OBJECTIVE:To examine whether the challenges of a cross-national adaptation of an American, evidence-based, illness self-management module for people with serious mental illnesses could be met. The UCLA Medication Management Module was adapted for use in Japan with individuals experiencing short-stay, acute care in an inpatient setting.METHOD:Two evaluations were conducted with 37 and 63 persons diagnosed as having schizophrenia and bipolar disorder, respectively, to test the feasibility and impact of the module as an intervention for illness self- management in an academic, Japanese psychiatric unit.RESULTS:The short-term feasibility was demonstrated by consumers' enhanced comprehension of the value and benefits of antipsychotic medication as well as their gaining positive, therapeutic attitudes toward use of medication. A second evaluation of the module revealed that consumers who participated in the skills training developed better understanding of the purposes of medication, more positive attitudes toward medication, and superior coping skills in dealing with medication side effects than their counterparts who received standard treatment. The greater benefits achieved from participating in the module persisted for 7 months postdischarge.CONCLUSIONS AND IMPLICATIONS FOR PRACTICE:While preliminary, these studies suggest the applicability of the Medication Management Module for illness management for Japanese hospital practice.

We tried L-arginine for the treatment of pulmonary hypertension secondary to pulmonary embolism. The plasma brain natriuretic peptide (BNP) level inversely correlated with the plasma concentration of L-arginine. After oral supplementation of L-arginine, patient's symptoms (shortness of breath and general malaise), state of congestive heart failure, and exercise capacity all improved. L-arginine may be effective in the treatment of pulmonary hypertension secondary to pulmonary embolism.

To evaluate the quality and stability of limaprost-alfadex generics,we carried out a comparative study on 5 generics and 2 branded products.The limaprost contents were higher in 2 of the generics than in the 2 branded products,and 1 generic had a higher level of 17S,10-dimethyl-trans -δ2-PGA1(11-deoxy congener),the major degradation product of limaprost,than the specification for the branded products (=5.0%).To compare the stability of the tablets in the PTPs,they were removed from the aluminum pillow and stored under the conditions of 25°C and 57.5% relative humidity (RH),25°C and 75.0% RH and 40 °C and 75.0% RH.At 25°C and 57.5% RH,though the limaprost contents of the generics were similar to those of the branded products after 3 months,the 11-deoxy congener levels in 2 of the generics had increased to over 5.0%.Moreover,the percentage degradation of limaprost and 11-deoxy congener levels were particularly marked in some of the generics under the more humid conditions of 25°C and 75.0% RH and 40°C and 75.0% RH.On comparing the stability in cellophane paper at 25°C and 57.5% RH for 3 months,the limaprost content only remained above 90% in the branded products.These results indicate that the limaprost-alfadex generics could be less stable than the branded products in a PTP and one-dose package made of cellophane paper.Therefore,when deciding to use generics or not,it is necessary to evaluate them on the results of stability tests as well as those of bioequivalence and dissolution tests.

In the present study, we examined the clinical significance and utility of measuring salivary valproic acid (VPA) levels in saliva samples taken at patients' homes for therapeutic drug monitoring (TDM). The subjects were 74 patients (33 males and 41 females ; mean age 30.8 ± 1.9 years) under treatment at Outpatient Clinic, Department of Neuropsychiatry, Fukushima Medical University Hospital. For the VPA measurements, saliva samples and blood samples were taken at the Outpatient clinic simultaneously. Salivary VPA levels showed significant correlations with total and free VPA serum concentrations (r=0.71 and r=0.77, respectively) but were not significantly correlated with serum albumin concentration or salivary pH.From a preliminary experiment that we conducted, salivary VPA levels were found to remain stable when saliva samples were kept in home freezers at 4 and -20°C.Based upon the above results, we concluded that TDM based on measurements on saliva samples taken by patients receiving VPA has significant clinical utility because 1) saliva sampling is less invasive than blood sampling and easy to carry out for patients who do not wish their blood to be taken, 2) saliva sampling at home is convenient because either patients or their family members can take the samples and 3) samples taken at home can accurately show VPA levels as they are in everyday life.

