Lymphocyte Perturbations in Malawian Children with Severe and Uncomplicated Malaria

Lymphocytes are implicated in immunity and pathogenesis of severe malaria. Since lymphocyte subsets vary with age, assessment of their contribution to different etiologies can be difficult. We immunophenotyped peripheral blood from Malawian children presenting with cerebral malaria, severe malarial anemia, and uncomplicated malaria (n = 113) and healthy aparasitemic children (n = 42) in Blantyre, Malawi, and investigated lymphocyte subset counts, activation, and memory status. Children with cerebral malaria were older than those with severe malarial anemia. We found panlymphopenia in children presenting with cerebral malaria (median lymphocyte count, 2,100/μl) and uncomplicated malaria (3,700/μl), which was corrected in convalescence and was absent in severe malarial anemia (5,950/μl). Median percentages of activated CD69⁺ NK (73%) and γδ T (60%) cells were higher in cerebral malaria than in other malaria types. Median ratios of memory to naive CD4⁺ lymphocytes were higher in cerebral malaria than in uncomplicated malaria and low in severe malarial anemia. The polarized lymphocyte subset profiles of different forms of severe malaria are independent of age. In conclusion, among Malawian children cerebral malaria is characterized by lymphocyte activation and increased memory cells, consistent with immune priming. In contrast, there are reduced memory cells and less activation in severe malaria anemia. Further studies are required to understand whether these immunological profiles indicate predisposition of some children to one or another form of severe malaria.     

Anemia and Interleukin-10, Tumor Necrosis Factor Alpha, and Erythropoietin Levels among Children with Acute, Uncomplicated Plasmodium falciparum Malaria

Anemia is an important complication of malaria, and its pathogenesis is not well understood. To gain insight into potential age-related relationships between tumor necrosis factor alpha (TNF-α), interleukin 10 (IL-10), erythropoietin, and anemia during acute malaria, 273 children of ages 12 to 120 months presenting with acute, uncomplicated malaria in Kampala, Uganda, were monitored at enrollment and 3 and 7 days later. Younger children had higher geometric mean erythropoietin, TNF-α, and α₁-acid glycoprotein (AGP) concentrations than older children. Univariate regression analysis revealed that age, log₁₀ erythropoietin levels, IL-10/TNF-α ratio, and AGP levels were each significantly associated with hemoglobin levels at baseline. Hemoglobin concentrations were inversely correlated with the log₁₀ erythropoietin level at all three visits. For the older age groups, higher levels of TNF-α were significantly associated with higher IL-10 levels at all three visits, but this relationship was significant only at baseline for younger children. These data suggest that younger children do not maintain IL-10 production in response to the inflammatory process, and this mechanism may contribute to the more severe anemia found in younger children. Acute malaria is an illness whose incidence and severity are largely age dependent. Further studies are needed to understand the relationships between age-related immune responses to malaria and their role in the pathogenesis of malarial anemia.     

Aberrantly Decreased Levels of NKG2D Expression in Children with Kawasaki Disease

This study is designed to investigate the changes of NKG2D expression on CD8⁺T cells and CD3^?CD56⁺NK cells in Kawasaki disease (KD). NKG2D/NKG2A expression on CD3^?CD56⁺NK cells and CD8⁺T lymphocytes, and NKG2D ligands such as major histocompatibility complex I chain‐related molecules A(MICA) and UL‐16‐binding proteins (ULBP‐1) expression on CD14⁺ mononuclear cells (MC) were analysed by flow cytometry in patients with KD. Real‐time polymerase chain reaction (PCR) was used to evaluate the mRNA levels of interleukin (IL)‐1β, IL‐6 and tumour necrosis factor (TNF)‐α in CD14⁺ cells. Plasma cytokine [IL‐7, IL‐12, IL‐15, interferon (IFN)‐γ and transforming growth factor (TGF)‐β] concentrations were measured by ELISA. The levels of NKG2D on NK cells and CD8⁺T cells expression in acute phase of KD were significantly lower than those in normal controls (P < 0.05), and the levels of NKG2D expression in the patients with coronary artery lesion (KD‐CAL⁺) were lower than those in patients with KD‐CAL^?. There was an upregulated tendency after treatment with IVIG. We found higher expression levels of proinflammatory cytokines from MC, such as IL‐1β, IL‐6 and TNF‐α in patients with KD compared with the healthy controls (P < 0.05). The concentrations of IL‐7 and IL‐15 were significantly decreased in acute phase of KD (P < 0.05) and to some extent elevated after therapy with IVIG (P < 0.05), while antagonistic cytokines like IFN‐γ were increased in acute phase of KD (P < 0.05) and reduced after therapy with IVIG (P < 0.05). These results suggest that aberrantly decreased levels of NKG2D expression on NK cells and CD8⁺T cells might be one of the factors led to disturbed immunological function in patients with KD. Cytokines milieu could be important factors causing reduced expression of NKG2D.     

