Biomedical subjects
Publications and source records attributed to P J Gannon.
This article reviews in detail the gross anatomy of the auditory and language areas, the present concepts of unimodal and multimodal association cortices, the classic model of language, problems with the classic model, and newer approaches to conceptualizing the structural interconnections that subserve audition and language.
The neurochemical basis of cholinergic efferent modulation of afferent function in the vestibular periphery remains incompletely understood; however, there is cellular, biochemical and molecular biological evidence for both muscarinic and nicotinic acetylcholine (ACh) receptors (nAChRs) in this system. This study examined the topographic distribution of alpha-bungarotoxin (alpha-BTX) nAChRs in the cristae of a turtle species. Cristae were perfusion-fixed, cut at 20 micrometer on a cryostat and incubated with alpha-BTX or polyclonal antibodies raised against Torpedo nAChR. Light microscopy showed abundant specific labeling of nAChR in the central zone of each hemicrista on the calyx-bearing afferents surrounding type I hair cells and on the base of the type II hair cells. Within the peripheral zone, dense labeling of type II hair cells near the torus and sparse or no label was observed on type II hair cells near the planum. The alpha-BTX binding showed a similar pattern within the cristae. The similarity between the topographic distribution of alpha-BTX binding nAChR and of efferent inhibition of afferents supports the notion that the inhibitory effect of afferents is mediated by nAChR.
OBJECTIVE: To investigate the technical aspects of the canine model of human tracheal transplantation for potential application to reconstruction of extremely long tracheal defects (> 10 cm). DESIGN: In phase 1, long tracheal segments were skeletonized and pedicled with the thyroid glands, cranial thyroid arteries and veins, and internal jugular vein branches. The segments were elevated completely, attached to the vascular pedicle only, and replaced with primary tracheal anastomoses. In phase 2, long segments were elevated along with a diffuse soft tissue "blanket" that envelops the trachea and thyroid glands. Because this study was designed to primarily address, in situ, tracheal perfusion territories of a cranially located vascular pedicle, microvascular anastomoses were not conducted. SUBJECTS: Two small-bodied beagles (10-15 kg) and 5 large-bodied mixed-breed dogs (20-30 kg) were humanely killed 2 to 41 days after surgery, and anatomic and histological analyses were conducted. RESULTS: Unlike that of humans, the thyroid gland complex of dogs is not intimately associated with the trachea but is conjoined with a peritracheal soft tissue "fold." Within this fold, blood is transmitted to the trachea via a diffuse, segmental vascular plexus. In phase 1, pronounced tracheal necrosis occurred within 2 to 5 days. In phase 2, extremely long tracheal segments (10-12 cm), based only on a cranially located pedicle, were still viable at 2 to 6 weeks. CONCLUSIONS: Preservation of the "peritracheal fold" in the dog model of tracheal transplantation is critical to the onset and maintenance of vascular perfusion in a long tracheal segment. Furthermore, the use of large-bodied dogs is necessary to provide for a usable venous efflux component.
The management of long-segment tracheal stenosis remains an unsolved clinical problem that has significant implications for the survival of some patients and the quality of life of others. However, recent advances in microvascular tissue transfer may allow tracheal transplantation to be used as a treatment option. Studies in dogs have demonstrated that the reanastomosis of the cranial thyroid artery (CTA) after the transplantation of a short segment of trachea sustains cartilage viability. However, the distal perfusion zone of the CTA within the canine trachea has not been described. Hence it is unclear what length of trachea can be safely harvested, with use of the CTA as the donor artery, without risking ischemia of the distal trachea. This study determined the perfusion territory of the CTA by use of latex or dye infusion via the thyroid branches of the CTA. Findings in five perfusion-fixed cadaver mongrel dogs (8 to 12 kg) were studied. In each dog, both common carotid arteries were dissected and the CTAs identified. The right CTA was ligated and the left common carotid artery was ligated cranial to the CTA. The left common carotid artery was perfused for 10 minutes under 100 mm Hg pressure with black india ink/saline solution (20:1000 ml) or with blue latex solution. Perfusion territories were determined by grossly and microscopically measuring the region of stain in the endolaryngeal and endotracheal airways. The results demonstrated that up to 18 ipsilateral rings of the canine trachea are perfused after injection of dye under physiologic pressure into the CTA. Contralateral staining was also noted, but to a lesser degree. These results suggest that the canine CTA may perfuse, on average, a 16- to 17-ring tracheal segment.
