DNA damage in children with asthma bronchiale and its association with oxidative and antioxidative measurements

Increased production of reactive oxygen species leading to an imbalance between the oxidative forces and the antioxidant defense systems favoring an oxidative injury has been implicated in the pathogenesis of asthma. The aim of the study was to investigate the peripheral DNA damage, and its association with oxidative and antioxidative measurements in children with asthma bronchiale. The study population contained 42 children with asthma bronchiale and 32 healthy controls. DNA damage was assessed by alkaline comet assay in peripheral lymphocytes. Plasma levels of total antioxidant status (TAS), total peroxide concentration (LOOHs), and total oxidant status (TOS) were determined. In asthma bronchiale patients, DNA damage was significantly higher than in controls (17.9 ± 11.8 AU vs. 1.2 ± 2.0 AU, p < 0.001). Plasma TOS and LOOHs were higher in patients than in healthy controls (13.4 ± 7.0 vs. 9.0 ± 3.5, p = 0.002; 9.9 ± 3.4 vs. 4.4 ± 1.5, p < 0.001, respectively). Plasma TAS level in patients was higher than in healthy controls (5.5 ± 2.5 vs. 1.0 ± 0.6, p < 0.001). DNA damage was correlated with TOS ( r  = 0,616, p < 0.001). The findings indicated that lymphocyte DNA damage level increases in children with asthma bronchiale. Elevated DNA damage may be related to increased oxidative stress. However, the mechanism of this association, and whether it is direct or indirect, remains to be explored.     

Subclinical atherosclerosis after heart and heart-lung transplantation in childhood

Abstract:  Children after heart transplantation are considered as at-risk patients for extracardiac atherosclerotic complications. Noninvasive ultrasound measurement of the common carotid artery (IMT) provides valid information about the endothelial structure of the vascular system. Twenty-two patients (17 male, mean age 12.4 ± 4.5 yr) after heart and (5.7 ± 4.5 yr) heart–lung transplantation were enrolled. The mean IMT was measured and compared with a control group (18 children, 10 male, mean age 11.8 ± 1.8 yr) and to normative data. Transplanted children had a higher IMT than controls (0.453 ± 0.003 vs. 0.424 ± 0.002 mm, p < 0.001). IMT-SDS was increased as well (1.6 ± 0.1 vs. 0.8 ± 0, p < 0.001). Transplanted children had a higher LDL/HDL-ratio (2.2 ± 0.2 vs. 1.2 ± 0.1, p < 0.001). Time after transplantation, age at the time of transplantation, or medical therapy did not influence the findings. We found evidence for subclinical atherosclerosis in children after heart and heart–lung transplantation. Even if single atherosclerotic risk factors could not be identified, transplanted children seem to be at risk for atherosclerosis. Our findings support the recently published statement of the AHA-Expert panel: after heart transplantation atherosclerotic complications may occur with increased incidence. We propose the IMT-measurement in these patients as an easy method to assess the vascular status and to guide preventive measures.     

Nitrites in induced sputum as a simple and cheap non-invasive marker of airway inflammation for asthmatic schoolchildren

To determine if there are differences in the nitric oxide metabolites (nitrites) in sputum of patients with persistent asthma and healthy schoolchildren, we performed a case-control study in a tertiary care hospital in Arequipa, Perú. Nitrites in induced sputum samples were measured using the Griess assay in 30 persistent asthmatics (mean age of 10.1 yr) and 30 controls (mean age of 11.9 yr). The mean ± s.d. of nitrites among asthmatics was significantly higher than the controls (16.30 ± 8.6 vs. 10.25 ± 4.68 nmol/ml, respectively, p = 0.001). Moreover, the nitrite level in the sputum in children with severe persistent asthma was higher than in the level found in the moderate and mild asthmatics (32.83 ± 9.48 vs. 18.10 ± 1.96 vs. 11.84 ± 4.73 nmol/ml, respectively, p < 0.01 for linear trend). This study showed for the first time in children that asthmatics have significantly higher levels of nitrites in induced sputum than healthy controls and that the level of nitrite correlates with the severity of the asthma. Nitrite levels in sputum, a simple and cheap, non-invasive method, may be a good alternative to measure the severity of inflammation in asthmatic children.     

