无创血流动力学监测对儿童脓毒性休克液体复苏容量反应性的预测价值

目的　探讨无创血流动力学监测对脓毒性休克液体复苏容量反应性的预测价值。方法　选取2018年2月至2020年3月于湖南省儿童医院儿童重症监护病房（PICU）确诊的脓毒性休克患儿92例纳入研究, 患儿均给予无创心输出量测量仪床旁监测心脏指数（CI）、 每搏输出量指数（SVI）、 系统血管阻力指数（SVRI）等指标。根据液体复苏治疗前后每搏输出量指数变化率（△SVI）分为有反应组（△SVI≥10%）和无反应组（△SVI＜10%）。观察患儿治疗前后各项血流动力学指标的变化, 并行受试者工作特征（ROC）曲线分析预测儿童脓毒性休克液体复苏容量反应性。 结果　（1）两组患儿年龄、 性别、 感染源及感染部位儿童危重病例评分（PCIS）、 序贯器官衰竭（SOFA）评分、 输液量及机械通气各参数等比较差异均无统计学意义（P＞0.05）, 液体复苏后无反应组较有反应组肺水肿发生率及病死率增高, 住院时间及机械通气时间延长（P＜0.05）。（2）治疗前有反应组患儿CI、 SVI与无反应组比较差异有统计学意义（P＜0.05）［CI（2.55±0.63） L/（min·m2） vs. （3.12±0.75） L/（min·m2）; SVI （35.8±10.3） mL/（min·m2） vs. （40.5±6.3） mL/（min·m2）］, 治疗后CI、 SVI较治疗前明显增高, 心率（HR）、 系统血管阻力指数（SVRI）及每搏变异率（SVV）较治疗前下降, 差异有统计学意义（P＜0.05）, 但胸腔液体水平（TFC）增高不明显（P＞0.05）; 无反应组CI、 SVV、 SVI及SVRI等治疗前后变化不明显（P＞0.05）, 但TFC经液体复苏治疗后明显高于治疗前（P＜0.05）。（3）ROC曲线分析显示SVV, SVI和CI对液体治疗容量反应性有预测价值。SVV, SVI和CI预测液体治疗反应性的AUC分别为0.836（95%CI 0.725～0.947 ）、 0.778（95%CI 0.651～0.905）、 0.793（95%CI 0.663～0.922）（P＜0.005）。且当SVV≥13%时, 其预测液体治疗反应性的敏感度为85.8%,特异度为80.3%, 当SVI≤38 mL/（min·m2）, 其敏感度为81.0%, 特异度为75.8%, 当CI≤2.865 L/（min·m2）时, 其敏感度为78.5%, 特异度为79.2%。结论　无创心输出量测量仪可动态监测无创血流动力学指标, 且SVV、 SVI、 CI可预测儿童脓毒性休克液体治疗的容量反应性, 对指导脓毒性休克早期液体复苏和优化液体管理及预负荷有重要意义,值得临床推广。     

累及神经系统手足口病患儿临床特征及危重症危险因素分析

目的 探讨重症和危重症手足口病患儿典型的临床体征和辅助检查指标,丰富卫生部《手足口病诊疗指南》（2008年版）的内容。方法 以2008年5～12月在广州市妇女儿童医疗中心儿童医院住院治疗的累及神经系统手足口病重症和危重症患儿为研究对象。对临床特征和辅助检查结果进行汇总分析,比较重症组和危重症组神经、呼吸和循环系统表现,以及辅助检查结果的差异,Logistic回归分析重症进展为危重症的危险因素。结果 142例患儿进入分析,其中男88例,女54例;<3岁110例（77.5％）。重症组75例,危重症组67例。①高热82例(57.7％),热程(5.68±3.19) d;典型皮疹88例（62.0％）;②神经系统主要表现：肢体震颤107例(75.4%)、精神差93例(65.5%)、烦躁86例(60.6%)、双膝反射活跃或亢进79例(55.6%)、惊跳78例(54.9%)、呕吐73例(51.4%);③循环和呼吸系统主要表现：心率增快35例(24.6%)、CRT 3~5 s 34例(23.9%)、呼吸浅快31例(21.8%)、呼吸节律不规则29例(20.4%)、血压升高21例(14.8%)、CRT>5 s 19例(13.4%)、肺出血9例(6.3%);④辅助检查：WBC>12×109·L-1 55例(38.7%)、血糖升高90例(63.4%)、胸部X线片提示肺部渗出性病变36例(25.4%);⑤危重症组颈抵抗、肌张力增高或减低、抽搐、肢体无力、眼球运动异常、心率增快、血压升高、CRT 3~5 s或>5 s、呼吸浅快、呼吸节律不规则和肺部渗出性病变发生率均显著高于重症组;⑥多因素Logistic回归分析显示,心率增快（OR=17.918,95%CI:4.634~69.284）、CRT>5 s(OR=8.985, 95%CI: 1.568~51.488)、颈抵抗(OR=8.467,95%CI: 1.964~36.513)和肺部渗出性病变(OR=7.692, 95%CI:2.345~25.235)是重症患儿进展为危重症的危险因素;⑦治疗和预后：6例死亡,136例治愈或好转出院,随访6～12个月,未发现明显的智力落后、继发性癫及肢体瘫痪。结论 肢体震颤、精神差、烦躁、惊跳、呕吐及膝反射活跃或亢进是神经系统病变的早期症状和体征;心率增快、CRT>5 s、颈抵抗及肺部渗出性病变是手足口病重症患儿进展为危重症的高危因素。     

