Albuterol delivery in an in vitro pediatric ventilator lung model: comparison of jet, ultrasonic, and mesh nebulizers.

OBJECTIVE: : To determine the influence of nebulizer types and nebulization modes on bronchodilator delivery in a mechanically ventilated pediatric lung model. DESIGN: : In vitro, laboratory study. SETTING: : Research laboratory of a university hospital. INTERVENTIONS: : Using albuterol as a marker, three nebulizer types (jet nebulizer, ultrasonic nebulizer, and vibrating-mesh nebulizer) were tested in three nebulization modes in a nonhumidified bench model mimicking the ventilatory pattern of a 10-kg infant. The amounts of albuterol deposited on the inspiratory filters (inhaled drug) at the end of the endotracheal tube, on the expiratory filters, and remaining in the nebulizers or in the ventilator circuit were determined. Particle size distribution of the nebulizers was also measured. MEASUREMENTS AND MAIN RESULTS: : The inhaled drug was 2.8% ± 0.5% for the jet nebulizer, 10.5% ± 2.3% for the ultrasonic nebulizer, and 5.4% ± 2.7% for the vibrating-mesh nebulizer in intermittent nebulization during the inspiratory phase (p < 0.01). The most efficient nebulizer was the vibrating-mesh nebulizer in continuous nebulization (13.3% ± 4.6%, p < 0.01). Depending on the nebulizers, a variable but important part of albuterol was observed as remaining in the nebulizers (jet and ultrasonic nebulizers), or being expired or lost in the ventilator circuit (all nebulizers). Only small particles (range 2.39-2.70 µm) reached the end of the endotracheal tube. CONCLUSIONS: : Important differences between nebulizer types and nebulization modes were seen for albuterol deposition at the end of the endotracheal tube in an in vitro pediatric ventilator-lung model. New aerosol devices, such as ultrasonic and vibrating-mesh nebulizers, were more efficient than the jet nebulizer.

Is intra-operative blood flow predictive for early failure of radiocephalic arteriovenous fistula?

BACKGROUND: For over 50 years, radiocephalic wrist arteriovenous fistulae (RCAVF) have been the primary and best vascular access for haemodialysis. Nevertheless, early failure due to thrombosis or non-maturation is a major complication resulting in their abandonment. This prospective study was designed to investigate the predictive value of intra-operative blood flow on early failure of primary RCAVF before the first effective dialysis. METHODS: We enrolled patients undergoing creation of primary RCAVF for haemodialysis based on the pre-operative ultrasound vascular mapping discussed in a multidisciplinary approach. Intra-operative blood flow measurement was systematically performed once the anastomosis had been completed using a transit-time ultrasonic flowmeter. During the follow-up, blood flow was estimated by colour flow ultrasound at various intervals. Any events related to the RCAVF were recorded. RESULTS: Autogenous RCAVFs (n = 58) in 58 patients were constructed and followed up for an average of 30 days. Thrombosis and non-maturation occurred in eight (14%) and four (7%) patients, respectively. The intra-operative blood flow in functioning RCAVFs was significantly higher compared to non-functioning RCAVFs (230 vs 98 mL/min; P = 0.007), as well as 1 week (753 vs 228 mL/min; P = 0.0008) and 4 weeks (915 vs 245 mL/min, P < 0.0001) later. Blood flow volume measurements with a cut-off value of 120 mL/min had a sensitivity of 67%, specificity of 75% and positive predictive value of 91%. CONCLUSIONS: Blood flow <120 mL has a good predictive value for early failure in RCAVF. During the procedure, this cut-off value may be used to select appropriately which RCAVF should be investigated in the operation theatre in order to correct in real time any abnormality.

Robust discrimination between EEG responses to categories of environmental sounds in early coma.

