Neuronal loss in the rostral ventromedial medulla in a rat model of neuropathic pain.

Cell death has been reported in the CNS in models of neuropathic pain (Sugimoto et al., 1990; Whiteside and Munglani, 2001; Scholz et al., 2005; Fuccio et al., 2009). In our present study, we examined the effects of spinal nerve ligation (SNL) on the number of neurons in the rostral ventromedial medulla (RVM), a brainstem region involved in modulation of nociception. In rats receiving SNL, we found that the number of RVM neurons decreased by 23% in the side ipsilateral to the surgery. The loss of RVM neurons was also associated with a bilateral increase in the number of glia as well as bilateral activation of both astrocytes and microglia. Administration of tauroursodeoxycholic acid (TUDCA), which reportedly inhibits apoptosis, significantly reduced the loss of neurons, the increase in glia, and the mechanical hypersensitivity induced by SNL. Among RVM neurons, we found that serotonergic (5-hydroxytryptamine, 5-HT) neurons decreased by 35% ipsilateral to SNL. Consistent with these findings, the density of 5-HT-immunoreactive varicosities in the superficial dorsal horn of the spinal cord was 15-30% lower, ipsilateral to SNL. To test the function of the remaining 5-HT neurons, we administered the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT). Interestingly, after 5,7-DHT, mechanical withdrawal thresholds increased significantly. We conclude that nerve injury induces death of antinociceptive RVM neurons that can be reduced or abolished by TUDCA. We propose that the loss of RVM neurons shifts the balance of descending control from pain inhibition to pain facilitation.

Young adults' favorable perceptions of snus, dissolvable tobacco products, and electronic cigarettes: findings from a focus group study.

OBJECTIVES: We explored young adults' perceptions of snus (spitless moist snuff packed in porous bags), dissolvable tobacco products, and electronic cigarettes and intention to try these products. METHODS: We conducted 11 focus group discussions involving a total of 66 young adults (18-26 years old) on these new tobacco products (e.g., harmfulness, potential as quit aids, intention to try) held between July and December 2010. We analyzed discussions using a thematic approach. RESULTS: Participants generally reported positive perceptions of the new products, particularly because they came in flavors. Few negative perceptions were reported. Although some participants believed these products were less harmful than cigarettes and helpful in quitting smoking, others thought the opposite, particularly regarding electronic cigarettes. Participants also commented that these products could be gateways to cigarette smoking. Half of the participants, including a mix of smokers and nonsmokers, admitted they would try these products if offered by a friend. CONCLUSIONS: Young adults perceive the new tobacco products positively and are willing to experiment with them. Eliminating flavors in these products may reduce young adults' intentions to try these products.

Time-of-day and appendicitis: Impact on management and outcomes.

BACKGROUND: Observational research has shown that delayed presentation is associated with perforation in appendicitis. Many factors that affect the ability to present for evaluation are influenced by time of day (eg, child care, work, transportation, and office hours of primary care settings). Our objective was to evaluate for an association between care processes or clinical outcomes and presentation time of day. METHODS: The study evaluated a prospective cohort of 7,548 adults undergoing appendectomy at 56 hospitals across Washington State. Relative to presentation time, patient characteristics, time to operation, imaging use, negative appendectomy, and perforation were compared using univariate and multivariate methodologies. RESULTS: Overall, 63% of patients presented between noon and midnight. More men presented in the morning; however, race, insurance status, comorbid conditions, and white blood cell count did not differ by presentation time. Daytime presenters (6 am to 6 pm) were less likely to undergo imaging (94% vs 98%, P < .05) and had a nearly 50% decrease in median preoperative time (6.0 h vs 8.7 h, P < .001). Perforation significantly differed by time-of-day. Patients who presented during the workday (9 am to 3 pm) had a 30% increase in odds of perforation compared with patients presenting in the early morning/late night (adjusted odds ratio 1.29, 95% confidence interval, 1.05-1.59). Negative appendectomy did not vary by time-of-day. CONCLUSION: Most patients with appendicitis presented in the afternoon/evening. Socioeconomic characteristics did not vary with time-of-presentation. Patients who presented during the workday more often had perforated appendicitis compared with those who presented early morning or late night. Processes of care differed (both time-to-operation and imaging use). Time-of-day is associated with patient outcomes, process of care, and decisions to present for evaluation; this association has implications for the planning of the surgical workforce and efforts directed at quality improvement.

Time to appendectomy and risk of perforation in acute appendicitis.

IMPORTANCE: In the traditional model of acute appendicitis, time is the major driver of disease progression; luminal obstruction leads inexorably to perforation without timely intervention. This perceived association has long guided clinical behavior related to the timing of appendectomy. OBJECTIVE: To evaluate whether there is an association between time and perforation after patients present to the hospital. DESIGN, SETTING, AND PARTICIPANTS: Using data from the Washington State Surgical Care and Outcomes Assessment Program (SCOAP), we evaluated patterns of perforation among patients (≥18 years) who underwent appendectomy from January 1, 2010, to December 31, 2011. Patients were treated at 52 diverse hospitals including urban tertiary centers, a university hospital, small community and rural hospitals, and hospitals within multi-institutional organizations. MAIN OUTCOMES AND MEASURES: The main outcome of interest was perforation as diagnosed on final pathology reports. The main predictor of interest was elapsed time as measured between presentation to the hospital and operating room (OR) start time. The relationship between in-hospital time and perforation was adjusted for potential confounding using multivariate logistic regression. Additional predictors of interest included sex, age, number of comorbid conditions, race and/or ethnicity, insurance status, and hospital characteristics such as community type and appendectomy volume. RESULTS: A total of 9048 adults underwent appendectomy (15.8% perforated). Mean time from presentation to OR was the same (8.6 hours) for patients with perforated and nonperforated appendicitis. In multivariate analysis, increasing time to OR was not a predictor of perforation, either as a continuous variable (odds ratio = 1.0 [95% CI, 0.99-1.01]) or when considered as a categorical variable (patients ordered by elapsed time and divided into deciles). Factors associated with perforation were male sex, increasing age, 3 or more comorbid conditions, and lack of insurance. CONCLUSIONS AND RELEVANCE: There was no association between perforation and in-hospital time prior to surgery among adults treated with appendectomy. These findings may reflect selection of those at higher risk of perforation for earlier intervention or the effect of antibiotics begun at diagnosis but they are also consistent with the hypothesis that perforation is most often a prehospital occurrence and/or not strictly a time-dependent phenomenon. These findings may also guide decisions regarding personnel and resource allocation when considering timing of nonelective appendectomy.