Sequential single doses of cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: A randomized, placebo-controlled, crossover study

Objective: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN). Design: A randomized, crossover study. Setting: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital. Patients: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume \u3e150 mL or two aspirated gastric residual volumes \u3e120 mL during a 12-hr period. Interventions: Patients received 10 mg of cisapride, 200 mg of erythromycin ethylsuccinate, 10 mg of metoclopramide, and placebo as 20 mL of sterile water every 12 hrs over 48 hrs. Acetaminophen solution (1000 mg) was administered concurrently. Gastric residual volumes were assessed, and plasma acetaminophen concentrations were serially determined by TDx between 0 and 12 hrs to evaluate gastric emptying. Measurements and Main Results: Gastric residual volumes during the study were not significantly different between agents. No differences in area under the concentration vs. time curve or elimination rate constant were identified between agents. Metoclopramide and cisapride had a significantly shorter mean residence time of absorption than erythromycin (6.3 ± 4.5 [SEM] mins and 10.9 ± 5.8 vs. 30.1 ± 4.5 mins, respectively [p \u3c .05]). Metoclopramide (9.7 ± 15.3 mins) had a significantly shorter time to peak concentration compared with erythromycin and placebo (60.7 ± 8.1 and 50.9 ± 13.5 mins, respectively [p \u3c .05]). The time to onset of absorption was significantly shorter for metoclopramide vs. cisapride (5.7 ± 4.5 vs. 22.9 ± 5.7 mins [p \u3c .05]). Conclusion: In critically ill patients intolerant to EN, single enteral doses of metoclopramide or cisapride are effective for promoting gastric emptying in critically ill patients with gastric motility dysfunction. Additionally, metoclopramide may provide a quicker onset than cisapride

The relationship between cannabis outcome expectancies and cannabis refusal self-efficacy in a treatment population

Background and aims: Self-efficacy beliefs and outcome expectancies are central to Social Cognitive Theory (SCT). Alcohol studies demonstrate the theoretical and clinical utility of applying both SCT constructs. This study examined the relationship between refusal self-efficacy and outcome expectancies in a sample of cannabis users, and tested formal mediational models. Design: Patients referred for cannabis treatment completed a comprehensive clinical assessment, including recently validated cannabis expectancy and refusal self-efficacy scales. Setting: A hospital alcohol and drug out-patient clinic. Participants: Patients referred for a cannabis treatment [n=1115, mean age 26.29, standard deviation (SD) 9.39]. Measurements: The Cannabis Expectancy Questionnaire (CEQ) and Cannabis Refusal Self-Efficacy Questionnaire (CRSEQ) were completed, along with measures of cannabis severity [Severity of Dependence Scale (SDS)] and cannabis consumption. Findings: Positive (β=-0.29,

Complex Evolutionary History With Extensive Ancestral Gene Flow in an African Primate Radiation

Understanding the drivers of speciation is fundamental in evolutionary biology, and recent studies highlight hybridization as an important evolutionary force. Using whole-genome sequencing data from 22 species of guenons (tribe Cercopithecini), one of the world's largest primate radiations, we show that rampant gene flow characterizes their evolutionary history and identify ancient hybridization across deeply divergent lineages that differ in ecology, morphology, and karyotypes. Some hybridization events resulted in mitochondrial introgression between distant lineages, likely facilitated by cointrogression of coadapted nuclear variants. Although the genomic landscapes of introgression were largely lineage specific, we found that genes with immune functions were overrepresented in introgressing regions, in line with adaptive introgression, whereas genes involved in pigmentation and morphology may contribute to reproductive isolation. In line with reports from other systems that hybridization might facilitate diversification, we find that some of the most species-rich guenon clades are of admixed origin. This study provides important insights into the prevalence, role, and outcomes of ancestral hybridization in a large mammalian radiation

Abnormal Locus Coeruleus Sleep Activity Alters Sleep Signatures of Memory Consolidation and Impairs Place Cell Stability and Spatial Memory

Sleep is critical for proper memory consolidation. The locus coeruleus (LC) releases norepinephrine throughout the brain except when the LC falls silent throughout rapid eye movement (REM) sleep and prior to each non-REM (NREM) sleep spindle. We hypothesize that these transient LC silences allow the synaptic plasticity that is necessary to incorporate new information into pre-existing memory circuits. We found that spontaneous LC activity within sleep spindles triggers a decrease in spindle power. By optogenetically stimulating norepinephrine-containing LC neurons at 2 Hz during sleep, we reduced sleep spindle occurrence, as well as NREM delta power and REM theta power, without causing arousals or changing sleep amounts. Stimulating the LC during sleep following a hippocampus-dependent food location learning task interfered with consolidation of newly learned locations and reconsolidation of previous locations, disrupting next-day place cell activity. The LC stimulation-induced reduction in NREM sleep spindles, delta, and REM theta and reduced ripple-spindle coupling all correlated with decreased hippocampus-dependent performance on the task. Thus, periods of LC silence during sleep following learning are essential for normal spindle generation, delta and theta power, and consolidation of spatial memories

The causative–instrumental syncretism

Causative and applicative morphemes have been central in work on the morphosyntax of argument structure. However, several genetically unrelated languages use a single, syncretic form for both functions, which complicates the traditional view that a causative adds a new subject and an applicative adds a new object. In this paper, I propose an analysis of a morphological syncretism found in the Bantu language Kinyarwanda where the morphological causative and instrumental applicative are both realized by the morpheme –ish. I argue for Kinyarwanda that both causation and the introduction of an instrument are analyzable as two outgrowths of the same semantic notion of introducing a new link into the causal chain described by the verb. The different causative and instrumental readings derive from underspecification of the position of the new link in the causal chain, although its placement is restricted via general constraints on possible event types as well as constraints on verb meaning and argument realization. This analysis provides an explanation for the presence of the causative–instrumental syncretism as well as provides insight into the interface between verb meaning and valency-changing morphology

Enteral cisapride, erythromycin, and metoclopramide in critically ill patients intolerant to enteral nutrition: a randomized, placebocontrolled, cross-over study

Abstract from American College of Clinical Pharmacy 1997 Annual Meeting, Phoenix, AZ, November 9-12, 1997