Increased lipid peroxidation in children with autoimmune diseases

To examine the role of oxidative damage in children and adolescents with autoimmune diseases, we compared blood serum levels of the lipid peroxidation (LPO) products 4-hydroxynonenal (HNE) and malondialdehyde (MDA) in 22 children with systemic lupus erythematosus (SLE), 13 children with focal type of scleroderma, and 21 healthy controls. In order to study the influence of disease activity in SLE on serum LPO product levels, the SLE group was divided into one group with active disease ( n = 11) and one group with non-active disease ( n = 11) according to SLEDAI-score, 15.1 and 1.8, respectively. SLE patients with active SLE (146 ± 14nmol/l, median 145nmol/l) have significantly higher HNE levels compared to controls (61 ± 10nmol/l, median 52nmol/l), whereas the MDA serum levels are similar to those of the control group, 1.94 ± 0.18μmol/l (median: 2.02μmol/l) and 1.58 ± 0.11 μmol/1 (median: 1.52 μmol/l), respectively. Children with SCL had HNE and MDA levels similar to the control group.     

Glycemic control in adolescents with type 1 diabetes mellitus improves lipid serum levels and oxidative stress

Introduction:  Atherosclerosis begins in childhood, and diabetes is a risk factor for coronary heart disease. Dyslipidemia is prevalent in children with type 1 diabetes mellitus (T1DM), with an association between elevated hemoglobin A1c (HbA1c), serum lipid levels, and oxidative stress. Our aim was to examine the effect of metabolic control on serum lipid levels and oxidative stress in adolescents with T1DM.
Methods:  Twenty-six adolescents (13 boys and 13 girls), aged 15.65 ± 1.5 yr, with disease duration of 5.9 ± 2.8 yr and average HbA1c 10.8 ± 1.9% were assigned to intensive insulin therapy for 3 months. Comparisons for HbA1c, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein cholesterol, total triglycerides (TG), total cholesterol (TC), apolipoprotein AI, apolipoprotein AII, apolipoprotein B (ApoB), and thiobarbituric acid reactive substances (TBARS) were done between patients whose HbA1c improved by 0.5% or more (GR1) and the rest of the cohort (patients whose HbA1c improved by <0.5%, did not change, or increased) (GR2).
Results:  ApoB (p = 0.047) and TBARS (p = 0.01) were significantly lower at the end of the study in GR1. In GR2, TC (p = 0.01) and LDL (p = 0.03) were significantly higher at study end. Overall, significant beneficial changes in TC (p = 0.006), TG (p = 0.04), LDL (p = 0.02), ApoB (p = 0.015), and oxidative stress (p = 0.001) were found in GR1 compared with GR2.
Conclusions:  We provide direct evidence for the beneficial effect of tight metabolic control on serum lipids and oxidative stress in adolescents with T1DM, indicating that tight metabolic control may reduce cardiovascular risk in these patients.     

Effect of Carelink, an internet-based insulin pump monitoring system, on glycemic control in rural and urban children with type 1 diabetes mellitus

