Sudigdo Sastroasmoro

Effect of 12-week administration of 20-mg long-acting methylphenidate on Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the prefrontal cortices of school-age children in Indonesia: a study using 1H magnetic resonance spectroscopy (MRS).

ObjectivesRecent studies on the neurobiology of attention-deficit/hyperactivity disorder (ADHD) have suggested that there is dysregulation of dopamine-mediated neurotransmission, particularly in the prefrontal cortex and basal ganglia, and that treatment with methylphenidate reverses this dysregulation. Using methodology similar to previous studies involving putative markers of brain functioning, we used 1H magnetic resonance spectroscopy to study the effect of 12-week treatment with daily 20-mg long-acting methylphenidate on the glutamate/creatine, N-acetyl-aspartate/creatine, choline/creatine, and myoinositol/creatine ratios in the prefrontal cortices of medication-naive children with ADHD. MethodThis was a prospective study, using a pretest and posttest design, on a single group of 21 children (mean age, 8.52 years; 17 males and 4 females) with a diagnosis of ADHD. A low time echo (TE) magnetic resonance spectroscopic scans sampled voxels of interest (1.5 × 1.5 × 2.0) from both the right and left prefrontal cortices. ResultsAfter treatment, the N-acetyl-aspartate/creatine ratio increased 18.8% in the right prefrontal cortex (P = 0.001) and 10% in the left prefrontal cortex (P = 0.007); the glutamate/creatine ratio decreased 15% in the right prefrontal cortex (P = 0.005) and 14.1% in the left prefrontal cortex (P = 0.005); the choline/creatine ratio decreased 12.4% in the right prefrontal cortex (P = 0.037) and 16% in the left prefrontal cortex (P = 0.006); and the myoinositol/creatine ratio decreased 14.7% in the left prefrontal cortex (P = 0.011) and 7.7% in the right prefrontal cortex (P = 0.129). ConclusionNotwithstanding the limitations of this pilot study, we found, after stimulant treatment, significant neurochemical changes (thought to reflect functional improvement and improved neuroplasticity) in the prefrontal cortices of children with ADHD.

Exclusive Breastfeeding Plan of Pregnant Southeast Asian Women: What Encourages Them?

OBJECTIVES This study investigated factors involved in breastfeeding planning of pregnant Asian women. SUBJECTS AND METHODS A cross-sectional study was conducted on 207 pregnant women visiting the Budi Kemuliaan Hospital, Jakarta, Indonesia, between June and August 2011. The planned breastfeeding duration and determinants were sought using a standardized self-reported questionnaire. RESULTS Most subjects had low income (84.1%) and education (79.7%). Women who had been informed about breastfeeding had a higher likelihood to plan longer (≥6 months) breastfeeding (odds ratio [OR] 1.97; 95% confidence interval [CI] 1.04-3.75; p=0.04), whereas women who had breastfed previous children over a shorter period had a lower likelihood (OR 0.26; 95% CI 0.11-0.59; p=0.001). Age, low education level, first pregnancy, and low income had no association with breastfeeding plans. Working mothers who had to return to work before 6 months and worked for >8 hours/day were less likely to plan longer breastfeeding (OR 0.14; 95% CI 0.02-0.83; p=0.03 vs. OR 0.53; 95% CI 0.17-1.63; p=0.27), whereas those intending to express their milk were more likely to breastfeed longer (OR 16.85; 95% CI 4.21-67.48; p<0.001). CONCLUSIONS Planning of prolonged breastfeeding has little to do with maternal age, education, or number of pregnancies. However, mothers who work, who had previously breastfed for a short period, and who are not well informed about breastfeeding tend to plan shorter breastfeeding. Among mothers who work, it is the length of maternal leave and required working hours that determine the plans.

The role of allergic risk and other factors that affect the occurrence of atopic dermatitis in the first 6 months of life.

