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Biomedical subjects

D Ramaekers

Publications and source records attributed to D Ramaekers.

At least 19 recordsLinked to original sources

[The gap between evidence-based medicine (EBM) and practice: how is the "evidence" brought together?].

The implementation of the growing body of evidence in health care is a major matter of concern. Health care professionals and policy makers often only had a limited if any training in searching for relevant and objective information efficiently. Furthermore, information sources of high quality are not readily available in the health care system or are often not accessible in daily practice. Health care workers depend on other sources for information about newest developments: marketing from the industry, media, opinion leaders, CPD, etc. In this lecture, three possible ways to summarize the available evidence and to forward pre-appraised sources of information to health care professionals are discussed: systematic reviews, practice guidelines and health care technology assessment reports. Finally, the recently founded Belgian health care knowledge centre is presented. This government agency has the mission to diminish the gap between the scientific community and health care policy makers.

Evidence-Based Medicine↗

[Systemic validation of clinical practice guidelines: the AGREE network].

INTRODUCTION: Over recent decades, the number of available clinical practice guidelines has enormously grown. Guidelines should meet specific quality criteria to ensure good quality. There is a growing need for the developement of a set of criteria to ensure that potential biases inherent in guideline development have been properly addressed and that the recommendations for practice are valid and reliable. AIM: The AGREE-collaboration is an international network that developed an instrument to critically appraise the methodological quality of guidelines. AGREE promotes a clear strategy to produce, disseminate and evaluate guidelines of high quality. METHOD: In the first phase of the international project the AGREE-instrument was tested in 11 different countries. Based on this experience the instrument was refined and optimised. In the second phase it was disseminated, promoted and evaluated in 18 participating countries. Belgium was one of them. RESULTS: The Belgian partner in the AGREE-project developed 3 workshops and established 13 validation committees to validate guidelines from Belgian developer groups. We collected 33 questionnaires from participants of the workshops and the validation committees, in which we asked for primary experiences and information on the usefulness and applicability of the instrument. We were also interested in the shortcomings of the instrument and potential strategies to bridge them. DISCUSSION: More efforts should be made to train methodological experts to gain certain skills for a critical appraisal of clinical practice guidelines. Promoting the AGREE-instrument will lead to a broader knowledge and use of quality criteria in guideline development and appraisal. CONCLUSION: The development and dissemination of an international list of criteria to appraise the quality of guidelines will stimulate the development of methodologically sound guidelines. International comparisons between existing guidelines will lead to a better collaboration between guideline developers throughout the world.

Canada↗

Parasympathetic heart rate modulation during parabolic flights.

During parabolic flight short periods of microgravity and hypergravity are created. These changes influence cardiovascular function differently according to posture. During the 29th parabolic flight campaign of the European Space Agency (ESA), the electrocardiogram (ECG) was recorded continuously in seven healthy volunteers in two positions (standing and supine). Five different phases were differentiated: 1 g (1 g=9.81 m/s(2)) before and after each parabola, 1.8 g at the ascending leg of the parabola (hypergravity), 0 g at the apex, 1.6 g at the descending leg (hypergravity). We assessed heart rate variability (HRV) by indices of temporal analysis [mean RR interval (meanRR), the standard deviation of the intervals (SDRR), and the square root of the mean squared differences of successive intervals (rMSSD) and coefficient of variation (CV)]. In the supine position no significant differences were shown between different gravity phases for all HRV indices. In the standing position the 0 g phase showed a tendency towards higher values of meanRR compared to the control and to the other phases ( p=NS). SDRR, rMSSD and CV were significantly higher compared to control ( p<0.05). Significantly higher values for meanRR in the supine position at 1 g and hypergravity ( p<0.05) were found when compared to standing. SDRR was significantly higher at 0 g in the standing position compared to supine [95 (44) ms vs. 50 (15) ms; p<0.05] and lower in other phases. rMSSD and CV showed the same trend ( p=NS). We confirm that, during parabolic flights, position matters for cardiovascular measurements. Time domain indices of HRV during different gravity phases showed: (1) higher vagal modulation of the autonomic nervous system in microgravity, when compared with normo- or hypergravity in standing subjects; and (2) no differences in supine subjects between different g phases.

Adaptation, Physiological↗

Effects of melanocortins on cardiovascular regulation in rats.

