A Cross-Sectional Examination of the Factors Related to Emergency Nurses' Motivation to Protect Themselves Against an Ebola Infection.

INTRODUCTION: The 2014-2016 West African Ebola outbreak impacted the United States. Owing to the sporadic occurrence of the Ebola infection, there is insufficient research regarding how US emergency nurses provide care to patients potentially infected with the Ebola virus and the nurses' motivation to protect themselves when providing care to these patients. This study aimed to investigate the predictors of emergency nurses' protection motivation. METHODS: A cross-sectional design was employed. A survey developed based on a modified Protection Motivation Theory was administered to randomly selected members of the Emergency Nurses Association. Descriptive statistics, nonparametric Kruskal-Wallis H test (as well as post hoc Dunn-Bonferroni test), Spearman rho correlation, and stepwise multiple linear regression were conducted for data analysis. RESULTS: Protection motivation was found in 2 components: proactive and passive protection motivation. Regression analysis indicated that response efficacy (ß = 0.27, P < 0.001) and self-efficacy (ß = 0.17, P < 0.01) significantly predict emergency nurses' proactive protection motivation, whereas perceived vulnerability (ß = 0.26, P < 0.001), response cost (ß = 0.19, P = 0.001), and knowledge (ß = -0.15, P < 0.01) significantly predict emergency nurses' passive protection motivation. DISCUSSION: The results indicate the need for interventions to improve emergency nurses' response efficacy, self-efficacy, and knowledge, while simultaneously reducing the nurses' perceived vulnerability and response cost. Such interventions would be expected to proactively motivate nurses to protect themselves when providing care to patients who exhibit the signs and symptoms of an Ebola infection and reduce their passive protection motivation.

Development of a Reliable and Valid Survey Instrument to Measure Nurses' Health Behaviors Towards an Infectious Disease.

Background and Purpose: The purpose of this study is to describe the process for developing a reliable and valid survey instrument guided by the protection motivation theory (PMT) to evaluate nurses' health behaviors toward an infectious disease such as Ebola. Methods: The instrument was developed and tested through a systematic process that included a literature review, focus group, validity testing, and reliability testing. Results: The outcome variable, protection motivation, contained two elements, determined by principal component analysis. The instrument's internal consistency had a Cronbach's alpha of .80 or greater. Conclusion: The development and testing of an instrument based on PMT constructs as the theoretical framework have demonstrated a relationship between the perceived threat toward the disease and the proposed coping process needed to address the disease.

Central and peripheral airway/alveolar sites of exhaled nitric oxide in acute asthma.

INTRODUCTION: Central airway nitric oxide flux (J'(awNO)) and peripheral airway/alveolar nitric oxide concentration (C(ANO)) during asthma exacerbation has not been investigated after correction for axial NO back-diffusion. METHODS: After measuring exhaled NO (fraction of exhaled nitric oxide (F(E)NO); ppb) at 50, 100, 150 and 200 ml/s, J'(awNO) (nl/s) and C(ANO) (ppb) were calculated using the two-compartment model and corrected for axial NO back-diffusion. Fifteen (8 males), non-smoking, patients with moderate-to-severe treated (inhaled corticosteroid (ICS) and inhaled long-acting beta(2)-agonist (LABA)) asthma, age 57+/-13 years (mean+/-SD), were studied at baseline, during exacerbation prior to oral corticosteroid, and during recovery after an 8 day tapering prednisone course. Based on earlier asthma studies without correction, it was hypothesised that with correction for NO axial back-diffusion, the incidence of abnormal J'(awNO) and C(ANO) at baseline and after exacerbation would be > or = 30% in 15 patients with asthma with 80% power. RESULTS: At baseline when clinically stable, after 180 microg of albuterol, forced expiratory volume in 1 s (FEV(1); litres) was 78+/-26% predicted (p=0.009) with increased F(E)NO at 50 ml/s (p=0.01) and J'(awNO) (p=0.02), but C(ANO) was normal compared with the controls. During exacerbation FEV(1) (litres) was 57+/-20% predicted (p=0.02), with increased F(E)NO at 50 ml/s (p=0.01) and J'(awNO) (p=0.004), but C(ANO) was normal. Recovery results were similar to baseline. Two of 15 patients with asthma always had normal exhaled NO gas exchange. CONCLUSIONS: The central airways were the major site of abnormal NO flux in 13 of 15 patients with moderate-severe asthma when stable and during exacerbation and could be easily detected with abnormal F(E)NO at 50 ml/s. C(ANO) was normal.

