Medial pneumothorax: a radiographic sign that should not be overlooked on the supine view.
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Contusions↗
Biomedical subjects
L Chan
Publications and source records attributed to L Chan.
ED echocardiography for peripartum cardiomyopathy.
Although peripartum cardiomyopathy is uncommon, emergency physicians should be knowledgeable of it because of its high morbidity and mortality. Emergency physicians should be alert to the fact that the clinical presentation of peripartum cardiomyopathy is nonspecific. Its clinical manifestations are found in other medical conditions that can present in the late prepartum or postpartum patient. We present a case of peripartum cardiomyopathy that illustrates how its nonspecific respiratory signs and symptoms led to an initial diagnosis of pulmonary embolism. The case also highlights the need for echocardiography in the evaluation of peripartum cardiomyopathy. We discuss the clinical presentation, diagnosis, and treatment of peripartum cardiomyopathy.
Adult↗
The absence of p53 accelerates atherosclerosis by increasing cell proliferation in vivo.
The tumor suppressor protein p53 is an essential molecule in cell proliferation and programmed cell death (apoptosis), and has been postulated to play a principal part in the development of atherosclerosis. We have examined the effect of p53 inactivation on atherogenesis in apoE-knockout mice, an animal model for atherosclerosis. We found that, compared with p53+/+/apoE-/- mice, p53-/-/apoE-/- mice developed considerably accelerated aortic atherosclerosis in the presence of a similar serum cholesterol in response to a high-fat diet. Furthermore, the atherosclerotic lesions in p53-/-/apoE-/- mice had a significant (approximately 280%) increase in cell proliferation rate and an insignificant (approximately 180%) increase in apoptosis compared with those in p53+/+/apoE-/- mice. Our observations indicate that the role of p53 in atherosclerotic lesion development might be associated with its function in cell replication control, and that p53-independent mechanisms can mediate the apoptotic response in atherosclerosis.
Animals↗
A randomized trial of nasopharyngeal-synchronized intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation.
OBJECTIVE: To prospectively compare the incidence of respiratory failure in premature infants randomized to receive either nasopharyngeal continuous positive airway pressure (NPCPAP) or nasopharyngeal-synchronized intermittent mandatory ventilation (NP-SIMV) in the immediate postextubation period. STUDY DESIGN: This is a prospective study of very low birth weight (VLBW) infants randomized at the time of extubation to receive either NPCPAP or NP-SIMV in a university-based level III neonatal intensive care unit. Statistical analysis were performed with the Mann-Whitney U test for continuous and ordinal variables, and with the chi-squared test or Fisher's exact test for categorical variables. RESULTS: A total of 41 VLBW infants were studied; 19 were in the NPCPAP group, and 22 were in the NP-SIMV group. Respiratory failure after extubation in the NP-SIMV group was significantly lower that in the NPCPAP group (5% vs 37%, respectively (p = 0.016). No statistically significant differences between groups with regard to demographics, severity of initial illness and associated complications, time to extubation, ventilatory management before extubation, weight, age, or nutritional status at the time of extubation were noted.
Female↗
The implementation of business process reengineering in American and Canadian hospitals.
This study of more than 215 U.S. and Canadian hospital executives indicates that improved service quality to patients and enhanced financial performance are the driving forces for hospitals that undertake business process reengineering (BPR) activities. Despite reporting moderate success in achieving organizational objectives through BPR, these executives identified lack of staff cooperation, buy-in, and skill as important factors that derail BPR implementation efforts.
Canada↗
Predicting the need for thoracoscopic evacuation of residual traumatic hemothorax: chest radiograph is insufficient.
