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Differential effects of myeloid dendritic cells retrovirally transduced to express mammalian or viral interleukin-10 on cytotoxic T lymphocyte and natural killer cell functions and resistance to tumor growth.

BACKGROUND: Genetic engineering of dendritic cells (DC) to express immunosuppressive molecule(s) offers potential for therapy of allograft rejection and autoimmune disease. Viral (v) interleukin (IL)-10, encoded by the Epstein-Barr virus, is highly homologous to mammalian (m) IL-10, but lacks certain of its T-cell stimulatory activities. Our aim was to evaluate and compare the influence of vIL-10 and mIL-10 gene transfer on the T-cell and natural killer (NK) cell stimulatory activity of DC, and their impact on the growth of transplantable tumors. METHODS: Myeloid DC progenitors, propagated from the bone marrow of C57BL/6J (H2b) mice in granulocyte-macrophage colony-stimulating factor + IL-4, were transduced using retroviral supematant from the BOSC ecotropic packaging cell line. The function of the IL-b gene-modified DC was assessed by examining their ability to induce naive allogeneic T-cell proliferation and cytotoxic T lymphocyte (CTL) generation. MCA205 (H2b) sarcoma cells mixed with either vIL-10-, mIL-10-, or Zeo (control gene)-transduced DC were inoculated intradermally into C57BL/6J (syngeneic) or BALB/cJ (H2d) (allogeneic) recipients, which were monitored for tumor growth. The role of specific host effector cell populations in tumor resistance was determined by antibody depletion. RESULTS: Compared with control gene-modified DC, both vIL-10- and mIL-10-transduced DC, which secreted the transgene product, showed reduced surface expression of MHC class II and costimulatory molecules, and impaired ability to induce T-cell proliferation. vIL-10-transduced DC were also inhibited with respect to CTL induction but did not affect the generation of NK cells. By contrast, mIL-10-transduced DC augmented CTL generation and NK cell activity. In the tumor transplant model, vIL-10-transduced DC enhanced tumor growth both in syngeneic and allogeneic hosts, whereas mIL-10-transduced cells inhibited tumor development. Depletion of CD4+ or CD8+ T cells or NK cells in mice given mIL-10-transduced DC reversed this therapeutic effect. CONCLUSION: mIL-10 gene-modified myeloid DC promote CTL and NK cell-mediated responses and inhibit tumor growth. By contrast, vIL-10-engineered DC, which elicit diminished CTL responses and do not promote NK cell activity, seem to have therapeutic potential for inhibition of T cell-mediated immunity.

Animals↗

Ultrasound transducer modeling--general theory and applications to ultrasound reciprocal systems.

A tutorial presentation on the theory of reciprocal ultrasound systems is given, and a complete set of modeling equations for one-dimensional multi-layer ultrasound transducers is derived from first principles. The model includes dielectric losses and mechanical losses in the transducer material layers as well as sound absorption in the transmission medium. First, the so-called constitutive relations of a piezoelectric body are derived based on general thermodynamic considerations, assuming that transducer operation takes place under almost isentropic conditions. Second, full attention is given to transducers oscillating in the thickness mode, discarding all other vibration modes. Dynamic transducer equations are determined using Newton's Second Law, Poisson's equation, and the definition of strain applied to a piezoelectric transducer with one or more non-piezoelectric layers on the front surface (multilayer transducer). Boundary conditions include continuity of normal velocity and stress across material interfaces as well as a subsidiary electrical condition over the piezoceramic electrodes. Sound transmission is assumed to take place in a water bath such that the Rayleigh equation can be used to obtain the incoming pressure at the receiver aperture from the acceleration of the opposing transmitter. This allows, e.g., a detailed treatment of receiver signal variations as the receiver moves from the near-field zone to the far-field zone of the transmitter. In the remaining part of the paper, receiver voltage and current signals are obtained by solving the full set of dynamic equations numerically. Special attention is given to transducers consisting of a) a pure piezoceramic layer only, b) a piezoceramic layer and a quarter-wavelength matching layer of polyphenylensulphide (PPS), c) a piezoceramic layer and a half-wavelength matching layer of stainless steel, and d) a piezoceramic layer and a half-wavelength matching layer of stainless steel tuned to resonance by a parallel inductance. Results are also given for receiver incoming pressure and receiver voltage signals when sound reception takes place in the near-field and far-field zones of the transmitter.