The Cognitive Content of Thought-Listed Worry Episodes in Clinic-Referred Anxious and Nonreferred Children

We investigated the cognitive content of worry in 8- to 13-year-old clinic-referred anxious (n = 38) and nonreferred (n = 51) children. The children were interviewed individually. They thought-listed their latest worry episodes, rated the uncontrollability of the episodes, and reported on the strategies they used to terminate worry. Content analyses showed that children's worry episodes contained predominantly thoughts reflecting negative outcome anticipation, but other types of thought content also were present. These included problem-solving, ruminating, and self-blaming thoughts. Compared to clinic-referred children, nonreferred children reported more problem solving and less ruminating. In the nonreferred group, increasing age was associated with more problem solving and less ruminating. No such age-related associations were found in the clinic-referred group. The 2 groups did not differ in the types of worry-termination strategies they reported, but clinic-referred children were more likely to keep worrying until the perceived threat was removed. The results suggest that the problem-solving function of worry is still emerging during late childhood and that developmental delays in problem solving may be associated with excessive and uncontrollable worrying.     

Decreased Activities of Apolipoprotein M Promoter Are Associated with the Susceptibility to Coronary Artery Diseases

The present study investigated the correlation among genetic polymorphisms of the proximal promoter region of apolipoprotein M (apoM) gene, the polymorphisms in relation to apoM expressions and the susceptibility to coronary artery diseases (CAD) in a Han Chinese population. Four common polymorphic sites, i.e., T-1628G, C-1065A, T-855C and T-778C, were confirmed, and a new deletion mutation C-724del was found, in 206 CAD patients and 209 non-CAD patients using direct DNA sequencing analyses. Occurrences of alleles T-1628G, T-855C and C-724del were significantly higher in CAD patients compared to non-CAD patients. Moreover we examined all these polymorphisms in relation to apoM expression by applying luciferase reporter assay. It demonstrated that constructs -855C and 724del showed obvious decreased luciferase activities, i.e., (0.93±0.15 vs. 2.11±0.15; P=0.012) and (1.13±0.25 vs. 2.11±0.15; P=0.009) respectively, which indicates these two polymorphisms could confer decreased apoM expressions. Meanwhile the occurrences of these two SNP were also significantly higher in the CAD patients than in non-CAD patients. It is therefore reasonable to speculate that down-regulated apoM expressions in relation to these polymorphisms may affect HDL and cholesterol metabolism in vivo and further influence the susceptibility to CAD, although the underlying mechanisms need further investigation.     

Targets and Mechanisms Associated with Protection from Severe Plasmodium falciparum Malaria in Kenyan Children

