R v Stone [1999] 2 SCR 290

The recent Canadian Supreme Court decision in R v Stone [1999] 2 SCR 290 goes some way toward clarifying the factors that need to be taken into account in distinguishing between mental disorder and non‐mental disorder automatism. A majority of five judges to four held that the burdon of proof in relation to both types of automatism is on the accussed to prove on the balance of probabilities. This is a radical departure from previous case law and part of the decision is criticised on a number of grounds.     

Chest radiography in acute aortic syndrome: pearls and pitfalls

Acute aortic syndrome is a group of life-threatening diseases of the thoracic aorta that usually present to the emergency department. It includes aortic dissection, aortic intramural hematoma, and penetrating aortic ulcer. Rare aortic pathologies of aorto-esophageal fistula and mycotic aneurysm may also be included in this list. All these conditions require urgent treatment with complex clinical care and management. Most patients who present with chest pain are evaluated with a chest radiograph in the emergency department. It is important that maximum diagnostic information is extracted from the chest radiograph as certain signs on the chest radiograph are extremely useful in pointing towards the diagnosis of acute aortic syndrome.     

Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model

OBJECTIVE: To establish the generality of cerebrovascular pathology frequently observed with Alzheimer disease, we have assessed blood-brain barrier (BBB) integrity using the Alzheimer disease model Tg2576 mice in which cognitive deficits and neuritic plaque formation develop around 10-12 months of age. METHODS: We assessed BBB integrity using well-established methods involving albumin and Evans blue uptake and introduce the use of a novel perfusion protocol using succinimidyl ester of carboxyfluorescein diacetate. RESULTS: BBB permeability is increased in the cerebral cortex of 10-month-old Tg2576 mice preceding Alzheimer disease pathology presentation. Furthermore, when compared with their nontransgenic littermates, 4-month-old Tg2576 mice exhibit compromised BBB integrity in some areas of the cerebral cortex. An age-related increase in albumin uptake by the brains of Tg2576 mice, compared with nontransgenic mice, was also observed. These findings were supported by quantitative Evans blue analysis (p = 0.07, two-way analysis of variance). CONCLUSION: A breakdown of BBB was evident in young 4- to 10-month-old Tg2576 mice. Compromised barrier function could explain the mechanisms of Abeta entry into the brain observed in experimental Alzheimer disease vaccination models. Such structural changes to the BBB caused by elevated Abeta could play a central role in Alzheimer disease development and might define an early point of intervention for designing effective therapy against the disease.     

Computed tomographic evaluation of the role of craniofacial and upper airway morphology in obstructive sleep apnea in Chinese

OBJECTIVES: To evaluate the relationship between cephalometric parameters, upper airway morphological factors and obstructive sleep apnea (OSA) in Chinese subjects. DESIGN: Polysomnogram (PSG) were performed and scored using standard criteria. Supine lateral cephalometric parameters and pharyngeal cross-sectional areas at the level of velopharynx (VA) and hypopharynx (HA) were measured from computed tomographic scans. The roles of these parameters and other anthropometric/demographic characteristics in OSA (apnea hypopnea index, AHI > or = 5) and their relationship with severity of OSA were explored by multiple logistic and multinominal regression analysis. RESULTS: Ninety-two subjects, ranging from normal (n = 36), mild/moderate OSA (n = 34) to severe OSA (n = 22), were evaluated. Compared with normal subjects, OSA subjects were heavier (body mass index 27 vs. 24 kg/m2) and older (47 vs. 42 years of age); had smaller VA size and VA to HA ratio, lower positioned hyoid bone, longer and thicker soft palate, and more retropositioned mandible relative to maxilla. After controlling for body mass index and age, subjects with severe OSA (AHI > 30) had more retropositioned mandible relative to maxilla (odds ratio, OR 1.31, P = 0.044) and longer soft palate (OR 1.16, P = 0.01), while those with mild/moderate OSA had larger VA to HA ratio (OR 0.17, P = 0.018). CONCLUSIONS: Craniofacial factors and upper airway morphology contributed to severity of OSA in Chinese subjects. Having controlled for obesity, more retropositioned mandible was associated with more severe OSA.     

Fecal Steroid 21-Dehydroxylase, a Potential Marker for Colorectal Cancer

Eubacterium lentum and phenotypically similar organisms synthesize a steroid 21-dehydroxylase which converts biliary tetrahydrodeoxycorticosterone to pregnanolone. Tetrahydrodeoxycorticosterone, in contrast to pregnanolone, is carcinogenic for hamster embryonic cells (HECT test). In patients with recently diagnosed, untreated sigmoidal or rectal cancer the fecal concentration of 21-dehydroxylating organisms is reduced by more than 99% as compared with age-matched controls. The lack of fecal 21-dehydroxylating organisms, therefore, is a potential marker for the disorder. The role of steroid 21-dehydroxylase in the pathogenesis of colorectal cancer is unknown.     

The dystrophin gene and cognitive function in the general population

The aim of our study is to investigate whether single-nucleotide dystrophin gene (DMD) variants associate with variability in cognitive functions in healthy populations. The study included 1240 participants from the Erasmus Rucphen family (ERF) study and 1464 individuals from the Rotterdam Study (RS). The participants whose exomes were sequenced and who were assessed for various cognitive traits were included in the analysis. To determine the association between DMD variants and cognitive ability, linear (mixed) modeling with adjustment for age, sex and education was used. Moreover, Sequence Kernel Association Test (SKAT) was used to test the overall association of the rare genetic variants present in the DMD with cognitive traits. Although no DMD variant surpassed the prespecified significance threshold (P<1 × 10⁻⁴), rs147546024:A>G showed strong association (β=1.786, P-value=2.56 × 10⁻⁴) with block-design test in the ERF study, while another variant rs1800273:G>A showed suggestive association (β=−0.465, P-value=0.002) with Mini-Mental State Examination test in the RS. Both variants are highly conserved, although rs147546024:A>G is an intronic variant, whereas rs1800273:G>A is a missense variant in the DMD which has a predicted damaging effect on the protein. Further gene-based analysis of DMD revealed suggestive association (P-values=0.087 and 0.074) with general cognitive ability in both cohorts. In conclusion, both single variant and gene-based analyses suggest the existence of variants in the DMD which may affect cognitive functioning in the general populations.