Eight-month repellency and efficacy of an imidacloprid/flumethrin (Seresto® ) collar against the eastern paralysis tick (Ixodes holocyclus) on cats.

OBJECTIVE: The objective of this study was to determine the repellency and efficacy of a 10% imidacloprid/4.5% flumethrin (Seresto® , Elanco) collar over an 8-month period against the eastern paralysis tick (Ixodes holocyclus) on cats. METHODS: Two non-blinded, open gender, randomised, placebo-controlled pen studies were conducted, with 26 cats enrolled in each study. Prior to inclusion, cats were immunised with I. holocyclus holocyclotoxin. Cats were treated on Day 0 with either an imidacloprid/flumethrin or placebo collar. Tick infestations with 20 unfed adult female eastern paralysis ticks commenced on Day 7, and were repeated monthly for 8 months. Repellency was determined by comparing the mean number of attached ticks on imidacloprid/flumethrin treated cats, to placebo collar treated cats at 6 and 24 h post infestation. Efficacy was determined by comparing the mean number of live ticks on imidacloprid/flumethrin collar treated cats to placebo collar treated cats at 72 h post infestation. RESULTS: Efficacy was 100% (P < 0.001) at 72 h, and repellency was greater than 96% (P < 0.001) at 24 h for every tick challenge in each of the two studies, from Day 7 to the final infestation at 8 months for imidacloprid/flumethrin collar treated cats. CONCLUSIONS: In two pen studies, an imidacloprid/flumethrin collar controlled and repelled the eastern paralysis tick (I. holocyclus) on cats for 8-months. The marked repellency effect in addition to controlling tick paralysis would be beneficial in preventing tick bites and their sequelae.

Dark Matter Search Results from the PICO-2L C3F8 Bubble Chamber.

New data are reported from the operation of a 2 liter C3F8 bubble chamber in the SNOLAB underground laboratory, with a total exposure of 211.5 kg days at four different energy thresholds below 10 keV. These data show that C3F8 provides excellent electron-recoil and alpha rejection capabilities at very low thresholds. The chamber exhibits an electron-recoil sensitivity of <3.5×10(-10) and an alpha rejection factor of >98.2%. These data also include the first observation of a dependence of acoustic signal on alpha energy. Twelve single nuclear recoil event candidates were observed during the run. The candidate events exhibit timing characteristics that are not consistent with the hypothesis of a uniform time distribution, and no evidence for a dark matter signal is claimed. These data provide the most sensitive direct detection constraints on WIMP-proton spin-dependent scattering to date, with significant sensitivity at low WIMP masses for spin-independent WIMP-nucleon scattering.

Cost-free and sustainable incentive increases healthy eating decisions during elementary school lunch.

We aimed to develop a cost-free and sustainable program to influence healthier eating decisions during elementary school lunch. Baseline food and beverage choices were assessed for 9 days during lunch service at two racially and economically diverse elementary schools in Spartanburg County, SC, USA. After being informed that the labeled items on the daily lunch menu represented the healthiest choice, students were allowed to ring a call bell in the cafeteria for public recognition when they chose all of the identified healthiest food and beverage items during lunch service. Using menus matched to the baseline phase, food and beverage choices were measured during a 9-day intervention phase. After 30 days, food and beverage choices were reassessed during a 3-day follow-up phase. Healthiest food & beverage choices increased 49% with >60% of students choosing non-flavored milk over flavored milk during the intervention phase. There was no difference in the success of the program between the two schools. The program continued and healthy eating decisions were significantly sustained at a 30-day follow-up assessment. Public recognition through bell ringing appears to be an effective practice to sustain increases in healthy eating decisions during elementary school lunch and warrants expansion to larger scale, longitudinal trials.

Measurement of the ßß decay half-life of 130Te with the NEMO-3 detector.

