High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.     

T-Lymphocytes bearing the γδ T-cell receptor in cutaneous lesions of langerhans' cell histiocytosis

The aim of this study was to investigate the regional importance of γδ T cells in cutaneous lesions of Langerhans' cell histiocytosis. Six cases of Langerhans' cell histiocytosis were investigated by immunohistochemical techniques (alkaline phosphatase-antialkaline phosphatase complex and indirect immunoperoxidase). Increase of γδ T cells was observed in 3 cases of Langerhans' cell histiocytosis. In these cases up to 30% of CD3⁺ cells stained with an anti-TCR γδ monoclonal antibodies and in two of them γδ T cells showed a marked epidermotropism. In the specimens of the remaining three cases γδ T cells were found in an overall percentage of 5% of CD3⁺ cells, but in two cases a significant increase of epidermal γδ T cells was observed. The finding of numerous γδ T cells in Langerhans' cell histiocytosis is provocative and supports the suggestion of a functional relationship between γδ T cells and LCH cells. © 1993 Wiley-Liss, Inc.     

X-linked severe combined immunodeficiency with γδT cells

A patient with X-linked severe combined immunodeficiency (X-SCID) was found to have a deletion mutation of a four base pair in the transmembrane domain of the IL-2 receptor γ chain gene, a subunit shared by the receptors for IL-4, IL-7, IL-9, and IL-15 (common γ chain; γc). He had very few αβT cells but had a considerable number of γδT cells in his peripheral blood. Fluorescence in situ hybridization (FISH) analysis showed that the γδT cells in his peripheral blood were not of maternal origin. He had received a Bacillus Calmette-Guerin (BCG) vaccination before recognition of the disease, and the BCG infection remained quiescent with no reaction for 19 months. After successful bone marrow transplantation, the site of the BCG vaccination showed a reaction, and live BCG were detected. It is useful to consider the relationship between the existence of γδT cells and BCG in this case, and it is suggested that γδT cells may be, in a given situation, less dependent on the γc chain than are αβT cells.     

Peripheral expansion of Vδ1-Jδ1/Jδ2+γδT cells and large granular lymphocytes in a patient with Wiskott-Aldrich syndrome

A 7 month old Japanese boy was diagnosed to have Wiskott-Aldrich syndrome (WAS) because of eczema, thrombocytopenia, progressive immune defect and CD43 (sialophorin) abnormality. He had developed repeated infections since 16 months of age. γδT cell-receptor positive T cells in the peripheral blood were gradually increased from 3.1% (7 months of age) to 5.6% (12 months), 19.6% (18 months) and 56.7% (25 months). The phenotypes of expanded γδT cells were δTCS1-positive (Vδ1-Jδ1/Jδ2) and CD8 dim-positive. The proportion of increased granular lymphocytes correlated well with that of γδT cells. The significance of peripheral expansion of γδT cells and granular lymphocytes in WAS is discussed.     

Chemotherapy and interferon‐α treatment of Erdheim–chester disease

Erdheim–Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis of an unknown origin. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized. Interferon‐α (IFN) has been reported to be effective in the management of ECD. We report here on an uncommon case with ECD in a 17‐year‐old female who had multiple lesions in the whole body and she was treated with chemotherapy and IFN. She has remained disease‐free for 2 years after the completion of treatment. Pediatr Blood Cancer. 2010;55:745–747. © 2010 Wiley‐Liss, Inc.     

超声引导内镜下逆行阑尾炎治疗术在阑尾相关慢性腹痛患儿中的应用价值

目的探讨超声引导内镜下逆行阑尾炎治疗术在儿童阑尾相关慢性腹痛中的临床疗效。方法回顾性收集2019年8月至2021年5月收治的以慢性腹痛为主诉，超声提示阑尾炎症或腔内粪便或粪石且行超声引导内镜下逆行阑尾炎治疗术患儿30例的临床资料，分析其临床表现、内镜下表现、白细胞计数及中性粒细胞百分比、住院时间、治愈率。结果30例慢性腹痛患儿中，男童13例（43%），女童17例（57%），平均确诊年龄（9±3）岁，年龄范围3~15岁，中位病程持续时间12个月，中位住院时间3 d；中位白细胞计数6.7×10⁹/L，中性粒细胞百分比为（50±13）%。21例（70%）术中阑尾腔内冲洗出粪石及大量粪渣。随访率97%（29/30），中位随访时间11（范围：5~26）个月，27例（93%）腹痛症状完全消失。结论超声引导内镜下逆行阑尾炎治疗术对阑尾腔内粪便或粪石引起的儿童慢性腹痛治疗有效。     

