Lymphocyte stimulation test (LST) is one of the useful laboratory tests for identification of allergy to a specific drug.The present study was conducted to examine utility of LST using ethidium bromide (EB) fluorescence assay as a method for diagnosis of drug allergy.In a preliminary experiment, phytohemagglutinin (PHA) was used instead of suspected drugs.PHA at concentrations between 0.001-1.2% caused an activation of lymphocytes with elevation on stimulation index (SI).Interleukin 2 at concentrations between 1-100 ng/ml enhanced PHA-induced activation of lymphocytes. From these results, LST using EB fluorescence assay would be available for diagnosis of drug allergy.
At first we carried out LST on 22 cases of suspicious drug-induced hepatitis.As a result, 9 cases were positive and 13 cases were negative.In order to analyze the relationship between background of the patients and LST, we studied transaminase (GOT and GPT) activities in the sera which were obtained from the patients in different states (remission and acute disease states). As a result, when LST was carried out in remission state, relatively high positive incidence (50%) was obtained.When LST was carried out in acute disease state, positive incidence of LST was low (25%).
These results indicate that this method is useful for clinical diagnosis of drug allergy, And in the case of the diagnosis of drug-induced hepatitis, LST would be recommended to be carried out in remission state.

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As a preliminary study, the bacterial endotoxin test using an injection with a strong color (hematoporphyrin sodium) was examined. With the method in the 11 th edition of the Japanese Pharmacopoeia, the detection sensitivity was 0.25 endotoxin units/ml.This method did not have sufficient detection sensitivity for endotoxin in human.Therefore, a nephelometry method using a multiplate was studied.With this method, it was possible that of 96 samples was measured in only 30 minutes. The sensitivity of this method was 0.1 endotoxin units/ml for hematoporphyrin sodium injection.When an analytical curve was prepared using standard endotoxin, high linearity was obtained. This result demonstrated that the bacterial endotoxin test by the nephelometry method will be useful as replacement for the pyrogen test in hospital pharmacy.

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The morphine preparations, which have the rapid initial absorption and the subsequent prolonged absorption simultaneously, are desired to manage the pain of the terminal cancer patients. The clinical analgesic and sedative effects and the side effects of a slow release morphine hydrochloride-sodium alginate suppository, MA suppository, were evaluated in the cancer inpatients and outpatients.The MA suppository analgesia appeared within 20 minutes after rectal administration, regardless of the intensity of the initial pain of the patients. Of 17 cancer patients, nine patients and six patients required the MA suppository every 24 hours and 12 hours for optimal analgesia, respectively. No clinical problem in transition sedation was observed by use of MA suppository from the view point of quality of life for the patients. The extent of the other side effects is vanishingly mild, and then the administration of the suppository to the patients could be continued to their dying day. MA suppository is very safe and useful to care for a cancer patient at home.

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Phenobarbital (PB) pharmacokinetics were studied in order to find the optimal intravenous dose for neonatal convulsion. The subjects consisted of twenty-nine neonates (17males and 12 females) with seizure or intraventricular hemorrhage or asphyxia at birth.The mean gestational age and birth weight of the subjects were 37 weeks and 2.61 kg. The subjects over1, 000 g received 10 to 20 mg/kg of PB, and blood samples for assay of PB serum concentration were collected several times for one week after the intravenous administration. Pharmacokinetic parameters of one-compartment model for i. v. were calculated in each subject and compared with the results of laboratory examination.
Twenty-one (95%) in twenty-two subjects who received single intravenous injection of 20mg/ kg PB showed serum concentration over 15, ug/ml within 6 hours after the administration.The i.v.dose of 20mgfkg was considered to be enough to protect neonatal convulsion. Calculated volume of disribution index (Vd) and elimination constant (Ke) were 0.924 +/0.247 (mean +/-SD) 1/kg and0.00512+/-0.00297 1/hr, respectively. There were positive correlation between total volume of distribution and body weight and negative one between Ke and serum creatinine concentration or blood urea nitrogen.

