10 research outputs found
Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon alpha/ara-C
We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated
The Consequences of Cardiac Autonomic Dysfunction in Multiple Organ Dysfunction Syndrome
The impact of air power on navies
This thesis examines how air power has affected navies using the case of the United Kingdom between 1945 and 1957. Air power has given rise to numerous theories about its effect on the use of force, in which its impact on navies has been a particular theme. Many thinkers have interpreted air power as a strategic, operational and tactical challenge to navies, which would render them redundant and obsolete. Such ideas originated between the two World Wars but have continually reappeared since 1945 and were often influential in the British debate. During the period under consideration, the Royal Navy was challenged in a series of defence reviews. Although these serious and repeated attacks were generally motivated by financial considerations, they were justified primarily by claims relating to air power. It was argued that nuclear-armed air power would be sufficient to win wars, while any nuclear war would leave little role for navies. Later, this argument shifted to an emphasis on deterrence of war and it was suggested that naval forces were not vital to this deterrent. Although the Admiralty continued to justify a capability to defend sea communications as both a deterrent to war and vital in it, this case did not find favour with the government. During the mid-1950s, however, an alternative focus for the Navy emerged in the form of policing and limited wars, east of Suez. Conflicts in Korea and the Suez demonstrated that such conflicts could occur and that mobile naval forces, particularly carrier aviation, were well suited to intervention in them. It was also argued that land-based aircraft could take over some of the roles traditionally performed by naval forces, notably that of strike (against warships and shore targets) but also that of protecting shipping. These arguments were successfully defeated by the Admiralty. Land-based aircraft proved a useful complement to warships and naval aviation in protecting shipping but could only replace them in very limited areas. The Royal Navy differed from the US Navy in its conception of power projection against the land. Its capability for this task was thrown increasingly into doubt by growing Soviet submarine and air power and came to be justified by east of Suez commitments.</p