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Biomedical subjects

L Walløe

Publications and source records attributed to L Walløe.

At least 19 recordsLinked to original sources

The introduction of pharmacoeconomic analysis in Norway--are the users prepared?

OBJECTIVE: The aim of this study was to investigate existing perceptions and knowledge of pharmacoeconomic analyses, and attitudes towards them, among personnel from the pharmaceutical authorities and the pharmaceutical industry in Norway who work with medicines in various capacities, and to investigate whether there were evident differences between the two groups. METHODS: Personal interviews were conducted with 33 employees from the public authorities and 46 from the pharmaceutical industry, using a semi-structured questionnaire. This focused on knowledge of and attitudes towards pharmacoeconomics. MAIN OUTCOME MEASURE: A factor analysis conducted on questions related to attitude. RESULTS: The factor analysis showed that the employees from the public authorities were significantly more positive to the introduction and use of pharmacoeconomic analyses than those from the industry, and they were less skeptical about how well prepared or receptive the market is. In addition the informants from both groups had a relatively good understanding of the terms most commonly used in the field of pharmacoeconomics. They were also aware of some of the costs and outcomes involved in the analyses. CONCLUSION: If the groups interviewed are to become more involved in actual decision-making on the basis of pharmacoeconomic analyses, they need more training to gain the necessary in-depth knowledge, since their knowledge of the field was somewhat superficial.

Attitude↗

Recording of short-term finger blood pressure changes induced by an arterial occlusive thigh cuff: comparison between the modified oscillometric and Finapres techniques.

Blood pressure recordings obtained by the volume clamp method (Finapres monitor, Ohmeda, USA) were compared with measurements by using a novel modification of the oscillometric method (UT9201 beat-to-beat monitor, University of Tartu, Estonia). Step changes in total peripheral resistance were introduced in 11 healthy volunteers by rapid inflation to the suprasystolic pressure of bilateral thigh cuffs during a rhythmical exercise with the quadriceps muscles and simultaneously performed handgrip compression. The provoked short-term changes in mean arterial pressure (MAP) were similarly tracked by both devices. The agreement between the methods was better for MAP rise than drop. The group-averaged difference UT9201 minus Finapres did not exceed 1.2 mmHg (NS, p = 0.46) after cuff successive inflation but yielded 3.8 mmHg (significant, p < 0.05) after cuff successive deflation.

Blood Pressure↗

Beat-to-beat cardiovascular responses to rapid, low-level LBNP in humans.

The hypothesis tested was that there are significant transient changes in the cardiovascular variables after rapid onset and release of mild lower body negative pressure (LBNP, -20 mmHg), even in experimental situations where there is no detectable change in steady-state values. Twelve subjects participated in the study. Heart rate, stroke volume (SV), cardiac output, mean arterial pressure (MAP), total peripheral resistance (TPR), acral and nonacral skin blood flow, and blood flow velocity in the brachial artery were continuously recorded during the pre-LBNP period (0-120 s), during LBNP (120-420 s), and during the post-LBNP period (420-600 s). The main finding was that MAP is transiently but strongly affected by rapid changes in LBNP as small as -20 mmHg. There was also a characteristic asymmetry in cardiovascular responses to the onset and release of LBNP, particularly in the responses in SV. The transient changes in MAP indicate that the neural responses that affect TPR are not fast enough to compensate for the rapid changes in LBNP. In this case, the arterial baroreceptors will be activated as well as the low-pressure baroreceptors that sense central venous pressure. This must be taken into consideration in future discussions of the results of LBNP protocols.

Adult↗

Heart rate response to transient chemoreceptor stimulation in term infants is modified by exposure to maternal smoking.

