Release of Proinflammatory Cytokines During Pediatric Cardiopulmonary Bypass: Heparin-Bonded Versus Nonbonded Oxygenators

Background. Heparin bonding of the cardiopulmonary bypass (CPB) circuit may be associated with a reduced inflammatory response and improved clinical outcome. The relative contribution of a heparin-bonded oxygenator (ie, >80% of circuit surface area) to these effects was assessed in a group of pediatric patients.

Methods. Twenty-one pediatric patients undergoing CPB operations were assigned randomly to receive either a heparin-bonded oxygenator (group H, n = 11) or a nonbonded oxygenator (group C, n = 10) in otherwise nonbonded circuits. The two groups were similar in pathology, age, weight, CPB time, and cross-clamp time. Plasma levels of the cytokines tumor necrosis factor-, interleukin-6, and interleukin-8, as well as terminal complement complex, neutrophils, and elastase, were analyzed before, during, and after CPB.

Results. Significant levels of tumor necrosis factor- were not detected in either group. Plasma levels of all other markers increased during and after CPB compared with baseline. Plasma levels of interleukin-6 peaked in both groups 2 hours after the administration of protamine but remained significantly higher in group C 24 hours after operation. Plasma concentrations of interleukin-8 peaked at similar levels in both groups 30 minutes after protamine administration and returned to baseline thereafter. Levels of terminal complement complex and elastase peaked in both groups 30 minutes after protamine administration. Plasma levels of terminal complement complex were significantly higher at the end of CPB and after protamine administration in group C. Elastase levels were significantly higher 2 and 24 hours after CPB in group C. The ventilation time of patients in group H was significantly lower than that of patients in group C: 10 (range, 3 to 24) versus 22 (range, 7 to 24) hours, respectively (p < 0.01).

Conclusions. The present study confirms the proinflammatory nature of pediatric operations and demonstrates a lessened systemic inflammatory response with the use of heparin-bonded oxygenators. This is achieved without bonding of the entire circuit, which could have significant cost-benefit implications by negating the need for custom-built heparin-bonded circuitry.     

Regulation of PTC phenotype and function by TGF-β1: implications for transdifferentiation

Introduction There is now increasing evidence that proximal tubular cells (PTCs) contribute to renal interstitial fibrosis by alteration of matrix turnover and by the generation of pro‐fibrotic cytokines such as TGF‐β1. Recent studies suggest that, through a process of transdifferentiation, the PTCs are one source of the interstitial myofibroblasts that directly drive the fibrotic process. The aim of this work was to examine the role and mechanism by which TGF‐β1 may regulate PTC phenotype and function. Methods Experiments were performed using both primary‐cultures of PTC and the human PTC cell line HK2. All experiments were performed on growth‐arrested cells in the absence of serum. Results TGF‐β1 altered cell phenotype, assessed by light microscopy, with cells appearing elongated and spindle‐shaped. This was associated with loss of cell–cell contact and rearrangement of the actin cytoskeleton, increased formation of stress fibres and focal adhesions. Disruption of the actin cytoskeleton with cytochalasin‐D prevented phenotypic alterations following addition of TGF‐β1. Transient transfection with Smad‐2/‐4 or Smad‐3/‐4 expression vectors did not alter cell phenotype. Previously, we have demonstrated β‐catenin translocation to PTC nuclei and its association with Smad proteins following addition of TGF‐β1, suggesting the possibility that TGF‐β1 may modulate Wnt signalling. Wnt‐responsive Xtwn‐reporter construct was, however, silent in response to TGF‐β1. Similarly, a second Wnt‐/LEF‐1‐regulated element Toplflash, which does not contain Smad‐binding sites, was insensitive to TGF‐β1 signalling. In contrast, phenotypic changes in response to TGF‐β1 were abrogated by inhibitors of the RhoA downstream target ROCK, which also prevented loss of cell–cell contact and adherens junction disassembly. Removal of TGF‐β1 and addition of 1% FCS, however, reverted cell phenotype to a typical cobblestone epitheliod appearance, suggesting that TGF‐β1 did not result in terminal PTC transdifferentiation. Cells grown on tissue culture dishes coated with either type‐I or type‐III collagen also acquired an elongated fibroblastic phenotype; this effect was exaggerated by the addition of TGF‐β1. In contrast to the cells stimulated with TGF‐β1 alone, following stimulation by both TGF‐β1 and exposure to interstitial collagens, cell phenotype was stable in that it was not reversed upon removal of TGF‐β1 and addition of FCS. Addition of TGF‐β1 to cells grown on type‐IV collagen had no greater effect than TGF‐β1 alone. Addition of TGF‐β1 alone had little effect on the expression of α‐SMA. In contrast, cells grown on either type‐I or type‐III collagen, following addition of TGF‐β1, demonstrated marked increased expression of α‐SMA, which appeared to be incorporated into the cell cytoskeleton. Similarly, the combination of interstitial collagen (either type‐I or type‐III) and TGF‐β1 had synergistic effect on the relocation and down‐regulation of the epithelial markers E‐cadherin and cytokeratin. Finally, the results demonstrated synergistic effects of coating with interstitial collagen (either type‐I or type‐III), on cell ‘fibroblastic’ cell function as assessed by cell migration and by the synthesis of type‐III and type‐IV collagen. Conclusion The results of these in vitro experiments suggest that terminal transdifferentiation of proximal tubular epithelial cells is the result of a combination of the effects of the pro‐fibrotic cytokine TGF‐β1 and exposure of the cells to components of the interstitial extra‐cellular matrix to which the cells are not exposed in the absence of damage to the tubular basement membrane.     

