The use of doppler ultrasonography for the evaluation of cerebral artery flow patterns in infants with congenital heart disease

With the use of a two-dimensional range-gated pulsed-Doppler ultrasound system, Doppler examinations of the aorta and cerebral arteries were performed in 20 normal newborn infants and in 54 infants with various forms of congenital heart disease (i.e. patent ductus arteriosus, coarctation of the aorta, critical aortic stenosis, pulmonary atresia, truncus arteriosus). In the cerebral artery Doppler recordings of the normal infants, there was antegrade flow throughout systole and diastole. In the cerebral artery Doppler recordings of the infants with cardiac disease, various abnormal flow signals (i.e. retrograde or absent diastolic flow signals, increased systolic and diastolic flow signals, etc.) were found. Furthermore, the changes in the cerebral artery Doppler recordings were concomitant with changes in the aortic Doppler flow signals and the arterial blood pressure. Representative examples of the normal and abnormal Doppler flow patterns that were observed in the aorta and cerebral arteries are presented, and the mechanisms that could lead to these flow patterns are discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25687/1/0000241.pd

Transcatheter Atrial Septal Defect Closure: Preliminary Experience with the Rashkind Occluder Device

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72836/1/j.1540-8183.1989.tb00751.x.pd

Echocardiographic detection of anomalous course of the left innominate vein

Anomalous course of the left innominate vein beneath the aortic arch is a rare congenital anomaly. We report the case of a 3 year old child in whom this defect was detected by two-dimensional and Doppler echocardiography. The echocardiographic appearance of the anomalous course of the left innominate vein is illustrated and the importance of identifying this rare systemic venous anomaly is discussed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42535/1/10554_2005_Article_BF01784202.pd

Doppler detection of valvular regurgitation after radiofrequency ablation of accessory connections

Radiofrequency current was used recently to ablate accessory connections in patients with supraventricular tachycardia.1-5 After locating the accessory connection by electrophysiologic mapping, ablation is achieved by positioning a 7Fr catheter (with 4 mm electrode at distal tip) within the ipsilateral cardiac chamber and adjacent to the accessory connection. Radiofrequency current is then delivered at the point of earliest electrical activation along the atrioventricular valve annulus. For a left-sided accessory connection, the catheter is usually passed retrograde across the aortic valve into the left ventricle and under the posterior mitral valve leaflet. For a right-sided accessory connection, the catheter is passed anterograde into the right atrium or ventricle.1-5 Systematic evaluation of the effects of this technique on the function of all cardiac valves has not been reported. This study evaluates the effects of catheter manipulation and radiofrequency current delivery on valve competence.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29958/1/0000320.pd

Gene expression analysis to detect disseminated tumor cells in the bone marrow of triple-negative breast cancer patients predicts metastatic relapse

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse. METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed. RESULTS: Expression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0-84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%. CONCLUSIONS: We identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC

A microfluidic-based filtration system to enrich for bone marrow disseminated tumor cells from breast cancer patients

Disseminated tumors cells (DTCs) present in the bone marrow (BM) are believed to be the progenitors of distant metastatic spread, a major cause of mortality in breast cancer patients. To better understand the behavior and therapeutic vulnerabilities of these rare cell populations, unbiased methods for selective cell enrichment are required. In this study, we have evaluated a microfluidic-based filtration system (ParsortixR, Angle PLC), previously demonstrated for use in circulating tumor cell (CTC) capture, to capture BM DTCs. Performance using BM samples was also compared directly to enrichment of CTCs in the peripheral blood (PB) from both metastatic and non-metastatic breast cancer patients. Although the non-specific capture of BM immune cells was significant, the device could routinely achieve significant cytoreduction of BM and PB WBCs and at least 1,000-fold enrichment of DTCs, based on labeled tumor cell spike-in experiments. Detection of previously characterized DTC-associated gene expression biomarkers was greatly enhanced by the enrichment method, as demonstrated by droplet digital PCR assay. Cells eluted from the device were viable and suitable for single cell RNA sequencing experiments. DTCs in enriched BM samples comprised up to 5% of the total cell population, allowing for effective single cell and population-based transcriptional profiling of these rare cells. Use of the Parsortix instrument will be an effective approach to enrich for rare BM DTCs in order to better understand their diverse molecular phenotypes and develop approaches to eradicate these cells to prevent distant disease development in breast cancer patients

Gene expression analysis to detect disseminated tumor cells in the bone marrow of triple-negative breast cancer patients predicts metastatic relapse

