ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Failure of a Midnocturnal Insulin Infusion to Suppress the Increased Insulin Need for Breakfast in Insulin-dependent Diabetic Patients

Insulin requirements for meals were measured in eight insulin-dependent diabetic patients, using a closed-loop insulin infusion system. Patients required more insulin for breakfast than for an isocaloric lunch (35.7 ± 5.5 mU/kcal/3 h versus 26.9 ± 5.1 mU/kcal/3 h, P &amp;lt; 0.02) or an isocaloric supper (35.7 ± 5.5 mU/kcal/ 3 h versus 26.6 ± 6.6 mU/kcal 3 h, P = 0.05). To determine whether this insulin resistance at breakfast might be due to low basal insulin levels overnight, the insulin needs for breakfast were compared after an overnight fast (day 1) and after a midnocturnal (0200 h–0500 h) insulin infusion (day 2). Breakfast insulin requirements were similar on both days (35.7 ± 5.5 mU/kcal/3 h versus 37.7 ± 5.1 mU/kcal/3 h, P = NS). Whereas nonobese diabetic patients required approximately 60% more insulin for breakfast than for other meals, obese diabetic patients in this study did not demonstrate insulin resistance at breakfast. These findings provide a basis for the common clinical practice of allocating more insulin for breakfast than for other meals. The absence of an increased insulin need at breakfast in our obese patients cautions against a similar algorithm for obese diabetic patients. We postulate that growth hormone may be a cause for morning insulin resistance.</jats:p

Pump-induced Insulin Aggregation: A Problem with the Biostator

A fall in plasma IRI despite constant C-peptide levels during prolonged insulin euglycemic clamp studies using the Biostator (Ames Division, Miles Laboratories, Elkhart, Indiana) prompted a meticulous evaluation of the Biostator's insulin delivery system. At slow infusion rates, a striking loss of immunoreactive and biologically active insulin was observed after 6 h of the Biostator run. Studies with labeled insulin indicated that the loss of insulin was not due to adsorption of insulin to the tubing since recovery of labeled insulin was close to 100%. A variety of techniques (gel filtration, polyacrylamide gel electrophoresis, centrifugation, and Coomassie Brilliant Blue protein assay) indicated that the loss of insulin activity was due to insulin coming out of solution. The insoluble nature of the immunologically and biologically inactive insulin was confirmed by centrifugation, i.e., 88% 125I-insulin precipitated into the pellet. The dependency of this loss of insulin activity on flow rate was clearly demonstrable with activity (IRI) less than 20% of expected at flow rates of 2.1 ml/h, and 30% at 4.2 ml/h. Full recovery was observed only with flow rates of 16.8 ml/h or greater. At each flow rate, IRI rose only after delivery of the effluent between the pump and exit port, demonstrating that insulin alteration occurs within the pump assembly presumably from heat-induced aggregation. Investigators employing the Biostator should carefully examine their systems for this time- and flow ratedependent alteration of insulin. The loss of IRI at low flow rates (low-dose insulin clamp or insulin delivery during basal periods) will profoundly influence data generated from the Biostator.</jats:p

Fidelity of Implementation of Train-the-Trainer Methodology for Delivery of a Preschool Nutrition and Physical Activity Curriculum

&lt;p style="text-align: justify;"&gt;Train-the-Trainer (TTT) methodology uses an expert to train a non-expert on how to implement an intervention and is often used by Cooperative Extension personnel for delivery of programs in the natural setting. In these interventions using multiple educators and/or non-experts, a measure of implementation (fidelity of implementation) is necessary to determine if delivery of the instructional program is as it was designed to be. The objective of this paper is to report the fidelity of implementation (FOI) of iGrow Readers (a literacy-based curriculum that uses children’s books focusing on themes of healthy nutrition and physical activity behaviors) that was delivered by Extension personnel to preschool children in the natural setting of 14 childcare centers through TTT approach. Structural and instructional FOI were assessed by a trained Extension associate. Assessing the FOI of the curriculum delivered by TTT approach provides evidence that the TTT approach is a feasible method of delivery for programing provided by Extension personnel in the natural settings.&lt;/p&gt;</jats:p

Diabetic Ketoacidosis in Obese African-Americans

Our preliminary data indicate that 15% of African-American patients presenting with diabetic ketoacidosis (DKA) are obese. To determine underlying mechanisms, we analyzed the clinical characteristics and indexes of insulin secretion and insulin sensitivity in 35 obese patients with DKA, 22 obese patients with hyperglycemia, 10 lean patients with DKA, and 10 obese nondiabetic subjects. Studies were performed 1 day after resolution of DKA and after 12 weeks of follow-up. At presentation, both obese DKA and obese hyperglycemic patients had no detectable insulin response to intravenous glucose, but they did respond to glucagon administration. The acute insulin response (AIR) to glucagon in obese DKA patients (0.9 ± 0.1 ng/ml) was lower than in obese hyperglycemic subjects (1.5 ± 0.1 ng/ml, P &amp;lt; 0.01), but significantly greater than in lean patients with DKA (0.1 ± 0.1 ng/ml, P &amp;lt; 0.01). After 12 weeks of follow-up, the AIR to glucose improved in both groups of obese diabetic patients but remained significantly lower than in nondiabetic control subjects (both/* &amp;lt; 0.01). In contrast, the AIR to glucagon was not significantly different from that in obese control subjects. Insulin sensitivity was decreased in both groups of obese diabetic patients at presentation and improved after follow-up to levels similar to those in obese nondiabetic control subjects. Reactivity with islet cell antibodies was not detected in any of the patients. During follow-up, 25 of 35 obese DKA and 16 of 22 hyperglycemic patients were able to discontinue insulin therapy, with continued good metabolic control. Our results indicate that in African-Americans, obese patients with DKA represent a subset of type II diabetes. Although impaired insulin secretion and insulin action were found at presentation, decreased pancreatic insulin reserve appears to be the primary defect in the development of DKA in obese patients.</jats:p