1. Of the melanocortin peptides, gamma(2)-melanocyte-stimulating hormone (MSH) has been attributed a cardiovascular effect, inducing an increase in blood pressure and heart rate. Although still controversial, this effect, based on pharmacological blockade experiments, is supposed to be mediated through sympathetic activation. 2. The aims of the present study were to identify the N-terminal pro-opiomelanocortin (N-POMC) fragments and melanocortins that influence blood pressure and heart rate and to investigate the real-time changes in baroreflex sensitivity and in sympathetic and vagal modulation underlying cardiovascular effects in conscious rats without the use of pharmacological blockade. 3. Intracerebroventricular administration of different melanocortins and N-POMC induced a long-lasting dose- dependent pressor response from 1 nmol onwards, with only a small initial bradycardic response with the highest dose. 4. Coinciding with this pressor response, an elicitation of the low-frequency (LF) component was observed in spectral analysis of both blood pressure variability (BPV) and heart rate variability (HRV), followed by the high-frequency (HF) component in at least BPV. Baroreflex sensitivity remained unchanged. 5. After intravenous administration, gamma(2)-MSH produced a short-lasting dose-dependent pressor and cardioaccelerator response with very rapid onset with concentrations from 1 nmol onwards. 6. Continuous infusion of gamma(2)-MSH depressed baroreflex sensitivity and simultaneously increased both components of BPV, with a radical reduction of the LF component and a preserved vagal HF component in HRV. 7. Of all the intravenously administered melanocortins, only gamma(2)-MSH was active. The central effect is likely to depend on an increase of (alpha-)sympathetic outflow. 8. For the peripheral effect, gamma(2)-MSH appeared to act as a baroreceptor reflex-blocking agent, being compatible with a role in the acute stress response.

Animals↗

Analysis of heart rate variability with correlation dimension method in a normal population and in heart transplant patients.

INTRODUCTION: The correlation dimension (CD) method is related to chaos theory and is used to quantify heart rate variability (HRV). The CD is a measure for the amount of correlations present in the signal. METHODS: The algorithm used to calculate the CD is based on the method of Grassberger and Proccacia. The method was first validated on signals with known CD and then applied to HRV-signals of heart transplants and an age-matched control group of healthy subjects. The CD of the corresponding surrogate time series was calculated to investigate non-linear correlations in the HRV-signal. Circadian variations of the CD were studied in 20 healthy subjects, including men and women. RESULTS: The value of the CD for healthy subjects ranged from 2.12 to 5.53 with a mean value of 4.32. For heart transplants, only a few time series showed a finite value of the CD that varied between 2.10 and 5.60. Also, a significant difference was found between the CD of the original and the surrogate time series in healthy subjects. The CD of women is higher than the CD of men, and this difference was more pronounced during the night than during the day. CONCLUSIONS: This limited study shows that the CD alone cannot be used to make a distinction between HRV-signals of healthy subjects and of heart transplants. However, there is evidence that there are non-linear correlations present in the HRV-signal and that there are significant gender and circadian differences in the CD.

Algorithms↗

Wavelet decomposition analysis of heart rate variability in aerobic athletes.

Heart rate variability (HRV) can be quantified, among others, in the frequency domain using digital signal processing (DSP) techniques. The wavelet transform is an alternative tool for the analysis of non-stationary signals. The implementation of perfect reconstruction digital filter banks leads to multi resolution wavelet analysis. Software was developed in LabVIEW. In this study, the average power was compared at each decomposition level of a tachogram, containing the consecutive RR-intervals of two groups of subjects: aerobic athletes and a control group. Compared to the controls, the aerobic athletes showed an increased power in all frequency bands. These results are in accordance with values obtained by spectral analysis using the Fourier transform, suggesting that wavelet analysis could be an appropriate tool to evaluate oscillating components in HRV, but in addition to classic methods, it also gives a time resolution.

Adolescent↗

Short-term heart rate variability in young athletes.