儿童危重型手足口病死亡的危险因素分析

目的 探讨儿童危重型手足口病死亡的危险因素。方法 以2010 年5 月至2012 年9 月监护室住院治疗的164 例危重型手足口病患儿为研究对象,根据预后分为死亡组（33 例）和存活组（131 例）。比较两组在基本情况、临床症状、体征、辅助检查方面的差异;采用非条件logistic 回归分析死亡的危险因素。结果 死亡组和存活组在不典型皮疹、持续高热（≥ 3 d）、呼吸困难、肺出血、心率增快、血压异常、冷汗、毛细血管再充盈时间>3 s、频繁抽搐发生率及血糖、血清肌酸激酶同工酶、血清乳酸水平方面存在明显差异（P<0.05）。多因素logistic 回归分析显示：肺出血（OR=9.466,95%CI：1.786~21.256）、血压异常（OR=5.224,95%CI：1.012~28.985）、血清乳酸增高（OR=2.154,95%CI：1.020~8.253）是危重型手足口病死亡的独立危险因素。结论 肺出血、血压异常、血清乳酸增高是危重症手足口病患儿死亡的主要危险因素。     

维生素D缺乏性佝偻病患儿心功能评价

目的探讨VitD缺乏性佝偻病患儿治疗前后左心收缩功能。方法按佝偻病的生化分类将患儿分为Ⅰ组11例,Ⅱ组12例,Ⅲ组13例。使用彩色多普勒超声诊断仪对佝偻病36例治疗前后进行心功能测定,20例健康儿童作为健康对照组。结果佝偻病患儿治疗前心搏量（SV）、射血分数（EF）、左室射血前期（PEP）、射血时间（LVET）和PEP/LVET的比值与健康对照组比较均有显著差异（Pa〈0.01）;治疗后PEP、PEP/LVET恢复正常,SV、EF、LVET仍有差异（Pa〈0.01）。各组治疗前后比较以Ⅲ组心功能受影响最明显,EF、左室缩短分数（FS）、PEP、LVET和PEP/LVET治疗前、后均有显著差异（Pa〈0.01）。结论VitD缺乏性佝偻病患儿左心的收缩功能可受到影响,特别是佝偻病第3期心功能更易受累,且心功能异常随着佝偻病的治疗可恢复正常。     

