Continuous non-invasive blood pressure monitoring in patients with sleep disorders.

Sleep related breathing disorders are of high prevalence and are often associated with essential hypertension. It is therefore necessary to study blood pressure continuously in all patients with sleep related breathing disorders and arterial hypertension as well as in all patients with essential hypertension and suspected sleep apnoea. To investigate the usefulness of a non-invasive continuous volume-clamp method during sleep we used this technique in parallel with 130 sleep recordings and performed a validation study of the Finapres instrument on a subgroup where continuous invasive blood pressure recordings were available. Absolute pressure values of Finapres are valid when the position and the movement of the sensor were carefully observed and only appropriate segments of the recordings were taken for further evaluation. The high beat to beat resolution of the systolic and diastolic pressure is the main advantage of this non-invasive technique because it reflects rapid blood pressure variations as they occur in sleep related breathing disorders. This could be investigated only invasively until now.     

On-chip non-invasive and label-free cell discrimination by impedance spectroscopy

OBJECTIVES: Many flow-cytometric cell characterization methods require costly markers and colour reagents. We present here a novel device for cell discrimination based on impedance measurement of electrical cell properties in a microfluidic chip, without the need of extensive sample preparation steps and the requirement of labelling dyes. MATERIALS AND METHODS, RESULTS: We demonstrate that in-flow single cell measurements in our microchip allow for discrimination of various cell line types, such as undifferentiated mouse fibroblasts 3T3-L1 and adipocytes on the one hand, or human monocytes and in vitro differentiated dendritic cells and macrophages on the other hand. In addition, viability and apoptosis analyses were carried out successfully for Jurkat cell models. Studies on several species, including bacteria or fungi, demonstrate not only the capability to enumerate these cells, but also show that even other microbiological life cycle phases can be visualized. CONCLUSIONS: These results underline the potential of impedance spectroscopy flow cytometry as a valuable complement to other known cytometers and cell detection systems.     

Measurement of tidal volume by using transthoracic impedance variations in rats

Theapplication of impedance pneumography for monitoring respiration insmall animals has been limited by problems withcalibration. With improved instrumentation, we describethe calibration of tidal volume in anesthetized rats. The detection ofchanges in voltage, reflecting the electrical impedance variationsassociated with respiration, was optimized by using disposable adhesivesilver-silver chloride electrodes, advanced circuitry, andanalog-to-digital recording instrumentation. We found a linearrelationship between change in impedance and tidal volume in individualrats (R²  98%), which was strongly influenced by rat weight. Consequently, acalibration equation incorporating change in impedance and rat weightwas derived to predict tidal volume. Comparison of the predicted andtrue tidal volumes revealed a meanR²  98%,slopes of ~1, intercepts of ~0, and bias of ~0.07 ml. Thepredicted volumes were not significantly affected by either frequencyof respiration or pulmonary edema. We conclude that impedancepneumography provides a valuable tool for the noninvasive measurementof tidal volume in anesthetized rats.     

Measurement of tidal lung volumes in neonates during high-frequency oscillation

High-frequency oscillation (HFO) has been used clinically to ventilate infants with respiratory distress. However, there are problems in monitoring the effects on the respiratory system and in particular in measuring the volumes delivered; this is important information in terms of safety and mechanisms of action of HFO. We have validated two sizes of respiratory jacket for measuring oscillatory volume changes of 0.25–5 ml at frequencies of 2–25 Hz, the volume delivered from a purpose-built oscillator having first been validated. Different combinations of volume and frequencies were then oscillated into each jacket, while it was being worn by a well preterm baby. Studies were performed with each jacket on five babies with weights between 0.82 and 1.86 kg. The results showed that at any given frequency there was a linear relationship between the pressure oscillations measured from a side port of the jacket and the delivered volume. Both jackets showed the same pattern of frequency response, overreading at < 10 Hz and underreading at 10–25 Hz. When appropriately calibrated, the respiratory jacket can be used as a non-invasive method of measuring volumes delivered by HFO.     

Chip-based impedance measurement on single cells for monitoring sub-toxic effects on cell membranes

There is a lack of methods suitable for generation of data about the dynamics of effects on cell membranes with a high sensitivity. Such methods are urgently needed to support the optimisation of interaction of substances, particles or materials with cell. The goal of this article is to use an improved microhole chip system to monitor the alterations of cells due to the interactions of polymer-DNA complexes. This should demonstrate exemplarily that subtoxic effect of biological relevant particles or substances at relevant concentrations can be monitored for several hours. By using a microhole cell chip and a microfluidic unit single cells can be electrically interfaced via microholes and the use of small electrodes with high impedances is not necessary. For separation and positioning of the cells onto the hole negative pressure is applied on the reverse side of the chip. Under cell culture conditions the cell starts to spread on the biocompatible insulating chip membrane resulting in a stable interface to an adherent growing cell. After the spreading process is finished, the polymer/polyplex solution is added and the impedance is measured with respect to time. To illustrate the cellular parameter which can affect the measured impedance a simple simulation based on the finite element method (FEM) is performed. It was shown for the first time that the impedance-based method predicated on the microhole chip can be used for biological relevant substances at relevant concentrations and that it is more sensitive than the well-established biological marker.     

