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Biomedical subjects

R Graaff

Publications and source records attributed to R Graaff.

At least 19 recordsLinked to original sources

Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy.

AIMS/HYPOTHESIS: The accumulation of AGE is related to the progression of the renal, retinal and vascular complications of diabetes. However, the relationship with diabetic neuropathy remains unclear. We recently showed that skin autofluorescence, measured non-invasively with an AutoFluorescence Reader (AFR), could be used to assess skin AGE accumulation. We evaluated the relationship between skin autofluorescence and the severity of diabetic neuropathy. MATERIALS AND METHODS: Skin autofluorescence in arbitrary units (AU) was assessed in 24 diabetic patients with a history of neuropathic foot ulceration (NP(+)), 23 diabetic patients without clinical neuropathy (NP(-)) and 21 control subjects, using the AFR. Arterial occlusive disease was excluded in all. The severity of foot ulceration was assessed by the Wagner score. Peripheral nerve function was assessed by neurography, measuring motor and sensory nerve conduction velocity and amplitude of the median, peroneal and sural nerves. Heart rate variability (HRV) and baroreflex sensitivity (BRS) were measured by Finapres to assess autonomic nervous function. RESULTS: Autofluorescence was increased in NP(-) compared with control subjects. In NP(+) patients, autofluorescence was further increased and correlated with the Wagner score. Autofluorescence correlated negatively with nerve conduction velocity and amplitude, HRV and BRS in both NP(+) and NP(-) groups. Autofluorescence correlated with age, diabetes duration, mean HbA(1)c of the previous year, serum creatinine level, presence of microalbuminuria and severity of diabetic retinopathy. CONCLUSIONS/INTERPRETATION: Skin autofluorescence correlates with the severity of peripheral and autonomic nerve abnormalities in diabetes, even before being clinically manifest. The AFR may be a convenient and rapid clinical tool for assessing risk of progression of long-term diabetic complications.

Aged↗

Influence of hemodilution of plasma proteins on erythrocyte aggregability: an in vivo study in patients undergoing cardiopulmonary bypass.

Erythrocyte aggregation is known to be affected by a number of factors including the concentration of various plasma proteins. This study was performed to examine the in vivo effect of hemodilution of plasma proteins on erythrocyte aggregation in patients undergoing cardiopulmonary bypass (CPB) surgery. Blood samples were taken before, during, and after operation from 40 coronary artery bypass grafting patients who were operated with CPB and concomitant hemodilution (CPB, n=20) and who without (nonCPB, n=20). Erythrocyte aggregation was determined with a LORCA aggregometer, during which all samples were standardized to a hematocrit level of 40%. Results showed that in the CPB patients the aggregation index (AI) dropped to 44% of its preoperative baseline level 5 minutes after the start of hemodilution (from 47.7+/-10.1 to 26.6+/-11.4, p<0.01). Meanwhile, plasma concentration of fibrinogen (Fb) dropped to 55%, haptoglobin to 85%, ceruloplasmin to 55%, and albumin to 67%. In the nonCPB patients, however, there was only a slight drop in AI and the concentrations of plasma proteins during the similar period of time. On postoperative day 1, AI was rebounded to 37.1+/-12.4 in CPB patients compared with 44.3+/-11.7 in nonCPB patients. At baseline, AI was correlated only with Fb. During CPB and hemodilution, AI was correlated not only with Fb but also with haptoglobin and ceruloplasmin. Postoperatively, significant correlationship was found between AI and Fb, CRP, haptoglobin, ceruloplasmin, as well as albumin. These results indicate that hemodilution of plasma proteins significantly reduces the aggregability of erythrocytes in patients undergoing CPB. Besides Fb, other plasma proteins also contribute to AI during the early postoperative period when patients are recovering from CPB surgery.

Acute-Phase Proteins↗

Simple non-invasive assessment of advanced glycation endproduct accumulation.