颞部-颌下联合进路切除咽旁颞下区巨大肿瘤(附2例报道)

[目的]探讨切除侵犯中颅窝的咽旁颞下区巨大肿瘤安全而彻底的手术进路.利用颞部切口可充分暴露中颅窝底和颞下窝以及颌下进路显露咽旁区解剖的特点,联合进路切除2例咽旁颞下区巨大肿瘤.2例侵犯中颅窝底的咽旁颞下区肿瘤顺利切除,患者术中组织损伤、出血量相对较少,术后无严重并发症.[结论]颞部-颌下联合进路适合于侵犯中颅窝底的咽旁颞下区肿瘤的手术切除.     

Protection of chickens against highly lethal H5N1 and H7N1 avian influenza viruses with a recombinant fowlpox virus co-expressing H5 haemagglutinin and N1 neuraminidase genes

Inactivated whole avian influenza virus (AIV) vaccine provides protection against homologous haemagglutinin (HA) subtype virus, but poor protection against a heterologous HA virus. Moreover, it induces chickens to produce antibodies to cross-reactive antigens, especially nucleoprotein, which is limits AIV serological surveillance. In this study, a recombinant fowlpox virus co-expressing HA (H5 subtype) and NA (N1 subtype) genes of AIV was evaluated for its ability to protect chickens against intramuscular challenge with a lethal dose of highly pathogenic (HP) AIV. Susceptible chickens were also vaccinated by wing-web puncture with the parent fowlpox vaccine virus. Following challenge 4 weeks later with HPAIV, all chickens vaccinated with recombinant virus were protected, while the chickens vaccinated with either the unaltered parent fowlpox vaccine virus or unvaccinated controls experienced 100% mortality following challenge. This protection was accompanied by the high levels of specific antibody to the respective components of the recombinant vaccine. The above results showed that rFPV-HA-NA could be a potential vaccine to replace current inactivated vaccines for preventing AI.     

辨证治疗特发性水肿43例疗效观察

特发性水肿是一种原因不明的综合征.在祖国医学属水肿.郁证范畴.近几年笔者采用辨证论治治疗本病43例,取得满意疗效,现报告如下.     

全植入式药泵行肝血管灌注治疗晚期肝癌

对２４例不能切除的晚期肝癌采用完全植入式药泵行肝动脉和门静脉双灌注化疗。结果：部分缓解（ＰＲ）１５例（６２．５％），稳定（Ｓ）８例（３３．３％），进展（Ｐ）１例。平均生存期为９．１７月，半年生存率为６６．７％，１年为２５％。在ＡＦＰ＞４００μｇ／Ｌ的１０例中，５例下降。     

Additive effects of earthworm extract with HpD-laser on the enhancement of reactive oxygen production and the inhibition of[~3H]—thymidine.uptake in mouse ascitic tumor cells

The effects of combined use of earthworm extract(912)and HpD-laser on the produc-tion of reactive oxygen and the biosynthesis of DNA in S_(180) tumor cells were studied throughchemiluminescence measurement and[~3H]-TdR incorporation assay.The results showed that as com-pared with the control,the intensity of chemiluminescence emitted by tumor cells treatedsimultaneously with 912 and HpD-laser was enhanced more than ten-folds,while that treated with912 or HpD-laser alone was increased only 2～4 folds.The[~3H]-TdR incorporation into tumorcells of the former group was inhibited upto 74.1%,and that of the latter groups decreased onlyby 42.2% and 40.0%,respectively.In accordance with these biochemical changes,the ultrastructuraldamage of tumor cells of the former,combinedly treated group appeared to be the most serious.This suggests an additive effect of 912 with HpD-laser on tumor cells.In addition,if free radicalscavengers,such as catalase and superoxide dismutase,were added to the reaction systembefore chemiluminescence assay,the luminescent enhancement effect mentioned above was dramaticallyalleviated,implying the presence of O_2~ and H_2O_2 in the system.Therefore,as to the toxic effecton tumor cells,912 and HpD-laser are not only additive in efficiency,but also similar in theunderlying mechanism of action.     

老年冠心病患者的动态心电图观察

对97例老年冠心病患者进行动态心电图观察,共检出97例患者缺血性ST段发作347阵,心率减慢时发生缺血48例(49.5％),全程无症状者75例(77.4%),缺血时有无胸痛与ST段下降程度无必然联系。     

在音乐缭绕中痊愈

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