Nasal foreign bodies in children: kissing it better.

OBJECTIVE: To evaluate the use, success rate and time in the paediatric emergency department when employing the kissing technique to remove nasal foreign bodies from children. METHODS: The present work was a retrospective case note review for children attending with a nasal foreign body over a 15-month period. RESULTS: In all, 116 children had a confirmed nasal foreign body and 84 were treated by the kissing technique with a success rate of 48.8%. This group had lower rates of instrumentation (20.2% vs 53.1%) and general anaesthesia (11.9% vs 18.8%). The average time saved per patient who had the kissing technique attempted in the paediatric emergency department was 30.6 min. CONCLUSION: The kissing technique should be employed as a preferred technique to remove nasal foreign bodies in children.

Physician Assistant Students' Knowledge of Zika Virus: A Pilot Study.

OBJECTIVE: The aim of this study was to assess physician assistant students' knowledge about the screening, transmission, management, and prevention of Zika virus infection. BACKGROUND: It is important for health care providers in the United States to recognize the symptoms of Zika so that they can screen, diagnose, and or treat persons exposed to or infected by the virus. Physician assistant students, on completion of their educational program and passing their board examinations, provide care for patients in primary care or specialty settings where they may treat patients who either have the virus or post-virus exposure. METHODS: A convenience sample of 37 students enrolled in a physician assistant studies program in the Midwestern United States completed an in-person self-administered paper-and-pencil questionnaire that tested their knowledge about Zika virus infection. RESULTS: All the respondents knew that the disease is of viral origin; however, only 89% knew that mosquitoes were the natural host. Primary modes of transmission were identified as sexual contact and blood transfusion (47% and 44% of respondents respectively); 47% incorrectly identified amniotic fluid as a transmission mode. More than half (61%) knew that health care providers should ask pregnant women about any possible virus exposure before and during pregnancy at each prenatal visit. Most respondents knew that muscle/joint pain (67%) was one of the symptoms of Zika infection, but only 39%, 25%, and 19% also identified low-grade fever, maculopapular rash, and conjunctivitis respectively as other symptoms. Some participants incorrectly identified antivirals (44%) and nonsteroidal anti-inflammatory medications (36%) rather than the recommended treatments of pain relief (30%) and fever relief (42%) medications for clinical management of the disease.

Role of add-on zileuton on total exhaled, large airway, and small airway/alveolar nitric oxide in moderate-severe persistent adult asthmatics on fluticasone 250 microg/Salmeterol 50 microg.

BACKGROUND: Measuring non-invasive exhaled biomarkers of inflammation may be important in monitoring asthma therapy. OBJECTIVE: Evaluate exhaled nitric oxide with add-on leukotriene synthesis inhibitor in moderate-severe persistent asthmatics on combination controllers. METHODS: In a non-randomized, non-placebo, single-blind, fixed sequence, pilot study, we evaluated 22 non-smoking, stable, moderate-severe adult asthmatics on maintenance inhaled fluticasone 250 microg/salmeterol 50 microg (F/S) via MDI bid> or =1 yr, with add-on oral zileuton 600 mg qid. Exhaled fractional nitric oxide (FENO) gas exchange, large airway NO, small airway/alveolar NO concentration (CANO), Juniper score and lung function were measured. Asthmatics were studied at baseline only on F/S bid (visit 1), on F/S bid pre and 2 h post first dose zileuton 600 mg (visit 2), and post 4 weeks (visit 3) F/S bid plus zileuton 600 mg qid. Values were compared at each visit and to healthy non-smoking age matched healthy controls with normal lung function. RESULTS: Three asthmatics stopped zileuton prematurely (headache and/or nausea) and 19 (12F) age 55+/-17 yr (mean+/-SD) completed the 4-week study. Baseline forced expiratory lung volume in 1 sec (FEV(1)) was 1.6+/-0.7L (53+/-19% pred) (mean+/-SD), FEV(1) over FVC ratio was 64+/-11% and post 180 microg albuterol FEV(1) was 1.8+/-0.7L (56+/-21% pred), and FEV(1) over FVC ratio was 67+/-12%. Baseline Juniper scores were mild (10+/-10) and similar (p=ns) at all visits. Baseline FENO@50 mL/s was 48+/-27 ppb (mean+/-SD), and FENO@100 mL/s was 29+/-16ppb, and were similar (p=ns) at all visits. Large airway NO flux was 2.0+/-1.3 nL/s (52% asthmatics abnormal) and small airway/alveolar NO was 8.0+/-4.0 ppb (79% asthmatics abnormal) and were similar (p=ns) at all visits. Compared to baseline, post 26+/-6 days Zileuton, mean FEV(1) (L)% predicted increased 3.3% predicted (p=0.03), and FEV(1) over FVC ratio increased 2.2% (p=0.03). CONCLUSION: In stable, moderate-severe persistent adult asthmatics, large airway NO flux, small airway/alveolar CANO, and Juniper airway scores, were not significantly different on F/S bid vs F/S bid plus Zileuton for 4 weeks, despite significant small increase in FEV(1) over FVC ratio and FEV(1)% predicted.

