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

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

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Nucleotide diversity and population differentiation of the melanocortin 1 receptor gene, MC1R

The melanocortin 1 receptor gene (MC1R) is responsible for normal pigment variation in humans and is highly polymorphic with numerous population-specific alleles. Some MC1R variants have been associated with skin cancer risk