神经体液因子在兔血管迷走性晕厥中的变化

目的 通过兔急性失血建立血管迷走性晕厥(VVS)模型,研究其血浆肾上腺素(AD)、去甲肾上腺素(NE)、5-羟色胺(5-HT)、内皮素(ET-1)的变化,进一步了解VVS的发病机制.方法 取幼年健康新西兰大白兔12只,通过股动脉放血建立VVS模型.使用50 mL注射器以5 mL/min速度抽血,连续监测其血压、心率,直至血压显著降低,神志丧失或抽搐.采用BL-420E+生物机能实验仪器监测,分别于静止后5 min(T1),放血中升压最快点后1 min(T2),降压最快点后1 min(T3),呼吸、心跳消失或抽搐(T4)共取4次血样.比较各时间点兔血中AD、NE、5-HT、ET-1水平,并观察模型兔的最终状态.应用SPSS 12.0软件进行统计学分析.结果 在放血过程中各神经体液因子水平均呈上升趋势;在T2时,AD、NE、ET-1-水平均明显升高(Pa<0.01);在T3、T4时5-HT水平明显升高(T3 vs T1 P<0.01,T4 vs T3 P<0.01).实验结束时10只兔(83%)出现抽搐,最终血压、心率消失死亡.结论 AD、NE、5-HT、ET-1等神经体液因子可能介导VVS的发病机制,为VVS的临床治疗和预防奠定了理论基础.     

儿童血管迷走性晕厥的临床特征及血浆和血小板中5-羟色胺的变化

目的 探讨小儿血管迷走性晕厥的临床特征和血浆、血小板中5-羟色胺(5-HT)的变化.方法 2006年10月-2009年2月在首都儿科研究所经直立倾斜试验(head-up tilt test,HUTT)确诊为血管迷走性晕厥(VVS)患儿41例(HUTT阳性组),诊断标准参照基础HUTT对儿童不明原因晕厥的诊断研究,男17名,女24名,年龄6～14岁,平均年龄(10.5 ±1.8)岁.匹配健康儿童(对照组):当地幼儿园和中小学36名健康小儿,男16名,女20名,年龄9～14岁,平均年龄(10.7±1.5)岁.分析晕厥诱因和先兆症状、HUTT反应方式、晕厥发作时间、VVS患儿静息状态各亚型血压和心率变化等临床特点.全体研究对象抽取静脉血3 ml,用双抗体夹心酶标免疫分析(ELISA)法对41例血管迷走性晕厥患儿及36名健康儿童的血浆和血小板中5-HT进行测定.结果 ①41例血管迷走性患儿平均年龄为(10.5±1.8)岁,女童比例高于男童,为1.4:1.②VVS先兆症状:患儿中33例存在晕厥先兆(80.4%),其中头晕发生率高达78.8%.③VVS发生诱因:儿童VVS发作前常存在诱发因素,包括:长久站立、劳累、情绪影响等.其中长久站立比例最高,达90.2%.④HUTT平均反应时间及晕厥持续时间:基础直立倾斜试验(BHUT)阶段平均反应时间为(20.6±8.6)min;舌下含化硝酸甘油激发倾斜试验(SNHUT)阶段平均反应时间(5.0±2.2)min.晕厥持续时间均短于5 min.⑤HUTT不间反应类型的分布:血管抑制型61.0%,混合型24.4%,心脏抑制型14.6%.⑥血压和心率的比较:VVS患儿和正常儿童静息状态下基础心率、收缩压、舒张压相比差异无统计学意义;VVS患儿中血管抑制型、混合型和心脏抑制型静息状态下基础心率、收缩压、舒张压相比差异无统计学意义.⑦VVS患儿基础状态和HUTT阳性时血浆中5-HT较对照组差异无统计学意义[(27.51±1.32)μg/Lvs.(27.28±2.48)μg/L,t=0.518,P=0.606;(27.51±1.32)μg/L vs.(28.05 ±1.40)μg/L,t=2.044,P=0.167],基础状态下血小板5-HT与对照组之间差异无统计学意义[(82.30 ±6.06)10~9ng/L vs.(79.88±5.79)10~9ng/L,t=1.788,P=0.780].⑧VVS患儿基础状态下和HUTT阳性时的血小板5-HT比较差异有统计学意义[(82.30±6.06)10~9ns/L vs.(97.90±6.59)10~9ng/L,t=11.26,P=0.00].结论 VVS患儿具有明显的临床特征;VVS患儿基础状态和晕厥(或晕厥先兆发生时)血浆中5-HT变化不明显;VVS患儿晕厥或晕厥先兆发生时血小板5-HT明显升高,提示中枢5-HT系统可能参与了VVS的发病过程.     