High spatial resolution impedance measurement of EIS sensors for light addressable cell adhesion monitoring

In this paper, impedance measurement of electrolyte-insulator-semiconductor (EIS) structure with high spatial resolution was proposed to monitor cell adhesion. The light addressing ability of this work overcomes the geometrical restrict of cell culture on conventional impedance detection devices such as interdigitated electrode (IDE) and electric cell-substrate impedance sensing (ECIS). Instead of studying cells on predetermined sites of IDE and ECIS, cells cultured anywhere on EIS sensor surface can be addressed and selected as target cells. Principle and primary models for high resolution impedance detection were described and tested by experiments. The EIS sensor was investigated in terms of its intrinsic characteristics, like impedance behavior, voltage characteristic, frequency dependency and photovoltaic effect. Optimized working condition was studied for cell experiments. Cell adhesion under treatment of 0.1% Triton X-100 was monitored using rat kidney cells as the source. Results showed good sensitivity (10% change of impedance) and resolution (40 μm) for cell adhesion impedance detection and suggested this work should be suitable for monitoring cell impedance. Further improvements on sensitivity, spatial resolution were discussed as well as the further applications for single cell monitoring and cell adhesion imaging.     

On-line monitoring of yeast cell growth by impedance spectroscopy

The application of impedance spectroscopy to estimate on-line cell concentration was studied. The estimation was based on the relative variation between electrical impedance measured at low (10 kHz) and high frequencies (10 MHz). Studies were carried out to characterise the influence of changes in physical and chemical parameters on the impedance measurement. Two different possibilities to perform on-line measurements were tested: a simple set-up, based on an in situ probe, gave good results but was not suitable for high agitation and aeration rates. An ex situ flow-through on-line measuring cell was used to overcome these problems, showing a better performance. The use of this set-up for the growth monitorisation of a Saccharomyces cerevisiae culture showed an efficient performance, having the correlation between estimated and measured S. cerevisiae a Pearson coefficient of 0.999.     

Estimation of blood pressure-related parameters by electrical impedance measurement.

In 13 healthy volunteers a computerized experimental set-up was used to measure the electrical impedance of the upper arm at changing cuff pressure, together with the finger arterial blood pressure in the contralateral arm. On the basis of a model for the admittance response, the arterial blood volume per centimeter length (1.4 +/- 0.3 ml/cm), the venous blood volume as a percentage of the total blood compartment (49.2 +/- 12.6%), and the total arterial compliance as a function of mean arterial transmural pressure were estimated. The effective physiological arterial compliance amounted to 2.0 +/- 1.3 microliters.mmHg-1.cm-1 and the maximum compliance to 33.4 +/- 12.0 microliters.mmHg-1.cm-1. Additionally, the extravascular fluid volume expelled by the occluding cuff (0.3 +/- 0.3 ml/cm) was estimated. These quantities are closely related to patient-dependent sources of an unreliable blood pressure measurement and vary with changes in cardiovascular function, such as those found in hypertension. Traditionally, a combination of several methods is needed to estimate them. Such methods, however, usually neglect the contribution of extravascular factors.     

The measurement of cardia output by the thoracic impedance method

The aim of our experiments was to study the thoracic electrical impedance method as a method for measuring cardiac output in anesthetized dogs. Four electrodes were placed around the neck and thorax. A 50 kHz, 1 mA electric current was applied to the outer two electrodes and the two inner electrodes were used to measure impedance changes related to the stroke volume during the cardiac cycle at end-expiratory apnea. The cardiac output obtained by the impedance method was compared to the cardiac output measured by isotope dilution and by the electromagnetic flowmeter. Either mean cardiac output or cardiac output determined beat-to-beat from the pulsatile flow was measured with the latter method. Significant correlations were obtained between the impedance and the isotope dilution method (r = 0.8799), and between the impedance and the electromagnetic (mean) flow measurements (r = 0.7330). The comparison of impedance cardiac output to that determined from the pulsatile flow (beat-to-beat) also showed a good correlation (r = 0.7618). The effect of changing the fluid and air contents in the chest on the basal thoracic impedance was also studied.     

A non-invasive method of tendon force measurement

The ability to measure the forces exerted in vivo on tendons and, consequently, the forces produced by muscles on tendons, offers a unique opportunity to investigate questions in disciplines as varied as physiology, biomechanics, orthopaedics and neuroscience. Until now, tendon loads could be assessed directly only by means of invasive sensors implanted within or attached to these collagenous structures. This study shows that the forces acting on tendons can be measured, in a non-invasive way, from the analysis of the propagation of an acoustic wave. Using the equine superficial digital flexor tendon as a model, it is demonstrated that the velocity of an ultrasonic wave propagating along the main axis of a tendon increases with the force applied to this tendon. Furthermore, we show that this velocity measurement can be performed even in the presence of skin overlying the tendon. To validate this measurement technique in vivo, the ultrasonic velocity plots obtained in the Achilles tendon at the walk were compared to the loads plots reported by other authors using invasive transducers.     

