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Biomedical subjects

K J Dormer

Publications and source records attributed to K J Dormer.

At least 19 recordsLinked to original sources

Biomaterials for implantable middle ear hearing devices.

The use of biomaterials to ameliorate the effects of diseases dates back centuries to the ancient Greeks and Chinese. In the twentieth century, the use of synthetic and natural materials rapidly increased as clinicians developed problem-solving strategies. From replacement prostheses, to structural polymers, to the controlled release of engineered proteins into the body, to the present-day tissue engineering, biomaterials have transformed medicine. The ear is no exception. Various alloplastic and homograft biomaterials have been used to restore hearing with ossicular replacement prostheses, cochlear implants, and most recently, implantable middle ear devices. This article updates an earlier review of biomaterials used in implantable middle ear devices and focuses on biomaterials used in implantable middle ear devices currently under development or in clinical trials.

Biocompatible Materials↗

Mass loading on the ossicles and middle ear function.

The middle ear as a levered vibrating system for sound transmission from the external to the inner ear is affected by changes in ossicular chain mass. Mass loading of the ossicles may impair ossicular dynamics and sound transmission to the inner ear. It is incumbent on otologic surgeons and researchers of middle ear mechanics to consider the mass loading effect on middle ear function in clinical and physiological applications. The residual hearing and frequency response can change after surgery or implantation of middle ear prostheses. We conducted experiments on mass loading effects on the middle ear transfer functions by using laser Doppler interferometry and a human temporal bone model. Two implant mass loading conditions were tested on 17 fresh or fresh-frozen temporal bones and compared with the unloaded condition for the frequencies 250 to 8,000 Hz. The results show that the linearity of the middle ear function did not change, although displacement of the stapes footplate decreased after the increased masses were placed on the incudostapedial joint. The greater the mass of the implant, the less displacement was measured at the stapes footplate. We conclude that there is a quantitative limit to increased mass on the ossicular chain above which the mass will remarkably impair hearing thresholds.

Adult↗

Implantable hearing device performance measured by laser Doppler interferometry.

Recent application of the Doppler principle laser interferometry to audiology, acoustics and otology has facilitated the development of implantable hearing devices (IHDs). During the design and testing of two different electromagnetic middle ear implants for sensorineural hearing loss, we used single-point laser Doppler interferometry (LDI). A commercially available interferometer, internally calibrated and validated against a National Institute for Standards and Technology (NIST) standard, was used with both mechanical fixtures and fresh temporal bones to evaluate implant mass, shape and orientation, attachment, electromagnetic coupling and acoustic properties. At both Hough Ear Institute and Symphonix Devices, Inc., we have shown that high fidelity and amplitudes can be recorded in vitro over a frequency range of 500 Hz to 10 kHz. These data can provide greater assurance of safety and efficacy to regulatory agencies before entering clinical trials. We propose that LDI be considered as an international standard for accurate, consistent comparison of performances of all IHDs during development. Furthermore, the future availability of human IHD data will allow for the extrapolation of a mechanical bench model of the middle ear transfer function for use in quality control during manufacturing and diagnosis of failure in IHDs.

Cochlear Implants↗

Selection of biomaterials for middle and inner ear implants.

In the selection of biomaterials for middle ear applications of implantable devices, certainly the site of implantation and the mass of the implant will dictate the choice of biomaterials. Hermetic sealing of an implant is best achieved by the use of metals, not polymers. Osteocompatibility of an ossicular implant can be enhanced by the incorporation of calcium phosphates such as hydroxyapatite coatings. Finally, osseointegration or osseofixation is neither necessary nor desirable for ossicular implants, because (1) they may need to be removed or replaced in the future and (2) their solid fixation to an ossicle is not necessary for the vibratory function of hearing amplification.

Biocompatible Materials↗

Effects of magnetic resonance imaging on implantable permanent magnets.

Implantable permanent magnets are increasingly used in devices for otolaryngologic applications. It is likely that at least some of the patients with implanted magnets will be in need of magnetic resonance imaging (MRI). The effect of an MRI scan on the magnetic properties of implanted permanent magnets has not been previously demonstrated. Some of the basic concepts and descriptive terminology used in industry regarding permanent magnets are reviewed. Experiments presented show that the MRI scan is capable of demagnetizing permanent magnets. A case history is also presented that demonstrates demagnetizing of an implanted Audiant magnet by an MRI scan.

