Clinical application of tacrolimus with low-dose prednisone in 21 children with steroid-resistant nephrotic syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze and evaluate the efficacy and safety of tacrolimus and low-dose steroids in the treatment of steroid-resistant nephrotic syndrome in children.</p><p><b>METHOD</b>Twenty-one children with steroid-resistant nephrotic syndrome enrolled from October 2008 to July 2010 into this retrospective longitudinal study received oral tacrolimus treatment, 0.1 to 0.15 mg/kg per day and once every 12 hours, and prednisone 0.2 to 0.75 mg/kg per day simultaneously. During the treatment, the plasma concentration of tacrolimus, urine volume, urine, serum creatinine and liver function were regularly monitored.</p><p><b>RESULT</b>After 1 to 3 months treatment, 14 cases showed complete remission and 7 cases had partial remission. Sixteen patients received renal biopsy, of whom 6 revealed minimal change nephropathy with complete remission in 3 cases, 3 cases had partial remission;4 cases revealed focal segmental glomerulosclerosis with 2 complete remission and 2 partial remission; other 5 children with IgM nephropathy and 1 mesangial proliferative glomerulonephritis achieved complete remission. Within treatment period, 6 patients presented transient adverse reactions, without altering the principle treatment strategy, but only taking the symptomatic treatment. During follow-up, 1 case was lost to follow-up and the remaining 20 cases were followed up from 2 months to 21 months. In 4 patients the disease relapsed within 1st-year follow-up, while at 2nd-year follow-up, 4 cases had (6 times) recurrence.</p><p><b>CONCLUSION</b>Tacrolimus showed a reliable effect in children with steroid-resistant nephrotic syndrome. Less adverse reactions were seen, and most of them could be tolerated. Nevertheless, the patients had a higher relapse rate after 1 to 2 years treatment. Therefore, the long-term effects of tacrolimus for steroid-resistant nephrotic syndrome remains to be further evaluated.</p>

The relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 expression.

PURPOSE: The objective of our study was to characterize the relationship between the protective effect of amifostine and decreased intercellular adhesion molecule 1 (ICAM-1) expression in early-phase, radiation-induced otitis media and to illustrate the possible mechanism of early-phase radiation-induced otitis media. MATERIALS AND METHODS: A comparison study of middle ear tissue was performed by the expression of ICAM-1 and the electron microscope from total 38 guinea pigs. Group A, consisting of 2 pigs, was used as control, and these pigs were not irradiated. Groups B, C, D, and E, consisting of 9 pigs each, were irradiated. Sterile saline was administered intraperitoneally to the pigs in groups B and D before irradiation, and amifostine was administered intraperitoneally as an aqueous solution 30 minutes before irradiation to the pigs in groups C and E. The pigs in groups B and C were killed on the second day after irradiation, and the pigs in groups D and E were killed 30 days after irradiation. RESULTS: Intercellular adhesion molecule 1 was strongly expressed in the middle ear mucosa of the irradiated pigs after a 45-Gy dose of radiation was administered. Enhanced ICAM-1 expression was accompanied by pathomorphologic changes in the middle ear tissue. Scanning electron microscopy demonstrated the changes. Intercellular adhesion molecule 1 expression in the mucosa of the groups killed on the second day was stronger than that in the mucosa of the groups killed 30 days after irradiation. Amifostine protected the middle ear from radiation injury, and we found that the expression of ICAM-1 in the middle ear mucosa was down-regulated. However, slight expression of ICAM-1 remained 30 days after irradiation. CONCLUSIONS: Irradiation increased the expression of ICAM-1 in the middle ear mucosa. Amifostine protected the middle ear from early irradiation injury. There was a relationship between oxygen free radicals derived from irradiation and up-regulation of ICAM-1 expression. Continuous ICAM-1 expression might be related to stenosis of the eustachian tube.

Study on elimination delay in high dose methotrexate therapy in childhood acute lymphoblastic leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To observe the incidence of elimination delay in high dose methotrexate (HDMTX) therapy, its side effects and influence to next course of chemotherapy and analyze the relationship between the dosage, the duration of MTX infusion and the morbidity of the elimination delay.</p><p><b>METHODS</b>A total of 121 childhood acute lymphoblastic leukemia (ALL) (497 infusions of HDMTX) were analysed in this study. The elimination delay rate and the adverse effects in different dose groups (3 g/m2 vs 5 g/m2) and different infusion duration groups (7 h vs 24 h) were compared. The adverse effect evaluation was based on the World Health Organization (WHO) Toxicity Grading Criteria. The rescue dosages of calcium folinate (CF) among these groups were compared through CF/MTX index.</p><p><b>RESULTS</b>The overall morbidity of elimination delay was 12.1% with a relative risk of 30.6% for the first time. The relative risk for the second time of occurrence was increased to 45.9% (P < 0.01) and it was not significantly increased for the third time (35.3%). Children with elimination delay had lower platelet count (P < 0.01) and higher CF rescue dosage (P < 0.01), while the damage of oral mucous membrane was more severe (P < 0.05) and the next course of chemotherapy would be postponed for a median of 4 days in 3 g group. There was no significant difference in elimination delay rates between 3 g and 5 g groups (12.1% vs 12.0%, P > 0.05), and between 7 h and 24 h MTX infusion groups (13.6% vs 11.9%, P > 0.05). The only side effect occurred in 5 g group was gastrointestinal morbidity. The CF/MTX index of 5 g group without elimination delay was less than that of 3 g group (P < 0.01).</p><p><b>CONCLUSION</b>Elimination delay in HDMTX therapy accompanies the suppression of bone marrow and damage of oral mucous membrane, which need more CF rescues and will postpone the following course of chemotherapy. Elimination delay is not associated with the duration of the infusion and the dosage of MTX within the range of 3 approximately 5 g/m2 but there are individual differences.</p>