早产儿血清表皮生长因子水平与脑发育相关研究

目的 探讨早产儿血清表皮生长因子水平与脑发育的关系.方法 依据入选标准观察对象为自2005年8月起连续收治入本院新生儿病房、出生24 h内的胎龄为34周±3 d的"正常"早产适于胎龄儿30例.采用酶联免疫吸附测定(ELISA)法,分别测定30例早产儿生后24 h内和出生第8天空腹股静脉血清表皮生长因子(EGF)水平,分别为t0和t1值,计算血清EGF浓度变化的速率(△t).同时,在新生儿出生后6周(纠正胎龄接近40周)和纠正1月龄时进行NBNA评分测定.并将以上实验室数据与新生儿行为神经测定(NBNA)评分值及差值、早产儿出生后的头围增长值及增长速率进行Pearson相关分析.如果P值＜0.05,则认为差有统计学意义.结果 30例早产儿观察对象t0为(234.71±58.07)pg/ml,t1为(347.81±87.49)pg/ml,△t为(16.16±9.94)(12.14、15.20)pg/ml/d;Pearson相关分析显示2次NBNA评分结果及差值、出生后6周和纠正1月龄时的头围增长值/增长速率与t0值无相关性(P＞0.05);2次NBNA评分结果及差值、出生后6周和纠正1月龄时的头围增长值/增长速率与t1和△t之间有相关性(P＜0.05).结论 研究结果表明,早产儿出生后血清EGF浓度呈上升趋势,提示早产儿出生后体内EGF合成和释放增加,可能促进脏器成熟和组织修复;更重要的是,早产儿出生1周时高水平血清EGF浓度和/或较快上升速率者,其出生后头围增长速度也快,可能有较好的脑发育水平、远期预后良好.     

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目的 探讨血清表皮生长因子水平与早产儿脑发育的关系.方法 对2005年8月至2006年4月连续收入上海儿童医学中心新生儿病房、出生24h内、胎龄(238±3)d的30例早产适于胎龄儿,采用酶联免疫吸附测定法(ELISA)分别测定其生后24h内(t0值)和第8天(t1值)的空腹血清EGF水平,计算其血清EGF变化速率(△t);进行床边头颅B超检查以排除颅内病变;并在校正胎龄近40周(生后6周)和1月龄时(生后10周)分别测量其头围并进行NBNA评估,计算其头围增长速率及NBNA差值.应用Pearson方法对所有测定结果分别进行相关分析.结果 30例早产儿的血清EGFt0为(234.71±58.07)pg/mL,t1为(347.81±87.49)pg/mL,△t为(12.14±1.85)pg/(mL·d).Pearson相关分析显示,2次NBNA评分结果及其差值、出生后6周和10周时的头围增长值和增长速率,均与t0值无明显相关性(P均＞0.05);但上述测定结果均分别与t1和△t之间呈显著相关(P均＜0.05).结论 早产儿出生后血清EGF质量浓度呈上升趋势,提示早产儿出生后体内EGF合成和释放增加,可能促进脏器成熟和组织修复.尤其早产儿在出生1周时的血清EGF呈高水平和(或)上升速率较快者,其生后头围的增长速度也较快,提示其今后可能有较好的脑成熟发育水平、较低的精神神经系统后遗症的发生率,以及远期预后良好.     

影响早产儿行为神经测定因素的分析

目的 探讨新生儿行为神经测定(NBNA)在早产儿的应用及影响其评估指标的因素.方法 选择2006年1月至2007年6月在我院新生儿科住院治疗的123例早产儿,分别在纠正胎龄40周时进行NBNA评分,分析胎龄、出生体重、是否机械通气以及机械通气时间、围生期是否有致脑损伤的高危因素对NBNA评分的影响.结果 胎龄<30周、～32周、～34周早产儿及出生体重<1 250 g、～1 500 g、～2 000 g早产儿NBNA评分差异均具有显著性(P<0.01),胎龄越低、出生体重越低,NBNA评分越低;需机械通气的早产儿NBNA评分明显低于未上呼吸机者(P<0.01),机械通气时间＞7 d NBNA评分明显低于＜7 d者(P<0.05);围生期有出血性和缺血性脑损伤、间接胆红素≥256.5 μmol/L、血糖反复<2.6 μmol/L、发生感染者NBNA评分明显降低(P<0.01);臀位、钳产、吸引产早产儿NBNA评分明显低于剖宫产和顺产者(P<0.01);Apgar评分为0～3分者NBNA评分明显低于4～7分和≥8分者(P<0.01).结论 胎龄、出生体重、是否机械通气、机械通气时间、异常的分娩方式、合并重度窒息均影响早产儿的NBNA评分.对于早产儿,特别是胎龄<32周,出生体重<1 500 g,存在致脑损伤高危因素的早产儿,生后3～7 d内应行头颅B超检查,及早发现颅内病变,尽早干预,减少后遗症的发生.     