脑干听觉诱发电位对重症手足口病患儿脑损伤的评价

目的 探讨脑干听觉诱发电位（BAEP）对重症和危重症手足口病患儿脑损伤的评价作用。方法 以2010年8月至2011年12月在广州市妇女儿童医疗中心住院治疗的重症和危重症手足口病患儿作为重症组和危重症组,于入院时和病程2周时行BAEP检查,以同期住院的无神经系统受损表现的手足口病患儿为对照组,于入院时行BAEP检查。比较3组BAEP各项指标间的差异。采用脑干反应阈值及Hall分级法比较治疗前后BAEP的变化情况。结果 重症组121例,危重症组102例,对照组200例进入分析。①对照组未见BAEP异常病例,重症组34例(28.1%)BAEP异常,危重症组49例(48.0%)BAEP异常,差异有统计学意义（P<0.05）。BAEP Ⅲ波PL延长、Ⅲ或Ⅴ波波幅低平或分化不良的发生率危重症组显著高于重症组（P<0.05）。②重症组和危重症组脑干反应阈值在治疗后较治疗前均显著降低（P<0.05）。治疗前危重症组脑干反应阈值显著高于重症组（P<0.05）,治疗后两组差异不显著。重症组和危重症组治疗后BAEP 1级所占比例均较治疗前显著增加,2和3级比例均有下降。结论 重症和危重症手足口病患儿均存在脑干功能损伤,以脑干反应阈值升高、Ⅲ波PL延长、Ⅲ波和Ⅴ波波幅低平或分化不良为主。Hall分级法和脑干反应阈值可动态评估BAEP变化,推测病情可能的演变。     

心输出量监测系统在儿童危重症中的应用研究

目的 通过超声心输出量监测系统(ultrasonic cardiac output monitor,USCOM)记录危重症患儿的每搏心输出量(systolic volume,SV)、心输出量(cardiac output,CO)、外周血管阻力(systemic vascular resistance,SVR)、每搏输出量变量(systolic volume variance,SVV)等变化,了解心功能及血流动力状态.方法 研究对象为依据小儿危重病例评分标准符合危重症病例的11例患儿(观察组)及同期住院的未达到危重症病例标准的20例支气管肺炎患儿(对照组).对2组患儿行USCOM检查,分析2组在心功能及血流动力状态的差异.结果 观察组和对照组CO和SV差异有统计学意义(P＜0.05),SVV和SVR差异无统计学意义(P＞0.05).观察组治疗前后CO、SV、SVV差异有统计学意义(P＜0.05).结论 USCOM可以监测危重病患儿的SV、CO、SVR、SVV等,从而及时掌握患儿循环状态,且操作简便,数据准确,临床上值得推广.     

儿童早期预警评分在识别危重患儿病情中的价值

目的 探讨儿童早期预警评分（PEWS）识别危重患儿病情的价值。方法 选取2016年1~12月由中南大学湘雅医院普通病区转入PICU或急诊收入PICU的患儿120例为PICU组,该院该期间入住普通病房的120例患儿作为对照组。对PICU组的120例患儿根据病种的不同分为呼吸/循环系统疾病亚组（55例）和神经/其他系统疾病亚组（65例）。记录患儿入院时的PEWS评分,采用受试者工作特征（ROC）曲线分析PEWS评分对病情评估的价值。结果 PICU组PEWS评分显著高于对照组（P < 0.05）。呼吸/循环系统疾病亚组的PEWS评分显著高于神经/其他系统疾病亚组（P < 0.05）。以患儿是否收住PICU为预测指标时,PEWS评分的最佳截断值为3.5分,灵敏度为85%,特异度为95%,ROC曲线下面积为0.951（95% CI：0.923~0.980）。其中神经/其他系统疾病亚组的患儿ROC曲线下面积为0.768,呼吸/循环系统疾病亚组的患儿ROC曲线下面积为0.968。PEWS评分 > 6分、4~6分及 ≤ 3分患儿的病死率分别为40%、21%、0,组间比较差异有统计学意义（P < 0.001）。结论 PEWS对识别危重症患儿病情严重程度有重要价值,且不同病种对PEWS评分的敏感性有差异;PEWS评分对患儿的预后有预测价值。     

血液净化在重症腺病毒肺炎患儿中的临床应用

目的 探讨血液净化在救治重症腺病毒肺炎患儿中的作用。方法 将2019年2~6月行机械通气治疗的57例重症腺病毒肺炎患儿,根据是否进行血液净化分为净化组（n=22）和常规组（n=35）。收集两组患儿的临床指标,包括热程、机械通气时间、重症监护室（ICU）住院时间及病死率;净化组血液净化前及净化后48 h白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平,血液净化前及净化后6、12、24、48 h的每搏输出变异率（SVV）、胸腔液体水平（TFC）、氧合指数（P/F）、二氧化碳分压（PCO2）。结果 净化组热程、机械通气时间、ICU住院时间均要短于常规组（P < 0.05）,两组病死率比较差异无统计学意义（P > 0.05）。净化组患儿血液净化后IL-6、TNF-α水平较血液净化前均下降（P < 0.05）。血液净化后12、24、48 h ,净化组患儿SVV、TFC均较血液净化前下降（P < 0.01）。血液净化后6、12、24、48 h,净化组患儿P/F值均较血液净化前上升,PCO2均较血液净化前下降（P < 0.01）。结论 血液净化对重症腺病毒肺炎治疗具有辅助作用,可有效改善患儿的临床症状,是重症腺病毒肺炎有潜力的治疗选择。     

