D-AKAP2, a novel protein kinase A anchoring protein with a putative RGS domain

Subcellular localization directed by specific A kinase anchoring proteins (AKAPs) is a mechanism for compartmentalization of cAMP-dependent protein kinase (PKA). Using a two-hybrid screen, a novel AKAP was isolated. Because it interacts with both the type I and type II regulatory subunits, it was defined as a dual specific AKAP or D-AKAP1. Here we report the cloning and characterization of another novel cDNA isolated from that screen. This new member of the D-AKAP family, D-AKAP2, also binds both types of regulatory subunits. A message of 5 kb pairs was detected for D-AKAP2 in all embryonic stages and in all adult tissues tested. In brain, skeletal muscle, kidney, and testis, a 10-kb mRNA was identified. In testis, several small mRNAs were observed. Therefore, D-AKAP2 represents a novel family of proteins. cDNA cloning from a mouse testis library identified the full length D-AKAP2. It is composed of 372 amino acids which includes the R binding fragment, residues 333–372, at its C-terminus. Based on coprecipitation assays, the R binding domain interacts with the N-terminal dimerization domain of R^Iα and R^IIα. A putative RGS domain was identified near the N-terminal region of D-AKAP2. The presence of this domain raises the intriguing possibility that D-AKAP2 may interact with a Gα protein thus providing a link between the signaling machinery at the plasma membrane and the downstream kinase.     

Case Report: Utility of Ketamine,Lidocaine, and Mexiletine as Nonopioid Adjuvants in Complex Cancer-Associated Pain

ABSTRACT

Ketamine, lidocaine, and mexiletine are potential nonopioid adjuvant medications for the use of refractory cancer-related pain, particularly when opioids are demonstrating limited objective benefit. This is a case report of a single patient admitted to a large academic medical center in the United States. The patient is a 43-year-old woman with a history of Crohn's disease complicated by rectal squamous cell carcinoma and complex, progressive, and intractable pelvic and rectal pain. Over the course of hospitalization, her pain demonstrated limited opioid responsiveness despite marked fluctuations of her oral morphine equivalent doses. She also demonstrates variable responsiveness to ketamine. Lidocaine continuous infusion ultimately proves beneficial, and she is discharged after conversion to oral mexiletine. An overview of the hospital system's protocols for ketamine and lidocaine continuous infusions for pain and considerations for transitioning to mexiletine from lidocaine infusion are included.     

Synthetic cannabinoid “Black Mamba” infidelity in patients presenting for emergency stabilization in Colorado: a P SCAN Cohort

Background: Use of new psychoactive substances (NPS) has increased over the last decade. During this period, variability of both clinical presentations and chemical compositions of these compounds has increased. Synthetic cannabinoids (SCs) are the most commonly used NPS and there are more than 100 documented unique molecules in this class. “Black Mamba”, often associated to ADB-FUBINACA, is the most commonly used SC in Colorado. It has been linked to kidney injury, myocardial toxicity, seizures, and death.

Objectives: We aim to identify the chemical constituents and quantification of eight cases of reported “Black Mamba” use in order to further understand the clinical variability in patients presenting for emergency stabilization.

Methods: We report data from eight cases of reported “Black Mamba” use prospectively captured through the Colorado site of the Psychoactive Surveilance Consortium and Analysis Network (P SCAN). P SCAN is a geographically representative group of academic hospitals that capture clinical presentation, outcome, and biologic samples from patients that present for emergency stabilization following NPS use. Serum and urine samples were analyzed and quantified by liquid chromatography-quadrupole time-of-flight mass spectrometry after a qualitative screen for over 600 unique NPS compounds.

Results: In the reported eight cases, the median age was 28 years old. There were four male and four females. Four patients had agitation/delirium and four patients had chest pain. Normal saline, benzodiazepines and ondansetron were the common treatment provided in the emergency department (ED). Two patients were discharged from the ED and six patients being admitted for emergency observation with a median length of stay (LOS) of six hours. No deaths were reported. Confirmatory testing revealed that only five patients (62.5%) had SCs found in blood or urine samples. Cocaine, NRG-3, 3-methoxyphencyclidine hydrochloride (MeO-PCP), and methamfetamine were identified in other presentations.

Conclusions: The wide range of clinical presentations from “Black Mamba” use may be explained by the wide variability of chemical constituents found by laboratory analysis.     

Drivers of Inpatient Hospital Experience Using the HCAHPS Survey in a Canadian Setting

ObjectiveTo identify factors associated with patients’ overall rating of inpatient hospital care.ConclusionsOur results are novel in the Canadian population. Several questions for future research have been generated, in addition to opportunities for quality improvement within our own organization.     

肺应力和应变在肺损伤家猪机械通气中的作用

目的 研究不同平台压参数设置下,急性肺损伤(acute lung injury, ALI)家猪的跨肺压(transpulmonary pressure)等呼吸力学参数,明确平台压30cmH₂O能否全面准确反应ARDS呼吸力学情况。方法 将6只健康家猪麻醉、进行外科手术后,按照以下不同实验状态进行机械通气: A组平台压＜30cmH₂O、B组平台压＞30cmH₂O伴腹内高压(intra-abdominal hypertension, IAH)。观察不同分组通气参数设置下,肺应力、平台压等呼吸力学标。结果呼吸力学: A组肺应力为(15.07±1.47)cmH₂O高于 B组(10.92±1.28)cmH₂O;B组胸壁弹性阻力与呼吸系统弹性阻力之比(Ecw/Ers)为(0.36±0.06)高于A组(0.24±0.05);B组肺顺应性(Cdyn)为(13.38±2.79)ml/cmH₂O,明显高于A组(10.26±1.18)ml/cmH₂O ;差异均有统计学意义(P<0.01)。B组胸壁顺应性(Ccw)为(43.12±8.00)ml/cmH₂O,低于A组(63.28±36.71)ml/cmH₂O,差异均有统计学意义(P<0.01)。结论 单纯以平台压30cmH₂O作为机械通气的标准,不能准确地反映ARDS患者肺部的呼吸力学。腹内高压时,需要更高的平台压来改善氧合状况。肺应力和应变是真正反应ARDS肺呼吸力学的指标,将肺应力和应变理论引入临床,有利于为ARDS患者制定更加安全、合理的通气策略。