儿童血管迷走性晕厥临床分析

目的：研究儿童血管迷走性晕厥（vasovagal syncope，VVS）临床情况。方法：2000年1月至2009年9月在中南大学湘雅二医院儿科门诊就诊或住院的不明原因晕厥或先兆晕厥患儿841例，依据检查年限分为两组，2000年1月至2004年12月为A组，共129例；2005年1月至2009年9月为B组，共712例；并按照年龄分为4岁~、7岁~及11~18岁3个年龄组。经直立倾斜试验（head-up tilt table test，HUTT）检查诊断为VVS。结果：HUTT总阳性率为45.3% (381/841)，B组阳性率较A组明显增加（47.5% vs 33.3%，P7岁~组>4岁~组（49.2% vs 44.1% vs 37.1%），组间比较差异有统计学意义；7岁~组和11~18岁组中B组HUTT阳性率明显高于A组(46.2% vs 27.8%； 54.0% vs 32.6%，P＜0.05)。HUTT阳性率反应类型比较，依次为血管抑制型>混合型>心脏抑制型（70.9% vs 25.5% vs 3.6%），组间比较差异有统计学意义，其中血管抑制型表现为B组HUTT阳性率高于A组(72.5% vs 58.1%，P＜0.05)。结论：近5年VVS的发生率、反应类型发生显著变化，提示VVS的发生受社会因素、精神因素、生活方式等多种因素的影响。［中国当代儿科杂志，2010，12（9）：723-725］     

心脏变时性功能在血管迷走性晕厥患儿中的临床意义

目的　研究血管迷走性晕厥（vasovagal syncope,VVS）患儿的心脏变时性功能变化及其临床意义。方法　回顾性分析2011年3月至2017年1月在北京大学第一医院儿科39例不明原因晕厥患儿的临床资料。经详细病史询问及辅助检查,28例患儿确诊为VVS,其中血管抑制型15例,混合型9例,心脏抑制型4例,11例为不明原因晕厥患儿,比较VVS患儿与不明原因晕厥患儿及不同血流动力学类型的VVS患儿之间的一般情况及运动平板试验时心率变化及心脏变时功能等情况。进一步根据VVS患儿心脏变时性功能情况分为变时性功能正常组（10例）及变时性功能不全（chronotropic incompetence,CI）组（17例,1例患儿失访）,通过随访2组患儿晕厥复发情况,观察心脏CI对VVS患儿预后的影响。结果　VVS患儿与不明原因晕厥患儿相比较,人口学指标均无显著性差异,在运动平板试验中VVS患儿运动时最快心率及心脏变时性指数显著低于不明原因晕厥患儿（P＜0.05）,VVS患儿的CI发生率显著高于不明原因晕厥患儿（64.3% vs. 27.3%,P＜0.05）。不同血流动力学类型的VVS患儿比较,心脏抑制型及混合型患儿CI的发生率显著高于血管抑制型患儿。通过对27例VVS患儿随访发现,伴有CI的VVS患儿晕厥的复发率显著高于不伴有CI的患儿（P＜0.05）,以患儿晕厥复发的时间作为随访终点对VVS患儿进行生存分析,有CI的VVS患儿较无CI的患儿对治疗的反应不佳（Log-rank：P＝0.028）。结论　心脏变时性功能在VVS患儿中有显著的改变,尤其常见于心脏抑制型和混合型患儿。伴有CI的VVS患儿对治疗的反应不佳。     

