• 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 agricultural medicine and community health
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• v.9 no.1
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• pp.83-108
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• 1984

Out of a total of 58 species of helminthic and protozoan parasitic infections in Korea, so far 38 species were reported as intestinal parasites of man. Quite a few species of the intestinal parasitic infections have long been prevalent throughout the country and this has been a significant public health problem. In this paper, current status and transition of the intestinal parasitic infections in the past years were presented. Chronological reviewing of data show background and prospects of change in the prevalence of infections. In the national prevalence survey on parasitic infections conducted once every five years since 1971, stool examinations were done by both cellophane thick smear and brine flotation techniques. Every egg positive case of Ascaris lumbricoides and Clonorchis sinensis was further examined by Stoll's dilution egg counting technique. In 1981, perianal swab using adhesive cellulose tape was added for Enterobius infection. For protozoan cyst examination conducted by province and city in '81, fecal specimens were fixed in SAF solution and examined by the formalin-ether concentration technique. High prevalence of parasitic infection in ana before the 1960s can be easily understood from the data given by the Ministry of Health and Social Affairs in 1967. From a parasite control point of view, the 1960s was the preparatory period particularly for control of soil-transmitted helminthiasis. Several organizations which have contributed to parasite control were founded in this period and the prevention law of parasitic infections was passed in '66. In the '70s, overall prevalence rates of the common intestinal parasitic infections, which were highly prevalent in the past were turned into reduction phase for the first time. The '80s can be said to be an active control period of parasitic infections. Intestinal helminths According to the reports of the national prevalence survey on parasitic infections, the prevalence of helminthic infections was 84.3%(number of person examined:24,887) in '71, 63.2%(27,178) in '76, and 41.1%(35,018) in '81. By area, the prevalence rate in '81 was 35.1%(20,569) in urban areas and 49.6%(14,447) in rural areas. Intestinal nematodes Ascaris lumbricoides The prevalence of Ascaris infection has decreased significantly in recent years. Among students, the prevalence was 55.4%, in '69 and decreased to 4.7% in '83. In the national prevalence surveys, the prevalence decreased to 13.0% in '81 from 54.9% in '71. By area, the prevalence decreased to 8.5% in '81 from 46.4% in '71 in urban area and 19.4% in '81 from 59.6% in '71 in rural area. By age, the prevalence has become in recent years relatively even in all age groups, although higher prevalence used to be seen in young age groups of around 10 years old, particulary in the highly prevalent rural areas. By sex, the prevalence was higher in the female than in the male. Unfertilized egg positive rates among the ascariasis cases increased gradually up to 55.4% on the average in '81. The intensity of the infection was also significantly decreased. Trichuris trichiura Trichuris infection had also decreased to 23.4% in '81 from 65.4% in '71. By area, the decreasing tendency of the prevalence became faster in urban areas than in the rural areas. The prevalence in urban and rural areas in '71 was 69.7%, and 63.1% respectively and decreased to 19.5% and 29.0% respectively in '81. By age, the prevalence reached a peak at the 10-14 age group and showed relatively even distribution throughout all age groups. By sex, the prevalence was close in young age groups, but in the 30s or over age group, especially in rural area, the prevalence was significantly higher in the female than in the male. The prevalence has much fluctuated depending in the area. The prevalence in rural areas surveyed in the '80s shows a range between 20.9% and 73.7% by locality. It is anticipated that the prevalence of Trichuris infection will drop more rapidly, when mass treatment is conducted. Hookworms Hookworm infection by mostly Ancylostoma duodenale and a few by Necator americanus has decreased to a negligible levels in recent years. In the national prevalence surveys, the prevalence was 10.7% in '71, 2.2% in '76, and 0.5% in '81. The prevalence was higher in rural areas than in urban areas. Wide application of multi-specific anthelminthics in the ascariasis control programmes conducted in the past decade appear to have been effective against hookworm infection. Trichostrongylus orientalis As in the case with hookworm infection, the prevalence of Trichostrongylus infection has reached a negligible levels. In the national prevalence surveys, the prevalence was 7.7% in '71, 1.0% in '76 and 0.2% in '81. Enterobius