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Biomedical subjects

J H Meijer

Publications and source records attributed to J H Meijer.

At least 19 recordsLinked to original sources
PubMed2004

Convergence of circadian and sleep regulatory mechanisms on hypocretin-1.

Hypocretin is a potential regulator of sleep and wakefulness and its levels fluctuate with the day-night cycle with high levels during the animal's activity period. Whether the daily fluctuations are driven endogenously or by external light cycles is unknown. We investigated the circadian and homeostatic regulation of hypocretin in the absence of environmental light cycles. To this purpose we performed repetitive samplings of cerebrospinal fluid in rats through implanted microcannulas in the cisterna magna and determined hypocretin-1 levels by radioimmunoassay. These experiments were also performed in rats that received a lesion of the suprachiasmatic nucleus (SCN), a major pacemaker for circadian rhythms in mammals. The results showed sustained rhythmicity of hypocretin in constant dim red light in control animals. SCN-lesioned animals showed no circadian rhythms in hypocretin and mean hypocretin levels were remarkably low. The results indicate that the SCN is indispensable for rhythmicity in hypocretin and induces a daily increase in hypocretin levels during the animal's active phase. Additional sleep deprivation experiments were carried out to investigate homeostatic regulation of hypocretin. Hypocretin levels increased in response to sleep deprivation in both control and SCN-lesioned animals, demonstrating that sleep homeostatic control of hypocretin occurs independently from the SCN. Our data indicate that the circadian pacemaker of the SCN and sleep homeostatic mechanisms converge on one single sleep regulatory substance.

Analysis of Variance↗
PubMed2002

Comparing spot electrode arrangements for electric impedance cardiography.

This study investigates whether an arrangement with nine spot electrodes, for thoracic bio-impedance cardiography, can be replaced by an arrangement with five spot electrodes. The study was conducted on 15 healthy subjects, six females and nine males, in supine rest. The variables obtained from the measurements were the mean of the impedance of the thorax segment between the recording electrodes, the maximum negative deflection of the first derivative of the thoracic impedance, the left ventricular ejection time and an estimate of left ventricular stroke volume. An analysis of variance for a randomized complete block design was used to determine whether significant differences exist in the group means of the observed variables between six different electrode arrangements. If no statistically significant differences were found in these group means between pairs of arrangements, Bland and Altman analyses were used to determine the differences in the observed variables between pairs of arrangements for individual subjects. This study concludes that reducing the number of spot electrodes from nine to five, does not yield significant differences in the group means of the observed variables, but it could result in large differences in the values of these variables for individual subjects.

Cardiography, Impedance↗
PubMed2001

Phase differences in electrical discharge rhythms between neuronal populations of the left and right suprachiasmatic nuclei.

The circadian pacemaker of the suprachiasmatic nuclei is a complex multioscillator system, which controls circadian and seasonal rhythmicity. A number of clock genes have been identified that play a key role in the generation of circadian rhythms. These clock genes are expressed in a circadian manner as has been shown in mice, rats and hamsters. The time at which their expression reaches peak values differs among the several genes. Expression profiles for a specific gene may also differ among subdivisions of the suprachiasmatic nuclei. It has been shown that mPer1 peaks slightly out of phase in the left and right suprachiasmatic nuclei and that the rhythm in c-fos expression is significantly different between the dorsomedial and ventrolateral regions. In the special case that the animal shows splitting of its locomotor activity pattern, mPer1 in the left and right suprachiasmatic nuclei appeared to oscillate in antiphase. Whether the molecular organization within the suprachiasmatic nuclei plays a role in seasonal rhythmicity, allowing animals to track daylength and become reproductive at the proper phase of the annual cycle, receives increasing interest (). The differences in peak expression times that exist between different genes, and the spatial differences in peak time for single genes, are suggestive of a genetic mechanism underlying the multioscillator structure. It is unknown, however, whether phase differences that are observed at the molecular level exist at the level of electrical activity rhythms in the suprachiasmatic nuclei in order to become potentially functional. In this study we investigated the presence of phase differences in neuronal discharge rhythms in the suprachiasmatic nuclei of the rat. To this purpose we combined simultaneous electrophysiological recordings of neuronal populations in the left and right suprachiasmatic nuclei with a detailed analysis of the phase relationship between them. The results demonstrate that neuronal subpopulations of the suprachiasmatic nuclei show phase differences both in their peak and half-maximum times of up to 4 h. We propose that these phase differences may play a role in the plasticity of the circadian timing system.

