Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection

2003 ◽  
Vol 99 (1) ◽  
pp. 166-173 ◽  
Author(s):  
James C. Eisenach ◽  
David D. Hood ◽  
Regina Curry ◽  
Steven L. Shafer
Keyword(s):  
Time Course ◽  
Pharmacokinetic Model ◽  
Intrathecal Injection ◽  
Initial Distribution ◽  
Model Parameters ◽  
Resonance Imaging ◽  
Individual Model ◽  
Primary Determinant ◽  
The Individual ◽  
Lower Lumbar

Background Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection. Methods Eight healthy volunteers received intrathecal injection of morphine (50 microg) plus fentanyl (50 microg) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM. Results Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight. Conclusions Fentanyl is cleared more rapidly from CSF than morphine, although their initial distribution in the first hour after injection does not differ greatly. The pharmacokinetic model demonstrates that mixing is the primary determinant of early concentrations and is highly variable among individuals.

scholarly journals Effects of Blood Flow on [11C]Raclopride Binding in the Brain: Model Simulations and Kinetic Analysis of PET Data

1994 ◽  
Vol 14 (6) ◽  
pp. 995-1010 ◽  
Author(s):  
Jean Logan ◽  
Nora D. Volkow ◽  
Joanna S. Fowler ◽  
Gene-Jack Wang ◽  
Stephen L. Dewey ◽  
...  
Keyword(s):  
Blood Flow ◽  
Region Of Interest ◽  
Receptor Occupancy ◽  
Compartment Model ◽  
Model Parameters ◽  
Individual Model ◽  
Positron Emission ◽  
D2 Antagonist ◽  
The Stability ◽  
The Individual

To assess the stability of different measures of receptor occupancy from [11C]raclopride (a D2 antagonist) studies with positron emission tomography, we analyze data from five test/retest studies in normal volunteers in terms of individual model parameters from a three-compartment model, the distribution volume (DV) and the ratio of DVs from a receptor-containing region of interest to a non-receptor-containing region. Large variations were found in the individual model parameters, limiting their usefulness as an indicator of change in receptor systems. The DV ratio showed the smallest variation. Individual differences were reflected in the greater intersubject variation in DV than intrasubject variation. The potential effects of blood flow on these measurements were addressed both experimentally and by simulation studies using three models that explicitly incorporate blood flow into a compartmental model that also includes receptor–ligand binding. None of the models showed any variation in the DV with changes in blood flow as long as flow was held constant during the simulation. Experimentally, blood flow was significantly reduced by hyperventilation in a human subject. The DV was found to be reduced relative to baseline in the hyperventilation study, but the DV ratio remained unchanged. The effect of elevated and reduced flow was also tested in two baboon experiments in which Pco2 was varied. Some variability in the DV ratio was observed but was not correlated with changes in blood flow. This raises the possibility that other factors indirectly related to changes in blood flow (or Pco2) may cause changes in DV, and these effects need to be considered when evaluating experimental results.

Influence of stable iodine on the uptake of the thyroid – model vs. experiment

2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber
Keyword(s):  
Time Course ◽  
Compartment Model ◽  
The Body ◽  
Iodine Uptake ◽  
Model Calculations ◽  
Physiological Conditions ◽  
Iodine Supply ◽  
Predicted Values ◽  
The Individual ◽  
Stable Iodine

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.

Improved Contrast in Ultra-Low-Field MRI with Time-Dependent Bipolar Prepolarizing Fields: Theory and NMR Demonstrations

2013 ◽  
Vol 20 (3) ◽  
pp. 327-336 ◽  
Author(s):  
Jaakko O. Nieminen ◽  
Jens Voigt ◽  
Stefan Hartwig ◽  
Hans Jürgen Scheer ◽  
Martin Burghoff ◽  
...  
Keyword(s):  
Field Strength ◽  
Time Course ◽  
Signal Strength ◽  
Relaxation Rates ◽  
Resonance Imaging ◽  
New Approach ◽  
Spin Lattice ◽  
Low Field ◽  
Low Field Mri ◽  
Magnetic Resonance Imaging Mri

Abstract The spin-lattice (T1) relaxation rates of materials depend on the strength of the external magnetic field in which the relaxation occurs. This T1 dispersion has been suggested to offer a means to discriminate between healthy and cancerous tissue by performing magnetic resonance imaging (MRI) at low magnetic fields. In prepolarized ultra-low-field (ULF) MRI, spin precession is detected in fields of the order of 10-100 μT. To increase the signal strength, the sample is first magnetized with a relatively strong polarizing field. Typically, the polarizing field is kept constant during the polarization period. However, in ULF MRI, the polarizing-field strength can be easily varied to produce a desired time course. This paper describes how a novel variation of the polarizing-field strength and duration can optimize the contrast between two types of tissue having different T1 relaxation dispersions. In addition, NMR experiments showing that the principle works in practice are presented. The described procedure may become a key component for a promising new approach of MRI at ultra-low fields

scholarly journals Wearable robotic exoskeletons: A socio-philosophical perspective on Duchenne muscular dystrophy research