Journal Article↗

Experimental validation of two elastodynamic models for the wave field generated by ultrasonic transducers.

Two different three-dimensional elastodynamic models are introduced to simulate the wave field generated in steel by two types of surface mounted ultrasonic transducers. By replacing the actual transducer by an equivalent surface source distribution, the models become amenable to an exact analytical analysis. The first model simulates the action of a contact transducer through a distribution of nonmoving line segment sources. The second model simulates the action of an angle beam transducer through a single moving line segment source. Almost any transducer aperture shape may be modeled, while the source may apply a nonuniform traction. To speed up the numerical space-time domain calculations, the Cagniard-De Hoop method is employed to analytically evaluate the wave field produced by a single nonmoving line segment source. This solution provides the integrand for both single-integral models. The models are experimentally validated for a contact transducer and three different angle beam transducers. The validation involves a comparison of the wave-field patterns, the directivity curves and some time-domain signals from the wave field. It is shown that the models reliably identify the wide variety of waves generated by ultrasonic transducers, such as focused waves, edge waves, Rayleigh waves and head waves.

Journal Article↗

Concurrent changes in transducing efficiency and content of transforming deoxyribonucleic acid in Bacillus subtilis bacteriophage SP-10.

Taylor, Martha J. (Fort Detrick, Frederick, Md.), and Curtis B. Thorne. Concurrent changes in transducing efficiency and content of transforming deoxyribonucleic acid in Bacillus subtilis bacteriophage SP-10. J. Bacteriol. 91:81-88. 1966.-Spores of Bacillus subtilis W-23-S(r) infected with transducing phage SP-10 served as convenient inocula for broth cultures from which transducing phage was harvested. Methods are described for producing highly infected spores. The inoculum level of infected spores in nutrient broth-yeast extract-glucose medium affected the transducing efficiency of SP-10 in lysates of these cultures. Phage in lysates of cultures inoculated with about 10(5) or fewer spores per milliliter transduced 20- to 350-fold more efficiently than did phage in lysates from cultures inoculated with 10(6) to 10(7) spores per milliliter. Transduction frequencies in the order of 10(-5) per plaque-forming unit were obtained routinely, and some infected-spore preparations yielded phage that gave frequencies as high as 10(-4). The combination of inoculum level and incubation time required to produce the best transducing phage had to be determined empirically for each batch of infected spores. Several possible explanations for the difference between lysates having high (HTE) and those having low (LTE) transducing efficiency were ruled out by special experiments. The hypothesis is presented that some cultural condition resulting from a relatively low inoculum of phage-infected spores favors the incorporation by phage particles of bacterial deoxyribonucleic acid (DNA) in the manner required for the production of transducing phage. Support for this hypothesis is a demonstration, through transformation experiments with DNA extracted from HTE and LTE phage particles, that populations of HTE phage particles yielded significantly more (7 to 27 times) transforming activity per microgram of DNA than did populations of LTE phage.

Bacillus subtilis↗

Human telomerase reverse transcriptase-transduced human cytotoxic T cells suppress the growth of human melanoma in immunodeficient mice.

