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Efficacy of Interferon-Gamma Treatment in Bronchial Asthma (기관지천식에서 Interferon-Gamma 치료의 효과)

  • Kim, Kwan-Hyoung;Kim, Seok-Chan;Kim, Young-Kyoon;Kwon, Soon-Seog;Kim, Chi-Hong;Moon, Hwa-Sik;Song, Jung-Sup;Park, Sung-Hak;Lee, Choong-Eon;Byun, Kwang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.4
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    • pp.822-835
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    • 1997
  • Background : There have been many in vitro evidences that interleukin-4(IL-4) might be the most important cytokine inducing IgE synthesis from B-cells, and interferon-gamma(IFN-$\gamma$) might be a main cytokine antagonizing IL-4-mediated IgE synthesis. Recently some reports demonstrated that IFN-$\gamma$ might be used as a new therapeutic modality in some allergic diseases with high serum IgE level, such as atopic dermatitis or bronchial asthma. To evaluate the in vivo effect of IFN-$\gamma$ in bronchial asthma we tried a clinical study. Methods : Fifty bronchial asthmatics(serum IgE level over 200 IU/ml) who did not respond to inhaled or systemic corticosteroid treatment, and 17 healthy nonsmoking volunteers were included in this study. The CD 23 expressions of peripheral B-cells, the IL-4 activities of peripheral T-cells, the serum soluble CD23(sCD23) levels, and the superoxide anion(${O_2}^-$) generations by peripheral PMN were compared between bronchial asthmatics and normal subjects. The IL-4 activities of peripheral T-cells were analyzed by T-cell supernatant (T-sup)-induced CD23 expression from tonsil B-cells. In bronchial asthmatics the serum IgE levels and histamine $PC_{20}$ in addition to the above parameters were also compared before and after IFN-$\gamma$ treatment. IFN-$\gamma$ was administered subcutaneously with a weekly dose of 30,000 IU per kilogram of body weight for 4 weeks. Results : The ${O_2}^-$ generations by peripheral PMNs in bronchial asthmatics were higher than normal subjects($8.23{\pm}0.94$ vs $5.00{\pm}0.68\;nmol/1{\times}10^6$ cells, P<0.05), and significantly decreased after IFN-$\gamma$ treatment compared to initial values($3.69{\pm}0.88$ vs $8.61{\pm}1.53\;nmol/1{\times}10^6$ cells, P<0.05). CD23 expression of peripheral B-cells in bronchial asthmatics was higher than normal subjects($47.47{\pm}2.96%$, vs $31.62{\pm}1.92%$, P<0.05), but showed no significant change after IFN-$\gamma$ treatment. The serum sCD23 levels in bronchial asthmatics were slightly higher than normal subjects($191.04{\pm}23.3\;U/ml$ vs $162.85{\pm}4.85\;U/ml$), and 11(64.7%) of 17 patients showed a decreasing pattern in their serum sCD23 levels after IFN-$\gamma$ treatment. However the means of serum sCD23 levels were not different before and after IFN-$\gamma$ treatment. The IL-4 activities of peripheral T-cells in bronchial asthmatics were slightly higher than normal subjects($22.48{\pm}6.81%$ vs $18.90{\pm}2.43%$), and slightly increased after IFN-$\gamma$ treatment($27.90{\pm}2.56%$). Nine(60%) of 15 patients showed a decreasing pattern in their serum IgE levels after IFN-$\gamma$ treatment. And the levels of serum IgE were significantly decreased after IFN-$\gamma$ treatment compared to initial values ($658.67{\pm}120.84\;IU/ml$ vs $1394.32{\pm}314.42\;IU/ml$, P<0.05). Ten(83.3%) of 12 patients showed an improving pattern in bronchial hyperresponsiveness after IFN-$\gamma$ treatment, and the means of histamine $PC_{20}$ were significantly increased after IFN-$\gamma$ treatment compared to initial values ($1.22{\pm}0.29mg/ml$ vs $0.69{\pm}0.17mg/ml$, P<0.05). Conclusion : Our results suggest that IFN-$\gamma$ may be useful as well as safety in the treatment of bronchial asthmatics with high serum IgE level and that in vivo effects of IFN-$\gamma$ may be different from its in vitro effects on the regulations of IgE synthesis or the respiratory burst of PMN.

