IDDSI-compliant recipes containing oral contrast agents for radiological dysphagia diagnostics.

Videofluoroscopic swallowing study (VFSS), alongside flexible endoscopic evaluation of swallowing, represents the gold standard for diagnosing swallowing disorders and to determine severity, pathophysiology, and effective interventions, including texture modification. The clinical swallowing examination and assessment supplements these instrumental methods and serves as the basis for the modules of swallowing diagnostics. The adaptation of food and drink consistencies in dysphagia management has become widespread. For valid results of a VFSS with respect to confirming swallowing safety and efficiency of different liquid and food consistencies and textures, the use of uniform recipes containing radio-opaque contrast media is important. Our goal was to identify recipes that would produce consistencies that conform to the liquid and food levels of 0-7, as defined by the International Dysphagia Diet Standardization Initiative (IDDSI), with barium- and iodine-based contrast media, xanthan gum-based thickeners, and other edible components, which also show sufficient contrast on VFSS. In this study, we determined the different recipes using IDDSI testing methods and explored their radiological characteristics using a Philips MultiDiagnost Eleva fluoroscopy system and two different fluid contrast agents: barium- (Micropaque®) and iodine-based (Telebrix®). All recipes showed sufficient contrast on fluoroscopy and could be visualized in the amounts used for swallowing examinations. They were practical and easy to implement in terms of production and availability of the components. The homogeneity of the recipes diminished with higher IDDSI levels, which represent transitional food, but appeared still sufficient for fluoroscopic examination. The opacity did not significantly differ between the barium- and iodine-based contrast media.

Spinodal decomposition in a mean-field model of the cortex: Emergence of hexagonally symmetric activation patterns.

Spinodal decomposition is a well-known pattern-forming mechanism in metallurgic alloys, semiconductor crystals, and colloidal gels. In metallurgy, if a heated sample of a homogeneous Zn-Al alloy is suddenly quenched below a critical temperature, then the sample can spontaneously precipitate into inhomogenous textures of Zn- and Al-rich regions with significantly altered material properties such as ductility and hardness. Here we report on our recent discovery that a two-dimensional model of the human cortex with inhibitory diffusion can, under particular homogeneous initial conditions, exhibit a form of nonconserved spinodal decomposition in which regions of the cortex self-organize into hexagonally distributed binary patches of activity and inactivity. Fine-scale patterns precipitate rapidly, and then the dynamics slows to render coarser-scale shapes which can ripen into a range of slowly evolving patterns including mazelike labyrinths, hexagonal islands and continents, nucleating "mitotic cells" which grow to a critical size then subdivide, and inverse nucleations in which quiescent islands are surrounded by a sea of activity. One interesting class of activity coalesces into a soliton-like narrow ribbon of depolarization that traverses the cortex at ∼4cm/s. We speculate that this may correspond to the thus far unexplained interictal waves of cortical activation that precede grand-mal seizure in an epileptic event. We note that spinodal decomposition is quite distinct from the Turing mechanism for symmetry breaking in cortex investigated in earlier work by the authors [Steyn-Ross et al., Phys. Rev. E 76, 011916 (2007)PLEEE81539-375510.1103/PhysRevE.76.011916].

[The subjective perception of the vertical-a valuable parameter for determination of peripheral vestibular disorder in Menière's disease in the chronic phase?] / Die subjektive Vertikalenwahrnehmung ­ ein wertvoller Parameter für die Bestimmung der peripher vestibulären Störung bei M. Menière in der chronischen Phase?

The perception of verticality is mainly based on utricular afferent signals and central processing of the transmitted signals. However, there are also extracranial receptors that make a considerable contribution to the perception of verticality. With the subjective visual vertical (SVV) for the utricle and the subjective trunk vertical (STV), two different parameters are available that are not fully understood in terms of their response to physiologic and pathologic changes. The aim of this work was to determine SVV and STV under certain positions of the head and trunk as well as under the influence of Menière's disease (MD) as a chronic vestibular disease. In a prospective clinical study, 26 patients with MD and 39 healthy volunteers were recruited. Subjects were examined with C­SVV glasses and with the three-dimensional trunk excursion chair, while head and torso positions were varied. In both groups, SVV determination is clearly more accurate with an earth-vertical head alignment than with a lateral head tilt (right: MM and control group: p = 0.001; left: MM p = 0.001, control group p = 0.000). If the torso is deflected laterally and the head is held straight, the SVV is significantly more accurate (left p = 0.003, right p = 0.015). The SRV was not affected by the presence of unilateral MD, while pathologic SVV values, if present, indicated the affected side. The results of our study support the assumption that in addition to SVV, SRV is an independent parameter for verticality perception and differs from the SVV in terms of lateralizing a peripheral vestibular deficit. These results suggest that the STV may depend not only on utricular function but also on extracranial afferent signals, and not be significantly altered by the presence of a hydropic peripheral vestibular lesion.