OBJECTIVES: Ostial patency is thought to be essential to the function of the maxillary sinus. Ostiomeatal complex dysfunction has been implicated as a major factor in the pathogenesis of sinus disease. However, recent work in our laboratory has indicated that other factors may also contribute to this process. The objective of this study was to determine the effect of nasal obstruction in maxillary sinus gas composition, independent of its effect on ostial ventilation. STUDY DESIGN: Prospective controlled animal study. METHOD: Independent models of nasal obstruction and ostial occlusion in contralateral sinuses were established. Ipsilateral models of nasal obstruction and ostial occlusion were also created. Gas samples from each of the manipulated sinuses were analyzed on a gas chromatogram and compared. RESULTS: Results revealed a dramatic and highly significant increase in antral carbon dioxide (CO2) concentrations in the sinuses ipsilateral to either an occluded ostium or an obstructed nostril, compared with the controls. These effects on CO2 concentrations were additive when ipsilateral nasal obstruction and ostial occlusion were created. Furthermore, the effect of nasal obstruction in modulation of antral CO2 levels was found to be beyond its effect on hypoventilation of the sinus and to be independent of ostial functional status. CONCLUSIONS: We have established independent models of nasal obstruction and ostial occlusion in the same animal. Our findings suggest that ostiomeatal complex dysfunction might not be the sole underlying factor in the pathogenesis of sinus disease in all individuals. Integrity of nasal airflow seems to have a significant effect on the maintenance of the aerobic antral environment, essential to the maintenance of normal sinus function. Modulation of maxillary sinus gas composition by nasal airflow, independent of ostial patency, may be explained by the possible presence of flow-sensitive receptors in the upper respiratory tract mucosa. Work to identify such receptors is currently in progress.
The anatomic pattern and left hemisphere size predominance of the planum temporale, a language area of the human brain, are also present in chimpanzees (Pan troglodytes). The left planum temporale was significantly larger in 94 percent (17 of 18) of chimpanzee brains examined. It is widely accepted that the planum temporale is a key component of Wernicke's receptive language area, which is also implicated in human communication-related disorders such as schizophrenia and in normal variations such as musical talent. However, anatomic hemispheric asymmetry of this cerebrocortical site is clearly not unique to humans, as is currently thought. The evolutionary origin of human language may have been founded on this basal anatomic substrate, which was already lateralized to the left hemisphere in the common ancestor of chimpanzees and humans 8 million years ago.
OBJECTIVE: To determine the perfusion territories of the superior and inferior thyroid arteries in humans. Tracheal transplantation is a potential option for management of long-segment tracheal stenosis. However, the maximum length of vascularized trachea that can be reliably transplanted has not been established. STUDY DESIGN: The tracheal vascular territory of individual superior and inferior thyroid arteries was determined separately in 10 humans postmortem. METHODS: India ink was infused unilaterally under controlled pressure into the superior (n = 5) and inferior (n = 5) thyroid arteries of cadaveric tracheas. Tracheas were sectioned longitudinally and the caudalmost extent of mucosal dye staining was determined via microscopic assessment. RESULTS: The tracheal perfusion territory of the superior thyroid artery was two to five rings (1.7 +/- 0.5 cm) and the inferior thyroid artery, nine to 13 rings (6.5 +/- 1.1 cm). In both cases, the tracheal mucosa on the contralateral side was stained to the same caudal level. CONCLUSIONS: The inferior thyroid artery was shown to perfuse the trachea maximally to the 13th ring (8.1 cm). As such, the unilateral inferior thyroid artery would serve as a suitable vascular component for long-segment tracheal transplantation in humans.
OBJECTIVE: Currently, methods used to repair long segment tracheal stenosis are unreliable. Here, a new nonhuman primate model of tracheal transplantation is used based on its evolutionary proximity to humans. STUDY DESIGN: Prospective dye perfusion study in Macaca mulatta. METHODS: After anatomical characterization, Evan's blue solution was injected into the right superior thyroid artery unilaterally (n = 5). Staining of the tracheal vasculature was then examined. RESULTS: In M mulatta, the superior thyroid artery branched from the lingual-facial trunk and was 0.64 +/- 0.18 mm in diameter. Dye staining was bilateral, with the ipsilateral side extending to 2.98 +/- 0.58 cm and the contralateral to 2.88 +/- 0.88 cm, 12.9 +/- 3.45 rings (47% of trachea). CONCLUSIONS: The tracheal vasculature has extensive bilateral collateral vascular channels that may provide a graft survival advantage. Macaques may serve as a good model of tracheal transplantation because of the collateral vascularization of the trachea and the extensive tracheal segment supplied by the superior thyroid artery, and because the superior thyroid artery and vein are anastomosable.