宫外生长迟缓早产儿出院后不同营养策略对体格及神经发育的近期影响

目的对比分析宫外生长迟缓(extrauterine growth restriction,EUGR)早产儿出院后不同的强化营养策略对其生后1~6校正月龄体重、身长、头围等体格生长及神经发育指标的影响,为进一步寻找优化EUGR早产儿出院后的营养方案提供依据。方法收集连云港市第一人民医院新生儿重症监护病房2016年1月至2018年12月期间住院治愈出院的EUGR早产儿共178例,随机分为A、B两组,A组给予足量强化营养至校正胎龄40周后改半量强化营养至校正月龄6月龄,B组给予足量强化营养至体重达同校正胎龄平均体重的第10百分位后改半量强化营养至体重达同校正胎龄平均体重的第25百分位。分别在校正胎龄40周、校正月龄1~6月龄进行体格发育指标测定、校正月龄6月龄进行神经发育指标测定并比较两组的差异。统计学方法采用独立样本t检验和χ2检验。结果两组早产儿校正胎龄40周、校正月龄1月的体格发育情况比较差异无统计学意义(P>0.05)。校正月龄2月龄A组早产儿的体重、身长、头围均超过B组早产儿[体重(4692±196)与(4630±211)g,身长(55.7±0.8)与(55.3±0.9)cm,头围(37.4±0.6)与(37.0±0.6)cm,P<0.05]。校正月龄3月龄A组早产儿的体重、身长、头围均超过B组早产儿(P<0.05)。校正月龄4月龄A组早产儿的体重、身长、头围均超过B组早产儿[体重(6480±305)与(6385±270)g,身长(63.1±1.2)与(62.0±1.1)cm,头围(40.4±0.7)与(40.1±0.6)cm,P<0.05]。校正月龄5月龄A组早产儿的体重、身长、头围均超过B组早产儿(P<0.05)。校正月龄6月龄A组早产儿的体重、身长、头围均超过B组早产儿[体重(7643±359)与(7452±305)g,身长(66.1±1.3)与(65.7±1.0)cm,头围(42.2±0.7)与(42.0±0.6)cm,P<0.05]。校正胎龄40周两组早产儿新生儿神经行为评分以及异常率比较差异无统计学意义(P>0.05);校正月龄6月龄两组早产儿Gesell评分异常率、应物能、语言能、应人能评分比较均无统计学意义(P>0.05),A组早产儿粗大动作能及精细动作能评分明显高于B组早产儿(P<0.05)。结论两组所采用的强化营养策略均可帮助EUGR早产儿追赶性生长,足量强化营养至校正胎龄40周后改半量强化营养至校正月龄6月龄上在体格发育有明显优势,而神经发育的近期优势不明显。     

新生儿行为神经测定联合儿心量表评价院外转运早产儿的智能发育状况

目的评价院外转运对早产儿智能发育的影响。方法选取我院2007年院外转运的141例早产儿为转运组,同期在我院产科出生,胎龄、出生体重以及呼吸窘迫综合征(RDS)、颅内出血(ICH)和脑室周围白质软化(PVL)等疾病发病情况与转运组相匹配的早产儿100例为对照组,所有病例均没有窒息抢救史,均完成了新生儿行为神经测定(NBNA)及儿心量表检测(NET),每组分为<32周、32～34周及>34周3个胎龄段,根据两组NBNA评分及儿心量表评分情况分析各胎龄组早产儿的智能发育状况,通过比较两组智能发育状况评价院外转运对早产儿智能发育的影响。结果(1)胎龄<32周:转运组和对照组NBNA评分(34.6±1.5比35.0±1.3)及儿心量表评分(88.5±8.0比91.7±10.1)之间差异均无统计学意义(P>0.05);(2)胎龄32～34周:转运组NBNA评分(34.7±1.1)低于对照组(35.5±0.9),差异有统计学意义(P<0.05);两组儿心量表评分(92.0±8.8比97.1±11.3)差异无统计学意义(P>0.05);(3)胎龄>34周:转运组和对照组NBNA评分(35.5±1.3比35.5±0.8)及儿心...     