Electrical impedance of mouse brain cortex in vitro from 4.7 kHz to 2.0 MHz.

The electrical impedance of samples of mouse brain cortex has been measured between 4.7 kHz and 2.0 MHz. Brain slices of thickness 400 µm were prepared from two mice. Each slice was placed in either normal artificial cerebrospinal fluid or magnesium-free artificial cerebrospinal fluid; the latter induces seizure-like electrical behaviour. A total of 74 samples of cortex of approximate size 2 mm × 2 mm were then cut from these slices. Each sample in turn was placed between two flat Ag/AgCl electrodes and electrical impedance measured with an Agilent E4980A four-point impedance monitor. The measurements showed two regions of significant dispersion. Circuits based on the Cole-Cole and Fricke models, consisting of inductive, nonlinear capacitive and resistive elements were used to model the behaviour. Distributions of values for each circuit element have been determined for the samples prepared in seizing and non-seizing conditions. Few differences were found between the values of circuit elements between the seizing and non-seizing groups.

In vitro electrical conductivity of seizing and non-seizing mouse brain slices at 10 kHz.

The electrical conductivity of small samples of mouse cortex (in vitro) has been measured at 10 kHz through the four-electrode method of van der Pauw. Brain slices from three mice were prepared under seizing and non-seizing conditions by changing the concentration of magnesium in the artificial cerebrospinal fluid used to maintain the tissue. These slices provided 121 square samples of cortical tissue; the conductivity of these samples was measured with an Agilent E4980A four-point impedance monitor. Of these, 73 samples were considered acceptable on the grounds of having good electrical contact between electrodes and tissue excluding outlier measurements. Results show that there is a significant difference (p = 0.03) in the conductivities of the samples under the two conditions. The seizing and non-seizing samples have mean conductivities of 0.33 and 0.36 S m(-1), respectively; however, these quantitative values should be used with caution as they are both subject to similar systematic uncertainties due to non-ideal temperature conditions and non-ideal placement of electrodes. We hypothesize that the difference between them, which is more robust to uncertainty, is due to the changing gap junction connectivity during seizures.

Using the Hilbert-Huang transform to measure the electroencephalographic effect of propofol.

Monitoring the effect of anesthetic drugs on the central nervous system is a major ongoing challenge in anesthesia research. A number of electroencephalogram (EEG)-based monitors of the anesthetic drug effect such as the bispectral (BIS) index have been proposed to analyze the EEG signal during anesthesia. However, the BIS index has received some criticism. This paper offers a method based on the Hilbert-Huang transformation to calculate an index, called the Hilbert-Huang weighted regional frequency (HHWRF), to quantify the effect of propofol on brain activity. The HHWRF and BIS indices are applied to EEG signals collected from nine patients during a controlled propofol induction and emergence scheme. The results show that both the HHWRF and BIS track the gross changes in the EEG with increasing and decreasing anesthetic drug effect (the prediction probability P(k) of 0.85 and 0.83 for HHWRF and BIS, respectively). Our new index can reflect the transition from unconsciousness to consciousness faster than the BIS, as indicated from the pharmacokinetic and pharmacodynamic modeled parameters and also from the analysis around the point of reawakening. This method could be used to design a new EEG monitoring system to estimate the propofol anesthetic drug effect.

The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice.

