Adenosine monophosphate and histamine induced bronchoconstriction: repeatability and protection by terbutaline

BACKGROUND: Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies. METHODS: The response to histamine and AMP challenges and the protection afforded by terbutaline (500 micrograms) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement. RESULTS: Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (delta PD20 = 2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to -3.5 and from 3.78 to -4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD20 histamine and PD20 AMP values after placebo were similar, being from 3.73 to - 3.72 DD after allowing for the 17.8-fold higher PD20 values for AMP compared with histamine. CONCLUSIONS: Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD20 values was similar to the agreement between repeat histamine or repeat AMP PD20 values suggests that, within an asthmatic population, PD20 AMP may not be providing different information from that provided by PD20 histamine. 



Influence of strain rate on the structure/property behavior of the alpha-2 alloy Ti-24. 5Al-10. 5Nb-1. 5Mo

Preliminary dislocation g{center dot}b analysis revealed that following room temperature deformation at low strain rate the majority of the dislocations are a-dislocations lying on basal planes, 2nd order pyramidal (a/2 + c) slip on (1211), and 1st order pyramidal a-slip on (1011). Increasing the rate of deformation at room temperature to 6000 s{sup {minus}1} is seen to result in increased a-slip on prism planes and a decreased amount of basal slip. At high-strain-rates and elevated temperatures the substructure was seen to be generally similar to that observed following high-rate deformation at room temperature except for an increased amount of basal slip and a somewhat higher incidence of 2nd order pyramidal slip. The defect generation and the rate sensitivity of Ti-24.5Al-10.5Nb-1.5Mo are discussed as a function of strain rate and temperature and contrasted to that observed in conventional titanium alloys and TiAl