新生儿行为神经测定联合儿心量表评价院外转运早产儿的智能发育状况

目的 评价院外转运对早产儿智能发育的影响.方法 选取我院2007年院外转运的141例早产儿为转运组,同期在我院产科出生,胎龄、出生体重以及呼吸窘迫综合征(RDS)、颅内出血(ICH)和脑室周围白质软化(PVL)等疾病发病情况与转运组相匹配的早产儿100例为对照组,所有病例均没有窒息抢救史,均完成了新生儿行为神经测定(NBNA)及儿心量表检测(NET),每组分为＜32周、32～34周及＞34周3个胎龄段,根据两组NBNA评分及儿心量表评分情况分析各胎龄组早产儿的智能发育状况,通过比较两组智能发育状况评价院外转运对早产儿智能发育的影响.结果 (1)胎龄＜32周:转运组和对照组NBNA评分(34.6±1.5比35.0±1.3)及儿心量表评分(88.5±8.0比91.7±10.1)之间差异均无统计学意义(P＞0.05);(2)胎龄32～34周:转运组NBNA评分(34.7±1.1)低于对照组(35.5±0.9),差异有统计学意义(P＜0.05);两组儿心量表评分(92.0±8.8比97.1±11.3)差异无统计学意义(P＞0.05);(3)胎龄＞34周:转运组和对照组NBNA评分(35.5±1.3比35.5±0.8)及儿心量表评分(96.6±9.4比97.0±10.5)之间的差异均无统计学意义(P＞0.05).结论 掌握好转运指征、做好转运前准备、及时处理转运中出现的问题以及对早产儿进行早期干预可以减轻或消除院外转运对早产儿智能发育的影响.     

产前应用单疗程及多疗程地塞米松对早产儿脑发育的影响

目的 探讨产前应用单疗程及多疗程地塞米松对早产儿脑发育的影响.方法 选择本院2005年8月-2007年3月NICU收治的28～34周的早产儿118例,按母亲产前应用地塞米松的情况分为对照组、单疗程组、多疗程组.对照组未用地塞米松;单疗程应用地塞米松10 mg,1次/d,肌肉注射,3 d为1个疗程,仅用1个疗程;多疗程组应用地塞米松2个疗程以上.3组早产儿出生后均予对症支持治疗.纠正胎龄至预产期后行新生儿20项行为神经测定(NBNA),纠正胎龄至出生3、6、12个月时采用中国儿童发展中心(CDCC)制定的婴幼儿智力发育指数(MDI)和运动发育指数(PDI)量表进行检测.采用SPSS 11.0软件进行统计学分析.结果 纠正胎龄达预产期时及达预产期后7 d单疗程组NBNA评分明显高于对照组及多疗程组(Pa<0.05).纠正胎龄至出生3、6个月时行CDCC评分,单疗程组MDI和PDI均明显高于对照组及多疗程组(Pa<0.05);12个月多疗程组MDI和PDI明显低于单疗程组及对照组(Pa<0.05),单疗程组显著高于对照组(Pa<0.05).结论 产前单疗程应用地塞米松能明显提高早产儿近、远期预后;多疗程GCS对早产儿神经系统近、远期发育均有一定的不良影响.     