We report results from the NEMO-3 experiment based on an exposure of 1275 days with 661 g of (130)Te in the form of enriched and natural tellurium foils. The ßß decay rate of (130)Te is found to be greater than zero with a significance of 7.7 standard deviations and the half-life is measured to be T(½)(2ν) = [7.0 ± 0.9(stat) ± 1.1(syst)] × 10(20) yr. This represents the most precise measurement of this half-life yet published and the first real-time observation of this decay.

Supervised step-down of inhaled corticosteroids in the community--an observational study.

INTRODUCTION: Current asthma guidelines recommend step-down of inhaled corticosteroids (ICS) to the minimum dose required for control of symptoms. AIM: To determine if supervised step-down of (ICS) in the community has any effect on asthmatic inflammation. METHODS: 119 Community based asthmatics underwent progressive step-down of therapy until they became unstable or reached an (ICS) dose of ≤200 µg beclomethasone dipropionate (BDP) or equivalent. Once unstable, participants stepped back up to the last stable dose of ICS. Exhaled nitric oxide (NO) and mannitol challenge were performed at the start and end of step-down. Asthma Quality of Life Questionnaire (AQLQ) and spirometry were recorded at each step-down visit. RESULTS: The median (interquartile range) BDP equivalent dose was significantly higher pre vs. post step-down: 400 µg (400-800) and 250 µg (200-400) per day respectively (P < 0.05). Examination of change in PD(10) in individual patients revealed that 34% had an improvement (>+1 dd), 47% had no change (±-1 dd), and 19% had a worsening (<-1 dd). The geometric mean fold ratio in NO for pre vs. post was 0.96 (95% CI 0.87 to 1.06, P = 0.43). Mean (SEM) values for FEV(1) were 86.2% (1.51) vs. 84.5% (1.46) (P = 0.04). There was a significant improvement in AQLQ. CONCLUSIONS: We have demonstrated that a significant reduction in ICS dose may be achieved in a community setting without any worsening of airways inflammation or lung function, and with an associated improvement quality of life in the majority of patients. This apparent disconnect may reflect enhanced adherence due to supervision of step-down.

Diagnosis of fetal ductus arteriosus aneurysm: importance of the three-vessel view.

OBJECTIVE: To present four cases of ductus arteriosus aneurysm (DAA) detected by fetal echocardiography and highlight the value of the three-vessel view in the diagnosis of DAA. METHODS: In addition to the standard fetal echocardiographic views, we examined the three-vessel view in four cases of DAA. The three-vessel view was achieved by sliding the transducer cranially from the four-chamber plane toward the fetal upper mediastinum to demonstrate cross-sections of the main pulmonary artery, the ascending aorta and superior vena cava arranged in a straight line from the left anterior to the right posterior aspect of the mediastinum. DAA was diagnosed when there was a tortuous ductus arteriosus with a dilation that protruded leftward of the aortic arch. CASE SERIES: In the first case, an insulin-dependent diabetic woman underwent fetal ultrasound examination at 36 weeks' gestation showing right-to-left cardiac disproportion and bidirectional flow in the aorta and main pulmonary artery (PA). The three-vessel view showed a dilated ductus arteriosus (DA) which was stenosed at its distal end. In the second case, a woman had fetal ultrasound scans at 38 and 39 weeks' gestation for suspected intrauterine growth restriction and oligohydramnios. The scans identified an abnormal aortic arch and the three-vessel view showed an elongated vascular structure at the distal end of the PA, which was the DAA. In the third case, a woman with a high-risk obstetric history had multiple scans showing an abnormal PA to aorta relationship, with an apparent 'kink' in the PA. The three-vessel view clarified that this was the DAA. In the fourth case, a woman was scanned because of a 3-kg weight gain in 1 week. The fetal ultrasound scan showed moderate polyhydramnios with normal fetal growth and normal intracardiac anatomy and flow, and the three-vessel view demonstrated a large DA. In each of these cases, the DAA appeared to have occurred in isolation with non-specific clinical findings. CONCLUSION: We advocate the use of the three-vessel view, in conjunction with the standard echocardiography views currently employed, to assist in the diagnosis of DAA.

