Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly ...transduce muscle cells. We tested the impact of preexisting AAV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in AAV, rhesus serotype 74 sero-negative animals (mean: 48.0 ± 20.8%) that was attenuated in sero-positive animals (19.6 ± 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of AAV binding antibodies by plasmapheresis in AAV sero-positive animals resulted in high-level transduction (60.8 ± 18.0%), which is comparable with that of AAV sero-negative animals (53.7 ± 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 ± 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasmapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to AAV.
Pediatric chest ultrasound Coley, Brian D
The Radiologic clinics of North America,
03/2005, Letnik:
43, Številka:
2
Journal Article
Recenzirano
Ultrasound examination of the thorax can be quite rewarding in children, because their unique thoracic anatomy provides many acoustic windows into the chest. With only a modest effort, chest ...ultrasonography can provide many clinically relevant answers, without the radiation exposure from CT, or the need for sedation sometimes required for CT and MR imaging.
The purpose of this study was to describe the imaging and pathologic findings of 2 cases of complex neonatal abdominal masses and to discuss the probable common embryologic etiology of fetus in fetu ...(FIF) and fetaform teratomas.
Two male neonates had complex cystic abdominal masses, 1 of which was diagnosed prenatally, and both had abdominal sonography. One patient also had abdominal computed tomography. Both patients subsequently underwent surgical resection, with pathologic and genetic analysis of these masses.
One patient had typical imaging, pathologic, and genetic findings of FIF. The second patient had a well-formed mass that was diagnosed pathologically as a teratoma yet had most of the criteria for FIF that have been set forth in recent embryologic literature.
Recent concepts regarding the origin of FIF suggest that it is part of a spectrum of monozygotic twinning gone awry, ranging from conjoined twins at one end to fetaform teratomas at the other. The imaging and pathologic features of these 2 cases serve to reinforce this concept.
Cerebrospinal fluid (CSF) pseudocyst formation is an uncommon cause of ventriculoperitoneal shunt malfunction in children. Traditional staged treatment consists of shunt externalization, antibiotics, ...and later shunt revision and internalization. We sought to evaluate whether sonographically guided pseudocyst aspiration to alleviate acute symptoms and to exclude CSF infection could obviate shunt externalization and expedite the care of these patients.
Sonographically guided CSF pseudocyst aspiration is an effective technique, allowing exclusion or confirmation of infection and providing relief of abdominal symptoms. In patients with sterile collections, staged surgical revision with shunt externalization can be avoided, speeding and simplifying treatment.
Ultrasound is a remarkably powerful and versatile modality for pediatric imaging, without requiring exposure to radiation or sedatives. By providing information on blood flow, Doppler sonography can ...reveal details about normal physiology and disease processes not discernable from gray-scale anatomic images alone. However, in routine practice in many institutions Doppler remains underutilized, in part due to uncertainty of the meaning of changes in Doppler waveforms. In part I of this review, the basics of hemodynamics and how changes in blood flow affect the Doppler waveform are reviewed. Clinical applications in the investigation of hepatic disease are then discussed.
Ultrasound is a remarkably powerful and versatile modality for pediatric imaging, without requiring exposure to radiation or sedatives. By providing information on blood flow, Doppler sonography can ...reveal details about normal physiology and disease processes not discernable from gray-scale anatomic images alone. In part I, the basics of hemodynamics and effects on the Doppler waveform were discussed, along with clinical applications in hepatic disease. In part II, the application of Doppler in renal disease and in conditions affecting the deep abdominal vessels are discussed. The role of ultrasound contrast agents in pediatric Doppler imaging is briefly reviewed.