Animals↗
PubMed2001

Opposing effects of behavioural activity and light on neurons of the suprachiasmatic nucleus.

The mammalian circadian pacemaker is located in the suprachiasmatic nuclei. It can be shifted in phase by photic cues and by the behavioural activity of the animal. When presented together, light and behavioural activity attenuate each others' phase-shifting effect. Still unclear is how behavioural activity affects the suprachiasmatic nuclei and how it interacts with photic information. Previously, we reported the occurrence of behaviourally induced suppressions of neuronal activity. The present study investigates the characteristics of these suppressions as a function of circadian time and, additionally, in the presence of photic cues. We performed long-term multiunit activity recordings of neurons in freely moving rats and found that these suppressions of neuronal firing in the suprachiasmatic nucleus occurred at every phase of the circadian cycle. The magnitude of the suppressions showed a circadian variation, with larger suppressions during subjective day. When a light pulse was applied during a suppression, light and activity appeared to oppose each others' effects within the recorded population of neurons. The resulting discharge level appeared to be the sum of both responses. The opposing effects of light and activity were also found in single unit recordings, indicating that photic and behavioural stimuli interact at the level of a single neuron.

Animals↗
PubMed2001

Relationship between internal risk factors for development of decubitus ulcers and the blood flow response following pressure load.

The objective of this study was to investigate the extent to which internal risk factors for the development of decubitus ulcers are related to the blood flow response following the relief of a pressure load. There were 122 nursing home patients (43 men, 69 women, mean age: 81 +/- 8 years; range: 60-97). The following potential, internal risk factors for the development of decubitus ulcers were assessed: chronic disorders (diabetes mellitus, cardiovascular disease [congestive heart failure, history of myocardial infarct or angina pectoris] and cerebrovascular accident), fever, blood pressure, nutritional status, serum hemoglobin concentration, and serum urea and serum creatinine concentrations. Skin temperature response (latency time and total response time) was measured following relief of a 100 kPa test pressure. The presence of cardiovascular disease, cerebrovascular accident, poor nutritional condition, high serum urea and male gender showed a significant relationship with an impaired blood flow response. The delayed latency found showed a similarity to the so-called "no-reflow phenomenon." The association of cardiovascular disease and a cerebrovascular accident with a delay in the blood flow response may result from endothelial damage. A poor nutritional condition may be associated with a deficit of scavengers of oxygen-derived free radicals. The presence of free radicals may damage endothelium during reperfusion, thus influencing the blood flow response. The association of high serum urea with delayed vasodilatation may theoretically be explained by the association of serum urea and impaired kidney functioning, since the kidney is an important organ in the production of vasoactive substances. Serum urea can also be considered a measure for nutritional condition. Gender may function as a substitute for other, unmeasured factors that are related to blood flow response.

Age Distribution↗
PubMed2001

Light-Induced resetting of the circadian pacemaker: quantitative analysis of transient versus steady-state phase shifts.

