R Van Hoof

Hypertension in the Elderly

Secondary hyperparathyroidism plays an important role in the mineral and bone disorders that are associated with cardiovascular events in chronic kidney disease patients. Secondary hyperparathyroidism is partially due to decreased calcium-sensing receptor expression in parathyroid glands in these patients. Calcimimetics have been demonstrated to be particularly useful to control parathyroid hormone (PTH) oversecretion and concomitantly reduce serum Ca2+ and phosphorus levels in dialysis patients. However, recent findings highlight the role of calcium-sensing receptor allosteric coactivators as inhibitors of the development of vascular calcification. Calcimimetics could prevent the vascular calcification process by controlling not only PTH overfunction, hypercalcemia and hyperphosphatemia, but also by directly modulating vascular calcium-sensing receptors. In this review, the authors describe the recently demonstrated role played by calcium-sensing receptor and its modulation by calcimimetics on uremia-induced vascular calcification.

Highly reliable CMOS-integrated 11MPixel SiGe-based micro-mirror arrays for high-end industrial applications

In this paper we report for the first time on the fabrication of very reliable CMOS-integrated 10 cm2 11 MPixel SiGe-based micro-mirror arrays on top of 6 level metal CMOS wafers. The array, which is to be used as Spatial Light Modulator (SLM) for optical maskless lithography [1,2,3] consists of 8 mum x 8 mum pixels which can be individually addressed by an analog voltage to enable accurate tilt angle modulation. The pixel density is almost double compared to the state-of-the-art [4]. A stable average cupping below 7 nm, an RMS roughness below 1 nm and long lifetime (>1012 cycles, no creep [5]) are demonstrated.

The Trough-to-Peak Ratio as an Instrument to Evaluate Antihypertensive Drugs

The U.S. Food and Drug Administration designed the trough-to-peak ratio as an instrument for the evaluation of long-acting antihypertensive drugs, but the ratios are usually reported without accounting for interindividual variability. This study investigated how the trough-to-peak ratio would be affected by interindividual and intraindividual variability and by smoothing of the diurnal blood pressure profiles. The ambulatory blood pressure was recorded on placebo in 143 hypertensive patients (diastolic pressure on conventional measurement > 95 mm Hg). After 2 months, the recordings were repeated on 10 mg (n = 66) or 20 mg (n = 77) lisinopril given once daily between 7 and 11 PM. The baseline-adjusted trough-to-peak ratios were determined from diurnal blood pressure profiles with 1-hour precision. Lisinopril reduced (+/- SD) the 24-hour pressure by 16 +/- 17 mm Hg for systolic and 10 +/- 10 mm Hg for diastolic (P < .001). According to the usual approach, disregarding interindividual variability, the trough-to-peak ratio was 0.72 for systolic pressure and 0.67 for diastolic pressure. In the 143 patients the ratios were not normally distributed. They were the same on both lisinopril doses. When interindividual variability was accounted for, the median trough-to-peak ratio was 0.34 (P5 to P95 interval, -0.46 to 0.87) for systolic pressure and 0.26 (-0.44 to 0.84) for diastolic pressure. In 66 patients examined twice on 10 mg lisinopril at a median interval of 32 days, the trough-to-peak ratios were characterized by large intraindividual variability.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in plasma lipids and apoproteins associated with physical training in middle-aged sedentary men

The effect of endurance training on plasma lipoproteins was investigated in 27 healthy sedentary men between the ages of 20 and 55 years. During the first 4 months of the study, 13 of them (group A) participated in a training program (3 hours/wk), whereas the others served as control subjects (group B). At the end of this period the control subjects also underwent a 4-month training program. In both groups the training significantly increased physical working capacity at a heart rate of 130 bpm (PWC130), whereas it decreased the resting heart rate (p less than 0.05). Concomitantly with this improvement in cardiorespiratory fitness, a significant increase in the high-density lipoprotein (HDL) cholesterol concentration was observed (p less than 0.01); this was due to an increase in both HDL2 beta and HDL2 alpha + 3 cholesterol concentrations. The plasma total and HDL-apoprotein AI and apoprotein AII concentrations were not significantly affected by the training. Significant decreases in plasma triglyceride (p less than 0.05), very-low-density lipoprotein cholesterol (p less than 0.05), and low-density lipoprotein (LDL) cholesterol (p less than 0.001) concentrations were also observed, but only in group B, which showed a much greater increase in PWC130 at the end of the training period than group A; the decrease in the LDL cholesterol concentration in this group was accompanied by a slight decrease in the LDL-apoprotein B concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Above-IC generic poly-SiGe thin film wafer level packaging and MEM device technology: Application to accelerometers

We present an attractive poly-SiGe thin film packaging and MEM (Micro Electro-Mechanical) platform technology for integrating various packaged MEM devices above standard CMOS. The packages, having cavities as large as 1mm2, make use of pillars designed to withstand subsequent molding during 1st level packaging. Covers on top of the release holes avoid deposition inside the cavity during sealing. Hermeticity is proven in vacuum, air and N2 atmosphere and at different temperatures. Packaged functional accelerometers sealed at a pressure around 1bar, have an equivalent performance in measuring accelerations of about 1g compared to a piezoelectric commercial reference device.

