单纯性肥胖男童血清瘦素、性激素水平及其对性发育的影响

目的 探讨单纯性肥胖男性儿童血清瘦素、性激素水平及其对性发育的影响.方法 从8～14岁1 208例小学生中筛选出体质量指数(BMI)≥25 kg/m2的42例男童作为肥胖组,选择BMI 14.1～23.0 kg/m2的健康男童32例作为健康对照组,对所入选儿童用ELISA法测定其血清瘦素,放射免疫分析法测定其血清雌二醇(E2)、睾酮(T)水平,用游标卡尺测量其阴茎长度及睾丸体积.采用SPSS 10.0软件行组间t检验比较二组差异,直线相关分析单纯性肥胖儿童血清瘦素与E2、T的相关性.结果 肥胖组男童血清瘦素为(16.82±11.46)μg/L,较健康对照组(5.43±3.56)μ/L显著增高,二组比较有显著性差异(t=5.419 P<0.01).肥胖组男童血清E2水平为(20.51±16.42)ng/L,较健康对照组[(8.84±4.53)ng/L]显著增高,二组比较有显著性差异(t=3.903 P<0.01).肥胖组男童T水平为(1.64±0.85)μg,/L,低于健康男童[(2.07±0.98)μ/L],二组比较有显著性差异(t=2.018 P<0.05).肥胖组男童阴茎长度为(4.51±1.36)cm,低于健康男童[(5.64±0.99)cm],二组比较有显著性差异(t=3.965 P<0.01).肥胖组男童睾丸体积[(4.21±2.32)cm3]低于健康男童[(7.08±3.76)cm3],二组比较有显著性差异(t=4.043 P<0.01).瘦素与BMI、E2呈正相关(r=0.757,0.266 Pa<0.05),与T呈负相关(r=-0.368 P<0.01).结论 高水平瘦素可能是单纯性肥胖重要的生物学标志之一.单纯性肥胖男童存在性激素代谢紊乱、性发育落后,瘦素可能影响男性肥胖儿童的性发育.     

郑州地区儿童单纯性肥胖流行病学调查及中医循经推拿干预研究

目的了解郑州地区儿童肥胖发生情况和探索干预措施。方法于2001年抽样调查5688例中小学生,男2848名,女2840名,年龄7～18岁。肥胖标准以Cole等的诊断儿童肥胖的参考BMI值判断,并对筛选出的单纯性肥胖儿童22例(7～15岁,男18例,女4例)以中医循经推拿和行为矫正及饮食、运动调整综合治疗1个月,且于治疗结束6个月后随访。结果所调查的5688名中小学生超重发生率15.4%,肥胖发生率3.2%,男生超重、肥胖发生率(19.2%,4.6%)明显高于女生(11.5%,1.7%P<0.001);各年龄阶段超重发生率有明显差异(χ2=42.88P<0.001),高发年龄为8～15岁;各年龄阶段肥胖发生率亦有差异(χ2=21.28P<0.05),高发年龄为7～10岁和14～15岁;治疗1个月后22例肥胖儿童体质量均有下降,由入院时(76.45±19.87)kg下降至(69.06±17.98)kg,下降幅度(7.43±2.58)kg,BMI值由治疗前(31.05±3.96)下降至(27.72±3.54),治疗前后体质量和BMI值比较均有显著差异(t=13.6,12.88P<0.01),且体质量、BMI值下降幅度与入院时体质量、BMI值均呈明显相关性(r=0.77P<0.01;r=0.49P<0.05)。结论近年来儿童肥胖发生率增高,以中医循经推拿和行为矫正及饮食、运动调整综合治疗的方法疗效好且舒适,儿童易于接受。     