Tiotropium induced bronchodilation and protection from dynamic hyperinflation is independent of extent of emphysema in COPD.

BACKGROUND: The magnitude of tiotropium (1) induced bronchodilation and (2) protection against dynamic hyperinflation in COPD phenotypes has not been studied. METHODS: We studied moderate to severe COPD patients with varying extent of emphysema as evaluated by high-resolution thin-section lung CT. Spirometry including inspiratory capacity (IC) was measured before and immediately after metronome paced hyperventilation (MPH) at 2 times resting respiratory rate for 20s to induce dynamic hyperinflation. Spirometry was obtained at baseline and pre- and 1.5h post-18 microg tiotropium via HandiHaler after 30 day tiotropium treatment period in a single blind, open label intervention. RESULTS: In 29 COPD patients (15M), age 70+/-9 years (mean+/-SD) with smoking history of 53+/-37 pack years, baseline forced expiratory volume in 1s (FEV(1)) post-180 microg albuterol MDI was 1.6+/-0.4 L (61+/-8% predicted) and FEV(1)/FVC 59+/-6%. Lung CT emphysema score (LCTES) was 23+/-20 (mean+/-SD) on a scale of 0-100 (none to most severe emphysema). After 30-day tiotropium, FEV(1) increased 101+/-124 mL (mean+/-SD) (p<0.001) and Spearman correlation (r)=-0.04, p=0.8 with LCTES; IC increased 163+/-232 mL (p<0.001), and r=-0.2, p=0.3 with LCTES. Results following MPH induced DH before and after 30-day tiotropium were significant (p<0.001) and similar: IC decreased 340+/-280 mL before and 337+/-270 mL after tiotropium, and r=-0.3, p=0.9 with LCTES. CONCLUSION: Tiotropium significantly increased FEV(1) (L) and inspiratory capacity in moderate-severe COPD, independent of extent of lung CT emphysema score. Despite bronchodilation and lower resting lung volume, tiotropium did not abbreviate induced dynamic hyperinflation, which was also independent of underlying emphysema.

Synchronous CEA and CABG in asymptomatic carotid artery stenosis: A case study.

In the United States, there were 213,700 coronary artery bypass grafting (CABG) surgeries and 102,700 carotid endarterectomies (CEA) in 2011. Combined CEA and CABG surgeries are lower than either CEA or CABG, with an estimated 1,370 surgeries in 2012. There is some literature which supports that the surgeries can be performed safely together (referred to as combined, synchronous, tandem, or concomitant procedures). The purpose of this article is to describe the merits and potential complications involved with undergoing synchronous carotid artery and coronary artery bypass procedures. This purpose will be addressed by examining a case study of a patient who completed a synchronous procedure and by also reviewing the literature which addresses the benefits versus the risks associated with the synchronous procedures. Some studies found an increased incidence of perioperative and postoperative risks such as stroke, myocardial infarction, and death with the combined procedures, whereas some studies found no difference in the risks when the operations were performed sequentially. Combined or synchronous coronary artery bypass and carotid artery endarterectomy may be a safe surgical option for a specific subset of patients.

Evaluation of Selective 5-HT2C Agonists in Acute Seizure Models.