AIMS/HYPOTHESIS: The accumulation of AGE is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. All current measurements of AGE accumulation require invasive sampling. We exploited the fact that several AGE exhibit autofluorescence to develop a non-invasive tool for measuring skin AGE accumulation, the Autofluorescence Reader (AFR). We validated its use by comparing the values obtained using the AFR with the AGE content measured in extracts from skin biopsies of diabetic and control subjects. METHODS: Using the AFR with an excitation light source of 300-420 nm, fluorescence of the skin was measured at the arm and lower leg in 46 patients with diabetes (Type 1 and 2) and in 46 age- and sex-matched control subjects, the majority of whom were Caucasian. Autofluorescence was defined as the average fluorescence per nm over the entire emission spectrum (420-600 nm) as ratio of the average fluorescence per nm over the 300-420-nm range. Skin biopsies were obtained from the same site of the arm, and analysed for collagen-linked fluorescence (CLF) and specific AGE: pentosidine, N(epsilon)-(carboxymethyl)lysine (CML) and N(epsilon)-(carboxyethyl)lysine (CEL). RESULTS: Autofluorescence correlated with CLF, pentosidine, CML, and CEL ( r=0.47-0.62, p</=0.002). In 32 of 46 diabetic patients (70%), autofluorescence values were above the 95% CI of the mean value in control subjects, and correlated with age, diabetes duration, mean HbA(1)c of the previous year and creatinine levels. CONCLUSIONS/INTERPRETATION: The AFR offers a simple alternative to invasive measurement of AGE accumulation and, to date, has been validated in non-pigmented skin. The AFR may prove to be a useful clinical tool for rapid risk assessment of AGE-related long-term complications in diabetes mellitus and in other conditions associated with AGE accumulation.

Adult↗

Analysis of red blood cell aggregation in cardio-pulmonary bypass (CPB) surgery.

Not much is known about red cell aggregation during cardio-pulmonary bypass surgery (CPB). Blood samples from 19 patients undergoing CPB were anticoagulated with EDTA. Hematocrit was adjusted to 40%. A red blood cell aggregometer (LORCA) measured changes in light reflection from each blood sample after cessation of the rotation, and calculated an aggregation index (AI). Reflection measurements were stored. Because LORCA software failed for 87 of 171 samples, we developed new software, and applied it to the stored reflection measurements. This software failed only in 7 out of 171 cases and showed that all LORCA failures occurred for AI < 40%. The new calculations revealed that the aggregation index significantly decreased from 46.6 +/- 10.1 (mean +/- standard deviation) baseline to 22.8 +/- 8.3 at the end of CPB and recovered to 37.1 +/- 13.5 at day 1. It is concluded that the new software can be used to study decreased red cell aggregation during CPB.

Coronary Artery Bypass↗

Instrument-independent flux units for laser Doppler perfusion monitoring assessed in a multi-device study on the renal cortex.

To investigate the feasibility of instrument-independent perfusion units for laser Doppler flowmetry, a comparison was performed of two commercial fiberoptic laser Doppler perfusion monitors measuring the same flux situation for two different types of probes. In vivo measurements were performed on the cortex of pig's kidney, with an ultrasonic arterial flow meter as reference. The flow was mainly varied by internal arterial constriction using a balloon catheter. For each probe, instruments are compared in terms of the ratio of laser Doppler flux and arterial flow. For a given probe, the flux-to-flow ratios of the two instruments show a linear mutual relationship for a wide variety of arterial flows and laser Doppler fluxes. In vitro measurements were performed on an aqueous suspension of polystyrene microspheres. For the probe with interfiber distance 500 microm the ratio of the in vivo fluxes appears to agree within 16% to the value found in vitro, while for the 250-microm probe a difference of 28% was found. For a wide range of fluxes, the in vivo flux values of one instrument can be translated into flux values for the other instrument, in spite of the instrumental differences. This enables the user to render experimental results independent of the specific instrument, thus facilitating multi-center studies.

Animals↗

On the influence of flow conditions and wettability on blood material interactions.

In this review, we hypothesise that, next to biocompatibility, optimal blood compatibility depends on a combination of biomaterials wettability and the shear stress prevailing in the device. The wettability is discussed in seven different categories of devices, that differ substantially from each other with regard to shear stress and exposure time. These seven categories are stents, prosthetic heart valves, vascular prostheses, cardiopulmonary bypass, hemodialysis, vena cava filters and blood bags. In high shear applications, in combination with blood activation, platelet deposition and thrombosis appear to be major problems and platelet inhibitors are most effective. Exposure of blood to a large biomaterial surface, with or without antithrombotic coating, results in reduction of platelet function. Material-independent activation aggravates this process. In low shear applications, platelets only seem supportive for coagulation and anticoagulants should be used.