OBJECTIVES: The purpose of this study was to determine whether the type of training in a young population differentiates heart rate variability parameters between athlete groups and sedentary subjects. METHODS: The effect of different types of physical training on heart rate variability was evaluated in 10 aerobic trained athletes, in 7 anaerobic trained athletes, in 7 rugby players (mixed type training) and in 10 sedentary control subjects. All groups were age matched (18-34 years). Electrocardiogram tracings were recorded digitally in the supine position and standing position. Measures of heart rate variability were obtained, from both time- and frequency analysis of 10 min resting heart rate. After these tests, blood pressure was measured using an automatic inflation cuff. RESULTS: Resting heart rate was lower in aerobic and mixed type athletes compared to controls. Only aerobic athletes had evidence of increased vagal activity in the time domain compared with control subjects (increased SDNN supine, increased rMSSD supine and standing and pNN50 standing). In the frequency domain, aerobic athletes presented with both higher low-frequency and high-frequency power in the standing position and low-frequency power in the supine position compared to controls. CONCLUSIONS: It can be concluded that heart rate variability is affected by chronic exercise, especially in endurance trained athletes. This infers that especially aerobic exercising can have beneficial effects on the cardiovascular risk profile.

Adolescent↗

The analysis of heart rate variability in unrestrained rats. Validation of method and results.

An experimental setting and software were developed to evaluate cardiac autonomic function in unrestrained rats. Subcutaneously implanted ECG electrodes and an indwelling venous catheter were tunneled to a tail cuff in five rats. The ECG was A/D converted at 1000 Hz. After peak detection, a time series of RR intervals was obtained. Programs for the analysis of heart rate variability (HRV) were implemented in LabVIEW. Statistical properties were determined in the time domain. After cubic spline function curve fitting, resampling at 0.1 s and test for stationarity, power spectral analysis was performed on sampled records of 30 min duration after applying a sliding Hanning window (Welch method: 256 points (duration 25.6 s), 50% overlap and 0.039 Hz resolution). Algorithms were tested with simulated signals consisting of isolated frequency components, which were retrieved at their exact locations. Physiological validation of the system was performed by, beta-adrenergic and cholinergic blockade and by forced breathing at a fixed rate. Measurements were performed on five unrestrained rats under basal conditions. Mean RR was 174.2 +/- 3.6 ms; S.D., 13.3 +/- 4.6 ms; rMSSD, 5.2 + /- 1.2 ms; pNN10, 3.5 +/- 1.9% and pNN5, 18.7 +/- 6.4%. Low (0.19-0.74 Hz) and high frequency (0.78-2.5 Hz) power were determined (and also percent of low to total and high to total): 18.42 +/- 10.74 ms2 (22.9 +/- 6.5%) and 15.66 +/- 5.56 ms2 (19.9 +/- 2.7%), and the ratio low/high: 1.16 +/- 0.39. In conclusion, HRV analysis programs were developed and thoroughly tested through simulations and in vivo, under basal conditions and after pharmacological blockades. Using this software, HRV data from unrestrained rats were obtained.

Animals↗

Detection of melanocortin-3 receptor mRNA in immature rat pituitary: functional relation to gamma3-MSH-induced changes in intracellular Ca2+ concentration?

We have previously shown that gamma3-MSH stimulates DNA replication in lactotrophs, somatotrophs and thyrotrophs of early postnatal rat pituitary in culture. Since the melanocortin-3 (MC-3) receptor is the only known receptor displaying high affinity for gamma3-MSH, the present study explored whether mRNA of the latter receptor is present in the pituitary and whether the receptor is functional. RT-PCR of RNA extracts from 14-day-old rat pituitary revealed the presence of MC-3 receptor mRNA in both the anterior and the neurointermediate lobe. The identity of the amplified products was confirmed by sequence analysis. Dispersed cells of 14-day-old female rats (24 h in culture) were exposed to gamma3-MSH, and changes in intracellular free calcium levels ([Ca2+]i) were assessed by means of fluo-3 video imaging. Gamma3-MSH evoked a rapid and maintained oscillating [Ca2+]i increase in 5%, 10% and 15% of the cells at a dose of 0.1, 1 and 10 nM, respectively. The MC-3/MC-4 receptor antagonist Ac-Nle4-c[Asp5,(D-Nal(2)7,Lys10]alpha-MSH-(4-10)-NH2 (SHU 9119) blocked the effect of gamma3-MSH in about 50% of the responsive cells. The present data suggest that the MC-3 receptor is expressed in the rat pituitary but that this receptor mediates only half of the effects of its putative ligand, gamma3-MSH, on [Ca2+]i. Part of the effect of gamma3-MSH may be mediated by a MC-3 receptor in a functional state different from the one studied previously in transfected cell lines or by a hitherto unidentified MC receptor.

