Corticosteroid rescue in late paediatric acute respiratory distress syndrome

Late acute respiratory distress syndrome (ARDS) is associated with a mortality of more than 80%. Recent reports in adults have shown improved survival in late ARDS treated with prolonged course of steroids, however little data are available in children concerning its safety and efficacy. We report the successful treatment of a child dying from refractory late ARDS using a prolonged course of high-dose methylprednisolone instituted after 12 days of advanced mechanical ventilation. Progressive improvement was seen from days 3, 7, 10 and 14 after treatment with improvement in PaO2/fraction of inspired oxygen (FiO2) ratios, lung injury score and chest radiographical score. Treatment was complicated by a fungal urinary tract infection that was easily controlled. There were no major metabolic side effects. Steroid therapy can be considered in the treatment of children with refractory late ARDS but larger prospective studies are needed to define indications, timing, dosing and safety of this mode of treatment in children.     

糖皮质激素冲击治疗Ⅲ期结核性脑膜炎疗效观察

目的探讨糖皮质激素冲击治疗晚期结核性脑膜炎的有效性和安全性。方法将50例Ⅲ期结核性脑膜炎患者随机分为两组，在抗痨治疗的基础上，治疗组（25例）给予甲基强的松龙500mg/d静脉滴注冲击治疗5d后，迅速减至80mg/d后逐渐减量，对照组（25例）z给予地塞米松15mg/d治疗，症状明显好转后减量，两组激素使用疗程均最多10周。结果治疗组意识障碍恢复时间、体温恢复时间等均优于对照组（P〈0．05）；疗程12周时的治愈率、好转率及后遗症比较，治疗组均优于对照组（P〈0．05），不良反应间差异无统计学意义。结论大剂量甲基强的松龙冲击治疗Ⅲ期结核性脑膜炎疗效显著且不良反应无明显增加。     

甲泼尼龙、丙种球蛋白联合冲击治疗多发性硬化14例疗效分析

目的　分析大剂量甲泼尼龙联合丙种球蛋白冲击治疗多发性硬化 ( MS)的临床疗效。方法　对 1 994—2 0 0 2年采用大剂量甲泼尼龙、丙种球蛋白联合冲击治疗的 1 4例复发 -缓解型 MS患者进行回顾性分析。应用SPSS1 0 .0 ,进行两独立样本的 t检验。结果　治疗组见效时间、缓解时间、平均住院天数分别为 ( 4 .0± 1 .6)、( 2 1 .2± 3 .2 )、( 2 5 .0± 5 .9) d,均较对照组短 ( P <0 .0 5 )。结论　对于复发 -缓解型 MS,大剂量甲泼尼龙、丙种球蛋白联合冲击治疗可取得较好的疗效。     

High dose intravenous methylprednisolone for Kassabach-Merritt syndrome

Kassabach-Merritt syndrome involving the sternum in a 2-month-old child is described. Treatment with high dose intravenous methylprednisolone resulted in normalization of the platelet count and disappearence of haemangioma.Abbreviations K-MS Kassabach-Merritt syndrome - DIC disseminated intravascular coagulation - i.v. MP intravenous methylprednisolone     

Glucocorticoid mechanisms in acute spinal cord injury: A review and therapeutic rationale

This review seeks to provide pharmacological evidence that intensive glucocorticoid dosing can enhance sensorimotor recovery after blunt spinal cord trauma. It is suggested that high doses of glucocorticoids can beneficially affect the injured cord through the influence of at least three mechanisms. These are: (1) a facilitation of neuronal excitability and impulse conduction; (2) an improved blood flow; and, perhaps most importantly, (3) the preservation of cord ultrastructure through a reduction of injury-induced, free radical-catalyzed lipid peroxidation. In the case of methylprednisolone, the minimal intravenous dosage required to initially achieve each of these effects is in the range of 15 to 30 mg per kilogram of body weight, which is beyond that used currently for neurosurgical purposes. In addition, based upon the hypothesized mechanism of action and the tissue pharmacokinetics, the earliest possible initiation of therapy is imperative and rigorous maintenance dosing for an as yet undetermined length of time is needed.     

High-dose intravenous methylprednisolone for acute childhood idiopathic thrombocytopenic purpura

49 children with acute idiopathic thrombocytopenic purpura (ITP) were divided into non-treatment, oral prednisone (2 mg/kg), and high-dose intravenous methylprednisolone (HIVMP) treatment groups which consisted of 17, 16 and 16 children respectively. Platelet counts rose above 150,000/microliters over a 2-week period in 5 (29.4%) children in the first group, 5 (31.2%) in the second group and 15 (93.7%) children in the third group. Platelet counts reached the normal level in only 3 days in 11 (68.7%) children treated with HIVMP. Initially, antiplatelet antibodies (APA) were shown by the Handin and Stossel method in every patient. With normalization of platelet counts, the antibodies decreased but could still be detected in every case; antibody decrease was greater in the HIVMP group. With the exception of mild cushingoid appearance, none of the major corticosteroid side effects was observed in the treated children.     

