Magnesium in the prevention of lethal arrhythmias in acute myocardial infarction

Seven of 48 patients (14.6%) with acute myocardial infarction who were given 2.4 g of magnesium sulfate as a single intravenous dose had potentially lethal arrhythmias during the first 24 hours after admission, whereas 16 (34.8%) of 46 patients receiving placebo had similar arrhythmias. In addition, 14 of these 16 patients in the placebo group had their first arrhythmia (in the intensive coronary-care unit) within two hours after the start of the study, whereas in the magnesium-treated group, there were no such arrhythmias until some four hours later. The higher the lymphocyte potassium concentration, the greater the reduction in the incidence of arrhythmias. Serum magnesium levels increased by 16.5% and lymphocyte magnesium concentrations by 72% in the magnesium treated group. Intravenous magnesium reduces the incidence of serious arrhythmias after acute myocardial infarction.     

Clarifying confusion: the confusion assessment method. A new method for detection of delirium

OBJECTIVE: To develop and validate a new standardized confusion assessment method (CAM) that enables nonpsychiatric clinicians to detect delirium quickly in high-risk settings. DESIGN: Prospective validation study. SETTING: Conducted in general medicine wards and in an outpatient geriatric assessment center at Yale University (site 1) and in general medicine wards at the University of Chicago (site 2). PATIENTS: The study included 56 subjects, ranging in age from 65 to 98 years. At site 1, 10 patients with and 20 without delirium participated; at site 2, 16 patients with and 10 without delirium participated. MEASUREMENTS AND MAIN RESULTS: An expert panel developed the CAM through a consensus building process. The CAM instrument, which can be completed in less than 5 minutes, consists of nine operationalized criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM-III-R). An a priori hypothesis was established for the diagnostic value of four criteria: acute onset and fluctuating course, inattention, disorganized thinking, and altered level of consciousness. The CAM algorithm for diagnosis of delirium required the presence of both the first and the second criteria and of either the third or the fourth criterion. At both sites, the diagnoses made by the CAM were concurrently validated against the diagnoses made by psychiatrists. At sites 1 and 2 values for sensitivity were 100% and 94%, respectively; values for specificity were 95% and 90%; values for positive predictive accuracy were 91% and 94%; and values for negative predictive accuracy were 100% and 90%. The CAM algorithm had the highest predictive accuracy for all possible combinations of the nine features of delirium. The CAM was shown to have convergent agreement with four other mental status tests, including the Mini-Mental State Examination. The interobserver reliability of the CAM was high (kappa = 0.81 - 1.0). CONCLUSIONS: The CAM is sensitive, specific, reliable, and easy to use for identification of delirium.     

Sleep loss and sleepiness: current issues

Awareness of the consequences of sleep loss and its implications for public health and safety is increasing. Sleep loss has been shown to generally impair the entire spectrum of mental abilities, ranging from simple psychomotor performance to executive mental functions. Sleep loss may also impact metabolism in a manner that contributes to obesity and its attendant health consequences. Although objective measures of alertness and performance remain degraded, individuals subjectively habituate to chronic partial sleep loss (eg, sleep restriction), and recovery from this type of sleep loss is slow, factors that may help to explain the observation that many individuals in the general population are chronically sleep restricted. Individual differences in habitual sleep duration appear to be a trait-like characteristic that is determined by several factors, including genetic polymorphisms.     

Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance

Podocytes are specialized actin-rich epithelial cells that line the kidney glomerular filtration barrier. The interface between the podocyte and the glomerular basement membrane requires integrins, and defects in either α₃ or β₁ integrin, or the α₃β₁ ligand laminin result in nephrotic syndrome in murine models. The large cytoskeletal protein talin1 is not only pivotal for integrin activation, but also directly links integrins to the actin cytoskeleton. Here, we found that mice lacking talin1 specifically in podocytes display severe proteinuria, foot process effacement, and kidney failure. Loss of talin1 in podocytes caused only a modest reduction in β₁ integrin activation, podocyte cell adhesion, and cell spreading; however, the actin cytoskeleton of podocytes was profoundly altered by the loss of talin1. Evaluation of murine models of glomerular injury and patients with nephrotic syndrome revealed that calpain-induced talin1 cleavage in podocytes might promote pathogenesis of nephrotic syndrome. Furthermore, pharmacologic inhibition of calpain activity following glomerular injury substantially reduced talin1 cleavage, albuminuria, and foot process effacement. Collectively, these findings indicate that podocyte talin1 is critical for maintaining the integrity of the glomerular filtration barrier and provide insight into the pathogenesis of nephrotic syndrome.     

Behavioral Control of Respiration in Sleep

Three experiments are presented involving behavioral control of sleeping respiration during all-night sleep recording. Probability and latency of the breathing response to an auditory signal revealed that control over sleeping respiration was obtained in all sleep stages and was maintained over several nights. This control was especially marked when failure to respond was punished (contingency procedure) by increasing the intensity of the signal (Experiments 2 and 3). Few awakenings occurred to the signal but signs of brief arousal (bursts of alpha activity, increases in EMG activity, EEG “speeding”) often accompanied the behavioral response. Overall sleep patterns were only minimally disrupted by the procedure. Demonstrating behavioral control over sleeping respiration may be a promising step toward the development of behavioral therapies for certain sleep apnea disorders and hypoventilation syndromes.     

Performance and alertness effects of caffeine, dextroamphetamine, and modafinil during sleep deprivation

Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with dextroamphetamine on others. At the doses tested, caffeine, dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear.     

Translocations in Prader-WiIIi syndrome

The Prader-Willi Syndrome (PWS) has frequently been associated with chromosomal anomalies involving the region 15q11-q12. The first case of this syndrome associated with a de novo translocation involving chromosomes 11 and 15 is reported. The breakpoints were identified as 11q25 and 15q11 or q12[45, XX,t(11;15)(q25;q11-12)], resulting in the deletion of 15pter leads to 15q11-q12. Previously reported cases of PWS associated with translocations are reviewed in relation to the "deletion hypothesis."