PURPOSE: Disseminated tumor cells (DTCs) in the BM of breast cancer patients predict early disease relapse, but the molecular heterogeneity of these cells is less well characterized. Expression of a 46-gene panel was used to detect DTCs and classify patient BM samples to determine whether a composite set of biomarkers could better predict metastatic relapse. METHODS: Using a high-throughput qRT-PCR assay platform, BM specimens collected from 70 breast cancer patients prior to neoadjuvant therapy were analyzed for the expression of 46 gene transcripts. Gene expression was scored positive (detectable) relative to a reference pool of 16 healthy female control BM specimens. To validate findings from a subset of 28 triple-negative breast cancer (TNBC) patients in the initial 70 patient cohort, an independent set of pre-therapeutic BM specimens from 16 TNBC patients was analyzed. RESULTS: Expression of each of the 46 gene transcripts was highly variable between patients. Individual gene expression was detected in 0-84% of BM specimens analyzed and all but two patient BM specimens expressed at least one transcript. Among a subset of 28 patients with TNBC, positivity of one or more of eight transcripts correlated with time to distant relapse (p = 0.03). In an independent set of 16 triple-negative patient BM samples, detection of five of these same eight gene transcripts also correlated with time to distant relapse (p = 0.03) with a positive predictive value of 89%. CONCLUSIONS: We identified a set of gene transcripts whose detection in the BM of TNBC patients, prior to any treatment intervention, predicts time to first distant relapse, thus identifying a TNBC patient population which requires additional treatment intervention. Because these genes are presumably expressed in populations of DTCs and many encode proteins that are known therapeutic targets (e.g., ERBB2), these results also suggest a potential approach for targeted DTC therapy to mitigate distant metastases in TNBC

Tachycardia Related Cardiomyopathy: Response to Control of the Arrhythmia

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75609/1/j.1540-8183.1989.tb00780.x.pd

Usefulness of the doppler mean gradient in evaluation of children with aortic valve stenosis and comparison to gradient at catheterization

To assess the usefulness of the Doppler mean gradient as a noninvasive indicator of the need for intervention, 33 children (ages 3 months to 20 years) with valvular aortic stenosis (AS) underwent a 2-dimensional and Doppler echocardiographic examination a median of 1 day before cardiac catheterization. The clinical decision for intervention was based on finding a catheterization peak-to-peak pressure gradient of >75 mm Hg or from 50 to 75 mm Hg in the presence of symptoms or an abnormal exercise treadmill test result. Of the 33 patients, 23 required intervention. The decision for intervention was compared to the Doppler mean gradient, and the Doppler peak and mean gradients were compared to the catheterization peak-to-peak gradient. All 12 patients with a Doppler mean gradient >27 mm Hg had intervention and had a catheterization peak-to-peak gradient of >75 mm Hg. All 3 patients with a Doppler mean gradient From a chi-square table, a Dopppler mean gradient >27 mm Hg predicted the need for intervention with 100% specificity (no false positives) and 52% sensitivity (11 false negatives). if a Doppler mean gradient >24 mm Hg was used to predict intervention, the sensitivity increased to 91% (2 false negatives) but specificity decreased to 70% (3 false positives). To improve the ability to predict the need for intervention in patients with a Doppler mean gradient between 17 and 27 mm Hg, the presence of symptoms or an abnormal exercise treadmill test result was combined with the Doppler mean gradient as criteria for intervention. When the criteria for intervention were a Doppler mean gradient >27 mm Hg or a Doppler mean gradient from 17 to 27 mm Hg in the presence of symptoms or an abnormal exercise test, sensitivity was 96% (1 false negative) and specificity was 80% (2 false positives). Catheterization peak-to-peak gradients correlated well with Doppler mean and peak gradients (r = 0.74 and 0.73, respectively).Thus, the Doppler mean gradient is a useful indicator of the need for intervention in children with AS. A Doppler mean gradient >27 mm Hg indicates the need for intervention with 100% specificity while a Doppler mean gradient < 17 mm Hg predicts mild AS. For patients with Doppler mean gradient between 17 and 27 mm Hg, additional noninvasive data are necessary to determine the need for intervention.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27748/1/0000140.pd

Echocardiographic diagnosis of right aortic arch with a retroesophageal segment and left descending aorta

Two-dimensional echocardiography has been used extensively to assess aortic arch anatomy in infants and children. Echocardiographic techniques for examination of left and right aortic arch, coarctation and interruption of the aorta, aortic aneurysm and double aortic arch have been well described.1,2 Right aortic arch with retroesophageal segment and left descending aorta, an unusual form of vascular ring, has been described using angiography, barium swallow and computed axial tomography.3-5 In this report, we describe 2-dimensional (2-D) echocardiographic findings in an infant with this unusual form of vascular ring.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26188/1/0000267.pd