Background Atopic dermatitis (AD) is a chronic inflammation of the skin that often appears in early childhood. The manifestation is related to the tendency towards T helper 2 cytokine immune responses (interleukin (IL)-4, IL-5). Genetic factors are suggested to play important roles in AD, and it can be transmitted to newborns, increasing their risk of developing allergies. Objective To determine the association between cord-blood cytokine levels (IL-5, interferon (IFN) γ), cord-blood total immunoglobulin E (IgE) level, perinatal environmental exposure, and the risks of allergy as well as the development of AD in the first 6 months of life. Methods A 6-month cohort study with a nested case-control within was conducted on newborns in Jakarta from December 2008 until May 2009. After the umbilical cord blood samples were taken and stored, subjects were followed up monthly until 6 months old. The occurrence of AD and lifestyle or environmental exposures were recorded. The allergic risk was determined using a modified pediatric allergy immunology work groups scoring system based on allergic history (allergic rhinitis, asthma, AD) in the family. The levels of IL-5 and IFN-γ were measured using ELISA and total IgE by CAP system FEIA. Multivariate analysis was used to evaluate risk factors. Results This study was conducted on 226 subjects. The incidence of AD was 16.4%; of those, 59% had low risk allergy, 38.5% moderate, and 2% high risk. AD mostly occurred at the age of 1 month (57%). Cord blood samples were examined in 37 subjects with AD and 51 without AD; of those, 25% showed high levels of total IgE (>1.2 IU/µL), and 51% showed normally-distributed high absorbance IL-5 values (≥0.0715, absolute value was undetected). The increased level of IL-5 was directly proportional to IgE. High absorbance IFN-γ values (≥0.0795, absolute value = 18.681 pg/µL) were observed in 52% of subjects. Conclusion The associations between the risk of allergy in the family, cord-blood total IgE, IL-5, IFN levels, and some perinatal environmental exposure with AD in the first 6 months of life have not been established.

Effect of physical activity on vascular characteristics in young children

Background: Physical activity has long been proposed as an important modifiable cardiovascular risk factor in adults. We assessed whether physical activity already has an effect on childhood vasculature. Methods: In the Wheezing-Illnesses-Study-in-Leidsche-Rijn birth cohort, we performed vascular ultrasound to measure carotid intima–media thickness (cIMT) and functional properties (distensibility, elastic modulus) at 5 and 8 years of age. Child typical physical activities were inquired using a questionnaire completed by parents. Linear regression was used with physical activity level, expressed as a standardized value of time-weighted metabolic equivalent (MET) as the independent variable and vascular properties as dependent variables with further confounder adjustment and evaluation for possible body mass index and sex effect modifications. Results: In 595 5-year-old children and in 237 of those who had reached the age of 8 years, we did not find statistically significant associations between total time-weighted MET and each vascular parameter, neither in pooled nor stratified analysis. However, sport activities were associated with thinner cIMT (−3.20 µm/SD, 95% CI −6.34, −0.22, p = 0.04) at 5 years of age; a similar pattern was seen for organized sport. This effect was strongest in children in the highest body mass index tertile (−5.38 µm/SD, 95% CI −10.54, −0.19, p = 0.04). At the age of 8 years, higher sport level tended to be associated with higher vascular distensibility (2.64 × 103 kPa/SD, 95% CI −0.18, 5.45, p = 0.07) although this was not statistically significant. Conclusions: Sport activity may have beneficial effects on arteries of young children, particularly those with higher relative body weight.

Gluten and casein supplementation does not increase symptoms in children with autism spectrum disorder

A gluten‐ and casein‐free diet is often given to children with autism spectrum disorder (ASD). We aimed to determine the effect of gluten and casein supplementation on maladaptive behaviour, gastrointestinal symptom severity and intestinal fatty acids binding protein (I‐FABP) excretion in children with ASD.

