Status epilepticus triggers early and late alterations in brain-derived neurotrophic factor and NMDA glutamate receptor Grin2b DNA methylation levels in the hippocampus.

Status epilepticus (SE) triggers abnormal expression of genes in the hippocampus, such as glutamate receptor subunit epsilon-2 (Grin2b/Nr2b) and brain-derived neurotrophic factor (Bdnf), that is thought to occur in temporal lobe epilepsy (TLE). We examined the underlying DNA methylation mechanisms and investigated whether these mechanisms contribute to the expression of these gene targets in the epileptic hippocampus. Experimental TLE was provoked by kainic acid-induced SE. Bisulfite sequencing analysis revealed increased Grin2b/Nr2b and decreased Bdnf DNA methylation levels that corresponded to decreased Grin2b/Nr2b and increased Bdnf mRNA and protein expression in the epileptic hippocampus. Blockade of DNA methyltransferase (DNMT) activity with zebularine decreased global DNA methylation levels and reduced Grin2b/Nr2b, but not Bdnf, DNA methylation levels. Interestingly, we found that DNMT blockade further decreased Grin2b/Nr2b mRNA expression whereas GRIN2B protein expression increased in the epileptic hippocampus, suggesting that a posttranscriptional mechanism may be involved. Using chromatin immunoprecipitation analysis we found that DNMT inhibition restored the decreases in AP2alpha transcription factor levels at the Grin2b/Nr2b promoter in the epileptic hippocampus. DNMT inhibition increased field excitatory postsynaptic potential in hippocampal slices isolated from epileptic rats. Electroencephalography (EEG) monitoring confirmed that DNMT inhibition did not significantly alter the disease course, but promoted the latency to seizure onset or SE. Thus, DNA methylation may be an early event triggered by SE that persists late into the epileptic hippocampus to contribute to gene expression changes in TLE.

Pneumococcal meningitis in children: relationship of antibiotic resistance to clinical characteristics and outcomes.

BACKGROUND: The relationship of antibiotic susceptibility to clinical outcome in children with pneumococcal meningitis is uncertain. Previous studies have been limited by inclusion of relatively few patients infected with nonsusceptible pneumococci and inconsistent use of empiric vancomycin. METHODS: Medical records of 86 children with culture-confirmed pneumococcal meningitis at a single institution from October, 1991, to October, 1999, were retrospectively reviewed, and differences in presentation and outcome based on antibiotic susceptibility of pneumococcal isolates were assessed. RESULTS: Of 86 isolates 34 were nonsusceptible to penicillin (12 resistant). Of 60 isolates for which cefotaxime susceptibility data were available, 17 were nonsusceptible (12 resistant). Antibiotic susceptibility was not significantly associated with death, intensive care unit admission, mechanical ventilation, focal neurologic deficits, seizures, secondary fever, abnormal neuroimaging studies or hospital days. Children with penicillin-resistant isolates had significantly higher median blood leukocyte counts (24,100/microliter vs. 15,700/microliter, P = 0.03) and lower median CSF protein concentrations (85 mg/dl vs. 219 mg/dl, P = 0.04), were more likely to have a CSF glucose concentration of > or = 50 mg/dl (7 of 11 vs. 15 of 68, P = 0.009) and had lower rates of sensorineural hearing loss (1 of 8 vs. 25 of 40, P = 0.02) than children with isolates that were not resistant to penicillin. Children with cefotaxime-nonsusceptible isolates had an increased median duration of primary fever compared with those with nonsusceptible strains (6 days vs. 3.5 days, P = 0.02). CONCLUSIONS: In children with pneumococcal meningitis, penicillin resistance was associated with a reduced risk of hearing loss, while cefotaxime resistance was associated with a longer duration of fever. Other outcome measures were not significantly influenced by the antibiotic susceptibility of pneumococcal isolates.

Fungal peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis.

We report the first case of peritonitis caused by Curvularia species in a child undergoing peritoneal dialysis. He presented with gray-black proteinaceous material obstructing the lumen of his Tenckhoff catheter. Although the peritoneal fluid was cloudy, the patient suffered neither significant abdominal tenderness nor systemic symptoms. Catheter removal and treatment with amphotericin B allowed complete recovery and return to peritoneal dialysis within 7 days. Outdoor play in a wooded environment may have allowed contact of this saprophytic fungus with the child's indwelling catheter transfer set.

Respiratory syncytial virus infections in the pediatric intensive care unit: clinical characteristics and risk factors for adverse outcomes.