Diarrhea in neonatal piglets caused by K99+ST+ enterotoxigenic Escherichia coli

Enterotoxigenic Escherichia coli strains were isolated from the feces of 34.4% of 64 diarrheaic neonatal piglets on seven farms. Of a total of 518 isolates, 86 (16.6%) were enterotoxigenic and grouped into four phenotypes: K99+ST+ (K99 pilus antigen and heat-stable enterotoxin producing, 36 strains), ST+ (37 strains), K88+LT+ (K88 pilus antigen and heat-labile enterotoxin producing, 11 strains), and K88+ST+ (2 strains). K99+ST+ and ST+ isolates showed multiple drug resistance and most of those (58.3% and 56.8%, respectively) belonged to O serogroup 101. A K99+ST+ isolate proved to be capable of inducing diarrhea and death in hysterectomy-produced colostrum-deprived piglets when orally inoculated.     

Limitation of heart growth in neonatal piglets by simvastatin and atorvastatin: comparison with pravastatin

The pig heart grows rapidly in the first few days after birth. We examined the effects of simvastatin, atorvastatin, and pravastatin on heart growth in piglets. After vehicle, 2 mg x kg(-1) x day(-1) simvastatin, 2 mg x kg(-1) x day(-1) atorvastatin, or 4 mg x kg(-1) x day(-1) pravastatin were administered orally for 6 days, the thoracic cavity was opened, and the heart was removed under pentobarbital sodium (30 mg/kg ip) anesthesia. The heart was perfused to remove residual blood. After the heart was blotted dry, the right and left ventricular free walls were dissected. Each free wall was weighed and used for determination of DNA, RNA, and protein concentrations and mitogen-activated protein (MAP) kinase activity. Simvastatin and atorvastatin resulted in smaller increases with age in the weight, concentrations of RNA and protein, and activity of MAP kinase in the left ventricular free wall, whereas pravastatin did not. The parameters of heart growth in the right ventricular free wall were not appreciably affected by either drug. The blood pressure and heart rate were not changed by the treatments. These results suggest that simvastatin and atorvastatin interfere with heart growth in neonatal piglets after birth, especially in the left ventricular free wall.     

Oxygen monitoring in neonatal medicine

In perinatal intensive care medicine, hypoxia and hyperoxia are both detrimental to the patient. PO2 measurements of arterial blood can be done in different ways: (1) by analysing blood obtained from an arteriopuncture; (2) by analysing blood obtained from an indwelling arterial (usually umbilical) catheter; (3) by using an indwelling catheter with a built-in O2 electrode; (4) by analysing alveolar air for PO2; (5) by measuring cutaneous arterial PO2 transcutaneously. The common principle of all electrodes mentioned is the polarographic one. It appears that for the clinician, the transcutaneous electrode will become the method of choice in the future because of its non-invasiveness to the patient and because of its capability to provide a continuous PO2 record.     

NF-kappaB-mediated expression of iNOS promotes epithelial defense against infection by Cryptosporidium parvum in neonatal piglets

Cryptosporidium sp. parasitizes intestinal epithelium, resulting in enterocyte loss, villous atrophy, and malabsorptive diarrhea. We have shown that mucosal expression of inducible nitric oxide (NO) synthase (iNOS) is increased in infected piglets and that inhibition of iNOS in vitro has no short-term effect on barrier function. NO exerts inhibitory effects on a variety of pathogens; nevertheless, the specific sites of iNOS expression, pathways of iNOS induction, and mechanism of NO action in cryptosporidiosis remain unclear. Using an in vivo model of Cryptosporidium parvum infection, we have examined the location, mechanism of induction, specificity, and consequence of iNOS expression in neonatal piglets. In acute C. parvum infection, iNOS expression predominated in the villous epithelium, was NF-kappaB dependent, and was not restricted to infected enterocytes. Ongoing treatment of infected piglets with a selective iNOS inhibitor resulted in significant increases in villous epithelial parasitism and oocyst excretion but was not detrimental to maintenance of mucosal barrier function. Intensified parasitism could not be attributed to attenuated fluid loss or changes in epithelial proliferation or replacement rate, inasmuch as iNOS inhibition did not alter severity of diarrhea, piglet hydration, Cl- secretion, or kinetics of bromodeoxyuridine-labeled enterocytes. These findings suggest that induction of iNOS represents a nonspecific response of the epithelium that mediates enterocyte defense against C. parvum infection. iNOS did not contribute to the pathogenic sequelae of C. parvum infection.