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.     

Effect of sucrose ingestion on plasma glutamate concentrations in humans administered monosodium L-glutamate

Plasma glutamate concentrations in human subjects are markedly lower when monosodium L-glutamate (MSG) is ingested in consomme with starch than when ingested in consomme alone. This study investigated whether sucrose had a similar effect. Six normal adult subjects (three male, three female) ingested two servings of beef consomme each providing 50 mg MSG/kg body weight in a randomized crossover design. One serving of consomme contained no added carbohydrate; the other provided 0.5 g sucrose/kg body weight. Ingestion of the consomme without sucrose significantly (p less than 0.05) increased the mean plasma glutamate concentration from baseline (4.44 +/- 0.97 mumol/dl) to a peak value of 18.1 +/- 6.99 mumol/dl 30 min after dosing. The area under the plasma glutamate concentration-time curve was 553 +/- 238 mumol/dl X min. When the consomme contained 0.5 g sucrose/kg body weight, both the mean peak plasma glutamate concentration (5.48 +/- 2.19 mumol/dl) and the area under the curve (105 +/- 46 mumol/dl X min) were significantly lower. These data confirm that metabolizable carbohydrate has a significant effect on plasma glutamate concentration response after MSG loading.     

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.