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Serum levels of digoxin and methyldigoxin were measured with the cloned enzyme donor immunoassay (CEDIA) method and the fluorescence polarization immunoassay (FPIA) method.In other samples, both of those cardiac glycosides were measured with FPIA method and radioimmunoassay (RIA) method.
There was a significant correlation (r=0.835, n=85) between CEDIA and FPIA methods in serum levels of digoxin and an apparent that of methyldigoxin. But in some patients, especially in infants, the values of the CEDIA method were lower than those of FPIA method.In contrast, there was a higher significant correlation (r=0.939, n=63) between FPIA and RIA methods in serum levels of both cardiac glycosides.These results may indicate that sensitivities of these methods to the interfering substances (ex. endogenous digoxin-like substance) differ each other.

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We investigated the effectiveness of towels used for removing bacteria which had adhered to the sole of hospital footwear after walking a set number of steps.In addition to an absorbent mat, towels for wiping were saturated with chlorhexidine gluconate, benzalkonium chloride, sodium hypochlorite or sterile distilled water.Towels soaked with the three types of antiseptic solutions exhibited a uniform sterilizing effect of bacteria with almost no relation to the number of times of wiping.When a towel soaked with sterile distilled water was used, the sterilizing effect diminished with successive wipes.Compared with the five methods, the absorbent mat had the weakest average sterilizing effect.

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The drug adsorption onto membrane filters (MF) from five kinds of eyedrops, atropine sulfate (AT), pilocarpine hydrochloride (PC), amphotericin B, dibekacin sulfate, and disodium edetate eyedrops during sterilization by filtration was investigated.
The principal ingredients in eyedrops were scarcely adsorbed to MF.In the preservatives, methyl and propyl parahydroxybenzoates in AT eyedrops were almost adsorbed to acetylcellulose MF, while benzalkonium chloride in PC eyedrops was almost adsorbed to MF made from mixed esters of cellulose, nitrocellulose or polyvinyliden fluoride. However, the adsorption of the preservatives can be fairly prevented by discarding the first part of the filtrate from eyedrops. From these results, when eyedrops containing above preservatives are sterilized by filtration, the use of MF on which adsorption was observed should be avoided, or the first part of the filtrate should be discarded.

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The Levothyroxine sodium (T₄) tablet is the remedy of the dysthyreosis.When we prescribe that tablet to an infant and the patient who cannot swallow it, we provide the preparation of that obtained by crushing tablet.
In this study, we examined the dispersibility and the stability of T₄ in that preparations. The dispersibility of T₄ in that preparations was influenced in the kind of the constituents. However, the coefficient of variation were 2-3%. The stability of T₄ in that preparations was influenced in various cases.However, in all of the 3 kinds of the constituents examined, ingredient content ratio of T₄ was more than 98%, 30 days later. Using lactose+starch as the constituents, with preservation under total shading, ingredient content ratio of T₄ was 94.2%, 30 days later. On the other hand, with preservation in the light of indoors being scattered, ingredient content ratio of T₄ was 85.8%, 30 days later. Ingredient content ratio of T₄ was 91.6% under mild condition (5°C, C.R.H.52%), 81.8% under medium condition (20°C, C.R.H. 75%), 77.3% under severe condition (30°C, C.R.H.92%), 30 days later.

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The postantibiotic effect (PAE) of four kinds of antibiotics (Chloramphenicol, Gentamicin Sulfate, Cefazolin Sodium, Ampicillin) against Escherichia coli (E.coli) and the producing ability of bacterial β-glucuronidase in vitro were measured.The PAE was found in two kinds of non β-lactam antibiotics, and the β-glucuronidase production of E.coli was suppressed during the term of PAE.
These results suggest a promising development for PAE measurement against E.coli by utilizing β-glucuronidase produced by the organisms.

