The relationship between vascular calcifications and urolithiasis in a large, multiethnic patient population.

Several studies have reported associations between vascular calcifications and urinary stone disease (USD). However, results have been inconsistent and the majority of studies did not report on race/ethnicity. We examined the association between vascular calcifications and USD in a large, racially/ethnically diverse patient population. We identified 672 USD cases and 672 controls (i.e., patients without a history of USD) from patients who underwent non-contrast CT imaging at Montefiore Medical Center in Bronx, New York between 2004 and 2013. Controls were matched to cases on age, sex and race/ethnicity. The non-contrast CT imaging was used to measure abdominal aortic calcification (AAC) and calculate the AAC severity score. Logistic regression models were used to examine associations of AAC presence and severity score with risks of USD and stone types. Cases and controls had similar AAC prevalence (45.2% vs. 44.8%, p = 0.87), and AAC severity score (median 10 vs. 9.3, p = 0.47). The presence of AAC (OR = 0.98, 95% CI 0.78-1.23; p = 0.86) or AAC severity score were not associated with risk of USD: ORs of 0.96, 0.87, 1.07 and 1.03 for increasing AAC quartiles (p-trend = 0.54). There were also no associations in the stratified analyses by race/ethnicity or by sex. However, when USD patients were stratified by stone type, brushite/apatite stone formers had an inverse association with the lowest quartile of AAC severity score (OR = 0.35, 95% CI 0.11-0.84, p = 0.04) in comparison to patients without AAC. Overall, we found no association between vascular calcifications and risk of urinary stone disease in this large, hospital-based, case-control study.

Role of hepatic glycogen breakdown in defective counterregulation of hypoglycemia in intensively treated type 1 diabetes.

Impairment of hypoglycemic counterregulation in intensively treated type 1 diabetes has been attributed to deficits in counterregulatory hormone secretion. However, because the liver plays a critical part in recovery of plasma glucose, abnormalities in hepatic glycogen metabolism per se could also play an important role. We quantified the contribution of net hepatic glycogenolysis during insulin-induced hypoglycemia in 10 nondiabetic subjects and 7 type 1 diabetic subjects (HbA1c 6.5 +/- 0.2%) using 13C nuclear magnetic resonance spectroscopy, during 2 h of either hyperinsulinemic euglycemia (plasma glucose 92 +/- 4 mg/dl) or hypoglycemia (plasma glucose 58 +/- 3 mg/dl). In nondiabetic subjects, hypoglycemia was associated with a brisk counterregulatory hormone response (plasma epinephrine 246 +/- 38 vs. 2,785 +/- 601 pmol/l during hypoglycemia, plasma norepinephrine 1.9 +/- 0.2 vs. 2.5 +/- 0.3 nmol/l, and glucagon 38 +/- 7 vs. 92 +/- 17 pg/ml, respectively, P < 0.001 in all), and a relative increase in endogenous glucose production (EGP 0.83 +/- 0.14 mg x kg(-1) x min(-1) during euglycemia yet approximately 50% higher with hypoglycemia [1.30 +/- 0.20 mg x kg(-1) x min(-1)], P < 0.001). Net hepatic glycogen content declined progressively during hypoglycemia to 22 +/- 3% below baseline (P < 0.024). By the final 30 min of hypoglycemia, hepatic glycogen fell from 301 +/- 14 to 234 +/- 10 mmol/l (P < 0.001) and accounted for approximately 100% of EGP. In marked contrast, after an overnight fast, hepatic glycogen concentration in type 1 diabetic subjects (215 +/- 23 mmol/l) was significantly lower than in nondiabetic subjects (316 +/- 19 mmol/l, P < 0.001). Furthermore, the counterregulatory response to hypoglycemia was significantly reduced with small increments in plasma epinephrine and norepinephrine (126 +/- 22 vs. 448 +/- 16 pmol/l in hypoglycemia and 0.9 +/- 0.3 vs. 1.6 +/- 0.3 nmol/l, respectively, P < 0.05 for both) and no increase in plasma glucagon. EGP decreased during hypoglycemia with no recovery (1.3 +/- 0.5 vs. 1.2 +/- 0.3 mg x kg(-1) x min(-1) compared with euglycemia, P = NS), and hepatic glycogen concentration did not change significantly with hypoglycemia. We conclude that glycogenolysis accounts for the majority of EGP during the first 90 min of hypoglycemia in nondiabetic subjects. In intensively treated type 1 diabetes, despite some activation of counterregulation, hypoglycemia failed to stimulate hepatic glycogen breakdown or activation of EGP, factors that may contribute to the defective counterregulation seen in such patients.

Immunotherapy for pancreatic cancer: current concepts.

Despite advances in chemotherapy and surgical technique, patients with pancreatic cancer often succumb to local recurrence or metastatic spread. The need for new therapeutic strategies for this disease coupled with a better understanding of basic immunology have led to the development of novel anti-tumor vaccines. This review focuses on the historical development of tumor vaccines emphasizing the identification of potential pancreatic tumor antigens. The role of both B-cell and T-cell responses in tumor rejection will be reviewed. Methods for antigen presentation, including peptides, recombinant viral and bacterial vectors, dendritic cells, and whole cell approaches will be discussed. The use of immune adjuvants and improved methods of vaccine delivery will also be explored. The full potential for the immunotherapy of pancreatic cancer awaits the results of early phase clinical trials. The development of pancreatic cancer vaccines represents a useful paradigm for the translation of basic research into the clinical arena.