一氧化氮和内皮型一氧化氮合成酶与血管迷走性晕厥发病的关系

目的：探讨一氧化氮和内皮型一氧化氮合成酶与儿童血管迷走性晕厥发病的关系。方法：血管迷走性晕厥患儿14例（A组）,其他原因引起晕厥患儿10例（B组）,健康志愿者20例（C组）。于倾斜试验（HUT）前和倾斜不同时间测定A组与B组患儿的血浆一氧化氮（NO）水平,同时对3组儿童进行内皮型一氧化氮合成酶（eNOS）基因G894T多态性检测。结果：①A组患儿出现阳性反应时血浆NO水平较平卧时显著升高（76.7±9.6 vs 90.0±11.4 μmol/L, P<0.05）;②A组患儿在症状好转后血浆NO水平较试验前显著降低（82.7±9.2 vs 61.5±6.9 μmol/L,P<0.01）;③B组患儿倾斜时血浆NO水平较平卧时差异无显著性;④A,B两组患儿的血压、心率变化与NO水平无显著相关性;⑤A组患儿eNOS基因G894T突变型基因频率显著高于B组与C组(42.9% vs 10%, P<0.05)。结论： 倾斜体位时血浆NO水平异常升高可能参与了血浆血管迷走性晕厥的发病机制,而其升高水平可能与eNOS基因G894T多态性表达有关。     

直立倾斜试验在儿童血管迷走性晕厥中的诊断价值

目的：探讨直立倾斜试验儿童血管迷走性晕厥的诊断价值。方法：对24例不明原因晕厥的患儿进行基础直立倾斜试验，并以12名正常儿童作对照，在倾斜过程中动态观察心电图、血压、心率，并进行分析。结果：24例晕厥患儿中，基础直立倾斜试验阳性16例，而对照组为0.诊断敏感度为67%,特异度为100%,诊断价值为78%.16例阳性反应中，心脏抑制型反应3例（19%），表现为心动过缓，血压无变化；血管抑制型反应9例（56%），表现为血压下降，心率加快；混合型反应4例（25%），表现为心率、血压均有明显下降。结论：基础直立倾斜试验可作为儿童血管迷走性晕厥的一种重要诊断方法。     

患儿血管迷走性晕厥直立倾斜试验血浆C型钠尿肽变化及其意义

目的探讨血管迷走性晕厥(vasovagal syncope,VVS)患儿血浆C-型钠尿肽(c-type natriuretic peptide,CNP)含量的变化。方法研究对象包括31例VVS患儿,均为2013年12月至2014年6月在北京大学第一医院儿科以直立不耐受症状入院的患儿,均经过详细病史询问、体格检查及相关实验室检查以及直立倾斜试验(HUTT)确诊为VVS,平均年龄为(11±3)岁;32名健康儿童为对照组,均为经过详细病史及体格检查等确定为健康的儿童,平均年龄为(11±2)岁。心率、血压的监测采用无创连续血压监测仪连续监测。血浆CNP的测定采用夹心免疫发光法。结果 VVS组与对照组的性别比、年龄、身高、体重、平卧位血压及心率差异均无统计学意义(P0.05);VVS患儿血浆中CNP含量明显高于正常儿童[(35.7±21.5)ng/L vs.(23.2±8.0)ng/L,P0.01)];VVS患儿的晕厥频率与血浆中的CNP含量呈明显正相关(n=31,r=0.85,P0.01)。VVS组平卧状态下及HUTT中阳性反应时的血浆CNP含量差异无统计学意义[(36.3±21.0)ng/L vs.(42±57)ng/L,P0.05]。结论 VVS患儿血浆CNP含量高于对照组,且血浆CNP含量与患儿晕厥频率相关,可能参与了VVS的发病过程。     

