Growth of children with β-thalassemia major

Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5–1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.     

Are activated T cells regulators of bone metabolism in children with Crohn disease?

OBJECTIVES: To test the hypothesis that circulating activated T cells may release cytokines that decrease bone turnover in children with Crohn disease. STUDY DESIGN: Newly diagnosed Crohn disease and healthy controls of similar age were compared for bone age, bone mineral content and density, markers of bone remodeling, and serum concentration and in vitro T-cell production of receptor activator of nuclear factor kappaB ligand (RANKL), interferon (INF)-gamma, and osteoprotegerin (OPG). RESULTS: Newly diagnosed children with Crohn disease (n=23) had similar bone mineral density (BMD) z-scores and body mass index as the controls (n=40). Biochemical markers of bone remodeling indicated a state of low bone turnover in the Crohn disease patients compared with controls. Serum OPG (pmol/L; mean+/-SD, median) was higher (4.24+/-1.74, 3.98 vs 3.38+/-0.83, 3.41; P<.05), and serum RANKL (pmol/L) was lower in the Crohn disease patients (0.50+/-0.86, 0.28 vs 1.02+/-1.63, 0.49; P<.01), consistent with decreased bone resorption. Activated T cells from Crohn disease patients produced a higher concentration of INF-gamma (ng/microg protein) than those from controls (20.03+/-26.39, 8.70 vs 9.76+/-14.10, 6.17; P<.05). CONCLUSIONS: The newly diagnosed children with Crohn disease exhibited reduced bone remodeling, possibly due to T-cell INF-gamma and OPG.     

Evaluation of hepatic iron overload in Chinese children with β-thalassemia major

Patients with β-thalassemia major require long-term blood transfusions, resulting in hepatic iron overload. Thirty-five Chinese children with β-thalassemia major were recruited in the present studies. Hepatic iron overload was evaluated by histological grading. The relationships between hepatic iron overload and both serum biochemical markers and magnetic resonance imaging (MRI) examination were studied. The majority of the patients showed high degrees of hepatic iron overload by histological study. The degree of hepatic iron overload was correlated with serum ferritin (r = .70, P < .01), hyaluronic acid (r = .58, P = .011), and type III precollagen (r = .55, P = .035). Moreover, hepatic iron overload showed a negative correlation with liver to muscle signal intensity ratio (r = -.44, P = .012), and a positive correlation with red marrow area percentage (r = .52, P < .01). These results indicated that hepatic iron overload might be assessed by serum biochemical markers and MRI examination.     

Clinical efficacy of combined therapy in children with stage 4 neuroblastoma北大核心CSCD

目的 观察4期神经母细胞瘤联合治疗的早期疗效,探讨提高生存率及改善生活质量的治疗方案。 方法 对2016年1月至2021年6月在香港大学深圳医院确诊的14例4期神经母细胞瘤患儿的临床资料、治疗及随访情况进行回顾性分析。 结果 14例患儿中位发病年龄为3岁7.5个月。骨髓检查阳性9例,N-Myc基因扩增4例,神经元特异性烯醇化酶增高13例,尿香草扁桃酸增高7例。病理结果：分化型6例,未分化型1例,混合型1例,分化差型6例。N7方案化疗10例（含2例N7方案+三氧化二砷化疗患儿）,Rapid COJEC方案化疗4例。手术13例;自体造血干细胞移植14例;放疗10例。Ch14.18/CHO免疫治疗8例,其中1例因在治疗过程中出现过敏性休克而停止免疫治疗;其余7例完成治疗,期间未观察到严重不良反应。完成免疫治疗患儿中1例复发后进行3次Lu177 Dotatate治疗,目前仍在化疗中。14例患儿中位随访时间为45个月。2年内复发4例,2年内总生存率100%;3年内复发4例,3年内无病存活7例。 结论 儿童4期神经母细胞瘤建议选择多学科联合方案治疗,使4期神经母细胞瘤患儿获得更好的生存及预后。     

Pharmacodynamics and pharmacokinetics of esmolol,a short-acting β-blocking agent,in children