血液净化在重症腺病毒肺炎患儿中的临床应用

目的 探讨血液净化在救治重症腺病毒肺炎患儿中的作用。方法 将2019年2~6月行机械通气治疗的57例重症腺病毒肺炎患儿，根据是否进行血液净化分为净化组（n=22）和常规组（n=35）。收集两组患儿的临床指标，包括热程、机械通气时间、重症监护室（ICU）住院时间及病死率；净化组血液净化前及净化后48 h白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）水平，血液净化前及净化后6、12、24、48 h的每搏输出变异率（SVV）、胸腔液体水平（TFC）、氧合指数（P/F）、二氧化碳分压（PCO2）。结果 净化组热程、机械通气时间、ICU住院时间均要短于常规组（P < 0.05），两组病死率比较差异无统计学意义（P > 0.05）。净化组患儿血液净化后IL-6、TNF-α水平较血液净化前均下降（P < 0.05）。血液净化后12、24、48 h ，净化组患儿SVV、TFC均较血液净化前下降（P < 0.01）。血液净化后6、12、24、48 h，净化组患儿P/F值均较血液净化前上升，PCO2均较血液净化前下降（P < 0.01）。结论 血液净化对重症腺病毒肺炎治疗具有辅助作用，可有效改善患儿的临床症状，是重症腺病毒肺炎有潜力的治疗选择。     

地西泮预防热性惊厥复发的疗效与安全性的系统评价和Meta分析

目的 采用Meta分析方法评价间歇使用地西泮预防热性惊厥（FS）复发的疗效及安全性。方法 计算机检索The Cochrane Library(2014年第7期)、PubMed、EMBASE、中国生物医学文献数据库、中国知网、维普中文期刊数据库和万方数据库,收集使用地西泮预防儿童FS复发的RCT文献,检索时限均为建库至2014年7月。由2位研究者按照纳入与排除标准筛选文献,提取数据和评价纳入文献的方法学质量。根据FS复发危险因素行亚组分析。采用RevMan 5.2软件进行Meta分析。结果 9篇RCT文献（n=1 578）进入Meta分析。纳入文献的随机序列产生、分配隐藏和盲法为高度偏倚,选择性报告研究结果、结果的完整性和其他偏倚来源为低度偏倚。①随访6个月地西泮组与对照组FS复发率差异无统计学意义,RR=0.62(95% CI：0.34~1.13), P=0.12;RD=-0.07(95%CI:-0.16~0.02);对FS复发危险因素行亚组分析：地西泮低危险亚组与对照组FS复发率差异无统计学意义,RR=0.69（95%CI：0.40~1.21),P=0.20,中危险亚组与高危险亚组FS复发率显著低于对照组,RR分别为0.31（95%CI：0.15~0.62)和0.24（95%CI：0.10~0.56）。②随访12和24个月地西泮组FS复发率显著低于对照组,RR分别为0.59（95%CI：0.38~0.91）和0.54(95%CI:0.37~0.78);RD分别为-0.12(95%CI：-0.22~-0.02)和-0.17(95%CI:-0.27~-0.07)。对FS复发危险因素行亚组分析：地西泮低危险亚组与对照组FS复发率差异无统计学意义,RR分别为0.81(95% CI:0.47~1.42)和0.71（95%CI：0.45~1.11),中危险亚组与高危险亚组FS复发率显著低于对照组,12个月： RR分别为0.39(95% CI:0.20~0.75)和0.27(95%CI:0.13~0.58);24个月：RR分别为0.43(95%CI：0.24~0.77)和0.35(95%CI：0.19~0.62)。③纳入文献均无地西泮严重不良事件的报告。结论 地西泮间歇给药可有效降低12和24个月FS复发率,对于FS中高危人群显示出较好疗效的趋势,但仍需进一步补充研究明确。     

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.