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Biomedical subjects

Michael Edwards

Publications and source records attributed to Michael Edwards.

9 recordsLinked to original sources
PubMed2006

Balancing efficacy and safety in the use of oral sedation in dental outpatients.

BACKGROUND: Concerns about the safety of pediatric oral sedation and the incremental use of triazolam in adults prompted a workshop cosponsored by several professional organizations. OVERVIEW: There is a strong need and demand for adult and pediatric sedation services. Using oral medication to achieve anxiolysis in adults appears to have a wide margin of safety. Mortality and serious morbidity, however, have been reported with oral conscious sedation, especially in young children. Most serious adverse events are related to potentially avoidable respiratory complications. CONCLUSIONS: Clinical trials are needed to evaluate oral sedative drugs and combinations, as well as to develop discharge criteria with objective quantifiable measures of home readiness. Courses devoted to airway management should be developed for dentists who provide conscious sedation services. State regulation of enteral administration of sedatives to achieve conscious sedation is needed to ensure safety. PRACTICE IMPLICATIONS: Safety in outpatient sedation is of paramount concern, with enteral administration of benzodiazepines appearing safe but poorly documented in the office setting. Conscious sedation by the enteral route, including incremental triazolam, necessitates careful patient evaluation, monitoring, documentation, facilities, equipment and personnel as described in American Dental Association and American Academy of Pediatric Dentistry guidelines.

Adult↗
PubMed2005

Neuroimaging-detected late transient treatment-induced lesions in pediatric patients with brain tumors.

OBJECT: After the resection of brain tumors in pediatric patients, it can be difficult to differentiate recurrent tumor from treatment effects. Although late-delayed reactions are thought to be permanent, in this study the authors sought to characterize transient brain lesions (TBLs) in the late-delayed period that completely resolved without imaging or neurological sequelae. METHODS: In a retrospective review of an institutional neuroimaging brain tumor database, 11 patients were identified who met the imaging criteria (transient T2-weighted hyperintense enhancing lesions outside of the tumor bed, which occurred after radiation and/or chemotherapy) and had undergone three-dimensional dosimetry; their radiographic, clinical, and radiation-dosimetry results were analyzed. In the 11 patients who had been treated with multiple protocols 17 loci of abnormality, including 43 discrete, asymptomatic TBLs, were detected. The median TBL diameter was 1 cm or smaller, without mass effect or necrosis, and occurred 10 months after radiation therapy, 11 months after chemotherapy, resolved by 3 months, and occurred within the high-dose radiation treatment volume (median 55.8 Gy). The findings from extended follow up revealed the development of additional permanent complications of radiation therapy within the radiation port in five of the 11 patients. CONCLUSIONS: A benign form of treatment-induced brain injury in children, TBLs should be treated using short-interval follow up. When these lesions are identified as a result of their characteristic imaging features, location, and temporal course, TBLs may be clearly distinguished from recurrent tumor or radiation necrosis and do not require biopsy. Further studies are needed to determine whether patients with TBLs are at an increased risk of developing more severe treatment-related brain injury.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

Advantages of focused helical computed tomographic scanning with rectal contrast only vs triple contrast in the diagnosis of clinically uncertain acute appendicitis: a prospective randomized study.

HYPOTHESIS: Focused helical computed tomographic (CT) scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis. DESIGN: Prospective randomized analysis of both CT scan modalities. INTERVENTIONS: Only patients with uncertain diagnosis of acute appendicitis were entered in the study. The patients were then randomized to undergo the traditional triple-contrast CT scan or the new focused CT scan with rectal contrast only. Surgical management included operation or observation for 23 hours. RESULTS: Ninety-one patients participated in the study, including 52 in the triple-contrast group and 39 in the rectal-contrast group. The demographics of the triple-contrast vs the rectal-contrast groups were similar. The triple-contrast group had a sensitivity of 97%, specificity of 86%, positive predictive value of 90%, and negative predictive value of 93%. The rectal-contrast group had a sensitivity of 88%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 100%. There were 4 false-positive findings and 1 false-negative finding in the triple-contrast group compared with none in the rectal-contrast group. In the triple-contrast group, there were 13 perforated appendixes compared with 1 in the rectal-contrast group. The cost of a triple-contrast scan was 620 US dollars compared with 305 US dollars for a focused rectal-contrast scan. The negative appendectomy rate for the study was 8.0% (4 of 48 patients in the triple-contrast group vs 3 of 39 in the rectal-contrast group). CONCLUSIONS: The demographics, sensitivity, specificity, and positive and negative predictive values were comparable in both groups. The focused rectal-contrast procedure was better tolerated by patients and demonstrated decreased morbidity, delay to diagnosis, perforation rate, and negative appendectomy rate with no missed diagnosis and decreased cost. Therefore, we believe that focused helical CT scanning with rectal contrast only is a superior diagnostic modality compared with the traditional triple-contrast CT scan for the diagnosis of acute appendicitis.

Adult↗
PubMed2004

Characteristics of mutations at the D5S818 locus studied with a tightly linked marker.