新生儿重症监护病房极低出生体质量儿头围增长速度对1 岁龄神经发育结局的影响

目的以新生儿重症监护病房内极低出生体质量儿的不同头围增长速度预测纠正满1岁时的神经运动发育结局。方法前瞻性收集2016年6月至2017年12月入住新生儿重症监护病房的极低出生体质量(出生体质量1 500 g)早产儿,动态监测住院期间头围增长速度,按不同头围增长速度百分位数分为缓慢增长组(增长速度P_(10))、中度增长组(增长速度P_(10)～P_(90))和快速增长组(增长速度P_(90))。持续随访至纠正满1岁,运用贝利婴幼儿发育量表评估神经运动发育,分为发育迟缓(≤69分)、临界(70～79分)和正常(≥80分)组,比较各组体格发育及并发症情况。结果 131例研究对象,平均胎龄(30.29±2.06)周,平均出生体质量(1 280±184)g,住院期间头围增长平均速度为(0.49±0.19)cm/周。缓慢增长组、中度增长组和快速增长组的头围增长速度分别为(0.12±0.05)cm/周、(0.49±0.13)cm/周和(0.81±0.03)cm/周;中度增长组和快速增长组的纠正1岁龄的智力发育指数(MDI)和运动发育指数(PDI)均高于缓慢增长组,差异有统计学意义(P0.05)。MDI临界组和正常组的头围增长速度均大于发育迟缓组,PDI正常组的头围增长速度大于发育迟缓组,差异均有统计学意义(P0.05)。结论极低出生体质量儿住院期间头围增长速度与纠正满1岁时的神经运动发育结局具有相关性。     

早产儿血清脂联素水平测定的临床意义

目的 研究早产儿出生后血清脂联素水平动态测定的意义.方法 选取2007年1-10月出生的新生儿70例.其中40例早产儿为研究组,足月儿30例为对照组.新生儿出生时由专人准确测量新生儿净体质量、卧式身长并计算体质量指数(BMI).采用放射免疫法测定其血清脂联素水平.结果 28～33周早产儿出生第1、4、7、28天血清脂联素水平分别为(6.19±3.78)mg/L、(18.15±6.60)mg/L、(21.33±2.23)mg/L、(26.18±4.06)ms/L;>33～37周早产儿出生第1、4、7、28天血清脂联素水平分别为(12.91±4.26)mg/L、(20.27±5.33)mg/L、(19.08±7.32)mg/L、(23.34±1.55)mg/L;足月儿出生第1、4、7、28天血清联素水平分别为(19.59±5.25)mg/L、(26.55±8.76)mg/L、(21.07±4.31)mg/L、(25.38±7.32)mg/L,经统计学分析显示,新生儿出生第1天脂联素水平随着胎龄的增加呈上升趋势(F=32.27 P<0.05);脂联素与BMI呈正相关(r=1.24 P<0.05);早产儿第1天和第28天血清脂联素水平有明显差异,第1、4、7天血清脂联素水平无明显差异;足月儿第1、4、7、28天血清脂联素水平无明显差异.结论 早产儿脂联素水平与胎龄、BMI和日龄均密切相关,脂联素在早产儿生长发育中起重要作用.     

探讨健康足月新生儿NBNA的影响因素

目的 分析胎龄、日龄、体重及性别对健康足月新生儿行为神经测定(NBNA)的影响,并与常模数据进行比较,探讨NBNA的理想值范围.方法 选择2009年11月至2012年6月河北省三河市妇幼保健院出生的健康足月儿,生后1周内行NBNA测定,对得分情况进行统计学描述,对不同胎龄、检查日龄、体重及性别之间NBNA总分的差异应用秩和检验,探讨NBNA总分的影响因素.并且对比分析本项目与1988年中国12城市健康新生儿NBNA评分的差异.结果 共入选1345例健康足月新生儿,NBNA总分均在37分以上,平均(39.6±0.7)分.扣分项目主要出现在对光习惯的形成、对声音习惯的形成、握持反射及牵拉反应4个单项中,以牵拉反应扣分最多.不同胎龄、日龄、体重及不同性别之间NBNA总分差异无统计学意义(P＞0.05).但随胎龄增加,NBNA满分率有增加趋势.与1988年中国12城市健康新生儿NBNA评分结果进行比较,NBNA得分分布有显著差异,本项目得分无37分以下者,且39分及40分所占比例更高.结论 NBNA作为一种足月新生儿的行为神经评估方法,在健康足月儿中总分的分布不受性别、日龄及体重的影响,但NBNA评分的满分率存在随胎龄增加而增加的趋势.将生后7天以内新生儿NBNA总分35～36分视为正常须谨慎,足月新生儿NBNA评估中理想得分为37分以上.     

Resurgence of measles in Singapore: profile of hospital cases

OBJECTIVE: To ascertain the profile of cases of measles seen at a general hospital during a recent outbreak that occurred despite a measles vaccination program. METHODOLOGY: A retrospective study from January 1991 to March 1998. All patients with measles (ICD code 055. 9) seen at the emergency unit or as inpatients were included. RESULTS: There were 87 cases identified. The diagnosis was clinical in all and proven serologically in 71%. Eighty-five per cent of the cases occurred between January 1997 and March 1998. There was a bi-modal age distribution with peaks in the very young (相似文献   

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.     