Animals↗

Practical improvements on photon diffusion theory: application to isotropic scattering.

Based on the analysis of an isotropic point source in an infinite, isotropically scattering turbid medium, we suggest several modifications to the well-known diffusion theory. Compared with standard diffusion theory these modifications, which require very little extra mathematics, lead to a substantially better approximation of the exact expressions. The improved expression gives reasons to reconsider the basic concept of time-resolved diffusion theory.

Biophysical Phenomena↗

Corrections for inhomogeneities in biological tissue caused by blood vessels.

In tissue optics, the assumption that blood is homogeneously distributed in tissue can give rise to miscalculations because blood is found only in blood vessels. In our paper randomly oriented blood vessels are treated as particles for which we obtained apparent absorption and scattering coefficients by means of the Monte Carlo method. Apart from this correction for the contribution of blood properties in tissue, a correction for the contribution of the surrounding tissue proved to be needed as well. The results found with our model were compared with available results from the literature.

Blood Vessels↗

Pressure drop, shear stress, and activation of leukocytes during cardiopulmonary bypass: a comparison between hollow fiber and flat sheet membrane oxygenators.

The membrane oxygenator is known to be superior to the bubble oxygenator, but little information is available about the difference between the hollow fiber and flat sheet membrane oxygenators with regard to pressure drop, shear stress, and leukocyte activation. In this study, we compared these 2 types of membrane oxygenators in patients undergoing cardiopulmonary bypass (CPB) surgery with special focus on leukocyte activation and pressure drop across the oxygenators. Plasma concentration of elastase, a marker indicating leukocyte activation, increased to 593+/-68% in the flat sheet oxygenator group versus 197+/-42% in the hollow fiber oxygenator group (p<0.01) at the end of CPB compared to their respective baseline concentrations before CPB. Pressure drop across the oxygenator was significantly higher in the flat sheet group than in the hollow fiber group throughout the entire period of CPB (p<0.01). High pressure drop across the oxygenator as well as the calculated shear stress was positively correlated with the release of elastase at the end of CPB (r = 0.760, p<0.01, r = 0.692, p<0.01). However, this positive correlation existed in the flat sheet oxygenator but not in the hollow fiber oxygenator. Clinically, both membrane oxygenators have satisfactory performance in O2 and CO2 transfer. These results suggest that a higher pressure drop across the flat sheet oxygenator is associated with more pronounced activation of leukocytes in patients undergoing cardiopulmonary bypass.

Adult↗

A simple and accurate formula for the sound velocity in water.

The sound velocity in test objects and phantoms is often measured by performing a differential measurement with pure water. To promote standardization, a simple formula for the sound velocity in water is derived that renders true values within 0.20 m s(-1) over the temperature range 15-35 C. The formula is given by c = 1404.3 + 4.7 T - 0.04 T2, with sound velocity c in m s(-1) and temperature T in C.

Phantoms, Imaging↗

Effect of location of the sensor on reflectance pulse oximetry.

OBJECTIVE: The influence of the location of the sensor on reflectance pulse oximetry during fetal monitoring in labour was investigated using the newborn infant as a model. METHODS: Seven healthy infants were studied between 19 and 48 hours after term delivery. Recordings of reflectance pulse oximetry were obtained from eight different sites on the infant's head. The relative changes in red to infrared light (R/IR) were determined. In pulse oximetry R/IR values are converted to arterial oxygen values by means of an empirically derived calibration curve. RESULTS: Significantly lower R/IR values were found at the forehead compared with the fontanelle, the parietal and occipital position, and the temporal area. Conversion to oxygen saturation values revealed a difference of up to 13.4% in oxygen saturation between the forehead and the occipital area. CONCLUSION: Assuming that the arterial blood oxygen saturation did not change substantially, our findings indicate that in reflectance pulse oximetry there is no unique relation between R/IR and arterial oxygen saturation. The differences in reflectance pulse oximetry at the various sites are explained by differences in optical properties (scattering and absorption) of the tissue underneath the sensor. These will affect the red and infrared light reaching the detectors in a different way, and consequently R/IR changes. Because during intrapartum monitoring exact positioning of the sensor on the fetal head is usually impossible, the accuracy of fetal reflectance pulse oximetry is impaired.