vermicularis In the national prevalence survey in '81, the egg positive rate was 12.0%. Higher prevalence is expected when examined repeatedly. The prevalence rate was 10.3% in urban area and 14.6% in rural area. In recent surveys conducted in rural areas among schoolchildren, the prevalence was 32.4% in Gimhae Gun in '82 and 64.1% in Yeongyang Gun in '83. By age, the egg positive rate was higher in young age groups of around 10 and sharply decreased in age groups of around 20 and then somewhat increased again in middle age groups. By sex, the prevalence was higher in the female than in the male. Strongyloides stercoralis Strongyloides stercoralis infection has rarely been found in Korea. Three cases were reported in 1914. And 0.1-0.5% were found infected out of 2,642 persons examined at the prisoner-of-war camp on Geojedo in 1956. One case was reported in '54 and '82, respectively. Anisakis spp. No systematic survey has been conducted for anisakiasis In Korea. So far, only several cases have been found 1 case in Seoul in '71, 5 cases in Busan in '81 and 1 case in Busan in '84. Intestinal trematodes Metagonimus yokogawai In the national prevalence survey conducted in 1981, the egg positive rate was 1.24% on the average. High endemic areas are located in the southwestern part of Korea. The prevalence in Hadong Gun was 29.1% on the average in '79. In a survey conducted in 76, the prevalence was 44.0% in Gwangyang, 55.0% in Gogseung and 29.0% in Gurye. The infection is closely correlated with raw sweetfish consumption in these areas. Other intestinal trematodes A human case of Heterophyes heterophyes was reported in 1914. Several species were reported in the '80s : 17 cases of Fibricola seoulensis, 9 cases of Pygidiopsis summa, 8 cases of Heterophyes heterophyes nocens, 1case of Heterophyopsis continua, 2 cases of Stellantchasmus falcatus, 1 case of Stictodora sp., 1 case of Echinostoma hortense, and 4 cases of Echinochasmus japonicus. As the intermediate hosts, snakes and frogs play a role for F.seoulensis and fish for the rest of the species. Intestinal cestodes Taenia saginata and T. solium Egg positive rates in the national prevalence survey were 0.7% in '76 and 1.1% in '81. The prevalence in '81 was 0.6% in urban area and 1.8% in rural area. The proglottid positive rate in Jeju Do was 19.2% on the average. On Udo, Jeju Do in 1983, the egg positive rate among the inhabitants was 2.9%. Hymenolepis nana In the national prevalence survey, egg positive rates were 0.6% in '76 and 0.4% in '81. No difference was seen in the prevalence by area and sex. Hymenolepis diminuta Infected cases were reported : 3 in '64 and I in '66. Egg positive rate in '81 was 0.01% in the national prevalence survey. Diphylobothrium latum So far, about 30 cases have been reported. The cases have been reported more frequently in recent surveys. Mesocestoides sp. A case was reported from a hospitalized patient in Seoul in '67. Spirometra erinacei Two cases were reported in '84 following reidentification of the adult worms collected in '74. Intestinal protozoa Out of a total of 23 species of human protozoan infections in Korea, 13 species were reported as intestinal protozoa : Entamoeba histolytica, E coli, Endolimax nana, Iodamoeba b$\ddot{u}$tschlii, Dientamoeba fragilis, Giardia lamblia, Chilomastix mesnilii, Embadomonas sp., Enteromonas hominis, Trichomonas hominis, Isospora belli, I. Hominis(Sarcocystis hominis), and Balantidium coli. Since the first report on intestinal protozoan infections in 1925, there have been quite a few survey data on the prevalence of the infection. It was found reviewing the data chronologically that up to the early '70s the infection was prevalent around a 30-50%. After that, the protozoan cyst positive rate has shown the tendency of gradual decrease throughout the country. Protozoan cyst survey conducted in Seoul and several provinces in 1981 revealed infection rates of 8.9%(1,310) in Gangweondo, 10.7%(1,703) in Gyenggi Do, 11.7%(1,032) in Jeonra Buk Do, 9.1%(4,116) in Jeonra Nam Do, and 1.4%(5,275) in Seoul. Entamoeba histolytica In the survey conducted by province in '81, the cyst positive rate was 0.8% in Gangweon-do, 0.3% in Gyeonggi Do, 1.4% in both Jeonra Buk Do and Jeonra Nam Do, and 0.2% in Seoul. Giardia lamblia In the survey by province in '81, cyst positive rates were 2.2% in both Gyeonggi Do and Jeonra Buk Do, 1.9% in Jeonra Nam Do, 0.5% in Gangweon Do, and 0.9% in Seoul. Balantidium coli Two cases were reported. One in 1930 and the other in '74. Isospora belli and I. Hominis(Sarcocystis hominis) Isospora belli was reported : 1 case in '56 and 3 cases in '66. I. Hominis, recently identified to be synonymous with Sarcocystis hominis, was reported : 3 cases in '66. Other intestinal protozoa The protozoan parasites other than the above mentioned are generally treated as commensal, although some of them are considered to be pathogenic. The data of '81 show that about 10% of the inhabitants are still infected with protozoa.

