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For the first time, the (d,^{2}He) reaction was successfully used in inverse kinematics to extract the Gamow-Teller transition strength in the ß^{+} direction from an unstable nucleus. The new technique was made possible by the use of an active-target time-projection chamber and a magnetic spectrometer, and opens a path to addressing a range of scientific challenges, including in astrophysics and neutrino physics. In this Letter, the nucleus studied was ^{14}O, and the Gamow-Teller transition strength to ^{14}N was extracted up to an excitation energy of 22 MeV. The data were compared to shell-model and state-of-the-art coupled-cluster calculations. Shell-model calculations reproduce the measured Gamow-Teller strength distribution up to about 15 MeV reasonably well, after the application of a phenomenological quenching factor. In a significant step forward to better understand this quenching, the coupled-cluster calculation reproduces the full strength distribution well without such quenching, owing to the large model space, the inclusion of strong correlations, and the coupling of the weak interaction to two nucleons through two-body currents.

New

The discrepancy between observations from γ-ray astronomy of the ^{60}Fe/^{26}Al γ-ray flux ratio and recent calculations is an unresolved puzzle in nuclear astrophysics. The stellar ß-decay rate of ^{59}Fe is one of the major nuclear uncertainties impeding us from a precise prediction. The important Gamow-Teller strengths from the low-lying states in ^{59}Fe to the ^{59}Co ground state are measured for the first time using the exclusive measurement of the ^{59}Co(t,^{3}He+γ)^{59}Fe charge-exchange reaction. The new stellar decay rate of ^{59}Fe is a factor of 3.5±1.1 larger than the currently adopted rate at T=1.2 GK. Stellar evolution calculations show that the ^{60}Fe production yield of an 18 solar mass star is decreased significantly by 40% when using the new rate. Our result eliminates one of the major nuclear uncertainties in the predicted yield of ^{60}Fe and alleviates the existing discrepancy of the ^{60}Fe/^{26}Al ratio.

Efficacy and safety of budesonide/formoterol single inhaler therapy versus a higher dose of budesonide in moderate to severe asthma.

OBJECTIVES: This study evaluated the efficacy and safety of a novel asthma management strategy--budesonide/formoterol for both maintenance and symptom relief (Symbicort Single Inhaler Therapy)--compared with a higher maintenance dose of budesonide in patients with moderate to severe asthma. METHODS: This was a 12-month, randomised, double-blind, parallel-group study. Symptomatic patients with asthma (n = 1890; mean age 43 years [range 11 years-80 years], mean baseline forced expiratory volume in 1 s [FEV(1)] 70% of predicted, mean inhaled corticosteroid [ICS] dose 746 microg/day) received either budesonide (160 microg, 2 inhalations twice daily) plus terbutaline 0.4 mg as needed or a daily maintenance dose of budesonide/formoterol (160/4.5 microg, 2 inhalations once daily) with additional inhalations of budesonide/formoterol 160/4.5 microg as needed. Time to first severe exacerbation (hospitalisation/emergency room [ER] treatment or systemic steroids due to asthma worsening or a fall in morning peak expiratory flow [PEF] to < or = 70% of baseline on 2 consecutive days) was the primary outcome variable. RESULTS: A total of 1890 patients were randomised, of whom 1563 (83%) had severe asthma. The time to first severe exacerbation was prolonged by budesonide/formoterol single inhaler therapy (p < 0.001) compared with a higher dose of budesonide. The risk of having a severe exacerbation was 39% lower with budesonide/formoterol single inhaler therapy compared with budesonide (p < 0.001). The number needed to treat to prevent one severe exacerbation per year with budesonide/formoterol compared with budesonide was 5. The budesonide/formoterol group had 45% fewer severe exacerbations requiring medical intervention per patient compared with the budesonide group (p < 0.001). Budesonide/formoterol patients had fewer hospitalisations/ER treatments (15 vs 25 events, respectively [descriptive statistics]) and fewer treatment days with systemic steroids (1776 days vs 3177 days, respectively [descriptive statistics]) compared with budesonide patients. Budesonide/formoterol single inhaler therapy patients used less as-needed medication compared with budesonide patients (0.90 vs 1.42 inhalations/day; p < 0.001). The mean daily ICS dose was lower in the budesonide/formoterol group than in the budesonide group (466 microg/day vs 640 microg/day). Over the 12-month study period, the budesonide/formoterol group achieved asthma control sufficient to not require any additional as-needed medication on 60% of days. Overall, budesonide/formoterol single inhaler therapy gave 31 more asthma control days (a night and day with no asthma symptoms and no as-needed medication use) per patient-year and 12 additional undisturbed nights per patient-year compared with a higher dose of budesonide. Both treatments were well tolerated. CONCLUSION: Budesonide/formoterol single inhaler therapy has the potential to provide a complete asthma management approach with one inhaler, demonstrating a high level of efficacy in patients with moderate to severe asthma.