OBJECTIVE: To determine the effect of changes from nasal to tracheal respiration on maxillary sinus mucosal blood flow in rabbits with unobstructed sinus ostia. DESIGN: Animals underwent tracheotomy with a T tube and then a small window of intact maxillary sinus mucosa was exposed. Mucosal blood flow was recorded during normal nasal respiration using laser-Doppler velocimetry. At hourly intervals, respiration was changed from the nasal to the tracheal route and then back again. SUBJECTS: Ten anesthetized rabbits were used: 5 underwent single and 4 underwent multiple shifts in the respiratory route, while 1 was monitored continuously during long-term nasal breathing only. RESULTS: A significant decrease in maxillary sinus blood flow occurred on switching from nasal to tracheal respiration and a significant increase in blood flow occurred on return to nasal respiration. Where multiple switches were made, blood flow changes diminished in magnitude, but significant decreases (nasal to tracheal) or increases (tracheal to nasal) were evident in all cases. CONCLUSIONS: It is proposed that the maxillary sinus may act in an accessory capacity to the nose for humidification of inspired air via secretions liberated from the sinus ostium. Furthermore, we suggest that nasal airflow is involved with the reflex regulation of sinus blood flow, probably via stimulation of sensory receptors in the nasal cavity. Reduced maxillary sinus mucosal blood flow may thus contribute to supra-systemic levels of antral carbon dioxide. Since elevated carbon dioxide levels have been shown to reduce maxillary sinus mucociliary activity in vitro, nasal airflow compromise may contribute to the initiation of a cascade of pathophysiological events leading to acute sinusitis.
Explore the source record for details and available documents.
Activation of 5HT1A receptors produces many different physiologic responses, which may be due to their localization on diverse cells in the brain. A 5-HT1A receptor antipeptide (aa170-186) antibody was produced that showed both high titer for peptide binding and immunocytochemical staining. Studies performed in perfusion-fixed brain tissue showed immunoreactive neurons, glial, and ependymal cells in the rat, mouse, cat, and monkey. Results from our studies of Macaca fascicularis brains are presented. We observed two main neuronal labeling patterns in the primate brain: (1) A general, diffuse somatodendritic distribution of 5-HT1A receptor immunoreactivity is seen in the raphe nuclei where the dendritic shaft, its branches and spines, and the entire perikaryon are immunolabeled. This pattern is also observed in the nucleus locus coeruleus, in scattered large brainstem reticular neurons, and in dentate gyrus hilar interneurons. (2) A discrete localization of 5-HT1A receptor immunoreactivity on the initial axon segment (axon hillock) is noted in pyramidal neurons of layer III and V of cerebral cortex, Cornu Ammonus (1-4) of the hippocampus, and in most brainstem and cervical spinal cord motoneurons. In addition to neuronal labeling, 5-HT1A receptor immunoreactivity is seen in the cell body and processes of astrocytes, and other nonneuronal cells. This pattern is particularly evident in the white matter of cerebral cortex and spinal cord, the pontine nuclei, the brainstem tectum, and the hilus of the dentate gyrus. The clinical implications of 5-HT1A cellular localization are briefly discussed.
To better understand the mechanisms underlying maxillary sinus function, the gas composition of the sinus antrum in spontaneously breathing and tracheotomized rabbits (n = 17) was compared. The gas composition of samples (n = 117) obtained from rabbit maxillary sinuses was determined by gas chromatography. Results demonstrated significant differences (P < .005) in sinus gas composition between nasal breathing and tracheotomized animals for oxygen (02) and carbon dioxide (CO2). In tracheotomized animals O2 levels decreased while CO2 levels increased markedly to suprasystemic levels. This unexpected finding may be due to reduced sinus blood flow and the effects of nasal versus tracheal respiration. We conclude that the gaseous dynamics and perhaps the function of the maxillary sinus vary under different respiratory conditions. A better understanding of these processes may lead to earlier diagnosis and the development of improved treatments for sinus disease.