儿童血管迷走性晕厥QT间期离散度及心率变异性分析

目的探讨儿童血管迷走性晕厥（VVS）QT间期离散度（QTd）及心率变异性（HRV）的变化。方法采用日本光电9320K12导联同步心电图机及DeMar-K100动态心电图仪对52例VVS患儿及30例健康儿童的QTd及HRV进行测量。结果VVS患儿QTd、校正QT间期离散度和最长QT间期较对照组显著增大，差异具有显著性；直立倾斜试验（HUTT）阳性组和阴性组间QTd值比较差异无显著性。SDNN、SDANN及RMSSD病例组较对照组减小，且病例组SDNN、RMSSD与对照组相比差异有显著性；HUTT阳性组和阴性组间HRV差异无显著性。结论VVS的发病机制与交感神经和副交感神经调节存在障碍有关。HUTT作为诊断VVS的金标准，其阴性者不能除外VVS。QTd、HRV对于VVS患儿发生心肌缺血、心律失常等心血管事件具有一定的预测价值。     

心率及血压变异系数对可疑直立不耐受患儿快速识别的临床价值

目的探讨心率及血压变异系数在可疑直立不耐受(OI)患儿快速识别中的临床应用价值。方法回顾性研究。选取2015年1月至2020年1月山东大学齐鲁医院儿科诊治的379例因OI症状入院患儿为病例组;选取20名无晕厥及晕厥先兆症状的门诊健康查体儿童为无症状对照组。病例组根据直立试验及直立倾斜试验(HUTT)结果分为HUTT阴性组、血管迷走性晕厥(VVS)组、体位性心动过速综合征(POTS)组、POTS合并VVS组。分析所有入组儿童试验过程中的血压及心率数据, 分别计算各组研究对象卧立位及卧立倾斜位收缩压变异系数(SBPCV)、舒张压变异系数(DBPCV)及心率变异系数(HRCV)。5组研究对象各项指标的组间比较采用Kruskal-Wallis检验, 组间两两比较采用Dunnett′s T3法;5组内卧立位与卧立倾斜位变异系数比较采用配对样本t检验。通过受试者工作特征(ROC)曲线对卧立位心率及血压变异系数的预测价值进行评估。结果 379例患儿中, HUTT阴性组79例、VVS组208例、POTS组52例、POTS合并VVS组40例, 无症状对照组20名。无症状对照组、HUTT阴性组、VVS组、...     

经颅多普勒超声检测血管迷走性晕厥患儿脑血流动力学变化分析

目的 采用经颅多普勒超声（TCD）分析血管迷走性晕厥（VVS）的脑血流动力学特点,并探讨TCD对VVS的临床应用价值。方法 对2011年12月至2013年8月于兰州大学第二医院小儿心血管科就诊的38例血管迷走性晕厥患儿,及20名体检健康儿童行直立倾斜试验,并应用TCD进行监测。结果 基础状态下,观察组与对照组比较,左右大脑中动脉的收缩期血流速度（Vs）、舒张末期血流速度（Vd）、平均血流速度（Vm）差异无统计学意义（P＞0.05）,脉冲指数（PI）值差异无统计学意义（P＞0.05）;对照组行直立倾斜试验后与基础状态时比较,左右大脑中动脉的Vs、Vd、Vm差异无统计学意义（P＞0.05）,PI值差异无统计学意义（P＞0.05）;观察组通过直立倾斜试验诱发血管迷走性晕厥阳性反应时与基础状态时比较,左右大脑中动脉的Vs、Vd、Vm明显加快（P＜0.05）,PI值明显升高（P＜0.05）。结论 VVS发生时,脑血管阻力增加,脑血流调节障碍;TCD检查对于判断VVS患儿脑血流状态具有重要价值。     

