Doaa Mohammed Youssef

MicroRNA-21 as a novel biomarker in diagnosis and response to therapy in asthmatic children.

BACKGROUND The underlying molecular mechanisms leading to asthma remain largely unclear. MicroRNAs (miRNAs) are short noncoding RNAs exert powerful effects on immunological function by tuning networks of target genes that orchestrate cell activity. However, the role of miRNAs, specifically microRNA-21 (miRNA- 21), in the regulation of allergic airway inflammation is not well defined. Our aim was to investigate the serum miRNA- 21 expression levels as potential biomarker in childhood asthma [with, without inhaled corticosteroid (ICS) therapy, and steroid resistant (SR)]; and their possible contributions in disease status, its molecular target interleukin-12 (IL-12) p35, and response to therapy. MATERIALS AND METHODS This study included 175 children; 95 were asthmatic patients subdivided into 3 groups [40 asthmatic children without ICS, 40 steroid sensitive (SS) asthma children and 15 steroid resistant (SR) asthma children] and 80 were healthy children as healthy controls. The miRNA-21 expressions levels were determined by quantitative real-time polymerase chain reaction (qRT-PCR) in all children. Serum IL-12p35 and total IgE levels were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS The expression levels of miRNA-21 were significantly higher in the asthmatic children than in control group (P<0.001); with significantly higher levels in asthmatic patients without ICS or in SR patients compared to SS children (P<0.001). On contrast, serum IL-12p35 levels were significantly decreased in asthmatic patients without ICS therapy or in SR asthma patients as compared to SS patients (P<0.001). Our data revealed that serum miRNA-21 expression levels was significant negatively correlated with serum IL-12p35 levels and FEV1, while it was positively correlated with both sputum and blood eosinophils. Importantly, serum miRNA-21 had a predictive value in differentiating SS from SR patients, with an AUC value of 0.99, specificity of 86.7%, sensitivity of 97.5% and P<0.001. CONCLUSION This study suggested that serum miRNA-21 is stable and detectable in serum of asthmatic children, which could promise potential biomarker in diagnosis as well as in response to therapy of asthma.

The influence of leptin on Th1/Th2 balance in obese children with asthma

OBJECTIVE In individuals with asthma, obesity induces the production of leptin and is associated with disease severity. Our objective was to evaluate the levels of serum leptin and their effect on Th1/Th2 balance in obese and non-obese children with asthma, as well as to investigate the association between serum leptin levels and clinical outcomes. METHODS We evaluated 50 atopic children with physician-diagnosed moderate-to-severe persistent asthma and 20 controls. The children with asthma were divided into two groups, by body mass index percentile: obese (n = 25) and non-obese (n = 25). From all subjects, we collected peripheral blood samples in order to determine the levels of leptin, IFN-γ, and IL-4. Asthma severity was assessed by an asthma symptom score, and the results were correlated with the parameters studied. RESULTS Serum leptin levels were significantly higher in the obese asthma group than in the non-obese asthma group, as well as being significantly higher in the children with asthma than in the controls, whereas IFN-γ levels were significantly higher and IL-4 levels were significantly lower in the obese asthma group than in the non-obese asthma group. In addition, the obese asthma group showed higher asthma symptom scores and significantly lower FEV1 (% of predicted) than did the non-obese asthma group. There was a significant positive correlation between leptin and IFN-γ levels only in the obese asthma group. CONCLUSIONS Although leptin is involved in the pathogenesis of asthma in obese and non-obese children, its effect is more pronounced in the former. In the presence of high leptin levels, only obese children with asthma exhibited Th1 polarization, with higher IFN-γ levels and greater asthma severity.

Assessment of Hepatic and Pancreatic Iron Overload in Pediatric Beta-Thalassemic Major Patients by T2* Weighted Gradient Echo Magnetic Resonance Imaging

Background. MRI has emerged for the noninvasive assessment of iron overload in various tissues. The aim of this paper is to evaluate hepatic and pancreatic iron overload by T2∗ weighted gradient echo MRI in young beta-thalassemia major patients and to correlate it with glucose disturbance and postsplenectomy status. Subjects and Methods. 50 thalassemic patients, in addition to 15 healthy controls. All patients underwent clinical assessment and laboratory investigations. Out of 50 thalassemic patients, 37 patients were splenectomized. MRI was performed for all subjects. Results. All patients showed significant reduction in the signal intensity of the liver and the pancreas on T2∗GRD compared to controls, thalassemic patients who had abnormal glucose tolerance; diabetic and impaired glucose tolerance patients displayed a higher degree of pancreatic and hepatic siderosis and more T2∗ drop in their signal intensity than those with normal blood sugar level. Splenectomized thalassemic patients had significantly lower signal intensity of the liver and pancreas compared to nonsplenectomized patients. Conclusion. T2∗ gradient echo MRI is noninvasive highly sensitive method in assessing hepatic and pancreatic iron overload in thalassemic patients, more evident in patients with abnormal glucose tolerance, and is accelerated in thalassemic splenectomized patients.

