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目的了解不同初治年龄对先天性肾上腺皮质增生症(CAH)患儿身高、骨龄、性早熟等方面的影响。方法将1982～2004年在上海新华医院和上海市儿科医学研究所内分泌、遗传代谢病专科诊治的32例CAH患儿(年龄:女≥8岁,男≥9岁),按初治年龄分为≤3岁组(14例)和>3岁组(18例),观察两组间末次复诊时骨龄与身高龄之差、性早熟例数及男女患儿发生性早熟的不同。结果14例初治年龄≤3岁患儿末次复诊时骨龄与身高龄之差[(3.0±2.0)岁]与18例>3岁组[(4.6±1.6)岁]比较差异有显著性(P<0.05),初治年龄>3岁组发生真性性早熟(9例)与≤3岁组(2例)比较差异有显著性(χ2=4.453,P<0.05)。男性患儿发生真性性早熟(9例)与女性患儿(2例)比较差异有显著性(χ2=4.794,P<0.05)。结论CAH患儿≤3岁得到诊治者其预测终身高较>3岁方诊治者明显改善,其性早熟发生率明显减少,男性CAH患儿较女性CAH患儿更易发生性早熟。     

先天性肾上腺皮质增生症早期治疗回顾分析

目的探讨先天性肾上腺皮质增生症(CAH,21-羟化酶缺乏)早期治疗的疗效。方法回顾性分析1997年至2011年出生,在6月龄内诊断并开始治疗的69例CAH患儿病史资料,了解早期治疗对患儿生长发育的影响,探讨治疗随访的评估指标。结果 69例患儿于生后4~180 d开始接受治疗,平均中位年龄47 d;平均生长速率为(7.4±1.1)cm/年;末次随访中位年龄3.4岁(0.67~9.92岁),身高均位于正常儿童生长水平的第25~50百分位;76%患儿的骨龄接近实际年龄;预测男女患儿终身高分别为(168.9±8.5)cm和(155.4±8.0)cm,71%位于遗传靶身高范围内,优于以往报道的诊断和治疗年龄>1岁患儿的终身高[(151.0±7.0)cm];真性性早熟发生率为5.79%(4/69),低于以往报道≤3岁及>3岁治疗者性早熟发生率(分别为14%及50%);治疗期间电解质、促肾上腺皮质激素(ACTH)、睾酮水平控制正常比例占86%~93%,17-羟孕酮波动较大;促肾上腺皮质激素、17-羟孕酮、睾酮呈正相关。结论早期治疗能改善CAH患儿的生长,降低性早熟发生率,提高终身高。     

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目的分析男性儿童同性性早熟的病因及临床特点。方法回顾性分析1988年1月至2009年4月中山大学附属第一医院收治的明确病因诊断的78例男性同性性早熟病例的病因及临床特点。结果中枢性性早熟(CPP)55例(70.51%),按构成比前三位病因为特发性性早熟、下丘脑错构瘤、先天性肾上腺皮质增生症(CAH)继发,其中下丘脑错构瘤患儿就诊年龄小、GnRHa激发试验后LH浓度最高,CAH患儿骨龄提前最多、HtSDSba负值最大;外周性性早熟(PPP)23例(29.49%),分泌HCG生殖细胞瘤和CAH为主要病因,CAH患儿由PPP转变为CPP的比例较大(5/9),尤其是初治年龄较大者更易发生。分泌HCG的生殖细胞瘤血和(或)脑脊液的β-HCG水平均升高。结论男性儿童性早熟以器质性病变引起多见,在诊治过程中应积极寻找病因。     

长期延误治疗的甲状腺功能减低症患儿的追赶生长

目的研究长期延误治疗的甲状腺功能减低症(甲减)患儿治疗后身高增长的规律及青春期对其身高的影响,探讨使用促性腺激素释放激素拟似物(GnRHa)和生长激素(GH)治疗辅助生长的可能性。方法分析28例长期被忽视(3a以上)的甲减患儿的追赶生长,其中青春前期13例(A组),青春期诊断并开始治疗15例(B组)。治疗过程中每3个月门诊随访1次,监测患儿身高、体质量、性发育情况、骨龄、血清甲状腺功能等指标。在左旋甲状腺素治疗的基础上,应用GnRHa和GH联合治疗2例长期延误治疗且已进入青春期的患儿。结果2组患儿初诊时均有明显的生长落后、骨龄落后。A组年龄(7.1±2.0)岁,骨龄(3.0±1.5)岁,身高标准差评分(HTSDS)为-3.89±1.29;B组开始治疗的年龄(14.3±1.6)岁,骨龄(5.6±2.3)岁,HTSDS-5.55±1.38。2组靶身高(TH)比较无差异。治疗第3年末,A组HTSDS提高至-1.12±1.14,B组上升至-1.94±1.39;治疗后2组患儿骨龄改变3a依次为A组(2.5±0.5)岁.a-1、(1.6±0.5)岁.a-1、(1.4±0.6)岁.a-1;B组分别为(5.2±1.8)岁.a...     

