Charles F. Wilkinson

Urinary free cortisol and sleep under baseline and stressed conditions in healthy senior women: effects of estrogen replacement therapy

The purpose of this study was to examine the effects of a mild 24‐h stress (indwelling IV catheter) on cortisol and sleep in postmenopausal women, and to evaluate differences due to estrogen replacement therapy (ERT) status. This study, conducted in the General Clinical Research Center at the University of Washington Medical Center, examined sleep, cortisol and sleep‐cortisol relationships in both baseline and stress conditions, and compared women on ERT with women not on ERT. Forty‐two women (age=69.6 ± 6.2 years [SD]), of whom 20 were on ERT, participated. Urinary free cortisol (UFC) levels and sleep polysomnography were measured over both 24‐baseline and stress condition. Sleep was impaired in the stress condition for both groups; mean UFC levels were higher, sleep efficiency and minutes of stages 2, 3 and 4 sleep were reduced, and morning risetime was earlier in the stress than baseline condition. For the combined groups, age‐controlled correlations between 24‐h UFC and sleep were significant in both conditions: at baseline, UFC levels were associated with earlier time of rising and less REM sleep, and under stress with reduced sleep efficiency, there was reduced minutes of stages 2, 3, 4 sleep, reduced REM sleep, and an earlier risetime. The pattern of negative significant correlations between UFC and sleep/sleep timing remained when plasma estrogen was statistically controlled; however, when groups were examined separately, the significant negative UFC‐sleep relationships were confined to the non ERT group. Elevated 24‐h UFC is associated with impaired sleep and earlier awakening in older women not on ERT, but not in women on ERT.

Arteriopathy, D-Dimer, and Risk of Poor Neurologic Outcome in Childhood-Onset Arterial Ischemic Stroke

OBJECTIVE To assess whether acute findings of cerebral arteriopathy, large infarct, and acutely elevated plasma D-dimer levels are independently prognostic of poor long-term neurologic outcome as measured at ≥ 1 year post-event in children with arterial ischemic stroke (AIS). STUDY DESIGN Sixty-one patients with childhood-onset (ie, >28 days of life) AIS were enrolled in a single-institution cohort study at Childrens Hospital Colorado between February 2006 and June 2011. Data on demographic and diagnostic characteristics, antithrombotic treatments, and outcomes were systematically collected. RESULTS Cerebral arteriopathy and D-dimer levels >500 ng/mL (a measure of coagulation activation) were identified acutely in 41% and 31% of the cohort, respectively. Anticoagulation was administered in the acute period post-event in 40% of the children, in the subacute period in 43%, and in the chronic period in 28%. When not receiving anticoagulation, patients were routinely treated with aspirin 2-5 mg/kg once daily for a minimum of 1 year. Death, major bleeding (including intracranial hemorrhage), and recurrent AIS were infrequent. The Pediatric Stroke Outcome Measure at 1 year demonstrated poor outcome in 54% of the children. Acute cerebral arteriopathy and elevated D-dimer level were identified as putative prognostic factors for poor outcome; after adjustment for D-dimer, arteriopathy was an independent prognostic indicator (OR, 19.0; 95% CI, 1.6-229.8; P = .02). CONCLUSION Arteriopathy and coagulation activation are highly prevalent in the acute period of childhood AIS. Although recurrent AIS and intracranial hemorrhage were infrequent in our cohort, one-half of children experienced a poor neurologic outcome at 1 year, the risk of which was increased by acute arteriopathy. Substantiation of these findings in multi-institutional cohort studies is warranted, toward risk stratification in childhood-onset AIS.

American Indians, Time, and the Law: Native Societies in a Modern Constitutional Democracy

In 1959, the Supreme Court ushered in a new era of Indian law, which recognizes Indian tribes as permanent governments within the federal constitutional system and, on the whole, honors old promises to the Indians. Drawing together historical sources such as the records of treaty negotiations with the Indians, classic political theory on the nature of sovereignty, and anthropological studies of societal change, Wilkinson evaluates the Courts work in Indian law over the past twenty five years and considers the effects of time on law.

Intranasal insulin treatment response in Alzheimer's disease influenced by glucose-stimulated insulin secretion

properties. Molecular modeling studies have indicated the central fused acridine ring undergoes favourable interactions within the catalytic site of AChE enzyme. Preliminary data on their ability to inhibit both AChE and BuChEs, their ability to chelate metals and antioxidant properties along with detailed enzyme-ligand binding investigations will be discussed. Conclusions: It is anticipated that our research should lead to the development of novel class of disease-modifying agents to treat AD by developing novel (i) heterocyclic small molecules possessing dual ChE (AChE/BuChE) inhibition; (ii) identify metal chelating and antioxidant pharmacophores in the design of small molecule therapeutics to treat AD.