Allergic factors associated with the development of asthma and the influence of cetirizine in a double-blind, randomised, placebo-controlled trial: First results of ETA®

There is a common progression known as the allergic march from atopic dermatitis to allergic asthma. Cetirizine has several antiallergic properties that suggest a potential effect on the development of airway inflammation and asthma in infants with atopic dermatitis. Methods. Over a two year period, 817 infants aged one to two years who suffered from atopic dermatitis and with a history of atopic disease in a parent or sibling were included in the ETAC^® (Early Treatment of the Atopic Child) trial, a multi-country, double-blind, randomised, placebo-controlled trial. The infants were treated for 18 months with either cetirizine (0.25mg/ kg b.i.d.) or placebo. The number of infants who developed asthma was compared between the two groups. Clinical and biological assessments including analysis of total and specific IgE antibodies were performed. Results. In the placebo group, the relative risk (RR) for developing asthma was elevated in patients with a raised level of total IgE (≥ 30 kU/I) or specific IgE (≥ 0.35 kUA/I) for grass pollen, house dust mite or cat dander (RR between 1.4 and 1.7). Compared to placebo, cetirizine significantly reduced the incidence of asthma for patients sensitised to grass pollen (RR = 0.5) or to house dust mite (RR = 0.6). However, in the population that included all infants with normal and elevated total or specific IgE (intention-to-treat - ITT), there was no difference between the numbers of infants developing asthma while receiving cetirizine or placebo. The adverse events profile was similar in the two treatment groups. Discussion. Raised total IgE level and raised specific IgE levels to grass pollen, house dust mite or cat dander were predictive of subsequent asthma. Cetirizine halved the number of patients developing asthma in the subgroups sensitised to grass pollen or house dust mite (i.e. 20% of the study population). In view of the proven safety of the drug, we propose this treatment as a primary pharmacological intervention strategy to prevent the development of asthma in specifically sensitised infants with atopic dermatitis.     

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孤独症谱系障碍(autistic-spectrum disorders,ASDs)近年来患病率逐年攀升至1%左右,其症状往往伴随终生,成为严重威胁儿童健康和发展的神经发育性疾患;注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)是儿童期最常见的精神障碍,国内报道患病率为4.13%～5.83%,其症状可延续至青少年期,甚至到成年期[1]。这两类精神障碍在成年期的临床表现、共患病、治疗策略和预后与儿童期有哪些不同呢?本文通过回顾相     

EXCITING NEW TREATMENT APPROACHES FOR PATHYPHYSIOLOGIC MECHANISMS OF SICKLE CELL DISEASE

During the past several decades, our understanding of the complex pathophysiology of vasoocclusion associated with sickle cell disease has improved greatly. Interaction of genes, hemoglobin molecules, red cell membrane and metabolic changes, cell-cell interactions and cell-plasma interactions, red cell adhesion to vascular endothelium, activation of coagulation, and vascular reactivity play a role in vaso occlusion. Penicillin prophylaxis of pneumococcal infections and appropriate use of blood transfusions and other supportive measures improved survival of sickle cell patients. Hydroxyurea made a major impact on sickle cell therapy when it was shown to decrease acute painful episodes, acute chest syndrome, and the need for blood transfusion in adults. Significant experience in the use of hydroxyurea has been accumulated in older children. The benefits and risks of hydroxyurea for younger children and long-term risks in all patients will be evaluated in future investigations. Other promising therapies include butyrate compounds, clotrimazole, magnesium supplementation, poloxamer 188, antiadhesion agents, anticoagulant approaches, and nitric oxide. Hemopoietic transplantation remains the only curative therapy. However, several transgenic mouse models are available for studies of gene therapy or other treatment approaches on biochemical, cellular, and pathologic effects of mutant genes.     

