Aspartoacylase gene knockout results in severe vacuolation in the white matter and gray matter of the spinal cord in the mouse

Canavan disease (CD) is a neurodegenerative disorder characterized by the spongy degeneration of the white matter of the brain. Aspartoacylase (ASPA) gene mutation resulting enzyme deficiency is the basic cause of CD. Whether the ASPA defect in CD affects the spinal cord has been investigated using the ASPA gene knockout mouse. Luxol fast blue-hematoxylin and eosin staining in the spinal cord of the knockout mouse showed vacuolation in both white matter and gray matter areas of cervical, thoracic, lumbar, and sacral segments of the spinal cord. However, more vacuoles were seen in the gray matter than the white matter of the spinal cord. ASPA activity in the cervical, thoracic, lumbar, and sacrococcygeal regions of the spinal cord was significantly lower in the knockout mouse compared to the wild type. The enzyme defect in the knockout mouse was also confirmed using the Western blot method. These observations suggest that the ASPA gene defect in the mouse leads to spinal cord pathology, and that these changes may be partly involved in the cause of the physiological/behavioral abnormalities seen in the knockout mouse, if documented also in patients with CD.     

When to measure lipid profile after stroke?

BACKGROUND: Although acute decreases in total cholesterol (TC) are well documented in myocardial infarction, previous stroke studies have produced conflicting results. The timing of lipid estimation in ischemic stroke is becoming important with recent trial results indicating the benefits of statins. We therefore aimed to determine the optimal time for lipid measurements after stroke. We hypothesized that TC would acutely decrease after stroke and return to baseline by 12 weeks. METHODS AND RESULTS: We performed a prospective, observational study of 50 patients (age 68.5 +/- 11.2 years) who presented with acute ischemic stroke. Of these, 22 (44%) were HMG-CoA reductase (statin) na?ve, 15 (30%) had already been on statins and 13 (26%) were commenced on statins. Of the 50 patients, 38 (76%) completed 12 weeks of follow-up, 5 died, and 7 were lost to follow-up. Fasting lipid profile (TC, low-density lipoprotein, high-density lipoprotein, triglyceride) was measured <48 h, 4 weeks and 12 weeks following ictus. In patients who were statin na?ve, there was a significant increase in TC at the week 12 evaluation. CONCLUSIONS: Cholesterol levels in acute stroke are an unreliable measure of lipid status. Initiation of statins should ideally be based on measurements taken 12 weeks after stroke.     

The treatment of cardiac causes of sudden death, syncope, and seizure

The treatment for pediatric causes for sudden cardiac death can either be general and supportive or, in 2005, can be much more etiology specific. While antiarrhythmic therapy and activity restriction have been for years the mainstay of therapy, newer technologies such as radiofrequency ablation and automatic implantable cardioverter defibrillators (AICDs) are now more commonly applied for certain disease entities. The evolving role for clinical genetic testing to determine the specific etiology of pediatric sudden cardiac death continues to evolve. Further improvements in risk stratification will allow us to determine which patients are at greatest risk, so that aggressive treatment can be delivered to these subgroups. In the future, there may be gene-specific therapies and/or genetic modification.     

Radiofrequency Modification for Inducible and Suspected Pediatric Atrioventricular Nodal Reentry Tachycardia

Introduction: AV Node Reentry Tachycardia (AVNRT) is the second most common supraventricular tachycardia (SVT) undergoing pediatric radiofrequency ablation behind accessory pathway reentry tachycardias. AVNRT can be difficult to induce during electrophysiology study (EPS) and dual atrioventricular nodal (AVN) pathways physiology may not be demonstrated in young patients.Purpose: This report is the largest single center long term pediatric experience of radiofrequency modification of slow AVN input fibers for inducible or suspected (non-inducible) AVNRT.Results: One hundred thirty-two patients underwent slow input AVN modification from 1993 to 2002. The mean patient age was 13.7 years (4–20 yrs) with 62M/70F. Outpatient tachycardia was documented by ambulatory monitoring in all patients. AVNRT was induced in 98/132 patients during EPS (group A) with mean SVT cycle length of 324 msec (230–570 msec). Initial AVN modification (group A) was successful in 97/98 patients (99%). During 34/132 EPS, AVNRT was non-inducible; dual AVN physiology was present in 19/34 (group B), and 15/34 did not show evidence for dual AVN physiology (group C). These 34 patients underwent empiric AVN modification following discussion with patients’ families. Freedom of recurrence from SVT at 1 year was 96% for group A (94/98), 89% (17/19) for group B and 93% (14/15) for group C. 1 major and 6 minor complications occurred.Conclusions: AVN modification for AVNRT can be performed safely and effectively in pediatric patients with good long-term results. Empiric slow pathway AVN modification for non-inducible SVT results in a high rate of freedom from recurrence of tachycardia.     