Relation between serum IL‐4, IL‐13 and IFN‐γ levels and recurrence of wheezing episodes in infants with acute bronchiolitis

Lower respiratory tract infections are the most important factors among various causes which trigger wheezing in the first year of life. The factors associated with episodic wheezing in children with acute bronchiolitis are still subjects of research. Infections, environmental factors, immunologic mechanisms are sorted as etiologic risk factors of episodic wheezing. We aimed to investigate the relationship between serum interleukin (IL)‐4, IL‐13 and γ‐interferon (IFN‐γ) levels and recurrence of wheezing episodes in infants with acute bronchiolitis. One hundred twenty infants between 3 and 36 months with acute bronchiolitis enrolled in the study. Personal histories, clinical and laboratory data of infants were recorded. The patients were followed for a year. Venous blood samples were obtained to determine serum IL‐4, IL‐13, and IFN‐γ levels during acute bronchiolitis episode. The number of wheezing episodes was significantly higher in infants with a positive family history of allergy. A statistically significant correlation was determined between serum IL‐13 levels of infants and number of wheezing episodes. High serum IL‐13 levels and a positive history of allergy may have important roles in the recurrence of acute bronchiolitis.     

Citrin缺陷病患儿体格和神经心理发育状况

目的探讨Citrin缺陷病（Citrin deficiency，CD）患儿的体格和神经心理发育情况。方法选择2010年8月至2015年8月于暨南大学附属第一医院就诊，经SLC25A13基因分析确诊的93例CD患儿（年龄：1.9~59.8个月）为研究对象，对其出生情况、体格生长及神经心理发育指标进行回顾性分析。其中7例患儿1岁内及1岁后各做过1次体格测量及神经心理发育评估，故共纳入100例次进行分析。结果93例患儿中，生长发育落后发生率为25%（23例），小于胎龄儿比例为47%（44例）。生长迟缓、低体重、消瘦、超重及小头畸形发生率分别为23%（23例次）、14%（14例次）、4%（4例次）、8%（8例次）、9%（9例次）。神经心理发育迟缓率为25%（25例次），适应性、大运动、精细动作、语言、个人社交5个能区发育迟缓率分别为7%（7例次）、15%（15例次）、7%（7例次）、9%（9例次）、7%（7例次）。结论CD患儿存在体格及神经心理发育落后，建议对其体格及神经心理发育进行定期评估。     

Interleukin‐6, interleukin‐8, interleukin‐11, and interferon‐γ levels in nasopharyngeal aspirates from wheezing children with respiratory syncytial virus or influenza A virus infection

The differences between respiratory syncytial virus (RSV) and influenza A virus (IFAV) in the pathogenesis of wheezing in young children have not been clearly defined. The aim of this study was to assess the contributions of RSV vs IFAV in the pathogenesis of upper airway inflammation in wheezy young children. We compared interleukin (IL)‐6, IL‐8, IL‐11, and interferon‐γ (IFN‐γ) levels in nasopharyngeal aspirates (NPA) from non‐asthmatic children with respiratory virus infections (RSV in 17 children and IFAV in 13 children), asthmatic children with viral infections (RSV in nine children, IFAV in 10 children), and 22 unaffected healthy children (controls). Levels of IL‐11 in NPA from asthmatic children were significantly higher than those from non‐asthmatic children with RSV infection, and RSV infection enhanced the IL‐11 production in NPA significantly compared to IFAV infection. Nasopharyngeal epithelium from children with RSV infection secreted more IL‐6 than that of children with IFAV infection. There was little difference in the IL‐8 and IFN‐γ levels between asthmatic and non‐asthmatic children with RSV or IFAV infection. In conclusion, asthma enhanced IL‐11 production in RSV infection rather than IFAV infection in early childhood. There was a trend towards greater IL‐6 production in RSV infection compared with IFAV infection.     

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

1 Background

Low bone mass is common among adolescents with transfusion‐dependent β‐thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion‐dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion‐dependent (NTD) β‐thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β‐thalassemia.

2 Objective

To determine the prevalence of low bone mass among adolescents with NTD Hb E/β‐thalassemia and factors relating to low bone mass.

3 Methods

We investigated BMD of lumbar spine (L2–L4; BMDLS) and total body (BMDTB), as measured by dual‐energy X‐ray absorptiometry, in 22 adolescents (aged 13.2–20 years) with NTD Hb E/β‐thalassemia.

4 Results

Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z‐score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z‐score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z‐scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z‐scores adjusted for bone age.