Objective:  To determine whether use of the internet-based insulin pump monitoring system, Carelink, improved glycemic control in rural and urban children treated with insulin pump therapy.
Research design:  We reviewed records of 94 children treated with insulin pump therapy between the years 2004 and 2007 and compared glycemic control, diabetes self-care measures, frequency of clinic visits, and geographic location associated with Carelink use.
Results:  Carelink users showed improvement in hemoglobin A1c (HbA1c) levels [8.0 ± 0.1 (SE) vs. 7.7 ± 0.1 (SE), p = 0.002]. Carelink users uploaded pump and glucometer data 2.2 ± 1.8 (SD) times per month over 0.8 ± 0.4 (SD) yr. Patients who had no access to carelink software and were followed in a conventional manner showed no change in HbA1c levels [8.0 ± 0.2 (SE) vs. 8.1 ± 0.2 (SE), p = 0.17] during the study period. Carelink non-users, defined as patients who had Carelink access but did not use it, had a higher HbA1c level at the start of the study and did not change over the study period [8.9 ± 0.2 (SE) vs. 9.0 ± 0.3 (SE), p = 0.82]. Rural Carelink users showed improvement in HbA1c levels following Carelink use [7.9 ± 0.2 (SE) vs. 7.4 ± 0.2 (SE), p = 0.001], yet had significantly fewer clinic visits per year compared with urban patients [2.8 ± 0.2 (SE) vs. 3.5 ± 0.1 (SE), p = 0.001].
Conclusion:  Use of the Carelink system was associated with improved glycemic control in children with type 1 diabetes on insulin pump therapy.     

Insulin glargine improves hemoglobin A1c in children and adolescents with poorly controlled type 1 diabetes

Abstract:  The pediatric diabetes team at the University of Minnesota made a clinical decision to switch patients with type 1 diabetes with a hemoglobin A1c level greater than 8.0% to insulin glargine in an effort to improve glycemic control. Retrospective chart analysis was performed on 37 patients 6 months after the switch to insulin glargine therapy.
Results:  After 6 months, the average hemoglobin A1c level in the entire cohort dropped from 10.1 ± 2.0 to 8.9 ± 1.6% (p = 0.001). Thirty patients responded with an average hemoglobin A1c drop of 1.7 ± 1.5%, from 10.3 ± 2.2 to 8.6 ± 1.5% (p < 0.001). Seven patients did not respond to insulin glargine therapy, with an average hemoglobin A1c rise of 1.0 ± 0.8% from a baseline of 9.5 ± 1.0% to 10.4 ± 1.4% (p = 0.01). The greatest response was seen in children with an A1c > 12.0%, who dropped their hemoglobin A1c by 3.5 ± 1.9%. Compared with responders, non-responders had significantly less contact with the diabetes team in the form of clinic visits and telephone conversations both before and after initiation of glargine therapy. Sixty-two per cent of patients received insulin glargine at lunchtime, when injections could be supervised at school. Three episodes of severe hypoglycemia occurred after initiation of insulin glargine therapy.
Conclusions:  Insulin glargine substantially improved glycemic control in children and adolescents with poorly controlled type 1 diabetes. This response was most remarkable in those with a baseline hemoglobin A1c level > 12.0%, and may have been related to increased supervision of injections.     

Improved glycemic control and lower frequency of severe hypoglycemia with insulin detemir; long-term experience in 105 children and adolescents with type 1 diabetes

Objective:  To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes.
Research design and methods:  A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy.
Results:  In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 ± 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 ± 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 ± 1.2 vs. 7.6 ± 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents.
Conclusions:  Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.     

Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function

Abstract:  Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 ± 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 ± 81 mg/m²/day vs. 747 ± 98 mg/m²/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 ± 1.7 mg/kg/day at conversion to 4.6 ± 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 ± 23.3 mL/min/1.73 m² at the time of conversion to 80.7 ± 30.7 mL/min/1.73 m² at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.     