Background: Surveillance of ventilator-associated pneumonia (VAP) is an essential part of quality patient care. Very-low-birth-weight (VLBW) infants, many with tracheal microbial colonization and ...bronchopulmonary dysplasia (BPD), comprise a difficult group in whom to make a diagnosis of pneumonia with the Centers for Disease Control and Prevention (CDC) criteria for infants younger than 1 year. Objective: Our objective was to retrospectively compare VAP surveillance diagnoses made by the hospital infection control practitioner (ICP) with those made by a panel of experts with the same clinical and laboratory evidence and supportive radiologic data. A secondary objective was to compare radiologic diagnosis of pneumonia made by the general hospital radiologists, by the panel of experts, and by a pediatric radiologist from another hospital. Study Population: Thirty-seven VLBW infants identified as at risk for VAP by the ICP on the basis of a positive bacterial tracheal culture and the application of CDC criteria for the definition of pneumonia were studied. Methods: Clinical and laboratory evidence and routine radiologic reports made by the general radiologist were reviewed independently by a panel of experts composed of 3 experienced neonatologists. Chest x-rays from the day before, day of, and day after the surveillance date were reviewed separately by the 3 neonatologists and also by a pediatric radiologist. Results: After inter-reader reliability was found satisfactory (kappa's coefficient, 0.47-0.75; P <.05), the panel of neonatologists determined that the 37 VLBW infants represented 4 distinct clinical categories. Group 1 comprised 12 airway-colonized infants, aged 14 to 30 days, who on the surveillance date, albeit intubated, were asymptomatic, not treated with antibiotics, and survived. Group 2 comprised 11 airway-colonized infants, aged 7 to 42 days, who presented with equivocal clinical, laboratory, or radiologic signs of VAP and survived. Group 3 comprised 7 airway-colonized infants, aged 14 to 21 days, who were acutely ill (3 died) and had clinical and laboratory evidence of nosocomial bloodstream infection (BSI) but no radiologic signs of pneumonia. Group 4 comprised 7 infants, aged 14 to 28 days, who were acutely ill (4 died) and had clinical and laboratory evidence of infection and radiologic changes consistent with VAP. Radiologic Findings: General radiologists, neonatologists, and the pediatric radiologist agreed that none of the asymptomatic airway-colonized infants (Group 1) had VAP. General radiologists reported signs suggestive of pneumonia in 8 of 11 infants (Group 2), a finding not corroborated by the others. Everybody agreed on the absence of radiologic pneumonia in 6 of 7 patients with nosocomial BSI (Group 3) and on the presence of signs consistent with pneumonia in the remaining 7 infants (Group 4). Conclusion: Surveillance diagnosis of VAP in VLBW infants is difficult because current CDC definitions are not specific for this population. Isolated positive tracheal culture alone does not distinguish between bacterial colonization and respiratory infection. Clinical and laboratory signs of VAP, mostly nonspecific, can be found in other conditions such as bronchopulmonary dysplasia and nosocomial BSI. Routine radiologic reports suggestive of pneumonia in airway-colonized infants without definitive clinical and laboratory evidence of infection could be misleading. To improve accuracy, surveillance diagnosis of VAP in special populations such as VLBW infants should be reformulated; meanwhile, ICPs should seek consultation with experienced clinicians for interpretation of data. (Am J Infect Control 2002;30:32-9.)
Lumbar puncture (LP) may be unsuccessful clinically, prompting image-guided LP by radiologists. Objective. To investigate the utility of ultrasound (US) in diagnosing the cause of failed LP and in ...guiding LP.
Neonates and infants referred for image-guided LP underwent spine US of the thecal sac. When indicated, image-guided LP was performed.
Forty-seven evaluations and interventions were performed in 32 patients. All patients were initially evaluated after failed blind LP attempts. Twenty-three of the initial US studies showed intrathecal and/ or epidural echogenic hematoma, which obliterated the CSF space; 5 showed minimal fluid, and 4 had normal examinations. LP was deferred or cancelled in 14 cases based upon initial US findings. Image-guided LP was performed 32 times in 19 patients. US guidance was used in 26, fluoroscopy in 3, and fluoroscopy with US assistance in 3. Using US, LP was performed in 9 patients with no visible CSF: 2 samples were sufficient for culture only. Six patients had minimal CSF US: 4 provided usable CSF samples. Clear CSF space was seen in 11: all had successful LP.
US can disclose the cause of failed LP, can help determine whether or not to intervene further, and can provide guidance for LP.
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