Do epoch lengths of hypnotic depth indicators affect estimated of blood-brain equilibration rate constants of propofol?

This study aimed to investigate the effect of epoch length of hypnotic depth indicators on the blood-brain equilibration rate constant (ke0) estimates of propofol. Propofol was administered by zero-order infusion (1.5, 3.0, 6, and 12 mg·kg-1·h-1) for one hour in 63 healthy volunteers. The ke0 of propofol was estimated using an effect-compartment model linking pharmacokinetics and pharmacodynamics, in which response variables were electroencephalographic approximate entropy (ApEn) or bispectral index (BIS) (n = 32 each for propofol infusion rates of 6 and 12 mg·kg-1·h-1). Epoch lengths of ApEn were 2, 10, 30, and 60 seconds (s). The correlations between plasma propofol concentrations (Cp) and BIS and ApEn 2, 10, 30, and 60 s were determined, as was the Ce associated with 50% probability of unconsciousness (Ce50,LOC). The pharmacokinetics of propofol were well described by a three-compartment model. The correlation coefficient between Cp and ApEn 2, 10, 30, and 60 s were -0.64, -0.54, -0.39, and -0.26, respectively, whereas correlation coefficient between Cp and BIS was -0.74. The blood-brain equilibration half-life based on the ke0 estimates for ApEn at 2, 10, 30, 60 s and BIS were 4.31, 3.96, 5.78. 6.54, 5.09 min, respectively, whereas the Ce50,LOC for ApEn at 2, 10, 30, 60 s and BIS were 1.55, 1.47, 1.28, 1.04, and 1.55 µg·ml-1, respectively. Since ke0, which determines the onset of drug action, varies according to the epoch length, it is necessary to consider the epoch length together when estimating ke0.

Performance of the MP570T pulse oximeter in volunteers participating in the controlled desaturation study: a comparison of seven probes.

BACKGROUND: The performance of the pulse oximeter was evaluated based on the ISO 80601-2-61:2011 (E) guidelines. This study aimed to determine whether the various finger probes of the MP570T pulse oximeter (MEK-ICS Co., Ltd., Korea) would provide clinically reliable peripheral oxygen saturation (SpO2) readings over a range of 70-100% arterial oxygen saturation (SaO2) during non-motion conditions. METHODS: Each volunteer (n = 12) was connected to a breathing circuit for the administration of a hypoxic gas mixture. For frequent blood sampling, an arterial cannula was placed in a radial artery. The following seven pulse oximeter probes were simultaneously attached to each volunteer's fingers: (1) WA-100 reusable finger probe (MEDNIS Co., Ltd., Korea), (2) MDNA disposable finger probe (MEDNIS Co., Ltd.), (3) IS-1011 disposable finger probe (Insung Medical Co., Ltd., Korea), (4) CJ340NA disposable finger probe (CHUN JI IN Medical Co., Ltd., Korea), (5) NellcorTM OxiMax DS-100A reusable finger probe (Medtronic, USA), (6) NellcorTM OxiMax MAX-N disposable finger probe (Medtronic), and (7) OXI-PRO DA disposable finger probe (Bio-Protech Inc., Korea). RESULTS: A total of 275 SpO2-SaO2 pairs were included in the analysis. The accuracy of the root mean square (Arms ) of each probe was 2.83%, 3.98%, 3.75%, 6.84%, 3.43%, 5.17%, and 3.84%, respectively. CONCLUSIONS: The MP570T pulse oximeter with WA-100 reusable, MDNA disposable, IS-1011 disposable, NellcorTM OxiMax DS-100A reusable, and OXI-PRO DA disposable finger probes meets an acceptable standard of SpO2 accuracy under non-motion conditions.

Quantitative analysis of the effect of fraction of inspired oxygen on peripheral oxygen saturation in healthy volunteers.

BACKGROUND: The international organization for standardization (ISO) 80601-2-61 dictates that the accuracy of a pulse oximeter should be assessed by a controlled desaturation study. We aimed to characterize the relationship between the fraction of inspired oxygen (FiO2) and peripheral oxygen saturation (SpO2) using a turnover model by retrospectively analyzing the data obtained from previous controlled desaturation studies. MATERIALS AND METHODS: Each volunteer was placed in a semi-Fowler's position and connected to a breathing circuit to administer the hypoxic gas mixture containing medical air, oxygen, nitrogen, and carbon dioxide. Volunteers were exposed to various levels of induced hypoxia over 70-100% arterial oxygen saturation (SaO2). The study period consisted of two rounds of hypoxia and the volunteers were maintained in room air between each round. FiO2 and SpO2 were recorded continuously during the study period. A population pharmacodynamic analysis was performed with the NONMEM VII level 4 (ICON Development Solutions, Ellicott City, MD, USA). RESULTS: In total, 2899 SpO2 data points obtained from 20 volunteers were used to determine the pharmacodynamic characteristics. The pharmacodynamic parameters were as follows: kout = 0.942 1/min, Imax = 0.802, IC50 = 85.3%, γ = 27.3. CONCLUSION: The changes in SpO2 due to decreases in FiO2 well explained by the turnover model with inhibitory function as a sigmoidal model.

