Levamisole therapy in corticosteroid-dependent nephrotic syndrome

The effect of prolonged treatment with levamisole was examined in 43 patients (30 boys) with steroid-dependent nephrotic syndrome (SDNS). The mean age at institution of treatment was 4.0±2.0 years. Fourteen patients had previously received cyclophosphamide with an ensuing remission of 8.5±10 months. Following induction of remission with prednisolone, levamisole was administered at a dose of 2.5 mg/kg body weight on alternate days. Prednisolone was tapered by 2.5 – 5 mg every 4 weeks to 0.5 mg/kg on alternate days. The duration of levamisole therapy ranged from 6 to 31 months (mean 17.4±8.4 months); 15 patients received levamisole for more than 18 months and 10 for more than 24 months. Prednisolone was discontinued in 18 patients after a mean duration of 11.7±7.1 months, whereas in 21 patients its dose was reduced to 0.2 – 0.4 mg/kg on alternate days. The mean relapse rate prior to levamisole therapy was 3.0±1.5 relapses/year, which reduced to 0.9±0.7 relapses/year during levamisole treatment (P <0.001). A comparison of the response in 14 patients who had previously received cyclophosphamide with the other 29 patients did not show any significant difference. There were no side effects of levamisole therapy. Our findings suggest that prolonged treatment with levamisole is beneficial and safe in SDNS, with a marked steroid-sparing effect. A significant proportion of these patients can be kept in remission on levamisole alone. Received March 26, 1996; received in revised form and accepted January 16, 1997     

Effects of Levamisole on Ethanol-Induced Suppression of Lactational Immune Transfer in Rats

Maternal ethanol consumption in rats has been shown to inhibit lactational transfer of immunity to Trichinella spiralis (T. spiralis) from dams to their neonates. The purpose of this study was to determine if this depressed immune transfer could be altered by treating the dams with a known immunostimulatory drug during pregnancy and lactation. Groups of female rats were fed ethanol-containing or were pair-fed isocaloric control liquid diets for 30 days, infected orally with 1,000 T. spiralis larva, and then continued on diet for 10 days to allow the adult worms to establish. The animals were placed on chow diets (maximum 5 days) and mated 1 to 1 with males. On day 1 of pregnancy the animals were returned to their respective liquid diets through pregnancy and lactation. One-half of the ethanol-treated animals was given 15 mg/kg body weight of levamisole in the diet beginning on day 10 of pregnancy and continuing until day 17 of lactation. On day 19 of lactation, pups from all experimental groups were challenged orally with 200 T. spiralis larva, and killed at 3 or 8 days postchallenge. Assays for intestinal worm burdens, IgG anti-T. spiralis serum antibodies, and mesenteric lymph node cell proliferation were conducted. At both sacrifice periods, pups from ethanol-treated animals showed significantly higher intestinal worm counts (decreased immunity) and significantly lower titers of specific antibodies than the pups of pair-fed animals or pups of animals receiving levamisole in addition to ethanol. There were no differences between pups of the ethanol/levamisole dams and pair-fed dams in worm counts or antibody titers. No differences in mesenteric lymph node cell proliferation in response to T. spiralis antigen or to concanavalin A was observed between the three groups. These results indicate that administration of levamisole to ethanol-induced, immunosuppressed dams can reverse some of the deleterious effects normally seen in lactational immune transfer to suckling pups.     

Restoration of Defective Cellular Immunity by Levamisole in a Patient with Immunoblastic Lymphadenopathy

A 71-year-old woman presented with acutely developed symptoms of generalized lymphadenopathy, intermittent maculo-papular skin rash, pruritus, weight loss, hepato-splenomegaly, pleural exsudate and alternating breast swellings. The histo-pathological picture of biopsies from a lymph node and from the skin was diagnostic for immunoblastic lymphadenopathy, and the serum concentrations of IgG and IgA were increased. Delayed cutaneous hypersensitivity reactions to various antigens were totally extinguished and the number of T-lymphocytes in the peripheral blood was consistently very low. The number of both T- and B-lymphocytes further decreased during cytostatic treatment and the patient contracted numerous infections. During intermittent treatment with Levamisole the infectious episodes ceased, the cellular immune response was reestablished and the pathological hyperimmuneglobulinaemia suppressed. It is suggested that the primary immunological defect in this disease could be a failing cellular immunity, and that the hyperplasia and hyper-reactivity of the B-cell system are a secondary phenomenon.     

Antirheumatic drugs ands macrophage function: Effects on tumour cell crowth in vitro

Summary The ability of the antirheumatic drugs D-penicillamine, chloroquine and levamisole to modify macrophage-mediated inhibition of tumour cell growth in vitro was investigated. Increasing numbers of rat peritoneal macrophages were cocultured with a fixed number of ascites hepatoma AH-13 rat tumour cells. Tumour cell growth was assessed as the uptake of³H-thymidine (³H-TdR) by AH-13 cells at the end of a 24h period of coculture with macrophages treated in vitro or in vivo with the various drugs. In vitro, preincubation of macrophages with D-penicillamine or chloroquine (50 – 250 g/ml) increased tumour cell³H-TdR incorporation, compared to cultures with untreated macrophages. Macrophages from rats treated with D-penicillamine or chloroquine (50 mg/kg/day orally) for 4 days similarly increased tumour cell³H-TdR incorporation, compared to cultures with macrophages from untreated rats. These effects persisted for at least 3 to 4 weeks of treatment. Preincubation with levamisole (10 – 100 g/ml) in vitro had no effect on macrophage-mediated inhibition of tumour cells, whereas increased tumour cell³H-TdR incorporation was observed in cultures with macrophages from rats treated with levamisole (5 mg/kg/day orally) in vivo. Macrophages from rats with experimentally induced chronic inflammation, i.e. adjuvant arthritis, were found to increase tumour cell³H-TdR incorporation, compared to macrophages from nonarthritic rats. This trend was further enhanced by treatment with D-penicillamine, chloroquine or levamisole.     