Summary Esmolol, a short-acting intravenous cardioselective -blocking agent, was evaluated for age-dependent pharmacodynamic and pharmacokinetic features in 17 young patients (6 months to 14 years). A loading dose (500 g/kg/min) alternating with a maintenance dose (25–200 g/kg/min, titrating by 25 g/kg/min every 4 min) was infused until the heart rate or mean arterial pressure decreased 10%. Cardiac index, left ventricular shortening fraction, and systemic vascular resistance were measured at baseline, peak esmolol effect, and recovery. Serum esmolol concentrations were obtained to determine the half-life and the elimination rate constant.Esmolol reduced the heart rate, blood pressure, shortening fraction, and cardiac index in all patients, but it did not change systemic vascular resistance. Maintenance esmolol dose was 118 ±49 g/kg/min, and the half-life was 2.88±2.67 min. Blood pressure and heart rate returned to normal within 2–16 min, but cardiac index and shortening fraction took longer to recover. There were no statistically significant age-dependent pharmacodynamic effects, but blood pressure decreased prior to heart rate and cardiac index took longer to recovery in patients who weighed15kg. The pharmacokinetic profile in young patients was similar to that of older patients, but the half-life was shorter. The only side effeect was transient nausea and vomiting in one patient. Esmolol is a safe and efficacious -blocking agent in young patients.     

Prevalence of MEFV gene mutations and their clinical correlations in Turkish children with Henoch-Schönlein purpura

Aim: To investigate the frequency of MEFV mutations and their associations with the clinical and laboratory findings in children with Henoch–Schönlein purpura (HSP). Methods: One hundred and seven children with HSP were investigated for 12 common MEFV mutations. Results: Forty‐seven patients (43.9%) were found to have one of the MEFV mutations. Eight patients (7.5%) were homozygous for one mutation, 33 (30.8%) were heterozygous for one and six (5.6%) were compound heterozygous for two mutations. There were no age and sex differences between patients with or without mutations. Scrotal involvement was statistically more frequent in patients with mutations. Leucocyte counts, erythrocyte sedimentation rates, serum C‐reactive protein (CRP) concentrations, number of patients with increased CRP levels and number of patients with increased immunoglobulin A concentrations were found to be higher in patients with MEFV mutations. p.M694V was the most frequent mutation and was found to have effects on clinical and laboratory findings in children with HSP. Fifteen patients were started on colchicine with the diagnosis of familial Mediterranean fever (FMF). Conclusion: MEFV mutations are more frequent in HSP than in the general population, and mutation carriers may have more severe clinical findings with higher inflammatory response, suggesting a dysregulation of the inflammatory response because of defective gene encoding the protein pyrine. Investigation of these mutations may be beneficial to follow‐up the susceptible patients more closely leading to early diagnosis and treatment of FMF.     

Does epilepsy influence the outcome of antireflux procedures in neurologically impaired children?

In neurologically impaired patients (NIP), surgical management of gastroesophageal reflux disease (GERD) has become a widespread standard. Several follow-up studies have shown a high incidence of complications and recurrent reflux. As one of the possible causes epilepsy is mentioned repeatedly in the literature. The aim of this study was to determine the effective impact of epilepsy on the postoperative outcome by comparing results of our patients suffering from epilepsy to those without this disorder. From 1984 to 1999, a total of 45 NIP underwent antireflux surgery, including 20 patients suffering from epilepsy (EP) and 25 patients without this disorder (nEP). The existence of epileptic disorders, incidence of epileptic seizures and administration of anticonvulsatory drugs as well as results of diagnostic procedures, postoperative complications and incidence and time of recurrence of pathologic GER were recorded and analysed retrospectively. Preoperatively all patients had pathologic results in 24 h pH-monitoring. Median RI was 15.75 (EP, range 5.2–28.6) and 17.55 (nEP; range 7.2–26.5). 12-months-postoperative 24 h pH-monitoring showed a median RI of 3.8 (EP; range 1.3–25.6) versus a median RI of 3.3 (nEP; range 0.7–26.3). During the long-term follow-up evaluation of 3.9 years, 17 EP suffered from persistent epileptic seizures despite medical treatment. 19 patients (42%) developed recurrent reflux. This included seven EP (35%) and 12 nEP (48%). The necessity of reoperation was higher in nEP (n = 5, 20%) than in EP (n = 1, 5%). This analysis did not show a significant correlation between recurrence of pathologic GER after fundoplication and the incidence of epileptic seizures. We consider our findings to strongly question the widespread opinion considering this correlation. We conclude, that cerebral seizures alone do not alter the operative outcome of antireflux surgery in NIP.     

Deficits in selective and sustained attention processes in early treated children with phenylketonuria — result of impaired frontal lobe functions?