A profile of respiratory symptoms in urban and rural South Australian school children

This report describes the cross-sectional analyses of data from the first year of a longitudinal study using questionnaire and respiratory function data over a 5 year period from a sample of rural South Australian school children. The cumulative or lifetime prevalences of respiratory symptoms were estimated in 825 rural and 1261 urban school children aged between 5 and 15 years in order to determine if the prevalence rates differed between rural and urban school children. The study found the overall cumulative prevalence of asthma and/or wheezy breathing (AWB) to be 24.1% in the rural school children compared to 27.6% in the urban school children. Most children developed AWB symptoms before the age of 7 years, with 20% reporting moderately severe symptoms and 10% having more than one attack per fortnight. The cumulative prevalence of bronchitis, loose/rattly cough (BLRC) differed significantly between the rural school children (34.1%) and urban school children (47.9%). The BLRC symptoms preceded the development of AWB in many cases. Urban school children also reported a higher prevalence of atopic conditions.     

Hauttemperaturen verschiedener Körperoberflächenareale des Rumpfes bei Säuglingen

Summary In two groups of infants (3–53 weeks old) skin temperatures were controlled in different areas of the trunk—i.e.: regions of sternum, lungs, heart, liver, spleen, kidneys—at different room-temperatures (group I: 21–25°C; group II: 29–32°C). Rectal temperatures of some probands in both groups also had been controlled simultaneously. A definite change in the reaction to heat was proofed in different periods of the first year of life. In higher environmental temperatures the skin temperature was almost constant at every controll-point of the skin, even in older infants. In lower environmental temperatures the skin temperatures lowered continuously with age till 7. to 9. moth. From 10. to 12. month the lowering of skin temperature discontinued. The rectal temperatures were relatively constant in all infants. Only in infants from 7. to 12. month, whose skin temperatures were controlled in lower as well as in higher environmental temperatures, a tendency to higher rectal temperatures was proofed in warmer environmental temperatures.The significance of these results is discussed.

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Untersuchungen mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Psychopathologie du syndrome d’Asperger et « aspérigisation » de la société contemporaine

The author has attempted here to point out, just for a start, the characteristics of Asperger syndrome from the point of view of psychopathology through a rereading of Hans Asperger's original paper (1944). This thesis merits reevaluation, if for no other reason than to fill the gaps in operational diagnostics based on the DSM. It is found by rereading that Asperger's view of the principal disturbances of autistic psychopathy include a “disturbance of natural evidence” or a “crisis of common sense”. This question of natural evidence that he evokes with regard to autistic psychopathy corresponds to W. Blankenburg's natural evidence, which constitutes a key concept for comprehending schizophrenia in the form poor-symptom (“symptomarme Schizophrenie”) that he observes in the speech of his patient Anne Rau. One can deduce from this that in terms of fundamental disturbances, Asperger syndrome and this “symptom-poor” schizophrenia overlap at the level of loss of natural evidence. It is moreover possible to classify Asperger syndrome among the disturbances of spacing in the sense meant by the evolutionary psychiatry of A. Stevens and J. Price. The author then develops our comprehension of Asperger syndrome from the point of view of the perspective proposed by the notion of resilience in people with Asperger syndrome and of the possibility for them, through these mechanisms of adaptation, to find in the organization of the personality of the “as if” type a position of relative equilibrium. They concur or overlap in the creation of crutches, of borrowed personalities secondarily legitimated by the reaction of the socius. This will end up in the production of inventions and œuvres (works). Clearly, one rarely encounters several cases that one could consider pertinently to be “successful” Asperger syndrome. Finally, the author notes that one can find a sort of isomorphism between Asperger syndrome and contemporary society when he proposes the term “asperigisation” to characterize our society, given that the equilibrium between emotion and logic is strongly disturbed in these patients, in whom logic undergoes hypertrophy while emotion is impoverished. From this perspective, the author hopes to suggest reasons for the increase in the number of cases of Asperger syndrome in the clinical setting and in society in general in our contemporary era.     

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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     

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.     

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.