Severe malaria (SM) is a life-threatening complication of infection with Plasmodium falciparum. Epidemiological observations have long indicated that immunity against SM is acquired relatively rapidly, but prospective studies to investigate its immunological basis are logistically challenging and have rarely been undertaken. We investigated the merozoite targets and antibody-mediated mechanisms associated with protection against SM in Kenyan children aged 0 to 2 years. We designed a unique prospective matched case-control study of well-characterized SM clinical phenotypes nested within a longitudinal birth cohort of children (n = 5,949) monitored over the first 2 years of life. We quantified immunological parameters in sera collected before the SM event in cases and their individually matched controls to evaluate the prospective odds of developing SM in the first 2 years of life. Anti-AMA1 antibodies were associated with a significant reduction in the odds of developing SM (odds ratio [OR] = 0.37; 95% confidence interval [CI] = 0.15 to 0.90; P = 0.029) after adjustment for responses to all other merozoite antigens tested, while those against MSP-2, MSP-3, Plasmodium falciparum Rh2 [PfRh2], MSP-1₁₉, and the infected red blood cell surface antigens were not. The combined ability of total IgG to inhibit parasite growth and mediate the release of reactive oxygen species from neutrophils was associated with a marked reduction in the odds of developing SM (OR = 0.07; 95% CI = 0.006 to 0.82; P = 0.03). Assays of these two functional mechanisms were poorly correlated (Spearman rank correlation coefficient [r_s] = 0.12; P = 0.07). Our data provide epidemiological evidence that multiple antibody-dependent mechanisms contribute to protective immunity via distinct targets whose identification could accelerate the development of vaccines to protect against SM.     

Neuropsychological Diagnosis of Decreased Consciousness after Severe Craniocerebral Trauma in Children

Neuroscience and Behavioral Physiology - Objectives. To identify the features of the recovery of consciousness and higher mental function in children aged 6–17 years during the first four...     

Malaria and Nutritional Status in Children Living on the Coast of Kenya

The relationship between malnutrition and malaria is controversial. On one hand, malaria may cause malnutrition, while on the other, malnutrition itself may modulate susceptibility to the disease. We investigated the association between Plasmodium falciparum malaria and malnutrition in a cohort of children living on the coast of Kenya. The study involved longitudinal follow-up for clinical malaria episodes and anthropometric measurements at four cross-sectional surveys. We used Poisson regression analysis to investigate the association between malaria and nutritional status. Compared to baseline (children with a WAZ or HAZ score of ≥−2), the crude incidence rate ratios (IRRs) for malaria in children with low HAZ or WAZ scores (<−2) during the period prior to assessment were 1.17 (95% CI 0.91–1.50; 0 = 0.21) and 0.94 (0.71–1.25; 0.67), respectively, suggesting no association between malaria and the subsequent development of PEM. However, we found that age was acting as an effect modifier in the association between malaria and malnutrition. The IRR for malaria in children 0–2 years old who were subsequently characterized as wasted was 1.65 (1.10–2.20; P  = 0.01), and a significant overall relationship between malaria and low-HAZ was found on regression analysis when adjusting for the interaction with age (IRR 1.89; 1.01–3.53; P  < 0.05). Although children living on the coast of Kenya continue to suffer clinical episodes of uncomplicated malaria throughout their first decade, the association between malaria and malnutrition appears to be limited to the first 2 years of life.     

伴品行障碍多动症儿童的临床观察

儿童多动症是常见的一种精神障碍 ,主要临床表现是注意力集中困难、活动过度、情绪不稳定、行为冲动等。研究显示这类儿童常伴有其他精神障碍如品行障碍、抑郁障碍、焦虑障碍、物质滥用障碍等。临床实践发现伴有品行障碍多动症预后较差 ,最后可发展为反社会人格障碍或严重的违法犯罪。本文对多动症的临床特点进行了初步探讨。对象　 2 0 0 0年 9月到 2 0 0 2年 4月于四川大学华西医院心理卫生中心就诊 ,符合CCMD -3中注意缺陷多动障碍(ADHD)和 /或品行障碍 (CD)的诊断标准的患者 ,其中ADHD患者 5 0名 ,男性 3 5人 ( 70 % ) ,女性 15人…     