CMOS High-Voltage Analog 1-64 Multiplexer/Demultiplexer for Integrated Ultrasound Guided Breast Needle Biopsy.

Ultrasound guided needle biopsy is an important method for collection of breast cancer tissue. In this paper, we report on the design and testing of a high-voltage 1 to 64 Multiplexer/Demultiplexer (MUX/De-MUX) integrated circuit (IC) for ultrasound-guided breast biopsy applications implemented in a high-voltage CMOS process. The IC is intended to be incorporated inside the breast biopsy needle and is designed to fit inside the needle inner diameter of 2.38 mm. The MUX/De-MUX electronics are made up of three parts, including a low-voltage 6 to 64 decoder, a level shifter to convert from low voltage to high voltage, and analog high-voltage switches. Experimental results show a -3-dB bandwidth of over 70 MHz, Rds (on) of , -2.279-dB insertion loss, and -17.5-dB off isolation at 70 MHz with low-voltage input. Finally, we present results obtained via synthetic aperture imaging using the fabricated MUX/De-Mux device and a high-frequency ultrasound array. This device and technique hold promise for high-frequency imaging probes where a limited number of elements are used and the depth of penetration is short such as in breast biopsy and intravascular applications.

Exploring the pros and cons of mechanistic case diagrams for problem-based learning.

PURPOSE: Mechanistic case diagram (MCD) was recommended for increasing the depth of understanding of disease, but with few articles on its specific methods. We address the experience of making MCD in the fullest depth to identify the pros and cons of using MCDs in such ways. METHODS: During problem-based learning, we gave guidelines of MCD for its mechanistic exploration from subcellular processes to clinical features, being laid out in as much detail as possible. To understand the students' attitudes and depth of study using MCDs, we analyzed the results of a questionnaire in an open format about experiencing MCDs and examined the resulting products. RESULTS: Through the responses to questionnaire, we found several favorable outcomes, major of which was deeper insight and comprehensive understanding of disease facilitated by the process of making well-organized diagram. The main disadvantages of these guidelines were the feeling of too much workload and difficulty of finding mechanisms. Students gave suggestions to overcome these problems: cautious reading of comprehensive texts, additional guidance from staff about depth and focus of mechanisms, and cooperative group work. From the analysis of maps, we recognized there should be allowance of diversities in the appearance of maps and many hypothetical connections, which could be related to an insufficient understanding of mechanisms in nature. CONCLUSION: The more detailed an MCD task is, the better students can become acquainted with deep knowledges. However, this advantage should be balanced by the results that there are many ensuing difficulties for the work and deliberate help plans should be prepared.

Automated Segmentation of Light-Sheet Fluorescent Imaging to Characterize Experimental Doxorubicin-Induced Cardiac Injury and Repair.

This study sought to develop an automated segmentation approach based on histogram analysis of raw axial images acquired by light-sheet fluorescent imaging (LSFI) to establish rapid reconstruction of the 3-D zebrafish cardiac architecture in response to doxorubicin-induced injury and repair. Input images underwent a 4-step automated image segmentation process consisting of stationary noise removal, histogram equalization, adaptive thresholding, and image fusion followed by 3-D reconstruction. We applied this method to 3-month old zebrafish injected intraperitoneally with doxorubicin followed by LSFI at 3, 30, and 60 days post-injection. We observed an initial decrease in myocardial and endocardial cavity volumes at day 3, followed by ventricular remodeling at day 30, and recovery at day 60 (P < 0.05, n = 7-19). Doxorubicin-injected fish developed ventricular diastolic dysfunction and worsening global cardiac function evidenced by elevated E/A ratios and myocardial performance indexes quantified by pulsed-wave Doppler ultrasound at day 30, followed by normalization at day 60 (P < 0.05, n = 9-20). Treatment with the γ-secretase inhibitor, DAPT, to inhibit cleavage and release of Notch Intracellular Domain (NICD) blocked cardiac architectural regeneration and restoration of ventricular function at day 60 (P < 0.05, n = 6-14). Our approach provides a high-throughput model with translational implications for drug discovery and genetic modifiers of chemotherapy-induced cardiomyopathy.

