白鼠感染 肝吸蟲幼蟲에 대한 Praziquantel(Biltricide^(�))의 殺蟲效果에 대하여

林漢鍾,梁元容,宋寅喆,金洙鎭 최신의학사 1981 最新醫學 Vol.24 No.4

人體囊尾蟲病에 있어서 Praziquantel(Embay 8440)의 治療效果에 관한 硏究

林漢鍾,元昶龍,朱正和 고려대학교 의과대학 1980 고려대 의대 잡지 Vol.17 No.3

Clinical and histopathological analysis were made on 47 cysticercosis patients who visited our institute during the years of 1972 to 1979. Among 47 cases 28 (59.6%) were males and ages ranged from 20 to 40. Of the total, 20 cases (42.6%) experienced vomiting by unknown cause before the occurrence of cysticercosis. This fact may be suggested that one of the modes of occurrence of cysticercosis is considered by the mechanism if internal autoinfection depending on the reverse peristalsis. Furthermore in this analysis, at least 18 cases (38.3%) were considered cerebral cysticercosis by the episodes of convulsive seizure in their history. For therapeutic trial, praziquantel, 3×25㎎/㎏/day, was administered orally for 3 or 4 consecutive days to 20 cases with or without cerebral cysticercosis. The assessment of drug efficacy of praziquantel was judged by comparing the numbers of cysticercus nodules in the subcutaneous tissues, histopathological findings of the biopsied parasites and the frequencies of epileptic seizures with those before and after treatment with the drug. From one month after the administration of the drug, some cysticercus nodules began to disappear in the subcutaneous tissues, and that, a large numbers of the nodules disappeared during the period of 3 to 6 months after the administration. In some patients, however, very few numbers of the nodules were remained over one year after the treatment. Among 20 cases treated with the drug, 8 had cerebral involvement of the parasite and had convulsive seizure. However there were no cessation of the seizure during the period of 6 months after the treatment. Among those cases with seizures, 4 cases were treated again with the same does of the drug for 4 consecutive days at 6 months after the first trial of treatment. No epileptic seizures were experienced in these cases over one years after the second treatment. Histopathologically the appearance of vesiculation in tegument as well as desquamation of tegument were observed in 2 week's specimens of the nodules. Some cysticerci biopsied at one month after the treatment were damaged with high disintegration, and some nodules were necrotized completely. Even some cysticerci which were remained in the subcutaneous tissue over one year were also observed to have some histopathological changes. None of the cases treated with the drug was observed with laboratory abnormalities in the findings of hematology, blood biochemistry and urinalysis. It may be well to say that praziquantel is effective for the treatment of human cysticercosis. However unwanted side effects, such as headache, nausea and vomiting were encountered in the group of patients with cerebral involvement. These side effects could be prevented and minimized by the application of dexamethasone during the course of treatment with praziquantel.