Hearing Aids↗

The cardiovascular effects of ricin in rabbits.

Ricin is a toxic lectin from the castor bean. The time course of its toxic effects on the cardiovascular system of rabbits was investigated after determining its LD50 and minimum lethal dose in rabbits by the Up and Down method, as a basis for dosing. Systolic and diastolic arterial pressures, electrocardiogram and heart rate were recorded for 48 hr following administration of either a toxic sublethal (0.22 microgram/kg) or minimum lethal dose (0.44 microgram/kg) of ricin. After a delayed onset of about 20 hr, the minimum lethal dose (0.44 microgram/kg) of ricin caused a significant decrease in both systolic and diastolic pressures (P < 0.05). The systolic and diastolic pressures decreased 0.47 and 0.39 mmHg/hr more so than control groups, respectively. A toxic sublethal dose (0.22 microgram/kg) of ricin did not significantly alter either systolic or diastolic pressure. Neither dose of ricin caused cardiac arrhythmias or significantly increased heart rate. We conclude that the lethal hypotensive sequelae of ricin toxicity in the rabbit were peripheral in origin and not cardiogenic at these two doses.

Animals↗

Pressor and endocrine responses to lesions of canine rostral ventrolateral medulla.

To understand the mechanism(s) of reduction in arterial pressure (AP) after kainic acid cytotoxic lesions in the rostral ventrolateral medulla (RVLM), recordings of AP, cardiac output (CO), heart rate (HR), plasma catecholamines, and cortisol were obtained from awake relaxed dogs. Mongrels (n = 12) were instrumented with a solid-state pressure transducer in the descending aorta and a pulse transit-time ultrasonic flowmeter on the aortic arch. After the dogs recovered from thoracotomy, AP, CO, HR, and plasma levels of epinephrine, norepinephrine, and cortisol were recorded periodically or measured at rest over 2-3 wk followed by unilateral, cytotoxic lesion placement in the rostral C1 area of the RVLM. After the dogs recovered from lesion surgery, the measurements were repeated, and, compared with prelesion control values, they showed significantly decreased AP (-23.1 mmHg) and total peripheral resistance (-0.014 peripheral resistance units) but no significant changes in CO or HR. The reduction in AP may be caused partially by significant reductions in plasma epinephrine (-47%), norepinephrine (-34%), and cortisol (-66%) levels. Lesion sites corresponded to the rostral C1 area, immunocytochemically positive for phenylethanolamine-N-methyltransferase (PNMT). These observations support the concept that a discrete site in the RVLM, demarcated by a rostral subgroup of PNMT-immunoreactive cell bodies, contributes to direct sympathoexcitatory support of resting AP. The neurotransmitter responsible for vasomotor tone, however, remains unknown. This study also provides new information suggesting a role for catecholamine and cortisol regulation from this putative vasomotor center.

Animals↗

The Audiant Bone Conductor: update of patient results in North America.

The Xomed Audiant Bone Conductor is an implantable hearing device for conductive hearing impairments not adequately relieved by surgical methods or hearing aid amplification. It has now been used long enough for analysis of its present position in our management armamentarium. Data obtained from respondents from the United States and Canada are presented and indicate that this device, properly prescribed and used, almost eliminates the conductive elements of the hearing impairment. During the early years of its use, the device was frequently implanted in patients outside the manufacturer's guidelines for use. Some of the reasons for this discrepancy, as well as evidence that this misapplication is lessening, are presented. When proper guidelines were used, however, the results presented here indicate that socially adequate hearing can be restored to patients with conductive loss by the Audiant. Complications have been few and appear to be diminishing. The results indicate that this device has, in its present state of development, a narrow and restrictive application, but a well-defined and efficient role to play in the management of conductive hearing impairment.

Adolescent↗

Organization of presumptive catecholamine-synthesizing neurons in the canine medulla oblongata.

