Allosteric SHP2 inhibition increases apoptotic dependency on BCL2 and synergizes with venetoclax in FLT3- and KIT-mutant AML.

Mutations in the receptor tyrosine kinases (RTKs) FLT3 and KIT are frequent and associated with poor outcomes in acute myeloid leukemia (AML). Although selective FLT3 inhibitors (FLT3i) are clinically effective, remissions are short-lived due to secondary resistance characterized by acquired mutations constitutively activating the RAS/MAPK pathway. Hereby, we report the pre-clinical efficacy of co-targeting SHP2, a critical node in MAPK signaling, and BCL2 in RTK-driven AML.

Comparison of automated oscillometric versus auscultatory blood pressure measurement.

Most clinical offices rely on automated oscillometric devices to measure blood pressure (BP), but the accuracy of this technique versus auscultatory determination using a mercury manometer is controversial. To assess the accuracy of automated oscillometric readings, BP was measured from the same site and cuff, in 337 consecutive patients seen in a routine cardiology office, using a simultaneous connection to an automated oscillometric and a mercury manometer technique. The mean systolic BP (133 +/- 20 mm Hg) and diastolic BP (72 +/- 11 mm Hg) were significantly greater using the mercury manometer than the automated oscillometric technique (systolic 131 +/- 18 and diastolic 70 +/- 12 mm Hg, p <0.

Repeatability of automatic left ventricular cavity volume measurements from myocardial perfusion SPECT.

Background: This study sought to assess the repeatability of automatic quantitative measurements of left ventricular (LV) cavity volumes in a large patient population (N = 926), to correlate those measurements to similarly obtained LV ejection fraction (LVEF) measurements, and to investigate the relationship between ungated and gated volumes.

Methods: All 926 patients underwent ungated single photon emission computed tomography (SPECT) immediately followed by 8-frame gated SPECT. LV cavity volumes were automatically measured from ungated (V), summed gated (SUMV), end-systolic (ESV) and end-diastolic (EDV) images, and LVEFs derived from the latter 2.

Demonstration of interstitial collagenase in abdominal aortic aneurysm disease.

This study was performed to evaluate the presence of interstitial collagenase, now known as matrix metalloproteinase-1 (MMP-1), in specimens of abdominal aortic aneurysms (AAA). Eight AAA and four control infrarenal aortas were evaluated. After homogenization and extraction of soluble proteins, immunoblots of the extracts equalized for protein content were performed with a specific antibody to MMP-1.

Selective coronary arteriography in infants and children.

The recent increase in incidence of Kawasaki disease with attendant coronary artery aneurysms spurred our interest in developing a technique for selective coronary arteriographic examination of infants and children. Right and left coronary artery catheters were shaped according to the aortic root diameters and ascending aorta lengths predicted from the patient's heights. Thirty-eight studies were done in 34 patients who were 7 months to 18 years of age (median 3.