The 5-HT releaser/reuptake inhibitor fenfluramine has been recently reported to provide benefit as an adjunctive treatment for Dravet and Lennox-Gastaut syndromes, two types of severe childhood epilepsy. Despite its enhancement of 5-HT function, many effects of fenfluramine have been demonstrated to be dependent on 5-HT2C receptor activation, suggesting that 5-HT2C receptor activation may have an anticonvulsant property. The present study was designed to evaluate fenfluramine and 5-HT agonists of varying 5-HT2C agonist selectivity, the relatively nonselective mCPP and Ro 60-0175, and the selective 5-HT2C agonists lorcaserin and CP-809101 across a variety of acute seizure tests conducted in adult rats and mice, which have been instrumental in identifying the majority of clinically efficacious antiepileptic drugs. Tests included the maximal electroshock seizure (MES), MES threshold, and 6 Hz electrical convulsive seizure models and the chemoconvulsant pentylenetetrazole test. The effect of mCPP, lorcaserin, and CP-809101 against electrically evoked seizures in amygdala kindled rats was also investigated. Overall, at doses known to interact with 5-HT2CR, there was no clear class-related effect of these agonists in any test. The only notable antiseizure effect of fenfluramine was inhibition of MES-induced tonic seizures in the rat. The current preclinical studies using the classical acute seizure tests and an amygdala kindling model do not identify a reliable antiseizure effect of fenfluramine, an agent now used in the treatment of human epilepsies, including Dravet syndrome and Lennox-Gastaut syndrome. Given the nature of these epilepsies, early life and/or genetic models may have better construct validity and be more appropriate for further study.

Effect of fluticasone 250 microg/salmeterol 50 microg and montelukast on exhaled nitric oxide in asthmatic patients.

BACKGROUND: Monitoring noninvasive biomarkers of inflammation is an important adjunct in asthma therapy. OBJECTIVE: The goal of the present study was to identify airway and alveolar site(s) of inflammation using exhaled nitric oxide (NO) as a marker in asthmatic patients, and to evaluate the NO response to maintenance fluticasone 250 microg/salmeterol 50 microg (F/S) and add-on montelukast 10 mg (M). METHODS: Thirty (24 women) nonsmoking, mild to moderate asthmatic patients were studied, mean age (+/- SD) 43+/-9 years, treated with F/S for more than one year. All were clinically stable for longer than eight weeks and had not taken oral corticosteroids and/or leukotriene antagonists for eight weeks before the present study. Spirometry, Juniper asthma symptom score, fractional exhaled NO (FENO) 100 mL/s, bronchial NO and alveolar NO concentration (CANO) were measured in a single-blind, nonrandomized crossover study. PROTOCOL: Visit 1: baseline F/S; visit 2: after four weeks of F/S plus M; visit 3: after four weeks of S plus M; and visit 4: after four weeks of S only. Values in asthmatic patients were also compared with 34 nonsmoking age-matched healthy controls with normal lung function. RESULTS: After 180 microg aerosolized metered dose inhaler albuterol, the forced expiratory volume in 1 s at baseline was 2.6+/-0.8 L (86%+/-16% of the predicted value) and the forced expiratory volume in 1 s over the forced vital capacity was 77%+/-9% (mean +/- SD), and was similar at visits 2 to 4. Juniper scores were mildly abnormal at visits 1 to 3, but significantly worse (P=0.03) at visit 4 versus visits 1 to 3. FENO values at visits 1 to 3 were similar but significantly increased (P=0.007) at visit 4. Bronchial NO was higher (P=0.03) at visit 4, versus visits 1 and 2, and was no different at visit 3. Compared with the healthy subjects, FENO and bronchial NO values were abnormal (greater than the normal mean plus 2 SD) in 33% of asthmatic patients at visits 1 to 3. CANO was similar for visits 1 to 4. CANO was abnormal (greater than the normal mean + 2 SD) in 20% of asthmatic patients. CONCLUSION: In clinically stable asthmatic patients, despite controller treatment including moderate-dose inhaled corticosteroids and add-on M, 33% of mild to moderate asthmatic patients have ongoing nonsuppressed bronchial sites of increased NO production, compared with healthy control subjects. These controllers have no effect on CANO, which was abnormal in 20% of the asthmatic patients studied. The addition of add-on M to baseline moderate-dose inhaled corticosteroid did not further reduce total exhaled, bronchial and/or alveolar NO production.

Army health care operations in Iraq.

