(The) rapeutic effect of rifampicin for the leprosy patients

의학과/박사[한글] DDS는 우수한 항나제로서 오늘날 임상적으로 널리 사용되고 있으나, 아직도 그 독성과 부작용에 대한 보고(Graham, 1975)와 함께 오랜 기간의 치료를 요하기 때문에 오는 불규칙적 복용, 복용중단해서 오는 재발등의 보고(Quagliato등, 1970)가 있으며 한편 설폰(sulfone) 내성 인나균(人癩菌)의 출현에 관한 보고도 있다(Pettit 및 Rees, 1966: Pearson등, 1976). 따라서 많은 연구자들은 더욱 강력하고 효과적이며 단기간내에 치료효과를 볼 수 있는 새로운 항나제의 개발에 노력하고 있다. Opromolla(1963)에 의해 처음으로 경구용 rifamycin SV를 10명의 나종양형 나환자 치료에 사용한 이래 rifampicin의 나병 치료효과에 관해서는 다양한 보고가 있으며, 근래에 새로운 항나제로서 각광을 받기 시작하였으나 아직도 rifampicin의 나병 치료에 있어서 유효 투여량, 적정투여기간 및 장기 치료효과등에 대하여 연구자들간에 논란이 되고 있다. 이에 저자는 1970년 1월부터 1976년 6월까지 세계 기독교 선명회 특수피부진료소에 등록된 나종양형 나환자 96예를 대상으로하여 DDS와 함께 rifampicin의 나병 치료효과를 비교 관찰하고자 세균학적 및 임상적 치료성적을 중심으로 비교검토한 바 다음과 같은 성적을 얻었다. 1. 신환자군의 rifampicin 단독투여 및 rifampicin과 DDS 병용투여군에서 25개월에서 36개월간 투여한 8예 및 2예 가운데 각각 3예 및 1예의 균음전예를 관찰할 수 있었으며 세균지수의 무변화 또는 악화됨 예는 관찰할 수 없었다. 한편 DDS 단독투여군에서는 25개월에서 36개월간 치료한 30예 가운데 2예의 균음전화를 관찰할 수 있었으며, 2예에서 세균지수의 무 변화를 관찰할 수 있었다. 구환자군에서는 rifampicin 단독투여군 및 rifampicin과 DDS 병용투여군의 치료 25개월에서 36개월까지 관찰한 4예 및 7예 가운데 각각 1예 및 5예의 균음전예를 나타냈으며 rifampicin 단독투여군에서만 1예의 세균지수 무변화를 나타냈다. 2. 신환자군의 rifampicin 단독투여군에서 치료 36개월 후에 있어서 평균세균지수의 감소는 3.3이었으며, rifampicin과 DDS병용투여군에서는 2.4, DDS 단독투여군에서는 1.4로서 rifampicin투여군의 평균세균지수 감소가 DDS 단독투여군에 비하여 현저함을 보였다. 구환자군의 평균세균지수의 감소는 치료 36개월 후에 rifampicin 단독투여군에서 1.2, rifampicin과 DDS 병용투여군에서 1.8의 감소를 보였다. 3. Rifampicin 단독투여 또는 rifampicin과 DDS 병용투여가 나종양형 나환자와 임상적 증상의 호전에 있어 DDS 단독투여시 보다 신속하며 우수한 치료효과를 나타냈다. 4. Rifampicin투여시 수반되는 부작용으로는 신경염을 수반한 신경통 및 ENL을 관찰할 수 있었으나 DDS 단독투여시에 비하여 낮은 발생율을 보였다. 이상의 성적으로 미루어 보아 나병치료에 있어서 rifampicin은 DDS에 비하여 신속하고 현저한 치료효과를 관찰할 수 있었다. [영문] Introduction DDS is an excellent antileprosy drug and has been a drug of choice to treat leprosy clinically. However, there are many reports that after taking DDS, mild toxic and hypersensitive reactions have been observed. Also, DDS requires such a long therapeutic period to be effective that partients take treatment irregularly and finally stop medication altogether. Because of this, relapses are often reported (Quagliato et al, 1970). Also, sulfone-resistant M. leprae have been reported (Pettit and Rees, 1966, Pearson, 1976). Therefore, there has been much research done to find more efficient and potent antileprosy drugs. Since Opromolla(1963) firsts introduced rifamycin SV as an antileprosy drug to 10 lepromatous type leprosy patients there have been many reports about the antileprosy effects of rifampicin. Nowadays rifampicin is appearing as a new antileprosy drug, but there is still much discussion about the most effective dosage, the duration of treatment, and therapeutic effects of rifampicin. In this study, ninety-six lepromatous type leprosy patients who had been registered at the World Vision Leprosy Research and Treatment Center from Jan. 1970 to June 1976 were treated with DDS and rifampicin. The therpeutic effects after taking rifampicin were compared with those after taking DDS by means of comparing the respective patients' bacteriological and clinical evaluations. Materials and Methods A. Materials Ninety-six lepromatous type leprosy patients, who were registered at the World Vision Leprosy Research and Treatment Center from January 1970 to June 1976 were selected. These patients were divided into two groups: the new patient group and the old patient group. 1. New Patient Group: For the new patient group, fifty-four patients were selected who had never been treated from the onset of their disease to the beginning of this study. These patients were divided into three classes. The first class( Ⅰ ) included fourteen patients who had been treated with rifampicin only, the second class( Ⅱ ) included ten patients who had been treated with rifampicin combined with DDS, and the third class( Ⅲ ) included thirty lepromatous type leprosy patients were selected who had been treated with DDS only since the beginning of their treatment. 