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Biomedical subjects

C R Perez

Publications and source records attributed to C R Perez.

6 recordsLinked to original sources

Timing of video-assisted thoracoscopic debridement for pediatric empyema.

BACKGROUND: Video-assisted thoracoscopic debridement (VATD) is a new method of managing pediatric empyema. The purpose of this retrospective study was to determine the relation between the timing of VATD and its success in avoiding the need for open decortication. STUDY DESIGN: Twenty-one children aged 3 to 16 years (mean, 8 years) with symptomatic, loculated, parapneumonic empyema were treated with VATD at two tertiary pediatric centers between 1994 and 1997. The preoperative duration of symptoms, hospitalization, and previous need for thoracostomy drainage were compared between patients having VATD only and those who subsequently required a thoracotomy and decortication. Statistical analysis used the Wald chi-square test or Fisher's exact test with p < 0.05 considered significant. RESULTS: Video-assisted thoracoscopic debridement was successful in 15 patients (group 1) and unsuccessful in six patients (group 2), who required a thoracotomy and decortication. Group 1 had a shorter mean duration of preoperative symptoms (13 versus 27 days; p=0.03), a shorter median duration of preoperative hospitalization (6 versus 18 days; p=0.04), and a lower incidence of previous thoracostomy drainage (4/15 versus 5/6; p=0.05). CONCLUSIONS: The technique of VATD is most likely to be successful when used within one week of diagnosis of a loculated parapneumonic empyema. A prospective trial comparing VATD with intrapleural fibrinolytic agents for the initial treatment of pediatric empyema is needed.

Adolescent↗

Safety of adenovirus-mediated transfer of the human cystic fibrosis transmembrane conductance regulator cDNA to the lungs of nonhuman primates.

To define the toxicity of cystic fibrosis transmembrane conductance regulator gene (CFTR) gene therapy with a replication-deficient recombinant adenovirus (Av1Cf2) in a nonhuman primate model, 10(10) plaque forming units (pfu) were instilled directly through a bronchoscope into the right lung of 5 macaques, and a lower dose of 4 x 10(6) pfu was administered to the right lung of 1 macaque. One sham-treated control received phosphate-buffered saline (PBS). The macaques were evaluated sequentially by clinical examination, vital signs, weight, hematology, blood chemistry, chest radiography, pulse oximetry, and bronchoalveolar lavage (BAL) at baseline and 3-28 days post-treatment. After the period of observation, macaques were sacrificed for autopsy and histological examination. The macaques tolerated the experimental therapy clinically with no changes in body temperature, oxygen saturation, heart rate, body weight, or blood pressure. However, 1 macaque with visible evidence of aspiration at the time of initial bronchoscopy developed tachypnea with right lower lobe (RLL) pneumonia on chest radiograph and by histology. There were no changes in Hgb, Wbc, BUN, plasma electrolytes, bilirubin, or hepatic transaminases. In the macaques that received 10(10) pfu, there was a progressive increase in the number of CD8+ lymphocytes in BAL that was maximal at 28 days. Histological examination of the treated lungs of the high-dose macaques at 3 days showed marked peribronchial and perivascular cuffing by inflammatory cells and alveolar accumulation of neutrophils and macrophages. The alveolitis appeared to be resolving at 28 days, although the perivascular and peribronchial aggregates of mononuclear cells were still present. In the high-dose macaques, BAL interleukin-8 (IL-8) was increased at all time points (256-388 pg/ml versus 1-84 pg/ml at baseline and in control), whereas IL-1 beta was increased only at days 21 and 28 (341-852 pg/ml versus 30-92 pg/ml at baseline and in control). There were no increases in BAL cell counts, IL-1 beta or IL-8, and histological changes were mild in the macaque that received 4 x 10(6) pfu. Evaluation for Av1Cf2-derived human CFTR expression using RS-PCR demonstrated expression at 3, 10, and 21, but not 28 days in macaques treated with 10(10) pfu of Av1Cf2. In situ hybridization analysis demonstrated human CFTR mRNA in the alveolar regions of the lobes that received the vector at 10 and 21 days. There was no evidence of expression after treatment with 4 x 10(6) pfu. This study showed that high-dose adenoviral vector administration to the lung achieved CFTR gene transfer and expression but was associated with increased concentrations of cytokines in BAL and alveolar inflammation. A low dose, equivalent to the maximum clinical dose currently proposed for phase I trials in human subjects, was not associated with cellular or cytokine evidence of inflammation, and histological abnormalities were mild.