Modulation of heart rate (HR) during transient hyperoxia, hypoxia, and hypercapnia was studied in 46 healthy term infants on 103 occasions (postnatal d 2 to 82). Twenty-three infants had smoking mothers (median, 11 cigarettes/d). Transient chemoreceptor stimuli (100% O(2), 15% O(2), or 3% CO(2)) were presented repeatedly during quiet sleep. Beat-by-beat HR and breath-by-breath ventilation were recorded continuously. The coherently averaged HR and ventilation responses to each stimulus were calculated for each infant at each age. Outcome variables (HR change from baseline to end of stimulation, maximum HR change, and time to half-maximum) were analyzed by ANOVA. Overall, HR declined during hyperoxia (median change, 4.2 beats/min) and rose during hypoxia (median change, 4.2 beats/min) and hypercapnia (median change, 4.6 beats/min). The percentage change in HR was positively correlated with the percentage change in ventilation (p < 0.001). Increasing number of cigarettes smoked by the mother was correlated with deeper HR declines and smaller HR rises (p = 0.02). For the population as a whole, the HR response lagged 3.8 s behind the ventilatory response during hyperoxia and hypoxia (p < 0.001), whereas during hypercapnia there was no significant lag. The lag in HR response in the smoke-exposed group was 2.5 s greater than that in the control group for all three stimuli (p = 0.001), and the difference increased with the number of cigarettes smoked by the mother (p < 0.01). Both pulmonary reflexes and the type of the chemoreceptor stimulus seemed to influence HR. Maternal smoking affected the magnitude and time-course of the HR response in a dose-dependent manner.

Case-Control Studies↗

Development of oxygen sensitivity in infants of smoking and non-smoking mothers.

AIMS: To assess the effect of prenatal cigarette smoke exposure on the postnatal resetting of oxygen sensitivity in term infants. METHODS: 15 healthy term infants of smoking mothers (median 10 cigarettes/day) and 16 controls were studied during quiet sleep 1, 3, and 10 days and 10 weeks postnatally. Strain-gauge respiratory trace was continuously recorded. Repeated 15-s challenges with 100% O2 and 15% O2 were presented in randomised order through a face mask. A median of six hyperoxic and six hypoxic challenges per recording were obtained. Breath-by-breath ventilation in a time-window from 20 s before onset of stimulus to 60 s after was extracted. For each infant at each age, the normalised coherently averaged response to hyperoxia and hypoxia was calculated. Mean ventilation at end of the 15-s stimulus was analysed with ANOVA, as were parameters describing a function fitted to each averaged response. RESULTS: During air breathing, smoke-exposed infants had higher respiratory rates and lower tidal volumes than controls. Nicotine concentration in infant hair, measured by gas chromatography, was positively correlated with maternal level of smoking. A long-term development in oxygen sensitivity was demonstrated in both groups. However, neither the time-course nor the magnitude of O2 responses was affected by maternal smoking. Overall, hyperoxia reduced ventilation by 6.3% at day 1, 13.2% at day 3, 29.6% at day 10, and 40.0% at week 10. Transient hypoxia increased ventilation by 3.5%, 3.2%, 6.4%, and 8.8%, respectively, at the four ages studied.

Adult↗

A method of assessing ventilatory responses to chemoreceptor stimulation in infants.

Various methods of assessing infant chemoreceptor responses have been reported in the literature. However, equipment dead space, trigeminal stimulation and inherent respiratory variability may have affected the results. A method is presented which attempts to reduce the effect of these factors and thereby isolate the chemoreceptor response. Inspiratory gas was delivered into a lightweight face mask with a pliable rim, minimal dead space and a connected pneumotachograph. Ventilatory data were computed breath by breath. Computer-controlled electromagnetic valves allowed instantaneous switching between air and different gas mixtures, repeated in a randomized sequence. In 18 healthy term neonates, the mask increased ventilation by 12% (95% confidence interval 6-18%), measured by calibrated strain-gauge bands. The effect on respiratory frequency and tidal volume differed significantly between sleep states. Neonates were challenged with short-lasting hyperoxia, mild hypoxia, rebreathing and mild hypercapnia. Coherent averaging of several ventilatory responses from each sleep state reduced the variability while maintaining a high time-resolution.

Analysis of Variance↗

Perfusion of the human finger during cold-induced vasodilatation.

We have investigated the effect of severe local cooling on the vasomotor activity of the arteriovenous anastomoses (AVAs) and other finger vessels. The right third finger was subjected to local cooling (3 degrees C) for 30-45 min in 21 healthy, thermoneutral subjects. Blood velocity in the third finger arteries of both hands was simultaneously recorded using ultrasound Doppler, and skin temperature and laser-Doppler flux from the pulp of the cooled finger were also recorded. The results demonstrate that the initial cold-induced vasoconstriction during severe local cooling involves constriction of the AVAs as well as the two main arteries supplying this finger. During cold-induced vasodilatation (CIVD), the maximum velocity values were not significantly different from those before cooling. Furthermore, the velocity fluctuations in the cooled finger were in most subjects found to be synchronous with the velocity fluctuations in the control finger. This indicates that the large blood flow to the finger and the high skin temperature during CIVD are caused by relaxation of the smooth muscle cells of the AVAs.