Gap junction blockade is a possible mechanism by which general anaesthetic drugs cause unconsciousness. We measured the sensitivity of connexin36 knockout mice to the hypnotic effects of isoflurane and propofol. The experimental endpoint was recovery of the righting reflex of the anaesthetised animals during 0.2% step-reductions in isoflurane concentration, or following intraperitoneal injection of propofol (100 mg.kg(-1) ). Connexin36 knockout animals were more sensitive to the hypnotic effects of isoflurane than 'normal' wild-type animals. The half maximal effective concentration (EC50) for recovery of righting reflex was 0.37% for connexin36 knockout vs 0.49% for wild-type animals (p < 0.001). For propofol, connnexin36 knockout animals showed more rapid loss of righting reflex than wild-type animals (mean (SD) 2.8 (0.13) vs 3.8 (0.27) min); and young (< 60 days) connexin36 knockout animals remained anaesthetised for longer than young wild-type mice (47.2 (2.9) vs 30.5 (1.7) min; p < 0.00001). These findings suggest that the hypnotic effects of anaesthetic drugs may be moderately enhanced by gap junction blockade.

Episodic waveforms in the electroencephalogram during general anaesthesia: a study of patterns of response to noxious stimuli.

Previous studies of the electroencephalogram (EEG) during anaesthesia have identified two distinct patterns of change in response to a noxious stimulus, a classical arousal pattern and a paradoxical arousal pattern. We developed methods of EEG analysis to quantify episodic EEG patterns--namely sleep spindle-like ('10 Hz-score') and burst-suppression-like fluctuations in high frequencies ('high frequency variation index')--and used traditional power spectral quantification of non-episodic delta waves. We studied 30 healthy adult patients undergoing elective surgery under general anaesthesia with propofol, fentanyl (1.0, 2.5 or 4.0 microg/kg, n=10 for each group), muscle relaxant and sevoflurane. Prefrontal EEG data were recorded during the operation and analysed for changes in episodic patterns before and after noxious stimuli (intubation and incision). Before noxious stimuli, the EEG patterns varied markedly between patients and were not strongly correlated to calculated effect-site concentrations of fentanyl, propofol or sevoflurane. Noxious stimuli reduced the 10 Hz-score from 0.25 to 0.20 (P = 0.01) after intubation and from 0.33 to 0.27 (P = 0.01) after incision; and high frequency variation index from 2.8 to 2.0 (P=0.02) after incision--the classical arousal pattern. The nociception-induced reduction in spindles was greater in the low-dose fentanyl group (P = 0.01). There was less tachycardia in the high-dose fentanyl group (P = 0.002). It is possible to quantify such episodic EEG patterns during general anaesthesia and in this study noxious stimulation tended to reduce the prevalence of these patterns.

Can anaesthetists be taught to interpret the effects of general anaesthesia on the electroencephalogram? Comparison of performance with the BIS and spectral entropy.

BACKGROUND: Unlike the other physiological waveforms monitored in anaesthesia, the EEG lacks a regularly repeating pattern, implying that it would be very difficult for an anaesthetist to obtain any useful information from the raw EEG. There are, however, clear changes in the EEG caused by GABA-ergic anaesthetic agents. The anaesthetized EEG still looks like a random waveform, but clearly a different random waveform from that seen when conscious. METHODS: The aim of this study was to assess how 40 anaesthetists would perform at interpreting intra-operative EEGs compared with two processed EEG (pEEG) monitors, BIS and entropy, after a short educational presentation. Short segments of EEGs were used from the pre-induction phase, the intra-operative phase with adequate surgical anaesthesia, and the transition phase between these two states. RESULTS: While anaesthetists' performance varied widely, most could reliably differentiate an anaesthetized from a conscious EEG. Further, both humans (41% wrong) and machines (30% wrong) made mistakes. Unlike the anaesthetists, the pEEG monitors did not make a major error (i.e. producing a number in the conscious range (>85) when analysing an anaesthetized EEG or the converse error). CONCLUSION: A brief PowerPoint presentation enables anaesthetists to recognize the effects on the EEG of GABA-ergic anaesthetic agents. In the clinical context, it remains likely that the combination of a pEEG monitor that clearly presents the EEG and a clinician who has a good, basic understanding of, and a willingness to look at, the raw EEG will result in more accurate interpretation of the intra-operative EEG.

Rapid measurement of blood propofol levels: a proof of concept study.