Changes in erythrocyte sodium and plasma lipids associated with physical training

The intracellular concentrations and transmembrane fluxes of Na+ and K+ in erythrocytes, and plasma lipids were investigated in 30 middle-aged volunteers, before and after physical training. During the first 4 months of the study, half of the subjects (group A) were subjected to a training programme (3 h/week), while the others (group B) served as controls. At the end of the control period the group B subjects also underwent a period of training. At the end of the training, in both experimental groups, the intra-erythrocyte Na+ concentration was decreased (P less than 0.001); the magnitude of this decrease was related to the increase achieved in physical working capacity (r = -0.44; P less than 0.05). After training the activity of the erythrocyte Na+-Li+ counter-transport system was decreased (P less than 0.001) in both groups, whereas Na+,K+ cotransport activity was increased (P less than 0.001). The training intervention did not affect erythrocyte ouabain-sensitive 86Rb uptake, or the calculated rate constant for ouabain-sensitive Na+ efflux. Furthermore, the plasma concentrations of high density lipoproteins (HDL)2- and HDL3-cholesterol (P less than 0.001) markedly increased in both groups during the training period. However, these changes were not significantly correlated with the observed training-induced changes in erythrocyte transmembrane cationic fluxes. It is concluded that physical training decreases intra-erythrocyte Na+ concentration. No significant associations between training-induced changes in plasma lipids and erythrocyte sodium balance could be demonstrated.

CMOS-integrated poly-SiGe cantilevers with read/write system for probe storage device

A poly-SiGe technology enabling a dense array of micro-cantilevers and tips on CMOS is demonstrated. Built from a dual-thickness structural layer, the cantilevers feature a very small initial bending and have a compliant torsional suspension with a stiffness of 3×10−10 Nm/rad. Sharp tips are formed in a low-temperature amorphous silicon layer by isotropic plasma etching. An electrical read/write system is formed by connecting the tip to the CMOS with a suspended platinum trace, running on top of the cantilever.

Poly-SiGe-Based MEMS Thin-Film Encapsulation

This paper presents an attractive poly-SiGe thin-film packaging and MEM (microelectromechanical) platform technology for the generic integration of various packaged MEM devices above standard CMOS. Hermetic packages with sizes up to 1 mm2 and different sealed-in pressures ( ~ 100 kPa and ~ 2 kPa) are demonstrated. The use of a porous cover on top of the release holes avoids deposition inside the cavity during sealing, but leads to a sealed-in pressure of approximately 100 kPa, i.e. atmospheric pressure. Vacuum ( ~ 2 kPa) sealing has been achieved by direct deposition of a sealing material on the SiGe capping layer. Packaged functional accelerometers sealed at around 100 kPa have an equivalent performance in measuring accelerations of about 1 g compared to a piezoelectric commercial reference device. Vacuum-sealed beam resonators survive a 1000 h 85°C/85%RH highly accelerated storage test and 1000 thermal cycles between -40°C and 150°C.

Highly reliable and extremely stable SiGe micro-mirrors

This paper presents very reliable and stable micro- mirrors made of hydrogenated microcrystalline SiGe (muc-SiGe:H) at temperatures that would allow processing above standard CMOS circuitry. Very flat micro-mirrors with sizes ranging between 7.5 x 7.5 and 16 x 16 mum2 size and submicron hinges are fabricated. No hinge creep is observed over a period of 20 days and no fatigue damage is seen after 5 x 1010 cycles.

Comparison of the effect of celiprolol and nifedipine on blood pressure and plasma lipids

Summary During a double-blind, randomized study in hypertensive patients, changes in blood pressure (BP) and in plasma lipid and lipoprotein levels during treatment with celiprolol were compared with those occurring during nifedipine treatment. Fifty-three patients (28 men and 25 women) with mild-to-moderate hypertension, aged 20–64 years, were studied. After a 1-month placebo run-in period, patients were randomly assigned to receive either nifedipine (40 mg daily) or celiprolol (200 mg daily) each time using a double dummy technique. After 6 weeks, dosages of each drug could be doubled. Both drugs caused similar reductions in blood pressure but after 12 weeks treatment, the percentage of decrease in diastolic BP (DBP) was more pronounced (p < 0.01) in the nifedipine group (-18%) than in the celiprolol group (-12%). After 6 weeks, there were no differences in plasma lipids between the two treatment groups. However, the changes after 12 weeks treatment were different (p < 0.05) between the groups, leading to lower levels of plasma esterified cholesterol, low-density lipoprotein (LDL) cholesterol and apoprotein AI, All, and B in the celiprolol group. Plasma lecithin cholesterol acyltransferase activity (LCAT) was not modified, suggesting that reverse cholesterol transport was not affected by the drugs. In both treatment groups, a significant positive relationship was observed between changes in LDL cholesterol and apoprotein B. As compared with nifedipine, celiprolol after 12-week therapy had a rather favorable plasma lipid profile. The clinical relevance of such findings, in terms of prevention of cardiovascular complications, has yet to be established.