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Pharmacokinetic Study of Isoniazid and Rifampicin in Healthy Korean Volunteers (정상 한국인에서의 Isoniazid와 Rifampicin 약동학 연구)

  • Chung, Man-Pyo;Kim, Ho-Cheol;Suh, Gee-Young;Park, Jeong-Woong;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.;Han, Yong-Chol;Park, Hyo-Jung;Kim, Myoung-Min;Choi, Kyung-Eob
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.3
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    • pp.479-492
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    • 1997
  • Background : Isoniazid(INH) and rifampicin(RFP) are potent antituberculous drugs which have made tuberculous disease become decreasing. In Korea, prescribed doses of INH and RFP have been different from those recommended by American Thoracic Society. In fact they were determined by clinical experience rather than by scientific basis. Even there has been. few reports about pharmacokintic parameters of INH and RFP in healthy Koreans. Method : Oral pharmacokinetics of INH were studied in 22 healthy native Koreans after administration of 300 mg and 400mg of INH to each same person successively at least 2 weeks apart. After an overnight fast, subjects received medication and blood samples were drawn at scheduled times over a 24-hour period. Urine collection was also done for 24 hours. Pharmacokinetics of RFP were studied in 20 subjects in a same fashion with 450mg and 600mg of RFP. Plasma and urinary concentrations of INH and RFP were determined by high-performance liquid chromatography(HPLC). Results : Time to reach peak serum concentration (Tmax) of INH was $1.05{\pm}0.34\;hrs$ at 300mg dose and $0.98{\pm}0.59\;hrs$ at 400mg dose. Half-life was $2.49{\pm}0.88\;hrs$ and $2.80{\pm}0.75\;hrs$, respectively. They were not different significantly(p > 0.05). Peak serum concentration(Cmax) after administration of 400mg of INH was $7.14{\pm}1.95mcg/mL$ which was significantly higher than Cmax ($4.37{\pm}1.28mcg/mL$) by 300mg of INH(p < 0.01). Total clearance(CLtot) of INH at 300mg dose was $26.76{\pm}11.80mL/hr$. At 400mg dose it was $21.09{\pm}8.31mL/hr$ which was significantly lower(p < 0.01) than by 300mg dose. While renal clearance(CLr) was not different among two groups, nonrenal clearance(CLnr) at 400mg dose ($18.18{\pm}8.36mL/hr$) was significantly lower than CLnr ($23.71{\pm}11.52mL/hr$) by 300mg dose(p < 0.01). Tmax of RFP was $1.11{\pm}0.41\;hrs$ at 450mg dose and $1.15{\pm}0.43\;hrs$ at 600mg dose. Half-life was $4.20{\pm}0.73\;hrs$ and $4.95{\pm}2.25\;hrs$, respectively. They were not different significantly(p > 0.05). Cmax after administration of 600mg of RFP was $13.61{\pm}3.43mcg/mL$ which was significantly higher than Cmax($10.12{\pm}2.25mcg/mL$) by 450mg of RFP(p < 0.01). CLtot of RFP at 450mg dose was $7.60{\pm}1.34mL/hr$. At 600mg dose it was $7.05{\pm}1.20mL/hr$ which was significantly lower(p < 0.05) than by 450mg dose. While CLr was not different among two groups, CLnr at 600 mg dose($5.36{\pm}1.20mL/hr$) was significantly lower than CLnr($6.19{\pm}1.56mL/hr$) by 450mg dose(p < 0.01). Conclusion : Considering Cmax and CLnr, 300mg, of INH and 450mg RFP might be sufficient doses for the treatment of tuberculosis in Koreans. But it remains to be clarified in the patients with tuberculosis.