Immunotherapy of melanoma by adoptive transfer of tumor-reactive T lymphocytes aims at increasing the number of activated effectors at the tumor site that can mediate tumor regression. The limited life span of human T lymphocytes, however, hampers obtaining sufficient cells for adoptive transfer therapy. We have shown previously that the life span of human T cells can be greatly extended by transduction with the human telomerase reverse transcriptase (hTERT) gene, without altering antigen specificity or effector function. We developed a murine model to evaluate the efficacy of hTERT-transduced human CTLs with antitumor reactivity to eradicate autologous tumor cells in vivo. We transplanted the human melanoma cell line melAKR or melAKR-Flu, transduced with a retrovirus encoding the influenza virus/HLA-A2 epitope, in RAG-2(-/-) IL-2Rgamma (-/-) double knockout mice. Adoptive transfer of the hTERT-transduced influenza virus-specific CTL clone INFA24 or clone INFA13 inhibited the growth of melAKR-Flu tumors in vivo and not of the parental melAKR melanoma cells. Furthermore, the hTERT-transduced CTL clone INFA13 inhibited tumor growth to the same extent in vivo as the untransduced CTL clone, as determined by in vivo imaging of luciferase gene-transduced melAKR-Flu tumors, indicating that hTERT did not affect the in vivo function of CTL. These results demonstrate that hTERT-transduced human CTLs are capable of mediating antitumor activity in vivo in an antigen-specific manner. hTERT-transduced MART-1-specific CTL clones AKR4D8 and AKR103 inhibited the growth of syngeneic melAKR tumors in vivo. Strikingly, melAKR-Flu cells were equally killed by the MART-1-specific CTL clones and influenza virus-specific CTL clones in vitro, but only influenza-specific CTLs were able to mediate tumor regression in vivo. The influenza-specific CTL clones were found to produce higher levels of IFNgamma on tumor cell recognition than the MART-1-specific CTL clones, which may result from the higher functional avidity of the influenza virus-specific CTL clones. Also, melAKR-Flu tumors were growing faster than melAKR tumors, which may have surpassed the relatively modest antitumor effect of the MART-1-specific CTL, as compared with the influenza virus-specific CTL. Taken together, the adoptive transfer model described here shows that hTERT-transduced T cells are functional in vivo, and allows us to evaluate the balance between functional activity of the CTL and tumor growth rate in vivo, which determines the efficacy of CTLs to eradicate tumors in adoptive transfer therapy.

Animals↗

P5L mutation in Ank results in an increase in extracellular inorganic pyrophosphate during proliferation and nonmineralizing hypertrophy in stably transduced ATDC5 cells.

Ank is a multipass transmembrane protein that regulates the cellular transport of inorganic pyrophosphate. In the progressive ankylosis (ank) mouse, a premature termination mutation at glutamic acid 440 results in a phenotype characterized by inappropriate deposition of basic calcium phosphate crystals in skeletal tissues. Mutations in the amino terminus of ANKH, the human homolog of Ank, result in familial calcium pyrophosphate dihydrate deposition disease. It has been hypothesized that these mutations result in a gain-of-function with respect to the elaboration of extracellular inorganic pyrophosphate. To explore this issue in a mineralization-competent system, we stably transduced ATDC5 cells with wild-type Ank as well as with familial chondrocalcinosis-causing Ank mutations. We evaluated the elaboration of inorganic pyrophosphate, the activity of pyrophosphate-modulating enzymes, and the mineralization in the transduced cells. Expression of transduced protein was confirmed by quantitative real-time PCR and by ELISA. Levels of inorganic pyrophosphate were measured, as were the activities of nucleotide pyrophosphatase phosphodiesterase and alkaline phosphatase. We also evaluated the expression of markers of chondrocyte maturation and the nature of the mineralization phase elaborated by transduced cells. The cell line expressing the proline to leucine mutation at position 5 (P5L) consistently displayed higher levels of extracellular inorganic pyrophosphate and higher phosphodiesterase activity than the other transduced lines. During hypertrophy, however, extracellular inorganic pyrophosphate levels were modulated by alkaline phosphatase activity in this cell system, resulting in the deposition of basic calcium phosphate crystals only in all transduced cell lines. Cells overexpressing wild-type Ank displayed a higher level of expression of type X collagen than cells transduced with mutant Ank. Other markers of hypertrophy and terminal differentiation, such as alkaline phosphatase, osteopontin, and runx2, were not significantly different in cells expressing wild-type or mutant Ank in comparison with cells transduced with an empty vector or with untransduced cells. These results suggest that the P5L Ank mutant is capable of demonstrating a gain-of-function with respect to extracellular inorganic pyrophosphate elaboration, but this effect is modified by high levels of expression of alkaline phosphatase in ATDC5 cells during hypertrophy and terminal differentiation, resulting in the deposition of basic calcium phosphate crystals.

Alkaline Phosphatase↗

Sonography during early pregnancy: dependence of threshold and discriminatory values on transvaginal transducer frequency.