Low-dose budesonide improves exercise-induced bronchospasm in schoolchildren.

The aim of this study was to compare the clinical efficacy of low-dose inhaled budesonide (once or twice daily) and placebo, administered via Turbuhaler, on exercise-induced bronchoconstriction (EIB) in children with mild asthma. Fifty-seven steroid-naive children (7-16 years old; 41 boys, 16 girls) with EIB participated in this sub-population study according to the following inclusion criterion: a maximum fall in forced expiratory volume in 1 s (FEV1) > or = 10% after a standardized treadmill test. Mean baseline FEV1 was 100.3% of predicted, and mean maximum fall in FEV1 after the standardized exercise test was 22%. The study was a double-blind, randomized, parallel-group design. After 2 weeks of run-in, the children received inhaled budesonide 100 microg or 200 microg once daily in the morning, 100 microg twice daily, or placebo, for 12 weeks. After 12 weeks of treatment, the fall in FEV1 after the exercise test was significantly less in all three budesonide groups (7.2-7.8%) vs. placebo (16.7%). Daytime symptom scores were significantly lower in all three budesonide groups compared with placebo (p <0.02). The three budesonide groups did not differ significantly, and no significant change in lung function was found in any group. Therefore children with mild asthma, but with significant EIB, improved their exercise tolerance and symptom control after 3 months of treatment with a low dose of inhaled budesonide given once or twice daily.

How much weight gain occurs following smoking cessation? A comparison of weight gain using both continuous and point prevalence abstinence.

Estimates of postcessation weight gain vary widely. This study determined the magnitude of weight gain in a cohort using both point prevalence and continuous abstinence criteria for cessation. Participants were 196 volunteers who participated in a smoking cessation program and who either continuously smoked (n = 118), were continuously abstinent (n = 51), or who were point prevalent abstinent (n = 27) (i.e., quit at the 1-year follow-up visit but not at others). Continuously abstinent participants gained over 13 lbs. (5.90 kg) at 1 year, significantly more than continuously smoking (M = 2.4 lb.) and point prevalent abstinent participants (M = 6.7 lbs., or 3.04 kg). Individual growth curve analysis confirmed that weight gain and the rate of weight gain (pounds per month) were greater among continuously smoking participants and that these effects were independent of gender, baseline weight, smoking and dieting history, age, and education. Results suggest that studies using point prevalence abstinence to estimate postcessation weight gain may be underestimating postcessation weight gain.

The effect of smoking and light activity on metabolism in men.

This experiment examined the metabolic effects of smoking during rest and light activity under naturalistic conditions. Thirty-nine male subjects first completed a submaximal graded exercise treadmill test to standardize activity level. Then 3 groups of subjects--smokers smoking (SS), smokers not smoking (SNS), and nonsmokers (NS)--were exposed to 3 stages of rest or 3 stages of light activity with order of rest or activity randomly determined over 2 different days. Energy expenditure was monitored continuously during these sessions. Significant increases in smokers' energy expenditure were observed during light activity when compared with smokers not smoking and nonsmokers. No differences were identified among groups at rest. These findings strengthen the conclusion that smoking or its components contribute to metabolic changes during typical levels of daily activity and suggest a mechanism for the frequently observed relationship between smoking status and body weight.

