What is driving health system change?

Socially amoral economic forces now drive health system change. The authors, assisted by a panel of experts on employers, health plans, providers, and consumers, discuss current drivers such as (1) employers' price-focused purchasing, without good quality/value measures; (2) health plans' growing successes and market clout; (3) providers declining prospects and fears about their future; and (4) consumers' worries about less choice. Future influences will include Medicare reforms, better information, and pro-consumer regulation of managed care, as well as rising social distress. The health system's future is now open for resolution in an evolving, imperfect market.     

Expression of interstitial collagenase (matrix metalloproteinase-1) is related to the activity of human endometriotic lesions

The effects of the competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, LY235959, were determined on the analgesic and hypothermic effects as well as on the development of tolerance to these effects of U-50,488H, a kappa-opioid receptor agonist in mice and rats. In the mouse, a single injection of LY235959 given 10 min prior to U-50,488H did not modify the analgesic action of the latter. Similarly, chronic administration of LY235959 twice a day for 4 days did not modify U-50,488H-induced analgesia in mice. Repeated pretreatment of mice with LY235959 dose-dependently attenuated the development of tolerance to the analgesic actions of U-50,488H. In the rat, LY235959 by itself produced a significant analgesia and prior treatment of rats with LY235959 enhanced the analgesic action of U-50,488H. Similar effects were seen with the hypothermic action. Pretreatment of rats with LY235959 attenuated the development of tolerance to the analgesic but not to the hypothermic action of U-50,488H. These results provide evidence that LY235959 produces differential actions on nociception and thermic responses by itself and when given acutely with U-50,488H in mice and rats. However, when the animals are pretreated with LY235959, similar inhibitory effects are observed on the development of tolerance to the analgesic action of U-50,488H in both the species. These studies demonstrate an involvement of the NMDA receptor in the development of kappa-opioid tolerance and suggest that the biochemical consequences of an opioid's interaction with the opioid receptor are not the only factors that contribute to the acute and chronic actions of opioid analgesic drugs.     

Reproducibility of brachial ultrasonography and flow-mediated dilatation (FMD) for assessing endothelial function

Minimally invasive plastic surgery has expanded beyond the original confines of aesthetic applications to encompass all our endeavors in an attempt to restrict the size of surgical scars, limit postoperative discomfort, and hasten recovery of function. This evolution has already delineated methods to raise our workhorse muscle flaps and has negated the risks of laparotomy for various visceral flaps. It is then only a logical progression to use these endoscopic techniques to harvest fascial flaps so as to avoid the notorious donor site morbidity of the fasciocutaneous flap, which has certainly hindered the rapid acceptance of these otherwise valuable flaps. Endoscopic-facilitated elevation of a local adipofascial flap is described for which little or no additional skin incisions need ever be made.     

Altered serial position learning after frontal lobe lesion

The serial position function is a powerful and highly reliable feature of human learning, with well-described primacy and recency effects. We tested the hypothesis that frontal lobe lesions in patients would disrupt the serial position function since such patients are known to have disturbed temporal ordering, learning in the presence of interference, encoding and organizational approaches to learning. Performance was compared in patients with focal, acquired lesions of frontal and non-frontal cortices, using a standardized paradigm of verbal list learning. Results indicated a similar pattern of performance on first trial learning for the two groups. However, across learning trials, frontal lesion subjects failed to maintain significant primacy and recency effects. Non-frontal lesion subjects consistently showed the expected U-shaped serial position curve across all trials. Subjective organization in learning was particularly deficient in the dorsolateral frontal lesion subjects. We propose that serial position effects are qualitatively different after frontal lobe lesion, being transitory and prone to alteration by the cumulative effects of disturbed temporal-spatial processing across learning trials.     

Writer's cramp--a focal dystonia: etiology, diagnosis, and treatment

The complaint of hand cramps is common among patients who consult the neurologist or the hand surgeon. Classic writer's cramp is best characterized as a focal dystonia, and electromyographic studies reveal a characteristic pattern of cocontraction of the agonist and antagonist muscles of the forearm and hand. Although the outcome of treatment in the past has been unsatisfying, recent experience with new pharmacologic therapy, such as injections of botulinum toxin, has produced promising results. Further experience and improvement in this area will likely increase the therapeutic success in the treatment of writer's cramp and other focal dystonias.     