减肥对单纯性肥胖儿童糖耐量及胰岛素分泌功能的影响

目的探索单纯性肥胖儿童糖耐量减低(IGT)的干预方法。方法测定14例单纯性肥胖儿童经日服葡萄糖耐量实验(OGTT),诊断为IGT,男10例,女4例;年龄8-15岁;体质量(57.7-114.0)kg,体质量指数(BMI)(30.18±1.71)。给予中医循经推拿和行为矫正及饮食、运动调整综合减重治疗2个月。结果14例IGT肥胖儿童减肥治疗2个月后9例OGTT恢复正常,体质量下降至(49-95)kg;BMI下降至(25.30±1.35)kg;治疗后空腹胰岛素、餐后2 h胰岛素、餐后2 h血糖[(14.23 ±2.35)mIU/L、(47.20±10.26)mIU/L、(5.63±0.91)mmol/L]较治疗前[(32.54±7.13)mIU/L、(164.53±33.60)mIU/ L、(8.75±1.09)mmol/L]明显下降(P<0.05,<0.01,<0.05);空腹血糖(4.80±0.52)mmol/L和治疗前(5.36±1.59) mmol/L比较无明显差异(P>0.05)。结论减肥是干预单纯性肥胖儿童IGT、改善胰岛素抵抗及预防2型糖尿病的最好方法。     

单纯性肥胖儿童骨龄与体质量指数及性激素水平的相关性

目的 检测单纯性肥胖儿童的骨龄和性激素水平,分析骨龄与体质量指数(BMI)和性激素水平之间的关系.方法 选取40例单纯性肥胖患儿(肥胖组)及40例体检健康儿童(健康对照组).常规测量二组儿童身高和体质量,并计算BMI.采用G-P图谱法对左手腕指关节正位片进行骨龄评定;采用罗氏E170化学发光免疫分析仪测定二组儿童血清雌二醇、睾酮水平.比较二组儿童骨龄、BMI和性激素水平间的差异,并对骨龄与BMI及性激素水平进行相关性分析.结果 肥胖组骨龄[(11.85±2.76)岁]、BMI[(27.26±5.16) kg·m-2]及雌二醇[(29.20±11.61) pmol·L-1]均显著高于健康对照组[(10.57±2.59)岁,(16.75±4 73) kg·m-2,(22.35±10.87) pmol·L-1](t=10.57、9.50、2.72,P<0.05、0.01、0.01);肥胖组睾酮[(0.07±0.04) μg·L-1]显著低于健康对照组[(0.10±0.05) μg·L-1](t=2.96,P<0.01).肥胖组骨龄与BMI、雌二醇均呈显著正相关(r=0.696、0.773,Pa<0 05);与睾酮呈负相关(r=-0.726,P<0.05).结论 单纯性肥胖儿童的骨龄较同龄健康儿童超前,骨龄超前与体内雌激素水平有关,雌二醇水平的升高可能是导致单纯性肥胖儿童骨龄超前的主要原因.     

单纯性肥胖对儿童肾功能的影响

目的探讨单纯性肥胖对儿童早期肾功能的影响及其发生机制。方法选择70例单纯性肥胖患儿为单纯性肥胖组,50例健康儿童为健康对照组,测量二组儿童身高和体质量,计算体质量指数(BMI);采用放射免疫法检测二组儿童24h尿微量清蛋白(Alb)、β2微球蛋白(β2-MG)和α1微球蛋白(α1-MG)水平,采用SAS8.0软件比较二组BMI、24h尿Alb、β2-MG及α1-MG的差异,分析二组BMI与24h尿Alb的相关性。结果单纯性肥胖组BMI、24h尿Alb水平均显著高于健康对照组(t=15.14,P<0.001;t=4.084,P<0.001),单纯性肥胖组尿β2-MG及α1-MG水平与健康对照组比较差异均无统计学意义(t=1.847,P>0.05;t=1.936,P>0.05),单纯性肥胖组BMI与24h尿Alb水平呈显著正相关(r=0.626,P<0.01)。结论儿童单纯性肥胖可致肾功能损伤,早期主要表现为肾小球功能受损,尿Alb可作为评价单纯性肥胖患儿早期肾功能损害的指标之一,单纯性肥胖患儿肾功能损害程度与肥胖程度有关。     

