核转录因子在细胞因子介导的川崎病血管内皮损伤中的作用机理

目的　探讨核转录因子 (NF κB)在诱导川崎病炎性细胞因子及血管内皮细胞损伤中的作用及机理。方法　建立人脐静脉内皮细胞培养模型 ,酶联免疫吸附实验 (ELISA)双抗体夹心法检测川崎病患儿外周血单个核细胞 (PBMC)活化后培养上清液白细胞介素 6 (IL 6 )、白细胞介素 1β(IL 1β)、肿瘤坏死因子α(TNF α)的分泌量 ;采用AnnexinⅤ /PI双染色法 ,流式细胞仪检测川崎病患儿PBMC培养上清液所诱导的内皮细胞凋亡率 ;凝胶电泳迁移率转换实验 (EMSA)检测所活化PBMC核因子NF κB的活性。结果　川崎病组患儿PBMC体外经刺激后IL 6、IL 1β、TNF α等炎性细胞因子的分泌均明显高于正常对照组 (P <0 0 1) ,其培养上清液所诱导的内皮细胞凋亡率 [(38 4± 7 8) %]则较正常对照组 [(2 8± 0 8) %]明显升高。分别加入足量白细胞介素 6单克隆抗体 (IL 6McAb)、肿瘤坏死因子α单克隆抗体 (TNF αMcAb)、白细胞介素 1β受体a(IL 1ra)或联合加入上述阻断剂于川崎病患儿PBMC培养上清液中 ,可不同程度地逆转川崎病患儿PBMC培养上清液所诱导内皮细胞的凋亡。川崎病患儿PBMC刺激活化后NF κB活性显著增高。NF κB抑制剂SN50 明显抑制川崎病患儿PBMC上述细胞因子的分泌 ,与此同时基本阻断川崎病患儿PBMC培养上清液所诱导内皮细     

过敏性紫癜患儿血清白细胞介素—6、肿瘤坏死因子—α、白细胞介素—10的变化

目的　探讨过敏性紫癜 (HSP)的免疫作用机制。方法　采用双抗体夹心酶联免疫吸附试验(ELISA) ,对 5 0例HSP患儿进行血清白细胞介素 6(IL 6)、肿瘤坏死因子 α(TNF α)、IL 10的测定 ,并与 3 0例正常对照组比较。结果　HSP组血清IL 6( 0 .0 72± 0 .0 2 6)ng/ml,对照组 ( 0 .0 42± 0 .0 15 )ng/ml;TNF α( 0 .92 7± 0 .3 80 )ng/ml,对照组 ( 0 .5 92± 0 .3 2 0 )ng/ml;IL 10 ( 0 .0 67± 0 .0 3 1)ng/ml,对照组 ( 0 .0 40± 0 .0 19)ng/ml;IgE( 12 .0 3± 2 .45 ) g/L ,对照组 ( 4.60± 3 .70 )g/L ;IgA( 1.75± 0 .3 5 ) g/L ,对照组 ( 1.0 0± 0 .5 0 ) g/L ;IL 6、IL 10、TNF α、IgA、IgE均明显高于对照组 ( P <0 .0 1) ,经相关分析发现IL 6、IL 10与IgA呈显著正相关 (r=0 .798,0 .82 9　P <0 .0 1)。结论　过敏性紫癜存在细胞免疫功能紊乱 ,其参与了HSP的发病过程     

细胞因子与婴幼儿轮状病毒肠炎的关系

目的　探讨婴幼儿轮状病毒 (RV)肠炎患儿细胞因子变化特点。方法　测定婴幼儿RV肠炎 2 6例血及 15例大便细胞因子 ,与同期 15例正常婴幼儿作对照。结果　血液及大便白细胞介素 1β(IL 1β)、IL 6、肿瘤坏死因子 α(TNF α)在重度RV肠炎较对照组升高 ,以TNF α升高为最显著。血IL 1β、IL 6、TNF α在重度RV肠炎患儿较轻度明显升高 ,以TNF α升高为最显著 (P <0 .0 0 1)。结论　测定TNF α水平可预测RV感染病情和病程。合理应用调节相关细胞因子的药物 ,可减轻症状 ,缩短疗程     