吸蟲類感染의 化學療法에 關한 硏究

林漢鍾 고려대학교 의과대학 1975 고려대 의대 잡지 Vol.12 No.2

Trematode infections, especially clonorchiasis, paragonimiasis, heterophyidiasis and fasciolopsiasis are the most important public health problems in certain countries in the Far East and South Eastern countries. Three common species of trematodes of medical importance have been reported in Korea, namely, Clonorchis stnensis, Paragonimus westermani and Metagonimus yokogawai. These trematode infections have long been recognized as an important public health problem in Korea. There is no report of human infection of Fasciola hepaiica and Eurytrema pancreaticum which common in Korean cattle. The occurrence of Fasciolopsis buski in Korea has not yet been reported. Some other small intestinal flukes, such as Echinostoma spp., Echinochasmus sp. And Heterophyes spp. Are also found in animals, however there are of no medical importance in Korea. Since last 10 years, there is no practically any big changes on the chemotherapy for the trematode infections except schistosomiasis. Bithionol is the drug of choice in the chemotherapy for paragonimiasis and tetrachlorethylene is the drug of choice for heterophyidiasis and fasciolopsiasis. However, there is none of the drug of choice for the treatment of clonorchiasis and opisthorchiasis up to now. In the present study several new drugs were attempted to the clinical trials for the treatment of clonorchiasis, paragonimiasis and metagonimiasis. The results are as follows: 1. Study on the chemotherapy for clonorchiasi Many earlier investigators have studied the treatment of clonorchiasis with various drugs, however none has proved to be effective as well as non-toxic to the host. Clonorchiasis is the most important disease in Korea, and this disease has been known to be of public health concern in many areas of southern part of Korea, but there is not any specific treatment for clonorchiasis. It would be desirable to find a therapeutic agent in the treatment of this disease. (1). Activity of drugs on Clonorchis sinensis infection of rabbits. In order to find a highly efficient compound against Clonorchis infection, the anthelmintic activiy of hetol (1,4 bis-trichloromethyl-benzol), dehydroemetine and bilevon (niclofolan) were tested against C. sinensis experimentally infected rabbits. All drugs showed a progressive increase in efficacy as the dose rate. They were highly efficient against Clonorchis infection if sufficiently high, potentially toxic doses were given. The efficacy was evaluated by the number of detected worms with vital condition at autopsy after the treatment with above drugs. The high efficacy was observed at the following dose rates of each drugs, i. e. hetol at the daily doses from 50 to 100㎎/㎏ for 5 to 10 consecutive days, dehydroemetine at the daily dose of 10㎎/㎏ for at least 10 consecutive days, and a single dose of 8 ㎎/㎏ of bilevon. (2). Clinical obser vation on the chemother apeutic effect of hetol. The therapeutic effect of hetol in various dosages and duration of medication was observed in 32 cases were treated with hetol at the dosage of 50 ㎎, 100 ㎎ and 150 ㎎ per ㎏ body weight daily or every other day for 5 to 12 medication days. The dosage of 50 ㎎ per ㎏ daily for 5 medication days can obtain complete cure in the light infection cases (1-1999 EPG), but the dosage for the treatment of the moderate infection(1,000-9,999 EPG) and heavy infection cases (10,000 and over EPG) require at least 50 ㎎ per ㎏ body weight daily for 12 medication days or 100 ㎎ per ㎏ daily for 7 medication days. However a dosage of 50 ㎎ per ㎏ daily for 5 to over 12 medication days depending on the severity of infection appears to be safe and appropriate for the treatment of clonorchiasis sinensis. (3) Clinical observation on the chemother apeutic effect of dehydroemetine Forty-five clonorchiasis patients were treated with dehydroemetine late-release tablets. These patients were divided into 5 groups and each group was given different dosages of dehydroemetine. In the results, high effectiveness showed at the dose of 2.5 ㎎/㎏ every other day for 25 to 30 days. In most of cases the EPG of faeces turned negative from the 30th day to the 40th day of treatment, but a very small number of eggs was detected again by concentration method at their follow up for over 6 months. During and after treatment, most patients showed marked improvement, usually with disappearance of upper abdominal pain and recovery of appetite. Some side effects such as diarrhea, anorexia, weakness and headache were reported in the most treated cases. However dehydroemetine should not be given to patients with cardiac insufficiency. (4) Clinical observation on