小儿类白血病反应的临床分析

目的:回顾性分析小儿类白血病反应(LR)患者的临床特点。方法:8例26天-2岁患儿资料,对其发病诱因、临床表现、实验室检查和治疗转归进行总结分析。结果:本组患儿全部以感染为诱发因素,包括百日咳2例,类百日咳综合征2例,病毒感染2例,细菌感染2例;均有肺炎表现、心率明显增快140-220次/min,平均173±22次/min,其中5例为痉挛性、刺激性咳嗽,且咳嗽时伴青紫和心率下降;全部患儿白细胞计数(WBC)明显升高58.00-213.60×109/L,平均104.50±60.10×109/L。所有患儿均采用抗生素治疗,部分患儿应用呼吸机或持续呼气末正压通气治疗,WBC过高者给予补液治疗,2例合并使用抗病毒治疗。病程中发生反复呼吸、心跳骤停3例;并发中毒性脑病3例;痊愈6例,死亡2例。结论:感染为小儿LR的主要诱因,其临床表现较严重,抗生素治疗有效,多数病例可以治愈。     

95例儿童孤独症临床分析

目的：探讨儿童孤独症的临床特征,展望相对应的干预措施。方法：调查孤独症患儿的父母文化的水平、城乡比例、首诊主诉、发病与就诊时间间隔。采用Gesell发育量表测定发育商。Car's量表进行症状行为评定,用社会生活能力量表进行适应性行为评定。检验分析孤独症行为与适应性行为的相关性。结果：孤独症患儿父母文化水平大多为初、高中以上文化。孤独症患儿城乡比例为：2．8：1。首诊主诉症状以语言障碍为主（占84％）。患者从发病到就诊时间平均延迟31个月。孤独症行为的严重程度与社会生活能力缺陷的程度无相关性,症状特点以语言障碍及社会交往障碍最为突出。作者对此进行了分析并提出早期干预及行为,语言训练的相应建议。     

Evaluation of Concurrent Malaria and Dengue Infections among Febrile Patients

Context: Despite a wide overlap between endemic areas for two important vector-borne infections, malaria and dengue, published reports of co-infections are scarce till date. Aims: To find the incidence of dengue and malaria co-infection as well as to ascertain the severity of such dengue and malaria co-infection based on clinical and haematological parameters. Setting and Design: Observational, retrospective cross-sectional study was designed including patients who consulted the tertiary care hospital of Ahmedabad seeking treatment for fever compatible with malaria and/or dengue. Subjects and Methods: A total of 8364 serum samples from clinically suspected cases of fever compatible with malaria and/or dengue were collected. All samples were tested for dengue NS-1 antigen before 5 days of onset of illness and for dengue IgM after 5 days of onset of illness. In all samples, malaria diagnosis was based on the identification of Plasmodium parasites on a thin and thick blood films microscopy. Results: Only 10.27% (859) patients with fever were tested positive for dengue and 5.1% (434) were tested positive for malaria. 3.14% (27) dengue cases show concurrent infection with malarial parasites. Hepatomegaly and jaundice 37.03% (10), haemorrhagic manifestations 18.51% (5) and kidney failure 3.7% (1), haemoglobin <12 g/dl 100% (27) and thrombocytopenia (platelet count <150,000/cmm) 96.29% (26) were common in malaria and dengue co-infections and were much more common in Plasmodium falciparum infections. Conclusion: All febrile patients must be tested for malaria and dengue, both otherwise one of them will be missed in case of concurrent infections which could lead to severe diseases with complications.     

Decreased Proinflammatory Cytokines Production in Children with Complicated Parapneumonic Pleural Effusion after Intrapleural Fibrinolytic Treatment