High-intensity light-emitting diode vs fluorescent tubes for intensive phototherapy in neonates

Background: Special blue fluorescent tubes are recommended by the American Academy of Pediatrics (AAP) as the most effective light source for lowering serum bilirubin. A high-intensity light-emitting diode (‘super LED’) could render intensive phototherapy more effective than the above conventional methods. This study compared the efficacy and safety of a high-intensity light-emitting diode bed vs conventional intensive phototherapy with triple fluorescent tube units as a rescue treatment for severe unconjugated neonatal hyperbilirubinaemia. Method: This was a randomised, prospective trial. Two hundred jaundiced neonates ≥ 35 weeks gestation who met the criteria for intensive phototherapy as per AAP guidelines were randomly assigned to be treated either with triple fluorescent tube units (group 1, n = 100) or a super LED bed (group 2, n = 100). The outcome was the avoidance of exchange transfusion by successful control of hyperbilirubinaemia. Results: Statistically significant higher success rates of intensive phototherapy were achieved among neonates treated with super LED (group 2) than in those treated conventionally (group 1) (87% vs 64%, P = 0.003). Significantly higher ‘bilirubin decline’ rates were reported in both haemolytic and non-haemolytic subgroups treated with the super LED bed compared with a similar sub-population in the conventionally treated group. Comparable numbers of neonates in both groups developed rebound jaundice (8% vs 10% of groups 1 and 2, respectively). Side-effects were mild in both groups, but higher rates of hyperthermia (12% vs 0%, P = 0.03), dehydration (8% vs 2%, P = 0.26) and skin rash (39% vs 1%, P = 0.002) were reported in the fluorescent tubes-treated group compared with the LED group. Conclusions: Super LED is a safe rescue treatment for severe neonatal hyperbilirubinaemia, and its implementation may reduce the need for exchange transfusion.

Incidence of acute kidney injury in the neonatal intensive care unit.

The aim of this work is to study the incidence of acute kidney injury (AKI) in neonates admitted to the neonatal intensive care unit (NICU) over a six-month period from September 2011 to March 2012. This prospective study was performed on 250 neonates admitted to the NICU at the Childrens Hospital, Faculty of Medicine, Zagazig University. All neonates were subjected to detailed history taking, including pre-natal, natal and post-natal history, with stress on symptoms suggestive of AKI. All neonates were examined thoroughly and the following investigations were performed: Blood urea nitrogen (BUN), serum creatinine, sodium, potassium, calcium, complete blood count, C-reactive protein, arterial blood gases, urine sodium and urine creatinine. AKI was diagnosed in 27 cases (10.8%), including 12 females and 15 males. 40.7% of the AKI cases were born after full-term pregnancy while 59.3% were pre-term babies. 29.6% of the AKI cases had oliguria, and there was male sex predominance, with a male-female ratio of 1.3:1. The cause of AKI was pre-renal in 96.3% and intrinsic renal in 3.7% of the cases. The predisposing factors for AKI were sepsis in 63% of the cases, respiratory distress syndrome in 55.6%, mechanical ventilation in 51.9%, peri-natal asphyxia in 18.5%, dehydration in 14.8%, surgical operation in 11.1%, congenital heart disease in 7.4%, sub-galeal hematoma in 3.7%, polycythemia in 3.7% and intra-ventricular hemorrhage in 3.7% of the cases. Our data suggest that pre-renal failure was the most common form of AKI in our patients. Early recognition of risk factors such as sepsis, peri-natal asphyxia or peri-operative problems and rapid effective treatment of contributing conditions will reduce the incidence of AKI in the neonatal period.

Value of renal resistive index as an early marker of diabetic nephropathy in children with type-1 diabetes mellitus

Constant increase in the incidence of type-1 diabetes (T1-DM) has made it necessary to have new markers for the early detection of diabetic nephropathy (DN). One of the markers that could be helpful in detecting functional alterations in renal hemodynamics is assessment of the renal resistive index (RI) by using renal Doppler. We studied 25 patients with T1-DM (Group-A), which comprised of 15 females and 10 males, with a mean age of 10.8 ± 2.2 years and duration of diabetes of 5 ± 1.1 years. A control group (Group-B) comprising 20 healthy children, 12 females and eight males with mean age of 11.6 ± 2 years, was also studied. The following parameters were studied in the two groups: age, serum creatinine, albumin excretion rate (AER), glomerular filtration rate (GFR), glycosylated hemoglobin (HbA1c) and mean renal RI of both kidneys. We found an increase in the mean RI in diabetic patients versus healthy children; the mean RI in Group-A was 0.64 ± 0.55 while it was 0.58 ± 0.0.28 in Group-B (P <0.000). This increase in RI had a positive correlation with duration of the disease, GFR and HbA1c levels, but there was no correlation with serum creatinine or AER. We conclude that RI is increased early in TI-DM, and it can be a predictor of DN.