Maladaptive Behavior and Gastrointestinal Disorders in Children with Autism Spectrum Disorder

Purpose Various gastrointestinal factors may contribute to maladaptive behavior in children with autism spectrum disorders (ASD). To determine the association between maladaptive behavior in children with ASD and gastrointestinal symptoms such as severity, intestinal microbiota, inflammation, enterocyte damage, permeability and absorption of opioid peptides. Methods This observational cross-sectional study compared children with ASD to healthy controls, aged 2-10 years. Maladaptive behavior was classified using the Approach Withdrawal Problems Composite subtest of the Pervasive Developmental Disorder Behavior Inventory. Dependent variables were gastrointestinal symptom severity index, fecal calprotectin, urinary D-lactate, urinary lactulose/mannitol excretion, urinary intestinal fatty acids binding protein (I-FABP) and urinary opioid peptide excretion. Results We did not find a significant difference between children with ASD with severe or mild maladaptive behavior and control subjects for gastrointestinal symptoms, fecal calprotectin, urinary D-lactate, and lactulose/mannitol ratio. Urinary opioid peptide excretion was absent in all children. Children with ASD with severe maladaptive behavior showed significantly higher urinary I-FABP levels compared to those with mild maladaptive behavior (p=0.019) and controls (p=0.015). Conclusion In our series, maladaptive behavior in ASD children was not associated with gastrointestinal symptoms, intestinal inflammation (no difference in calprotectin), microbiota (no difference in urinary D-lactate) and intestinal permeability (no difference in lactulose/manitol ratio). ASD children with severe maladaptive behavior have significantly more enterocyte damage (increased urinary I-FABP) than ASD children with mild maladaptive behavior and normal children.

Cardiovascular manifestations of HIV infection in children

Background HIV infection in children is now considered as a chronic condition, in which various non-infectious complications may occur, including those affecting the developing cardiovascular system. As children are expected to survive well into adulthood, understanding childhood as well as potential future cardiovascular complications is of major importance. Methods and results We reviewed published literature on childhood cardiac manifestations and longer term effects of pediatric HIV infection on the cardiovascular system. Evidence gaps that should be prioritized in research are highlighted. Through poorly understood mechanisms, HIV infection may cause various cardiac complications already manifesting in childhood, such as structural and functional myocardial derangements, pulmonary hypertension, pericardial effusion and possibly endocarditis. Evidence indicates that HIV infection in children also has unfavorable effects on the vasculature and cardiovascular biomarkers, such as increased intima-media thickness and decreased flow-mediated dilation, a marker of endothelial function. However, studies are small and predominantly include antiretroviral therapy-treated children, so that it is difficult to differentiate between effects of HIV infection per se and antiretroviral therapy treatment, reported in adults to have cardiovascular side effects. Conclusions HIV infection in children may greatly impact the cardiovascular system, including effects on the heart, which tend to manifest early in childhood, and on the vasculature. The underlying mechanisms, essential for targeted prevention, are poorly understood. Current evidence largely stems from research in adults. However, as modes of infection, immune maturity, growth and development, and treatment are markedly different in children, specific pediatric research, accounting for the complex interplay of normal growth and development, HIV infection and treatment, is clearly warranted.

The Amygdala's Neurochemical Ratios after 12 Weeks Administration of 20 mg Long-acting Methylphenidate in Children with Attention Deficit and Hyperactivity Disorder: A Pilot Study Using (1)H Magnetic Resonance Spectroscopy.