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한국 청소년의 약물남용과 비행행위

  • 김성이
    • Korea journal of population studies
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    • v.11 no.2
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    • pp.54-66
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    • 1988
  • I. Introduction Since the 1970's drug abuse among young people has increasingly become a social problem in Korea. In the 1980's, drug abuse, especially glue sniffing, has become the cause of many unfortunated incidents resulting in harm to others as well as the abusers themselves. Taking into consideration of the seriousness of this problem, the Republic of Korea National Red Cross initiated a nation-wide research programme, to understand the present situation and to raise the level of public awareness. The goal of this research was to begin a nation - wide campaign against drug abuse. The research team was composed of the Advisary Committee members and the staff of the Youth Department of the Republic of Korea National Red Cross. The data were collected in February 1988 with the collaboration of the staff and volunteers in the local Chapters. The respondents were allocated nation-wide by the quota sampling method. The questionnaires were distributed to the respondents in three groups :2, 700 to junior and senior high school students, 605 to working youths, and 916 to delinquent youths. A total of 4, 221 questionnaires were collected. II. Characteristics of the Respondents The respondents in each group were selected evenly from rural and urban areas. The general characteristics of the respondents can be described as follow: in case of students, the proportions between male and female respondents, and between senior high school and junior high school students were almost evenly distributed. In case of working youths, the proportion of females (80.5%) was higher than those of the students and the delinquents groups. Delinquent youths were defined as those currently being under custody of the centers for juvenile delinquents. Of this number, 38.8% and 68.2% were junior and senior high school drop-outs respectively. The majority of them (92.6%) were male. As for the family background of the respondents, the proportion of those residing in poverty - stricken areas, and the proportion of those from broken families were higher in case of working youths and delinquent youths than those in case of students. III. Present Patterns of Drug Abuse The following summarizes the presents of drug abuse, as tabulated from the results of the survey. 1. Smoking The percentage of youths who smoke was 36% in the student group, 32% m the working youths group, and 94.4% in the delinquent youths group. 2. Alcohol 50.3% of students, 71.6% of working youths, and 93.3% of delinquent youths has experienced drinking alcohol beverages. 3. Tonic: non - alcoholic, caffeinated beverages popular in Korea and Japan The percentage of those who have used tonic at least once was over 90% in all of the three groups. 4. Sedative About 70% of each group has used sedative with the proportion of working youths use higher than those in other groups. 5. Stimulants Those who have used stimulants comprised around 15% in each group. 6. Tranquilizers Somewhat less than 5% of students and working youths, and 28% of delinquent youths, have used tranquilizers. 7. Hypnotics The users of hypnotics amounted to 0.4% of students, 2.6% of working youths and 7.1% of delinquent youths. 8. Marihuana Those who have used marihuana indicated 0.7% of students, 0.8% of working youths, and 13% of delinquent youths. 9. Glue-sniffing The percentage of glue-sniffing was 3.7%, 5% in the students group and in the youths group respectively, but the proportion was unusually high, at 40.7% in the delinquent youths group. From the results of the survey the present situation of drug abuse in Korea can be summarized as follows: 1. A high percentage of Korean youths have experienced smoking cigarettes and drinking alcoholic beverages. 2. Tonics (non - alcoholic, caffeinated beverages), antipyretic analgesics and stimulants quite regularly used. 3. Tranquilizers, hypnotics, marihuana and glue-sniffing are more widely used among delinquent youths than the other youths. From this fact, there exists a correlation between drug abuse and juvenile delinquency. IV. Time-series Analysis of the First Experience of Drug Abuse and Deviant Behaviour The respoundents were asked when they were first exposed to drugs and when they committed deviant acts. By calculating the average age of each experience, the following pattern was found (See Figure 1). Youths are first exposed to drugs by abuse of tonic(non - alcoholic, caffeinated beverages). At the age of 13, they amoke cigarettes, the use of antipyretic analgesics begins at 14 year old, while at the age of 15, they use tranquilizers, and at 16 hynotics. The period of drug abuse which starts from drinking caffeinated beverages and smoking cigarettes and ends in the use of hypnotics takes about three years. During this period, other delinquent behaviours begin to surface, that is, at the age of 13 when smoking cigarettes begins, the delinquent behaviour pattern starts with truancy. Next, they start taking money from others by using physical force. Prior to the age of 15, they are suspended from school, become hostile to adults, begin running away from home, and start using stimulants and alcohol. Soon they become involved even in glue-sniffing and in the use of marihuana. At the age of 15, they begin to see adult videos and carry weapons. Sexual promiscuity and usage of tranquilizers follows the viewing of adult videos. Consequently, by the time they reach the age of 16, they visit drinking establishments, and are picked up by police for committing delinquent acts. And finally, they come to use hypnotic - type drugs. From the above descriptions, drug abuse can be assumed to have a close correlation with delinquent behaviour. V. Social Factors Related to Drug Abuse As for the Korean youths, glue-sniffing is found to he related to aggressive delinquency, in such cases as run - aways, being picked up by the police, and taking money by force. Smoking cigarettes and drinking alcohol is found to be related to seeing adult videos and visiting drinking establishments. Hypnotics and marihuana were found to be representive of drugs which are related to degenerational delinquency, irrespective of social delinquency. The social factors connected with these drug abuse are as follows: 1. Individual factors Male students were more heavily involved in the usage of drug than females. Youths who do not attend church were more likely to be involved in drugs than those who attend. 2. Family factors The youths who were displeased with their mothers smoking and those who thought their parents did not love each other, or those whose parents had used drugs without prescription, were more likely to he drug users. 3. School factors Those youths who found school life boring, were unsuccessful in their studies, spend most of their time with friends, feel their teachers smoke too much, those who had a positive perception of their teachers smoking were likely to he drug users. To sum up, drug abusers depend on the influence of their parents, teachers and peers. IV. Reasons for Drug Abuse Korean students have mainly used drugs to release stress (42.8%), to stay awake (19.7%), and because of the easy accessibility of drugs( 16.6%). Other reasons are due to their ignorance of the side effects of the drugs (3.6%), natural curiosity (4.2%), and to increase strength(3.O%). From the above facts, the major reasons for drug abuse among Korean youths are to release stress and to stay awake in order to prepare exams. Furthermore, since drugs are readily available, we can conclude that drug abuse is caused by the school system(such as entrance exams) in Korea. VII. Conclusion Drug usage among Korean youths are relatively less common than those of western youths. In some cases, such as, glue-sniffing and use of stimulants, the pattern of drug abuse is found. Moreover, early drug abuse is evident, and it has a close connection with deviant behaviour, resulting in juvenile delinquency. Drug abuse cannot be attributed to any one social factor. Specifically, drug abuse depends on parents, peers, teachers and other members of the community, and also is influenced by social institutions such as the entrance exam system. Every person and organization concerned with youth must participate collectively in restraining drug abuse. Finally, it is suggested that social agencial working for youth welfare should make every effort to tackle this serious problem confronted by the Korean youths today.

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