Relationships among regional diastolic impairment, elongation of global time to peak filling rate, and global diastolic function using ECG-gated myocardial perfusion SPECT in heart failure

OBJECTIVE: The relationships among regional diastolic impairment, the elongation of global time to peak filling rate (g-TPF), and global diastolic function were examined by a novel program using electrocardiography-gated myocardial perfusion single-photon emission computed tomography (SPECT) (GMPS) in heart failure (HF). METHODS: Fifteen control subjects and 70 HF patients, New York Heart Association functional classification I (N-1) 41 cases, classification II (N-II) 15 cases, and classification III (N-III) 14 cases, were examined by GMPS. Using the reference mean +2 SD (standard deviation) of g-TPF derived from control group (CG), HF patients were divided into a normal g-TPF group (NG) and elongated g-TPF group (EG). The distributions of g-TPF and regional (r-) TPF were estimated by histograms. The extension of regional diastolic impairment was estimated by the number of r-TPF elongated segments (NES). RESULTS: g-TPF and r-TPF mainly distributed from 100 ms to 220 ms and demonstrated a peak around 150 ms in CG and NG. g-TPF distributed from 240 ms to 560 ms, but r-TPF distributed from 90 ms to 690 ms and demonstrated two peaks around 150 ms and 350 ms in EG. NES significantly correlated with g-TPF (r=0.79, P=6x10(-10) in N-I; r=0.69 and P<0.005 in N-II; r=0.89, P=2x10(-5) in N-III). NES negatively correlated with first third filling fraction (1/3FF) (r=-0.83, P=3x10(-11) in N-I; r=-0.72, P<0.0005 in N-II) and first third filling rate (1/3FR) (r=-0.49, P=0.002 in N-I; r=-0.52, P=0.002 in N-II; r=-0.81, P<0.0005 in N-III). g-TPF significantly correlated with 1/3FF (r=-0.67, P=1.5x10(-6) in N-I; r=-0.69, P<0.005 in N-II) and 1/3FR (r=-0.41, P<0.01 in N-I; r=-0.69, P<0.01 in N-III). CONCLUSIONS: The development of regional early diastolic impairment makes g-TPF elongation and induces global dysfunction in early diastole.     

Mammary gland specific expression of Brk/PTK6 promotes delayed involution and tumor formation associated with activation of p38 MAPK

Introduction  

Protein tyrosine kinases (PTKs) are frequently overexpressed and/or activated in human malignancies, and regulate cancer cell proliferation, cellular survival, and migration. As such, they have become promising molecular targets for new therapies. The non-receptor PTK termed breast tumor kinase (Brk/PTK6) is overexpressed in approximately 86% of human breast tumors. The role of Brk in breast pathology is unclear.     

Endocrine therapy, new biologicals, and new study designs for presurgical studies in breast cancer

The preoperative setting is increasingly popular for the clinical investigation of hormonal agents and new biological drugs. The effectiveness of endocrine agents is well established for estrogen receptor-positive disease, and the emphasis in preoperative studies is on their combination with agents targeted at resistance mechanisms over 3 or more months. New agents are also being assessed for early evidence of clinical efficacy in shorter-term window-of-opportunity studies. The establishment of Ki67 as an intermediate marker of treatment benefit and of long-term outcome, with endocrine drugs, provides the opportunity for new trial designs with Ki67 as the primary endpoint. The PeriOperative Endocrine Therapy for Individualizing Care (POETIC) trial is randomizing (2:1) 4000 estrogen receptor-positive patients to 2 weeks presurgical treatment with a nonsteroidal aromatase inhibitor or no presurgical treatment. It provides a unique opportunity for detailed study of the determinants of response and resistance to estrogen deprivation as well as testing the role of presurgical therapy for improved biomarker-based estimates of prognosis.     

Mouse model of focal cerebral ischemia using endothelin-1

Intracerebral injection of the vasoconstrictor peptide, endothelin-1 (ET-1), has been used as a method to induce focal ischemia in rats. The relative technical simplicity of this model makes it attractive for use in mice. However, the effect of ET-1 on mouse brains has not been firmly established. In this study, we determined the ability of ET-1 to induce focal cerebral ischemia in four different mouse strains (CD1, C57/BL6, NOD/SCID, and FVB). In contrast to rats, intracerebral injection of ET-1 did not produce a lesion in any mouse strain tested. A combination of ET-1 injection with either CCA occlusion or N(G)-nitro-l-arginine methyl ester (l-NAME) injection produced only a small infarct and its size was strain-dependent. A triple combination of CCA occlusion with co-injection of ET-1 and l-NAME produced a lesion in all mouse strains tested, and this resulted in a significant motor deficit. However, lesion size was still relatively small and strain-dependent. This study shows that ET-1 has a much less potent effect for producing an infarct in mice than rats.     

Reducing barriers to interprofessional training: promoting interprofessional cultural competence

The need to train health professionals who can work across disciplines is essential for effective, competent, and culturally sensitive health care delivery. By its very nature, the provision of health service requires communication and coordination between practitioners. However, preparation for interdisciplinary practice within the health care setting is rare. The authors argue that the primary reason students are not trained across disciplines is related to the diverse cultural structures that guide and moderate health education environments. It is further argued that this profession specific "cultural frame" must be addressed if there is any hope of having interprofessional education accepted as a valued and fully integrated dimension of our curriculum. Each health discipline possess its own professional culture that shapes the educational experience; determines curriculum content, core values, customs, dress, salience of symbols, the meaning, attribution, and etiology of symptoms; as well as defines what constitutes health, wellness and treatment success. Most importantly, professional culture defines the means for distributing power; determines how training should proceed within the clinical setting; and the level and nature of inter-profession communication, resolution of conflicts and management of relationships between team members and constituents. It might be said that one factor limiting interdisciplinary training is profession-centrism. If we are to achieve effective and fully integrated interdisciplinary education, we must decrease profession-centrism by crafting curriculum that promotes interprofessional cultural competence. The article explores how to promote interprofessional cultural competence within the health education setting.