OBJECTIVE: Our goal was to determine if normal and abnormal pregnancies could be distinguished at smaller sac sizes with a higher frequency transvaginal transducer than with a 5-MHz transducer. SUBJECTS AND MATERIALS: Thirty-nine patients with potentially abnormal pregnancies identified with a 5-MHz transvaginal transducer were immediately reimaged with a 9-5-MHz transducer. We compared our ability to visualize the yolk sac, embryo, and cardiac activity relative to mean sac diameter on imaging at both frequencies in women with normal and abnormal pregnancies. RESULTS: Of the 39 pregnancies, 22 (56%) were normal or probably normal. Using the 5-MHz transducer, a yolk sac was first seen in a 6.4-mm gestational sac but was not definitively seen in 12 gestational sacs measuring 5-13 mm. Using the 9-5-MHz transducer, yolk sacs were identified in all gestational sacs measuring 4.6-13 mm, and live embryos were seen in five of eight sacs measuring 8.1-13 mm. The largest normal gestational sac without a live embryo measured 11 mm. When we compared these pregnancies with 17 (44%) abnormal pregnancies, we found that all pregnancies that had no yolk sac by the time the gestational sac measured 5.0 mm or no live embryo by 13 mm had abnormal findings on higher frequency imaging. CONCLUSION: The ability to visualize the yolk sac and embryo in early pregnancy is critically dependent on transvaginal transducer frequency. Threshold values and discriminatory sizes used to distinguish normal and abnormal pregnancies are smaller on higher frequency than on lower frequency imaging and, therefore, should be redetermined for specific transducer frequencies.

Adolescent↗

Loss of original antigenic specificity in T cell hybridomas transduced with a chimeric receptor containing single-chain Fv of an anti-collagen antibody and Fc epsilonRI-signaling gamma subunit.

T cell hybridomas HCQ6 and MD.45 acquired Ab-type specificity to collagen type II, when engrafted with a chimeric cell surface receptor, scC2Fv/gamma, which includes the single-chain Fv domain (scFv) of the anti-collagen type II mAb C2 and the signaling gamma subunit of the Fc epsilonRI. When transduced into MD.45 cells, scC2Fv/gamma or its mutated form lacking immunoreceptor tyrosine-based activation motif (ITAM), scC2Fv/gammaIC-, formed mainly homodimers. A small proportion of these molecules formed heterodimers with endogenous CD3zeta in these hybridoma cells. By contrast, in HCQ6 cells, the majority of scC2Fv/gamma and scC2Fv/gammaIC- molecules formed heterodimers with CD3zeta, and only a small proportion of them was expressed as homodimers. Stimulation with plastic-immobilized collagen induced IL-2 production in scC2Fv/gamma-transduced MD.45 cells, but not in MD.45 cells transduced with the ITAM-less chimera scC2Fv/gammaIC-. HCQ6 cells transduced with scC2Fv/gamma responded to plastic-bound collagen. Due to the high content of CD3zeta-associated chimeras, HCQ6 cells transduced with the ITAM-less scC2Fv/gammaIC- chimera were also responsive to plastic-bound collagen. When cells were stimulated with collagen in solution, MD.45 cells transduced with scC2Fv/gamma produced IL-2, whereas transduced HCQ6 cells were unresponsive, hence suggesting that the ability of cells transduced with scC2Fv chimeras to respond to soluble collagen correlated with predominant expression of divalent scC2Fv/gamma homodimers, but not monovalent scC2Fv/gamma-CD3zeta or scC2Fv/gammaIC(-)-CD3zeta heterodimers. Of interest, expression of CD3 subunits in hybridomas transduced with scC2Fv chimeras was reduced, resulting in decreased response to cognate Ags.

Animals↗

Analysis of the dynamic characteristics of pressure transducers for studying respiratory mechanics at high frequencies.

Differential pressure transducers are commonly used to study respiratory mechanics at physiological frequencies as well as during external forcing at high frequencies. In the latter condition, measuring errors could occur if the input impedance of the pressure transducers is not sufficiently large with respect to that of the respiratory system. In this work we analysed the input impedance Z and the transfer function H of two common pressure transducers (Validyne MP-45 and Celesco LCVR) equipped with membranes of different sensitivities and with connecting tubes of different lengths. Z was measured by the tube method and H was measured by comparison with a flat-response pressure transducer. In agreement with the predictions based on a simple lumped-parameters model, we found that Z reached very low values, especially at the frequencies where H had a resonance peak. For instance, for the widespread Validyne MP-45 transducer (200 Pa) with connecting tubes of 16 cm length and 3.8 mm internal diameter a minimum of Z of 8300 Pa s litre-1 at 96 Hz was measured; at that frequency the amplitude of H attained a value of 3.1. Using the above transducer model we simulated the measurement of a rat input impedance up to 128 Hz using Validyne and Celesco transducers. With the Validyne MP-45 (200 Pa), equipped with the same connecting tubes as above, the computed error reached up to 50 per cent for the real part and 140 per cent for the imaginary part.