单纯性肥胖儿童胰岛素抵抗与肿瘤坏死因子-α的关系

目的探讨单纯性肥胖儿童胰岛素抵抗与肿瘤坏死因子-α(TNF-α)的关系。方法单纯性肥胖患儿50例作为观察组(男23例,女27例);选取同期健康儿童30例为对照组(男14例,女16例)。采用发光免疫法、放射免疫法、快速测血糖法分别对两组儿童的血糖、血胰岛素、血脂和TNF-α进行检测。并作对比分析。结果观察组稳态模型胰岛素抵抗指数(HOMA-IR)、TNF-α及舒张血压(DBP),与对照组比较均明显升高(t=3.939,4.938,3.278 P均<0.01);收缩血压(SBP)、空腹三酰甘油(TC)与对照组比较均明显升高(t=2.536,2.573 P均<0.05);胰岛素敏感指数(HOMA-ISI)观察组明显低于对照组(t=-4.75 P<0.01)。观察组TNF-α与体质量指数(BMI)、TC、HOMA-IR均呈显著正相关(r=0.284,0.328,0.361 P均<0.05)。TNF-α与HOMA-ISI呈显著负相关(r=-0.36 P<0.01)。BMI与HOMA-IR呈显著正相关性(r=0.294 P<0.05)。结论单纯性肥胖儿童存在胰岛素抵抗,血清TNF-α与肥胖儿童的BMI、TC、BP、胰岛素抵抗密切相关,TNF-α可能参与胰岛素抵抗病理生理机制。     

单纯性肥胖儿童血浆卡尼汀、游离脂肪酸水平与胰岛素抵抗的相关性

目的了解单纯性肥胖儿童血浆卡尼汀(CT)、游离脂肪酸(FFA)水平与胰岛素抵抗相关参数的关系。方法选择56例确诊为单纯性肥胖的儿童作为研究对象(肥胖组),36例健康体检儿童为健康对照组。采用放射免疫法(RIA)测定二组血浆胰岛素,高效液相色谱法(HPLC)测定血浆CT水平,酶比色法测定血浆FFA及三酰甘油(TG)。计算体质量指数(BMI)及腰臀比(WHR),按稳态模式胰岛素(HOMA-IR)计算其胰岛素抵抗指数(InRI)和胰岛素敏感指数(InSI),应用SPSS13.0软件进行统计学分析。结果肥胖组血浆CT水平为(43.67±12.75)μmol/L,健康对照组为(58.31±21.25)μmol/L,二组比较差异有统计学意义(t=2.566P<0.05)。肥胖组血浆FFA水平为(785.32±284.91)μmol/L,健康对照组为(604.87±136.52)μmol/L,二组比较差异有统计学意义(t=2.143P<0.05)。肥胖组WHR、TG、胰岛素(Ins)水平、InRI与健康对照组比较差异均有统计学意义(Pa<0.05)。血浆FFA与BMI、WHR、TG均呈正相关(r=0.403,0.320,0.406Pa<0.05),与InSI呈负相关(r=-0.364P<0.01);血浆CT与空腹胰岛素(FINS)、InSI呈正相关(r=0.365,0.364Pa<0.01),与WHR呈负相关(r=-0.614P<0.01);肥胖组血浆CT水平与FFA水平呈负相关(r=-0.592P<0.01)。结论肥胖患儿存在明显的脂肪代谢紊乱,血浆FFA及CT水平的变化与胰岛素抵抗密切相关,这些变化可能参与肥胖及肥胖相关并发症的发生。     

肥胖儿童运动减肥治疗前后的瘦素抵抗血脂及炎症状态分析

目的：研究显示C-反应蛋白（CRP）、瘦素(Lp)、可溶性瘦素受体(sLR) 及多种血脂成分均参与了肥胖的发生发展。本研究旨在探讨运动减肥治疗前后肥胖儿童瘦素抵抗、血脂及炎症状态的改变,以期明确运动对肥胖儿童内分泌环境的影响。方法：对51例12岁肥胖儿童进行为期2月的运动减肥治疗,观察血清高敏C反应蛋白（hs-CRP）、Lp、sLR、甘油三酯(TG)、总胆固醇(TC)及低密度脂蛋白胆固醇(LDL-C)水平变化。40例健康体检儿童作为对照组。结果：肥胖儿童组血清Lp、TG、TC、LDL-C和hs-CRP水平及体重指数（BMI）均显著高于对照组（均P<0.01）,sLR水平低于对照组（P<0.05）。运动减肥治疗后肥胖儿童组血清hs-CRP、Lp、TC、TG和LDL-C水平及BMI与治疗前比较显著下降（P<0.05）。相关性分析显示肥胖儿童血清Lp水平与血脂及hs-CRP呈显著正相关（P<0.05）;Lp、hs-CRP与sLR呈显著负相关（P<0.05）;hs-CRP与血脂呈显著正相关（P<0.01）。结论：肥胖儿童已存在瘦素抵抗及血脂和炎症状态的改变,运动减肥治疗可不同程度地改善这些改变。［中国当代儿科杂志,2010,12（1）：40-42］     