Humans can recognize categories of environmental sounds, including vocalizations produced by humans and animals and the sounds of man-made objects. Most neuroimaging investigations of environmental sound discrimination have studied subjects while consciously perceiving and often explicitly recognizing the stimuli. Consequently, it remains unclear to what extent auditory object processing occurs independently of task demands and consciousness. Studies in animal models have shown that environmental sound discrimination at a neural level persists even in anesthetized preparations, whereas data from anesthetized humans has thus far provided null results. Here, we studied comatose patients as a model of environmental sound discrimination capacities during unconsciousness. We included 19 comatose patients treated with therapeutic hypothermia (TH) during the first 2 days of coma, while recording nineteen-channel electroencephalography (EEG). At the level of each individual patient, we applied a decoding algorithm to quantify the differential EEG responses to human vs. animal vocalizations as well as to sounds of living vocalizations vs. man-made objects. Discrimination between vocalization types was accurate in 11 patients and discrimination between sounds from living and man-made sources in 10 patients. At the group level, the results were significant only for the comparison between vocalization types. These results lay the groundwork for disentangling truly preferential activations in response to auditory categories, and the contribution of awareness to auditory category discrimination.

Direct Determination of mechanical properties in shallow formations by (ultra) sonic methods

For several decades mechanical properties of shallow formations (soil) obtained by sonic to ultrasonic wave testing were reported to be greater than those based on mechanical tests. The present article relying on a statistical analysis of more than 300 tests shows that elastic moduli of the soil can indeed be obtained from (ultra)sonic tests and that they are identical to those resulting from mechanical tests.

Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations

AIM: To discuss the use of new ultrasonic techniques that make it possible to visualize elastic (carotid) and muscular (radial) capacitance arteries non-invasively. RESULTS OF DATA REVIEW: Measurements of carotid wall thickness and the detection of atheromas are related to arterial pressure, to other risk factors and to the risk of subsequent complications. The use of high-frequency ultrasound (7.5-10 MHz), measurements of far wall thicknesses in areas free of atheromas at end-diastole (by ECG gating or pressure waveform recording) and descriptions of the size and characteristics of atherosclerotic plaques allow a non-invasive assessment of vascular hypertrophy and atherosclerosis in hypertensive patients. CONCLUSIONS: Careful attention to methodologic and physiologic factors is needed to provide accurate information about the anatomy of the dynamically pulsating arterial tree.

Ultimate test bench for pediatric biventricular assist device based on artificial muscles.

Ventricular assist devices (VADs) are used in treatment for terminal heart failure or as a bridge to transplantation. We created biVAD using the artificial muscles (AMs) that supports both ventricles at the same time. We developed the test bench (TB) as the in vitro evaluating system to enable the measurement of performance. The biVAD exerts different pressure between left and right ventricle like the heart physiologically does. The heart model based on child's heart was constructed in silicone. This model was fitted with the biVAD. Two pipettes containing water with an ultrasonic sensor placed on top of each and attached to ventricles reproduced the preload and the after load of each ventricle by the real-time measurement of the fluid height variation proportionally to the exerted pressure. The LabVIEW software extrapolated the displaced volume and the pressure generated by each side of our biVAD. The development of a standardized protocol permitted the validation of the TB for in vitro evaluation, measurement of the performances of the AM biVAD herein, and reproducibility of data.

Physicochemical aspects and efficiency of albuterol nebulization: comparison of three aerosol types in an in vitro pediatric model.

BACKGROUND: Advances in nebulizer design have produced both ultrasonic nebulizers and devices based on a vibrating mesh (vibrating mesh nebulizers), which are expected to enhance the efficiency of aerosol drug therapy. The aim of this study was to compare 4 different nebulizers, of 3 different types, in an in vitro model using albuterol delivery and physical characteristics as benchmarks. METHODS: The following nebulizers were tested: Sidestream Disposable jet nebulizer, Multisonic Infra Control ultrasonic nebulizer, and the Aerogen Pro and Aerogen Solo vibrating mesh nebulizers. Aerosol duration, temperature, and drug solution osmolality were measured during nebulization. Albuterol delivery was measured by a high-performance liquid chromatography system with fluorometric detection. The droplet size distribution was analyzed with a laser granulometer. RESULTS: The ultrasonic nebulizer was the fastest device based on the duration of nebulization; the jet nebulizer was the slowest. Solution temperature decreased during nebulization when the jet nebulizer and vibrating mesh nebulizers were used, but it increased with the ultrasonic nebulizer. Osmolality was stable during nebulization with the vibrating mesh nebulizers, but increased with the jet nebulizer and ultrasonic nebulizer, indicating solvent evaporation. Albuterol delivery was 1.6 and 2.3 times higher with the ultrasonic nebulizer and vibrating mesh nebulizers devices, respectively, than with the jet nebulizer. Particle size was significantly higher with the ultrasonic nebulizer. CONCLUSIONS: The in vitro model was effective for comparing nebulizer types, demonstrating important differences between nebulizer types. The new devices, both the ultrasonic nebulizers and vibrating mesh nebulizers, delivered more aerosolized drug than traditional jet nebulizers.