Ⅰ型糖尿病患儿血清肿瘤坏死因子和白细胞介素水平的变化

目的　探讨血清肿瘤坏死因子 (TNF α)、白细胞介素 2 (IL 2 )、白细胞介素 6 (IL 6 )在Ⅰ型糖尿病患儿发病中的作用。方法　应用放射免疫技术 ,对Ⅰ型糖尿病患儿 32例、健康儿童 2 2例的血清TNF α、IL 2、IL 6、C 肽 (C P)的水平进行测定。结果　 (1)糖尿病组TNF α水平 [(1.11± 0 .2 4) μg/L]低于正常对照组 (t=4.6 8P <0 .0 1) ,IL 6水平 [(0 .79± 0 .2 0 ) μg/L]低于正常对照组 (t=4.0 5 ,P <0 .0 1) ,IL 2水平 [(7.9± 2 .4) μg/L]高于正常对照组 (t=3.6 0 ,P <0 .0 1) ;C 肽水平 [(0 .79± 0 .19) μg/L]低于正常对照组 (t=7.0 8,P <0 .0 1)。正常对照组TNF α为 (1.37± 0 .12 ) μg/L ,IL 6为 (0 .98± 0 .11)μg/L ,IL 2为 (5 .9± 1.0 ) μg/L ,C 肽为 (1.14± 0 .16 ) μg/L。 (2 )血糖的变化与TNF α、IL 2、IL 6均无相关关系 (r=0 .2 47、0 .30 1、0 .2 38,P均 >0 .0 5 ) ,C 肽的降低与TNF α、IL 6的降低呈正相关 (r =0 .5 81、0 .491,P均 <0 .0 5 ) ,与IL 2的升高呈负相关 (r =- 0 .46 1,P <0 .0 5 )。结论　血清TNF α、IL 6、IL 2的变化可能与Ⅰ型糖尿病患儿自体免疫炎症反应的发生过程有一定关系     

Foxp3表达与CD+4CD+25调节性T细胞在儿童哮喘发病中的作用

目的研究Foxp3基因表达与CD+4CD+25调节性T细胞在哮喘发病中的作用.方法以确诊哮喘的患儿为研究对象,急性发作期15例、缓解期15例,同期选10例正常儿童作对照,提取外周血单个核细胞(PBMC)进行CD4、CD25表面标志及血浆、培养上清液IL-4、IFN-γ、IL-10和TGF-β等细胞因子的ELISA检测,同时收集哮喘患儿和正常儿童的诱导痰,用RT-PCR方法检测PBMC及诱导痰中转录因子Foxp3-mRNA的表达.结果 PBMC CD+4CD+25T细胞百分率在哮喘急性发作期、缓解期分别为(10.1±2.1)%、(11.7±2.5)%,低于对照组的(15.5±2.7)%(P分别<0.01、<0.05);对照组PBMC在体外培养后CD+4CD+25细胞百分率显著升高,同培养前比较差异有统计学意义(P<0.01).PBMC Foxp3-mRNA表达水平(Foxp3/β-actin) 在哮喘急性发作期、缓解期分别为0.46±0.14 、0.50±0.19,低于对照组0.77±0.22,诱导痰Foxp3-mRNA表达水平哮喘患儿也低于对照组;PBMC在体外培养后对照组Foxp3-mRNA表达水平较培养前升高(P<0.05),而哮喘患儿培养前后Foxp3-mRNA表达水平无显著变化.血浆及培养上清液IFN-γ、TGF-β在哮喘急性发作期、缓解期低于对照组 (P<0.05),且IFN-γ、TGF-β与PBMC Foxp3-mRNA水平、CD+4CD+25细胞百分率呈正相关. 哮喘患儿血浆及培养上清液IL-4显著高于对照组,急性发作期血浆IL-10显著高于对照组,而缓解期与正常组无显著性差异;IL-4、IL-10与PBMC Foxp3-mRNA水平、CD+4CD+25细胞百分率无相关性.结论哮喘患儿的TGF-β分泌不足、Foxp3基因表达降低、CD+4CD+25调节性T细胞数量减少及分化发育障碍可能在儿童哮喘的发病中起重要作用.     

肿瘤坏死因子α诱导K_(562)凋亡

为探讨肿瘤坏死因子 - α(TNF- α)诱导 K562 凋亡的作用 ,应用细胞形态学观察、DNA琼脂糖凝胶电泳 ,原位末端标记法检测 K562 、TNF-α诱导的 K562 。结果　表明 ,细胞形态学观察 K562 自然凋亡率 (2 .9± 0 .7) % ,TNF- α5 0 ng/ml、1 0 0 ng/ml诱导的 K562 凋亡率分别为 (1 6 .5± 4.1 ) % ,(2 3.9± 4.8) %。 (F=89.9,P<0 .0 1 )。 DNA琼脂糖凝胶电泳 TNF- α1 0 0 ng/ml诱导的 K562 DNA电泳呈梯状条带。原位末端标记法K562 自然凋亡率 (3.5± 1 .0 ) % ,TNF- α5 0 ng/ml、1 0 0 ng/ml诱导的 K562 凋亡率分别是(2 1 .4± 4.5 ) %、(2 7.4± 4.9) %。 (F=1 0 4.9,P<0 .0 1 )。结论　 TNF-α 5 0 ng/ml、1 0 0 ng/ml能诱导 K562 凋亡     