the chemother apeutic effect of bilevon(niclofolan) A new drug which is bilevon (niclofolan, menichlofolan) has been used in the treatment of clonorchiasis. In order to obtain a minimum effective dose, various dosages and duration of medication of bilevon were applied for the treatment of clinical cases with different degree of infection. Bilevon was given at the dosages of 0.2, 0.4, 0.8, 1.0, and 2.0 ㎎/㎏ body weight in once or twice equally divided doses for one to 15 medicaion days in 35 cases consistiog all degree of infection. In each 5 cases received bilevon at the doses of 0.2 ㎎/㎏ and 0.4 ㎎/㎏ body weight for 15 consecutive days, the mean egg reduction rates at 6 months after treatment were shown 69.1 per cent and 94.4 per cent respectively. On the other hand, in each 5 cases received a relatively higher doses at 0.8㎎/㎏ body weight for 5 consecutive days, 1.0 ㎎/㎏ for 3 consecutive days and 2.0 ㎎/㎏ for 2 consecutive days, the mean egg reduction rates were shown 95.4%, 98.9% and 99.5% respectively at 3 or 6 months after treatment. In the most cases the EPG falled rapidly in the number of Clonorchis ova within 20 days after the beginning of treatment. On follow-up examination on 3 to 5 months after treatment, most patients showed marked clinical improvement. And also in the cases previously affected liver, much improvement of their liver function test showed after treatment with bilevon. Bilevon was well tolerated, but some side effects were noted such as with weakness, muscle pain on sacral region and lower extremities. The possibility that human clonorchiasis could be successfully treated with a few doses of bilevon can be promised from this study. Therefore, bilevon is a very promising drug for mass treatment against Clonorchis sinensis infection. Ⅱ. Study on the chemotherapy for paragonimiasis Paragonimiasis has been known as a medically important endemic disease linked with eating habit of fresh water crustaceans, particularly in Far East Asian countries for a long time. Bithionol is the drug of choice in paragonimiasis and has been used extensively in the past 15 years. However, the multiple doses and it's side reactions are hampered in mass treatment with bithionol in the field. In the present study bilevon has been used in the treatment of paragonimiasis for the first time. The experimental chemotherapy with bilevon for the infected dogs and cats with P. westermani were carried out. It was proved that a single or two doses of 20. ㎎/㎏ of bilevon were evidently effective for the infected dogs or cats with the lung fluke. In the clinical trial 25 paragonimiasis cases who have shown the eggs in their bloody sputa were treated with bilevon at a single dose of 2.0 ㎎/㎏ body weight. The number of eggs and the amounts of sputa were gradually decreased until 3 weeks after medication. The eggs in sputa of all cases were disappeared within one month after medication, and no relapses were found from the results of the follow-up investigations during the period from 6 to 12 months after medication. Fifteen out of 25 cases were examined periodically chest X-ray. Among them 5 cases who have shown abnormal X-ray shadows disappeared between the period from 2 to 4 months after medication. Bilevon was well tolerated and side effects were noted as transient weakness and muscle pain on sacral region in some cases but did not require treatment. There was no significant alteration in ECG, blood counts, blood biochemistry and urine analysis of all 15 cases before and after medication. The possibility that human paragonimiasis could be successfully treated with a single dose of bilevon can be presumed from this study. Therefore, bilevon is a very promising drug for mass treatment against paragonimiases as well as clonorchiasis. Ⅲ. Study on the chemotherapy for metagonimiasis The heterophyids are extremely small flukes inhabiting the intestine of man and fish eating mammals and birds. The infection of Metagonimus yokogawai has been known to be present nationwidely and endemic in some parts of Korea. In order to select a highly effective compound against Metagonimus infection, the therapeutic effects were observed in 101 cases were treated with several anthelmintics, i. e. terachlorethylene, bephenium hydroxynaphthoate(alcopar), pyrantel pamoate(combantrin), oxantel and pyrantel pamoate mixture and niclosamide(yomesan). Among the above drugs Metagonimus was removed by tetrachlorethylene and niclosamide at a single dose. From the results niclosamide was well tolerated, and no side effects were observed. Overall egg reduction rate was 96.2 per cent and radical cure was obtained by using a dosage of 100-125㎎/㎏ body weight in children.