Fetal Monitoring↗

Reflectance pulse oximetry at the forehead of newborns: the influence of varying pressure on the probe.

OBJECTIVE: Transmission pulse oximetry (TPO) is not a practical method of intrapartum fetal monitoring of arterial oxygen saturation. Reflectance pulse oximetry (RPO) requires a sensor applied to the skin of the fetal head and may be a useful technique. During labor, various degrees of pressure will be exerted on the RPO sensor. Previous studies have shown that moderate pressure on the sensor can improve the RPO signal. At increasing pressure, however, blood flow underneath the sensor will be occluded. This study examines the influence of pressure applied to the RPO sensor on the signal from the forehead of healthy newborns as a model for the fetal situation. METHODS: After institutional approval, 12 healthy newborns were studied. The RPO probe was placed at the forehead. Pressure on the probe was increased stepwise from 0 to 80 mmHg, and the effect on the ratio between the relative changes of the red and infrared light intensities (R/IR, inversely related to oxygen saturation) and pulse sizes was evaluated. Additionally, the effect of firm pressure (> 150 mmHg) on the probe was evaluated. RESULTS: R/IR values remained virtually unchanged when pressure onto the probe was increased from 0 to 80 mmHg, although the standard deviation slightly decreased. The pulse size increased as pressure on the probe increased. During firm pressure on the probe (> 150 mmHg), plethysmographic signals remained detectable, but R/IR values markedly increased. CONCLUSIONS: In newborns, mild to moderate pressure on the probe has little influence on the RPO signal at the forehead. Even during firm pressure, RPO can be used to obtain pulsatile signals, that presumably derive from tissue underneath the skull, such as the cerebral circulation.

Fetal Monitoring↗

Aspects of similarity in tissue optics with strong forward scattering.

The similarity studied in this paper links the diffusion exponent to the reduced albedo. If F is the ratio of the diffusion exponent assumed by standard diffusion theory to the actual value of the diffusion exponent, it is shown that for forward-scattering functions, as often found in biological tissues, the values of F approach limiting curves. These curves depend on a constant in the homologous scattering patterns, which can describe Henyey-Greenstein scattering patterns, but which can also approximate Rayleigh-Gans phase functions. Finally, a practical approach for estimating the solution for mixtures of these forward-scattering phase functions with isotropic scatterers has been given.

Humans↗

Reflectance pulse oximetry at the forehead improves by pressure on the probe.

In this study, we investigated the possibility of improving reflectance (back-scatter) pulse oximetry measurements by pressure applied to the probe. Optimal signal detection, with the probe applied to an easily accessible location, is important to prevent erroneous oxygen saturation readouts. At the foreheads of 10 healthy adult volunteers, the effects of pressure applied onto the reflectance pulse oximeter probe were studied. Distances between the LEDs (660 nm and 940 nm) and the three photodiodes in the sensor were 4 mm, 7 mm, and 10 mm. For each detector, recordings were evaluated regarding red-to-infrared (R/IR) ratios and pulse sizes in relation to the stepwise increased pressure applied to the probe. R/IR variability decreased with applied pressures between 60 and 120 mm Hg. These findings are partly attributed to a corresponding increase in red and infrared pulse sizes at the detectors, which results in an improved signal-to-noise ratio. It is thought that pressure onto the oximeter sensor forces venous blood out of the tissues underneath the sensor. Consequently, the disturbing influence of pulsating and non-pulsating venous blood is reduced. Moreover, the increased difference in vessel diameter between diastole and systole and the corresponding difference in light absorption and an increase in flow velocities, causes an increase in pulse size with increasing pressure on the probe. Pressure applied to the probe may be useful in increasing the accuracy of reflectance pulse oximetry.

Adult↗