Nutritional status using the Mini Nutritional Assessment questionnaire and its relationship with bone quality in a population of institutionalized elderly women.

Malnutrition, a risk factor for osteoporotic fractures, is frequent in elderly people and, is underdiagnosed and undertreated. There are only few studies on the nutritional status of elderly people in Europe. The Mini Nutritional Assessment (MNA) is a non invasive and validated questionnaire to evaluate nutritional status in elderly people, classified in three groups: 1 degree score < 17: malnourished, 2 degrees score >17 and < 24: at risk of malnutrition, 3 degrees score >24: well-nourished, with a maximum of 30 points. Quantitative ultrasound of bone (QUS) is a method for assessing quality of bone which can be easily performed in nursing homes. Therefore, these two tests allowed to study the relationships between nutritional status and ultrasonic parameters of bone in 78 institutionalized women aged 86 +/- 6 years, living in 11 nursing homes around Lausanne (Switzerland). All were assessed by the MNA, had a measurement of the tricipital skin fold and of the grip strength. Functional status was evaluated by the scale "Activity of Daily Living" (ADL), and serum albumin level was measured when permitted. All had QUS of the calcaneus (with an Achilles, GE Lunar). The measured parameters are the Broadband Ultrasound Attenuation (BUA), attenuation of a band of ultrasonic frequencies through the medium, expressed in dB/MHz, and the Speed of Sound (SOS), speed of the ultrasounds through the medium, expressed in m/s. A third parameter, the stiffness index (SI), expressed as a percentage of the values obtained by the manufacturer in a young population and derived from BUA and SOS, was calculated automatically : SI = (0.67xBUA) + (0.28xSOS) - 420, expressed in percent compared to a young adult population (%YA). Fifteen percent of the women were undernourished and 58% were at risk of malnutrition. As expected, compared with the well-nourished minority, undernourished subjects had significant lower body mass index (BMI), tricipital skin fold (TSF), ADL score and albumin level (p < 0,01). The subjects "at risk of malnutrition" had significant lower BMI, ADL score (p < 0.01), tricipital skin fold and serum albumin (p < 0.05). Ultrasound parameters were low independently of the nutritional status. MNA score correlated significantly with tricipital skin fold (r = 0.508, p < 0.01), ADL (r = 0.538, p < 0.01) and albumin serum level (r = 0.409, p = 0.01). There was a trend for a correlation between the MNA and the ultrasound parameter BUA (r = 0.207, p = 0.07), whereas no correlation was found with SOS and SI. A multivariate analysis showed that tricipital skin fold and ADL explained 61% of the variance of the MNA. In conclusion, using simple and non invasive methods, this study showed that malnutrition and osteoporosis are frequent in institutionalized elderly persons in our country, and the ultrasound parameters are influenced by many others factors in addition to nutrition, especially at this age and in elderly residents of nursing homes.

The renin-angiotensin system and arterial wall behavior.