内皮素-1和C反应蛋白在单纯性肥胖儿童血管内皮细胞损伤中的作用

目的探讨内皮素-1(ET-1)和CRP在单纯性肥胖儿童血管内皮细胞损伤中的作用。方法选择2006年1月-2008年6月在本院儿科就诊的39例单纯性肥胖儿童(肥胖组)为研究对象,并选择21例年龄、性别具有可比性的健康儿童作为健康对照组。采用放射免疫法测定二组血浆ET-1、血清CRP水平,采用t检验和直线相关分析进行统计学处理。结果健康对照组21例儿童血浆ET-1水平和血清CRP水平分别为(43.5±10.2)ng·L-1和(1.2±0.5)mg·L-1,肥胖组39例儿童血浆ET-1水平和血清CRP水平分别为(57.8±19.7)ng·L-1和(2.7±1.2)mg·L-1。二组比较差异均有统计学意义(t=3.704,6.696,Pa<0.01)。单纯性肥胖儿童体质量与血浆ET-1水平和血清CRP水平均呈正相关(r=0.413,P<0.05;r=0.491,P<0.01)。结论单纯性肥胖儿童血浆ET-1、血清CRP水平升高,可能存在血管内皮细胞损伤,为成年后的高血压、高血脂、冠心病、糖尿病、肾损害等心血管相关疾病埋下隐患,检测血浆ET-1、血清CRP水平对于干预肥胖儿童的行为、饮食及运动具有重要指导意义。     

郑州地区4童单纯性肥胖流行病学调查及中医循经推拿干预研究

目的了解郑州地区儿童肥胖发生情况和探索干预措施.方法于2001年抽样调查5688例中小学生,男2848名,女2840名,年龄7～18岁.肥胖标准以Cole 等的诊断儿童肥胖的参考BMI值判断,并对筛选出的单纯性肥胖儿童22例(7～15岁,男18例,女4例)以中医循经推拿和行为矫正及饮食、运动调整综合治疗1个月,且于治疗结束6个月后随访.结果所调查的5688名中小学生超重发生率15.4%,肥胖发生率3.2%,男生超重、肥胖发生率(19.2%,4.6%)明显高于女生(11.5%,1.7% P<0.001);各年龄阶段超重发生率有明显差异(χ2=42.88 P<0.001),高发年龄为8～15岁;各年龄阶段肥胖发生率亦有差异(χ2=21.28 P<0.05),高发年龄为7～10岁和14～15岁;治疗1个月后22例肥胖儿童体质量均有下降,由入院时(76.45±19.87) kg下降至(69.06±17.98) kg,下降幅度(7.43±2.58)kg,BMI值由治疗前(31.05±3.96)下降至(27.72±3.54),治疗前后体质量和BMI值比较均有显著差异(t=13.6,12.88 P<0.01),且体质量、BMI值下降幅度与入院时体质量、BMI值均呈明显相关性(r=0.77 P<0.01;r=0.49 P<0.05).结论近年来儿童肥胖发生率增高,以中医循经推拿和行为矫正及饮食、运动调整综合治疗的方法疗效好且舒适,儿童易于接受.     

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.     

Bibliometric data: a disaster for many non-American biomedical journals

Bibliometric data published by the Institute of Scientific Information in Philadelphia (ISI), and which was previously discussed in Acta Paediatrica , has increasingly been used despite all the relevant and severe criticism that has been raised against this method of evaluating individual research results and grading scientific journals. It is obvious that the present trend regarding the use of bibliometric data as a basis for priorities and funding of research and for the promotion of individual scientists favours American-oriented research projects at the expense of those that are based on concepts of predominantly European relevance.

Conclusion: For the future of non-American research, it is important that no single super-power, i.e. the USA, should dominate scientific priorities. The condition for efficient European competition is that European Centres with high levels of competence for creative research and training of scientists from all over the world are established. In addition, it is important that the results of European research are published in prestigious European journals, as was the situation before World War II.     

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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.