Metabolism of the leukotriene receptor antagonist 5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid (SK&F 102922) in the guinea pig. Rearrangement of the acyl glucuronide.

A primary route of inactivation of leukotrienes and their receptor antagonists (LTRA) is metabolism by omega oxidation. SK&F 102922 [5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid] is a LTRA that was designed to be resistant to omega oxidation. Therefore, these experiments were designed to characterize the metabolic fate of [14C]SK&F 102922. Following iv administration of SK&F 102922 (5 mg/kg), 80% of injected radioactivity was excreted in bile in 1 hr. At least five metabolites and parent (18% of administered dose) were present in bile. One metabolite (M1), which accounted for less than 10% of the excreted radioactivity, was monohydroxylated. Three metabolites (M2, M3A, and M3B), which together accounted for greater than 50% of excreted radioactivity, had mass spectra consistent with acyl glucuronides. All three metabolites were alkali labile, whereas only one metabolite (M2) was susceptible to beta-glucuronidase hydrolysis. These data indicate that M3a and M3b are nonglycosidic isomers of M2 that were formed by a nonenzymic reaction involving migration of the aglycone (SK&F 102922) from C-1 to C-2, C-3, or C-4 of glucuronic acid. The 1-O-acyl-beta-glucuronide of SK&F 102922 (M2) exhibits pH dependent rearrangement, with half-lives ranging from 1 to greater than 1000 hr. Therefore, acyl glucuronidation can account for much of the metabolic fate of SK&F 102922 and, potentially, other structurally related LTRAs or endogenous leukotrienes themselves.     

Assessing reflective writing on a pediatric clerkship by using a modified Bloom's Taxonomy.

OBJECTIVE: Reflection enables learners to analyze their experiences and capture the wisdom that lies within. Effective teaching requires reliable methods of assessment. Several methods of assessing reflective writing have been described; however, they often require significant training, and reliability has seldom been assessed. This study was designed to determine the interrater reliability of a method of assessing reflective writing by using a modified Bloom's Taxonomy. METHODS: Twenty-one third-year medical students maintained reflective journals throughout their pediatric clerkship. A coding schema based on Bloom's Taxonomy was developed to assess the level of cognitive processing evident in the journals. Journals were independently assessed by 3 raters. Percent agreement, kappa statistics, and intraclass correlation coefficients (ICC [2,1]) were used to assess interrater reliability. RESULTS: Three hundred eight entries from 21 journals were assessed. Percent agreement ranged from 78.2% to 100%. Kappa statistic for each level ranged from 0.57 +/- 0.04 to 0.73 +/- 0.04, and for the highest level of processing evident it ranged from 0.52 +/- .04 to 0.58 +/- 0.04. ICC (2,1) for each level of cognitive processing ranged from 0.62 (F = 6.20; P = .000) to 1.00, and for the highest level of cognitive processing evident, it was 0.79 (F = 12.42; P = .000). Substantial to almost perfect agreement was attained. CONCLUSIONS: Reflective journals allow learners to revisit their experiences for critical analysis and deeper learning. This study describes a reliable method, based on Bloom's Taxonomy, of determining whether learners have achieved higher order thinking through reflective journal writing. This method can provide a baseline for facilitating higher order processing, critical thinking, and reflective practice.     

A population-based study of repeat hospital admissions due to interpersonal violence for children aged 0–9 years

To assess the magnitude and nature of interpersonal violence resulting in hospitalisation of children and to identify subgroups at risk of repeat hospital admissions, a population-based, retrospective study of all violence hospitalisations in Western Australia for children aged 9 years or less was undertaken, using the 1990–2004 linked data retrieved from the Western Australian Mortality Database and the Hospital Morbidity Data System.
Of the 747 patients aged <10 years incurring 834 hospitalisations for the consequences of violence during the study period, 570 (76%) were less than 4 years of age. A total of 43 deaths from violence were recorded and 74 (9%) patients were admitted for more than one episode of violence. Victims aged 0–4 years from rural (hazard ratio [HR] = 2.72; 95% confidence interval [CI] 1.35, 5.43) and remote parts (HR = 2.79; 95% CI 1.25, 6.25) of the state were at increased risk of a subsequent admission for violence compared with those residing within the metropolitan area. Indigenous children aged 5–9 years were significantly more likely (HR = 3.57; 95% CI 1.14, 11.13) to incur a second hospitalisation for violence than their non-Indigenous counterparts. The identification of young victim subgroups at high risk of repeat hospitalisations is important for developing intervention strategies to reduce the burden of interpersonal violence. Young children aged 0–4 years living in rural and remote locations and Indigenous children aged 5–9 years should be specifically targeted for attention.     

Frozen section analysis of esophageal endoscopic mucosal resection specimens in the real-time management of Barrett's esophagus.

BACKGROUND & AIMS: The aim of this study was to assess the validity of frozen section analysis of endoscopic mucosal resection (EMR) specimens from Barrett's esophagus as compared with permanent sections for the detection of neoplasia. Frozen sections help to give immediate feedback for surgical procedures. It has not been determined whether EMR can be adequately interpreted by using frozen sections to aid endoscopists in completely resecting neoplastic lesions. METHODS: EMR specimens from Barrett's esophagus with high-grade dysplasia (HGD) and/or carcinoma were tested by frozen section. Pathologists evaluated EMR specimens for the depth of invasion as well as the appearance of clear margins of resection. The kappa statistic was calculated to assess the degree of agreement between the frozen section and permanent section diagnoses. RESULTS: Twenty-three consecutive patients underwent 30 EMRs with frozen section diagnosis. Frozen section revealed a carcinoma in 7 specimens (23%) and dysplasia in 20 (66%). Permanent sections found carcinoma in 8 specimens (26%), dysplasia in 19 specimens (63%), and normal or nondysplastic Barrett's esophagus in the remainder. The kappa statistic for the depth of invasion of EMR specimens was 0.93 (near perfect agreement). The kappa statistic for the margins of the EMR specimens was 0.80 (excellent agreement). CONCLUSIONS: This study indicated that frozen section analysis of esophageal EMR specimens is valid as compared with permanent section. This technique might allow rapid evaluation about the degree and depth of involvement of cancers. This allows physicians to make decisions regarding further therapy if margins are involved or decrease the use of EMR for histologically benign-appearing lesions.