每六周皮下注射促性腺激素释放激素类似物缓释剂干预女孩特发性中枢性性早熟

目的　观察延长促性腺激素释放激素类似物 (GnRHa)缓释剂注射间期对特发性中枢性性早熟女孩下丘脑 垂体 性腺轴抑制情况和临床症状改善方面的效果。方法　 4 6例特发性中枢性性早熟女孩随机分为两组 ,A组 :2 6例 ,年龄 (8 3± 1 4 )岁 (6 1～ 11 2 )岁 ,乳房开始发育年龄 (6 6±1 4 )岁 (2～ 8)岁 ,骨龄 (8 9± 1 5 )岁 (6 8～ 11 5 )岁 ;每 6周腹部皮下注射曲普瑞林 3 75mg ,平均剂量为 2 8± 0 6 (1 8～ 4 1) μg/ (kg·d) ;B组 :2 0例 ,年龄 (8 1± 1 3)岁 (5 1～ 10 3)岁 ,乳房开始发育年龄 (7 0± 1 2 )岁 (4～ 8)岁 ,骨龄 (8 9± 1 4 )岁 (6～ 11 5 )岁 ;每 4周肌肉注射曲普瑞林 3 75mg,平均剂量为 4 8± 1 1(3 2～ 7 4 ) μg / (kg·d)。两组均连续用药 1年以上。治疗过程中注意监测以下指标 :性发育情况、身高、体重、生长速率、血性激素的水平、骨龄等。结果　每 6周皮下注射曲普瑞林3 75mg的治疗方案与每 4周肌肉注射普瑞林 3 75mg的治疗方案均能使患儿的第二性征减退、停止发育 ,乳房发育明显受到抑制 ,乳腺回缩或乳腺组织变松软 ;卵巢体积缩小 ,直径大于 0 4cm的卵泡消失 ;促性腺激素分泌减少 ,性激素下降至青春前期水平 ;A、B两组的年生长速率 (cm/年 )分别由治疗前的 6 3±     

女童性早熟38例

目的探讨女童真性性早熟和假性性早熟的早期鉴别及预防。方法对38例女童性早熟患儿详细询问病史,测身高、体质量,摄左腕正位X线片进行骨龄评价(Gmelich-Pyle法),B超检查,促性腺激素释放激素(LHRH)刺激试验:静脉注射戈那瑞林2.5μg.kg-1,分别于注射后0min、30min、60min静脉采血查血卵泡刺激素(FSH)、黄体生成素(LH)、雌二醇(E2)水平。结果38例中真性性早熟18例,其中17例为原发性;假性性早熟20例,均原因不明,但对各种儿童饮料、滋补保健品经常食用及各种肉类在饮食中比例较大者假性性早熟组明显高于真性性早熟组。LHRH刺激试验LH、FSH和E2的峰值升高均明显,其中以LH峰值升高最明显。2组比较,骨龄/身高年龄差异显著,骨龄/实际年龄无统计学差异。结论LH和骨龄/身高年龄是真假性早熟最重要的鉴别指标,性早熟应以早预防、早诊断、早治疗为主,同时应对其进行心理行为干预治疗。     

先天性肾上腺皮质增生症21-羟化酶缺乏患儿身高单中心25年随访研究

目的探讨先天性肾上腺皮质增生症(CAH)21-羟化酶缺乏(21-OHD)患儿近成年身高(NFH)的影响因素。方法对1989年3月至2015年5月中山大学附属第一医院儿童生长中心诊治的82例因21-OHD引起的CAH患儿的NFH进行随访,与正常人群身高及遗传身高(TH)进行比较,并对相关因素进行分析。结果 82例经随访10.6(0.5~25.5)年达NFH,NFH标准差分值(NFH SDS)为(-1.9±1.1),低于正常人群(P0.001)。治疗组NFH显著高于未治疗组(P=0.01);早诊断组NFH亦显著高于晚诊断组(P=0.019)。治疗组62例多因素回归分析显示,TH、依从性、氢化可的松(HC)剂量与NFH相关。治疗组HC与NFH有负相关趋势(r=-0.23,P=0.078)。对控制欠佳者,HC原剂量+来曲唑组NFH改善优于HC剂量增加组(P=0.064);对继发中枢性性早熟者,促性腺激素释放激素类似物(Gn RHa)+来曲唑组的NFH SDS显著高于未干预组(P0.005)。结论无论治疗与否,经典CAH 21-OHD患儿NFH均低于正常人群,未治疗者更甚;早诊断、早治疗,提高治疗依从性,较小剂量HC以及抑制骨龄等辅助治疗有助于改善NFH。     