We introduced a medication management module (MMM) for the education of psychiatric inpatients that uses a video (FMV) produced by Fukushima Medical University. We then asked 32 staff members to evaluate the usefulness of FMV by filling out a questionnaire. Nine of the staff (28 %) responded that it greatly improved the patients' comprehension level, 19 (59 %) felt that it had improved, and 4 (13 %) thought that there had been no change. We estimated that the workload of staff had decreased from 10 to 3.7 points. Further, by testing the 37 participants in MMM on their comprehension level before and after it with the same questions, the mean score was significantly higher after MMM (21.4 ± 0.9 points) than before (18.3 ± 3.5 points) (p< 0.001).To assess the effect of MMM on post-hospital self-medication behavior, we mailed another questionnaire to patients who had participated in MMM and those who had not. The sixty-three respondents (34 men and 29 women, aged from 15 to 78 years) consisted of 43 schizophrenia patients and 20 manic-depressive psychosis patients, of whom 33 had participated in MMM and 30 had not. The percentage of MMM-participants who were taking medication regularly was not significantly different from that of non-participants. However, the percentages of MMM participants who understood the necessity of medication and knew how to cope with side effects were significantly higher (p< 0.05 and p< 0.001, respectively).These results indicate that MMM is useful in raising patients' level of comprehension of medication and helping them acquire the proper post-hospital self- medication behavior.

One percentage Methylene Blue (MB) injection prepared in our hospital pharmacy has been used at concentrations of 0.05% and 0.25% for the treatment for methemoglobinemia and septic shock. In order to provide more information on “the package insert” which we have been making since 1996, we performed a pH variation test using a 1% MB injection and a stability test for 0.05% and 0.25% MB injections.The changes in MB absorbance were monitored by the UV spectrometry method. No significant changes in MB absorbance were observed either at room temperature and 40°C at 1000 Lux fluorescent light or in darkness for 48 hours, under 0.05% or 0.25% MB injection conditions. Based on these results, we were able to increase the amount of information regarding the pH variation tests and stability tests on our package insert.

Serotonin creatinine sulfate (5-HTCS) injection, one of our hospital pharmaceutical manufactured products, is used as a diagnostic reagent for small coronary resistance vessels. 5-HTCS injection was prepared in a clean room under sterile conditions. All lots of the 5-HTCS injections were checked for any foreign matter and particles, sterility, the presence of pyrogens and the content of 5-HTCS. The stability of 5-HTCS injections was investigated under various storage conditions. The remaining amount of 5-HTCS in the infusion solution was determined by spectrophotometry. The contents of 5-HTCS were unchanged for 6 months at -20°Cwhile kept in darkness and wrapped in foil. Under other storage conditions, at 5°C in darkness, at room temperature (25±0.5°C) in darkness wrapped in foil, at room temperature (25±0.5°C) under intense light (1000 Lux fluorescent light) and at 40°C in darkness wrapped in foil, a considerable rise of the peak at 275 nm was observed. These results shows that the degradation of 5-HTCS in infusion solutions is temperature dependent and 5-HTCS injections should thus be stored frozen and foil wrapped at -20°C until the day of the use. Furthermore, the effect of 5-HTCS on small coronary resistance vessels differed from acetylcholine which had been already been used as a daily diagnostic tool. This suggests that a 5-HTCS injection may be an effective diagnostic tool for evaluating the small coronary resistance vessels' functional level that can not be evaluated by coronary angiography.

For the purpose of determining the shelf life of 1% Methylene Blue (MB) injection, its stability was investigated under 4 storage conditions for 30 weeks. The content of MB in 1% MB injection started to decrease at 5°C in the dark 4 weeks after preparation, but no significant differences were observed under three other storage conditions (at room temperature (22.0±0.5°C) and at 40°C in the dark and at room temperature (22.0±0.5°C) in 1000 Lux fluorescent light) for 30 weeks. According to these results, we changed the shelf life of 1% MB injection from 2 to 6 months and the frequency of preparation from six times to twice/year. The unit cost before and after the change of shelf life was compared. One unit cost calculated according to materials costs and labor costs was ¥2, 738.6 during the 1993-1995 period (six times preparations/year), while it was ¥1, 545.9 during the 1996-1998 period (twice preparations/year). A cost savings of ¥1, 192.7/ampule (43.6%) was produced by changing the frequency of preparation from six times to twice/year. In addition, the discard cost for 1% MB injection past its shelf life was estimated. A discard cost saving of ¥85, 766.8/year (75.2%) was achieved by changing the frequency of preparation from six times to twice/year. Furthermore, the working hours were reduced by 9.58 hours/man/year and it allowed pharmacists to utilize the extra time gained by changing the frequency to other work.