BACKGROUND: Mutations to STR alleles are not well understood in terms of the mechanism(s) underlying such mutations or their relative frequency among different alleles at the locus. STUDY DESIGN AND METHODS: A cytosine/thymosine (C/T) polymorphism was discovered 13 nucleotides upstream from the 5'-end of the tandem array of the D5S818 locus (-13SNP). The -13SNP coincidentally creates a restriction site polymorphism for the restriction endonuclease SnaBI that is tightly linked to the tandem array of D5S818. Forty D5S818 addition/deletion mutations in the tandem array were characterized with RFLP analysis with SnaBI. RESULTS: Among 40 mutations studied, 34 (approximately 85%) were of paternal origin, 1 ( approximately 3%) was of maternal origin, and 5 (approximately 13%) had an unclear lineage of origin. In 26 cases where the magnitude of the repeat change could be determined, 23 (88%) involved changes of a single repeat unit, whereas 3 (12%) involved changes of 2 or more repeats. The number of additions to the tandem array was roughly equal to the number of deletions from the tandem array. In 19 instances it was possible to identify the parental allele that underwent the mutation. Alleles 13 and 14 were prone to mutation, whereas Allele 11 was resistant. Thus, there is an unequal sensitivity to mutation among D5S818 alleles. CONCLUSIONS: The use of the linked -13SNP marker has revealed several features of mutations at the D5S818 locus: 1) Single repeat changes are the most commonly observed. 2) Mutations are more likely in the paternal lineage. 3) Not all alleles undergo mutation with equal frequency.

Adult↗
PubMed2003

Structural analysis of the ErbB-2 receptor using monoclonal antibodies: Implications for receptor signalling.

The extracellular part of ErbB-2 is formed by 4 domains, specifically, L1, L2 that adopt a beta-helical structure and S1, S2 that consist of several cysteine-rich, EGF-fold modules. These ectodomains mediate ErbB-2 dimerisation with itself or with other members of the epidermal growth factor receptor (EGFR) family, events essential to both ErbB-2 signaling and the development of certain malignancies. The anti-ErbB-2 monoclonal antibodies N12, N28 and L87 bind to the polypeptides C531-A586, T216-C235 and C220-C235 respectively. In this study, glycine walking and random mutagenesis were used to further delineate the critical residues involved in antibody binding. A molecular model of ErbB-2 ectodomains was then constructed based on the recently published coordinates of the EGFR (EGFR) model. This model rationalized successfully many features of our epitope mapping, including their location in modules within the S1 and S2 domains and the importance of Arg545, Gln548 and Leu561 for N12 binding. Further investigation of the functional effects of the anti-ErbB-2 monoclonal antibodies demonstrated that N28 strongly stimulated ErbB-2 phosphorylation and MAPK activation whereas N12 had no effect. As bivalency is required for the action of these antibodies we propose that at least 2 different kinds of ErbB-2 homodimers can be formed as relative rotational isomers and that the S1 and S2 domains are instrumental in determining the relative orientations of the ErbB-2 homodimers, such that different signaling effects are induced.

Antibodies, Monoclonal↗
PubMed2003

Decreasing mortality of bile leaks after elective hepatic surgery.

BACKGROUND: Bile leak is a serious complication following major hepatic surgery. It is associated with significant mortality rates if reoperative management is attempted. We evaluated our experience with aggressive, nonoperative management of postoperative biliary complications. METHODS: All medical records of patients undergoing major liver resection, cryosurgery or radiofrequency ablation from September 1996 through March 1999 were reviewed. RESULTS: Seventy-four patients were identified, and 9 (12%) developed bile leaks. Biliary leaks were investigated with endoscopic retrograde cholangiopancreatography (ERCP) and treated with endoscopic stenting when possible. The bile leak was found to originate from the resected duct stump or ablated surface of the liver in all cases. Patients were treated with ERCP stent placement (5), computed tomography-guided percutaneous drainage (3), and hepaticojejunostomy "chimney" (1). Six of 9 patients had resolution of their bile leak with the mean time of removal of the drain of 4.7 months. There was only 1 death, and that patient died nearly 3 months after surgery from complications not directly related to the bile leak. CONCLUSIONS: Bile leak after liver resection can be managed nonoperatively in most cases with a combination of percutaneous drain placement and biliary stenting. Most bile leaks will close with time, although a drain may be required for many months.

Adult↗
PubMed2002

Attenuated transcriptional responses to oxidative stress in the aged rat brain.

The aged nervous system displays impaired cognitive functions, and these impairments are exacerbated in several neurodegenerative diseases. A role for oxidative stress has been suggested for several of these age-associated dysfunctions. In addition, recovery from more acute traumatic insults that also generate oxidative stress is impaired in the aged. Here we examine the response of aged rat hippocampi to normobaric hyperoxia treatments and demonstrate an attenuation in the DNA binding activity of the AP-1 and nuclear factor-kappa B transcription factors, which are important components of stress response signal transduction pathways and can determine shifts in cellular commitments to necrosis, apoptosis, or functional recovery in the central nervous system.

Aging↗