Early prophylactic inhaled beclomethasone in infants less than 1250 g for the prevention of chronic lung disease

OBJECTIVE:

Inflammation plays an important role in the development of chronic lung disease (CLD), which has become a major cause of morbidity in surviving infants less than 1250 g at birth. The authors hypothesized that the progression of this inflammation and, therefore, the establishment of CLD would be decreased with the use of early prophylactic inhaled corticosteroids. Short, and long term respiratory and neurodevelopmental outcomes were also examined.

DESIGN:

A double-blind, randomized placebo controlled trial.

SETTING:

Level-III neonatal intensive care unit.

POPULATION STUDIED:

Sixty infants less than 1250 g at birth, diagnosed with respiratory distress syndrome and requiring ventilatory support at 72 h of age were enrolled in the study.

INTERVENTION:

Infants enrolled received either placebo or beclomethasone diproprionate by a metered dose inhaler, which was used in-line with the ventilator circuit while the infant was ventilated and then via a spacer until 28 days of age.

RESULTS:

Thirty infants were given beclomethasone and 30 were given placebo. There were two deaths in each group. Among the surviving infants, the frequency of moderate-to-severe CLD was 17% in each study group. Mean time to extubation was not different for beclomethasone compared with placebo at 16.4 and 12.5 days (P=0.12), respectively. The requirement for intravenous corticosteroids was lower in the beclomethasone-treated group (RR 0.67, 95% CI 0.43 to 1.04), although this difference was not statistically significant. The incidence of growth failure, infection and intraventricular hemmorhage did not differ between the two groups. Long term outcomes were not different with respect to the incidence of respiratory re-admissions, cerebral palsy, developmental delay, blindness or deafness.

CONCLUSIONS:

Early treatment with inhaled beclomethasone diproprionate did not reduce the incidence of CLD or decrease the duration of mechanical ventilation. The decrease in intravenous corticosteroid use was not statistically significant. Long term outcome was not affected.     

Umbilical cord plasma interleukin-6 and fetal growth restriction in preeclampsia: a prospective study in Norway

OBJECTIVE: To study the association between umbilical plasma levels of interleukin-6 (IL-6) in relation to fetal growth in subgroups of preeclampsia, and in control pregnancies. METHODS: Umbilical cord plasma was collected from 12,804 consecutive births. A total of 271 singleton cases of preeclampsia were identified, and classified as mild or severe, and as disease with early or late onset. As controls, 611 singleton pregnancies without preeclampsia were selected, and the ratio between observed and expected birth weight was used as a measure of fetal growth. In the analysis, we also included maternal smoking during pregnancy. Umbilical cord plasma IL-6 concentration was measured with an IL-6 bioassay. Comparing controls with subgroups of preeclampsia (severe and early onset), this study had a statistical power of 90% to detect a difference in cord IL-6 of 10 pg/mL. RESULTS: In severe preeclampsia, cord plasma IL-6 concentration was lower than among controls (P <.001), and there was a sharp decrease in cord plasma IL-6 with decreasing birth weight ratio (P trend <.001). By further dividing the preeclampsia group into early or late onset, the strong association between low IL-6 levels and low birth weight ratio appeared to be present mainly in early-onset disease. These results were not confounded by maternal smoking. CONCLUSION: Restricted fetal growth related to preeclampsia is associated with reduced umbilical cord plasma IL-6 concentration in cases with early-onset disease. In these cases, fetal growth restriction could be mediated by impaired trophoblast function.     

TUBULAR PROTEINURIA AFTER PERINATAL HYPOXIA

ABSTRACT. Milt7eacute;nyi, M., Pohlandt, F., Bóka, G. and Kun, E. (2nd Department of Paediatrics, Semmelweis University, Medical School, Budapest, Hungary, and the Section of Neonatology, Centre of Paediatrics, University of Ulm, Federal Republic of Germany). Tubular proteinuria after perinatal hypoxia. Acta Paediatr Scand, 70:399, 1981.–Urinary total protein (UTP) and urinary protein pattern have been studied in 23 newborn infants with Apgar scores ±S3 at one minute or acidosis (pH ±7.15) on the first day. On the first and second day UTP excretion was increased in 13 out of 18 patients. At this time the excretion of low molecular weight microproteins (T-4 and T-5) was elevated in 12 patients without increased plasma urea concentration in any case. The increased excretion of the smallest microproteins T-4/T-5 is an early sign of an impaired tubular function.     