Clinical efficacy and safety of budesonide Turbuhaler in adults.

In two studies comparing budesonide delivered by Turbuhaler with budesonide delivered by pressurized metered dose inhaler (pMDI), a significantly higher morning peak expiratory flow (PEF), and a patient preference in favor of budesonide by Turbuhaler was found. Less cough was also noted. In a third study no difference was found between the two formulations. However, a meta-analysis of the three studies demonstrated a significant difference in favor of budesonide by Turbuhaler for forced expiratory volume in one second (FEV1) and morning PEF. These findings are supported by data on lung deposition showing the Turbuhaler to be twice as efficient as a pMDI. At the same time, the availability of budesonide from the gastrointestinal tract is reduced. Thus, a more beneficial ratio arises between local lung delivery and systemic availability. Inhaled glucocorticosteroids are now recommended for mild asthma. Thus once daily treatment with 400mug budesonide by Turbuhaler has been studied in two trials; a comparison with 200mug twice daily was also made. In both studies morning/evening PEF increased significantly over placebo and no difference was demonstrated between once- and twice-daily treatments. A study to determine the effect of placebo and 200mug twice daily and 400mug once daily of budesonide by Turbuhaler on 24-h plasma and urinary cortisol demonstrated no difference between the treatment regimens. Budesonide by Turbuhaler is at least as effective as budesonide by pMDI. When patients are switched to budesonide by Turbuhaler an attempt should be made to reduce the dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Gm allotypes as indicators of non-atopic and atopic bronchial asthma.

69 Caucasian children, 34 with non-atopic and 35 with atopic bronchial asthma, demonstrated different, Gm-associated IgG antibody responsiveness. The non-atopic bronchial asthma group showed a preponderance of the Gm(a,'',g) haplotype, while the atopic study group showed a preponderance of the haplotype with the alternative allotypes on all IgG subclass loci, namely Gm(f,n,b). Patients with non-atopic bronchial asthma showed a significantly increased frequency of the phenotypes containing the Gm(a,'',g) haplotype, namely the Gm(a,'',g/a,'',g) and Gm(a,'',g/f,'',b), and an increased number of individuals were homozygous G2m('','') on the IgG2 locus. The 2 asthma groups showed different characteristic IgG subclass patterns, the non-atopic group with significantly decreased IgG2 and IgG3, especially those of the Gm(a,'',g/a,'',g) phenotype, and the atopic group with significantly increased IgG1 and IgG4, especially those of the Gm(f,n,b/f,n,b) phenotype. The characteristic IgG subclass patterns originate from the different Gm phenotypes found in the 2 groups. The results emphasize the presence of qualitatively and quantitatively different IgG molecules in non-atopic and atopic bronchial asthma patients and show the interest in studying IgG genes and IgG molecules as markers of pathogenesis. G2m('','') homozygosity is a new important marker of non-atopic bronchial asthma.

Effect of inhaled terbutaline sulphate in relation to its deposition in the lungs.