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We studied secondary contamination of eyedrops at our university hospital and Okinaga Ophthalmic Hospital.We found that 14 (2.77%) of 506 eyedrops containing 31 kinds of ophthalmic solutions recovered from outpatients (203), were contaminated.We did not find relationship between secondary contamination and a kind of antiseptic on eyedrops.

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Dopamine hydrochloride is a drug frequently used in many departments to treat acute circulatory insufficiency.The pharmaceutical preparation for convenient use inside the hospital was made, and the time-course stability after 1, 2 and 3 months was examined.The test sample was prepared by injecting the commercial dopamine hydrochloride into plastic or glass bottles containing physiological saline or 5% glucose.
No abnormalities of the appearance, pH, osmotic pressure ratio and contents were recognized at any examination point, and sterility test after 3 months proved the sterility of the test sample.

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To reduce the working hours and manpower to edit the bound hospital formulary (bound HF), we tried to make the editing manuscript by using the datafiles of “on-line hospital formulary system (on-line HFS)” operating in Kanazawa University Hospital which was developed by our pharmacy staffs in October 1987.And the printing form of the new bound HF was changed to be same with the display image of the “on-line HFS” to use the two systems conveniently.
Because the data of “on-line HFS” is revised continually, the editing manuscript formed in floppy disk was prepared simply from “on-line HFS” for only 30 min and sent to the press. The works to write the manuscript and to correct proofs were considerably reduced by this way.Consequently, the time to publish the new bound HF which was 99 days was reduced as compared with 235 days for the last publishing.

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One of the serious problems for hospital pharmacy is a long waiting time of outpatients and it is a very uncomfortable time for them.In 1989, we brought a new system into our pharmacy for shortening the waiting time of them.Next year we interviewed a total of 300 outpatients at dispensing counter and asked about their desirable waiting time to verify the new system.Outpatients were classified as three groups consisting of each hundred of them, women (group I), men (group II), and the mothers who took their babies to the pediatric department (group III) The ratios of the desirable waiting time within twenty minutes in each group were 44% in group I, 46% in group II, and 65% in goup M.Then we conducted another investigation on the waiting time that outpatients experienced it at the pharmacy lobby. We selected a total of 800 outpatients at random and asked about it.It was found that 72.5% of them got their medicines within five minutes, and 91.6% of them got within 10 minutes. We can conclude from our investigations that group III wants shorter time to get their medicines than other two groups and the adopted new system have been bringing about good results.

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The modified Brown's method has been commonly used when preparing the colon for colonoscopy or colonic surgery.Recently, however, a new faster and simpler method, using orally administrable gastrointestinal lavage solution composed of polyethylene glycol 4000 and 4 types of electrolytes, has become recognized.This preparation has been already in market in U.S. A., under the name of Golytely^TM, though not available in Japan.We prepared the solution at our hospital, it is known as CCS (colon clean solution) for clinical use.
Due to the limited information available about the stability and bacteriological features of the pharmaceutical preparation, we attempted to corroborate it.Results showed that contents were stable for 8 weeks, but bacteriologically not stable without aseptic preparation.Therefore, it is recommended that storage should be limited to within 1 week at 5°C in general preparation.

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Recently, it has been reported that the side effect of benzodiazepine trends to occur frequently in aged people over 60 years.We examined how to use in outpatients over 60 years through interview by telephone.The results from 83 patients showed that triazolam led to awakening during the night in 29 cases (61.7%) out of 47.Nitrazepam was revealed in 25 cases (69.4%) out of 36.There was no significant difference between both drugs.
However, rebound insomnia as impossibility to return to sleep appeared in 18 cases (62.1%) of 29 for triazolam and 2 cases (8%) of 25 for nitrazepam.The incidence of rebound insomnia was higher for triazolam.Amnesia occurred in 2 cases (5.4%) out of 37 interviewed outpatients taking triazolam but in none of the case of nitrazepam.

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