1,560 research outputs found
Transplantation in children
Kidney transplantation in very young children, less than 2 years of age, has usually failed, mainly because of difficulties maintaining these patients on hemodialysis long enough to permit retransplantation after loss of the original graft. Liver replacement in the very young child has been associated with a higher frequency of vascular and biliary obstruction than in the older child, due to the small size of these structures. Such accidents have contributed to unsatisfactory results with biliary atresia. Transplantation of kidney or liver into older children has been more successful than transplantation of these organs into adults. Related or cadaveric kidney transplantation in the child has been followed by at least a 60 per cent patient survival for 6 to 13 years and a very acceptable quality of life. Liver replacement for diseases other than biliary atresia has been followed by a 56 per cent 1 year survival rate, and two children have survived for more than 5 years
Beneficial hemodynamic effects of intravenous and oral diltiazem in severe congestive heart failure
Concern persists about the potential negative inotropic effects of calcium channel blockers in patients with severely depressed myocardial function. Therefore, intravenous diltiazem (100 to 200 ltg/kg per min infusion) was administered for 40 minutes followed by oral diltiazem (90 to 120 mg/8 hours) for 24 hours to patients with advanced congestive heart failure (New York Heart Association class III to IV, mean ejection fraction 26 ± 4 [SD]). Intravenous diltiazem (eight patients) increased cardiac index 20% (2.05 ± 0.8 to 2.47 ± 0.8 liters/min per MZ, p < 0.01), stroke volume index 50% (22 ± 9 to 33 ± 12 MI/M2, p < 0.001) and stroke work index 27% (19 ± 10 to 24 ± 10 g-m/MZ, p < 0.05); while reducing heart rate 23% (97 ± 18 to 75 ± 11 beats/min, p < 0.01), mean arterial pressure 18% (95 ± 13 to 78 ± 7 mm Hg) and pulmonary wedge pressure 34% (29 ± 9 to 19 ± 7 mm Hg), without altering maximal first derivative of left ventricular pressure (dP/dtmax). Oral diltiazem (seven patients) produced equivalent hemodynamic effects. Transient junctional arrhythmias were observed in three of eight patients with intravenous diltiazem and one of seven patients with oral diltiazem.It is concluded that intravenous and short-term oral diltiazem improve left ventricular performance and reduce myocardial oxygen demand by heart rate and afterload reduction without significantly depressing contractile function in severe congestive heart failure. Caution should be exercised to avoid potential adverse, druginduced electrophysiologic effects in such patients
Students’ Perceptions of Factors that Affect College Funding Decisions
This exploratory study examines the factors that college students perceive are important in helping them make good financial decisions about paying for a college education. The study categorizes and summarizes students\u27 self-reported responses to an openended survey question about recommendations for changes in financial aid counseling practices. The 335 student responses had a recurring theme of better information provided through individual counseling sessions
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EM-mosaic detects mosaic point mutations that contribute to congenital heart disease.
BackgroundThe contribution of somatic mosaicism, or genetic mutations arising after oocyte fertilization, to congenital heart disease (CHD) is not well understood. Further, the relationship between mosaicism in blood and cardiovascular tissue has not been determined.MethodsWe developed a new computational method, EM-mosaic (Expectation-Maximization-based detection of mosaicism), to analyze mosaicism in exome sequences derived primarily from blood DNA of 2530 CHD proband-parent trios. To optimize this method, we measured mosaic detection power as a function of sequencing depth. In parallel, we analyzed our cohort using MosaicHunter, a Bayesian genotyping algorithm-based mosaic detection tool, and compared the two methods. The accuracy of these mosaic variant detection algorithms was assessed using an independent resequencing method. We then applied both methods to detect mosaicism in cardiac tissue-derived exome sequences of 66 participants for which matched blood and heart tissue was available.ResultsEM-mosaic detected 326 mosaic mutations in blood and/or cardiac tissue DNA. Of the 309 detected in blood DNA, 85/97 (88%) tested were independently confirmed, while 7/17 (41%) candidates of 17 detected in cardiac tissue were confirmed. MosaicHunter detected an additional 64 mosaics, of which 23/46 (50%) among 58 candidates from blood and 4/6 (67%) of 6 candidates from cardiac tissue confirmed. Twenty-five mosaic variants altered CHD-risk genes, affecting 1% of our cohort. Of these 25, 22/22 candidates tested were confirmed. Variants predicted as damaging had higher variant allele fraction than benign variants, suggesting a role in CHD. The estimated true frequency of mosaic variants above 10% mosaicism was 0.14/person in blood and 0.21/person in cardiac tissue. Analysis of 66 individuals with matched cardiac tissue available revealed both tissue-specific and shared mosaicism, with shared mosaics generally having higher allele fraction.ConclusionsWe estimate that ~ 1% of CHD probands have a mosaic variant detectable in blood that could contribute to cardiac malformations, particularly those damaging variants with relatively higher allele fraction. Although blood is a readily available DNA source, cardiac tissues analyzed contributed ~ 5% of somatic mosaic variants identified, indicating the value of tissue mosaicism analyses
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Systems Analysis Implicates WAVE2 Complex in the Pathogenesis of Developmental Left-Sided Obstructive Heart Defects.
Genetic variants are the primary driver of congenital heart disease (CHD) pathogenesis. However, our ability to identify causative variants is limited. To identify causal CHD genes that are associated with specific molecular functions, the study used prior knowledge to filter de novo variants from 2,881 probands with sporadic severe CHD. This approach enabled the authors to identify an association between left ventricular outflow tract obstruction lesions and genes associated with the WAVE2 complex and regulation of small GTPase-mediated signal transduction. Using CRISPR zebrafish knockdowns, the study confirmed that WAVE2 complex proteins brk1, nckap1, and wasf2 and the regulators of small GTPase signaling cul3a and racgap1 are critical to cardiac development
1,12-Diferrocenyldodecane at 100 K
1,12-Diferrocenyldodecane, [Fe2(C5H5)2(C22H32)], was synthesized from ferrocene and 1,12-dodecanedioyl chloride, followed by Clemmensen reduction. The single-crystal structure was determined at 100 K by X-ray diffraction and the spectroscopic and cyclic voltammetric data of 1,12-diferrocenyldodecane and its precursor are reported
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