Basal insulin and total daily insulin dose in children with type 1 diabetes using insulin pumps

Objective:  To assess the contribution of basal insulin to the total daily dose (CBITDD) and to identify the determinant factors in children with type 1 diabetes mellitus.
Study design:  Cross-sectional study in which the basal insulin requirement was established based on a memory read-out of insulin delivery from pumps. Factors such as glycated haemoglobin A1c (HbA1c), fasting C-peptide, standard deviation score of body mass index (sdsBMI) and demographic data were determined during routine hospital visits. Study group included a total of 90 well-controlled diabetic children with the mean HbA1c 6.6 ± 0.7 (5.2–7.9), age 10.4 ± 4.4 yr (1.1–17.9 yr), diabetes duration 3.0 ± 2.6 yr (0.3–10.9 yr) and sdsBMI 0.08 (−2.27 to 1.79), excluding patients with ketoacidosis or infectious diseases.
Results:  Correlations between CBITDD and age (r = 0.39 and p < 0.005) and diabetes duration (r = 0.61 and p < 0.0001) and an inverse correlation with C-peptide (r = −0.41 and p = 0.0001) were found. C-peptide-positive patients had a significantly lower percentage of basal insulin compared with C-peptide-negative patients (20.6 ± 11 vs. 31.6 ± 11.0%, respectively; p = 0.0004); yet, no significant difference in total insulin daily dose (0.65 ± 0.3 vs. 0.78 ± 0.2 U/kg/d, respectively) was observed.
Conclusions:  The percentage of basal insulin in diabetic children is below 50% and in well-controlled diabetic children is related to the fasting C-peptide level, age of patient and diabetes duration but not to HbA1c and sdsBMI.     

Hypogammaglobulinemia: Incidence, risk factors, and outcomes following pediatric lung transplantation

Abstract:  Infection is the leading cause of morbidity and mortality in the first year following lung transplantation. HG after adult lung transplantation has been associated with increased infections and hospitalization as well as decreased survival. The purpose of this study is to define the incidence, risk factors, and outcomes of HG in the first year following pediatric lung transplantation. A retrospective review of all lung transplant recipients at a single pediatric center over a four-yr period was performed. All serum Ig levels drawn within one yr of transplantation were recorded. An association between HG during the first year after transplantation and age, race, gender, diagnosis leading to transplantation and clinical outcomes including hospitalization, infections requiring hospitalization, viremia, fungal recovery from BAL lavage, and mortality was sought. HG was defined using age-based norms. Fifty-one charts were reviewed. Mean (±s.d.) post-transplantation levels for IgG, IgA, and IgM were 439.9 ± 201.3, 82.3 ± 50.2, and 75.2 ± 41.4 mg/dL, respectively. HG was present in 48.8%, 12.2%, and 17.1% of patients for IgG, IgA, and IgM, respectively. Patients with HG for IgG were older (14.3 ± 3.8 vs. 9.2 ± 5.4 yr; p < 0.01). IgA and IgM HG were associated with invasive aspergillosis (p < 0.01 and p = 0.05, respectively). IgG and IgM levels inversely correlated with bacterial infections and hospital days, respectively (p < 0.01, p < 0.05). HG is a frequent complication following pediatric lung transplantation. Low Ig levels are associated with increased infections and hospital stay.     

Cardiac Operations for North American Children with Rheumatic Diseases: 1985–2005

Certain pediatric rheumatic diseases are known to affect the heart, sometimes requiring surgical intervention. The Pediatric Cardiac Care Consortium database was used to characterize cardiac surgical intervention among children with rheumatic diseases from 1985 to 2005. From this large database, the records for patients younger than 21 years who underwent cardiac surgery for any rheumatic disorder were extracted. The data collected included the type of procedure performed, the age at the time of the procedure, and the year the procedure was performed. The 261 pediatric patients identified underwent 361 cardiac surgical procedures for complications of rheumatic heart disease (RHD; 160 patients), neonatal lupus (NLE; 53 patients), Kawasaki disease (KD; 28 patients), systemic lupus erythematosus (SLE; 13 patients), and juvenile rheumatoid arthritis (JRA; 7 patients). Multiple procedures were performed for 23% of the patients. The most common procedures included pacemaker implantations among infants with NLE, coronary artery bypass grafts for KD primarily in 5- to 15-year-olds, and cardiac valve operations among adolescents with RHD, SLE, and JRA. Six perioperative deaths occurred. The proportion of annual pediatric cardiac surgical volume attributable to rheumatic diseases did not change during the period studied. Despite advances in their medical care, children with rheumatic diseases continue to sustain measurable morbidity and mortality due to the cardiovascular manifestations of their disease.     