OBJECTIVE: Despite many advantages over traditional volatile anaesthetic techniques, propofol total intravenous anaesthesia (TIVA) makes up a small percentage of general anaesthetics administered. One of the reasons for this is the absence of a clinically useful method for measuring blood propofol concentrations. We have designed and tested a prototype system for rapidly measuring blood plasma levels of propofol using solid phase extraction (SPE) methodology, coupled with colorimetric and spectrometric techniques. METHODS: Multiple venous blood samples were taken from 17 subjects during induction of anaesthesia with propofol. Samples were analysed in duplicate on both the prototype system and using High Performance Liquid Chromatography (HPLC). The prototype monitor response was calibrated against known methanol-based propofol standards and an estimate of the plasma concentration of propofol derived from regression analysis of the standard responses. RESULTS: Bland Altman analysis from a total of 87 samples gave 95% limits of agreement between the two methods of -0.34 to 0.42 microg mL(-1) (with no significant bias). The mean absolute prediction error was 8.9(7.5)%. The run time per sample on the prototype system was 4.5 min, including sample preparation. CONCLUSION: The results show that this methodology may be suitable for rapid and accurate clinical monitoring of propofol levels during general anaesthesia.

Cerebral cortical effects of desflurane in sheep: comparison with isoflurane, sevoflurane and enflurane.

BACKGROUND: Different volatile anesthetic agents have differing propensities for inducing seizures. A measure of the predilection to develop seizures is the presence of interictal spike discharges (spikes) on the electrocorticogram (ECoG). In this study, we investigated the propensity of desflurane to induce cortical spikes and made a direct objective comparison with enflurane, isoflurane, and sevoflurane. The ECoG effects of desflurane have not been previously reported. METHODS: After establishment of invasive monitoring and a parasagittal array of eight electrodes to record the ECoG; eight adult merino sheep were given a series of short inhalational anesthetics (using desflurane, enflurane, sevoflurane and isoflurane); each titrated to ECoG burst suppression. Anesthetic effect was estimated by the effects on the approximate entropy of the ECoG. The effect of anesthetic on the spike-rate in the ECoG was analyzed using a non-linear mixed-effect method with a sigmoid Emax model. RESULTS: A similar 'depth of anesthesia' was achieved for each agent, as estimated by the approximate entropy. The mean (SD) values of Emax for the spike-rate vs. approximate entropy relationship were desflurane 0.5 (0.9), enflurane 17.2 (4.0), isoflurane 0.7 (1.2), and sevoflurane 5.3 (1.2) spikes/min. The spike rate caused by desflurane was similar to isoflurane and significantly lower than that of enflurane (P < 0.001), and sevoflurane (P = 0.009). CONCLUSION: Desflurane induces minimal cerebral cortical spike activity when administered to burst suppression, consistent with its low propensity for inducing seizures in non-epileptic brains. The agents can be ranked by their relative ability to cause spike activity: enflurane >> sevoflurane > isoflurane = desflurane.

Differential anaesthetic effects following microinjection of thiopentone and propofol into the pons of adult rats: a pilot study.

Identifying the central nervous system sites of action of anaesthetics is important for understanding the link between their molecular actions and clinical effects. The aim of the present pilot study was to compare the anaesthetic effect of bilateral microinjections of propofol and thiopentone (both 200 microg/microl, in Intralipid and 0.9% saline respectively) into a recently discovered anaesthetic-sensitive region in the rat brainstem, the "mesopontine tegmental anaesthetic area" (MPTA). Microinjections (1 microl per side) were made into the MPTA of fifteen male Sprague-Dawley rats. The effect of each agent on spontaneous behaviour, postural control and nociceptive responsiveness was subjectively assessed according to established criteria. The main finding was that thiopentone induced an "anaesthesia-like" state, including complete atonia and loss of righting ability, in 20% of the subjects. Overall, thiopentone significantly reduced postural control and had a moderate antinociceptive effect compared to saline microinjections (P < 0.01 and 0.05, respectively, Wilcoxon test). In contrast, propofol did not induce "anaesthesia" in any animal tested, although a similar antinociceptive effect to that of thiopentone was observed (P < 0.05, Wilcoxon test). In summary, propofol and thiopentone have different effects when microinjected into the MPTA. While both agents reduced reflex withdrawal to a nociceptive stimulus, only thiopentone induced an "anaesthesia-like" state.