Animals↗

Neurocardiology: the benefits of irregularity. The basics of methodology, physiology and current clinical applications.

Cardiovascular variability in heart rate and blood pressure can be used to quantify the autonomic modulation of cardiovascular function. Although the first studies were only published 10 to 20 years ago, there is presently a vast amount of knowledge from numerous publications that allows a better insight into the neural control mechanisms of the heart. The development of methods such as heart rate variability and baroreflex sensitivity prompted a multidisciplinary approach since many aspects were involved: mathematics, signal processing, physiology and cardiology. Therefore, it is obvious that an adequate understanding of certain basic principles is necessary before its clinical potential can be fully exploited. This current review outlines the physiological background and the fundamental methodology used in the field of neurocardiology by presenting the newer insights and developments from both fundamental and clinical sides. Recent publications indicate that neurocardiological applications in (risk stratification of) myocardial infarction, congestive heart failure and heart transplant patients can be expected to enter daily clinical practice in the next millennium.

Baroreflex↗

Heart rate variability and heart rate in healthy volunteers. Is the female autonomic nervous system cardioprotective?

AIMS: Heart rate variability has been proposed as an indicator of cardiovascular health. Since women have a lower cardiovascular risk, we hypothesized that there are gender differences in autonomic modulation. METHODS AND RESULTS: In 276 healthy subjects (135 women, 141 men) between 18 and 71 years of age, 24 h heart rate and heart rate variability were determined. All heart rate variability parameters, except for pNN50 and high frequency power, were higher in men. After adjustment for heart rate, we obtained gender differences for: the standard deviation (P=0.049), the standard deviation of the 5 min average (P=0.047), low frequency power (absolute values, P=0.002; normalized units, P<0.001) and ratio low frequency/high frequency (P<0.001). There were no significant gender differences in heart rate variability parameters denoting vagal modulation. Gender differences were confined to age categories of less than 40 years of age. The majority of heart rate variability parameters decreased with age. Only in men, was a higher body mass index associated with a higher heart rate and with lower heart rate variability parameters (P<0.001). CONCLUSION: Cardiac autonomic modulation as determined by heart rate variability, is significantly lower in healthy women compared to healthy men. We hypothesize that this apparently paradoxical finding may be explained by lower sympathetic activity (low frequency power) in women. This may provide protection against arrhythmias and against the development of coronary heart disease.

Adolescent↗

Association between cardiac autonomic function and coping style in healthy subjects.

The link between personality and cardiac function is insufficiently characterized. We postulated that in a healthy population, cardiac autonomic function is linked to coping style. In 276 healthy volunteers, between the ages of 18 and 71, the Utrecht Coping List was used to evaluate different coping strategies. Trait anxiety was scored by the Spielberger State Trait Anxiety Inventory. A 24-hour Holter recording was used to calculate heart rate variability (HRV). For HRV parameters and coping mechanisms this study demonstrated gender-specific differences and correlations with age. In men (n = 141) higher active coping was associated with less global autonomic activity or SDANN (rs = -0.27, P < 0.001). This relationship was most prevalent in young (18-30 years) men (rs = -0.45, P < 0.005). Higher expression of negative emotions or anger was related to both higher vagal (rs = 0.23 for rMSSD, P < 0.01) tone and higher LF power (rs = 0.23, P < 0.01). In young men expression of negative emotions or anger was associated with LF power (rs = 0.37, P < 0.01) and in middle-aged (31-50 years) men with vagal tone (rs = 0.43 for rMSSD, P < 0.005) and heart rate (rs = -0.41, P < 0.005). Higher comforting ideas was related to higher LF power (rs = 0.23 for LF power, P < 0.005), and this especially in middle-aged men (rs = 0.37, P < 0.01). In women (n = 135), no significant correlations between coping style and HRV indices were found. We conclude that in normal individuals, at least in men, our findings suggest a relationship between coping style and cardiac autonomic function.

Adaptation, Psychological↗

Expression of the low-affinity p75 nerve growth factor receptor in the developing rat pituitary gland.