The masking effects of BMI-40 on six kinds of bitter tasting medicines were investigated. As a result, BMI-40 alone significantly masked the bitterness of the ground Polymyxin B sulfate tablet (gPL-B). Thereafter, the masking effects of BMI-40 and flavored BMI-40 (with 10% milk cocoa+ 10% sugar) on gPL-B (a hundred thousand U/mL) were compared with those of BMI-60 and flavored BMI-60. After increasing the concentration of BMI-40 by 4%, the masking effects of BMI-40 were same as those of BMI-60 and both were below the threshold of bitterness which was reported to be 3.0 point (BMI-40: 2.5±0.3, BMI-60: 2.3±0.3). On the other hand, flavored BMI-40 was more effective than flavored BMI-60 at a 1-4% additional concentration (p<0.001), and its bitterness intensity was below the threshold (2.0±0.3-1.0±0).The mechanism of masking bitterness by using BMI-40, which contained about 50% branched dextran, was next investigated. At a 1% concentration, the rate of bitterness intensity of BMI-40 on gPL-B decreased after adding milk cocoa but not after adding sugar in comparison with that of BMI-60 (BMI-40: 42.5%, BMI-60: 64.6%).The masking effects of 3%, 5% branched dextran, which contained BMI-40 but not BMI-60, significantly increased by adding milk cocoa, while branched dextran alone was not effective.These results suggested that 1% flavored BMI-40 (with 10% milk cocoa and 10% sugar) is clinically useful for masking the bitterness of gPL-B. Furthermore, the masking mechanism of BMI-40 is also considered to be different from that of BMI-60.

It is important that hospital pharmaceutical manufacturing (HPM) is used rationally for both prescription and non-prescription drugs. However, at Fukushima Medical University Hospital, the rational use of HPM was not considered to be sufficient. A new system for regulation of the HPM is thus needed because HPM has to be used under strict controls as well as investigating drugs. As a result, an institutional review board for HPM was established at our hospital and the pharmaceutical quality control of HPM regarding factors as assurance or microbial control, was improved. Furthermore, for the rational use of HPM, we prepared information leaflets for patients, package inserts for doctors, and also developed a format for the clinical evaluation of HPM. 35 kinds of HPM are now being used under this new system.At the end of this chapter we proposed a system for the rational use of HPM at our hospital.

Taste acceptability of ground Polymyxin B sulfate and Bactramin C tablets was examined when flavored BMI-60, a food additive, was added. Both adult and child volunteers found the bitter taste of the two drugs markedly inhibited, making it clinically useful. Noncompliance, due to this bitterness, was improved using flavored BMI-60. The most striking characteristic of flavored BMI-60 is the ease of preparation compared with the manufacture of other hospital pharmaceuticals such as jelly, gummi and candy done to mask bitterness.

The actual state of re-examination of the pharmacist's fee claim forms is unsufficiently understood for both medical care institutions and insurance-pharmacies. Accordingly we analyzed contents of 881 among 1440 cases which had been actually re-examined by the National Health Insurance Examination Committee of Medical Fees in Fukushima Prefecture in January 1996.Three-fourths of assessment cases corresponded to one of the official reasons, “Not indication” . Pharmacists in the medical care institutions should examine the actual plan for contribution to appropriate legal prescription delivery. Moreover it is impossible for insurance-pharmacies to assess pharmaceutical management and counseling service when the patient's disese is unclear. It is thus necessary to construct the system based on the patient's information being mutually available to medical care institutions and insurance pharmacies.

We studied the steric course of the reaction catalyzed by the N-ethylmaleimide (NEM) reductase of Yarrowia (Candida) lipolytica (Y. lipolytica), using 4R-[4-2H1]NADPH and 4S-[4-2H1]NADPH as cofactors and N-ethylcitraconimide as substrate. Active substrates and inhibitors of NEM reductase and its subcellular distribution were also investigated to clarify the biochemical properties of this enzyme. NEM reductase catalyzes the reduction of N-ethylmaleimide to N-ethylsuccinimide with NAD(P)H as the cofactor. Several maleimide and cyclopentenone derivatives tested were also active substrates for NEM reductase of Y. lipolytica. Some pyrazolone derivatives, particularly 1-phenyl-5-pyrazolone, were found to be effective inhibitors of NEM reductase. Subcellular localization of NEM reductase was carried out using protoplast formation and differential centrifugation. Ninety-eight percent of the NEM reductase activity was recovered in the cytosolic fraction, indicating that NEM reductase in Y. lipolytica was the cytosolic enzyme. We also determined the stereochemical specificity of the reduction of N-ethylcitraconimide by NEM reductase in Y. lipolytica, showing that 4 Pro-R hydrogen of NADPH was abstracted for enzymatic hydride transfer by NEM reductase, and two hydrogen atoms from NADPH and H2O added to opposite faces of the double bond of N-ethylcitraconimide.