Four years of warfare in the urban environment of Iraq have produced fundamental changes in the Army's health-care system. First, improved communications and air evacuation have streamlined the transport of the wounded soldierfrom the battlefield to stateside medical centers. Second, individual ballistic armor has decreased the number of U.S. troops killed while the number of wounded soldiers has increased. Third, battling an unseen enemy has produced a marked increase in acute stress disorder, post-traumatic stress disorder and traumatic brain injury. Deployment of soldiers with chronic mental health disorders such as anxiety, attention deficit disorder, and depression is problematic. The stress of long combat tours has doubled the incidence of abuse and neglect in children of deployed service members. Comparedto active-componentsoldiers, the prevalence ofmental health disorders is twice as great in soldiers of the Army Reserve and Army National Guard. Finally, the difficulty in determining friend vs. foe in Iraq results in the incarceration of thousands of Iraqis creating both medical and ethical challenges for Army physicians.

Tiotropium and simplified detection of dynamic hyperinflation.

STUDY OBJECTIVE: To detect dynamic hyperinflation (DH) by evaluating reduction in inspiratory capacity (IC) during metronome-paced hyperventilation (MPH) in patients with moderate-to-severe COPD, studied before and after treatment with tiotropium. METHODS: IC and FEV(1) were measured before and immediately after MPH at two times resting the respiratory rate for 20 s in 60 COPD patients (28 men; mean age, 66 +/- 10 years [+/- SD]) before and after 30 days of treatment with tiotropium bromide, 18 mug. Patients were encouraged to maintain a constant tidal volume during MPH. RESULTS: At baseline, mean FEV(1) was 1.5 +/- 0.1 L (+/- SE) [57 +/- 1.6% of predicted], mean FVC was 2.6 +/- 0.1L (77 +/- 1.8% of predicted), and mean FEV(1)/FVC was 56 +/- 1%. After 180 mug of aerosolized albuterol sulfate, mean FEV(1) was 1.7 +/- 0.1 L (63 +/- 1.5% of predicted) [p < 0.001] and mean FEV(1)/FVC was 58 +/- 1%. Compared to baseline, after 30 days and 1.5 h after tiotropium there was an increase in IC of 0.18 +/- 0.04L (p < 0.0001); FEV(1) of 0.13 +/- 0.03 L (5.6 +/- 0.8% of predicted; p = 0.0002); FVC of 0.22 +/- 0.05 L (6.5 +/- 1.3% of predicted; p < 0.001); and decrease in end-expiratory lung volume (EELV)/total lung capacity (TLC) of - 3.1 +/- 0.6% (p = 0.0001); a decrease in end-inspiratory lung volume (EILV)/TLC of - 2.9 +/- 1.3% (p = 0.03); and no change in TLC (- 0.06 +/- 0.05 L). Results following MPH-induced DH at baseline and after 30 days of tiotropium were similar, with decreases in IC (- 0.35 +/- 0.03 L; p < 0.001); FEV(1) (- 0.05 +/- 0.04 L; p = 0.2); and FVC (- 0.22 +/- 0.03 L; p < 0.0001); no change in TLC; and increases in EELV/TLC (11.8 +/- 1.0% of predicted; p < 0.0001) and EILV/TLC (4.0 +/- 1.3% of predicted, p < 0.003). CONCLUSION: In patients with moderate-to-severe COPD, tiotropium did not reduce MPH-induced DH and reduction in IC, compared to baseline. However, because tiotropium induced bronchodilation and increased baseline IC, lower operational lung volumes may blunt the effect of MPH-induced DH. The noninvasive simplicity of MPH-induced DH provides a clinically useful screening surrogate to monitor changes in IC following treatment with tiotropium.

Predictors of Nurses' Intentions to Administer As-Needed Opioid Analgesics for Pain Relief to Postoperative Orthopaedic Patients in the Acute Care Setting.

BACKGROUND: Patients undergoing orthopaedic surgery experience severe postoperative pain that is frequently undertreated. No study was found that examined the predictors of nurses' intentions to administer as needed (PRN) opioid analgesics for postoperative pain relief. PURPOSE: The purpose of this study was to determine what constructs from the Integrated Behavioral Model (IBM) can predict nurses' intentions to administer PRN opioid analgesics for pain relief to hospitalized postoperative orthopaedic patients. METHODS: A nonexperimental, cross-sectional quantitative format was used. The sample consisted of 800 nurses. Data collection was done by survey. RESULTS: Path analysis revealed the significant predictors of nurses' intention to administer opioid analgesics to be self-efficacy (ß= 0.15), normative beliefs (ß= 0.21), and salience (importance) of the behavior (ß= 0.25). CONCLUSION: The study showed that the IBM constructs are useful for predicting intentions toward performance of a professional behavior. The inclusion of self-efficacy, underlying beliefs, and salience of the behavior was new and unique contributions to the existing body of knowledge.

