A neurotensin analog blocks cocaine-conditioned place preference and reinstatement.

Neurotensin (NT) is a neuropeptide that acts as a neurotransmitter and neuromodulator in the central nervous system. Several studies suggest a therapeutic role for NT analogs in nicotine and other psychostimulant addictions. We studied the effects of the nonselective NT receptor agonist NT69L, which has equal affinity for the two major NT receptors, NTS1 and NTS2, on the expression of cocaine-conditioned place preference (cocaine-CPP) and reinstatement after extinction. Robust cocaine-CPP was obtained after 5 days of conditioning. Extinction was induced using eight repeated daily injections of saline. Reinstatement was prompted by priming with one injection of cocaine (12 mg/kg intraperitoneally). On the test day, NT69L (1 mg/kg intraperitoneally) was administered 30 min before assessing cocaine-CPP. Extinction led to the loss of cocaine-CPP. One injection of cocaine (12 mg/kg intraperitoneally) for cocaine priming reinstated cocaine-CPP. NT69L blocked cocaine-CPP reinstatement in cocaine-primed animals. In addition, NT69L blocked cocaine-CPP reinstatement when administered before priming with cocaine. Thus, the NT agonist NT69L blocked both cocaine-CPP and reinstatement to cocaine preference. NT69L may exert this action by modulating the mesocorticolimbic dopamine and glutamatergic pathways involved in addiction and relapse processes. Therefore, NT agonists may represent a novel therapy for the treatment of addiction to cocaine and possibly to other psychostimulants.

Prevalence of restless legs syndrome in blood donors.

Iron deficiency anemia has been linked to restless legs syndrome (RLS) and regular blood donation may lead to iron deficiency. It has been reported that blood donations may be associated with RLS. A recent study from Sweden found that 25% of the women donors were affected by RLS. However, this type of study has not been replicated in the United States. We conducted a study in our blood donation unit between September and October 2008. To identify those with RLS, we used the RLS diagnostic index questionnaire by Benes et al. The proportion of blood donors with RLS was estimated and the number of blood donations and hemoglobin levels were compared according to RLS status. One hundred and fifty one patients were interviewed; 7 patients who donated only platelets were excluded, leaving 144 patients for analysis. There were 13 (9.0%, 95% confidence interval [CI]: 4.9-14.9%) patients with RLS. Of these, 7 (4.9%, 95% CI: 2.0-9.8%) had possible RLS and 6 (4.2%, 95% CI: 1.5-8.9%) had major or clinically relevant RLS. There was no dramatic association between RLS and number of blood donations or hemoglobin level (all P >or= 0.21). In our sample of blood donors in the United States, the prevalence of major RLS was 4%. We could not demonstrate an association between RLS and the frequency of blood donation or hemoglobin level in our relatively small sample; a larger sample is needed to better identify any associations.

Sleep Apnea in Patients Hospitalized With Acute Ischemic Stroke: Underrecognition and Associated Clinical Outcomes.

STUDY OBJECTIVES: To evaluate clinical recognition of sleep apnea and related outcomes in patients hospitalized with acute ischemic stroke. METHODS: A retrospective study of all patients hospitalized with acute ischemic stroke from April 2008 to December 2014. The primary predictor and outcome variables were sleep apnea and hospital mortality, respectively. Secondary outcomes were mechanical ventilation, hospital length of stay, and the survivor's functional level by the modified Rankin scale. A sensitivity multivariate regression analysis included the propensity score for cardiovascular comorbidities and sleep apnea. RESULTS: Of 989 patients, 190 (19%) were considered to have sleep apnea. Only 42 patients (22%) received any treatment for sleep apnea during the hospital stay. Despite higher prevalence of cardiovascular comorbidities, the patients with sleep apnea had lower hospital mortality, 1% versus 5.6% in patients without sleep apnea (odds ratio [OR] 0.18; 95% confidence interval [CI], 0.03-0.58, P = .002). Only the National Institutes of Health Stroke Scale (NIHSS) and the Glasgow coma scale (GCS) were significant predictors of adjusted hospital mortality (OR 1.06, 95% CI 1.01-1.11, P = .01 and OR 0.61, 95% CI 0.51-0.69, P ≤ .001, respectively). A composite clinical propensity score for sleep apnea and cardiovascular comorbidities was significantly associated with decreased mortality, independent to either NIHSS (OR 0.11, 95% CI 0.017-0.71; P = .02) or GCS (OR 0.07, 95% CI 0.01-0.52; P = .01). CONCLUSIONS: Prevalence of sleep apnea in our study was low, likely because of clinical underrecognition. Despite having more cardiovascular disease, the patients with acute stroke and sleep apnea had less severe neurological injury and lower unadjusted mortality than those without a history of sleep apnea.