Animals↗

Effects of gas density on the frequency response of gas-filled pressure transducers.

The effects of gas density on the frequency responses of four pressure transducers were determined at gas densities from 1.2 to 25.0 g/l. Transducers tested included three sensitive differential types used with pneumotachographs to measure respiratory flow (Validyne DP-45 and DP-103; Medistor P-11) and a transducer commonly used to measure esophageal pressure (Statham P23Dd). Three different responses were obtained. The Validyne DP-103 was overdamped and its response was essentially independent of gas density. The frequency response of this transducer is adequate for use with quiet breathing only. The Validyne DP-45 and Medistor P-11 responses were underdamped. The resonant peaks of these transducers decreased markedly in frequency as the gas density increased. The Statham P23Dd was also underdamped; however, its resonant frequency increased as gas density increased. An esophageal balloon did not alter the frequency response characteristics of this tubing-transducer system. Both increases in length and decreases in diameter of connecting tubing reduced the frequency of resonant peaks of underdamped pressure transducers.

Atmospheric Pressure↗

Evaluation of catheter-mounted transducers for intra-oesophageal pressure recording in respiratory function tests.

Oesophageal pressure measurements in respiratory function tests are commonly performed using a balloon-catheter system. This study investigates the usefulness of catheter-mounted pressure transducers as an alternative to balloon-catheter systems. Calibration related physical properties of the catheter mounted pressure transducers are evaluated in vitro. The behaviour of these transducers in vivo is evaluated in ten volunteers by relating pressures measured in the oesophagus to airway opening pressures and by comparing these relationships with those sequentially obtained by a balloon-catheter system. The catheter-mounted pressure transducers show no drift after a proper preparation procedure. These catheters, with integrated pressure transducers, are tolerated significantly better by the subjects than are balloon catheters. The catheter-mounted pressure transducers are found to give an equivalent performance compared with the balloon-catheter system, if relative pressures are of interest. However, unpredictable and uncontrollable shifts in offset occur during the in vivo measurements, disturbing absolute pressure readings. Possible explanations for these shifts are the presence of bubbles and adhesion of mucus to the transducers, exerting Van der Waals forces, and contact with the tissue of the oesophageal wall. These shifts are found to be quite stable throughout a period of measurement and therefore of minor disturbance to relative pressure measurements, for instance in assessing the elastic properties of lungs.

Adult↗

[An implantable piezoelectric hearing aid transducer for inner ear deafness. II: Clinical implant].

A miniature, hermetically sealed implant was development and manufactured in several clinical and technical iteration steps based on the prototype of an implantable piezo-electric hearing-aid transducer described in Part 1 of the work presented here. The transducer is made of pure titanium (medical grade 2, ASTM F67) and designed to be implanted into the mastoid cavity. Transfer of mechanical oscillations to an ossicle in the middle ear is effected by a fixed directly coupling rod of pure titanium or via suitable coupling elements. The transducer is highly tuned with a resonance frequency in the range of 7-10 kHz, depending on the dynamic mass load. Below this resonance and down to low frequencies, the frequency response of elongation is smooth with a very small ripple of less than +/- 1 dB. Unlike the prototype, an increase in vibration amplitude of around 10 dB was achieved for a comparable power consumption. Vibration amplitude at low and middle frequencies is about 60 nm with a transducer voltage of 1 V, corresponding to an equivalent sound-pressure level of around 100 dB SPL at up to 1 kHz. At higher frequencies of up to 10 kHz, the output level increases to beyond 130 dB SPL. Nonlinear distortions at maximum volume (1 V) are extremely small (THD < 0.1%) throughout the whole transfer range. Due to an extremely short attack time (50 microseconds) and short release time (approximately 2 ms), the dynamic properties of the transducer allow good transmission of audio signals with fast changes in the time domain, i.e., plosives in speech signals. Electric power consumption at full volume and broadband signals is in the region of 1 microW. Unlike electromagnetic transducers described in the literature, the low power consumption of this piezoelectric transducer allows the realization of fully implantable hearing aids for rehabilitation of moderate to severe sensorineural hearing loss.