Role of spirometry and exhaled nitric oxide to predict exacerbations in treated asthmatics.

OBJECTIVE: To evaluate the complementary roles of exhaled nitric oxide (NO) and spirometry to predict asthma exacerbations requiring one or more tapering courses of systemic corticosteroids. METHODS: We prospectively studied 44 nonsmoking asthmatics (24 women) aged 51 +/- 21 years (mean +/- SD) who were clinically stable for 6 weeks and receiving 250 mug of fluticasone/50 mug of salmeterol or equivalent for 3 years. Total exhaled NO (FENO), small airway/alveolar NO (CANO), large airway NO flux (J'awNO), and spirometry were measured. RESULTS: Baseline FEV(1) was 2.1 +/- 0.7 L, 70 +/- 20% of predicted after 180 mug of albuterol. Twenty-two of 44 asthmatics had one or more exacerbations over 18 months, 16 of 22 asthmatics had two exacerbations, and 6 of 22 asthmatics were hospitalized, including 1 asthmatic with near-fatal asthma. When baseline FEV(1) was 76% of predicted, exacerbations occurred only in 2 of 13 asthmatics (15%) [p = 0.003, chi(2)]. Using a receiver operating characteristic (ROC) curve for first exacerbation, the area under the curve was 0.67 with cutoff FEV(1) of 76% of predicted (sensitivity, 0.91; specificity, 0.50; positive predictive value, 0.65; negative predictive value, 0.85; positive likelihood ratio [LR(+)], 1.8; negative likelihood ratio [LR(-)], 0.18). When baseline FENO was >/= 28 parts per billion (ppb), exacerbations occurred in 13 of 17 asthmatics (76%); if baseline FENO was < 28 ppb, exacerbations occurred in only 9 of 27 asthmatics (33%) [p = 0.005, chi(2)]. Using the ROC curve for first exacerbation, the area under the curve was 0.71 with FENO cutoff point of 28 ppb (sensitivity, 0.59; specificity, 0.82; positive predictive value, 0.77; negative predictive value, 0.87; LR(+), 3.3; LR(-), 0.5). Independent of baseline FEV(1), FENO >/= 28 ppb increased the relative risk (RR) for exacerbation by 3.4 (95% confidence interval [CI], 1.3 to 9.1; Mantel-Haenszel, p = 0.007). An abnormal increase in CANO increased RR by 3.0 (95% CI, 0.9 to 9.9; p = 0.04), and abnormal J'awNO increased RR by 2.4 (95% CI, 1.0 to 5.6; p = 0.04). Independent of baseline FENO, FEV(1) /= 28 ppb and FEV(1) 76% of predicted had a 0% probability of exacerbation. CONCLUSION: Combining FENO and FEV(1) percentage of predicted can stratify risk for asthma exacerbation.

Atrial tachycardias arising from the atrial appendages and aortic sinus of valsalva.

Focal atrial tachycardias arising from the atrial appendages and the aortic sinuses of Valsalva are less frequently encountered in clinical practice. This review article describes the clinical presentation, surface P wave morphology, electrophysiologic characteristics and treatment of these arrhythmias. Catheter ablation of these focal tachycardias has a high success rate. It is however important to be aware of specific anatomic considerations in these locations for optimal treatment outcomes with low complication rates.

Simplified detection of dynamic hyperinflation.