脑脊液细胞因子检测在小儿中枢神经系统感染鉴别诊断中的意义

目的　探讨脑脊液 (CSF)γ 干扰素 (IFN γ)、粒细胞集落刺激因子 (G CSF)、α肿瘤坏死因子 (TNF α)、白细胞介素 6 (IL 6 )及白细胞介素 8(IL 8)的变化在小儿中枢神经系统感染 (CNSI)中的诊断价值。方法　采用双抗体夹心ELISA法检测 14例化脓性脑膜炎 (PM)、30例病毒性脑膜炎 (VM)及2 2例非中枢神经系统感染患儿CSF中IFN γ、G CSF、TNF α、IL 6及IL 8水平。结果　PM组G CSF及IL 8[(132± 4 1)、(2 5 3± 0 5 6 ) μg/L]水平明显高于VM组 [(5 3± 2 2 )、(0 5 3± 0 4 6 ) μg/L](P <0 0 0 1) ;IFN γ在VM组 [(2 0± 0 4 ) μg/L]水平明显高于PM组 [(0 8± 0 5 ) μg/L](P <0 0 1) ;各脑膜炎组中TNF α及IL 6水平均高于对照组 (P <0 0 0 1) ,但各组间比较差异无显著性。G CSF及IL 8水平增高程度与CSF中性粒细胞计数呈正相关 ;IFN γ增高程度与CSF白细胞数及葡萄糖定量间无相关性。结论G CSF、INF γ及IL 8在CSF中显著增高有助于PM与非PM的鉴别诊断 ;TNF α、IL 6在感染性脑膜炎发病过程中的作用是非特异性的 ,其在CSF中的变化对感染性脑膜炎患儿鉴别诊断无临床意义     

新生儿HIE血清IL-6、IL-8与TNF-α动态变化及临床意义探讨

为探讨新生儿缺氧缺血性脑病 (HIE)外周血IL -6、IL -8与TNF -α变化的临床意义 ,采用放射免疫法 ,对生后 1天 ( 2 4小时内 )、3天及 7天检测了 40例HIE患儿及 40例正常新生儿外因血IL 6、IL 8与TNF α水平。结果显示 ,与正常新生儿比较 ,HIE患儿生后 1天血清IL -6水平分别为 ( 5 2 6± 2 4 5 )对 ( 80 2± 2 9 4)ng L(P <0 0 1) ,IL -8分别为 ( 0 47± 0 13)对 ( 0 6 8± 0 16 ) μg L(P <0 0 1) ,TNF -α分别为( 1 18± 0 31)对 ( 0 91± 0 30 ) μg L(P <0 0 1) ,而且病情越重改变越明显 ;至生后 1周IL -6、TNF -α恢复至正常 ,与对照组水平相比P >0 0 5 ,而IL -8则仍显著低于正常新生儿 (P <0 0 1)。因此 ,认为围产期窒息与HIE患儿外周血IL -6与IL -8水平减低 ,TNF -α水平升高 ;它们可能参与了新生儿缺氧缺血性脑损伤的某些发病过程。     

环孢菌素A对儿童过敏性紫癜T细胞功能状态的干预作用

目的观察环孢菌素A(CsA)对儿童过敏性紫癜(HSP)T细胞功能状态的干预作用.方法采用流式细胞技术及ELISA法检测PBMC细胞膜上CD40L表达及PBMC培养上清中细胞因子水平.结果CsA在体外具有纠正HSP患儿PBMC异常表达CD40L的作用(P＜0.05),并抑制TH2类细胞因子(IL-4、IL-5、IL6)的过度产生,使TH1类细胞因子(IL-2、IFN-γ)的释放进一步减少(P＜0.05).结论CsA具有显著抑制HSP患儿T细胞功能作用,尤其是对T细胞亚群(TH1)细胞的功能抑制更强.     

宫内大肠杆菌感染导致新生大鼠脑白质损伤的实验研究

目的　探讨宫内感染后胶质纤维酸性蛋白 (GFAP)、GFAPmRNA和白介素 1βmRNA(IL 1βmRNA)、肿瘤坏死因子 αmRNA(TNF αmRNA)在新生大鼠脑组织中的变化。 方法　建立宫内大肠杆菌感染的大鼠模型 ,应用HE染色和免疫组化方法研究新生 1、3、7日龄大鼠脑白质组织病理特点和GFAP表达变化以及RT PCR法检测GFAPmRNA、IL 1βmRNA和TNF αmRNA的表达变化。结果　宫内感染后 7日龄大鼠脑白质病理改变包括脑白质染色淡 ,结构疏松等。感染组 7日龄大鼠GFAP阳性细胞数在脑室旁白质和海马区明显多于对照组 (脑室旁白质 9 73± 3 5 5vs 5 6 7± 1 90 ,P <0 0 5 ;海马 7 81± 3 6 1vs 2 16± 1 11,P <0 0 5 ) ;在胼胝体区两组比较差异无显著意义(P >0 0 5 )。感染组 1、3日龄大鼠GFAPmRNA表达水平明显高于对照组 (1日龄 0 2 5± 0 0 7vs0 15± 0 0 8,P <0 0 5 ;3日龄 0 5 0± 0 0 9vs 0 39± 0 0 8,P <0 0 5 ) ;而 7日龄大鼠GFAPmRNA表达水平两组比较差异无显著意义 (P >0 0 5 )。感染组 1日龄大鼠IL 1βmRNA和TNF αmRNA表达水平均明显高于对照组 (IL 1βmRNA :0 83± 0 19vs 0 5 0± 0 30 ,P <0 0 5 ;TNF αmRNA :0 74±0 30vs 0 30± 0 2 0 ,P <0 0 5 )。 3、7日龄大鼠IL 1βmRNA和TNF      

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.