2. Old Patient Group: For the old patient group, forty-two lepromatous type leprosy patients were selected who had been treated with DDS and other antileprosy drugs for one year or more before the start of the study and had shown no change in their symptoms from taking DDS or other antileprosy drugs. We divided these patients into two classes. One( Ⅳ ) included nine patients who had been treated with rifampicin only and the other included thirty-three patients who had been treated with rifampicin combined with DDS( Ⅴ ). B. Methods 1. Administration of antileprosy drugs; Each of the classes was subdivided into three subclasses which were treated for 12 months(C), 13-24 months(B) and 25-36 months(A) respectively. In classes Ⅰ, patients were given 150-300 mg of rifampicin per day. In classes Ⅱ and Ⅴ, patients were given a dose of 150-300 mg of rifampicin per day and 200-300 mg of DDS per week. In class Ⅲ, DDS was administered in dose or 350-600 mg per week. 2. Method of Evaluation a. Bacteriological Evaluation; The bacteriological evaluation was based on a comparision of the change of the Bacterial Index(B.I.), Granularity Index(G.I.) and Solid Fragmented and Granulearity(S.F.G.) value of the patients in the new and old patient group. b. Clinical evaluation; The clinical evaluation was based on the clinical improvement in the lepromatous infiltrations and nodules from the start of the study. The degree of clinical improvement was graded as deterioration of the condition, no change, a easily visible improvement, a marked diminution of the cutaneous signs, and a complete disappearance of all cutaneous signs. Conclusions 1. Among new patient groups, 3 out of 8 patients treated with rifampicin alone and 1 out of 2 patients treated with rifampicin and DDS together became B.I. negative after thirty-six months treatment No aggrevated or stationary cases in B.I. were observed. Among the 30 cases who were treated with DDS alone for thirty-six months, 2 cases were found to be B.I, negative and 2 cases without changes in B.I. inspite of the treatment. In tHe old patient group of 7 patients treated with rifampicin alone and 7 patients treated with a combination of rifampicin and DDS, 4 cases and 5 cases respectively were found to be negatively converted. I case among the cases who received rifampicin alone showed no change in B.I. 2. In the new patient group, the decrease in average B.I. of the patients who were treated with rifampicin only was 3.3, while the decrease on average B.I. of the patients treated with a combination of rifampicin and DDS was 2.4 and that of the patients treated with DDS only was 1.4 after taking drugs for thirty six months. With this, the decrease in average B.I. of the group treated with rifampicin was more pronounced than that of the group treated with DDS. In the old patient group, the decrease in average B.I. of the patients treated with rifampicin alone was 1.2 and of the patients treated with rifampicin combined with DDS, 1.8, after taking drugs for thirty-six months 3. When looking at the clinical symptoms of lepromatous type leprosy patients, the regimen of rifampicin alone or rifampicin combined with DDS proved more effective and faster than giving the patients DDS alone. 4. The side reactions after taking rifampicin were neuralgia and E.N.L., but these were more mild and of lower frequency than the side reactions after taking DDS alone. From the above results, it is concluded that rifampicin has greater and faster therapeutic effects in the control of leprosy than DDS.restrictio

Effects of iproniazid and lithium on blood alcochol level in rabbits

의학과/석사[한글] [영문] In recent years, it has been known that lithium has marked psychotropic effects in controlling manic excitement, various other psychotic excitements and the recurrence of both manic and depressive symptoms. Iproniazid is the very first antidepressant which first introduced in medicine as a antituberculous agent in 1951. Thereafter many investigators established that iproniazid waw of particular value in treating patients with depression and that iptoniazid was an inhibitor of monoamine oxidase. Its usage, however, gad been discontinude around 1960 due to severe hepatotoxicity. It has lately been reported that lithium and several other psychotrophic drugs elevated the blood alcohol level in rabbits. In view of these reports the author conducted an animal experiment to investigate the effects of iproniazid, alone or in combination with lithium ion, on blood alcohol level in rabbits. Materials and Method 1. The experimental work was dome with mature rattits of both sexes, weighing between 2.0kg and 3.0kg. 2. The experimental animals were divided into 2 groups ; control and experimental. The control group was given alcohol alone and the experimental group was divided into 3 subgroups ; alcohol + iproniazid group, alcohol + lithium group and alcohol + iproniazid + lithium group. 