Adult↗

Electrophysiological evidence of reinnervation of the transplanted human heart.

Beat-by-beat heart rate (HR) changes during exercise were studied in two young and fit heart-transplanted humans at different time intervals following transplantation. Upon the start of the exercise, a slow gradual increase in HR was seen during the early experiments after the transplantation, whereas an immediate rapid increase in HR was observed during the later experiments. From standard ECGs obtained 32 months after transplantation, two P waves at somewhat different rates could be identified in both subjects, probably arising from donor and recipient sinoatrial nodes, respectively. The two P wave rate changes during and following exercise were very similar. We conclude that these changes in the HR pattern and ECG must be due to reinnervation of the donor hearts, most likely by parasympathetic cardiac fibers.

Adult↗

Local constriction of arteriovenous anastomoses in the cooled finger.

We have examined the influence of local cooling from 35 to 19 degrees C on spontaneous arterial blood velocity fluctuations in the acral skin of thermoneutral subjects. The skin temperature of one hand was gradually lowered in a water bath in two separate experimental runs. Simultaneous continuous blood velocity was measured from the third finger artery of both hands using ultrasound-Doppler. The large blood velocity fluctuations assumed to be caused by synchronous vasomotion of the arteriovenous anastomoses were invariably seen in the control finger artery throughout the two cooling periods, indicating that the subjects were in their thermoneutral zone. The velocity fluctuations on the cooled side remained nearly unchanged and closely correlated with those in the control finger artery during local cooling from 35 to approximately 21.5 degrees C. Below this temperature (range 23-20 degrees C) the velocity fluctuations ceased abruptly, and the velocity was nonfluctuating and continuously low. These results indicate a local thermal level below which there is abrupt, sustained closure of the arteriovenous anastomoses.

Adult↗

Olfaction in bird dogs during hunting.

The ability to catch scent continuously while running, which may be an essential skill for many animals of prey, requires that ambient air flows inward through the nose also during expiration. In this study on bird dogs, the direction of air flow was detected by measuring the temperature in the air inside the nostril. While resting, nose ventilation was synchronous with lung ventilation. While searching for ground scent, the dog was sniffing at a frequency of up to 200 s-1, a strategy which may create turbulence in the nasal passages and thereby enhance transport of scent molecules to the receptors in the ethmoidal cavity. When the bird dog was searching for game while running with its head high against the wind, it maintained a continuous inward air stream through the nose for up to 40s spanning at least 30 respiratory cycles. We suggest that expiratory gas flowing at high velocity from the trachea to the mouth cavity creates a lower pressure than in the nose thus causing an inward air stream through the nose during expiration by a Bernoulli effect.

Animals↗

Short-term control of cardiovascular function: estimation of control parameters in healthy humans.

In a previous study, we recorded short-term cardiovascular responses after a steep increase in arterial pressure in healthy humans [Am. J. Physiol. 266 (Heart Circ. Physiol. 35): H199-H211, 1994]. The aim of the present study was to develop a mathematical model of the baroreflex control of arterial pressure, to use this model with the previously recorded data to estimate unknown parameters in the reflex control loop, and then to analyze the overall open- and closed-loop performance of the system by model simulations with use of individual sets of optimal parameters. The mathematical model consists of a heart, a linear elastic arterial reservoir, and two parallel resistive vascular beds. The arterial baroreflex loop is modeled by two separate time domain processing objects, each with its own gain, time constant, and delay, to simulate the action of a sympathetic signal to the peripheral vascular bed and a parasympathetic signal to the heart. In repeated model simulations, the control parameters in the model were systematically adjusted by an automated algorithm that minimized the deviations between the time courses of the cardiovascular variables simulated by the model and the previously recorded responses in each individual. In all 10 subjects, the short-term cardiovascular responses were adequately simulated by using individual sets of parameters in the model. Open-loop transfer functions for arterial pressure control were obtained by using the individual sets of optimal model parameters in new simulation runs. Open-loop gain for arterial pressure control at nearly zero frequency (steady state) was between 0.9 and 4. Model simulations also indicated an underdampened response at 0.05-0.07 Hz in the closed-loop situation in four subjects, corresponding to peaks in the mean arterial pressor power spectra obtained from separate recordings of spontaneous variations in the resting situation.

Baroreflex↗

Effect of local warming on hand and finger artery blood velocities.