Intrapleural fibrinolytic therapy (IFT) provides clinical benefit in the treatment of complicated pleural parapneumonic effusion (CPE). Whether IFT influences the proinflammatory cytokines production and fibrinlytic activity is currently unclear. Therefore, we collected pleural effusion samples from CPE patients with IFT (study group) and patients without IFT (control group). A membrane human inflammatory cytokines array kit was used to compare the difference of targeted cytokine production between these two groups. Enzyme-linked immunosorbent assay (ELISA) methods were used for quantitative analysis of targeted cytokines and fibrinolytic enzymes. The results showed there were no significant differences between the study (n = 16) and control (n = 14) groups in patients’ demographic data. After fibrinolytic therapy, the patients in the study group had significant lower plasminogen activator inhibitor (PAI) level (732.36?±?254.09 ng/mL vs 1,509.36?±?1,340.11 ng/mL, p?<?0.05) and higher urokinase plasminogen activator (u-PA) level (75.56?±?41.70 ng/mL vs 6.87?±?5.07 ng/mL, p?<?0.05) than they did before treatment. Moreover, the tissue inhibitors of metalloproteinase-2 (TIMP-2) (1,560.03?±?403.49 pg/mL vs 3,686.45?±?1,263.83 pg/mL, p?<?0.05) and inflammatory chemokine, regulated on activation normal T-cell expressed and secreted/chemokine (C-C motif) ligand 5 (RANTES), (293.58?±?212.93 pg/mL vs 749.27?±?53.79 pg/mL, p?<?0.05), were also significantly lower in the study group after fibrinolytic therapy, but not in the control group. In conclusion, intrapleural fibrinolytic treatment with urokinase could enhance fibrinolytic activity and decrease TIMP-2 and RANTES production.     

Clinical and Economic Impact of Cytomegalovirus Infection among Children Undergoing Allogeneic Hematopoietic Cell Transplantation

The literature on the impact of cytomegalovirus (CMV)-related hospitalization in pediatric allogeneic hematopoietic cell transplantation (alloHCT) recipients is limited. The aim of this study was to determine utilization and outcomes of CMV-related hospitalization in alloHCT recipients using a single-center clinical database. This was a retrospective study of 240 children aged 3 months to 21 years (median age, 9.5 years) who underwent alloHCT between 2005 and 2016. The impacts of CMV-related length of stay (LOS) and total healthcare costs were quantified. Factors associated with prolonged CMV viremia (>25 days’ duration) were also examined. In at-risk patients with CMV infection, the incidence of CMV viremia was 38% (59 of 155), the median time to onset was 33 days (range, 0 to 292 days), and the median time to resolution was 25 days (range, 3 to 48 days; n = 53). CMV infection was associated with a 23.3-day increase in LOS (P = .004) and added hospital costs of $45,443 (P = .162) compared with patients without CMV infection. In multivariable analysis, receipt of alemtuzumab (P = .027) was associated with CMV viremia of >25 days’ duration. Our data show that CMV viremia is associated with prolonged LOS and higher hospital costs and indicate the need for improved and cost-effective CMV prevention strategies. Further studies of patient outcomes and costs in pediatric alloHCT recipients is needed.     

Acquired Antibodies to Merozoite Antigens in Children from Uganda with Uncomplicated or Severe Plasmodium falciparum Malaria

Malaria can present itself as an uncomplicated or severe disease. We have here studied the quantity and quality of antibody responses against merozoite antigens, as well as multiplicity of infection (MOI), in children from Uganda. We found higher levels of IgG antibodies toward erythrocyte-binding antigen EBA181, MSP2 of Plasmodium falciparum 3D7 and FC27 (MSP2-3D7/FC27), and apical membrane antigen 1 (AMA1) in patients with uncomplicated malaria by enzyme-linked immunosorbent assay (ELISA) but no differences against EBA140, EBA175, MSP1, and reticulocyte-binding protein homologues Rh2 and Rh4 or for IgM against MSP2-3D7/FC27.Patients with uncomplicated malaria were also shown to have higher antibody affinities for AMA1 by surface plasmon resonance (SPR). Decreased invasion of two clinical P. falciparum isolates in the presence of patient plasma correlated with lower initial parasitemia in the patients, in contrast to comparisons of parasitemia to ELISA values or antibody affinities, which did not show any correlations. Analysis of the heterogeneity of the infections revealed a higher MOI in patients with uncomplicated disease, with the P. falciparum K1 MSP1 (MSP1-K1) and MSP2-3D7 being the most discriminative allelic markers. Higher MOIs also correlated positively with higher antibody levels in several of the ELISAs. In conclusion, certain antibody responses and MOIs were associated with differences between uncomplicated and severe malaria. When different assays were combined, some antibodies, like those against AMA1, seemed particularly discriminative. However, only decreased invasion correlated with initial parasitemia in the patient, signaling the importance of functional assays in understanding development of immunity against malaria and in evaluating vaccine candidates.     

