George Mckelvey

Ketamine reverses stress-induced depression-like behavior and increased GABA levels in the anterior cingulate: an 11.7 T 1H-MRS study in rats.

Gamma-aminobutyric acid (GABA) is the major inhibitory amino acid neurotransmitter in the brain and is primarily responsible for modulating excitatory tone. Clinical neuroimaging studies show decreased GABA levels in the anterior cingulate of patients with mood disorders, including major depressive disorder. Chronic unpredictable stress (CUS) is an animal model thought to mimic the stressful events that may precipitate clinical depression in humans. In this study male Sprague-Dawley rats were subjected to a modified CUS paradigm that used a random pattern of unpredictable stressors twice daily for 10 days to explore the early developmental stages of depression-like endophenotypes. Control rats were handled daily for 10 days. Some rats from each treatment group received an injection of ketamine (40 mg/kg) after the final stressor. One day following the final stressor rats were tested for behavioral effects in the forced swim test and then euthanized to collect trunk blood and anterior cingulate brain samples. GABA levels were measured in anterior cingulate samples ex vivo using proton magnetic resonance spectroscopy ((1)H-MRS) at 11.7 T. Animals subjected to CUS had lower body weights, higher levels of blood corticosterone, and increased immobility in the forced swim test; all of which suggest that the stress paradigm induced a depression-like phenotype. GABA levels in the anterior cingulate were significantly increased in the stressed animals compared to controls. Administration of ketamine on the last day of treatment blunted the depression-like behavior and increased GABA levels in the anterior cingulate following CUS. These data indicate that stress disrupts GABAergic signaling, which may over time lead to symptoms of depression and ultimately lower basal levels of cortical (1)H-MRS GABA that are seen in humans with depression. Furthermore, the data suggests that ketamine modulates cortical GABA levels as a mechanism of its antidepressant activity.

Phantom shocks unmasked: clinical data and proposed mechanism of memory reactivation of past traumatic shocks in patients with implantable cardioverter defibrillators

BackgroundImplantable cardioverter defibrillators (ICD), despite an unequivocal clinical benefit, are known to have a complex psychosocial impact on the patients. ICD shocks and the resultant psychobiological changes are known to contribute to increased levels of anxiety, depression, and post-shock stress symptoms in these patients. Phantom shock is a patient-reported perception of an ICD shock in the absence of any actual shock; however, its pathophysiological understanding is poor.MethodsA retrospective chart review of the University hospital ICD patients’ database from June 2006 to April 2010 was conducted. A total of 38 patients with documented phantom shocks as cases and 76 age- and sex-matched patients with no phantom shocks as controls were selected from the database. Patient characteristics were analyzed for their potential association with the occurrence of phantom shocks.ResultsPhantom shock patients had higher prevalence of documented depression (31.6%), anxiety (23.7%), and cocaine use (42.1%). Additionally, patients who had previous ICD shock storms were more likely to have phantom shocks (39.5%; p = 0.001). More importantly, no phantom shocks were reported in patients who did not receive defibrillation threshold testing or past ICD shock storms.ConclusionsPhantom shocks are primarily observed in ICD patients who had prior exposure to traumatic device shocks and are more common in patients with a history of depression, anxiety, or substance abuse. A pathophysiological mechanism is proposed as a guide to potential prevention.

Nicotinic Acetylcholine Receptor Gene Expression Is Altered in Burn Patients

INTRODUCTION: Burn patients have been observed to be more susceptible to the hyperkalemic effect of the depolarizing muscle relaxant succinylcholine. Changes in nicotinic acetylcholine receptor (nAChR) subunit composition may alter electrophysiologic, pharmacologic, and metabolic characteristics of the receptor inducing hyperkalemia on exposure to succinylcholine. No studies have been performed that show the upregulation and/or alteration of nAChR subunit composition in human burn patients. The scarcity of studies performed on humans with burn injury is mainly attributable to the technical and ethical difficulties in obtaining muscle biopsies at different time frames of illness in these acutely injured patients. nAChRs are expressed in oral keratinocytes and are upregulated or altered in smokers. However, no studies have addressed the expression of nAChRs in the oral mucosa of burn patients. METHODS: Buccal mucosal scrapings were collected from 9 burn patients and 6 control nonburn surgical intensive care unit patients. For burn and control patients, tissues were collected upon presentation (time: 0 hour) and at time points 12, 24, and 48 hours, 1 week, and 2 weeks. Gene expression of the nAChR subunits &agr;1, &agr;7, &ggr;, and ε were performed using real-time reverse transcriptase polymerase chain reaction. RESULTS: &agr;7 and &ggr; nAChR genes were significantly upregulated in burn patients, whereas &agr;1 and ε nAChR genes were minimally affected, showing no significant changes over time. DISCUSSION: Over the 2 weeks of measurement, an upregulation of the &agr;7 and &ggr; genes occurred in both burn and control patients; however, the proportion of &agr;7 and &ggr; subunit increases was significantly higher in burn patients than in control surgical intensive care unit patients. The relationship between the thermal injury and the observed alteration in gene expression suggests a possible cause/effect relationship. This effect was observed at a site not affected by the burn injury and in nonmuscle tissues, thus emphasizing the systemic nature of the effect caused by the thermal injury. Because gene expression is the basis of protein production, the upregulation of &agr;7 and &ggr; genes might translate into more &agr;7 and &ggr; protein subunits. These proteins can also combine with each other or with other types of subunits (&agr;1, &bgr;, ε . . .) to form nAChRs with altered electrophysiologic characteristics leading to the observed abnormal clinical outcomes. CONCLUSION: Thermal injury may infer a systemic effect because upregulation/alteration of nAChRs occurs in nonmuscle tissues distant from the site of injury. The effect of thermal injury on nAChR gene subunits can be studied using a minimally invasive method (buccal mucosal scraping) and a highly sensitive technology (real-time reverse transcriptase polymerase chain reaction) obviating the need for more invasive methods.