Fabrication and Characterization of a 20-MHz Microlinear Phased-Array Transducer for Intervention Guidance.

This paper describes the design and fabrication of a miniature ultrasonic phased-array transducer used for intervention guidance. Currently, ultrasound probes are often placed at the body surface of the patients, leading to several drawbacks including the limitation of penetration and image quality. In order to improve the reliability of the guiding process, we propose a miniature phased-array transducer that can be placed adjacent to the intervention device during the interventional procedure. In this paper, we report the work that has been carried out on the development of this miniature phased-array transducer. It comprised 48 elements housed in a 3-mm-diameter needle. A specially designed flexible circuit was used for accommodating the transducer array in the long, thin needle housing. The center frequency and the fractional bandwidth were approximately 20 MHz and 42%, respectively, with an average crosstalk lower than -30 dB. The axial and azimuth resolutions were approximately 80 and [Formula: see text], respectively. The imaging capability of the transducer was further evaluated by acquiring the B-mode images of a needle in a cow liver. The performance of the proposed phased-array transducer demonstrates the feasibility of such an approach for interventional guidance.

Jitter reduction technique for acoustic radiation force impulse microscopy via photoacoustic detection.

We demonstrate a jitter noise reduction technique for acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), which promises to be capable of measuring cell mechanics. To reduce the jitter noise induced by Q-switched pulsed laser operated at high repetition frequency, photoacoustic signals from the surface of an ultrasound transducer are aligned by cross-correlation and peak-to-peak detection, respectively. Each method is then employed to measure the displacements of a target sample in an agar phantom and a breast cancer cell due to ARFI application, followed by the quantitative comparison between their performances. The suggested methods for PA-ARFI significantly reduce jitter noises, thus allowing us to measure displacements of a target cell due to ARFI application by less than 3 µm.

Dual-element needle transducer for intravascular ultrasound imaging.

A dual-element needle transducer for intravascular ultrasound imaging has been developed. A low-frequency element and a high-frequency element were integrated into one device to obtain images which conveyed both low- and high-frequency information from a single scan. The low-frequency element with a center frequency of 48 MHz was fabricated from the single crystal form of lead magnesium niobate-lead titanate solid solution with two matching layers (MLs) and the high frequency element with a center frequency of 152 MHz was fabricated from lithium niobate with one ML. The measured axial and lateral resolutions were 27 and [Formula: see text], respectively, for the low-frequency element, and 14 and [Formula: see text], respectively, for the high-frequency element. The performance of the dual-element needle transducer was validated by imaging a tissue-mimicking phantom with lesion-mimicking area, and ex vivo rabbit aortas in water and rabbit whole blood. The results suggest that a low-frequency element effectively provides depth resolved images of the whole vessel and its adjacent tissue, and a high-frequency element visualizes detailed structure near the surface of the lumen wall in the presence of blood within the lumen. The advantages of a dual-element approach for intravascular imaging are also discussed.

Electrical and Mechanical Strategies to Enable Cardiac Repair and Regeneration.

Inadequate replacement of lost ventricular myocardium from myocardial infarction leads to heart failure. Investigating the regenerative capacity of mammalian hearts represents an emerging direction for tissue engineering and cell-based therapy. Recent advances in stem cells hold promise to restore cardiac functions. However, embryonic or induced pluripotent stem cell-derived cardiomyocytes lack functional phenotypes of the native myocardium, and transplanted tissues are not fully integrated for synchronized electrical and mechanical coupling with the host. In this context, this review highlights the mechanical and electrical strategies to promote cardiomyocyte maturation and integration, and to assess the functional phenotypes of regenerating myocardium. Simultaneous microelectrocardiogram and high-frequency ultrasound techniques will also be introduced to assess electrical and mechanical coupling for small animal models of heart regeneration.

Angled-focused 45 MHz PMN-PT single element transducer for intravascular ultrasound imaging.