We investigated, by means of in situ hybridization with a digoxigenin-labelled RNA probe, the expression of the low-affinity p75 nerve growth factor receptor (NGFR) in the developing pituitary primordium of the rat. In 13-day pc embryos, intense staining of p75 NGFR mRNA was present in the cytoplasm of all cells of Rathke's pouch. In day-17 pc embryos p75 NGFR expression was present primarily in the cells of the intermediate lobe. In the newborn rat pituitary only very weak staining was observed, predominantly in the intermediate lobe. In neural structures the staining at day 13 pc was comparable to that of day 17 pc. Since p75 expression is seen very early during pituitary development and declines during the time the expression of pituitary hormonal phenotypes are steadily increasing, we suggest that the p75 NGFR expression in Rathke's pouch may play a temporally defined role in the commitment rather than in the differentiation of the various pituitary cell types.

Animals↗

Effect of POMC(1-76), its C-terminal fragment gamma3-MSH and anti-POMC(1-76) antibodies on DNA replication in lactotrophs in aggregate cell cultures of immature rat pituitary.

Treatment of aggregate cell cultures of 14-day-old rat pituitary for 40 h with purified human (h) POMC(1-76) dose-dependently augmented the number of DNA replicating lactotrophs as estimated by autoradiography of [3H]-thymidine (3H-T) incorporation in cells immunostained for prolactin (PRL). No such effect was seen on the total number of 3H-T labelled cells (the majority of which did not contain any pituitary hormone in a detectable amount) or on the total number of lactotrophs. The effect of hPOMC(1-76) on 3H-T incorporation in lactotrophs was blocked by concomitant treatment with anti-hPOMC(1-76) monoclonal and polyclonal antibodies cross-reactive with rat POMC(1-74). The latter anti-hPOMC(1-76) antibodies also decreased the number of 3H-T incorporating lactotrophs in the absence of hPOMC(1-76). Gamma3-MSH, which is the C-terminal domain of hPOMC(1-76), mimicked the effect of hPOMC(1-76) on 3H-T incorporation in lactotrophs but its potency was lower than that of hPOMC(1-76). Other melanocortin (MC) peptides such as alpha- and beta-MSH were also effective but were less potent than gamma3-MSH. The difference in potency was not due to partial degradation of the peptides. hPOMC(1-76) did not affect 3H-T incorporation in other pituitary cell types. In contrast gamma3-MSH also augmented the number of 3H-T labelled somatotrophs and thyrotrophs. In the embryonic kidney 293 cell line stably transfected with the MC-3 receptor, gamma3-MSH (10 nM) augmented cAMP formation up to 30 times. In contrast, hPOMC(1-76) (100 nM) was inactive in this test system, indicating this peptide is not an agonist at the MC-3 receptor. The present investigation further supports the role of rat POMC(1-74) as a paracrine growth factor in the development of lactotrophs. The active core of POMC(1-76) does not seem to be restricted to its C-terminal domain gamma3-MSH as the latter peptide displays a growth promoting effect that is different from that of POMC(1-76): it is less potent, it is not specific for lactotrophs and whereas the effect of gamma3-MSH may be mediated by the MC-3 receptor that of POMC(1-76) is not.

Animals↗

Heart rate variability after cardiac transplantation in humans.

The reappearance of cardiac innervation after cardiac transplantation remains a matter of debate. We evaluated the ability of heart rate variability (HRV) analysis to detect the extent and time course of functional cardiac allograft reinnervation. Time- and frequency-domain analysis of heart rate was performed on Holter recordings of 120 heart transplant and four heart-lung transplant recipients. A high frequency (HF) component was clearly distinguished on visual inspection of power spectral density in 42 patients. In eight patients an HF component of normal magnitude was detected. The other 34 patients in this group, including all four heart-lung transplants, presented with a very small HF component. The other 82 patients showed a flat spectrum. The group with an HF component of normal amplitude was significantly different, compared to the other groups, for all HRV parameters. Serial plotting of HRV parameters of the patients with an HF component of normal amplitude against time posttransplant, revealed, from 12 months onwards, a progressive increase of parameters denoting HF variability. In five heart transplant patients with acute allograft rejection, the use of HRV analysis for rejection monitoring was unsuccessful. These results suggest that, inasmuch as the HF component of HRV is caused by parasympathetic cardiac innervation, the HF component of normal amplitude, observed in only a minority of cardiac transplant recipients (6%), is a marker for parasympathetic reinnervation. The evolution over time of this HF component is compatible with a biological phenomenon as gradual parasympathetic reinnervation of the sinus node.

Autonomic Nervous System↗