ANTI-IgG ANTIBODIES IN JUVENILE RHEUMATOID ARTHRITIS

ABSTRACT. Egeskjold, E.-M., Permin, H., Hørbov, S. and Graudal, H. (Rheumatism Research Unit of Aarhus University, Aarhus, Denmark). Anti-IgG antibodies in juvenile rheumatoid arthritis. Acta Paediatr Scand, 70:711,.–Sixty-two patients, 48 children and 14 adults, with juvenile rheumatoid arthritis (JRA) and 62 age and sex matched controls were studied for anti-IgG antibodies of the classes IgG, IgM and IgA by an indirect immunofluorescence method. 88 % of 48 children =≤16 years and in 64 % of 14 patients >16 years with JRA against 2 % of the controls. IgM anti-IgG occurred inIgG anti-IgG occurred in 4 % of the children, in 24 % of the adults and in 2 % of the controls. IgA anti-IgG occurred in 2 % of the patients and in none of the controls. The prevalence of IgG anti-IgG was the same in pauciarticular, polyarticular and systemic cases, whereas the titres were higher in polyarticular than in pauciarticular cases, and higher in children with a disease duration of more than 5 years. Higher titres were related to higher ESR and lower hemoglobin values. The relationship of higher titres to clinically active disease was not statistically significant. No relationship was found to age, sex, age at onset, or to the dureation of disease. The titres were not related to the concentrations of serum IgG or to the titres of antinuclear antibodies. IgG anti-IgG are common to all the clinical types of JRA, whereas antinuclear antibodies separate the systemic type from pauci- and polyarthritis. Their possible pathogenic significance must therefore be different.     

No Influence of bcl-2, p53, and p21waf1 protein expression on the outcome of pediatric Hodgkin lymphomas

In Argentina, lymphomas account for 13.6% of all pediatric tumors and 47% of them are Hodgkin lymphoma. Previous studies of lymphoma series have reported the expression of apoptotic and cell cycle proteins. Our aim was to study these markers in our pediatric patients and correlate them with their outcome. Immunohistochemical staining with monoclonal antibodies anti-p53, bcl-2, p21, and mdm2 were performed on formalin-fixed paraffin-embedded Hodgkin lymphoma lymph node biopsies from 54 pediatric patients. The analyzed oncogenes p53, bcl-2, p21, and mdm2 exhibited 81%, 44%, 76%, and 90% positive staining, respectively. The most prevalent p53/p21 expression pattern was p53+/p21+, in 57% of cases, whereas concerning p53/mdm2 expression pattern p53+/mdm2+ was observed in 61% of cases. We failed to find any statistically significant correlation between oncogene expression and patient's survival. It seems that p53 plays an important role in lymphomagenesis in our studied population, because it is overexpressed in 81% of Hodgkin lymphoma cases and in more than 50% of cases, it might be able to activate its cellular effectors. Bcl-2 staining observed in 44% of our cases could represent a failure in bcl-2 down-regulation that leads to a rescue event in defective germinal center B-cells, that allows them to develop into Reed-Sternberg and Hodgkin cells.     

p53免疫组化判定肾母细胞瘤预后的研究

目的探讨p53免疫组化的表达与肾母细胞瘤侵袭性的关系,及对术前化疗的评估。方法收集2007年一2009年本院收治的44例肾母细胞瘤患儿,25例患儿未接受化疗而直接手术,19例术前化疗后再做手术。患儿术后病理组织学检查均证实为肾母细胞瘤,年龄0.4~10岁,平均年龄(2.7±2.0)岁。所有病理切片做p53免疫组化。根据p53染色密度和强度进行计分。结果 p53高强度、综合得分在术后和术前化疗患儿之间有统计学意义(P=0.003;P=0.006),综合得分为1的术后化疗患儿死亡、复发及组织结构分型有统计学意义(P值分别为0.034、0.035、0.02)。综合得分为1的术前化疗患儿死亡、复发及组织结构分型无统计学意义(P=0.271)。结论本研究初步表明,肾母细胞瘤术后化疗的肿瘤侵袭性较术前化疗肾母细胞瘤强,p53免疫组化的表达与肾母细胞瘤分期和预后相关,可能成为肾母细胞瘤肿瘤组织病理学分析的补充。     