Immunocytochemical methods were used to identify cells and processes containing two major catecholamine (CA)-biosynthetic enzymes in areas of the canine medulla implicated in autonomic control. Antisera were employed against tyrosine hydroxylase (TH) and phenylethanolamine N-methyltransferase (PNMT). These enzymes respectively catalyze the conversions of tyrosine to L-DOPA and noradrenaline to adrenaline. Immunocytochemical studies laid the groundwork for subsequent investigations in conscious dog in which we characterized an area of cardiovascular control in the rostral ventrolateral medulla (RVLM). In the anatomical studies, previously unidentified neuronal somata and processes were demonstrated in the canine medulla. Presumptive adrenergic (CI) neurons in the canine RVLM were subjacent to the nucleus ambiguous (NA) and most numerous at a level where the compact and semicompact divisions of NA merged. In contrast to their distribution in rodents, C1 neurons were skewed caudally and did not extend rostrally to the caudal pole of the facial nucleus. C1 neurons were also relatively less concentrated in the RVLM. A large number of C1 neurons extended dorsally into the lateral tegmental field (LTF). Most C1 neurons in the LTF (like those in the A1 area) were aligned with catecholaminergic (TH- and PNMT-ir) processes traversing the intermediate reticular zone. Since the numbers and locations of TH- and PNMT-ir neurons in the C1 area of the RVLM and rostral LTF were virtually identical on adjacent sections, it can be implicitly inferred that the enzymes are co-localized to the same somata and that these neurons are capable of biosynthesizing adrenaline. The C1 and A5 areas were clearly separated by a transitional zone, sparsely populated by TH-ir somata (1-2 cells per section), where the facial nucleus and rostral pole of the NA pars compacta (NAc) occupied the same level. A5 neurons were more abundant and complexly organized than suggested by previous CA-histofluorescence data. In addition, a new parvicellular subgroup was identified and composed of neurons containing TH but not PNMT. In contrast to other species, the A1 cell group was not confined to the VLM. A large number of A1 neurons extended into the caudal LTF and were situated between the nucleus tractus solitarii-motor vagal complex (NTS-X) and caudal VLM (CVLM). In contrast to previous reports, presumptive adrenergic (TH- and PNMT-ir) cell groups were more densely represented in the C2-3 areas of the canine NTS and dorsomedial reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effects of labetalol on uterine blood flow and cardiovascular hemodynamics in the hypertensive gravid baboon.

OBJECTIVE: The purpose of this study was to investigate the effects of labetalol on uterine blood flow and cardiovascular parameters in acutely instrumented, hypertensive gravid baboons. STUDY DESIGN: During the latter half of pregnancy six gravid baboons were acutely instrumented, with ultrasonic flow probes placed on ipsilateral, external iliac, and uterine arteries and a flow-directed pulmonary artery catheter in the pulmonary artery. After a stable arterial pressure baseline was obtained, norepinephrine was infused to increase mean arterial pressure by at least 20%. A 20-minute hypertensive steady state was obtained. Labetalol at 0.5 and 1.0 mg/kg was randomly infused, followed by a 2.0 mg/kg dose, each over 1 minute. A 20-minute recovery period followed every labetalol infusion, allowing the hypertensive steady state to reestablish. External iliac and uterine blood flow measurements were continuously recorded during the baseline and experimental trials. Mean arterial blood pressure, heart rate, pulmonary artery and capillary wedge pressure, central venous pressure, and cardiac output were obtained at 5, 10, and 15 minutes during each steady state and after each labetalol infusion. RESULTS: Labetalol at all dosages significantly reduced the mean arterial pressure and the systemic vascular resistance at 1.0 and 2.0 mg/kg. External iliac blood flow was not consistently significantly reduced; however, uterine blood flow was significantly reduced after the 1.0 and 2.0 mg/kg labetalol dosages (p < 0.05). Although uterine vascular resistance tended to increase after the 1.0 and 2.0 mg/kg doses, statistical significance was not achieved. CONCLUSION: Low-dose labetalol (0.5 mg/kg) significantly reduces the pharmacologic hypertensive gravid baboon's mean arterial blood pressure without adversely affecting uterine blood flow.

Animals↗

Ventrolateral medullary lesions and fastigial cardiovascular response in beagles.