5 Conclusion

We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β‐thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long‐term bone health.     

经外周静脉穿刺中心静脉置管患儿相关性血源感染的危险因素分析

目的对新生儿重症监护室（neonatal intensive care unit，NICU）患儿经外周静脉穿刺中心静脉置管（peripherally inserted central catheterization，PICC）后发生导管相关血源感染（catheter-related bloodstream infection，CRBSI）或中心静脉伴随血源感染（central line-associated bloodstream infection，CLABSI）进行特征分析并评估CRBSI或CLABSI的危险因素。方法回顾性收集2018年6月1日至2020年5月1日在浙江大学医学院附属儿童医院NICU需要PICC置管的患儿临床资料。同时采集导管数据，包括置管时间、置管部位、拔除日期和PICC抗生素锁等。采用多因素logistic回归模型分析PICC患儿发生CRBSI或CLABSI的危险因素。结果NICU患儿中共446例需要PICC置管，平均胎龄为（30.8±4.0）周；平均出生体重为（1 580±810）g；中位年龄为9 d；PICC留置的中位持续时间为18 d。CLABSI和CRBSI的发生率分别为每1 000导管日5.6和1.46。PICC致CLABSI的常见病原菌为表皮葡萄球菌（n=19）和肺炎克雷伯菌（n=11），CRBSI的常见病原菌为肺炎克雷伯菌（n=6）。PICC致CLABSI的风险随着PICC置管持续时间和抗生素的持续使用时间延长而显著增加，头颈部位置管的感染概率低于上下肢置管（P<0.05），且上述情况在出生体重<1 500 g的患儿中更加显著。PICC致CRBSI的风险随着胎龄增加而降低（P<0.05）。结论CRBSI和CLABSI仍然是NICU医院感染中的重要问题。识别导致CRBSI和CLABSI的危险因素可为临床治疗及管理质量改进提供依据。     

A novel tissue‐based ß‐catenin gene and immunohistochemical analysis to exclude familial adenomatous polyposis among children with hepatoblastoma tumors

1 Background

The Wnt/β‐catenin pathway plays a central role in the pathogenesis of most hepatoblastomas (HBs), that is, up to 60–80% carry activating CTNNB1 mutations. HBs can however also be the first manifestation of familial adenomatous polyposis (FAP). As this is a severe disease, it is important for the patient and related family members to firmly exclude FAP at an early stage. Current diagnosis largely depends on APC germline mutation detection on genomic DNA, which is associated with 10–20% false‐negative results. Here, we establish and validate a tissue‐based β‐catenin gene and immunohistochemical analysis, which complements germline mutation screening to exclude the diagnosis of FAP among HB patients.

2 Methods

Tumor tissues of 18 HB patients, including three FAP cases were subjected to CTNNB1 exon 3 mutational analysis and immunohistochemistry comparing staining patterns for total and exon 3 specific β‐catenin antibodies.

3 Results

Our novel tissue‐based method reliably identified all three FAP patients. Their tumors were characterized by a wild‐type exon 3 sequence and a comparable nuclear staining for both antibodies. In contrast, the non‐FAP tumors carried missense CTNNB1 mutations combined with a clearly reduced staining for the exon 3 antibody, or complete loss of staining in case of lesions with exon 3 deletions.

4 Conclusion

We have successfully established and validated a novel ß‐catenin gene and immunohistochemical diagnostic method, which, when combined with routine germline DNA testing, allows the exclusion of the diagnosis of FAP among HB patients.     

Low frequency of CD4+, but not CD8+, T cells expressing interferon‐γ is related to cow's milk allergy in infancy

Low interferon‐γ (IFN‐γ) and tumor necrosis factor‐α (TNF‐α) production in peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis and food allergy have been reported previously. However, it remains unclear whether the weak cytokine production is caused by the imbalance of specific T‐cell subsets or by dysregulation of T‐cell function. In the present study we investigated the intracellular expression of these cytokines at a single‐cell level to clarify the background of the disruption. Twelve of 27 breast‐fed infants (0.1–8.8 months of age) had challenge‐proven cow's milk allergy (CMA), and 15 infants were studied as a healthy control group. PBMC were stimulated with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The frequencies of the cells expressing intracellular IL‐4, IFN‐γ, and TNF‐α were assessed using flow cytometry. In addition, at this time‐point leucocyte subsets from the milk of mothers of these infants were evaluated using light microscopy. A lower number of CD8⁺ T cells and the defective capability of CD4⁺ T cells to express IFN‐γ in infant's peripheral blood co‐existed with a lower number of macrophages in their mother's milk.