2020 ◽  
Vol 11 (1) ◽  
pp. 404-413
Author(s):  
Alexandra Kapeller ◽  
Michael H. Nagenborg ◽  
Kostas Nizamis
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Disability Studies ◽  
Philosophy Of Technology ◽  
Research Projects ◽  
Philosophical Perspective ◽  
Individual Model ◽  
Engineering Sciences ◽  
The Social ◽  
The Individual

AbstractRecently, several research projects in the Netherlands have focused on the development of wearable robotic exoskeletons (WREs) for individuals with Duchenne muscular dystrophy (DMD). Such research on WREs is often treated solely within the disciplines of biomedical and mechanical engineering, overlooking insights from disability studies and philosophy of technology. We argue that mainly two such insights should receive attention: the problematization of the ableism connected to the individual model of disability and the stigmatization by assistive technology. While disability studies have largely rejected the individual model of disability, the engineering sciences seem to still locate disability in an individual’s body, not questioning their own problematization of disability. Additionally, philosophy of technology has argued that technologies are not neutral instruments but shape users’ actions and perceptions. The design of WREs may convey a message about the understanding of disability, which can be comprehended as a challenge and an opportunity: stigmatization needs to be avoided and positive views on disability can be evoked. This article aims to highlight the benefits of considering these socio-philosophical perspectives by examining the case of WREs for people with DMD and proposing design principles for WREs. These principles may enhance acceptability of WREs, not only by individuals with DMD but also by other users, and help engineers to better place their work in the social context.

Use of ionic currents to identify and estimate parameters in models of channel blockade

1990 ◽  
Vol 259 (2) ◽  
pp. H626-H634
Author(s):  
C. F. Starmer ◽  
V. V. Nesterenko ◽  
F. R. Gilliam ◽  
A. O. Grant
Keyword(s):  
Time Course ◽  
Experimental Studies ◽  
Ionic Currents ◽  
Blocking Agent ◽  
Model Parameters ◽  
Protein Conformations ◽  
Channel Blockade ◽  
Channel Blocking ◽  
Individual Contributions ◽  
Modulated Receptor

Models of ion channel blockade are frequently validated with observations of ionic currents resulting from electrical or chemical stimulation. Model parameters for some models (modulated receptor hypothesis) cannot be uniquely determined from ionic currents. The time course of ionic currents reflects the activation (fraction of available channels that conduct in the presence of excitation) and availability of channels (the ability of the protein to make a transition to a conducting conformation and where this conformation is not complexed with a drug). In the presence of a channel blocking agent, the voltage dependence of availability appears modified and has been interpreted as evidence that drug-complexed channels exhibit modified transition rates between channel protein conformations. Because blockade and availability both modify ionic currents, their individual contributions to macroscopic conductance cannot be resolved from ionic currents except when constant affinity binding to a bindable site is assumed. Experimental studies of nimodipine block of calcium channels and lidocaine block of sodium channels illustrate these concepts.

scholarly journals Dentinal anomalies in teeth of harbour porpoises (Phocoena phocoena) from Scottish waters: are they linked to sexual maturation and environmental events?

2009 ◽  
Vol 89 (5) ◽  
pp. 893-902 ◽  
Author(s):  
P.L. Luque ◽  
G.J. Pierce ◽  
J.A. Learmonth ◽  
M.B. Santos ◽  
E. Ieno ◽  
...  
Keyword(s):  
Life History ◽  
Sexual Maturation ◽  
Time Course ◽  
Physiological Stress ◽  
Organic Pollutant ◽  
Additive Models ◽  
Phocoena Phocoena ◽  
Major Life ◽  
The Individual ◽  
Pulp Stones

We examined the tooth ultra-structure of harbour porpoises (Phocoena phocoena) from Scottish waters to determine whether the incidence of mineralization anomalies could be related to certain life history events (e.g. the achievement of sexual maturation) as well as other factors that affect the general health of the individual (e.g. persistent organic pollutant (POP) concentrations in blubber). Five distinct types of mineralization anomalies were recorded: accessory lines, marker lines, dentinal resorption, cemental disturbance and pulp stones and the occurrence of these anomalies was scored by sex, age and maturity state. Overall, the incidence of mineralization anomalies was high and tended to increase with age. Marker lines and accessory lines were the most commonly recorded anomalies while pulp stones were least frequent. Duplicate teeth (i.e. from the same individual) always showed the same pattern of anomaly occurrence.Fitted binary generalized linear and additive models indicated that the presence of dentinal resorption, cemental disturbance and marker lines in harbour porpoise teeth increased with age, body length and maturity. Males displayed marker lines more frequently than females. Age was the best predictor of the incidence of dentinal resorption and cemental disturbance while age and sex were the best predictors of the incidence of marker lines. The time course of appearance of dentinal resorption and cemental disturbance suggests that their occurrence could be related to physiological stress linked to sexual maturation. Marker lines were found within growth layer groups which coincided with the beginning of weaning and sexual maturation, suggesting an association with these two major life history events. Accessory lines were found in most teeth and may be a normal characteristic of porpoise teeth or reflect regular events. Pulp stones appeared only in mature animals. We found no evidence that the presence of anomalies in teeth was significantly related to POP concentrations in the blubber.