• Advances in pediatric surgery
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• v.8 no.2
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• pp.143-155
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• 2002

A survey on biliary atresia was made among 26 members of the Korean Association of Pediatric Surgeons. The members were required to complete a questionnaire and a case registration form for each patient during the twentyone-year period of 1980-2000. Three hundred and eighty patients were registered from 18 institutions. The average number of patients per surgeon was one to two every year. The male to female ratio was 1:1.3. The age of patients on diagnosis with biliary atresia was on average $65.4{\pm} 36.2$ days old. The national distribution was 32.8% in Seoul, 25.3% in Gyoungki-Do, 21.6% in Gyoungsang-Do, 9.27% in Choongchung-Do, etc. in order. The most common clinical presentation was jaundice (98.4%) and change of stool color (86.2%) was second. Two hundred eighty (74.7%) of 375 patients were operated by 80 days of age. Three hundred thirty six (9 1.9%) of 366 patients were operated on by the original Kasai procedure, and 305 (84.3%) of 362 patients were observed by bile-drainage postoperatively. The overall postoperative complication rate was 18.5% and the overall postoperative mortality rate was 6.8%. The associated anomalies were observed in 72 cases (22.5%). One hundred ninty five (64.7%) of 302 patients have been alive in follow-up and 49 (25.1%) have survived over 5 years without problem after operation. Ascending cholangitis, varices and ascites affected survival significantly, and the important long-term prognostic factor was the occurrence of complications.

• The Korean Journal of Nuclear Medicine
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• v.4 no.1
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• pp.19-26
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• 1970

1. Sixteen normal healthy subjects free from occult blood in the stool were selected and administered with their $^{51}Cr$ labeled own blood via duodenal tube and the recovery rate of radioactivity in feces and urine was measured. The average fecal recovery rate was 90.7 per cent ($85.7{\sim}97.7%$) of the administered radioactivity, and the average urinary excretion rate was 0.8 per cent ($0.5{\sim}1.5%$) 2. There was a close correlation between the amount of blood administered and the recovery rate from the feces; the more the blood administered, the higher the recovery rate was. It was also found that the administration of the tagged blood in the amount exceeding 15ml was suitable for measuring the radioactivity in the stools. 3. In five normal healthy subjects whose circulating erythrocytes had been tagged with $^{51}Cr$, there was little fecal excretion of radioactivity (average 0.9 ml of blood per day). This excretion is not related to hemorrhage and the main route of excretion of such an negligible radioactivity was postulated as gastric juice and bile. 4. A comparison of the radioactivity in the blood and feces of the patients with $^{51}Cr$ labeled erythrocytes seems to be a valid way of estimating intestinal blood loss.