Receptor-mediated methylprednisolone pharmacodynamics in rats: Steroid-induced receptor down-regulation

Several approaches to receptor down-regulation were examined to extend previous receptor/ genemediated pharmacokinetic/dynamic models of corticosteroids. Down-regulation of the glucocorticoid receptor was considered as an instantaneous event or as a gradual steroid-receptor-mediated process. Concentrations of plasma methylprednisolone, free hepatic cytosolic receptors, and the activity of hepatic tyrosine aminotransferase (TAT) enzyme were measured for 16 hr following administration of 0, 10, and 50 mg/kg methylprednisolone sodium succinate to 93 adrenalectomized rats. Receptor down-regulation was best described by a fractional decrement in the rate of return of free cytosolic glucocorticoid receptor. Predicted values for free receptor, bound receptor, nuclear bound receptor, and transfer compartments were in accord with the expected rank order values based on the high and low steroid doses. Model parameter estimates were independent of dose and described the rapid depletion of free cytosolic receptor, latephase return of cytosolic receptor to a new baseline level that was 20–40% lower than control, and the TAT induction/dissipation pattern following steroid dosing. The microscopic association and dissociation constants describing the steroidreceptor interaction were 0.23 L/nmole per hr (k_on and 4.74 hr^–1 (k_off) for methylprednisolone compared to previously obtained values of 0.20 L/nmole per hr and 15.7 hr^–1 for the related steroid prednisolone. The time course of TAT induction was similar to that observed previously for prednisolone. Efficiency of TAT induction was more closely related to steroid receptor occupancy than plasma methylprednisolone concentrations due to receptor saturability and receptor recycling.Supported in part by Grant No. 24211 from the National Institutes of General Medical Sciences, NIH, and by a Fellowship from the American Foundation for Pharmaceutical Education for D.H.     

The effect of oral prednisolone on visual evoked potential latencies in acute optic neuritis monitored in a prospective,randomized, controlled study

The Tübingen study of optic neuritis treatment was started in 1980 to apply new and sensitive tests for monitoring a potential therapeutical steroid effect on the course of acute optic neuritis. Visual evoked potentials were used to assess an effect of oral methylprednisolone in a randomized, controlled trial. Forty-eight patients with acute optic neuritis were treated orally either with methylprednisolone (100 mg per day initially, dosage reduction every 3 days; n = 15) or with thiamine (100 mg per day; n = 33) in the control group, 36 of them in a double-blind procedure. A comparison of the two treatment groups indicated that oral methylprednisolone resulted in a faster improvement in visual evoked potential latency in the initial phase (p = 0.015, 4 weeks after onset), but had no benefit after 12 weeks and 12 months. Follow-up showed different types of courses in the visual evoked potential latencies. The visual evoked potential latencies were correlated to other outcome variables, such as visual evoked potential amplitudes, visual acuity, Aulhorn flicker test and perimetry. We were able to handle nonmeasurable latencies in highly pathologic cases by means of ranks (taking into account censored observations).Abbreviations ON optic neuritis - Vitamin B1 thiamine     

Endothelin-1, atrial natriuretic peptide and pathophysiology of pulmonary hypertension in porcine meconium aspiration

To evaluate the role of endothelin-1 (ET-1) and atrial natriuretic peptide (ANP) in the development of meconium aspiration-induced pulmonary hypertension, plasma ET-1 and ANP levels were measured serially for 6h after meconium instillation in juvenile pigs. Eleven 10-week-old, anaesthetized and catheterized pigs received intratracheally a bolus of 3 ml kg^-1 20% human meconium, and five of them were premedicated with 30 mg kg methylprednisolone i.v. Another six pigs served as controls and were given 3 ml kg^-1 sterile saline intratracheally. Meconium instillation resulted in an increase in plasma ET-1 levels with a significant correlation to the simultaneously increasing PVR ( r = 0:72). Methylprednisolone had no effect on the early (0-1 h) ET-1 increase, but prevented significantly the second phase (1–6 h) rise with a concomitant attenuation of the progressive pulmonary hypertension. ANP concentrations were higher in the meconium than in the control group throughout the study and further increased after steroid treatment with a good correlation to ET-1 ( r = 0:86). Thus, the postinjury rise in circulating vasoactive peptides, together with the pulmonary hypertensive response, and modulation of the peptide balance and pressor reaction by steroids, suggest a contributory role for ET-1 and ANP in the development of pulmonary hypertension after meconium aspiration.