Twenty normally intelligent children with early treated phenylketonuria (PKU) (IQ: mean=101.4, SD=10.0; age: mean=10 years 11 months, SD=1.3 years) and 20 healthy controls, matched for age, sex and IQ, were assessed for their selective (Stroop Task) and sustained attention (Test-d-2). Using positron emission tomography an activation of the frontal lobe during the Stroop task had previously been demonstrated. In addition to the Stroop Task and the Test-d-2, a short-term memory test as a non-frontal-lobe-function-task was administered to all subjects. Group comparisons demonstrated that PKU children had specific deficits in selective and sustained attention, which were significantly correlated with the concurrent serum phenylalanine concentration.Conclusion The results give evidence that even dietary treated children with PKU were suffering from impaired attentional control mechanisms in spite of a normal IQ. The deficits might be the result of impaired frontal lobe functions.     

Myelofibrosis: a cause of increased transfusion requirement in a child with β-thalassemia intermedia

A 10-year-old girl presented with gradually increasing pallor and abdominal distension for 1 year and fever for 6 months. She required 3 packed cell transfusions during this interval. Investigations done revealed that the child had thalassemia intermedia and parents were carrier of β-thalassemia gene. The increased transfusion requirement in this case prompted further investigations, which revealed the presence of myelofibrosis. Case reports of myelofibrosis and myelodysplastic syndromes with acquired hemoglobin disorders exist in literature, especially α-thalassemia. To the best of our knowledge, this is the first reported case of β-thalassemia intermedia in association with myelofibrosis.     

Evaluation of β-cell function in diabetic Taiwanese children using a 6-min glucagon test

This study evaluates the effects of glucagon 30 μg/kg (maximal 1 mg) on β-cell function in children by C-peptide determined before and 6 min after intravenous administration. From 1990 to 2005, 118 Taiwanese children with newly diagnosed diabetes mellitus (98 children with type 1 and 20 children with type 2) and 29 normal Taiwanese children were enrolled in this study. Fasting and 6-min post-glucagon C-peptide levels were analyzed. In the pre-pubertal group, the median fasting serum C-peptide levels were 0.2 and 0.8 nmol/l in type 1 diabetes and normal children, respectively. These levels rose to 0.3 and 1.9 nmol/l after glucagon stimulation. In the pubertal group, the median fasting serum C-peptide levels were 0.3, 1.0 and 0.9 nmol/l in type 1 diabetes, type 2 diabetes and normal children, respectively. They rose to 0.4, 2.5 and 2.7 nmol/l after glucagon stimulation. Both fasting and post-glucagon C-peptide levels in type 1 diabetes patients were significantly lower than those of normal children and children with type 2 diabetes. The optimal cut-off values to distinguish type 1 diabetes patients from those with type 2 as determined by the receiving operating characteristic curve were 0.7 and 1.1 nmol/l, respectively. The sensitivities of both C-peptide values were 93%. The post-glucagon C-peptide level was more powerful in distinguishing type 1 diabetes from type 2 diabetes with higher specificity (95% vs. 85%). The 6-min glucagon test is valuable in assessing β-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children.     

Combined therapy in human immunodeficiency virus-infected children —a 4-year experience

From 1988 to 1991 the long-term efficacy of a combined therapy with a polyvalent immunoglobulin/cytomegalovirus (CMV) hyperimmunoglobulin, oral low dose zidovudine, oral cotrimoxazole or inhaled pentamidine was investigated in three groups of human immunodeficiency virus (HIV)-infected children. Group 1A consisted of three perinatally infected children with a CD4 cell decrease of >400, cells/l per year. Group 1B were 17 perinatally infected children with a CD4 cell decrease of <400 cells/l per year. Group 2 comprised eight haemophilic children infected by clotting factors. Despite combined therapy none of group 1A survived longer than 12 months showing a rapid loss of CD4 cell counts, progressive encephalopathy, wasting syndrome and severe bacterial, fungal and CMV reactivation. Under pure intravenous immunoglobulin (IVIG) therapy severe bacterial infections were seen in 1 of 12 children in group 1B. The majority of these patients showed increases or stabilisation of length and weight percentiles. In this group low dose zidovudine therapy was of benefit in HIV-associated neurological symptoms. Nevertheless combined therapy could not prevent further deterioration of CD4 cell counts. In group 2 severe bacterial infections were not seen under IVIG therapy. In this group a temporary increase (6 months) of CD4 cell counts under IVIG/zidovudine combined therapy occurred.Pneumocystis carinii pneumonia (PCP) prophylaxis with oral cotrimoxazole or inhaled pentamidine successfully prevented PCP in all three groups. Under CMV hyperimmunoglobulins (n=22), ten out of ten patients did not acquire primary CMV infection, whereas CMV reactivations mainly located in the CNS could not be prevented in 5 of 12 patients. Our findings indicate that this combined therapy showed remarkable differences in therapeutic efficacy in children with different modes of HIV progression. These modes must be considered for correct timing, dosage and evaluation of therapeutic measures.