Auditory Threshold↗

[In vivo studies of a piezoelectric implantable hearing aid transducer in the cat].

Recently, we presented an implantable piezoelectrical hearing aid transducer. Its characteristics make it suitable for implantation in patients with sensorineural hearing loss. The transducer transmits micromechanical vibrations instead of sound into the hearing organ. Efficiency of the transducer implant was investigated in ten cat ears. After determining preoperative (acoustical) BERA threshold, the middle ear was opened and the piezoelectrical transducer coupled to various ossicles or the perilymph. BERA responses were recorded following stimulation of umbo, long incus process, stapes head, stapes foot plate, and vestibulum. By comparing the acoustical and mechanical threshold, a correlation was found between the stimulus level of acoustical and mechanical stimulation. An electrical transducer voltage of 1 Vrms was equivalent to sound-pressure levels between 100 and 128 dB SPL at the tympanic membrane. To judge hearing impression, stimulus-dependent latencies of the early acoustically and mechanically evoked potentials (waves P1 to P5) and their thresholds were analyzed. After coupling the piezoelectrical transducer to the long incus process, latencies corresponded well to stimulation. They were almost completely similar when the equivalent sound-pressure level of 100 dB SPL was achieved by the transducer voltage level.

Animals↗

[An osseointegrated micromanipulator as anchor for implantable hearing aid transducers. 1: Fitting to the surgical anatomy of the temporal bone and surgical technical properties].

The first electronic implantable hearing aids for patients with hearing loss are coupled to the ossicular chain or perilymph during implantation and are now available. Our new Tübingen implant designed for sensorineural hearing loss (SNHL) is the combination of an implantable microphone and piezotransducer. To avoid hearing losses during implantation, the Tübingen piezotransducer will be (1) fixed to the mastoid cavity and (2) positioned to one of the ossicular target points. This can be done with a micromanipulator which will be implanted together with transducer and microphone in the mastoid cavity. The manipulator weights 0.7 g. With four degrees of freedom, it allows highly secure and safe positioning of the transducer's probe tip to the ossicular chain under close to stereotactic conditions. The main advantages of the present micromanipulator are (1) easy handling during surgery, (2) the transducer's precise positioning to the ossicular target point with sufficient degrees of freedom, and (3) the transducer's stable fixation in the mastoid cavity in the final position. Following integrated safety as the leading principle, ossicular or inner ear injuries caused, e.g., by the patient's head movement or unintentional manual contact by the surgeon, are minimized. The micromanipulator is, as it were, the surgeon's vibration-free "artificial hand". The manipulator's development and its optimization to the mastoid cavity by test implantation in 50 human temporal bones are shown in detail. While coupling the transducer to the body of the incus, transducer, microphone, and micromanipulator can be implanted into 76% of all mastoid cavities without protrusion. In the case of transducers coupling to the long process of the incus, the protrusion-free implantation rate of the above-mentioned three implant modules is 78%.

Bone Plates↗

In vivo experiments in the cat with an implantable piezoelectric hearing aid transducer.

We have recently developed an implantable piezoelectric hearing aid transducer that is suitable for implantation in patients with sensorineural hearing loss. The transducer does not transmit sound but conducts micromechanical vibrations to the cochlea. In ten cat ears we investigated the efficiency of the implantable transducer with respect to the direct transfer of vibrations within the audible frequency range via the ossicles to the cochlea or directly into the vestibule. The acoustically evoked brainstem potential (ABR) threshold was determined prior to implantation, and the middle ear was then opened and the piezoelectric transducer coupled to the ossicles or to the perilymph. Acoustically evoked brainstem potentials were recorded following stimulation at the umbo, long process of the incus, stapes head, stapes foot plate, and in the vestibulum. Comparisons of the acoustically and mechanically evoked thresholds revealed a good correlation of the two stimulation levels. An electrical transducer voltage of 1 V(RMS) produced equivalent sound pressure levels (SPL) of 100-128 dB at the tympanic membrane. To assess the hearing we compared stimulus-dependent latencies of the early potentials (peaks P1-P5) and thresholds. This evaluation was based on four ears with normal hearing in which the piezoelectric transducer was coupled to the long process of the incus. The mean values of the latencies and their scattering range correlated extremely well in the two stimulation modes. They were nearly identical when the equivalent SPL of 100 dB was assigned to the maximally applied electrical level of 0 dB. These in vitro and in vivo findings demonstrate that the characteristics of the transducer warrant its development further from the prototype stage to become a component of an implantable hearing device for patients with sensorineural hearing loss.