The effect of local heating on blood velocities in arteries supplying the skin of hand and fingers was studied in subjects kept in their thermoneutral zone. The temperature of one hand was steadily raised from 35 to 43 degrees C in 15 min, whereas the control hand was kept in the air or immersed in a water bath at 35 degrees C. Simultaneous blood velocity recordings from the two hands were made continuously using ultrasound Doppler. In the heated hand, a general rise in blood velocity level was seen. However, the spontaneous fluctuations in blood velocity assumed to be caused by synchronous vasomotor activity of the arteriovenous anastomoses (AVAs) remained unchanged and closely correlated with those in the control hand throughout the experiment. Thus the central nervous control of AVA vasomotion seems to be unaffected by local heating. The elevation of blood velocity in the heated hand is probably due to dilatation of other parts of the vascular bed, e.g., ordinary arterioles in the skin. Earlier investigators, using venous occlusion plethysmography, have reported vasoconstriction in the locally heated human finger. No sign of such heat-induced vasoconstriction was found in this study.

Adult↗

Thermoregulatory fluctuations in heart rate and blood pressure in humans: effect of cooling and parasympathetic blockade.

The spontaneous fluctuations in acral skin blood flow, mean blood pressure (MAP), and heart rate (HR) were studied in 9 healthy supine volunteers in a thermoneutral and in a cool environment, and after parasympathetic blockade by atropine. In skin areas with a high density of arteriovenous anastomoses (AVAs), there were large, spontaneous fluctuations in blood flow in a thermoneutral environment. The fluctuations were nearly abolished in a cool environment, while they seemed unaffected by atropine administration. Power spectral analysis demonstrated a reduction in HR and MAP variability in the low- and mid-frequency (LF) (< 0.15 Hz) band after cooling, and a prominent reduction in HR variability in both the LF and the high-frequency (HF) (< 0.15 Hz) band after atropine administration. A sudden drop in skin vascular conductance was accompanied by diphasic HR changes and an increase in MAP. After atropine administration, the initial HR acceleration was delayed and reduced in magnitude. The secondary HR deceleration, which probably represents baroreceptor modulation, was abolished. Atropine administration caused a delayed, but augmented increase in MAP, which was probably related to the loss of baroreceptor control of HR. The presence of an autonomic rhythm, consisting of sympathetic vasoconstrictor impulses to skin AVAs, connected with reciprocal sympathetic and vagal impulses to the heart, is indicated. The HR changes were mainly determined by vagal activity. The rhythmic changes in skin blood flow, HR and MAP were suppressed in a cool environment.

Adult↗

Short-term cardiovascular responses to a step decrease in peripheral conductance in humans.

A step decrease in total peripheral conductance (TPC) was introduced in 10 healthy volunteers by rapid inflation to suprasystolic pressure of bilateral thigh cuffs. This provoked a sudden statistically significant increase in mean arterial blood pressure (MAP) of 5 mmHg during supine rest and of 8 mmHg during moderate supine exercise by the quadriceps muscles. Central venous pressure was not changed by cuff inflation. The increase in MAP was blunted by a rapid but transient decrease in both heart rate (HR) and cardiac stroke volume. At rest, a gradual increase in TPC, starting after 4 s, nearly fully restored MAP to its original value at 10 s. During exercise, MAP was halfway corrected at 10 s but then started to increase again, probably as a result of an ischaemic muscle pressor response. After cholinergic blockade by atropine, the immediate HR response was eliminated, but HR decreased gradually after a delay of 3 s. The time development of the slow increase in TPC was not changed by atropine. In conclusion, the regulatory correction of a sudden increase in arterial pressure in supine unanesthetized healthy humans is achieved through an immediate transient parasympathetic bradycardia during the first few seconds and a more gradual sympathetic peripheral vasodilation after 4 s. After cholinergic blockade, a slow presumably sympathetic HR response was observed.

Adult↗

Fluctuations in blood flow to acral skin in humans: connection with heart rate and blood pressure variability.