A transducer with an angled and focused aperture for intravascular ultrasound imaging has been developed. The acoustic stack for the angled-focused transducer was made of PMN-PT single crystal with one matching layer, one protective coating layer, and a highly damped backing layer. It was then press-focused to a desired focal length and inserted into a thin needle housing with an angled tip. A transducer with an angled and unfocused aperture was also made, following the same fabrication procedure, to compare the performance of the two transducers. The focused and unfocused transducers were tested to measure their center frequencies, bandwidths, and spatial resolutions. Lateral resolution of the angled-focused transducer (AFT) improved more than two times compared to that of the angled-unfocused transducer (AUT). A tissue-mimicking phantom in water and a rabbit aorta tissue sample in rabbit blood were scanned using AFT and AUT. Imaging with AFT offered improved contrast, over imaging with AUT, of the tissue-mimicking phantom and the rabbit aorta tissue sample by 23 dB and 8 dB, respectively. The results show that AFT has strong potential to provide morphological and pathological information of coronary arteries with high resolution and high contrast.

Non-contact acoustic radiation force impulse microscopy via photoacoustic detection for probing breast cancer cell mechanics.

We demonstrate a novel non-contact method: acoustic radiation force impulse microscopy via photoacoustic detection (PA-ARFI), capable of probing cell mechanics. A 30 MHz lithium niobate ultrasound transducer is utilized for both detection of phatoacoustic signals and generation of acoustic radiation force. To track cell membrane displacements by acoustic radiation force, functionalized single-walled carbon nanotubes are attached to cell membrane. Using the developed microscopy evaluated with agar phantoms, the mechanics of highly- and weakly-metastatic breast cancer cells are quantified. These results clearly show that the PA-ARFI microscopy may serve as a novel tool to probe mechanics of single breast cancer cells.

High-frequency dual mode pulsed wave Doppler imaging for monitoring the functional regeneration of adult zebrafish hearts.

Adult zebrafish is a well-known small animal model for studying heart regeneration. Although the regeneration of scars made by resecting the ventricular apex has been visualized with histological methods, there is no adequate imaging tool for tracking the functional recovery of the damaged heart. For this reason, high-frequency Doppler echocardiography using dual mode pulsed wave Doppler, which provides both tissue Doppler (TD) and Doppler flow in a same cardiac cycle, is developed with a 30 MHz high-frequency array ultrasound imaging system. Phantom studies show that the Doppler flow mode of the dual mode is capable of measuring the flow velocity from 0.1 to 15 cm s(-1) with high accuracy (p-value = 0.974 > 0.05). In the in vivo study of zebrafish, both TD and Doppler flow signals were simultaneously obtained from the zebrafish heart for the first time, and the synchronized valve motions with the blood flow signals were identified. In the longitudinal study on the zebrafish heart regeneration, the parameters for diagnosing the diastolic dysfunction, for example, E/Em < 10, E/A < 0.14 for wild-type zebrafish, were measured, and the type of diastolic dysfunction caused by the amputation was found to be similar to the restrictive filling. The diastolic function was fully recovered within four weeks post-amputation.

Multi-particle trapping and manipulation by a high-frequency array transducer.

We report the multiple micro-particle trapping and manipulation by a single-beam acoustic tweezer using a high-frequency array transducer. A single acoustic beam generated by a 30 MHz ultrasonic linear array transducer can entrap and transport multiple micro-particles located at the main lobe and the grating lobes. The distance between trapped particles can be adjusted by changing the transmit arrangement of array-based acoustic tweezers and subsequently the location of grating lobes. The experiment results showed that the proposed method can trap and manipulate multiple particles within a range of hundreds of micrometers. Due to its simplicity and low acoustic power, which is critical to protect cells from any thermal and mechanical damages, the technique may be used for transportation of cells in cell biology, biosensors, and tissue engineering.

Trigemino-cardiac reflex: occurrence of asystole during trans-sphenoidal adenomectomy: a case report.

The trigemino-cardiac reflex has been reported to occur during various craniofacial surgeries or procedures including manipulation of the trigeminal ganglion, tumor resection in the cerebellopontine angle, various facial reconstructions and trans-sphenoidal adenomectomy. Regarding risk factors during trans-sphenoidal adenomectomy, invasiveness closely related to the size of tumor and the degree of manipulation of cavernous sinus wall have been reported. We report the case of a 40-year-old female patient who had a relatively small-sized (< 10 mm) pituitary adenoma. Repetitive asystoles occurred during microscopic trans-sphenoidal operation of the wall of the cavernous sinus, which strongly suggests the importance of careful manipulation of the cavernous sinus wall. In addition to reporting this rare complication of trans-sphenoidal adenomectomy, we reviewed its clinical management by performing a literature search.

Hemodynamics and ventricular function in a zebrafish model of injury and repair.