A model of corrective gene transfer in X-linked ichthyosis

Single gene recessive genetic skin disorders offer attractive prototypes for the development of therapeutic cutaneous gene delivery. We have utilized X-linked ichthyosis (XLI), characterized by loss of function of the steroid sulfatase arylsulfatase C (STS), to develop a model of corrective gene delivery to human skin in vivo. A new retroviral expression vector was produced and utilized to effect STS gene transfer to primary keratinocytes from XLI patients. Transduction was associated with restoration of full-length STS protein expression as well as steroid sulfatase enzymatic activity in proportion to the number of proviral integrations in XLI cells. Transduced and uncorrected XLI keratinocytes, along with normal controls, were then grafted onto immunodeficient mice to regenerate full thickness human epidermis. Unmodified XLI keratinocytes regenerated a hyperkeratotic epidermis lacking STS expression with defective skin barrier function, effectively recapitulating the human disease in vivo. Transduced XLI keratinocytes from the same patients, however, regenerated epidermis histologically indistinguishable from that formed by keratinocytes from patients with normal skin. Transduced XLI epidermis demonstrated STS expression in vivo by immunostaining as well as a normalization of histologic appearance at 5 weeks post-grafting. In addition, transduced XLI epidermis demonstrated a return of barrier function parameters to normal. These findings demonstrate corrective gene delivery in human XLI patient skin tissue at both molecular and functional levels and provide a model of human cutaneous gene therapy.      

病灶清除内固定植骨治疗胸椎结核

目的;探讨手术治疗胸椎结核的更好方法。方法;自１９９０年以来,对２１例胸椎结核导致椎柱不稳的患者,应用病灶清除,哈氏棒内固定,椎间及椎板植骨的手术方法。本组平均３３．２岁。胸７椎体６例,胸８椎体８例,胸１０椎体７例,椎体压缩〈１／２椎体高度１３例,〉１／２椎体高度８例,并不全瘫１４例。手术中先行病灶清除,然后哈氏棒内固一,撑开后再次清除病灶,取肋骨和髂骨行椎间及椎板上植骨。术后化疗１２～１５月。结     

金藤清痹颗粒治疗急性痛风性关节炎的作用机制研究

目的 应用网络药理学分析金藤清痹颗粒治疗急性痛风性关节炎（acute gouty arthritis,AGA）的作用机制,并建立AGA大鼠模型进行验证。方法 在清热解毒、活血止痛治法指导下,通过TCMSP数据库搜集金藤清痹颗粒的活性成分及靶点,利用GeneCards、NCBI数据库等搜集AGA相关靶点,与金藤清痹颗粒作用靶点整合后,构建共有靶点蛋白质-蛋白质相互作用（protein-protein interaction,PPI）网络和“金藤清痹颗粒-中药-活性成分-靶点-AGA”网络,并进行基因本体（gene ontology,GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes,KEGG）通路富集分析。雄性SD大鼠随机分为空白组、模型组、秋水仙碱（0.3 mg/kg）组和金藤清痹颗粒低、中、高剂量（1.05、2.10、4.20 g/kg）组,每组6只,踝关节注射单钠尿酸盐（monosodium urate,MSU）晶体建立AGA大鼠模型。采用游标卡尺测量大鼠踝关节直径,计算踝关节肿胀度;采用全自动生化仪检测血清尿酸（serum uric acid,SUA）、C反应蛋白（C-reactive protein,CRP）水平;采用苏木素-伊红（HE）染色观察踝关节组织病理变化;采用qRT-PCR、ELISA和Western blotting检测踝关节组织及血清中关键靶点和信号通路的表达。结果 共检索到金藤清痹颗粒110种活性成分、212个作用靶点,272个AGA治疗靶点,共有靶点29个,关键靶点有白细胞介素-1β（interleukin-1β,IL-1β）、肿瘤坏死因子（tumor necrosis factor,TNF）及IL-6,涉及TNF信号通路、IL-17信号通路和NOD样受体信号通路等。大鼠踝关节注射MSU晶体后明显肿胀（P<0.01）,SUA及CRP显著升高（P<0.05、0.01）,滑膜组织增生明显、结构紊乱,有大量炎症细胞浸润,NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3,NLRP3）、NIMA相关蛋白激酶7（NIMA-related kinases 7,NEK7）、凋亡相关斑点样蛋白（apoptosis-associated speck-like protein containing a CARD,ASC）、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1,Caspase-1）、消皮素D（gasdermin D,GSDMD）、IL-18、IL-1β、IL-6及TNF-α表达水平明显升高（P<0.01）;秋水仙碱或金藤清痹颗粒治疗后,有效缓解踝关节肿胀（P<0.05、0.01）,SUA及CRP均显著降低（P<0.05、0.01）,关节滑膜增生、炎症细胞浸润均得到改善,同时显著抑制IL-1β、TNF-α及IL-6等靶点和NOD样受体信号通路的表达（P<0.05、0.01）。结论 金藤清痹颗粒对AGA大鼠具有明显的保护作用,其机制可能与抑制NOD样受体信号通路的异常激活,降低炎症因子水平,改善关节滑膜增生、炎症细胞浸润有关。