Prevalence of restless legs syndrome among native South Americans residing in coastal and mountainous areas.

OBJECTIVE: To determine the prevalence of restless legs syndrome (RLS) in native South Americans and identify the impact of geographic location. PARTICIPANTS AND METHODS: An epidemiological telephone survey of RLS symptoms involving natives from coastal and mountainous areas was performed during July 2, 2004, through September 28, 2004. The process consisted of 2 phases: the creation of the epidemiological instrument and the telephone survey. RESULTS: Five hundred adults, 250 from the mountainous regions and 250 from the coastal region (190 men and 310 women; age range, 25-85 years) were interviewed and subsequently divided on the basis of International Restless Legs Syndrome Study Group criteria into those who had RLS (RLS+ group) and those who did not (RLS- group). Ten (2.0%) had RLS. The overall rate of RLS in adults living in the mountainous region at 2816 m above sea level (3.2% [8/250]) was significantly higher than that for adults living in the coastal region at 4 m above sea level (0.80% [2/250]; P = .002). The mean age of the RLS+ group was 49.5 years (SD, 15.20 years; range, 25-85 years). CONCLUSION: Native South American adults have a prevalence of RLS well below that reported in populations with European ancestry but similar to that in Asian and Turkish populations. Furthermore, in Ecuador, geographic differences were identified in areas of similar population density.

Studies of humoral immunity to preprohypocretin in human leukocyte antigen DQB1*0602-positive narcoleptic subjects with cataplexy.

BACKGROUND: Canine models for narcolepsy have mutations of the hypocretin receptor 2 gene, and preprohypocretin knockout murine lines exhibit narcoleptic-like behaviors. Human narcolepsy with cataplexy is associated with human leukocyte antigen DQB1*0602 and reduced hypocretin levels in cerebrospinal fluid, suggesting an autoimmune diathesis. We tested the hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have immunoglobulin (Ig)G reactive to human preprohypocretin and its cleavage products. METHODS: Serum samples of 41 DQB1*0602-positive narcoleptic subjects with cataplexy and 55 control subjects were studied, as were 19 narcoleptic and 13 control samples of cerebrospinal fluid. We tested for IgG reactive to preprohypocretin and its major cleavage products (including hypocretin 1 and 2), using immunoprecipitation assays (IP), immunofluorescence microscopy (IF) of Chinese hamster ovarian cells expressing preprohypocretin, and Western blots. RESULTS: There was no evidence for IgG reactive to preprohypocretin or its cleavage products in CSF of subjects with narcolepsy as measured by IPs, Western blots, and IF. Although the IP with CSF and the C-terminal peptide showed significant differences by two methods of comparison, the control subjects had higher counts per minute than narcoleptic subjects, which was opposite to our hypothesis. CONCLUSIONS: The hypothesis that DQB1*0602-positive narcoleptic subjects with cataplexy have IgG reactive to preprohypocretin or its cleavage products was not supported.

Analysis of hypocretin (orexin) antibodies in patients with narcolepsy.

STUDY OBJECTIVES: We tested the hypothesis that patients with narcolepsy have serum antibodies specific for preprohypocretin and its derivatives. DESIGN: We tested sera from strictly diagnosed HLA DQB1*0602-positive narcoleptic patients with cataplexy for evidence of autoantibodies against human preprohypocretin, hypocretin 1 and 2, N-terminal leader and C-terminal peptides of preprohypocretin using enzyme-linked immunosorbent assays (ELISA). These results were compared to samples from nonnarcoleptic psychiatric and sleep apnea controls. Laboratory personnel were blinded to subject status. SETTING: Narcoleptic patients and nonnarcoleptic controls were recruited from the Mayo Clinic facilities in Rochester, Minnesota; Scottsdale, Arizona; and Jacksonville, Florida. Laboratory testing was conducted in the Mayo Psychogenomic Laboratory at the Rochester Mayo Clinic. PARTICIPANTS: A sample of 34 narcoleptic patients and 49 nonnarcoleptic controls. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: ELISA measurements were in optical density. Primary analyses were of the entire narcoleptic and control groups for each potential antigen, and none of the differences reached P values required for significance after Bonferroni adjustment. Secondary analyses by age and sex yielded P values that were significant after Bonferroni adjustment in only 2 cases, but further statistical analyses cast doubt on the veracity of these differences. In all cases where a significant difference was recorded, the hypothesis was not supported because the control optical density reading was higher than the narcoleptic values. CONCLUSIONS: These ELISA assay results do not support the hypothesis that HLA DQB1*0602-positive narcolepsy with cataplexy is associated with serum antibodies against preprohypocretin or its cleavage products.