Firstborn offspring sex ratio is skewed towards female offspring in anesthesia care providers: A questionnaire-based nationwide study from United States

Background: A parental occupation such as anesthesia care provider can involve exposure of the parent to various chemicals in the work environment and has been correlated to skewed offspring sex ratios. Objectives: The objective was to conduct a nation-wide survey to observe (a) whether firstborn offspring sex ratio (OSR) in anesthesia providers is skewed towards increased female offspring, and (b) to identify potential factors influencing firstborn OSR, particularly those relating to the peri-conceptional practice of inhalational anesthesia induction among anesthesia providers. Materials and Methods: After institutional review board approval, a questionnaire was uploaded on SurveyMonkey and sent to anesthesia providers through their program coordinators in United States (US) to complete the survey. Results: The current US national total-population sex ratio is 0.97 male (s)/female with an at-birth sex ratio of 1.05 male (s)/female; comparatively, the results from anesthesia providers’ survey respondents (n = 314) were a total OSR of 0.93 male (s)/female (P = 0.61) with firstborn OSR 0.82 male (s)/female (a 6% increase in female offspring; P = 0.03), respectively. The only significant peri-conceptional factor related to anesthesia providers’ firstborn OSR’s skew was inhalational induction practice by anesthesia care provider favoring female offspring (P < 0.01). Conclusion: Based on the results of this limited survey, it can be concluded that anesthesia care providers who practice inhalation induction of anesthesia during the peri-conceptional period are significantly more likely to have firstborn female offspring.

Effect of Substance Abuse on Defibrillation Threshold in Patients with Implantable Cardioverter‐Defibrillator

Background:  The use of recreational drugs has been observed to have deleterious effects on the heart. The aim of our study was to evaluate the effect of substance abuse on the defibrillation threshold (DFT) in patients with implantable cardioverter‐defibrillators (ICDs).

Recent Respiratory Tract Infection and Additional surgeries Increase Risk for Surgical Site Infection in Total Joint Arthroplasty: A Retrospective Analysis of 2255 patients

Abstract Background Surgical site infections (SSI) are one of the most common healthcare-associated infections contributing to high economic burden. Around 658,000 total joint arthroplasties (TJA) are performed annually in the Unites States, estimated 0.9–2.5% develop surgical site infection. Despite following prevention guidelines, SSI continues to occur. The aim of our study was to identify perioperative risk factors for SSI in patients undergoing TJA. Methods A retrospective cohort study was performed of patients at the Detroit Medical Center from 2011 to 2015. All adult patients undergoing primary or revision total knee or hip joint arthroplasty were included. Patients were divided into SSI (prosthetic joint infections) and non-SSI group. Baseline characteristics and perioperative variables influencing SSI were assessed. Statistical analysis was performed using SAS software. Continuous variables were compared using Wilcoxon–Rank-sum test and categorical variables using Fischer’s exact test. Results Among 2255 included patients, 1203 had knee arthroplasties (53%), 1052 had hip arthroplasties (47%) and SSI occurred in 46 patients (2%). Overall, mean age was 58.81 ± 11 years; 64% were females, 57% were African American, and 41% were smokers. Diabetes did not increase risk for SSI (37% with SSI vs. 26% without SSI; P = 0.09). Administration of general anesthesia, American Society of Anesthesiologists score of ≥2, the presence of hypothermia and hyperglycemia did not statistically increase the risk for SSI. Patients with recent respiratory tract infection in previous 30 days prior to surgery were more likely to develop infection compared with patients without recent infection (20% vs. 6.6%, OR 3.42; 95% confidence interval 1.62–7.22, P = 0.0034). Any additional surgery within 90 days of arthroplasty increased risk for infection (22% vs. 11%, P = 0.03). Among the 46 SSIs, knee surgeries experienced more infections than hip surgeries (67% vs. 33%, P = 0.07). Conclusion In this study, recent respiratory tract infection in 30 days prior to surgery and additional surgeries within 90 days after arthroplasty increased risk for SSI. Careful preoperative assessment and sufficient time to postoperative recovery is essential to reduce SSI. Further multicenter studies are needed to validate our findings. Disclosures All authors: No reported disclosures.