STUDY OBJECTIVE: To detect dynamic hyperinflation by comparing reduction in inspiratory capacity (IC) during both paced hyperventilation and cycle ergometry in patients with moderate-to-severe COPD, studied before and after acute bronchodilation. METHODS: IC and FEV(1) were measured before and after metronome-paced hyperventilation at twice the resting respiratory rate for 20 s in 16 patients with COPD before and after 54 microg aerosolized ipratropium bromide (IB). We also studied the same 16 patients before and after administration of 54 microg aerosolized IB during symptom-limited incremental cycle ergometry when the final respiratory rate was also twice the resting rate. RESULTS: Resting IC was 2.23 +/- 0.53 L (mean +/- SD), and the mean decrease in IC from baseline was 0.36 +/- 0.25 L after exercise (p < 0.001), and not significantly different (p = 0.64) from mean decrease in IC of 0.40 +/- 0.29 L following hyperventilation. Results following hyperventilation and exercise were similar after bronchodilator. The mean difference for decrease of IC between hyperventilation and exercise was 0.138 L (95% confidence interval, - 0.347 to 0.622; r = 0.66, p = 0.006). The decrease in FEV(1) was 0.01 +/- 0.13 L after exercise and 0.06 +/- 0.18 L after hyperventilation. Separately, baseline and peak end-expiratory and end-inspiratory lung volumes were similar with hyperventilation vs exercise both before and after bronchodilator. CONCLUSION: Both metronome-paced hyperventilation and incremental cycle ergometry, when resting respiratory rate was doubled, provoked similar significant decrease in IC, even after administration of 54 microg aerosolized IB. The noninvasive simplicity of hyperventilation for 20 s provides a clinically useful screening surrogate to monitor changes in IC following exercise.

Development of glucose intolerance in male transgenic mice overexpressing human glycogen synthase kinase-3beta on a muscle-specific promoter.

Glycogen synthase kinase-3 (GSK-3) protein levels and activity are elevated in skeletal muscle in type 2 diabetes, and inversely correlated with both glycogen synthase activity and insulin-stimulated glucose disposal. To explore this relationship, we have produced transgenic mice that overexpress human GSK-3beta in skeletal muscle. GSK-3beta transgenic mice were heavier, by up to 20% (P < .001), than their age-matched controls due to an increase in fat mass. The male GSK-3beta transgenic mice had significantly raised plasma insulin levels and by 24 weeks of age became glucose-intolerant as determined by a 50% increase in the area under their oral glucose tolerance curve (P < .001). They were also hyperlipidemic with significantly raised serum cholesterol (+90%), nonesterified fatty acids (NEFAs) (+55%), and triglycerides (+170%). At 29 weeks of age, GSK-3beta protein levels were 5-fold higher, and glycogen synthase activation (-27%), glycogen levels (-58%) and insulin receptor substrate-1 (IRS-1) protein levels (-67%) were significantly reduced in skeletal muscle. Hepatic glycogen levels were significantly increased 4-fold. Female GSK-3beta transgenic mice did not develop glucose intolerance despite 7-fold overexpression of GSK-3beta protein and a 20% reduction in glycogen synthase activation in skeletal muscle. However, plasma NEFAs and muscle IRS-1 protein levels were unchanged in females. We conclude that overexpression of human GSK-3beta in skeletal muscle of male mice resulted in impaired glucose tolerance despite raised insulin levels, consistent with the possibility that elevated levels of GSK-3 in type 2 diabetes are partly responsible for insulin resistance.

Anorectic, thermogenic and anti-obesity activity of a selective orexin-1 receptor antagonist in ob/ob mice.

A single dose of the orexin-1 (OX1) receptor antagonist 1-(2-methylbenzoxazol-6-yl)-3-[1,5] naphthyridin-4-yl urea hydrochloride (SB-334867-A) reduces orexin-A-induced feeding and natural feeding in Sprague Dawley rats. In this study, the anti-obesity effects of SB-334867-A were determined in genetically obese (ob/ob) mice dosed with SB-334867-A (30 mg/kg, i.p.) once daily for 7 days, and then twice daily for a further 7 days. SB-334867-A reduced cumulative food intake and body weight gain over 14 days. Total fat mass gain, determined by Dual Emission X-ray Absorptiometry, was reduced, while gain in fat-free mass was unchanged. Fasting (5 h) blood glucose was also reduced at the end of the study, with a trend to reduced plasma insulin. Interscapular brown adipose tissue (BAT) weight was reduced, the tissue was noticeably darker in colour and quantitative PCR (TaqMan) analysis of this tissue showed a trend to an increase in uncoupling protein-1 mRNA expression, suggesting that SB-334867-A might stimulate thermogenesis. This was confirmed in a separate study in which a single dose of SB-334867-A (30 mg/kg, i.p.) increased metabolic rate over 4 h in ob/ob mice. OX1 receptor mRNA was detected in BAT, and its expression was increased by 58% by treatment with SB-334867-A. This is the first demonstration that OX1 receptor antagonists have potential as both anti-obesity and anti-diabetic agents.