Patient selection critical for calcineurin inhibitor withdrawal in pediatric kidney transplantation

Abstract:  CNI withdrawal may be employed as a "rescue" strategy for patients with established renal allograft injury and/or declining allograft function, with the aim at eliminating CNI-associated nephrotoxic effects. This analysis reviews outcomes in a pediatric population and identifies risk factors for adverse events post-CNI withdrawal. We performed a retrospective analysis of 17 pediatric renal transplants who underwent CNI withdrawal, with conversion to sirolimus and MMF. Mean CrCl decreased from 64.3 ± 22 to 59.38 ± 28.6 mL/min/1.73 m² (p = 0.04) at six months and 57.46 ± 31.1 mL/min/1.73 m² (p = 0.02) at 12 months post-withdrawal. Forty-one percent of patients experienced AR. Increased risk for AR was associated with prior AR history, lower sirolimus trough levels, and lower CNIT biopsy scores. Graft loss (24%) was associated with worse CrCl, proteinuria, and histologic chronicity. Proteinuria (spot protein/creatinine ratio) increased from 0.75 ± 1.0 to 1.71 ± 2.0 (p = 0.03), unrelated to de novo sirolimus use. Four patients returned to CNI-based immunosuppression due to AR (n = 3) and gastrointestinal side effects (n = 1). Careful selection of pediatric candidates for CNI withdrawal is recommended. Worsening graft function and graft loss may be minimized by selecting patients with high CNIT scores and low biopsy chronicity and excluding patients with prior AR history.     

Safety and efficacy of autologous endothelial progenitor cells transplantation in children with idiopathic pulmonary arterial hypertension: open-label pilot study

Abstract:  Experimental data suggest that transplantation of EPCs attenuates monocrotaline-induced pulmonary hypertension in rats and dogs. In addition, our previous studies suggested that autologous EPC transplantation was feasible, safe, and might have beneficial effects on exercise capacity and pulmonary hemodynamics in adults with IPAH. Thus, we hypothesized that transplantation of EPCs would improve exercise capacity and pulmonary hemodynamics in children with IPAH. Thirteen children with IPAH received intravenous infusion of autologous EPCs. The right-sided heart catheterization and 6-MWD test were performed at baseline and at the time of 12 wk after cell infusion. At the time of 12 wk, mPAP decreased by 6.4 mmHg from 70.3 ± 19.0 to 63.9 ± 19.3 mmHg (p = 0.015). PVR decreased by approximately 19% from 1118 ± 537 to 906 ± 377 dyn s/cm⁵ (p = 0.047). CO increased from 3.39 ± 0.79 to 3.85 ± 0.42 L/min (p = 0.048). The 6-MWD increased by 39 m from 359 ± 82 to 399 ± 74 m (p = 0.012). NYHA functional class also improved. There were no severe adverse events with cell infusion. The small pilot study suggested that intravenous infusion of autologous EPCs was feasible, safe, and associated with significant improvements in exercise capacity, NYHA functional class, and pulmonary hemodynamics in children with IPAH. Confirmation of these results in a randomized controlled trial are essential.     