The suprachiasmatic nuclei of the hypothalamus contain the major circadian pacemaker in mammals, driving circadian rhythms in behavioral and physiological functions. This circadian pacemaker's responsiveness to light allows synchronization to the light-dark cycle. Phase shifting by light often involves several transient cycles in which the behavioral activity rhythm gradually shifts to its steady-state position. In this article, the authors investigate in Syrian hamsters whether a phase-advancing light pulse results in immediate shifts of the PRC at the next circadian cycle. In a first series of experiments, the authors aimed a light pulse at CT 19 to induce a phase advance. It appeared that the steady-state phase advances were highly correlated with activity onset in the first and second transient cycle. This enabled them to make a reliable estimate of the steady-state phase shift induced by a phase-advancing light pulse on the basis of activity onset in the first transient cycle. In the next series of experiments, they presented a light pulse at CT 19, which was followed by a second light pulse aimed at the delay zone of the PRC on the next circadian cycle. The immediate and steady-state phase delays induced by the second light pulse were compared with data from a third experiment in which animals received a phase-delaying light pulse only. The authors observed that the waveform of the phase-delay part of the PRC (CT 12-16) obtained in Experiment 2 was virtually identical to the phase-delay part of the PRC for a single light pulse (obtained in Experiment 3). This finding allowed for a quantitative assessment of the data. The analysis indicates that the delay part of the PRC-between CT 12 and CT 16-is rapidly reset following a light pulse at CT 19. These findings complement earlier findings in the hamster showing that after a light pulse at CT 19, the phase-advancing part of the PRC is immediately shifted. Together, the data indicate that the basis for phase advancing involves rapid resetting of both advance and delay components of the PRC.

Activity Cycles↗
PubMed2000

Fentanyl, a upsilon-opioid receptor agonist, phase shifts the hamster circadian pacemaker.

The phase-shifting effects of the mu-opioid receptor agonist fentanyl on the circadian timing system were investigated in the hamster. Fentanyl injections during the mid-subjective day induced phase advances of the hamsters' wheel-running activity rhythm. The shifts were not accompanied by an increase in locomotor activity but instead a decrease of activity was often observed. A dose-response curve indicated that with increasing dosage, the response probability increased, while the magnitude of the induced shift remained stable. The present data suggest that there is some role for opioid regulation of the circadian system.

Analgesics, Opioid↗
PubMed1999

Functional absence of extraocular photoreception in hamster circadian rhythm entrainment.

The mammalian circadian pacemaker is entrainable by light via the retina. The putative role of extraocular light perception was investigated in blinded hamsters. These animals were shaved and exposed to a light-emitting pad for either 30 min or 3 h. The absence of any phase-shifting effects on wheel running activity rhythms indicates that extraocular light perception plays no functional role in photic entrainment of the circadian pacemaker in the hamster.

Animals↗
PubMed1999

Towards a theoretical understanding of stroke volume estimation with impedance cardiography.

In electrical impedance cardiography, Kubicek's formula is often used to measure stroke volume from thoracic impedance variations synchronously to heart activity. To calculate stroke volume from impedance variations, the so-called outflow problem should be adequately solved. This outflow problem refers to the joint causes of impedance change due to blood entering the aorta from the heart, as well as blood leaving the aorta due to arterial runoff. The aim of this study was to investigate the Kubicek formula as a solution of the outflow problem. Kubicek's formula was theoretically investigated using a simple model of the volume-conducting properties of the thorax (two-cylinder model), as well as the hemodynamics of the systemic circulation (three-element "windkessel" model). The mathematical analysis showed that the outflow problem was not solved by the Kubicek formula. Moreover, this theoretical result was experimentally confirmed.

Adult↗
PubMed1999

Neurons of the rat suprachiasmatic nucleus show a circadian rhythm in membrane properties that is lost during prolonged whole-cell recording.