Myocardial infarction results in scar tissue and irreversible loss of ventricular function. Unlike humans, zebrafish has the capacity to remove scar tissue after injury. To assess ventricular function during repair, we synchronized microelectrocardiogram (µECG) signals with a high-frequency ultrasound pulsed-wave (PW) Doppler to interrogate cardiac hemodynamics. µECG signals allowed for identification of PW Doppler signals for passive (early [E]-wave velocity) and active ventricular filling (atrial [A]-wave velocity) during diastole. The A wave (9.0±1.2 cm·s(-1)) is greater than the E wave (1.1±0.4 cm·s(-1)), resulting in an E/A ratio <1 (0.12±0.05, n=6). In response to cryocauterization to the ventricular epicardium, the E-wave velocity increased, accompanied by a rise in the E/A ratio at 3 days postcryocauterization (dpc) (0.55±0.13, n=6, p<0.001 vs. sham). The E waves normalize toward the baseline, along with a reduction in the E/A ratio at 35 dpc (0.36±0.06, n=6, p<0.001 vs. sham) and 65 dpc (0.2±0.16, n=6, p<0.001 vs. sham). In zebrafish, E/A<1 at baseline is observed, suggesting the distinct two-chamber system in which the pressure gradient across the atrioventricular valve is higher compared with the ventriculobulbar valve. The initial rise and subsequent normalization of E/A ratios support recovery in the ventricular diastolic function.

The effects of ethnic, social and cultural factors on axis I comorbidity of bipolar disorder: results from the clinical setting in Korea.

OBJECTIVE: Ethnic, social and cultural factors contribute to axis I comorbid conditions in bipolar disorder (BPD). Korea has strict laws against illicit drugs and a relatively permissive prevailing attitude toward alcohol. The present study aimed to explore the lifetime axis I comorbidity rate in patients with BPD in Korea. METHODS: Clinically stable patients with bipolar I (n=222) and bipolar II (n=194) disorders were recruited from four tertiary medical centers in Korea. The subjects׳ diagnoses and axis I comorbid conditions were evaluated using the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID) and the Korean version of the Diagnostic Interview for Genetic Studies (K-DIGS). The lifetime prevalence of anxiety disorders, substance use disorders and eating disorders was explored. The prevalence of these axis I comorbid conditions was compared with data from prior studies in other countries and to data concerning the general Korean population. RESULTS: A total of 45.1% of all subjects had at least one axis I comorbid condition. Anxiety disorders (30.2%) were the most common comorbidity, followed by alcohol use disorders (16.8%). Males with BPD showed a higher rate of alcohol dependence compared to the general male population and females with BPD showed a greater risk of having alcohol use disorder compared to the general female population. The rate of drug use disorder was extremely low (1.7%), and only one subject had an illicit-drug-related problem. LIMITATION: Cross-sectional studies. CONCLUSION: Comorbid conditions of Korean patients with BPD showed a distinct pattern, which is associated with the ethnic, social and cultural characteristics in Korea.

Non-contact high-frequency ultrasound microbeam stimulation for studying mechanotransduction in human umbilical vein endothelial cells.

We describe how contactless high-frequency ultrasound microbeam stimulation (HFUMS) is capable of eliciting cytoplasmic calcium (Ca(2+)) elevation in human umbilical vein endothelial cells. The cellular mechanotransduction process, which includes cell sensing and adaptation to the mechanical micro-environment, has been studied extensively in recent years. A variety of tools for mechanical stimulation have been developed to produce cellular responses. We developed a novel tool, a highly focused ultrasound microbeam, for non-contact cell stimulation at a microscale. This tool, at 200 MHz, was applied to human umbilical vein endothelial cells to investigate its potential to elicit an elevation in cytoplasmic Ca(2+) levels. It was found that the response was dose dependent, and moreover, extracellular Ca(2+) and cytoplasmic Ca(2+) stores were involved in the Ca(2+) elevation. These results suggest that high-frequency ultrasound microbeam stimulation is potentially a novel non-contact tool for studying cellular mechanotransduction if the acoustic pressures at such high frequencies can be quantified.

Effectiveness of milrinone for cardiogenic shock due to massive pulmonary aspiration: a case report.

Pulmonary aspiration of gastric contents is one of the most frightening complications during anesthesia. Although pulmonary aspiration of gastric contents in general surgical patients is not common and resulting long-term morbidity and mortality are rare, severe hypoxemia and other sequelae of pulmonary aspiration continue to be reported. We report a case of massive aspiration of gastric contents during induction of general anesthesia, resulting in cardiac arrest due to severe pulmonary hypertension and myocardial infarction. Sustained cardiac arrest and shock that did not respond the conventional resuscitation was successfully treated using milrinone. The patient was discharged without complications in 20 days.