Herceptin (Trastuzumab) is a widely used and effective drug for the treatment of Her2+ breast cancer but its cardiotoxic side effects require regular monitoring by echocardiography. A 10% reduction in left ventricular ejection fraction can lead to suspension of treatment and therefore has significant implications for patient prognosis in terms of cardiac and cancer outcomes. Assessment of LV function by conventional 2D biplane method of discs (2DEF) has limitations in accuracy and reproducibility. Global longitudinal strain (GLS) is becoming more widely available and user friendly. It has been shown to demonstrate myocardial damage earlier in treatment than 2DEF, allowing the option of pharmacological intervention at a pre-clinical stage and preventing the interruption of Herceptin. This study compares the reproducibility of GLS with that of 2DEF in a routine clinical environment. Fifty echocardiograms performed on female patients undergoing Herceptin treatment were used to measure both 2DEF and GLS within the recommended standard appointment time of 40 min. The data were re-measured (blind) by the same operator a minimum of 14 days later to determine intra-operator variation. These data were also measured by a second operator (blind), to assess inter-operator variation. Analysis by direct comparison, intra-class correlation (ICC), coefficient of variation (CV) and Bland–Altman plots demonstrated that GLS is a more reproducible measurement than 2DEF. This is important to prevent clinical decisions being erroneously based on variation in operator measurement. The investigation also shows that with advances in machine software this is a practical addition to routine assessment rather than merely a research tool.
OBJECTIVE: To investigate how hepatopoietin (HPO) and partial hepatectomy induce the expression of immediate early genes.METHODS: mRNA expression related to liver regeneration was investigated within 1 h after a two‐thirds partial hepatectomy by representational difference analysis and with the addition of HPO in a primary cultured hepatocyte system by reverse transcription polymerase chain reaction.RESULTS: In the expressed sequence tag library, most of the genes identified were immediate early genes, and one Tec gene that might be associated with liver regeneration was found. Moreover, the Tec gene was rapidly induced after partial hepatectomy, with peak expression (7−10‐fold) within 1−2 h after the operation as identified by northern blotting. Hepatopoietin was able to rapidly induce the expression of immediate early genes (e.g. c‐fos, LRF‐1, Tec) in primary cultured rat hepatocytes. The c‐fos and LRF‐1 mRNA were also known to be induced during the early hours of liver regeneration, and increased after treatment of isolated hepatocytes with HPO. Addition of HPO resulted in rapid and transient induction of Tec mRNA with a peak at 0.5−2 h (3−5‐fold), which might be one of the molecular mechanisms of the effect of HPO on the stimulation of hepatocyte proliferation.CONCLUSION: Hepatopoietin and partial hepatectomy can rapidly induce the expression of the immediate early genes. Our results suggest that the Tec gene is an immediate early gene related to liver regeneration.
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