Objective Recent pediatric studies have suggested a correlation between decreased amygdala volume and attention deficit and hyperactivity disorder (ADHD) symptoms, including the emotional dysregulation. To investigate the hypothesis that medication treatment of ADHD specifically improves amygdala function, we used 1H magnetic resonance spectroscopy (MRS) to study the effect of 12 weeks of treatment with daily 20 mg long-acting methylphenidate on the Glu/Cr, NAA/Cr, Cho/Cr, and mI/Cr ratios in the amygdala of medication-naïve children with ADHD. Methods This was a prospective study, using a pre- and post-test design, on a single group of 21 children (average age 8.52 years, 17 males and 4 females) diagnosed with ADHD. Low Time Echo MRS scans sampled voxels of interest (1.5×1.5×2.0) from both the right and left amygdala. Results There was significant clinical improvement after 12 weeks of treatment with 20 mg long-acting methylphenidate. On 1H MRS, there were no statistical significant differences of NAA/Cr ratio, Cho/Cr ratio, mI/Cr ratio before and after 12 weeks administration of 20 mg long-acting methylphenidate both in the right and left amygdala. In addition, Glu/Cr ratio decreased 14.1% in the right amygdala (p=0.029) and 11.4% in the left amygdala (p=0.008). Standardized mean effect sizes ranged from 0.14-0.32. Conclusion The findings are consistent with the possibility that hyperglutamatergic processes in the amygdale are related to the hyperactive-impulsive symptoms of ADHD.

The role of curcumin as an inhibitor of oxidative stress caused by ischaemia re-perfusion injury in tetralogy of Fallot patients undergoing corrective surgery.

BACKGROUND Cardiopulmonary bypass during tetralogy of Fallot corrective surgery is associated with oxidative stress, and contributes to peri-operative problems. Curcumin has been known as a potent scavenger of reactive oxygen species, which enhances the activity of antioxidants and suppresses phosphorylation of transcription factors involved in inflamation and apoptosis. OBJECTIVES To evaluate the effects of curcumin as an antioxidant by evaluating the concentrations of malondialdehyde and glutathione, activity of nuclear factor-kappa B, c-Jun N-terminal kinase, caspase-3, and post-operative clinical outcomes. METHODS Tetralogy of Fallot patients for corrective surgery were randomised to receive curcumin (45 mg/day) or placebo orally for 14 days before surgery. Malondialdehyde and glutathione concentrations were evaluated during the pre-ischaemia, ischaemia, re-perfusion phases, and 6 hours after aortic clamping-off. Nuclear factor-kappa B, c-Jun N-terminal kinase, and caspase-3, taken from the infundibulum, were assessed during the pre-ischaemia, ischaemia, and re-perfusion phases. Haemodynamic parameters were monitored until day 5 after surgery. RESULTS In all the observation phases, malondialdehyde and glutathione concentrations were similar between groups. There was no significant difference in nuclear factor-kappa B activity between the groups for three observations; however, in the curcumin group, c-Jun N-terminal kinase significantly decreased from the pre-ischaemia to the re-perfusion phases, and caspase-3 expression was lower in the ischaemia phase. Patients in the curcumin group had lower temperature and better ventricular functions, but no significant differences were found in mechanical ventilation day or length of hospital stay in the two groups. CONCLUSION Cardioprotective effects of curcumin may include inhibition of the c-Jun N-terminal kinase pathway and caspase-3 in cardiomyocytes, particularly in the ischaemia phase.

Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) in the Asia Pacific region (Round Table Forum)

Clinical Epidemiology (CE) and Evidence-Based Medicine (EBM) have become increasingly important in an era of rising costs, patient safety concerns and evidence-based health care. CE and EBM research in the Asia Pacific region have grown significantly. However, there are three main challenges such as linking evidence to practice and policy; developing a strong collaborative network; and a need for resources and technical expertise to produce evidence. The Cochrane Collaboration is a possible solution to resolve above challenges identified, particularly the challenge of transforming evidence to practice. In addition, training can be carried out to enhance technical expertise in the region and there is also the promising potential that collaborations could extend beyond systematic reviews. To improve the adoption of evidence-based health policy, selection of the best evidence for the right audience and focusing on the relevant issues through appropriate methodology are essential. Information on effectiveness and cost effectiveness needs to be highlighted for policy makers. The way forward to strengthen research and capacity building is to establish the Asia Pacific Consortium for CE and EBM. The consortium would help to create mutually rewarding scientific research and collaborations that will augur well for advances in CE and EBM.