3. Iproniazid was given orally in a capsule form, 30mg/kg of body weight, in 3 divided doses a day for 5 days. The last dose of iproniazid was given 1.5 hours before alcohol administration. 4. Lithium chloride solution, 6.36%, was given in a dose of 3.0mEq/kg of body weight a day for 4 days by intravenous route. The last dose was given 1 hour before alcohol administration. 5. In all group, 20 Vol. % ethanol solution was given in a dose of 5.0ml/kg of body weight in 5 minutes by intravenous route. 6. All of the blood specimens were obtained by cardiac puncture at 10 and 30 minutes respectively after alcohol administration, but additional blood specimens were obtained form the alcohol + iproniazid group at 20 minutes after alcohol administration. 7. The blood alcohol level was determined by Cavett's method. 8. In order to observe histopathological changes of the liver cell, the experimental animals were divided into 2 groups, control and experimental. To control group, normal saline was given in a dose of 5.0ml/kg body weight for 5 days by intravenous route. Experimental group was diveded into 3 subgroups. To the first subgroup, iproniazid was given for 10 days, to the second subgroup, lithium was given for 9 days and to the third subgroup, iproniazid combined with lithium were given. All animals were sacrefied by intravenous injection of air. 9. For the light microscopic examinations. histopathological alteration of the liver cells was observed by the routine hematoxilin-eosin staining techique. 10. For the electron microscopic examinations, the liver tissue was fixed in 1% osmium tetroxide(OsO4), dehydrated with graded alcohol and embedded with Epon 812. The sections were cut with a glass knife in 400-500 thickness and stained with uranyl acetate and lead hydroxide. The pictures were taken with the Hitachi model HU 11E-1 type electron microscope. Results 1. Alcohol + iproniazid group : Iproniazid significantly elevated the blood alcohol level at 10, 20 and 30 minutes after alcohol administration(P<0.05). 2. Alcohol + lithium group : Lithium elevated the blood alcohol level significantly at both 10(P<0.01) and 30 miniter(P<0.05) after alcohol administration. 3. Alcohol + iproniazid + lithium group : Iproniazid combined with lithium elevated significantly the blood alcohol level at both 10 and 30 minutes after alcohol administration(P<0.01). The blood alcohol levels of these groups were significantly higher than those of alcohol + iproniazid group and alcohol + lithium group(P<0.05). 4. Electron microscopic findings : Inproniazid group revealed mild swelling of mitochondria loss of cristae and dense body in cytoplasm. Lithium group revealed enlarge nucleus and nucleolus and scattered glycogen in cytoplasm. Iproniazid + lithium group revealed separated nucleolus in enlarged nucleus with irregular nuclear membrane and dilatated rough endoplasmic reticulum and several vacuoles in cytoplasm. Conclusions 1. the orally administered iproniazid in a dose of 30mg/kg a day for 5 days elevated significantly the blood alcohol level in rabbits at 10, 20 and 30 minutes after alcohol administration. 2. The intravenous injection of lithium cholride in a dose of 3.0mgEq/kg a day for 4 days elevated significantly the blood alcohol level in rabbits at both 10 and 20 minuter after alcohol administration. 3. The iproniazid combined with lithium cholride elevated significantly the blood alcohol level in rabbits at both 10 and 30 minutes after alcohol administration. 4. On electron microscopy, iproniazid group, in which iproniazid was given orally in a dose of 30mg/kg of body weight a day for 10 days revealed mild swelling of mitochondria loss of cristae and dense body in cytoplasm, lithium group, in which lithium chloride solution, 6.36% was given intravenousely in dose of 3.0 mEq/kg of body weight a day for 9 days revealed enlarged nucleus and nucleolus and scattered glycogen in cytoplasm and iproniazid combined lithium group, in which iproniazid was given for 10 days and lithium was given for 9 days revealed separated nucleolus in enlarged nucleus with irregular nuclear membrane and dilatated rough endoplasmic reticulum and vacuoles in cytoplasm.restrictio