University of Colorado Denver

About: University of Colorado Denver is a education organization based out in Denver, Colorado, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 27444 authors who have published 57213 publications receiving 2539937 citations. The organization is also known as: CU Denver & UCD.

Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (2)

Abstract: This article has analyzed the pathogenesis of sodium and water retention in several circumstances. The initiator of retention has been proposed to be either a fall in cardiac output (e.g., low-output cardiac failure and vasoconstrictor hypovolemic nephrotic syndrome) or peripheral arterial vasodilatation (e.g., high-output cardiac failure, cirrhosis, arteriovenous fistula, and pregnancy). In the only state discussed, in which the kidney is diseased and not merely responding to extrarenal reflexes--i.e., nephrotic syndrome--intrarenal mechanisms may predominate and lead to expansion of the arterial vascular tree and suppression of the renin-angiotensin-aldosterone system (i.e., hypervolemic nephrotic syndrome). Otherwise, when kidneys are healthy, either a fall in cardiac output or peripheral arterial vasodilatation may diminish arterial vascular filling and thereby initiate a series of hemodynamic and hormonal events that result in renal sodium and water retention (Fig. 7). Finally, the approach presented in this article should be considered to be a vantage point from which to evaluate states of sodium and water retention, but not to be an exclusive position.

Radiation Dose–Volume Effects in the Stomach and Small Bowel

Abstract: Published data suggest that the risk of moderately severe (≥Grade 3) radiation-induced acute small-bowel toxicity can be predicted with a threshold model whereby for a given dose level, D, if the volume receiving that dose or greater (VD) exceeds a threshold quantity, the risk of toxicity escalates. Estimates of VD depend on the means of structure segmenting (e.g., V15 = 120 cc if individual bowel loops are outlined or V45 = 195 cc if entire peritoneal potential space of bowel is outlined). A similar predictive model of acute toxicity is not available for stomach. Late small-bowel/stomach toxicity is likely related to maximum dose and/or volume threshold parameters qualitatively similar to those related to acute toxicity risk. Concurrent chemotherapy has been associated with a higher risk of acute toxicity, and a history of abdominal surgery has been associated with a higher risk of late toxicity.

Imatinib for Melanomas Harboring Mutationally Activated or Amplified KIT Arising on Mucosal, Acral, and Chronically Sun-Damaged Skin

Abstract: Purpose Amplifications and mutations in the KIT proto-oncogene in subsets of melanomas provide therapeutic opportunities. Patients and Methods We conducted a multicenter phase II trial of imatinib in metastatic mucosal, acral, or chronically sun-damaged (CSD) melanoma with KIT amplifications and/or mutations. Patients received imatinib 400 mg once per day or 400 mg twice per day if there was no initial response. Dose reductions were permitted for treatment-related toxicities. Additional oncogene mutation screening was performed by mass spectroscopy. Results Twenty-five patients were enrolled (24 evaluable). Eight patients (33%) had tumors with KIT mutations, 11 (46%) with KIT amplifications, and five (21%) with both. Median follow-up was 10.6 months (range, 3.7 to 27.1 months). Best overall response rate (BORR) was 29% (21% excluding nonconfirmed responses) with a two-stage 95% CI of 13% to 51%. BORR was significantly greater than the hypothesized null of 5% and statistically significantly different by mu...

Expert consensus document: Mitochondrial function as a therapeutic target in heart failure

Abstract: Heart failure is a pressing worldwide public-health problem with millions of patients having worsening heart failure. Despite all the available therapies, the condition carries a very poor prognosis. Existing therapies provide symptomatic and clinical benefit, but do not fully address molecular abnormalities that occur in cardiomyocytes. This shortcoming is particularly important given that most patients with heart failure have viable dysfunctional myocardium, in which an improvement or normalization of function might be possible. Although the pathophysiology of heart failure is complex, mitochondrial dysfunction seems to be an important target for therapy to improve cardiac function directly. Mitochondrial abnormalities include impaired mitochondrial electron transport chain activity, increased formation of reactive oxygen species, shifted metabolic substrate utilization, aberrant mitochondrial dynamics, and altered ion homeostasis. In this Consensus Statement, insights into the mechanisms of mitochondrial dysfunction in heart failure are presented, along with an overview of emerging treatments with the potential to improve the function of the failing heart by targeting mitochondria.