Cross tolerance to salbutamol occurs independently of beta2 adrenoceptor genotype-16 in asthmatic patients receiving regular formoterol or salmeterol.

BACKGROUND: The development of tolerance following the use of long acting beta(2) agonists in asthmatic patients with either the homozygous arginine (Arg-16) or glycine (Gly-16) genotypes is poorly documented, especially in relation to the acute reliever response to salbutamol in constricted airways. A study was undertaken to evaluate the Arg-16 and Gly-16 genotypes for the acute salbutamol response following methacholine bronchial challenge between the first and last doses of formoterol (FM) and salmeterol (SM) combination inhalers. METHODS: Parallel groups of 10 matched homozygous Arg-16 and 10 homozygous Gly-16 patients completed a randomised, double blind, double dummy, crossover study. Following a 1 week washout period, patients received treatment for 2 weeks with either inhaled budesonide (BUD) 200 micro g + FM 6 micro g (two puffs twice daily) or inhaled fluticasone propionate (FP) 250 micro g + SM 50 micro g (one puff twice daily). After washouts and randomised treatments (1 hour after the first and last inhalation) a methacholine challenge was performed followed by salbutamol 200 micro g, with recovery over 30 minutes (the primary outcome). RESULTS: Washout values for forced expiratory volume in 1 second (FEV(1)), methacholine hyperreactivity, and salbutamol recovery were similar for both treatments and genotypes. Pre-challenge FEV(1) values for both genotypes did not differ significantly between the first and last doses of each treatment. Salbutamol recovery as mean (SE) area under the 30 minute time-response curve was significantly delayed (p<0.05) equally in both genotype and treatment groups. There were no differences in salbutamol recovery in either genotype or treatment group. CONCLUSION: Acute salbutamol recovery in methacholine constricted airways was significantly delayed to a similar degree in both genotypes due to cross tolerance induced by FM or SM.

Allergen sensitization and bronchial hyper-responsiveness to adenosine monophosphate in asthmatic patients.

BACKGROUND: Indirect bronchoprovocation using adenosine monophosphate (AMP) is related to atopic phenotype expression. OBJECTIVE: To evaluate the putative relationship between skin prick allergen sensitization and bronchial hyper-responsiveness to AMP in a retrospective cross-sectional database analysis. METHODS: We retrospectively evaluated two groups of non-smoking asthmatics (forced expiratory volume in 1 s (FEV)1>/=60% predicted) who were reactive (responders) or unreactive (controls) to inhaled AMP. The main outcome measure was the difference in sensitization to individual allergens and the total atopic load according to the presence or absence of bronchial hyper-responsiveness. RESULTS: We initially identified 180 (44%) non-smoking asthmatics with PC20/=1600 mg/mL. For those who had a skin prick test, the responders (n=151) and controls (n=151) were found to be matched for age, sex, inhaled corticosteroid dose and number of patients using inhaled corticosteroids. There were significant differences in the number of responders vs. controls in terms of sensitization to house dust mite (77% vs. 62%, P=0.004), aspergillus (19% vs. 9%, P=0.014), cat (61% vs. 48%, P=0.028), total atopic load (493 vs. 380 positive tests, P<0.001) and forced mid-expiratory flow (60% vs. 68% predicted, P<0.001). CONCLUSION: Sensitization to common aeroallergens increased the likelihood of bronchial inflammation as reflected by bronchial hyper-responsiveness to inhaled AMP, independently of both FEV1 or inhaled corticosteroid use. This in turn suggests an association between allergen exposure and AMP responsiveness in asthmatics. Further prospective long-term evaluation is indicated to assess whether allergen avoidance strategies can modify the airway response.

Butterbur, a herbal remedy, attenuates adenosine monophosphate induced nasal responsiveness in seasonal allergic rhinitis.

