Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and parathyroid ultrasound in comparison with bone histology

Bone biopsies were studied in 73 patients to determine if a two-site radioimmunometric assay for serum bone alkaline phosphatase (BAP), total serum alkaline phosphatase (ALP), serum intact parathyroid hormone (iPTH), hand X-rays, regional bone mineral density (BMD) measurements and parathyroid enlargement detected by ultrasonography could accurately predict renal osteodystrophy. In the patients studied 57 had hyperparathyroid bone disease, 4 mixed renal osteodystrophy, 3 adynamic bone disease, 1 osteomalacia and 8 normal histology. Serum BAP, ALP and iPTH correlated positively with mineral apposition rate, osteoblastic, osteoid and eroded surface. In the diagnosis of hyperparathyroid bone disease serum iPTH was the most sensitive investigation, detecting 81% of patients at a level > 100 pg/ml but with a specificity of only 66%. Serum BAP was more sensitive, 70% at a level of > 10 ng/ml, than serum total ALP, 30% at a level of 300 IU/l, with similar specificities, 92 and 100%, respectively. Ultrasound detection of an enlarged parathyroid gland had a sensitivity of 64% and a specificity of 100% for the diagnosis of hyperparathyroid bone disease. Hand X-rays had a poor sensitivity, 47%, but a high specificity, 92%, for the detection of hyperparathyroid bone disease. The majority of patients had regional BMD values within the normal reference range and this test was of poor discriminatory value. The non-invasive markers were unable to distinguish between patients with low turnover, mild hyperparathyroidism and patients with normal histology. In conclusion the measurement of serum iPTH is a useful screening tool for the detection of hyperparathyroid bone disease which can be confirmed by the finding of a raised serum BAP or parathyroid enlargement. For definitive diagnosis, however, the gold standard remains bone biopsy and at present one cannot recommend any non-invasive method as an adequate substitute.     

Quenched BODIPY dye-labeled casein substrates for the assay of protease activity by direct fluorescence measurement

We have prepared casein conjugates of two BODIPY dyes for use as fluorogenic protease substrates in homogeneous assays. Both conjugates are labeled to such an extent that the dyes are efficiently quenched in the protein, yielding virtually nonfluorescent substrate molecules. These fluorogenic substrates release highly fluorescent BODIPY dye-labeled peptides upon protease digestion, with fluorescence increases proportional to enzyme activity. These quenched substrates are suitable for the continuous assay of enzymatic activity using standard fluorometers, filter fluorometers, or fluorescence microplate readers using either fluorescein excitation and emission wavelengths to measure BODIPY FL casein hydrolysis or Texas Red wavelengths to detect proteolysis of BODIPY TR-X casein. Most current techniques for detecting protease activity, such as the fluorescein thiocarbamoyl casein (FTC-casein) protease assay, require extensive manipulation, including separation steps, and are therefore labor intensive and error-prone. In comparison, we found the BODIPY dye-labeled casein protease assays to be simple and precise and to have greater sensitivity and a broader dynamic range of detection than the FTC-casein assay. We were able to sensitively detect the activities of a wide variety of enzymes with these new substrates, including serine, acid, sulfhydryl, and metalloproteases. We also found the assay suitable for quantitating protease inhibitor concentrations and for real-time analysis of proteolysis.     

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.     

Increase of striatal dopamine release by cadmium in nursing rats and its prevention by dexamethasone-induced metallothionein

Repeated daily intraperitoneal (i.p.) administrations of cadmium (CdCl2, 1 mg/kg per day for 5 days) increased striatal dopamine (DA) release (180% of controls) and turnover (150% of controls) in 13-day-old rats. Cd treatment also increased striatal metallothionein (MT) content (161%), Cd (127%) and lipid peroxidation (LPO, 190%). In addition, Cd treatment decreased striatal tyrosine hydroxylase (TH) activity (-28%), and such an effect may result from D-2 receptor blockade as a consequence of excessive dopamine release, since sulpiride (a specific D-2 receptor antagonist) administration to Cd-treated rats abolished the effect of Cd on TH. No effect was observed on striatal monoamine oxidase (MAO) activity. Dexamethasone (Dx) treatment increased striatal MT content and caused no effect on either DA release or turnover. However, Dx administration prevented the effects caused by Cd, including the increased DA release and enhanced striatal lipid peroxidation. These results indicate that toxic effects on the brain are to be expected as a result of Cd exposure and that Dx administration can attenuate them.     

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.     

How office space affects programming productivity

The relationship between office size and noise level is one of the most significant, yet least investigated, factors affecting software productivity. According to Tom DeMarco and Tim Lister (1992), US programmers with more than 80 square feet of private, noise-free office space consistently outperform programmers who occupy two- or three-person cubicles. The result was the Santa Teresa Programming Laboratory in San Jose, California, which opened in 1978. The author discusses some requirements of an optimal programming office environment. He considers the effectiveness of home working     

Using neural networks to learn hand-eye co-ordination

The work presented in this paper shows how the association of proprioceptive and exteroceptive stimuli can enable a Kohonen neural network, controlling a robot arm, to learn hand-eye co-ordination so that the arm can reach for and track a visually presented target. The approach presented in this work assumes no a priorimodel of arm kinematics or of the imaging characteristics of the cameras. No explicit representation, such as homogeneous transformations, is used for the specification of robot pose, and camera calibration and triangulation are done implicitly as the system adapts and learns its hand-eye co-ordination by experience. This research is validated on physical devices and not by simulation.