癫痫儿童脑功能成像的临床应用研究进展

癫痫在儿童和青少年神经疾病中的发病率非常高 ,癫痫反复发作不仅影响患儿的运动功能 ,还影响其感知觉、记忆和语言等认知功能的健康发展。目前手术治疗是控制顽固性癫痫的重要手段 ,能否取得良好的手术效果有赖于癫痫灶的确定和认知功能皮层的准确定位。癫痫灶确定和认知功能皮层准确定位问题的解决不仅有利于癫痫儿童的诊断和治疗 ,也有利于更深入地了解癫痫发病机制 ,还有助于人类对语言、记忆等认知功能及其发展机制的深入认识。1　认知功能的手术前评估1.1　语言侧化与语言优势半球定位近三十年来 ,胼胝体切除术、脑叶切除术、大脑半球…     

发育性阅读障碍儿童的临床特征

目的:评估汉语发育性阅读障碍儿童的临床特征。方法:采用韦氏儿童智力量表(WSIC-CR)、学习障碍儿童筛查量表(PRS)、儿童阅读与书写能力家长问卷对17例汉语发育性阅读障碍(SRD)儿童和与之匹配的32名正常儿童的临床特征进行调查评估。结果:SRD组在WISC-CR中的言语智商、总智商、言语理解因子、记忆/注意因子分值均低于对照组(98·3±13·5/111·7±13·7,97·1±14·5/110·2±14·3,40·4±9·2/47·6±7·7,25·9±6·3/32·0±7·3,OR=0·88~0·94,P<0·05),回归分析表明,只有言语理解因子进入回归方程(OR=0·90);PRS中五大功能区得分、言语分、非言语分及总分,SRD儿童均显著低于对照组(9·6±1·5/13·3±2·6,10·8±3·1/15·6±3·6,11·1±1·4/14·1±3·6,7·1±1·9/9·7±1·9,19·7±3·5/24·7±5·7,20·3±4·1/28·9±5·7,37·9±5·6/48·5±7·0,58·2±8·5/77·3±11·9,P<0·05)。回归分析表明,只有言语分进入回归方程(OR=0·69);儿童阅读与书写能力家长问卷中,SRD儿童在除家庭阅读背景外其余七个因素得分均比对照组高(P<0·05),但只有朗读听写进入回归方程(OR=2·14)。结论:汉语SRD儿童言语能力明显损害;其阅读各环节均受损,但朗读听写能力缺陷可能是主要问题;记忆/注意集中困难、书写困难、动作技能、口语能力及社会适应能力的缺陷可能是汉语SRD儿童临床普遍伴发的症状。     

儿童孤独症的临床及脑影像学研究

目的：对儿童孤独症的临床特征及脑影像学进行研究。方法：病例确诊依据“中国精神疾病分类方案与诊断标准（修订第二版）”中有关孤独症的诊断标准。临床资料收集来源于病史、躯体检查及精神状况检查。用单光子发射CT检查患儿的脑影像。结果：共确诊患儿86例（男75,女11）,占精神专科门诊人数的3％。他们在孕产期有明确并发症的占27％,4人有阳性家族史。言语发育和交往障碍是所有患儿的核心症状,多数有多动表现,部分患儿还伴有明显的情绪及其它行为障碍。做过头部CT或／和MRI检查的44人中,42例报告无异常。32例完成脑SPECT检查,其中24人（男23,女1）存在局部放射性分布减低,这种异常主要见于大脑皮质的额叶和颞叶,以左侧额叶最为常见。结论：SPECT在反映儿童孤独症的病理生理方面比结构性脑成像更为敏感。本病患儿大脑以质额叶和颞叶存在局部血流灌注或／和细胞功能障碍,以左侧额叶最明显。