BACKGROUND: Butterbur (BB) or Petasites hybridus, a herbal remedy, exhibits in vitro inhibition of cysteinyl leukotriene biosynthesis. However, no placebo-controlled studies have been performed to evaluate the effectiveness of BB on objective outcomes such as nasal provocation testing in seasonal allergic rhinitis (SAR). METHODS: Twenty patients with grass-pollen-sensitized SAR were randomized in a double-blind, cross-over manner to receive for 2 weeks either BB 50 mg twice daily or placebo (PL) twice daily during the grass pollen season. Nasal adenosine monophosphate (AMP) challenge (the primary outcome) was administered as a single 400 mg/mL dose after each randomized treatment. RESULTS: Spontaneous recovery following AMP challenge (area under the response time profile curve as % x min+/-SEM) was significantly attenuated (P=0.028) with BB (584+/-289) compared to PL (1438+/-240); mean difference: 854 (95% CI 95-1614), and the maximum % peak nasal inspiratory flow reduction from baseline following AMP challenge was significantly blunted (P=0.036) with BB (30+/-4) compared to PL (43+/-5); mean difference: 13 (95% CI 1-25). CONCLUSIONS: BB exhibited protection against AMP-induced nasal responsiveness during the grass pollen season in sensitized patients. This is turn may explain its potential clinical efficacy in patients with SAR.

Airway-stabilizing effect of long-acting beta2-agonists as add-on therapy to inhaled corticosteroids.

BACKGROUND: The protection afforded by long-acting beta(2)-agonists against bronchoconstrictor stimuli can be regarded as a surrogate for their stabilizing effects on airway smooth muscle. AIM: To determine the magnitude of residual bronchoprotection after chronic dosing with long-acting beta(2)-agonists. DESIGN: Retrospective meta-analysis. METHODS: Medline, BIDS and Cochrane Library databases were searched from 1990. A meta-analysis was then performed of 13 eligible randomized placebo-controlled trials (596 patients) in which second-line treatment with a long-acting beta(2)-agonist (salmeterol or formoterol) was used for 1 week or more. The residual protection against bronchoconstrictor stimuli as doubling dose/dilution shift was the main outcome measure. RESULTS: Data were assessed according to Quorum criteria. Combining the results of the meta-analysis, the overall estimated protection amounted to a 0.79 (95%CI 0.63-0.96) doubling dose/dilution shift from placebo. Subgroup analysis showed greater protection at peak vs. trough, but no difference between formoterol vs. salmeterol, or between direct vs. indirect challenge. There was no evidence of significant heterogeneity across all the studies, or within any of the subgroups. DISCUSSION: When used as second-line treatment, the overall additive protective effect of long-acting beta(2)-agonists amounts to a 0.8 doubling dose/dilution shift. This stabilizing effect on airway smooth muscle may explain their beneficial effects on exacerbations.

A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke.

BACKGROUND: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. METHODS: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. RESULTS: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke (1237 patients had had previous small-vessel or lacunar infarcts, 576 had had cryptogenic infarcts, and 259 had had infarcts designated as due to severe stenosis or occlusion of a large artery). CONCLUSIONS: Over two years, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives.

Safety of inhaled and intranasal corticosteroids: lessons for the new millennium.