To assess the behavior of the arterial wall in hypertensive patients, we developed a noninvasive ultrasonic device. Simultaneous recordings of internal diameter and blood pressure over the whole cardiac cycle are used to establish compliance-pressure curves. Blood pressure, which is a co-determinant of compliance, is thus taken into account. This method allows one to compare arteries from patients with different blood pressures. Arterial compliance and distensibility were first investigated in healthy young volunteers administered either lisinopril (20 mg), atenolol (100 mg) or nitrendipine (20 mg) once a day. After 8 days of treatment, only lisinopril was found to increase arterial compliance. Subsequently, we compared arterial diameter- and distensibility-pressure curves from newly diagnosed and untreated hypertensive patients with those of matched normotensive control patients. Diameter-pressure curves did not differ significantly between the groups and distensibility was not reduced. Similar findings were later obtained in an animal model, when mechanical properties of carotid arteries were compared between spontaneously hypertensive rats and normotensive counterparts (Wistar-Kyoto rats). These results, although interesting by providing noninvasive information on the elastic response of the wall, call for further development of the technique to be able to measure arterial wall thickness. Stress-strain relationship could ultimately be established to thoroughly characterize physical properties of blood vessel walls.

Use of accuracy profile for the validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method: quantification of ethyl glucuronide in hair

Introduction: Ethylglucuronide (EtG) is a direct and specific metabolite of ethanol. Its determination in hair is of increasing interest for detecting and monitoring alcohol abuse. The quantification of EtG in hair requires analytical methods showing highest sensitivity and specificity. We present a fully validated method based on gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS). The method was validated using French Society of Pharmaceutical Sciences and Techniques (SFSTP) guidelines which are based on the determination of the total measurement error and accuracy profiles. Methods: Washed and powdered hair is extracted in water using an ultrasonic incubation. After purification by Oasis MAX solid phase extraction, the derivatized EtG is detected and quantified by GC-NCI-MS/MS method in the selected reaction monitoring mode. The transitions m/z 347 / 163 and m/z 347 / 119 were used for the quantification and identification of EtG. Four quality controls (QC) prepared with hair samples taken post mortem from 2 subjects with a known history of alcoholism were used. A proficiency test with 7 participating laboratories was first run to validate the EtG concentration of each QC sample. Considering the results of this test, these samples were then used as internal controls for validation of the method. Results: The mean EtG concentrations measured in the 4 QC were 259.4, 130.4, 40.8, and 8.4 pg/mg hair. Method validation has shown linearity between 8.4 and 259.4 pg/mg hair (r2 > 0.999). The lower limit of quantification was set up at 8.4 pg/mg. Repeatability and intermediate precision were found less than 13.2% for all concentrations tested. Conclusion: The method proved to be suitable for routine analysis of EtG in hair. GC-NCI-MS/MS method was then successfully applied to the analysis of EtG in hair samples collected from different alcohol consumers.

Sib-sib communication and the risk of prey theft in the barn owl Tyto alba

Conflicts among siblings are widespread and their resolution involves complex physical and communication tools. Observations in the barn owl Tyto alba showed that siblings vocally communicate in the absence of parents to negotiate priority of access to the impending food resources that parents will bring. In the present paper, we hypothesize and provide correlative evidence that after a parent brought a food item to their progeny, sibling competition involves vocal sib-sib communication. A food item takes a long time to be entirely consumed, and hence siblings continue to compete over prey monopolization even after parents gave a food item to a single offspring. When physical competition is pronounced and thereby the risk of prey theft is high, the individual that received a prey item consumes it in a concealed place. Concomitantly, nestlings vocalize intensely probably to indicate their motivation to siblings to not share their food item, since this vocal behaviour was particularly frequent in younger individuals for which the risk of being robbed is higher than in their older siblings. Furthermore, nestlings consumed more rapidly a food item when their siblings vocalized intensely presumably because the intensity of siblings' vocalizations is associated with a risk of prey theft. Our correlative study suggests that sibling competition favoured the evolution of sib-sib communication under a wide range of situations.

Quantitative ultrasound of bone in institutionalized elderly women: a cross-sectional and longitudinal study.

Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85 +/- 7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p < 0.001) with age in BUA, SOS and stiffness index (-0.47%, -0.06%, and -1.01% respectively per year). In the 94 women, (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p < 0.0001) than in the 176 women with no history of fracture (-8.3% for BUA, -1.3% for SOS, -18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4 +/- 0.8 months showed no significant decrease in BUA (-1%) but a significant decrease in SOS (-0.3%, p < 0.0001) and in stiffness index (-3.6%, p < 0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.