BACKGROUND: The early removal of large residual posttraumatic hemothorax by videothoracoscopy is increasingly used to avoid the late sequelae of trapped lung and empyema. Plain chest radiography (CXR) is the tool most frequently used to select such cases for operation. Our recent experience has demonstrated that what appears to be a large retained hemothorax on CXR may turn out to be intrapulmonary or extrapleural conditions not amenable to thoracoscopic removal. Our objective was to evaluate the accuracy of CXR in detecting significant residual hemothorax and compare its clinical value to thoracic computed tomography (CT) when used to select patients for thoracoscopic evacuation. METHODS: All patients requiring tube thoracostomy for traumatic hemothorax were prospectively evaluated during a 22-month period (n = 703). Patients who, on the second day after admission, demonstrated opacification on CXR involving more than the costophrenic angle were evaluated by thoracic computed tomography for the presence of undrained fluid. Second-day CXR (CXR2) results were compared with the CT findings. Incorrect interpretation was defined as a difference of more than 300 mL between the two readings. All CXR2 and CT results were reviewed in the same fashion by a radiologist blinded to the surgeon's interpretations. Data on injury mechanism, hemodynamic status, laboratory values, interventions, and outcome were collected prospectively. RESULTS: Fifty-eight patients had clinically significant opacifications on CXR2. The surgeon's and radiologist's CXR2 interpretations were incorrect in 48 and 47% of the cases, respectively. The CT interpretations by the two specialists were in agreement in 97% of the cases. Management that would have been instituted on the basis of CXR2 findings was changed in 18 cases (31%). Twelve patients (21%) required early thoracoscopic evacuation of undrained collections. There was good correlation between the CT estimation and the thoracoscopically retrieved amount of blood. CONCLUSION: Although CXR is useful as a screening tool, it cannot be used to reliably select patients for surgical evacuation of retained traumatic hemothorax. Decision-making should be based on thoracic CT findings.
Adult↗
Hypertrophic scars, keloids, and laryngotracheal stenosis.
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Cicatrix, Hypertrophic↗
Comparative study of the anti-human cytomegalovirus activities and toxicities of a tetrahydrofuran phosphonate analogue of guanosine and cidofovir.
Cidofovir is the first nucleoside monophosphate analogue currently being used for the treatment of human cytomegalovirus (HCMV) retinitis in individuals with AIDS. Unfortunately, the period of therapy with the use of this compound may be limited due to the possible emergence of serious irreversible nephrotoxic effects. New drugs with improved toxicity profiles are needed. The goal of this study was to investigate the anticytomegaloviral properties and drug-induced toxicity of a novel phosphonate analogue, namely, (-)-2-(R)-dihydroxyphosphinoyl-5-(S)-(guanin-9'-yl-methyl) tetrahydrofuran (compound 1), in comparison with those of cidofovir. The inhibitory activities of both compounds on HCMV propagation in vitro were similar against the AD 169 and Towne strains, with 50% inhibitory concentrations ranging from 0.02 to 0.17 microgram/ml for cidofovir and < 0.05 to 0.09 microgram/ml for compound 1. A clinical HCMV isolate that was resistant to ganciclovir and that had a known mutation within the UL54 DNA polymerase gene and a cidofovir-resistant laboratory strain derived from strain AD 169 remained sensitive to compound 1, whereas their susceptibilities to ganciclovir and cidofovir were reduced by 33- and 10-fold, respectively. Both compound 1 and cidofovir exhibited equal potencies in an experimentally induced murine cytomegalovirus (MCMV) infection in mice, with a prevention or prolongation of mean day to death at dosages of 1.0, 3.2, and 10.0 mg/kg of body weight/day. In cytotoxicity experiments, compound 1 was found to be generally more toxic than cidofovir in cell lines Hs68, HFF, and 3T3-L1 (which are permissive for HCMV or MCMV replication) but less toxic than cidofovir in MRC-5 cells (which are permissive for HCMV replication). Drug-induced toxic side effects were noticed for both compounds in rats and guinea pigs in a 5-day repeated-dose study. In guinea pigs, a greater weight loss was noticed with cidofovir than with compound 1 at dosages of 3.0 and 10.0 mg/kg/day. An opposite effect was detected in rats, which were treated with the compounds at relatively high dosages (up to 100 mg/kg/day). Compound 1 and cidofovir were nephrotoxic in both rats and guinea pigs, with the epithelium lining the proximal convoluted tubules in the renal cortex being the primary target site. The incidence and the severity of the lesions were found to be dose dependent. The lesions observed were characterized by cytoplasm degeneration and nuclear modifications such as karyomegaly, the presence of pseudoinclusions, apoptosis, and degenerative changes. In the guinea pig model, a greater incidence and severity of lesions were observed for cidofovir than for compound 1 (P < 0.001) with a drug regimen of 10 mg/kg/day.