肝吸蟲症의 化學療法

林漢鍾 고려대학교 의과대학 1982 고려대 의대 잡지 Vol.19 No.2

Many earlier investigators have studied the treatment of clonors have studied the treatment preparations, gentian violet, emetine hydrochloride, chloroquine diphosphate, bithionol and dithiazanine iodide etc. However, clinical improvement and negative or reduced egg counts were temporarily noted but the permanent results were questionable. Since 1965, in Japan and Korea, the extensive investigations of 1,4-bis-trichloromethyl-benzol (Hetol) in human clonorchiasis have been strongly suggested that the drug is highly promising as the therapeutic agent. Hexachloroparaxylol, which is supposed to be the same compound as Hetol, is used for the treatment of clonorchissis in China and opisthorchissis in USSR. However, Hoechst AG, the maker of Hetol, stopped its production because in chronic toxicity tests using even 60 ㎎/㎏ bwt for 30 consecutive days on dogs, it caused remarkable hypochromic anemia by the end of study. Prolonged oral dehydroemetine treatment and only two doses of niclofolan (Bayer 9015, Bilevon® treatment are shown both therapeutic effect on Clonorchis infection in animals as well as in human being by killing the flukes in bile ducts. However the side reactions are observed in the most of treated cases. Recently Rim et al. treated successfully human clonorchiasis with a new drug, praziquantel (Embay 8440; Biltricide®), which is known as an excellent activity against all species of cestodes and schistosomes in man and animals. According to them, 3 doses of 25 ㎎/㎏ bwt of praziquantel in a single day or 2 days treatment could obtain complete cure without any serious side effects. Praziquantel has shown marked biological activity against C. sinensis in vitro and in experimental animals. It was found that worms were contracted and intensive vacuolization occurred at distinct sites of the tegument in vitro experiments. In the fine structural changes of C. sinensis obtained from experimentally infected rats after treatment, the degeneration of mitochondria and vesicles in the nerve bulb of the sensory papillae around two suckers and excretory pore was observed at 6 hours after treatment. After 12 hours degenerated changes on the tegument of C. sinensis were occurred by a considerable vacuolization of the tegumental syncytium near the sensory papillae. The vacuolization had increased markedly in the course of time and formed bleb-like structures. The bleb-like structures were increased in number a11 over the surface of the worm. The balloon-shaped structure formed at anterior part of worm from 12 hours after treatment is supposed to be caused by the accumulated excretory material due to the loss of excretory function. Therefore the bleb-like structure on the surface of worms led to its death by the bursting of the tegument in this region. From the above results, in the activity of praziquantel against C. sinensis, contraction and subsequent paralysis due to the degeneration of vesicle in the nerve bulb of the sensory papillae around the suckers must be regarded as a primary effect of praziquantel. We know that most of Clonorchis worms are primarily affected in such a way that they are immobilized and dislodged through common bile duct into the intestine This result was demonstrated by collecting the nor-damaged Clonorchis worms from the diarrheic stools in a few hours after the application of a single dose of 40㎎/㎏ of praziquantel. In the animal experiments, praziquantel showed a high degree of activity against young larvae as well as adult worms of C. sinensis. It was equally effective against all developmetnal stages of C. sinensis. Therefore praziquantel has a high chemoprophylactic activity against C. sinensis infection. Praziquantel was well tolerated and side effects consisted particularly of mild and transient headache, dizziness end abdonimal discomfort etc. However, there was no any differences in regard to frequency and intensity of untoward side effects among the different dosage groups. Concerning of the Clonorchis infection in Korean populztion, clonorchiasis represents a major clinical and socio-economic problems in the southern Korea. It is therefore important that effort should be made to control of clonorchiasis in endemic area. The results obtained in the field studies suggest that a single dose of 40 ㎎/㎏ bwt for light infection, 2×30 ㎎/㎏ bwt for moderate infection and 3×25㎎/㎏ bwt for heavy infection group will be recommended for mass campaigns to the clonorchiasis patients with praziquantel. This may have important financial implications, especially in population control programmes. Considering the ease of administration and the good acceptance 8s well as very good efficacy, praziquzntel will have a great role to play in the control of clonorchiasis in the near future.

高興郡 浦頭面에 있어서의 肺吸蟲症의 疫學的 推移

林漢鍾,李駿商,金東彦,鄭城守 고려대학교 의과대학 1980 고려대 의대 잡지 Vol.17 No.1

It is recognized that Ko Heung Gun is the most well known endemic foci of paragonimiasis in Korea. Authors carried out the survey for human paragonimiasis in Po Du Myun, Ko Heung Gun (from 1968 to 1979) by the use of intradermal screening test with Veronal buffered saline antigens. In 1968 and 1979, inhabitants, of all age groups in these areas were examined. In 1979, 1,484 middle school students in Po Du Myun and 1,247 high school students in Ko Heung Eup were examined. The infestation rate of crabs with Paragonimus metacercaria was also examined. The following results were obtained in this survey. 1. In 1968, 353 inhabitants were showed 56.9% positive reaction, with sexual difference of 60.2% in male and 50.8% in female. The positive rate was shown over 50% in the age groups of over 10 years old. 2. In 1979, 387 inhabitants were showed 48.8% positive reaction, with sexual difference of 61.0% in male and 38.6% in female. The positive rate was shown over 50% in the age groups over 40 years old. 3. In 1979, middle school students in Po Du Myun were showed 16.4% positive reaction and high school students in Ko Heung Eup were showed 5.7% positive reaction. 4. The positive rate of Paragonimus metacercariae was 25.0% in crabs (Eriocheir japonicus) and the mean number of metacercaria per crab was 0.6.