Although inhaled and intranasal corticosteroids are first-line therapy for asthma and allergic rhinitis, there has recently been an increasing awareness of their propensity to produce systemic adverse effects. The availability of more potent and lipophilic corticosteroids and new chlorofluorocarbon (CFC)-free formulations has focused attention on these safety issues. The main determinant of systemic bioavailability of these drugs is direct absorption from the lung or nose, where there is no first-pass inactivation. Consequently, the systemic bioavailability of inhaled corticosteroids is greatly influenced by the efficiency of the inhaler device. Thus, when comparing different inhaled corticosteroids it is imperative to consider the unique drug/device interaction. The pharmacokinetic profile is important in determining the systemic bioactivity of inhaled and intranasal corticosteroids. For highly lipophilic drugs, such as fluticasone propionate or mometasone furoate, there is preferential partitioning into the systemic tissue compartment, and consequently a large volume of distribution at steady state. In contrast, drugs with lower lipophilicity, such as triamcinolone acetonide or budesonide, have a smaller volume of distribution. The systemic tissue compartment may act as a slow release reservoir, resulting in a long elimination half-life for the lipophilic drugs. For intranasal corticosteroids, a high degree of lipophilicity diminishes water solubility in mucosa and therefore increases the amount of drug swept away by mucociliary clearance before it can gain access to tissue receptor sites. This may reduce the anti-inflammatory efficacy in the nose, but might also reduce the propensity for direct systemic absorption from the nasal cavity. The hydrofluoroalkane (HFA) formulations of beclomethasone dipropionate are solutions and exhibit a much higher respirable fine particle dose than do the CFC formulations. Dose-response studies with one of the HFA formulations have shown therapeutic equivalence at half the dosage, with little evidence of adrenal suppression at dosages up to 800 microg/day. A lack of similar studies for another of the available HFA formulations has led to a discrepancy in the recommendations for equivalence. Although in vitro studies have pointed to a similar fine particle distribution for the HFA and CFC formulations of fluticasone propionate, this is not supported by in vivo data for lung bioavailability, suggesting that care will be required when switching these formulations. Prescribers of inhaled and intranasal corticosteroids should be aware of the potential for long term systemic effects. The safest way to use these drugs is to 'step-down' to achieve the lowest possible effective maintenance dosage.

Frequency of pulmonary hemosiderosis in Eastern North Carolina.

Pulmonary hemosiderosis has been attributed to airborne fungi in water-damaged homes in studies of a cluster of cases in infants and children in Cleveland, Ohio, in 1997. We have searched for such emerging infectious agents in the Coastal Plain of North Carolina, which is subject to intermittent flooding. Pulmonary tissue from 206 infants and young children whose deaths had been investigated from October 1978 to September 1996 was retained at East Carolina University School of Medicine. Ages ranged from premature newborns to 49-months. One hundred and ten deaths were attributed to sudden infant death syndrome (SIDS). New sections were cut and analyzed using hematoxylin and eosin, Prussian blue for iron, and Gomori methenamine silver for fungal organisms. Twenty-three infants and children had iron-containing macrophages. Sixteen of these had underlying illnesses, but 4 were originally diagnosed as SIDS. Only one of these had sufficient hemosiderosis to be considered as having pulmonary hemosiderosis and no fungi were present. One case without iron had fungi and was not originally diagnosed as SIDS. The single case of pulmonary hemosiderosis found in this rural area is not similar to the cluster in Cleveland. The study identifies no fungal organisms as emerging infectious diseases in this area.

Consequences of the non-specific binding of a protein to a linear polymer: reconciliation of stoichiometric and equilibrium titration data for the thrombin-heparin interaction.

Theoretical aspects of the thermodynamic characterization of cooperative protein interactions with non-specific segments of a linear polymer lattice have been re-examined. This reconsideration has not only provided an alternative derivation of recursive expressions for the stoichiometry of random ligand binding prior to elimination of the parking problem but also extended that treatment to include binding with overlap of additional lattice units. The major obstacle to thermodynamic characterization of non-specific protein-polymer interactions is determination of the lattice capacity for ligand, which in turn defines the length of the polymer segment to which the protein binds. Although these parameters are most readily obtained from studies under conditions that ensure essentially stoichiometric interaction, the endpoint of such a titration is likely to reflect the irreversible rather than the equilibrium binding capacity of the lattice for ligand. Consideration of published results for spectrofluorometric titrations of the thrombin-heparin system under stoichiometric conditions in such terms has permitted their reconciliation with results of a later publication on the interaction under equilibrium conditions.