These studies were designed to verify that the putative vasomotor center in the rostral ventrolateral medulla (RVLM) contained the outflow paths for the fastigial nucleus (FN) sympathoexcitatory cardiovascular response. If so, then lesions placed by radiofrequency heating (75 degrees C) or application of kainic acid (40 mM) pledgets would reduce or ablate the pressor-tachycardia response after electrical stimulation of FN. Anesthetized beagles (alpha-chloralose, 115 mg/kg) were used in this study to maintain consistency in medullary brain stem anatomy. A ventral brain stem approach exposed the three chemosensitive zones of Mitchell, Schlaefke, and Loeschcke. In other species the intermediate zone and a portion of the rostral zone underlie the Hokfelt C1 cell group and the putative RVLM vasomotor center. Heart rate, arterial and left ventricular (LV) pressures, and maximal rate of pressure development (LV dp/dt) increased 14-84% above control levels in response to stimulating FN 5-10 times the stimulation threshold. The cardiovascular response was abolished in four of six dogs that received bilateral radiofrequency lesions at a depth of 1-2 mm. In five of seven dogs that received kainate surface lesions, the response was substantially reduced but not abolished. These lesions were effective only in the RVLM, above the corresponding intermediate, but not adjacent rostral or caudal chemosensitive areas. The data support the hypotheses of others that an epinphrine-containing cell group in this region is a final common pathway of sympathoexcitation. Expression of the FN cardiovascular response is primarily mediated through this vasomotor region previously identified by others in the rat, cat, rabbit, and primate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of amrinone and dopamine on uterine blood flow and vascular responses in the gravid baboon.

Amrinone is a bipyridine derivative with positive inotropic and vasodilator properties. We investigated its effects on uterine and iliac artery blood flow, blood pressure, and heart rate in 10 acutely instrumented gravid baboons. Amrinone was compared with dopamine, infused systemically or regionally via the common iliac artery. When given intravenously at a constant rate of 40 micrograms/kg/min, amrinone produced a slight increase in iliac artery blood flow but did not significantly alter mean arterial pressure, heart rate, or uterine artery blood flow. Dopamine at an intravenous dose of 40 micrograms/kg/min produced a mean (+/- SD) 49.2% +/- 18.7% increase in mean arterial pressure (p less than 0.01) and a 84.2% +/- 56.1% increase in uterine vascular resistance (p less than 0.01), but caused no changes in heart rate, uterine artery blood flow, or iliac artery blood flow. Regional infusion of amrinone at the rate of 25 micrograms/kg/min produced a significant increase in iliac artery blood flow (p less than 0.01) without changing uterine artery blood flow, heart rate, or mean arterial pressure. Regional infusion of dopamine at concentrations of 2.5 to 25 micrograms/kg/min produced decreases in flow (p less than 0.01) and increases in resistance (p less than 0.01) in the uterine and iliac vascular beds. We conclude that amrinone dilates the vascular bed of the external iliac artery, but has no remarkable effect on the uterine vascular bed. Dopamine increases uterine vascular resistance and may impair uteroplacental perfusion.

Amrinone↗

Arterial hemodynamics during head-up tilt in conscious dogs.

The purpose of this study was to measure the major arterial hemodynamic responses to head-up tilt in the conscious dog. After recovery from surgery for instrumentation, and after habituation to tilt, the dogs were tilted from horizontal to 75 degrees for 5 min. The arterial hemodynamic response after the initial cardiovascular adjustments to the tilt consisted of no change in heart rate and significantly increased arterial blood pressure, with significantly reduced stroke volume and cardiac output. Both renal blood flow and terminal aorta blood flow declined significantly, even more than cardiac output. Muscular exertion was not part of the tilt response because upright standing on the hindlimbs elicited a sustained increase in heart rate and a significantly smaller increase in estimated total peripheral resistance. When compared with the orthostatic response in humans, the increase in arterial pressure was exaggerated in the dogs.

Animals↗

Digitizing and signal averaging of left ventricular pressure signals using a dedicated radionuclide imaging system.

A method for obtaining left ventricular (LV) volume curves, synchronized with average LV pressure (LVP) curves for calculation of LV contractility, is described. Multiple gated blood pool imaging was performed to calculate average LV volume curves. Simultaneously with this acquisition, LVPs and aortic pressures were measured by indwelling catheters and recorded on an FM tape recorder. These signals were fed to the computer as image information and averaged and processed by the software developed for this purpose. Pressure resolution of the calibrated images was 4 mmHg/pixel when provision was made for a maximum pressure of 200 mmHg. A good correlation (r = 0.99) was obtained between the calculated peak LVPs and mean peak LVPs read from the chart recorder. The regression equation was: digitized peak LVP = 1.04 x chart recording--5.11 mmHg and the standard error of the estimate was 2.9 mmHg. Similar results were obtained with the aortic pressure (AP) measurements (digitized AP = 0.94 x chart recording + 6.37 mmHg, the standard error of the estimate was 3.8 mmHg). The digitized data also allowed the construction of pressure-volume loops for interpretation of ventricular contractility.

Animals↗

Fastigial nucleus modulation of medullary parasolitary neurons.