Intrapulmonary percussive ventilation vs incentive spirometry for children with neuromuscular disease

BACKGROUND: Pulmonary infections can be life threatening for children with neuromuscular diseases who have impaired ability to clear secretions. Intrapulmonary percussive ventilation (IPV) is a pneumatic device that delivers air and aerosol to the lungs at frequencies of 200 to 300 cycles per minute at peak pressures from 20 to 40 cm H(2)O. Anecdotal reports and pilot studies show its safety and effectiveness in mobilizing secretions in patients with cystic fibrosis. OBJECTIVE: To test the hypothesis that IPV used in a pulmonary program for adolescents with neuromuscular disease would reduce the number of days of antibiotic use for pulmonary infection. METHODS: A randomized, controlled study was conducted to compare efficacy of IPV with incentive spirometry (IS) in reducing number of days of antibiotic use in adolescents with neuromuscular disease. The secondary endpoints were the number of respiratory infections, hospitalizations, and school days missed. RESULTS: A total of 18 patients were enrolled (9 IPV, 9 IS). Antibiotic use was significantly higher with IS (24/1000 patient-days) compared with IPV (0/1000 patient-days), (incidence rate ratio, 43; 95% confidence interval, 6-333). The IS group spent more days hospitalized (4.4/1000 patient-days vs 0/1000 patient-days) than the IPV group (incidence rate ratio, 8.5; 95% confidence interval, 1.1-67). The IPV group had 0 episodes of pneumonia or bacterial bronchitis compared with 3 events in the IS group, although this did not meet statistical significance. CONCLUSION: Intrapulmonary percussive ventilation as part of a preventive pulmonary regimen reduced days of antibiotic use and hospitalization for respiratory illness in adolescents with neuromuscular disease.     

Immunization of pediatric solid-organ transplantation candidates: immunizations in transplant candidates

Many children who receive solid-organ transplants have not completed their primary immunizations prior to transplantation. This leaves pediatric transplant recipients susceptible to the vaccine preventable illness of childhood, which if acquired post-transplantation are associated with increased rates of complications, hospitalization, graft rejection and mortality. The administration of vaccines to transplant candidates earlier and more rapidly than in the healthy child will improve vaccination rates among transplant recipients while not compromising immunogenicity. The recommended vaccines and vaccine schedule are discussed in detail.     

Uterine tissue development in healthy women during the normal menstrual cycle and investigations with magnetic resonance imaging

OBJECTIVE: High-resolution magnetic resonance imaging (MRI) was used to monitor both uterine endometrial and junctional zone morphometry during the normal menstrual cycle. STUDY DESIGN: Twenty-four healthy, ovulating women were studied during a single menstrual cycle. Three scans were performed to prospectively coincide with the follicular, periovulatory, and luteal phases of the cycle. RESULTS: MRI data showed a significant increase in endometrial and junctional zone volume, between the follicular and periovulatory phases, with a significant decrease in endometrial volume observed from the periovulatory to luteal phases. The regularity index, which is a novel subjective assessment of junctional zone structure, varied significantly and demonstrated a less regular junctional zone in the luteal phase. CONCLUSION: This study has quantified the normal developmental changes of uterine tissue during the menstrual cycle with MRI. Junctional zone data from MRI may play a major role in future studies that investigate menstrual disorders, subfertility, and pathologic changes.