Effects of prior hypoxia exposure, endotoxin and sleep state on arousal ability to airway obstruction in piglets: implications for sudden infant death syndrome.

BACKGROUND: Respiratory tract infections may be an important component in many deaths attributed to sudden infant death syndrome (SIDS), although the mechanism of involvement remains unclear. OBJECTIVES: The hypothesis was tested that prolonged hypoxia and a thermogenic state (simulating a fever due to respiratory tract infection) would impair respiratory responsiveness to airway obstruction during sleep. METHODS: Thirty nine piglets aged 5-7 days were exposed to 24 h of moderate hypoxia and/or a low dose of endotoxin derived from Salmonella abortus equi. Responsiveness to complete and subtotal upper airway obstruction was tested during non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. The end-point for airway obstruction tests was taken as the first protective response, either arousal or initiation of mouth breathing. Responsiveness was assessed as response time and response threshold (measured as respiratory effort, i.e. esophageal pressure swing). RESULTS: All animals demonstrated a thermogenic state following endotoxin delivery (drop in ear temperature of 5.8 +/- 0.2 degrees C and a small but significant increase in rectal temperature). Response time to subtotal airway obstruction was reduced during the heat conserving phase of the fever (thermogenesis; 2.8 +/- 0.5 s compared to 4.3 +/- 0.7 s during pre-endotoxin tests), but markedly increased during the recovery period (20.3 +/- 5.1 compared to 14.0 +/- 2.5 s pre-endotoxin) in NREM sleep. Response threshold was not significantly affected by either endotoxin or hypoxia in NREM sleep. Respiratory responsiveness to subtotal obstruction was markedly reduced during REM sleep (response time 40.3 +/- 10.9 s compared to 14.7 +/- 2.2 s in NREM; response threshold -14.0 +/- 1.3 mm Hg compared to -11.7 +/- 1.0 mm Hg in NREM). CONCLUSIONS: This study has demonstrated in a neonatal animal model that respiratory responsiveness to airways obstruction is delayed during recovery from fever. The findings may have implications for the human infant recovering from a respiratory illness.

Endotoxin effects on markers of autonomic nervous system function in the piglet: implications for SIDS.

The hypothesis was tested in 30 newborn piglets that the effects of a low dose of endotoxin (1 microg i.v. bolus; Salmonella abortus equi) would impair autonomic nervous system function. Two tests of autonomic function were performed following external warming (pre-endotoxin) and during endotoxin-generated thermogenesis: (1) analysis of heart rate variability in the time and frequency domains and (2) baroreflex sensitivity measured following intravenous injection of the vasoactive drugs nitroprusside and phenylephrine. Beat-to-beat heart rate variability (SDDeltaRR) fell by 2.2 ms from 7.0 ms before fever (p < 0.05). Low-frequency spectral power fell by 2.4 ms(2) from 4.1 ms(2) before fever (p < 0.05). The sensitivity of the baroreflex to changes in blood pressure induced by the vasoactive drugs decreased during fever by 0.72 ms/mm Hg for the nitroprusside test (p < 0.0005) and by 0.31 ms/mm Hg for the phenylephrine test (p < 0.005). These results indicate that in the piglet the balance of autonomic tone is altered and autonomic responsiveness reduced during the thermogenic phase of a fever. These findings are consistent with known risk factors for sudden infant death syndrome.

The effect of cold stimulation to the face on the metabolic rate of the febrile piglet.

Sudden infant death syndrome has been associated with winter climates, infection, and overwrapping of babies. The hypothesis has been tested in this laboratory that two different causes of increased metabolic rate, high core temperature (via the van't Hoff or 'Q10' effect) and face-cooling, might synergistically induce hyperthermia. This proved not to be the case. We now report on a 'febrile' state adding Salmonella abortus equi pyrogens. The combination of face-cooling and pyrogen administration to 14 already hot piglets produced an increase in oxygen consumption of 47% in 6 of the animals (19% overall). Face-cooling alone caused a 6.5% fall in oxygen consumption, and injection of pyrogens alone had no effect on oxygen consumption. We conclude that there may be a danger of life-threatening hyperthermia in the combination of a cold face and febrile state.