Protein C levels in β-thalassemia major patients in the east Nile delta of Egypt

BACKGROUND AND OBJECTIVES Thalassemic patients have an increased risk for thromboembolic complications. To determine if this might be due to a deficiency in protein C, we investigated the status of the protein C anticoagulant pathway in thalassemia major patients and its relationship to the hypercoagulable state. PATIENTS AND METHODS Fifty patients with β-thalassemia major (30 non-splenectomized and 20 splenectomized) and 20 healthy children as a control group were tested for levels of serum ferritin, liver enzymes, serum albumin, fibrinogen, protein C and protein S, thrombin antithrombin complex (TAT) and D-dimer. RESULTS Thalassemic patients had lower levels of protein C and S and higher levels of D-dimer and TAT than the control group. These findings were more obvious in splenectomized patients and in those with infrequent blood transfusion. CONCLUSIONS Protein C plays a major role in the hypercoagulable state in thalassemic patients. These findings raise the issue as to whether it would be cost-beneficial to recommend prophylactic antithrombotic therapy in high-risk thalassemic patients. A wider prospective study is necessary to delineate under which circumstances therapy might be needed, and at what level of protein C deficiency to start prophylactic antithrombotic therapy.

Prospective study of nephrolithiasis occurrence in children receiving cefotriaxone.

Ceftriaxone is a commonly used antibiotic among the paediatric population. Various reports have associated high doses of Ceftriaxone with the development of nephrolithiasis; our aim was to test this association with a 5 day course of treatment.

Pediatric systemic lupus erythematosus in a single nephrology unit

Clinical manifestations of systemic lupus erythematosus (SLE) are widely variable, and its course is unpredictable. SLE that begins in childhood has been considered more severe than SLE with onset during adulthood. Our aim was to determine the presentation and the outcome of SLE of 26 children (20 females and 6 males, with a female to male ratio of 3.8:1) with SLE in our center, their ages ranging from 5 - 18 years and followed from 2005 till October 2011. They were diagnosed according to the American Rheumatism Associations revised criteria. Complete blood count, erythrocyte sedimentation rate, C3, urine analysis, 24-h urinary protein, antinuclear antibodies, anti-ds DNA and renal biopsy were obtained for the patients. We found that the most extra-renal manifestation of SLE was fever (57.7%), while lupus nephritis (LN) was the most commonly affected organ (50%). Hemolytic anemia was the most common hematological abnormality (80.8%), while immunological characteristics were positive in all the patients. Remission in patients without LN was more than 5.3-times the remission in LN patients. The outcome of the patients without LN was better than the patients with LN.

Results of recombinant growth hormone treatment in children with end-stage renal disease on regular hemodialysis

Children with chronic kidney disease are at high risk for growth retardation and decreased adult height. Growth hormone (GH) treatment is known to stimulate growth in children with short stature suffering from chronic kidney disease. However, the extent to which this therapy affects final adult height is not known. This study was performed on 15 patients with end-stage renal disease (ESRD) on regular hemodialysis to detect the effect of using recombinant human growth hormone (rhGH) on growth of patients with ESRD on regular hemodialysis and comparing this effect with the growth velocity in the same group without using rhGH in the year before therapy. There were eight females and seven males with mean age 10.6 ± 2.8 (range 5-14 years). For each patient, recombinant GH was given for one year, three-times weekly. The data of these 15 patients was compared with the year before treatment versus data of the same group of patients after six months and after one year of rhGH therapy. Our results showed that, in the year before therapy, height of these patients increased from a mean of 112.1 ± 11.6 cm to 112.7 ± 11.5 cm, which is a non-significant increase statistically (P >0.05) as well as clinically (mean growth velocity 0.6 cm/year), while height of these patients increased from a mean of 112.7 ± 11.5 cm at the start of therapy to 116.8 ± 11 cm after therapy for one year, which, although statically not significant (P >0.05), was of clinical significance as it makes rate of increase, i.e. the mean growth velocity, 4.1 cm/year close to the normal growth velocity, which is 5 cm/year, before puberty. rhGH therapy for patients with ESRD on regular hemodialysis is helpful in height gain and catch-up growth even when given three-times per week instead of five- or six-times per week. We recommend giving rhGH therapy as a routine supplementation to pediatric patients before epiphyseal closure.