Acoustic Stimulation↗

The cushion scanning technique: a method of dynamic tongue sonography and its comparison with the transducer-skin coupling scanning technique during swallowing.

RATIONALE AND OBJECTIVES: We describe the cushion scanning technique (CST), which solves common difficulties encountered during ultrasound investigations of swallowing. These problems arise when the transducer is held in direct contact with the submental area. Some of these problems include movements of the ultrasound transducer during swallowing and compression of the submental region, which causes abnormal swallowing patterns. METHODS: To compare ultrasound images produced with the conventional hand-held transducer-skin coupling scanning technique with the CST, we studied five participants with no clinical signs of tongue dysfunction. All tongue movements were recorded by real-time B+M-mode sonography. RESULTS: Images produced with the hand-held transducer were found to be unstable because the transducer moved during swallowing, thereby changing the scanning section. By contrast, the transducer and the participant's head remained in a constant position throughout the CST trial. There was no obvious compression of the submental muscles. CONCLUSION: The CST allows for a better intraindividual reproducibility of the swallowing pattern and for a more standardized and objective ultrasound examination than the hand-held transducer-skin coupling scanning technique.

Adult↗

Real time monitoring of oxygen saturation in extracorporeal circulation using an optical reflectance transducer.

A novel optical reflectance transducer for continuous and real time monitoring of oxygen saturation (So2) in extracorporeal tubings during cardiopulmonary bypass (CPB) is described. The optical transducer integrates 2 light-emitting diodes and a photodiode. The transducer is attached to the extracorporeal tubing by a transparent flow through a 3/8 x 3/8 inch connector/cuvette. Four transducers were built and evaluated in vitro in a mock extracorporeal system at a controlled So2. The correlation index (r2) between the So2 measured by the transducers and values determined by a commercial blood gas analyzer was 0.998 with an absolute difference < 0.5%. The performance of the transducer was also evaluated during 16 CPB surgeries in patients with an r2 of 0.873 and an absolute difference < 3.5%. The results obtained demonstrate the applicability of the optical reflectance transducer for monitoring So2 in the tubings of the CPB circuit.

Extracorporeal Circulation↗

Prediction of cerebral blood flow in fetal lambs by carotid artery ultrasonic flow transducer.

To determine whether common carotid artery blood flow measured with an ultrasonic flow transducer would predict brain blood flow in fetal sheep, we measured unilateral common carotid artery blood flow and compared this to simultaneous measurements of total brain blood flows made by radioisotope-labelled microsphere techniques. We studied anaesthetized, exteriorized fetal sheep with intact umbilical circulation after ligation of extracranial, extracerebral arteries and placement of a common carotid artery flow transducer; five fetuses at 120 d gestation had 19 total comparison measurements. As measured by microsphere technique, mean basal blood flow during undisturbed conditions to regional brain areas were similar to normal values reported for the exteriorized ovine fetus; these flows were highly correlated to fetal PaCO2 and successfully varied over a wide range (total brain 9.1-200.4 ml/min/100g and total cortex 6.1-153.1 ml/min/100g) in subsequent experimental conditions of hypercapnia or occluded blood flow. Blood flow as measured by flow transducer significantly correlated (P < or = 0.01) with microsphere measurements of blood flow to total brain (r = 0.56) and total cortex (r = 0.62); regional flow to cerebellum (r = 0.70) and thalamus (r = 0.60) also correlated to transducer measurements. Stronger correlations were observed at low-flow conditions to total brain (r = 0.83) and to total cortex (r = 0.90). As measured by microsphere technique, right and left cortical blood flows were highly correlated (P = 0.0001, r = 0.97), indicating that the flow transducer or surgical manipulation did not disturb the distribution of cerebral blood flow. The mean values for zero flow reference of the transducer were < 1.5% of mean basal flow values. It is concluded that the common carotid artery flow transducer technique developed in this study provides an accurate prediction of blood flow to total brain and total cortex over a wide range of values in fetal sheep. This technique provides a methodologic advantage to sequential experimental interventions and may prove advantageous to studies of fetal sheep cerebral circulation.

Animals↗