Psychological distress in patients with restless legs syndrome (Willis-Ekbom disease): a population-based door-to-door survey in rural Ecuador.

BACKGROUND: Reported prevalence of restless legs syndrome (RLS), also known as Willis-Ekbom disease (WED), varies from country to country, and methodologic inconsistencies limit comparison of data. Impact of RLS on quality of life and health has been studied primarily in industrialized countries, particularly Europe and the United States. Many studies have relied exclusively on self-report of symptoms or have assessed only medical populations. Recently, interest has emerged on the impact of WED in rural, underserved populations globally. METHODS: In a population-based survey conducted in rural Ecuador, we assessed the relationship of psychological distress to WED, evaluated with the Depression Anxiety Stress Scales-21. WED was diagnosed through a 2-phase method in which all residents were screened with the International Restless Legs Syndrome Study Group (IRLSSG) questionnaire and all suspected cases were subsequently confirmed through expert medical examination. WED severity was assessed with the IRLSSG rating scale. RESULTS: Of 665 persons (mean [SD] age, 59.5 [12.6] years; women, 386 [58%]), 76 had depression, 93 had anxiety, and 60 reported stress. Forty persons (6%) had WED, with 15 (38%) having severe disease. In a regression model adjusted for age and sex, the prevalence of depression, anxiety, and stress was about 3 times greater among persons with WED than the general population. CONCLUSIONS: Although cross-sectional data cannot establish causation, this study shows the large behavioral health burden associated with WED in an untreated, rural population.

Resolution of syncope with treatment of sleep apnea.

Sleep apnea is a common disorder associated with obesity and related health problems. Although treatment of sleep apnea may relieve some autonomic symptoms, it is currently unknown whether treatment of sleep apnea is specifically associated with the resolution of orthostatism and syncope. Herein we describe a 73-year-old man who had recurrent episodes of syncope. An extensive work-up, including cardiac and neurologic consultations, failed to identify the cause. An objective sleep evaluation led to the diagnosis of sleep apnea. Accordingly, the patient was treated with continuous positive airway pressure, which resolved the syncopal episodes. This case report generates a potentially important hypothesis that recurrent syncope may be effectively treated, in part, by correcting apnea. In patients with recurrent syncope of unknown etiology, a diagnosis of sleep apnea should be considered.

Expressive writing as a smoking cessation treatment adjunct for young adult smokers.

This investigation evaluated the efficacy of expressive writing as a treatment adjunct to a brief office smoking cessation intervention plus nicotine patch therapy in young adults. Participants aged 18-24 years were randomized to a brief office intervention (n=99) or to an expressive writing plus brief office intervention (n=97). Both conditions received four individual visits plus 6 weeks of nicotine patch therapy, which began on the quit date following the week 2 visit. Participants in the expressive writing plus brief intervention condition wrote for 2 consecutive days before and 3 consecutive days after the quit date. The brief office intervention group completed a control writing assignment. At end of treatment (week 8), biochemically confirmed 7-day point-prevalence abstinence for the expressive writing plus brief office intervention condition was significantly greater than for the brief office condition (33% vs. 20%, p=.043, OR=2.0, 95% CI=1.0-3.7, from a logistic regression adjusting for gender). At 24 and 52 weeks, abstinence rates were similar for the brief office intervention versus expressive writing plus brief office intervention (12% vs. 11% at 24 weeks; 11% vs. 11% at 52 weeks). The results suggest that expressive writing has promise as a smoking cessation treatment adjunct for young adults. Lengthier interventions or the use of boosters should be tested to extend treatment effects. However, participants reported a low level of enthusiasm for the expressive writing, which may be a barrier to implementing it over a longer time frame. Therefore, other modes of delivering expressive writing to young adult cigarette smokers should be explored.