We studied the effects of inhaled terbutaline on FEV1 and gas exchange, and the pattern of deposition within the lungs. To document this and to estimate the dose of terbutaline administered to the lungs, [99mTc]DTPA was added to nebulised terbutaline solution. The aerosol was deposited preferentially in large or small airways by using aerosols with different particle mass median diameters (1.5 and 4.8 microns) and different inhalation flow rates (0.25 and 1.0 l/s). The patients inhaled placebo and then three increasing doses of terbutaline (0.006, 0.02 and 0.08 mg to the lungs). Finally, 2 mg terbutaline was inhaled from a metered dose inhaler via a spacer. After each inhalation FEV1, PaO2 and PaCO2 was measured. The inhalation of small particles at a low flow resulted in a fairly uniform lung deposition, while larger particles at a higher flow resulted in heavy central deposition. Penetration index for small and large particles were 1.3 +/- 0.2 and 0.8 +/- 0.3 (P less than 0.001), respectively. In both groups FEV1 increased similarly with each dose, and at 0.02 and 0.08 mg the increase was significant (P less than 0.01). After eight metered doses of terbutaline sulphate (0.25 mg per dose) inhaled via a spacer, there was a further increase in FEV1 (P less than 0.001). Gas exchange did not differ between the two groups but if they were combined the DA-aO2 was significantly lower after metered doses than control (P less than 0.05). Thus, it appears that the site of deposition is not important for the bronchodilator effect of terbutaline, and gas exchange tended to improve with both modes of administration.

Relationships among smoking status, body composition, energy intake, and physical activity in adult males: a longitudinal analysis.

This study evaluates the longitudinal relationships among smoking and adiposity, dietary intake, and physical activity in a group of adult males. Subjects were 101 nonsmokers and 19 regular cigarette smokers. Adiposity, dietary intake, and physical activity were assessed annually for three consecutive years. Results indicated that nonsmokers had larger tricep skinfold measurements than smokers over the 3-year period. However, dietary intake and physical activity did not differ between groups. Due to the absence of differences on these two variables for the smoking and nonsmoking groups, it was concluded that the lower adiposity in smokers was largely metabolically determined, which may make difficult the treatment of postcessation weight gain.

A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma.

Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use.

Pharmacokinetics of intravenous terbutaline in asthmatic children.

Seven asthmatic children were given terbutaline intravenously. The intact drug was measured in plasma and urine, and its conjugates were measured in urine. The decreasing plasma concentrations of terbutaline did not attain a terminal slope until 8-12 h after dosing. This was most likely due to different kinetics of the enantiomers. The terminal half-life was 8.8-15.8 h. Body clearance was 2.73-5.44 ml/min/kg, two-thirds of which were of renal origin. The volume of distribution (Vss) was 1.28-1.83 l/kg. The disposition pharmacokinetics of terbutaline do not rationalize a higher dose per kg body weight in children than in adults.

Kinetics of terbutaline in asthmatic children.

Seven asthmatic children (8-12 years) were given terbutaline sulphate intravenously (5.5 micrograms/kg) and orally (50 micrograms/kg) one week apart. Unchanged terbutaline was measured in plasma and urine. In urine, conjugates were also assayed. The intravenous plasma concentration-time curve declined in a multiexponential manner. The terminal half-life ranged from 8.8 to 15.8 (mean 12.1) h. Body clearance (mean +/- SD) was 3.76 +/- 0.86, renal clearance 2.42 +/- 0.49 mL/min/kg. The volume of distribution at steady state was 1.57 +/- 0.19 L/kg. The extrapolated recovery of intact terbutaline in urine was 65.4 +/- 6.5% of the dose and the total recovery 80.8 +/- 8.4%. After oral administration, the recovery of intact terbutaline in urine was 6.2 +/- 1.1%. Absorption was on average 33%, but because of a mean first-pass elimination of 70%, bioavailability was 9.5 +/- 2.4%. It seems that children as a group have shorter terminal half-lives than adults and slightly higher weight-corrected clearances.

Reflex sympathetic dystrophy in two young females.

Reflex sympathetic dystrophy in paediatric patients is a rarely recognized pain syndrome probably of neurovascular origin. The manifectations in two young females consisted of disabling pain and localized hyperesthesia in lower extremities without evident trauma. Sympathetic block followed by active mobilization and, in the patient with atrophic changes, lumbar sympathectomy, resulted in complete recovery. Reflex sympathetic dystrophy should be considered in the differential diagnosis of pain and tenderness in an extremity.