Animals↗
Novel immunoblot assay using four recombinant antigens for diagnosis of Epstein-Barr virus primary infection and reactivation.
A new immunoblot assay, composed of four Epstein-Barr virus (EBV)-encoded recombinant proteins (virus capsid antigen [VCA] p23, early antigen [EA] p138, EA p54, and EBNA-1 p72), was compared with an immunofluorescence assay on a total of 291 sera. The test was accurate in 94.5% of cases of primary EBV infection, while an immunoglobulin G anti-VCA p23 band with strong intensity correlated with reactivation.
Antigens, Viral↗
Three-dimensional ultrasonographic technology to assess and compare echodensity of fetal bowel, bone, and liver in the second trimester of pregnancy.
Increased fetal bowel echogenicity in the second trimester is used as a marker for prenatal diagnosis of Down syndrome. The diagnosis of hyperechogenicity is subjective. We sought to quantify and correlate fetal bowel echogenicity with liver and bone in 47 normal fetuses, using three-dimensional ultrasonographic technique and objective measurement of gray scale distribution. No significant change was found in the organs' echogenicity between 15 and 24 weeks of gestation, the optimal time for detection of fetal chromosomal anomalies. A wide variability in bowel density was noted within the normal group, which could explain its poor sensitivity for the detection of Down syndrome. Bowel echodensity correlates better with liver density than with bone density. Thus, comparison of bowel to liver echogenicity, even with two-dimensional sonography, may prove to be a more effective clinical tool in the evaluation of fetal intra-abdominal echodensities.
Adult↗
Critical incident involving a heat and moisture exchanger with attached flexible connector.
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Anesthesiology↗
Mutational analysis of apolipoprotein B mRNA editing enzyme (APOBEC1). structure-function relationships of RNA editing and dimerization.
APOBEC1 is the catalytic subunit of an enzyme complex that mediates apolipoprotein (apo) B mRNA editing. It dimerizes in vitro and requires complementation factor(s) for its editing activity. We have performed a systematic analysis of the structure-functional relationship of APOBEC1 by targeted mutagenesis of various sequence motifs within the protein. Using in vitro RNA editing assay, we found that basic amino acid clusters at the amino-terminal region R15R16R17 and R33K34, are essential for apoB mRNA editing. Mutation of R15R16R17 to K15K16K17 and mutation of R33K34 simultaneously to A33A34 almost completely abolished in vitro editing activity. The carboxy-terminal region of APOBEC1 contains a leucine-rich motif. Deletion analysis of this region indicates that residues 181 to 210 are important for in vitro apoB mRNA editing. Single amino acid substitutions demonstrate that L182, I185, and L189 are important residues required for normal editing function. Furthermore, the double mutant P190A/P191A also lost >90% of editing activity which suggests that a beta turn in this region of the molecule may be essential for proper functioning of APOBEC1. It was suggested that dimerization of APOBEC1 creates an active structure for deamination of apoB mRNA. When we examined the dimerization potential of truncated APOBEC1s using both amino and carboxy termini deletion mutants, we found that amino-terminal deletions up to residue A117 did not impair dimerization activity whereas carboxy-terminal deletions showed diminished dimerization. The systematic and extensive mutagenesis experiments in this study provide information on the role of various sequence motifs identified in APOBEC1 in enzyme catalysis and dimerization.
APOBEC-1 Deaminase↗
Design and synthesis of a novel class of nucleotide analogs with anti-HCMV activity.