Input from the cerebellar fastigial nuclei to neurons at the lateral margin of the nuclei of the solitary tract, particularly to the area identified as the nucleus parasolitarius was investigated in acutely prepared, anesthetized dogs. Fastigial nucleus stimulation led to short latency excitation of nucleus parasolitarius units often followed by prolonged inhibition of spontaneous activity. Excitation from deep skeletal muscle afferents, converged on 25% of the spontaneously active units excited from the fastigial nuclei; these afferents originated primarily from the ipsilateral forelimb muscles. This study provides electrophysiological evidence for fastigial modulation of neurons previously demonstrated autoradiographically to receive presumed monosynaptic fastigial nucleus efferents. The convergence of forelimb muscle afferent information tentatively identified as being from Group Ia or Group II pressure stretch receptors suggests that the nucleus parasolitarius may be an integrative area for cerebellar, sensorimotor and/or autonomic information.

Animals↗

Fastigial nucleus projections in the midbrain and thalamus in dogs.

Efferent connections to midbrain and thalamus from portions of the cerebellar fastigial nucleus were investigated using autoradiographic techniques. Bipolar stimulating electrodes were placed in the fastigial nucleus of anesthetized beagles and the area which produced maximal increases in blood pressure and heart rate was localized in each dog. A mixture of [3H]leucine and [3H]proline (4:1) was injected into that area and autoradiograms were prepared. Injections filled the rostral and various parts of the caudal fastigial nucleus. The rostral-caudal extent of injection sites were mapped in the horizontal plane from sequential coronal, thionin-stained sections and "primary" and "secondary" injection zones were defined according to specific criteria. Labeled axons reached the mesencephalon via the contralateral uncinate fasiculus. Ascending fibers assembled in a diffuse contingent at the prerubral level adjacent to the ventrolateral periaqueductal gray. The heaviest projections were contralateral to the injection site, but ipsilateral terminals were observed as well. In the midbrain, axons entered the contralateral and ipsilateral superior colliculus to branch repeatedly and terminate in the deep and intermediate layers. Additional terminals were observed bilaterally in the nuclei of the posterior commissure and pretectal areas at the midbrain-diencephalic junction. In the thalamus, labeled axons formed into three groups which terminated in: the contralateral paraventricular complex and medial dorsal nucleus; the contralateral central medial, paracentral, parafasicular and central lateral nuclei, and the contralateral ventral medial and ventral lateral nuclei. There was a sparse projection to the ipsilateral ventral lateral nucleus. The contralateral projection to the ventral medial and ventral lateral nuclei was marked by dense clusters of label ventral to the internal medullary lamina extending, in the dorsal ventral lateral nucleus, to its rostral pole. Projections to specific somesthetic thalamus or the hypothalamus were not observed. These ascending projections in the canine brain generally conform to those described in other nonprimate mammals. The fastigial nucleus presumably provides information concerning equilibrium and body proprioception to the superior colliculus and to thalamic nuclei including both specific motor relay and "nonspecific" midline and intralaminar nuclei, much the same as reported in the cat. The projection to the ventral medial and ventral lateral thalamic nuclei terminate in areas known to participate in the control of axial and proximal limb muscle activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Fastigial nucleus cardiovascular response and brain stem lesions in the beagle.

Changes in the excitatory cardiovascular response (heart rate, arterial blood pressure, left ventricular pressure, and LV dP/dt as an index of myocardial contractility) resulting from electrical stimulation of the cerebellar fastigial nucleus (FN) were recorded after placement of DC or radio-frequency lesions or after microinjections of kainic acid into brain stem areas that receive FN projections and have been shown to be involved in central cardiovascular control. FN-induced increases in heart rate, blood pressure, and contractility were reduced or abolished by lesions made in the restiform body or the A5 area, which is homologous to the catecholamine-containing region in cats and rats. Lesions in the paramedian reticular nucleus, rostral and caudal to obex, failed to reduce the FN cardiovascular response. Nucleus of the solitary tract lesions augmented the FN pressor response and tachycardia. Kainic acid (1 microliter of 100 mM solution) caused profound depression of heart rate, blood pressure, and contractility and reduced or eliminated the FN-induced cardiovascular response when injected into the A5 area, previously identified by the pressor response following electrical stimulation. We concluded from these observations that a descending fastigiobulbar sympathoexcitatory pathway courses through a previously identified A5 pressor area that is also capable of a depressor response when the cell bodies alone are activated.

Animals↗