The suprachiasmatic nucleus is commonly considered to contain the main pacemaker of behavioral and hormonal circadian rhythms. Using whole-cell patch-clamp recordings, the membrane properties of suprachiasmatic nucleus neurons were investigated in order to get more insight in membrane physiological mechanisms underlying the circadian rhythm in firing activity. Circadian rhythmicity could not be detected either in spontaneous firing rate or in other membrane properties when whole-cell measurements were made following an initial phase shortly after membrane rupture. However, this apparent lack of rhythmicity was not due to an unhealthy slice preparation or to seal formation, as a clear day/night difference in firing rate was found in cell-attached recordings. Furthermore, in a subsequent series of whole-cell recordings, membrane properties were assessed directly after membrane rupture, and in this series we did find a significant day/night difference in spontaneous firing rate, input resistance and frequency adaptation. As concerns the participation of different subpopulations of suprachiasmatic nucleus neurons expressing circadian rhythmicity, cluster I neurons exhibited strong rhythmicity, whereas no day/night differences were found in cluster II neurons. Vasopressin-containing cells form a subpopulation of cluster I neurons and showed a more pronounced circadian rhythmicity than the total population of cluster I neurons. In addition to their strong rhythm in spontaneous firing rate they also displayed a day/night difference in membrane potential.

Action Potentials↗
PubMed1998

Light responsiveness of the suprachiasmatic nucleus: long-term multiunit and single-unit recordings in freely moving rats.

The suprachiasmatic nuclei (SCN) of the hypothalamus contain a pacemaker that generates circadian rhythms in many functions. Light is the most important stimulus that synchronizes the circadian pacemaker to the environmental cycle. In this paper we have characterized the baseline neuronal firing patterns of the SCN as well as their response to light in freely moving rats. Multiunit and single-unit recordings showed that SCN neurons increase discharge during daytime and decrease discharge at night. Discharge levels of individual neurons that were followed throughout the circadian cycle appeared in phase with the population and were characterized by low discharge rates (often below 1 Hz), with a twofold increase during the day. The effect of light on the multiunit response was dependent on the duration of light exposure and on light intensity, with light thresholds of approximately 0.1 lux. The light response level showed a strong dependency on time of day, with large responsiveness at night and low responsiveness during day. At both phases of the circadian cycle, the response level could be raised by an increase in light intensity. Single-unit measurements revealed that the time-dependent light response of SCN neurons was present also at the level of single units. The results show that the basic light response characteristics that were observed at the multiunit level result from an integrated response of similarly behaving single units. Research at the single-unit level is therefore a useful approach for investigating the basic principles of photic entrainment.

Animals↗
PubMed1998

Evaluation of catheter-mounted transducers for intra-oesophageal pressure recording in respiratory function tests.

Oesophageal pressure measurements in respiratory function tests are commonly performed using a balloon-catheter system. This study investigates the usefulness of catheter-mounted pressure transducers as an alternative to balloon-catheter systems. Calibration related physical properties of the catheter mounted pressure transducers are evaluated in vitro. The behaviour of these transducers in vivo is evaluated in ten volunteers by relating pressures measured in the oesophagus to airway opening pressures and by comparing these relationships with those sequentially obtained by a balloon-catheter system. The catheter-mounted pressure transducers show no drift after a proper preparation procedure. These catheters, with integrated pressure transducers, are tolerated significantly better by the subjects than are balloon catheters. The catheter-mounted pressure transducers are found to give an equivalent performance compared with the balloon-catheter system, if relative pressures are of interest. However, unpredictable and uncontrollable shifts in offset occur during the in vivo measurements, disturbing absolute pressure readings. Possible explanations for these shifts are the presence of bubbles and adhesion of mucus to the transducers, exerting Van der Waals forces, and contact with the tissue of the oesophageal wall. These shifts are found to be quite stable throughout a period of measurement and therefore of minor disturbance to relative pressure measurements, for instance in assessing the elastic properties of lungs.

Adult↗
PubMed1998

Thoracic geometry and its relation to electrical current distribution: consequences for electrode placement in electrical impedance cardiography.