45,X Turner综合征合并中枢性性早熟1例报告并文献复习

目的总结Turner综合征(TS)合并中枢性性早熟的诊断和治疗经验,提高对该病的认识。方法报道1例45,X TS合并中枢性性早熟诊断、治疗和随访病例,对相关文献进行复习。结果患儿,女,7.5岁,因"乳房增大半年"就诊。身高117.9 cm(P_(7.2)),体重32.5 kg,肥胖外观,无高腭弓、颈蹼、盾形胸和肘外翻,乳房Tanner分期Ⅱ期,心肺查体未见异常,外阴阴毛Tanner分期Ⅰ期。辅助检查:促性腺激素释放激素(LHRH)激发试验峰值:黄体生成素(LH)11.9 U·L~(-1),卵泡刺激素(FSH)34.2 U·L~(-1),雌二醇(E2)39.3 ng·L~(-1)。盆腔超声示卵巢增大。骨龄9.7岁。应用促性腺激素释放激素类似物(GnRHa)治疗2.7年后,身高131.4 cm,骨龄12岁,联合重组人生长激素(rh GH)继续治疗2.3年,身高148.4 cm,骨龄13岁。停药1年半后身高154.2 cm,接近遗传靶身高,检测LH 11.9 U·L~(-1),FSH 50.5 U·L~(-1),E2 38.9ng·L~(-1),染色体:45,X。系统文献检索国外仅有6例TS合并中枢性性早熟的病例报告,其中5例染色体为嵌合体,1例为1条X染色体的片段缺失。结论单体型TS可出现中枢性性早熟,GnRHa联合rh GH治疗能够改善患儿成年终身高。     

中枢性性早熟患儿5种骨龄测定方法的比较研究

目的探讨CHN法、TW2法中日英3种标准、TW3法5种骨龄测定方法对中枢性性早熟(CPP)患儿的诊断价值及正常值临界点的确定。方法由两名医师采用盲法回顾性分析CPP患儿61例(病例组),与每一个CPP患儿性别相同,年龄、身高、体质量基本一致的同期体检者61例、8岁以后出现乳房发育的女童6例(均为对照组)治疗前左手腕部X线片,用CHN法、TW2法中英日3种标准和TW3法进行骨龄判定,计算骨龄与年龄的差值,用SPSS13.0统计软件进行受试者工作特征(ROC)分析。结果 (1)两名医师骨龄测定结果的Kappa值为0.776(u=16.128,P<0.05);(2)5种骨龄测定方法的ROC曲线下面积分别为:CHN法0.921±0.024,95%可信区间为0.875～0.967;TW2法中国南方人标准为0.947±0.019(0.910～0.983);TW2法日本人标准为0.937±0.023(0.892～0.982);TW2法英国人标准为0.931±0.022(0.888～0.975);TW3骨龄测定法为0.924±0.023(0.879～0.969);5种方法的诊断价值差异无统计学意义(Z=0.85,P>0.05...     

女性特发性中枢性性早熟 GnRHa治疗探讨

目的对GnRHa治疗特发性中枢性性早熟(ICPP)效果进行评价,并对影响其疗效的相关因素进行探讨。方法对72例特发性中枢性性早熟患儿治疗中进行定期随访,对患儿实际年龄、骨龄和身高的变化进行观察比较。根据患儿身高和骨龄的变化对成年期终身高进行预测,观察药物对患儿治疗后预测身高(PAH)的影响,并对影响GnRHa药物治疗疗效的相关因素进行分析。结果GnRHa治疗2年后SDSca由1.10±1.12下降到0.80±1.07,SDSba由-1.98±1.01升高到-0.97±1.48,PAH由(152.93±8.10)cm增加到(158.93±9.01)cm。对照组的患儿虽保持了比较高的生长速度,但是其SDSca、SDSba无显著变化,PAH由(157.81±9.53)cm下降到(150.69±12.43)cm。经统计学处理,GnRHa治疗后PAH与治疗开始时CA和BA的差值和BA/CA值呈负相关,与治疗开始的SDSba呈正相关,并与SDS呈负相关。结论GnRHa治疗后患儿PAH增加,其PAH与治疗前身高、SDSca、SDSba、BA和CA的差值有相关关系。     

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.