OBJECTIVES: To describe the clinical characteristics of infants admitted to a pediatric intensive care unit (PICU) with respiratory syncytial virus (RSV) infection, including the prevalence of indications for RSV passive antibody prophylaxis (as currently recommended by the American Academy of Pediatrics), and to identify risk factors that predict adverse outcomes among this population. DESIGN: Retrospective medical record review. SETTING: Tertiary care PICU. PATIENTS: Children <2 yrs of age admitted to PICU for the management of RSV disease during the 1994-95, 1995-96, and 1996-97 RSV seasons. MEASUREMENTS AND MAIN RESULTS: The medical records of 89 infants were reviewed. Of these, 55% were born before 36-wks gestation, 14% had chronic lung disease that required medical therapy within the previous 6 months, and 30% met at least one indication for RSV passive antibody prophylaxis. Seven infants had congenital heart disease, five had upper airway abnormalities, and six had various noncardiac congenital malformations. Logistic regression was used to determine which characteristics were associated with prolonged durations (>75th percentile) of mechanical ventilation, PICU stay, and hospital stay. Prolonged mechanical ventilation was associated with congenital heart disease (p = 0.014), chronic lung disease (p = 0.007), and noncardiac congenital malformations (p = 0.022). Only congenital heart disease was associated with prolonged PICU stay (p = 0.004) or prolonged hospital stay (p = 0.006). All of the infants with airway abnormalities had prolonged ventilator days, PICU days, and hospital days. Currently recommended indications for RSV passive antibody prophylaxis were not predictive of prolonged ventilation, PICU stay, or hospital stay. CONCLUSIONS: A minority of infants admitted to our PICU for severe RSV disease meet currently recommended indications for RSV passive antibody prophylaxis. Risk factors that predict prolonged durations of ventilation, PICU stay, or hospital stay among this population include congenital heart disease, chronic lung disease, upper airway abnormalities, and noncardiac congenital malformations.

Nasal quantity of respiratory syncytical virus correlates with disease severity in hospitalized infants.

OBJECTIVE: To evaluate the relationship between nasal quantity of respiratory syncytial virus (RSV) and disease severity in hospitalized infants without underlying cardiopulmonary disease or immunodeficiency. METHODS: Nasal aspirates were obtained from hospitalized infants <24 months of age with recently identified RSV infection and evaluated for RSV quantity by a standard plaque assay on HEp-2 cell monolayers. Subjects were classified as having "severe" disease if they required mechanical ventilation at the time of sample collection and as having "nonsevere" disease if they did not. Linear modeling was used to determine the relationship between nasal RSV quantity and various independent variables, including disease severity. RESULTS: Nasal aspirates from 39 patients were evaluated. Age, gender and mean duration of time from symptom onset to sample acquisition (5 days) were similar between the severe (n = 15) and nonsevere (n = 24) groups. Significantly more infants were born at <35 weeks gestation in the severe disease group (7 of 15 vs. 3 of 24, P = 0.017), and infants born at <35 weeks gestation were significantly more likely to be of non-Caucasian ethnicity than were infants born at > or =35 weeks gestation (8 of 10 vs. 12 of 29, P = 0.035). The linear model found that higher nasal RSV quantities were associated with severe disease [mean +/- SEM, 5.06 +/- 0.34 log plaque-forming units (pfu)/ml vs. 3.91 +/- 0.35 log pfu/ml, P = 0.022], gestational age > or =35 weeks (5.44 +/- 0.27 log pfu/ml vs. 3.52 +/- 0.45 log pfu/ml, P = 0.002) and non-Caucasian ethnicity (5.16 +/- 0.30 log pfu/ml vs. 3.80 +/- 0.37 log pfu/ml, P = 0.006). CONCLUSIONS: Nasal RSV quantity correlates with disease severity in hospitalized infants with recently identified RSV infection.

Primary central nervous system lymphoma in a child with acute B-cell lymphoblastic leukaemia: consecutive Epstein-Barr virus-related malignancies.

Primary central nervous system lymphoma (PCNSL), observed among immunocompromised AIDS patients, has not been reported during chemotherapy for acute lymphoblastic leukaemia (ALL). We report a case of PCNSL occurring in a child receiving intensive multiagent chemotherapy for B-cell ALL. In situ hybridization studies demonstrated Epstein-Barr virus genome in both tumours, suggesting a possible link between the two diseases. The clinical response of the PCNSL to conservative therapy highlights the importance of accurately diagnosing such EBV-related disorders, especially in patients where immune compromise can be reversed.

Breakthrough bacteremia and meningitis during treatment with cephalosporins parenterally for pneumococcal pneumonia.

An extended-spectrum cephalosporin has been considered appropriate therapy for non-meningeal infections caused by drug-resistant Streptococcus pneumoniae. We report a toddler who had breakthrough bacteremia and meningitis develop because of drug-resistant pneumococcus while receiving treatment with cefotaxime and cefuroxime for pneumonia.

Magnetic resonance imaging of the triangular fibrocartilage complex.

Magnetic resonance imaging of seven fresh human cadaveric specimens was used to evaluate the integrity of the triangular fibrocartilage complex of the wrist. A variety of imaging parameters were systematically investigated, including T1-weighted images with and without contrast, long repetition times, short echo time images, and T2-weighted sequences. A variety of imaging planes were also evaluated. Wrist arthrography, dissection, and frozen coronal sections were done to substantiate our interpretations of the magnetic resonance images. T2-weighted images in the coronal plane proved to be of the greatest diagnostic value because the synovial fluid of the joint spaces serves as an excellent endogenous contrast agent. Long repetition time, short echo time sequences could be simultaneously obtained with T2-weighted sequences with the use of a multi-echo pulse sequence to provide an excellent diagnostic package in the future. On the basis of our investigation, the triangular fibrocartilage complex can be consistently and accurately evaluated with magnetic resonance imaging. As magnetic resonance imaging technology improves, wrist probes and suitable magnets should become available that will make the evaluation of triangular fibrocartilage complex abnormalities with magnetic resonance imaging clinically useful.