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The subcellular distribution of 2,4-dienoyl-CoA reductase (EC. 1.3.1.34, DCR) in rat liver was studied biochemically and immunochemically after the induction of clofibrate. DCR activity was mainly detected in the mitochondrial fraction by sucrose density gradient centrifugation in the livers of both normal and clofibrate-treated rats. It was also shown that the polyclonal antibody against purified DCR detected the enzyme in the mitochondrial fraction. However, the antibodies, which were affinity purified using the purified mitochondrial DCR or were epitope-selected using the fusion-polypeptide expressed from the mitochondrial cDNA clone (lambda gt11-RDR181), were cross-reacted with the peroxisomal DCR. These results suggest that peroxisomal DCR is immunochemically indistinguishable from mitochondrial DCR.

The Japanese Society of Hospital Pharmacists started a continuing education (CE) system for its members in April 1993. The program issues a certificate of completion to those who earn more than 70 credits a year. This paper presents the one year's trial of the CE activities conducted during April 1993 to March 1994 for the pharmacists working in the Fukushima Medical College Hospital Pharmacy.The average pharmacists partipated in 64.5 credits of CE activities. The average credits earned by 11 male pharmacists and 11 female pharmacists at our hospital pharmacy were 68.4 and 60.7, respectively. A total of 32%(7/22) of our pharmacists were able to earn 70 credits. No relationship was noted between the credit values earned by the pharmacists and their ages. Sixty-three percent of the total credits earned by the pharmacist were achieved in our hospitalbased and pharmacy-based conferences and 13% of total credits earned by pharmacists was responsible for lectures and studies held out-of-hospital, for example, at meetings sponsored by the branch of the Japanese Society of Hospital Pharmacists.It is necessary to encourage all pharmacists to keep up-to-date and improve their knowledge and judgment through CE.

The pharmacist-examiner's business at the National Health Insurance Examination Committee of Medical Fees (NHIECMF) in Fukushima Prefecture is described. The most important business of pharmacist-examiner in the committee comprises two parts. One is examination of the pharmacist's fee claim forms and the issue of cautions, and the other is the explanation of various notifications concerning medicine at conferences attended by all examiners including doctors and dentists.We recognize four problems concerning the pharmacist-examiner's role in NHIECMF system:1) The number of pharmacist-examiner is so few that pharmacist-examiner can hardly contribute to safe and cost-effective use of medicines, 2) The pharmacist-examiner has no power to delete medical fees for unnecessary treatments, 3) The pharmacist-examiner cannot confirm whether the usage of medicines is suitable for the presented indications or not because there is no column describing patient's diseases in the phamacist's fee claim form, and 4) It is impossible for the pharmacist-examiner to check pharmaceutical management and counseling service.It is therefore necessary for us to improve these problems immediately.

[11C]Methamphetamine, a psychotropic agent, was synthesized by N-methylation of amphetamine with [11C]CH3I in hopes that it could be applied in the near future to assist positron emission tomography (PET) in the imaging of its distribution in the human brain. The regional distribution of [11C]methamphetamine was investigated in the mice brain at various intervals after an intravenous (i.v.) injection. Radioactivity was higher in the hypothalamus, cortex, striatum and hippocampus. Furthermore, in chronically administered mice, the uptake of [11C]methamphetamine was higher in the striatum than those in other regions. The regional differences in the distribution of methamphetamine in the mice brain may enable the imaging of its distribution by PET using [11C]methamphetamine.

The regulations formulated in the past 10 years for morphine preparations at Fukushima Medical College Hospital are described. The amount of morphine preparations, which were returned and reused, increased in parallel with the number of prescriptions for morphine preparations. In contrast, the volume of morphine preparations disposed dramatically decreased during the past 2 years. During the past 10 years, no problems arose concerning the regulations for morphine preparations.

A segment of the neocarzinostatin apoprotein gene corresponding to T30 to A91 of the protein was amplified using a polymerase chain reaction (PCR) with total DNA from Streptomyces carzinostaticus subsp. neocarzinostaticus E-793 (ATCC 15944) as the template and with 5'- and 3'-primers synthesized in consideration of the codon usage of streptomyces. The PCR product was cloned, sequenced and confirmed to direct an amino acid sequence reasonably well matching that reported. Using the PCR product as a probe, we cloned a DNA segment (2580 bp) spanning an open reading frame (ORF) for preapoprotein (leader peptide plus apoprotein) and its upstream and downstream flanking regions. The amino acid sequence deduced from the base sequence of the DNA clearly identified those amino acid residues which had remained inconsistent among different research groups. The base sequence homology with other apoprotein genes of related antibiotics was analyzed and was found to be limited within the structural gene.