Quantification of diffusion tensor imaging in normal white matter maturation of early childhood using an automated processing pipeline.

OBJECTIVES: The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas. METHODS: Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction. RESULTS: DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued. CONCLUSION: DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data. KEY POINTS: Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

Clinical relevance of VKORC1 (G-1639A and C1173T) and CYP2C9*3 among patients on warfarin.

WHAT IS KNOWN AND OBJECTIVES: Testing for cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) variant alleles is recommended by the FDA for dosing of warfarin. However, dose prediction models derived from data obtained in one population may not be applicable to another. We therefore studied the impact of genetic polymorphisms of CYP2C9 and VKORC1 on warfarin dose requirement in Malaysia. METHODS: Patients who were attending clinics at our hospital and prescribed warfarin with stabilized INR levels of 2-4 were selected. DNA was extracted from blood samples and subsequently genotyped for CYP2C9*1, *2, *3, VKORC1 (G-1639A) and VKORC1 C1173T. Linear regression modelling using age, CYP2C9 and VKORC1 genotypes, sex, weight and height was undertaken to define a warfarin dosing algorithm. An initial model was developed using data from one cohort of patients and validated using data from a second cohort. RESULTS AND DISCUSSION: A model which included age and variants of CYP2C9 and VKORC1 account for about 37% of the variability in warfarin dose required to achieve INR of 2-4. Among the parameters evaluated, only VKORC1 (G-1639A) and (C1173T) alleles, and age correlated with warfarin dose at 6 month. The mean dose predicted using the algorithm derived from cohort 1 was lower than the actual dose for cohort 2 (3·30mg, SD 0·84 vs. 3·45mg, SD 1·42). There was no relationship between INR values and the dose taken by the patients. Race, sex, weight and height did not correlate with dose. WHAT IS NEW AND CONCLUSION: This study identifies factors which affect warfarin dosing in the Malaysia population. However, our best model does not account sufficiently for the variability in dose requirements for it to be used in dose prediction for the individual patient. Other important influential factors affecting warfarin dose requirement remain to be identified.

Low-dose inhaled nitric oxide in term and near-term infants with hypoxic respiratory failure: a Malaysian experience.

Inhaled nitric oxide (iNO) improves oxygenation in term and near-term infants with persistent pulmonary hypertension of the newborn (PPHN) and decreases the need for treatment with extracorporeal membrane oxygenation (ECMO). This mode of treatment is currently being introduced in Malaysia. We report our preliminary experience using low dose inhaled nitric oxide (20 parts per million) in three newborn infants (meconium aspiration syndrome, primary PPHN and congenital diaphragmatic hernia) with severe PPHN who fulfilled criteria for ECMO with a mean oxygenation index (OI) of 40. Two of the infants showed rapid and sustained improvement in oxygenation with a reduction in oxygenation index (OI) over 24 hours. The infant with diaphragmatic hernia showed an initial improvement in OI, which was unsustained and subsequently died. All three infants did not show significant elevation of methemoglobin or nitrogen dioxide (NO2). Inhaled nitric oxide is an effective and safe treatment for severe PPHN that can be used in a developing country like Malaysia.

Corticosteroid rescue in late paediatric acute respiratory distress syndrome.

Late acute respiratory distress syndrome (ARDS) is associated with a mortality of more than 80%. Recent reports in adults have shown improved survival in late ARDS treated with prolonged course of steroids, however little data are available in children concerning its safety and efficacy. We report the successful treatment of a child dying from refractory late ARDS using a prolonged course of high-dose methylprednisolone instituted after 12 days of advanced mechanical ventilation. Progressive improvement was seen from days 3, 7, 10 and 14 after treatment with improvement in PaO2/fraction of inspired oxygen (FiO2) ratios, lung injury score and chest radiographical score. Treatment was complicated by a fungal urinary tract infection that was easily controlled. There were no major metabolic side effects. Steroid therapy can be considered in the treatment of children with refractory late ARDS but larger prospective studies are needed to define indications, timing, dosing and safety of this mode of treatment in children.

Surfactant replacement therapy in RSV-induced acute respiratory distress syndrome (ARDS).

Acute respiratory distress syndrome (ARDS) associated with severe respiratory syncytial virus infection is rare. We report a 5-month-old Indian girl who was admitted to our intensive care ward with severe respiratory failure who fulfilled the criteria for ARDS using both Murray's Lung Injury Score of > 2.5 and the American-European Consensus Conference definition for ARDS. She developed diffuse bilateral alveolar infiltrates, severe hypoxaemia (PaO2/FiO2 < 100) and required high PEEP (> 15 cm H2O) 24 hours after admission. RSV was isolated from her nasopharyngeal secretion. She also had clinical features suggestive of a primary immunodeficiency and had laboratory evidence of combined T and B cell defect. There was unsustained clinical improvement with a dose of surfactant administered at 36 hours of PICU stay, and she continued to deteriorate and succumbed after 19 days in the PICU.

Incidence of acute respiratory distress syndrome: a comparison of two definitions.

OBJECTIVES: To determine the incidence and outcome of acute respiratory distress syndrome (ARDS) in children by comparing two commonly used definitions: the lung injury score and the American-European Consensus Conference definition. The causes and risk for developing ARDS were also studied. METHODS: Part prospective and retrospective analysis of 8100 consecutive hospital admissions from 1 June 1995 to 1 April 1997. RESULTS: Twenty one patients fulfilled the criteria for ARDS. Both definitions identified the same group of patients. The incidence was 2.8/1000 hospital admissions or 4.2% of paediatric intensive care unit admissions. The main causes were sepsis and pneumonia. Mortality was 13 of 21. Factors predicting death were a high admission paediatric risk of mortality (PRISM) score (30.38 v 18.75) and the presence of multiple organ dysfunction syndrome (92% v 25%). CONCLUSION: Both definitions identified similar groups of patients. The incidence in this population was higher than that reported elsewhere, but mortality and cause were similar to those in developed countries. Poor outcome was associated with sepsis, a high admission PRISM score, and simultaneous occurrence of other organ dysfunction.

Percutaneous central venous catheterisation in critically ill children.

An 18-month analysis of 52 percutaneously placed central venous catheters in 48 critically ill children was done. Success rate were 91.7% (33/36) and 93.8% (15/16) for femoral and non-femoral catheters respectively. Presence of hypotension (48.1%) and significant coagulopathy (26.9%) did not affect the success rate significantly. Minor bleeding and venous congestion was seen in 5.5% (2/36) of patients with femoral catheters. Infections were found in 2.7% (1/36) of femoral and 6.6% (1/15) of non-femoral catheters. The low incidence of complications and the relative ease of insertion makes the femoral route the preferred site for trainee medical officers in critically ill children when central access is indicated.