The Diagnostic Value of MRI in Traumatic Brachial Plexus Injury

1994 ◽  
Vol 19 (1) ◽  
pp. 55-59 ◽  
Author(s):  
M. OCHI ◽  
Y. IKUTA ◽  
M. WATANABE ◽  
K. KIMOR ◽  
K. ITOH
Keyword(s):  
Brachial Plexus ◽  
Nerve Root ◽  
Brachial Plexus Injury ◽  
Diagnostic Value ◽  
Resonance Imaging ◽  
Nerve Roots ◽  
Surgical Exploration ◽  
Nerve Root Avulsion ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual

Findings in 34 patients with traumatic brachial plexus injury documented by surgical exploration and intra-operative somatosensory-evoked potentials were correlated with findings on myelography and magnetic resonance imaging (MRI) to determine whether MRI can identify nerve root avulsion. The coronal and sagittal planes were not able to demonstrate avulsion of the individual nerve roots. The axial and axial oblique planes did provide useful information to determine which nerve root was avulsed in the upper plexus, although it was difficult to clearly delineate the lower cervical rootlets. The accuracy of MRI was 73% for C5 and 64% for C6 and that of myelograpby 63% for C5 and 64% for C6. Thus, the diagnostic accuracy of MRI for upper nerve roots was slightly superior to myelography. Although its primary diagnostic value is limited to the upper nerve roots whose avulsion is relatively difficult to diagnose by myelography, MRI can provide useful guidance in the waiting period prior to surgical exploration after brachial plexus injury.

scholarly journals Use of Magnetic Resonance Imaging to Predict Outcome after Stroke: A Review of Experimental and Clinical Evidence

2010 ◽  
Vol 30 (4) ◽  
pp. 703-717 ◽  
Author(s):  
Tracy D Farr ◽  
Susanne Wegener
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Complete Recovery ◽  
Research Translation ◽  
Resonance Imaging ◽  
Preclinical Research ◽  
Stroke Research ◽  
Future Potential ◽  
Magnetic Resonance Imaging Mri ◽  
The Individual

Despite promising results in preclinical stroke research, translation of experimental data into clinical therapy has been difficult. One reason is the heterogeneity of the disease with outcomes ranging from complete recovery to continued decline. A successful treatment in one situation may be ineffective, or even harmful, in another. To overcome this, treatment must be tailored according to the individual based on identification of the risk of damage and estimation of potential recovery. Neuroimaging, particularly magnetic resonance imaging (MRI), could be the tool for a rapid comprehensive assessment in acute stroke with the potential to guide treatment decisions for a better clinical outcome. This review describes current MRI techniques used to characterize stroke in a preclinical research setting, as well as in the clinic. Furthermore, we will discuss current developments and the future potential of neuroimaging for stroke outcome prediction.

Some alternatives for the individual model

1994 ◽  
Vol 15 (2-3) ◽  
pp. 127-132 ◽  
Author(s):  
R. Kaas ◽  
H.U. Gerber
Keyword(s):  
Individual Model ◽  
The Individual

A mathematical model of cardiovascular dynamics for the diagnosis and prognosis of hemorrhagic shock

2021 ◽  
Author(s):  
Laura D’Orsi ◽  
Luciano Curcio ◽  
Fabio Cibella ◽  
Alessandro Borri ◽  
Lilach Gavish ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Arterial Pressure ◽  
Hemorrhagic Shock ◽  
Time Course ◽  
Differential Algebraic Equations ◽  
Model Parameters ◽  
Algebraic Equations ◽  
Cardiovascular Dynamics ◽  
Compensation Mechanisms

Abstract A variety of mathematical models of the cardiovascular system have been suggested over several years in order to describe the time-course of a series of physiological variables (i.e. heart rate, cardiac output, arterial pressure) relevant for the compensation mechanisms to perturbations, such as severe haemorrhage. The current study provides a simple but realistic mathematical description of cardiovascular dynamics that may be useful in the assessment and prognosis of hemorrhagic shock. The present work proposes a first version of a differential-algebraic equations model, the model dynamical ODE model for haemorrhage (dODEg). The model consists of 10 differential and 14 algebraic equations, incorporating 61 model parameters. This model is capable of replicating the changes in heart rate, mean arterial pressure and cardiac output after the onset of bleeding observed in four experimental animal preparations and fits well to the experimental data. By predicting the time-course of the physiological response after haemorrhage, the dODEg model presented here may be of significant value for the quantitative assessment of conventional or novel therapeutic regimens. The model may be applied to the prediction of survivability and to the determination of the urgency of evacuation towards definitive surgical treatment in the operational setting.

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