Adenoviridae↗

Ambulatory monitoring devices and the forensic autopsy.

Ambulatory monitoring devices (AMDs) such as Holter (ECG) and apnea (respiratory) monitors with built-in date- and time-correlated memories are occasionally encountered in the forensic autopsy. Diagnostic data are usually readily obtained by returning the device to the hospital department or rental company. This data can be easily correlated with autopsy findings to arrive at surprisingly precise conclusions in some cases. We present two illustrative cases: an elderly man wearing a Holter monitor who shot himself in the mouth with a shotgun, and a 15-month-old oxygen-dependent prematurely born boy with bronchopulmonary dysplasia whose apnea monitor had been turned off 5 days before he died of bronchopneumonia. We discuss other kinds of AMDs that may be encountered in the forensic autopsy and suggest that information from these monitors perhaps should become part of the forensic autopsy report.

Apnea↗

Structural and electrophysiological analysis of annexin V mutants. Mutagenesis of human annexin V, an in vitro voltage-gated calcium channel, provides information about the structural features of the ion pathway, the voltage sensor and the ion selectivity filter.

Annexin V binds to phospholipids in a calcium-dependent manner and exhibits calcium channel activity in vitro. We prepared a variety of mutants yielding information about the structure-function relationship of the ion channel activity. All mutants were characterized by X-ray crystallography, electron microscopy and electrophysiological measurements. Their structures are insignificantly changed whereas their electrophysiological properties are drastically different. Glu95, located in the central hydrophilic pore of the molecule, is crucial for the ion selectivity filter as its exchange leads to reduced calcium and increased sodium conductance. The removal of Glu17, located on the protein surface and far from the ion conduction pathway, leads to the appearance of a second conductance level of 9 pS in addition to the conductance level of about 30 pS in the wild-type molecule. This was also the case for Glu78, which is part of a weak calcium binding site. The exchange of Glu17 and Glu78 produced a mutant retaining only the smaller conductance level. We conclude that these two residues influence the angle between the two halves of the molecule, which determines the diameter of the ion conduction pathway, thereby leading to the occurrence of a second conductance level.

Amino Acid Sequence↗

Update on pediatric flexible bronchoscopy.

Technological advances in flexible bronchoscopy have expanded the clinician's ability to diagnose and treat pulmonary disease in children. During the neonatal period, flexible bronchoscopy has contributed to the understanding of the incidence and factors responsible for acquired airway lesions. The ability to selectively collect lower airway secretions has contributed to the care of immunocompromised patients with new pulmonary infiltrates. New therapies may use the flexible bronchoscope to specifically target lower airway tissues of interest. Because of the breadth of both current and future applications, most pediatricians will require a working familiarity with the benefits of flexible bronchoscopy in their patients.

Bronchoscopes↗

Mycoplasma pneumoniae as the causative agent for pneumonia in the immunocompromised host.

A young man undergoing chemotherapy for Ewing's sarcoma presented with fever, neutropenia, anemia, thrombocytopenia, and a new infiltrate on the chest roentgenogram. Routine cultures and cytopathologic examination of bronchoalveolar lavage fluid provided no evidence for an etiology; however, special cultures of the BAL fluid demonstrated heavy growth of Mycoplasma pneumoniae. We recommend that evaluation of pneumonia in the immuno-compromised host include appropriate cultures of BAL fluid for M pneumoniae, particularly when the patient is 5 to 25 years old, the age of high incidence of mycoplasmal pneumonia.

Adult↗