• The Korean Journal of Pharmacology
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• v.16 no.2 s.27
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• pp.55-70
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• 1980

The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

• Journal of The Korean Society of Clinical Toxicology
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• v.3 no.2
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• pp.79-85
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• 2005

Purpose: With the recent boom in 'eating healthy', many adults are interested in dieting to prevent future diseases. However only well trained experts can distinguish between what are edible vegetables and herbs from their poisonous look-alikes. In cases where a patient unknowingly ingests a poisonous herb, is caught off guard by the poisonous side effects that occur because of their lack of knowledge of what they have ingested. This paper will focus on the need to educate the public about the risks involved with ingesting wild vegetables and herbs and study the emergency diagnosis and treatment of poisoned patients that enter the emergency room. Method: This study was done in the spring of 2004 (from March to May) in the Kangwon Young-Seo districts of Korea. 15 subjects used in this study, entered the emergency room showing signs of toxic symptoms. Data was collected by examining subject's records. Additional data was collected by collaborating with physicians in the hospital that diagnosed and treated the subjects. Identifying the poisonous vegetable or herb is the first step to proper diagnosis and treatment. Subjects admitted to the emergency room, underwent a battery of tests: laboratory examination, ECG, radiological exam and etc. Results: The demographics of the study encompassed subjects with the average age of $50{\pm}19$ years old. There were 10 men and 5 women. Common symptoms of this study included; gastrointestinal symptoms such as nausea, vomiting, epigastric pain and so on. In the case of Caltha palustris ingestion, additional symptoms were present; bradycardia and hypotension which lasted for a long time. While cases that ingested Scopolia parviflora had little effect on vital signs but manic episodes lasted for about three days. Veratrum patulum ingestion showed signs of bradycardia and hypotension but contrary to Caltha palustris recovery was shorten by treating with dopamine. However, dizziness, headache and paresthesia of the extremities continued for a long time. Finally Sium ninsi ingestion showed visual disturbance, paresthesia of the extremities, dizziness as their initial symptoms. Conclusion: The risks involved with ingesting wild plants without the proper knowledge can lead to serious side effects and steps need to be taken to educate the public. In addition, all emergency physicians need to have a working knowledge of the symptoms and signs associated with ingesting toxic wild plants and need to treat accordingly.

• Clinical and Experimental Pediatrics
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• v.52 no.12
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• pp.1364-1369
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• 2009

Purpose : To analyze abnormal ventricular activation in childhood congenital heart disease induced by postoperative changes in ventricular volume and pressure and ventricular scar formation using signal-averaged electrocardiography (SAECG). Methods : Fifty-two patients who had undergone open heart surgery (OHS) were enrolled. Patients were divided into the following 3 groups: right ventricular volume overload (atrial septal defect, group1), left ventricular volume overload (ventricular septal defect, group2), and right ventricular pressure overload (tetralogy of Fallot, group 3). The patients were monitored by standard 12-lead ECG and SAECG before and 2 months after the operation. QRS duration, QT and QTc intervals, filtered QRS (f-QRS), high frequency low amplitude potential (HFLA), and root mean square (RMS) voltage in the terminal 40 ms of SAECG were determined. Results : In the preoperative period, group1 showed significant increase in QRS (P=0.011) compared to those of the other 2 groups. In the postoperative period, group3 showed significant increase in the QTc interval (P=0.004) compared to those in the other 2 groups. SAECG parameters showed no significant differences among the groups in the pre- or postoperative period. Of the 52 patients, 12 (23%) in the preoperative period and 21 (40%) in the postoperative period had at least 1 SAECG abnormality. The prevalence of SAECG abnormalities was significantly higher in the postoperative group 2 and group 3 (preoperative: 20% versus postoperative: 28%, P<0.001, preoperative: 14% versus postoperative: 64%, P<0.001, respectively). Conclusion : Abnormal SAECG patterns may be attributed to postoperative scars, OHS itself, and/or ventricular overload.

• The Korean Nurse
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• v.36 no.1
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• pp.108-117
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• 1997

This study was carried out to examine the standards for evaluation of laboratory facilities and equipment. These constitute the most important yet vulnerable area of our system of higher education among the six school evaluation categories provided by the Korean Council for University Education. To obtain data on the present situation of holdings and management of laboratory facilities and equipment at nursing schools in Korea, questionnaires were prepared by members of a special committee of the Korea Nursing Education Society on the basis of the Standards for University Laboratory Facilities and Equipment issued by the Ministry of Education. The questionnaires were sent to nursing schools across the nation by mail on October 4, 1995. 39 institutions completed and returned the questionnaires by mail by December 31 of the same year. The results of the analysis of the survey were as follows: 1. The Physical Environment of Laboratories According to the results of investigation of 14 nursing departments at four-year colleges, laboratories vary in size ranging from 24 to 274.91 pyeong ($1{\;}pyeong{\;}={\;}3.3m^2).$. The average number of students in a laboratory class was 46.93 at four-year colleges, while the number ranged from 40 to 240 in junior colleges. The average floor space of laboratories at junior colleges, however, was almost the same as those, of laboratories at four-year colleges. 2. The Actual State of Laboratory Facilities and Equipment Laboratory equipment possessed by nursing schools at colleges and universities showed a very wide distribution by type, but most of it does not meet government standards according to applicable regulations while some types of equipment are in excess supply. The same is true of junior colleges. where laboratory equipment should meet a different set of government standards specifically established for junior colleges. Closer investigation is called for with regard to those types of equipment which are in short supply in more than 80 percent of colleges and universities. As for the types of equipment in excess supply, investigation should be carried out to determine whether they are really needed in large quantities or should be installed. In many cases, it would appear that unnecessary equipment is procured, even if it is already obsolete, merely for the sake of holding a seemingly impressive armamentarium. 3. Basic Science Laboratory Equipment Among the 39 institutions, five four-year colleges were found to possess equipment for basic science. Only one type of essential equipment, tele-thermometers, and only two types of recommended equipment, rotators and dip chambers, were installed in sufficient numbers to meet the standards. All junior colleges failed to meet the standards in all of equipment categories. Overall, nursing schools at all of the various institutions were found to be below per in terms of laboratory equipment. 4. Required Equipment In response to the question concerning which type of equipment was most needed and not currently in possession, cardiopulmonary resuscitation (CPR) machines and electrocardiogram (ECG) monitors topped the list with four respondents each, followed by measuring equipment. 5. Management of Laboratory Equipment According to the survey, the professors in charge of clinical training and teaching assistants are responsible for management of the laboratory at nursing schools at all colleges and universities, whereas the chief of the general affairs section or chairman of the nursing department manages the laboratory at junior colleges. This suggests that the administrative systems are more or less different. According to the above results, laboratory training could be defined as a process by which nursing students pick up many of the nursing skills necessary to become fully qualified nurses. Laboratory training should therefore be carefully planned to provide students with high levels of hands-on experience so that they can effectively handle problems and emergencies in actual situations. All nursing students should therefore be thoroughly drilled and given as much on-the-job experience as possible. In this regard, there is clearly a need to update the equipment criteria as demanded by society's present situation rather than just filling laboratory equipment quotas according to the current criteria.