Infiltrations of Epstein-Barr virus-carrying cells in granular lymphocyte-proliferative disorders corresponding to chronic active Epstein-Barr virus infection

A 21-year-old man with granular lymphocyte-proliferative disorders (GLPD) associated with chronic active Epstein-Barr virus (EBV) infection is described. Chromosomal analyses revealed several clonal abnormalities and two of them were mainly repetitious. High copy numbers of monoclonal EBV genome were also detected in the proliferative large granular lymphocytes (LGLs), indicating the monoclonal expansion of EBV-infected LGLs. The patient had an indolent course for several years, and there was no evidence of infiltrations of his bone marrow until the end stage. At autopsy, microscopic studies revealed marked infiltrations of LGL in the liver and spleen, and the infiltrating cells were NK-cell immunophenotype. The infiltrated LGLs showed latency I.     

LUTEINIZING HORMONE RECEPTOR MUTATIONS IN DISORDERS OF SEXUAL DEVELOPMENT AND CANCER

Human male sexual development is regulated by chorionic gonadotropin (CG) and luteinizing hormone (LH). Aberrant sexual development caused by both activating and inactivating mutations of the human luteinizing hormone receptor (LHR) have been described. All known activating mutations of the LHR are missense mutations caused by single base substitution. The most common activating mutation is the replacement of Asp-578 by Gly due to the substitution of A by G at nucleotide position 1733. All activating mutations are present in exon 11 which encodes the transmembrane domain of the receptor. Constitutive activity of the LHR causes LH releasing hormone-independent precocious puberty in boys and the autosomal dominant disorder familial male-limited precocious puberty (FMPP). Both germline and somatic activating mutations of the LHR have been found in patients with testicular tumors. Activating mutations have no effect on females. The molecular genetics of the inactivating mutations of the LHR are more variable and include single base substitution, partial gene deletion, and insertion. These mutations are not localized and are present in both the extracellular and transmembrane domain of the receptor. Inactivation of the LHR gives rise to the autosomal recessive disorder Leydig cell hypoplasia (LCH) and male hypogonadism or male pseudohermaphroditism. Severity of the clinical phenotype in LCH patients correlates with the amount of residual activity of the mutated receptor. Females are less affected by inactivating mutation of the LHR. Symptoms caused by homozygous inactivating mutation of the LHR include polycystic ovaries and primary amenorrhea.     

Personality profiles and heart rate variability (vagal tone) in children with recurrent abdominal pain

The aim of the study was to explore psychological factors and autonomic activity in children with recurrent abdominal pain and to compare them with those in a control group of healthy children. The Personality Inventory for Children was used for assessment of developmental, emotional and psychosocial factors in 25 children with recurrent abdominal pain (age, 7-15 y). Parasympathetic and sympathetic functions in these children and in 23 healthy control subjects (age, 7-13 y) were also investigated, non-invasively using a computerized polygraph. Vagal tone (parasympathetic function) was indexed by calculation of respiratory sinus arrhythmia in beats/min. Skin conductance (sympathetic function) was recorded by the constant current method. On the Personality Inventory for Children, 16 patients had high scores on somatic concern. Several patients had scores in the clinical range for depression, withdrawal and anxiety, but the mean scores for these personality profile scales were well within the normal range of healthy children. Interestingly, there was a spike on the L (Lie)-scale for most of the patients and 15 patients had scores above or close to the clinical cut-off value. As compared with the scores in healthy children, vagal tone and sympathetic tone were normal. Conclusion: Many children with recurrent abdominal pain have scores in the clinical range for depression, withdrawal, anxiety and L-scale indicating coping problems, denial and a trend towards somatic concern that may contribute to the evolution of abdominal pain. Autonomic nerve activity was not disturbed in these children.     

