Circulating levels of interleukin-6 and tumor necrosis factor-alpha are elevated in primary hyperparathyroidism and correlate with markers of bone resorption--a clinical research center study

The pathogenesis of PTH-induced bone loss is uncertain. Experimental evidence suggests that PTH induces the production by osteoblasts of the bone-resorbing cytokine, interleukin-6. We measured the circulating levels of interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta and examined their relationship to biochemical markers of bone turnover in 38 patients with primary hyperparathyroidism (7 of whom also were studied after successful parathyroid adenomectomy), 6 patients with hypoparathyroidism, and 12 subjects with normal parathyroid function. The patients with untreated primary hyperparathyroidism had mean serum levels of interleukin-6 that were 16-fold higher than control values (mean +/- SEM; primary hyperparathyroidism 18.6 +/- 2.1 pg/mL, controls 1.1 +/- 0.1; P < 0.001). Circulating levels of interleukin-6 soluble receptor (primary hyperparathyroidism 41.7 +/- 1.2 ng/ mL, controls 25.1 +/- 1.0; P < 0.001), and tumor necrosis factor-alpha (primary hyperparathyroidism 11.6 +/- 0.8 pg/mL, controls 2.5 +/- 0.2; P < 0.001) were also elevated. After successful parathyroid adenomectomy, levels of each of these cytokines fell into the normal range. The mean levels of interleukin-6, its soluble receptor, and tumor necrosis factor-alpha in the subjects with hypoparathyroidism were lower than control values (P < 0.001 for each variable). There was no difference between subjects with primary hyperparathyroidism and controls in the circulating level of interleukin-1 beta. In the subjects with untreated primary hyperparathyroidism, serum levels of interleukin-6 correlated strongly with those of intact PTH (r = 0.47, P = 0.003) and biochemical markers of bone resorption: serum deoxypyridinoline (r = 0.93, P < 0.001), serum type I collagen carboxyterminal telopeptide (r = 0.87, P < 0.001), urinary pyridinoline (r = 0.81, P < 0.001), and urinary deoxypyridinoline (r = 0.63, P = 0.005). Levels of tumor necrosis factor-alpha correlated less strongly with the same variables: PTH (r = 0.41, P = 0.01), serum deoxypyridinoline (r = 0.48, P = 0.002), serum type I collagen carboxyterminal telopeptide (r = 0.46, P = 0.004), urinary pyridinoline (r = 0.61, P = 0.008), and urinary deoxypyridinoline (r = 0.61, P = 0.007). Levels of interleukin-6 also correlated with those of tumor necrosis factor-alpha (r = 0.44, P = 0.005). Multiple regression analysis indicated that interleukin-6, but not tumor necrosis factor-alpha, was independently predictive of bone resorption. We conclude that serum levels of interleukin-6 and tumor necrosis factor-alpha are increased in patients with primary hyperparathyroidism and are normalized by successful surgical treatment. The finding that these cytokines correlate with biochemical markers of bone resorption suggests that they play a role in the pathogenesis of bone loss in primary hyperparathyroidism.     

Fault model for sub-micron CMOS ULSI circuits reliability assessment

A new fault model, based on the general Percolation theory applied to long-channel CMOS VLSI circuits, has been recently introduced. It was shown that a reliability risk appears only when process-related defects create a pattern independent current path in standby mode. An acceptable reliability risk defines pass/fail criteria. A screening technique, based on this model, presents a strong correlation between rejected devices and Early Failure Rate.In this paper, the general Percolation approach was applied to short-channel CMOS VLSI circuits. Unlike long-channel CMOS VLSI, defect-free short-channel CMOS VLSI circuits inherently have a pattern-independent standby current. It results from a short-channel MOSFET current in the off state. In this case, the defect-related component of this current might be released only by means of a multi parameter fail criterion. Experimental results that confirm this conclusion are presented and discussed. The Reliability Risk assessment technique employing this model shows a strong correlation between rejected devices and long term reliability for 32-bit 0.35 μM CMOS microprocessors.     