1. Spontaneous fluctuations in blood flow in arteries supplying acral skin were investigated with Doppler ultrasound in human subjects. Finger blood pressure, heart rate (HR) and cardiac output were measured simultaneously and noninvasively. 2. Synchronous fluctuations in flow were found in arteries supplying the hands and feet. The fluctuations were larger and more rapid than the flow variations which have been demonstrated with other methods. The magnitude of the total flow fluctuations in the hands and feet was estimated to be 5-10% of cardiac output in resting subjects. This range of flow fluctuations is made possible by spontaneous opening and closing of skin arteriovenous anastomoses (AVAs). 3. The fluctuations in skin blood flow were accompanied by inverse fluctuations in mean blood pressure (MAP). The power spectra of skin vascular conductance and MAP both contained maximum intensity at low frequencies, below 0.15 Hz, with high coherence. 4. The central circulatory events connected with the skin blood flow fluctuations were calculated from the experimental data with the use of transfer function analysis. There was a rise in HR, cardiac output and MAP starting 1-4 s before a cutaneous vasoconstriction. This indicates that the HR and MAP responses are not only passive effects of changes in peripheral resistance, but are the result of a simultaneous activation of the peripheral vascular and cardiac efferent branches of the autonomic nervous system. The HR and MAP responses are then modified, probably by baroreceptor activation.

Adult↗

Arm and leg blood pressures--are they really so different in newborns?

Controversy still exists over differences between upper and lower limb blood pressures (BP) in neonates. We measured upper arm and calf systolic (S) and diastolic (D) BP and heart rate (HR) using 2 Dinamap 847 instruments simultaneously every half minute for several measurement periods of 5-10 min. Nine healthy term newborns were studied in active (AS) and quite (QS) sleep on post-natal days 1 and 5. The results were examined using unbalanced analyses of variance. Arm SBP was 62.3 +/- 1.6 mmHg and DBP 35.5 +/- 1.0 mmHg on day 1 in AS and QS. Calf values were not significantly different but were slightly higher (by 2-3 mmHg) in AS. Arm SBP and DBP rose by 8.5 and 5 mmHg, respectively, between days 1 and 5 but calf pressures rose less. Calf SBP and DBP were significantly lower (by 4.6 and 3.4 mmHg, respectively) than the arm values in QS on day 5. Arm SBP and DBP were dependent on post-natal age but not on sleep state while calf SBP and DBP and HR were dependent on both. Mean HR rose with age from 114 to 117.6 bpm in QS and from 118.6 to 122.4 bpm in AS. Our non-invasive BP measurements were similar to available invasive data. We postulate that differences in arm and calf vasoreactivity account for the different dependence on sleep state and for the unequal changes in arm and calf BE from days 1 to 5.

Age Factors↗

Cardiovascular responses to tilting in healthy newborn babies.

It has been suggested that newborn infants have immature baroreceptor responses and they are unable to maintain their blood pressure (BP) by appropriate reflex peripheral vasoactivity and heart rate (HR) changes in response to tilting. We have measured simultaneously upper arm and calf systolic and diastolic BP and HR every 30 s using an oscillometric method (Dinamap 847) in quiet and active sleep in 9 term babies. Measurements were performed continuously with 5-min periods in each of three positions; horizontal, 30 degrees head up and 30 degrees head down tilt. The results were analysed using unbalanced analyses of variance and multivariate regression. All responses were proportional to the angle of the tilt. The observed values were very close to those predicted from the model. HR increased and decreased by 3.25 beats/min (bpm) on 30 degrees up and down tilting respectively and by twice this amount when tilting through 60 degrees. Arm systolic and diastolic BP both decreased by 1.3 mmHg when tilting through 60 degrees from down to up and increased correspondingly with down-tilting. Calf systolic BP changed appropriately for the change in hydrostatic pressure (+7.37 mmHg with 30 degrees up tilting), but diastolic BP rose only by 60% of this value. The results showed no individual variation, were independent of day, sleep state, the number of tilts, the starting value of the BP and the direction of the previous tilt. This study shows that the healthy newborn has a well developed baroreceptor reflex.

Blood Pressure↗

Sequential or fixed sample trial design? A case study by stochastic simulation.

The properties of Wilcoxon's rank sum test for fixed sample size and a Wilcoxon-type two-sample sequential test have been illustrated and compared by means of stochastic simulation. Data from a real fixed sample trial have been used, both for resampling from the original data, and for construction of an idealized theoretical distribution. The sequential and the fixed sample test obtain equal power, but the sequential test mostly includes considerably fewer patients to reach a conclusion, i.e. the mean and median number of patients included are both much lower than the fixed sample size. Under the hypotheses only a small fraction of the simulation runs exceed the fixed sample size. These findings exemplify results obtained in theoretical analyses and simulation studies covering a wide range of distributions. In our opinion sequential tests have obvious advantages and are in many cases better alternatives than fixed sample tests in clinical trials.

Clinical Trials as Topic↗