A temporal hierarchy for conspecific vocalization discrimination in humans.

Introduction: Discrimination of species-specific vocalizations is fundamental for survival and social interactions. Its unique behavioral relevance has encouraged the identification of circumscribed brain regions exhibiting selective responses (Belin et al., 2004), while the role of network dynamics has received less attention. Those studies that have examined the brain dynamics of vocalization discrimination leave unresolved the timing and the inter-relationship between general categorization, attention, and speech-related processes (Levy et al., 2001, 2003; Charest et al., 2009). Given these discrepancies and the presence of several confounding factors, electrical neuroimaging analyses were applied to auditory evoked-potential (AEPs) to acoustically and psychophysically controlled non-verbal human and animal vocalizations. This revealed which region(s) exhibit voice-sensitive responses and in which sequence. Methods: Subjects (N=10) performed a living vs. man-made 'oddball' auditory discrimination task, such that on a given block of trials 'target' stimuli occurred 10% of the time. Stimuli were complex, meaningful sounds of 500ms duration. There were 120 different sound files in total, 60 of which represented sounds of living objects and 60 man-made objects. The stimuli that were the focus of the present investigation were restricted to those of living objects within blocks where no response was required. These stimuli were further sorted between human non-verbal vocalizations and animal vocalizations. They were also controlled in terms of their spectrograms and formant distributions. Continuous 64-channel EEG was acquired through Neuroscan Synamps referenced to the nose, band-pass filtered 0.05-200Hz, and digitized at 1000Hz. Peri-stimulus epochs of continuous EEG (-100ms to 900ms) were visually inspected for artifacts, 40Hz low-passed filtered and baseline corrected using the pre-stimulus period . Averages were computed from each subject separately. AEPs in response to animal and human vocalizations were analyzed with respect to differences of Global Field Power (GFP) and with respect to changes of the voltage configurations at the scalp (reviewed in Murray et al., 2008). The former provides a measure of the strength of the electric field irrespective of topographic differences; the latter identifies changes in spatial configurations of the underlying sources independently of the response strength. In addition, we utilized the local auto-regressive average distributed linear inverse solution (LAURA; Grave de Peralta Menendez et al., 2001) to visualize and statistically contrast the likely underlying sources of effects identified in the preceding analysis steps. Results: We found differential activity in response to human vocalizations over three periods in the post-stimulus interval, and this response was always stronger than that to animal vocalizations. The first differential response (169-219ms) was a consequence of a modulation in strength of a common brain network localized into the right superior temporal sulcus (STS; Brodmann's Area (BA) 22) and extending into the superior temporal gyrus (STG; BA 41). A second difference (291-357ms) also followed from strength modulations of a common network with statistical differences localized to the left inferior precentral and prefrontal gyrus (BA 6/45). These two first strength modulations correlated (Spearman's rho(8)=0.770; p=0.009) indicative of functional coupling between temporally segregated stages of vocalization discrimination. A third difference (389-667ms) followed from strength and topographic modulations and was localized to the left superior frontal gyrus (BA10) although this third difference did not reach our spatial criterion of 12 continuous voxels. Conclusions: We show that voice discrimination unfolds over multiple temporal stages, involving a wide network of brain regions. The initial stages of vocalization discrimination are based on modulations in response strength within a common brain network with no evidence for a voice-selective module. The latency of this effect parallels that of face discrimination (Bentin et al., 2007), supporting the possibility that voice and face processes can mutually inform one another. Putative underlying sources (localized in the right STS; BA 22) are consistent with prior hemodynamic imaging evidence in humans (Belin et al., 2004). Our effect over the 291-357ms post-stimulus period overlaps the 'voice-specific-response' reported by Levy et al. (Levy et al., 2001) and the estimated underlying sources (left BA6/45) were in agreement with previous findings in humans (Fecteau et al., 2005). These results challenge the idea that circumscribed and selective areas subserve con-specific vocalization processing.