In thoracic impedance cardiography (TIC) measurements the neck electrodes are often positioned at the basis of the neck, close to the neck-thorax transition. Theoretically, this neck-thorax transition will cause inhomogeneities in the current density and potential distribution. This was simulated using a 3D finite element method, solely representing the geometrical neck-thorax transition. The specific conductivity was 7 10(-3) (omega cm)-1 and the injected current was 1 mA. As expected, the model generated inhomogeneities in the current distribution at the neck-thorax transition, which reached as far as 5 cm into the neck and 20 cm into the thorax. These results are supported by in vivo measurements performed in 10 young male subjects, in which the position of the neck electrodes was varied. A two-way ANOVA revealed that the stroke volume of the lowest neck position was significantly different from the other positions. Small shifts in the position of the neck electrode resulted in large changes in impedance and stroke volume (127 to 82 ml for the Kubicek equation). To standardise the electrode position, the authors strongly recommend placement of the neck electrodes at least 6 cm above the clavicula.

Cardiography, Impedance↗
PubMed1997

Multiunit activity recordings in the suprachiasmatic nuclei: in vivo versus in vitro models.

The suprachiasmatic nuclei (SCN) of the hypothalamus continue to oscillate when they are isolated in a brain slice preparation. We recorded multiunit activity in the SCN of the rat both in vivo and in vitro to determine the circadian discharge pattern. The variability of the discharge pattern is larger and the amplitude of the rhythm is smaller in vivo than in vitro. Moreover we found evidence for a direct effect of the animal's behavioural activity on electrical activity of the SCN in vivo. These findings may provide an electrophysiological basis for the known effects of behavioural stimuli on the circadian pacemaker. This study underscores the importance of recordings in intact preparations in addition to in vitro work when generalisations to physiological conditions are to be made.

Animals↗
PubMed1997

Impaired blood flow response following pressure load in diabetic patients with cardiac autonomic neuropathy.

OBJECTIVE: An impaired blood flow response is associated with an increased risk of developing decubitus ulcers. This study investigated whether diabetic patients with autonomic neuropathy show an impaired blood flow response following pressure load, compared with healthy controls. DESIGN: Before-after trial. SETTING: University hospital. PATIENTS: Eighteen patients with type I diabetes and autonomic neuropathy, and 15 healthy volunteers. RESULTS: The blood flow response starts with a latency period, followed by a temperature increase (described by the "time constant"). The blood flow response in both groups showed significant (p < .01) differences. In diabetic patients, the latency time was 312 +/- 221 sec, the time constant was 339 +/- 149 sec, and the recovery time was 538 +/- 184 sec. In controls, latency time was 83 +/- 47 sec, time constant was 79 +/- 69 sec, and recovery time was 162 +/- 103 sec. The velocity of the blood flow response decreased with increasing duration of diabetes mellitus (p = .02). CONCLUSIONS: Diabetic patients with autonomic neuropathy show an impaired blood flow response after pressure relief. This finding suggests that these patients have an increased risk of developing decubitus ulcers.

Adult↗
PubMed1996

Circadian rhythm in light response in suprachiasmatic nucleus neurons of freely moving rats.

Long-term recordings of single SCN units were performed in freely moving rats simultaneously with multiunit recordings and evidence is presented for a daily change in light-responsiveness. SCN light response is high during the night and low during the day. We conclude that this difference is caused by a change in sensitivity, with higher sensitivities at night. Moreover, we demonstrate that the circadian rhythm in SCN light response is the result of the integrated behaviour of similarly behaving single SCN units.

Animals↗
PubMed1995

Skin temperature response to a pressure load: studies in subjects before and during spinal anesthesia.

The Pressure-Temperature-Time method (PTT-method) is a method to investigate skin temperature changes in response to a pressure load. This method was used to investigate the effect of an acute nerve conduction block on the skin temperature increase of the trochanter major, after the pressure load was removed. The PTT-method was used in a group of 30 subjects, undergoing minor surgical procedures, before and during an anesthetic nerve conduction block at L2-L3. In comparison with the results before spinal anesthesia, the skin temperature responses were significantly delayed (p < .01) and slower (p < .001) after the spinal blockade. We concluded, therefore, that the nervous system has an important effect on the recovery of skin temperature after a pressure load.

Adult↗