肝 및 肺吸蟲病의 化學療法

林漢鍾 대한화학요법학회 1983 대한화학요법학회지 Vol.1 No.1

肝吸蟲症 및 肺吸蟲症은 우리나라를 위사하여 極東 및 東南亞地域에 있어서 重要한 風土病性疾患으로 알려져 있다. 그러나 오랫동안 適切한 治療劑가 없었다. 1961年 이래 bithionol이 肺吸蟲症의 治療劑로서 愛用되어 왔으나 長其間의 投藥과 그 副作用 때문에 個人的治療에 있어서는 별로 지장이 없었으나 集團治療에는 實效를 거두지 못하였다. 최근에 이르러 새로 開發된 Isoquinolin pyrazino誘導體인 praziquantel(Embay 8440: Biltricide)는 肝吸蟲症뿐만 아니라 肺吸蟲症治療에 있어서도 現在까지 알려진 他藥劑와 比較할 수 없을 만큼 治療效果가 우수하고 安全하게 治療에 使用할 수 있게 되었다. 肝吸蟲症治療에 있어서는 praziquantel을 25㎎/㎏의 用量을 5~6時間간격으로 3回(總量 75㎎/㎏)單1回만 服用하여도 完全治療가 가능하고 肺吸蟲症에 있어서는 같은 用量을 2回 連用하면 된다. 副作用에 있어서 다만 輕微하나 頭痛과 眩氣症이 있을 뿐이고 小數例에서 惡心, 腹痛 및 泄瀉를 호소하는 일이 있다. 따라서 praziquantel은 投與方法이 쉽고 副作用이 적어 우수한 受容性을 나타내고 卓越한 治療效果 등으로 장차 肝 및 肺吸蟲症管理에 큰 役割마을 하게 될 것으로 기대된다. Trematode infections, especially clonorchiasis and paragonimiasis are the most important endemic diseases in certain countries in the Far East and South Eastern countries. For a long time, there is no any effective drug for the treatment of these trematode infections. Since 1961 bithionol has been used extensively for the treatment of paragonimiasis westermani and it was proved as a drug of choice for paragonimiasis caused by all kinds of Paragonimus. However the multiple doses and its side reactions are hampered in mass treatment with bithionol in the field. On the other hand, many earlier investigators have studied the treatment of clonorchiasis with many drugs. However, clinical improvement and negative or reduced egg counts were temporarily noted hut the permanent results were questionable. Although Hetol(1.4-bis-trichloromethylhenzol), dehydroemetine and niclofolan were shown therapeutic effects on Clonorchis infection in animals as well as in human being by killing the flukes in bile ducts, those are not applicable for clinical use, because the side reactions or toxic effects were observed in most of treated cases. Newly developed praziquantel(Embay 8440: Biltricide) is ar anthelmintic agent with high activity against abroad spectrum of cestode and.trematode infections in man and animals. Recently it was proven that praziquantel is the drug of choice for all species of schistosomes, liver flunkes(e.g. C. sinensis, Opisthorchis viverrini) and lung flukes (e.g. P. westermani and other species) pathogenic to man. Praziquantel cured completely in the patients with clonorchiasis with three doses of 25 ㎎/㎏ body weight given in a single day; for paragonimiasis the drug should be administered in three doses of 2㎎/㎏ per day for 2 days. Praziquantel is well tolerated, and side effects consist mainly of mild and transient headache and dizziness. Considering the ease of administration and the good acceptance as well as very good efficacy, praziquantel will have a great role to. play in the control of clonorchiasis and paragonimiasis in the near future.

寄生蟲性疾患의 治療 : 特히 새로 開發된 藥劑

林漢鍾 대한의학협회 1974 대한의학협회지 Vol.17 No.7

寄生蟲疾患의 化學的 療法

林漢鍾 대한의학협회 1979 대한의학협회지 Vol.22 No.11

우리나라의 풍토병 : 디스토마증에 대하여 The Liver and Lung Fluke Diseases

임한종 의학교육출판사 1988 Korean Journal of Family Medicine Vol.4 No.12

축분 퇴비화의 최적 환경조건에 관한 연구

임재명,오종민,박완철,한동준 경희대학교 환경연구소 1994 環境硏究 論文集 Vol.5 No.-

The composting process is a suitable to dispose the livestock manure in terms of resources recovery. However the performance of composting process is greatly affected by the environmental conditions such as characteristics of manure, type of the bulking agent, Initial moistuer contents, temperature, recycle and so on. The purpose of this study is to evaluate the optimum environmental conditions of composting process for livestock manure. The analytical results indicated that no bulking agent was necessary for the cow manure because of the proper C/N ratio. However the pig manure required a bulking agent since the pig manure had not only low in C/N ratio but poor ventilation characteristics. In addition, the initial moisture content for optimum composting appeared to be about 60%. The temperature control was also an essential factor to enhance the activity of thermophilic microorganisms in the laboratory composting unit. It was further found that the recycle of composts may contributed the completion of composting precess as well as C/N ratio reduction and moisture control.