Pyrenebutyric acid as an optical oxygen probe in the intact cerebral cortex

The application of the fluorochrome pyrenebutyric acid (PBA) as an in vivo quantitative probe for intracellular oxygen tension (iPO2) is reported. PBA is nontoxic, noninvasive, nonconsumptive, and allows optical monitoring of iPO2 on line. Cats were anesthetized with ether and lesioned midcollicularly to produce cerveau isolé preparations with optical monitoring via a compensated microfluorometer. The "normal" iPO2 was determined to be 42.8 /- 8.6 (SD) mmHg. Decrease in cerebral perfusion results in observing a decreased iPO2. This method of monitoring iPO2 was found to overcome drawbacks inherent in the polarographic technique and to posess additional advantages.     

Parathyroid hormone-related protein-(1-36) is biologically active when administered subcutaneously to humans

PTH-related protein (PTHrP) is responsible for most cases of humoral hypercalcemia of malignancy (HHM). It mimics the actions of PTH as a result of its structural homology with PTH and its ability to bind to and signal via the PTH/PTHrP receptor in bone and kidney. PTHrP-(1-36) appears to be one of several secretory forms of PTHrP. This peptide has been administered iv to normal volunteers previously and has been shown to produce effects that are qualitatively and quantitatively the same as those produced by PTH-(1-34). To determine whether PTHrP-(1-36) could be used sc in humans as a diagnostic reagent for elucidating the differences between HHM and hyperparathyroidism, we performed a 12-h dose-finding study examining whether sc PTHrP-(1-36) could elicit effects on mineral homeostasis. PTHrP-(1-36) administered sc in three doses (0.82, 1.64, and 3.28 micrograms/kg) to 21 normal women produced increases in circulating PTHrP-(1-36), reductions in serum phosphorus and the renal phosphorus threshold, increments in fractional calcium excretion and nephrogenous cAMP excretion, and increases in plasma 1,25-dihydroxyvitamin D. These changes were highly significant in statistical terms and were observed at doses that had no effect on serum calcium or endogenous PTH. These studies demonstrate the feasibility of using PTHrP-(1-36) as a diagnostic probe for future studies aimed at elucidating the differing pathophysiologies of HHM and hyperparathyroidism.     

Changes in relationship satisfaction across the transition to parenthood: A meta-analysis.

The U.S. government has recently spent several hundred million dollars to promote healthy relationships in new parents. The influx of money implies that relationships of new parents are at elevated risk for declining satisfaction and dissolution. This meta-analysis aggregates data from 37 studies that track couples from pregnancy to after the birth of the first child and 4 studies that track childless newlywed couples over time and compare couples who do and do not become parents. Results indicate significant, small declines in relationship satisfaction for both men and women from pregnancy to 11 months postbirth; 5 studies that followed couples for 12–14 months found moderate-sized declines. Seven variables moderated the decrease in relationship satisfaction from pregnancy to early parenthood. However, the decrease in satisfaction may not indicate anything unique about the transition to parenthood; the 4 studies following newlyweds indicated that those who do not become parents experience a decrease in relationship satisfaction similar to that of parents across a comparable span of time. Implications for prevention and future directions are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The differential association between change request qualities and resistance, problem resolution, and relationship satisfaction.

Although research supports the negative sequelae of the “demand/withdrawal” pattern, research is scant on the impact of “nondemanding” change requests (e.g., specific, increasing, “we” requests). We hypothesize that such change requests will be associated with less partner withdrawal/resistance, better problem resolution, and greater relationship satisfaction. Seventy-two conversations between couples who were recruited through random digit dialing were coded for change request qualities. Results indicate that wife specific and “we” requests led to less husband resistance, and husband increasing and “we” requests led to less wife resistance. Greater percentages of wife and husband specific and “we” requests were related to better problem resolution in the conversation, and greater percentages of wife specific and “we” requests were related to greater wife satisfaction. Research and clinical implications are detailed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influencing ethnocentrism in small discussion groups through a film communication.

Method and procedure described with tables and graphs. 12 experimental groups using the California Ethnocentrism Scale. "Extent of participation in discussion depends upon the amount of learning that has taken place." 18 references. (PsycINFO Database Record (c) 2010 APA, all rights reserved)