions/month),the most common of which were those to prevent the adverse effects of drugs.The major recommendations made by pharmacists were additions to medication (26.3%) and discontinuation of medication (19.0%).The main high risk medicines were those usually given in emergencies,such as antimicrobial agents (17.5%) and medication for electrolytes (12.4%) that need adjustments (dose,administration timing,route etc.) based on a pharmacist’s advice.From our findings,it was clear that pharmacists in the ICU/ CCU had been playing an important role as risk manager and we feel that hospitals should therefore promote the direct involvement of clinical pharmacists in the care of patients in the ICU/CCU.

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In the Radiology Department of Kochi University Hospital,many patients complain of venous pain following treatment with EC (cyclophosphamide+epirubicin hydrochloride).On investigating the incidence of venous pain in 20 breast cancer patients who had received EC treatment,such pain was found to have occurred in 56 of 64 instances (87.5%),and epirubicin hydrochloride was thought to have caused it.As preventive measures,we suggested changing the dissolution liquid from injection water to isotonic sodium chloride solution and shortening the infusion time from 30 minutes to either 5 or 10 minutes.These changes in injection procedure decreased the incidence of the venous pain to 4 of 49 instances (8.2%) in 23 patients.(p<0.01,relative risk : 0.093).
Our suggestions helped greatly in ensuring that there was no decrease in patients’willingness to receive treatment or QOL due to venous pain resulting from anti-cancer drug treatment.

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Starch is often used as a pharmaceutical diluent in dispensing.However,starch is susceptible to large errors in dividing weight because of its low fluidity.In the present study,we prepared granulated starch and a potato starch containing a stearic acid magnesium salt (St-starch) to improve the dispensing of powder medicines with starch diluent.These 2 starch diluents caused no problems in dispensing powder medicines in terms of pharmaceutical characteristics.In a dividing test,the coefficients of variation (C.V.) of the granulated starch and St-starch were much less than for potato starch,and met the dispensing criteria.In addition in the evaluation of ease of handling,St-starch was the best.Furthermore,the time for preparing the St-starch was much shorter (20 minutes for 2 persons) than that for granulated starch (3.5 hours).These results clearly show that St-starch is a useful starch diluent and enhances efficiency in the preparation of powder medicines with starch.

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The purpose of this study was to provide guidance to patients with type 2 diabetes mellitus when their insulin device was changed since insulin therapy may be hampered when a device change is made.Informed consent was obtained from the 18 patients who took part in it.They had been using NovoRapid® 30 Mix FlexPen® (30 MixF).After replacing it with Humalog® Mix 25 MirioPen® (Mix 25 M),we checked usability for the new device.
After replacement,there was no significant change in HbA_1C or quality of life (QOL) and patients expressed their positive feelings regarding the replacement device as follows:“It is easy to hold”,“I only have to press lightly to inject”and“There is no sound when injecting”.Negative impressions were expressed as follows:“I cannot tell when the end of injection is”,“The cap does not open”,and“It is difficult to sterilize”.
In conclusion,we obtained good feedback on how patients felt about changing to the MirioPen® .In the future,we will make efforts to provide proper guidance to patients on the basis of the opinions we obtained from the patients in this study.

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In the clinical setting,the frequency of adverse effects is directly linked to the results of treatment.However,in the case of head and neck radiotherapy for cancer,adverse effects are unavoidable and among them,oral mucositis is considered to be the most significant and debilitating acute complication associated with such radiation therapy.In patients receiving head and neck radiotherapy,the prevalence of mucositis is 85-100% and mucositis-associated pain is the main type of cancer treatment-related pain.
A mouthwash or iceball containing sodium alginate,sodium azulene sulfonate and fibrinolysin deoxyribonuclease is widely used for the prevention and treatment of mucositis.In the USA,many strategies for the prevention of oral mucositis have been evaluated,but conflicting data has made the results inconclusive.Keratinocyte Growth Factor 1 (KGF citation=1)has achieved promising results in therapy and is the only medication currently approved by the FDA,though in Japan,it is not covered by the National Health Insurance scheme.Therefore,we feel it is important to establish useful strategies for the prevention and treatment of radiotherapy-induced mucositis based on significant scientific evidence.
As oxidative stress is associated with radiation-induced mucositis,in this study,we used ⁶⁰Co-γ ray-induced HO-1-N-1 cell injury to studying the characteristics of mucositis in this regard and found that two well-known antioxidants,N-AcetylL-cysteine and catechins,had preventive effects against γray-induced cytotoxicity.N-Acetyl-L-cysteine and catechins would therefore be good materials for the prevention of mucositis in patients undergoing cancer radiotherapy.

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