Overcoming surfactant inhibition with polymers

Inhibition of the function of pulmonary surfactant in the alveolar space is an important element of the pathophysiology of many lung diseases, including meconium aspiration syndrome, pneumonia and acute respiratory distress syndrome. The known mechanisms by which surfactant dysfunction occurs are (a) competitive inhibition of phospholipid entry into the surface monolayer (e.g. by plasma proteins), and (b) infiltration and destabilization of the surface film by extraneous lipids (e.g. meconium-derived free fatty acids). Recent data suggest that addition of non-ionic polymers such as dextran and polyethylene glycol to surfactant mixtures may significantly improve resistance to inhibition. Polymers have been found to neutralize the effects of several different inhibitors, and can produce near-complete restoration of surfactant function. The anti-inhibitory properties of polymers, and their possible role as an adjunct to surfactant therapy, deserve further exploration.     

How well are we doing? – Metabolic control in patients with diabetes

OBJECTIVE: To compare the present level of metabolic control in children and adolescents with insulin-dependent diabetes mellitus (IDDM) attending Brisbane paediatric diabetes clinics with published overseas data. METHODOLOGY: Blood HbA1c concentrations, population characteristics, current treatment practices and short-term complications were recorded in all patients, aged 19 years and under, attending the diabetes clinics of the two Brisbane Children's Hospitals or the private practice of one of the authors (MJT) in the first quarter of 1998. RESULTS: Two hundred and sixty-eight patients were assessed (M/F 142/126). Ages ranged from 1 to 19 years (mean 11. 2 years); duration of IDDM was 0-16 years (mean 4.4 years); and 141 (53%) were pubertal. Of those aged less than 13 years, only 4% had more than two injections daily. Insulin doses (U/kg/day) rose with increasing age. Larger doses were required in regimens involving more than two injections per day than those involving one to two injections per day. Ketoacidosis or severe hypoglycaemia in the last 3 months were reported in eight (2.7%) and 17 (6.3%) of patients, respectively. Mean HbA1c (+/- SD) was 8.6 +/- 1.4% (range 5.2-14.0%), with 33% of children having a HbA1c concentration < 8%. HbA1c concentrations were significantly related (P < 0.05) to insulin dose and to duration of diabetes, but not to severe hypoglycaemia, ketoacidosis, age, frequency of injections, or number of clinic visits per year. Mean HbA1c concentration was significantly higher (P < 0.05) in those children in puberty (8.7 +/- 1.5%) than in those not in puberty (8.5 +/- 1.2%). CONCLUSION: Only 33% of patients had a HbA1C concentration less than 8% and 6.3% had a severe hypoglycaemic episode in the 3 months. These results are similar to published overseas data.     

MAINTENANCE OF DIFFERENTIATED FUNCTION OF THE SURFACTANT SYSTEM IN HUMAN FETAL LUNG TYPE II EPITHELIAL CELLS CULTURED ON PLASTIC

We report a simplified culture system for human fetal lung type II cells that maintains surfactant expression. Type II cells isolated from explant cultures of hormone-treated lungs (18-22 wk gestation) by collagenase + trypsin digestion were cultured on plastic for 4 days in serum-free medium containing dexamethasone (Dex, 10 nM) + 8-bromo-cAMP (0.1 mM) + isobutylmethylxanthine (0.1 mM) or were untreated (control). Surfactant protein (SP) mRNAs decreased markedly in control cells between days 1 and 4 of culture, but mRNA levels were high in treated cells on day 4 (SP-A, SP-B, SP-C, SP-D; 600%, 100%, 85%, 130% of day 0 content, respectively) . Dex or cAMP alone increased SP-B, SP-C, and SP-D mRNAs and together had additive effects. The greatest increase in SP-A mRNA occurred with cAMP alone. Treated cells processed pro-SP-B and pro-SP-C proteins to mature forms and had a higher rate of phosphatidylcholine (PC) synthesis (2-fold) and higher saturation of PC (~34% versus 27%) than controls. Only treated cells maintained secretagogue-responsive phospholipid synthesis. By electron microscopy, the treated cells retained lamellar bodies and extensive microvilli. We conclude that Dex and cAMP additively stimulate expression of surfactant components in isolated fetal type II cells, providing a simplified culture system for investigation of surfactant-related, and perhaps other, type II cell functions.