No effects of levamisole on cytotoxic drug-induced changes of human granulopoiesis

Summary The effect of Levamisole on the human granulopoiesis was studied in patients randomized to receive, in addition to adjuvant chemotherapy for primary breast cancer, either no other treatment or additional unspecific immune therapy with Levamisole. The reaction of granulopoiesis to the cytostatic drugs, as characterized by changes of peripheral blood polymorphonuclear neutrophils (PMN), functional bone marrow granulocyte reserve, serial bone marrow cytology, and granulopoietic stem cells (CFU-C) in marrow and blood, was not affected by administration of Levamisole. The data support the concept that Levamisole has no direct effect on human bone marrow granulopoiesis, but that an allergic mechanism is involved in the pathogenesis of Levamisole-induced agranulocytosis. The expectation that Levamisole exerts a beneficial effect by stimulation of the granulopoiesis, as previously suggested for BCG and Corynebacterium parvum, could not be substantiated in our studies.Levamisole was kindly supplied by Janssen GmbH, Dtisseldorf     

百蕊片联合左旋咪唑治疗多发性寻常疣50例临床观察

目的探讨百蕊片治疗多发性寻常疣的疗效。方法105例多发性寻常疣患者分成两组,治疗组口服百蕊片和左旋咪唑,对照组只口服左旋咪唑,6周后对比疗效。结果治疗组与对照组的有效率分驯为86．0％、62．5％,两组有效率差异有统计学意义（P〈0．01）。结论百蕊片治疗多发性寻常疣有效。     

左旋咪唑搽剂联合拉咪夫啶治疗慢性乙型肝炎对HBeAg血清转换率的影响

 目的观察左旋咪唑搽剂联合拉咪夫啶治疗慢性乙型肝炎对HBeAg血清转换率的影响.方法108例慢性乙型肝炎患者根据治疗前血清ALT水平,分为A、B、C 3组,各组随机分为两组,用药方式:(1)联合用药组:左旋咪唑搽剂(LL)5ml均匀涂于四肢皮肤上,2/周,拉咪夫啶(LMI)100mg口服,1/d,连续用药6个月.(2)单一用药组:拉咪夫啶(LMI)100mg口服,1/d,连续用药6个月.结果在A、B、C 3组中联合用药组HBeAg血清转换率明显高于单-用药组(P＜0.05);治疗前血清ALT＞ULN(正常上限)2～5倍者HBeAg血清转换率明显高于ALT在ULN＜2倍或正常者.结论联合用药可提高HBeAg血清转换率;治疗前ALT水平也是影响HBeAg血清转换率的一个重要因素.     

小剂量环孢素联合左旋咪唑治疗非重型再生障碍性贫血的临床探讨

目的探讨小剂量环孢素联合左旋咪唑治疗非重型再生障碍性贫血的临床疗效,为临床诊断治疗提供参考。方法将该组82例非重型再生障碍性贫血患者按照随机数字表法将其分为对照组和治疗组,每组41例;对照组给予一定剂量环孢素治疗,治疗组给予小剂量环孢素及左旋咪唑治疗;两组治疗均以6个月为1个疗程。结果治疗组总有效率（73.17%）与对照组（78.05%）对比,差异无统计学意义（P〉0.05）;两组患者治疗后血红蛋白、血小板、中性粒细胞水平与治疗前对比差异有统计学意义（P〈0.05）;治疗组治疗后血红蛋白、中性粒细胞水平与对照组治疗后对比,差异无统计学意义（P〉0.05）;治疗组治疗后血小板水平显著高于对照组治疗后,且差异有统计学意义（P〈0.05）;治疗组总不良反应率（51.52%）显著低于对照组（7.32%）,且差异有统计学意义（P〈0.05）。结论小剂量环孢素联合左旋咪唑治疗费重型再生障碍性贫血疗效确切,可显著减少环孢素的不良反应发生,该治疗方案值得临床推广。     

Nafion修饰玻碳电极测定微量左旋咪唑的研究

以玻碳电极为基体,制备了nafion修饰电极,研究了非电活性阳离子药物左旋咪唑在该电极上的测定方法及作用机理。将左旋咪唑加到含电活性阳离子药物多巴胺的电解质溶液中,使多巴胺峰电流下降,峰电流的降低与左旋咪唑的浓度对数在2×10^-6～8×10^-5mol·r^-1范围内呈良好线性关系,本方法的检测下限为1×10^-6mol·L⁶,回收范围为96.8%～105.8%,相对标准偏差为3.2%(n=10)。     

Steroid sensitive nephrotic syndrome

Nephrotic syndrome in children is a common recurrent disease. Most of the cases are due to minimal change disease with a favourable outcome. More than 90% of children with minimal change disease respond to corticosteroid therapy (steroid sensitive nephrotic syndrome). 40–60% experience frequent relapses or have steroid dependence. These children require frequent corticosteroid therapy andJor immunomodulators or treatment with immunosuppressants, and are at high risk of cumulative steroid toxicity and side effects of cytotoxic therapy. Children with frequent relapses or steroid dependence should be managed in consultation with a pediatric nephrologist. Despite relapsing course, progression of minimal change nephrotic syndrome to end stage renal disease is extremely rare.