Effects of Na+ and Mg2+ on the structures of supercoiled DNAs: comparison of simulations with experiments

Recent cryo-electron microscopy (cryo-EM) results suggest that sufficient NaCl concentration (> or approximately 0.1 M) and superhelix density (> or approximately-0.05) cause circular DNAs to adopt highly extended, tightly interwound configurations, in which the strands are laterally contiguous along almost their entire length. Millimolar levels of MgCl2 reportedly act synergistically with NaCl to produce similar conformations. However, Monte Carlo simulations with purely repulsive interduplex forces failed to reproduce such structures. In the present work, solution measurements of particular physical properties were performed both to characterize the effects of Na+ and Mg2+ on DNA structure and to provide quantitative tests of Monte Carlo simulations of circular DNAs. Supercoiled p30 delta DNAs in 10 mM Tris plus 0, 0.122, and 0.1 M NaCl, and 0.1 M NaCl plus 4 mM Mg2+ were examined by static and dynamic light scattering (LS and DLS), time-resolved fluorescence polarization anisotropy (FPA) of intercalated ethidium, and circular dichroism (CD) spectroscopy. Upon addition of 0.122 M NaCl, the radius of gyration (Rg) decreased substantially, which indicates that p30 delta adopts a more compact structure. This contradicts the cryo-EM studies, where molecular extension and Rg both increase upon adding 0.1 M NaCl. In 0.1 M NaCl, the torsion constant measured by FPA is practically invariant to superhelix density, and the plateau diffusion coefficient at large scattering vector (Dplat) is likewise nearly the same at both relaxed and native superhelix densities. Such invariance is difficult to reconcile with any transition from relaxed circles to tightly interwound structures with laterally contiguous strands. Metropolis Monte Carlo simulations were performed to generate canonically distributed sets of structures, from which average Do values and scattered intensity ratios, [symbol: see text]I (zero) [symbol: see text]/[symbol: see text] l(k) [symbol: see text], were calculated. Agreement between simulations and experiments in regard to [symbol: see text] I(O) [symbol: see text] /[symbol: see text] I(k) [symbol: see text], D(zero) and the supercoiling free energy, delta Gsc (delta l), is remarkably good for the most extensively studied p30 delta samples. The simulated structures exhibit no sign of very tight interwinding with extensive lateral contacts, but instead exhibit most probable superhelix diameters of 85 to 90 A. When 4 mM Mg2+ was added to native supercoiled p30 delta in 0.1 M NaCl, Rg decreased, D(zero) increased, and the longest internal relaxation rate (1/tau 2(zero)) increased, all of which indicate a further overall contraction of the molecular envelope. The torsion constant exhibited a slight increase that is hardly statistically significant. In this case, agreement between the simulations and experiments was only semi-quantitative for most samples investigated, although the predicted contraction was exhibited by all five samples of p30 delta and one of pBR322 DNA. The simulated structures in 0.1 M NaCl plus 4 mM Mg2+ again showed no sign of extensive lateral contacts. A plausible explanation is proposed for the highly extended, tightly interwound structures seen in cryo-EM, and explicitly tested by Monte Carlo simulations of a 1000 bp circular DNA at +25 and -50 degrees C. Structures identical to those seen in cryo-EM are in fact the equilibrium structures in the simulations at -50 degrees C, and the estimated time for equilibration (2.3 x 10(-6) second) is much smaller than the estimated time for vitrification (1 x 10(-4) second).     

Vector characterization of photodetectors, photoreceivers, andoptical pulse sources by time-domain pulse response measurements

Deconvolution of measurement system effects from pulse response measurements is demonstrated to yield reproducible, accurate characterization of the impulse response (and vector frequency response) of a photodetector or photoreceiver, as well as the intensity waveform of an optical pulse. Calibration is based on a <3-ps FWHM (full width at half maximum) optical pulse and a 50-GHz 3-dB bandwidth electrical sampling system. Vector characterization of a photodetector/photoreceiver to >40 GHz and an optical pulse source to >30 GHz are demonstrated. Calibration and effects of noise are discussed     

A New Approach to Solving Applied Location/AIIocation Problems

Abstract: Facility location and customer allocation problems are pervasive in industry and in the private sector. In this paper, we outline a new approach to solving these problems that avoids the need to resort to integer programming techniques. The approach exploits the mathematical structure of the problem as well as characteristics frequently found in applied location/allocation problems. Using this approach, large scale problems are readily solvable on personal computers. We illustrate the approach on a small example and provide computational results based on a real-world application of the technique. Extensions to include additional problem features are also discussed.     

ACAT inhibitors derived from hetero-Diels-Alder cycloadducts of thioaldehydes

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.