Systemic lupus erythematosus of childhood onset: correlation between T cells expressing early and late activation antigens and disease activity

Correlation between T cell phenotypes, especially activated T cells expressing early (EA1) and late (HLA-DR) activation antigens and clinical features were investigated in 22 patients with systemic lupus erythematosus (SLE) of childhood onset. Percentages of T cells expressing EA1 and HLA-DR in 22 patients with SLE were significantly higher than those in controls. Comparison of T cell phenotypes between patients with active and inactive SLE showed that eight patients with active disease had significantly increased percentages of HLA-DR positive T cells than 14 with inactive disease (P<0.01). Serial examinations showed that the percentages of HLA-DR positive T cells were decreased after therapy in seven with active non-renal or active non-renal and renal diseases but not in one with only active renal disease. A possible significance of T cells expressing EA1 and HLA-DR in the management of patients with SLE is discussed.Abbreviations HLA-DR human leukocyte antigens-DR - SLE systemic lupus erythematosus     

Anti-centromere antibodies as a marker of Raynaud's phenomenon in pediatric rheumatologic diseases

To examine the possible relationship between anti-centromere antibodies (ACA) and pediatric rheumatologic diseases, we investigated the presence of ACA (using enzyme immunoassay) in the sera of 45 children and adolescents with such diseases and compared the results with a group of 42 age- and gender-matched healthy subjects. ACA were present (≥ 10 U/ml) in three out of five patients (60%) with scleroderma (SCD), in seven out of 16 (43.8%) patients with systemic lupus erythematosus (SLE), in two out of five patients (40%) with mixed connective tissue disease (MCTD), in one out of four patients (25%) with dermatomyositis (DMS), and in two out of 14 patients (14.3%) with juvenile rheumatoid arthritis (JRA). ACA were also detected in a single patient with anti-phospholipid syndrome (APL) who had digital gangrene and hemiparesis, as well as in two healthy subjects. ACA positivity was related to the presence of Raynaud's phenomenon in the studied sample, as 86% of patients suffering from the phenomenon were ACA positive. ACA positivity was associated with older age, high blood pressure and high erythrocyte sedimentation rate (ESR) values, and lower hemoglobin and weight and height percentile values. It was also higher among anti-nuclear antibody-positive subjects. Raynaud's phenomenon and ACA positivity shared almost the same clinical and laboratory associations in the studied patients. Thus, ACA are probably among the markers of Raynaud's phenomenon in pediatric rheumatologic diseases. Their value as predictors of future development of the phenomenon needs further evaluation.     

Antineuronal antibodies and electroneurophysiological studies in pediatric patients with neuropsychiatric systemic lupus erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most difficult manifestations of lupus to diagnose. Measurement of serum brain autoantibodies and assessment of cognitive function by electroneurophysiological studies (electroencephalogram (EEG) and P300) have contributed to an earlier and a more specific diagnosis of NPSLE. Thus, we were stimulated to assess the value of serum antineuronal antibodies and electroneurophysiological studies in diagnosis and early prediction of NPSLE. To investigate this, assessment of serum antineuronal antibodies and cognitive function (clinically and by electroneurophysiological studies) was done in 30 lupus patients [14 (46.7%) with and 16 (53.3%) without clinical evidence of NPSLE] in comparison with 30 healthy matched subjects. Patients without clinical evidence of NPSLE were followed-up clinically by monthly neuropsychiatric evaluation for 18 months. Seropositivity for antineuronal antibodies and abnormalities of EEG and P300 (prolonged latency and/or low amplitude) were found in 60%, 50% and 70%, respectively of lupus patients. During follow-up, 8 out of the 16 patients without clinical evidence of NPSLE developed such evidence [six (75%) had antineuronal seropositivity, five (62.5%) had abnormal EEG, six (75%) had P300 abnormalities and all had at least one abnormal result of these parameters at the time of initial evaluation before clinical presentation of NPSLE]. In conclusion, serum antineuronal antibodies and electroneurophysiological studies may be reliable parameters for diagnosis and early prediction of NPSLE, especially when combined together, before clinical manifestations ensue. Further studies on a large scale are warranted to evaluate the predictive value of these parameters in NPSLE.