A novel class of cyclic nucleotide analogs has shown anti-HCMV activity. The synthesis as well as structure-activity relationship studies are presented.
Antiviral Agents↗
Identification of novel nucleotide phosphonate analogs with potent anti-HCMV activity.
We have recently described the discovery of new leads in the area of anti-HCMV research. Further structure-activity relationship studies have allowed us to identify potent and selective anti-HCMV nucleotide analogs. The synthesis as well as structure-activity relationship studies are described.
Antiviral Agents↗
Proteasome-mediated degradation of apolipoprotein B targets both nascent peptides cotranslationally before translocation and full-length apolipoprotein B after translocation into the endoplasmic reticulum.
A major portion of newly synthesized apolipoprotein B (apoB) is degraded intracellularly. This degradation has been demonstrated to be mediated largely by the ubiquitin-proteasome pathway. We examined whether nascent apoB polypeptides or full-length apoB is selectively retrotranslocated from the endoplasmic reticulum into the cytosol for degradation. Herein, we found that full-length apoB as well as partial-length apoB peptides are ubiquitinated in HepG2 cells, and ubiquitination is an exclusively cytosolic process. Calnexin, which binds specifically to glycoproteins, has been postulated to promote apoB folding and complete translocation; we found that ubiquitinated apoB is bound to calnexin, suggesting that ubiquitinated apoB is glycosylated. In addition to calnexin binding, we have other pieces of evidence that the full-length intracellular ubiquitinated apoB is glycosylated, because (i) it binds to concanavalin A, and (ii) glycan can be demonstrated in the full-length ubiquitinated apoB by a chemical detection method involving oxidation of adjacent hydroxyl groups in the glycan moiety. Because glycosylation occurs inside the endoplasmic reticulum, the full-length glycosylated apoB must have been retrotranslocated into the cytosol for ubiquitination and proteasome-mediated degradation. Next we synchronized translation in HepG2 cells by puromycin treatment. A pulse-chase experiment using [35S]methionine labeling of intracellular apoB in these synchronized cells demonstrated that nascent partial-length apoB peptides are also ubiquitinated cotranslationally. We conclude that the ubiquitin proteasome-mediated degradation of apoB targets both nascent peptides cotranslationally before translocation as well as full-length apoB after its translocation into the endoplasmic reticulum.
Acetylcysteine↗
Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation.
BACKGROUND: Thymoglobulin, a rabbit anti-human thymocyte globulin, was compared with Atgam, a horse anti-human thymocyte globulin for the treatment of acute rejection after renal transplantation. METHODS: A multicenter, double-blind, randomized trial with enrollment stratification based on standardized histology (Banff grading) was conducted. Subjects received 7-14 days of Thymoglobulin (1.5 mg/kg/ day) or Atgam (15 mg/kg/day). The primary end point was rejection reversal (return of serum creatinine level to or below the day 0 baseline value). RESULTS: A total of 163 patients were enrolled at 25 transplant centers in the United States. No differences in demographics or transplant characteristics were noted. Intent-to-treat analysis demonstrated that Thymoglobulin had a higher rejection reversal rate than Atgam (88% versus 76%, P=0.027, primary end point). Day 30 graft survival rates (Thymoglobulin 94% and Atgam 90%, P=0.17), day 30 serum creatinine levels as a percentage of baseline (Thymoglobulin 72% and Atgam 80%; P=0.43), and improvement in posttreatment biopsy results (Thymoglobulin 65% and Atgam 50%; P=0.15) were not statistically different. T-cell depletion was maintained more effectively with Thymoglobulin than Atgam both at the end of therapy (P=0.001) and at day 30 (P=0.016). Recurrent rejection, at 90 days after therapy, occurred less frequently with Thymoglobulin (17%) versus Atgam (36%) (P=0.011). A similar incidence of adverse events, post-therapy infections, and 1-year patient and graft survival rates were observed with both treatments. CONCLUSIONS: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.
Acute Disease↗