Serotonin (5-HT) has direct and specific effects on the activity of spinal cord motoneurons. The 5-HT1A receptor has been shown to mediate motoneuron responses in spinal reflex pathways using the highly selective 5-HT1A receptor agonist 8-OH-DPAT. We have developed an antipeptide antibody that recognizes a specific region (the second external loop) of the 5-HT1A receptor. This 5-HT1A receptor antibody labels populations of neurons and glia in the primate cervical spinal cord. The highest receptor density is present in the superficial lamina of the dorsal horn, around the central canal, and on the axon hillock of large ventral horn motoneurons. The cellular labeling pattern on motoneurons shows a single, densely stained, tapering process emanating from the perikaryon. A more diffuse label is also present throughout the soma. Dendritic labeling was not apparent. These results suggest that post-synaptic 5-HT1A receptors may be involved in modulating spinal motoneuron activity at the key site of action potential initiation, the axon hillock.
Occlusion of the maxillary ostium is considered to be a key factor in the pathogenesis of maxillary sinusitis. In this study, the authors determined the effect of ostial occlusion on pressure in the rabbit maxillary sinus which, like most humans, has only one ostium. We compared pressures in the normal and occluded maxillary sinus and the nasal cavity during spontaneous breathing in anesthetized adult animals. Serial pressure measurements were obtained from sinuses with patent ostia in nasal-breathing rabbits and with occluded ostia in both nasal-breathing and tracheotomized animals. Sinuses with patent ostia showed pressure curves synchronous with the respiratory cycle. Inspiratory and expiratory pressures in the nasal cavity and the sinus were isobaric. Sinuses with occluded ostia initially developed a positive pressure followed by a negative pressure that reached a subatmospheric plateau of -28.2 +/- 7.3 mm H2O (mean +/- standard deviation [SD]) within 20 to 50 minutes. This is the first quantitative study of sinus pressures using the rabbit as an animal model. The findings may contribute to a better understanding of the role of ostial occlusion in the pathogenesis of maxillary sinusitis in humans.
OBJECTIVE: To evaluate a dual role for the tensor veli palatini muscle in tubal and palatal function. MATERIALS AND METHODS: The eustachian tube region of guinea pigs and macaques was fixed and processed for analysis by serial section histologic examination, micro-dissection, or both. The attachment, fiber direction, and regional relations of potentially discrete functional compartments in eustachian tube muscles were noted. RESULTS: The tensor veli palatini muscle in macaques has two anatomic sub-bellies. One appears to be a tubal dilator, the other to make the tube rigid along its longitudinal axis. No other muscle is directly associated with the eustachian tube in macaques. The tensor veli palatini muscle in guinea pigs has one gross belly that may affect palatal tensing and tubal dilation, rigidification, and stabilization. Other muscles of the eustachian tube in guinea pigs are a medial sub-belly of the medial pterygoid muscle, not previously described, and the levator veli palatini muscle. CONCLUSIONS: The muscular elements underlying tubal-palatal function in guinea pigs are more distinct and spatially separated than in macaques or humans. These differences may explain the confusion about the role of accessory muscles in tubal function. Muscular compartments of the eustachian tube complex in guinea pigs are easily accessible, which facilitates a more discrete and confident placement of electromyography electrodes. The guinea pig may be a useful model to better understand the interaction of multilevel compartmentalized physiologic sequences that underlie coordination of swallowing, breathing, and middle ear aeration.
The brainstem location of motoneurons innervating eustachian tube-associated muscles in the adult guinea pig was determined using intramuscular injections of the neural tracer horseradish peroxidase (HRP). Following HRP injections into the tensor veli palatini and the eustachian tube belly of the medial pterygoid muscle, an ipsilateral column of HRP-labeled motoneurons was present medial to the dorsolateral division of the trigeminal motor nucleus. Following HRP injection into the levator veli palatini, labeled motoneurons were present in the ipsilateral dorsal division of nucleus ambiguus. The locations of the tensor veli palatini and levator veli palatini motoneurons are similar to those found in studies of other animals. A distinct eustachian tube belly of the medial pterygoid muscle was also identified. This sub-belly had a motoneuron pool distinct from the main medial pterygoid muscle group. The authors have provided the gross anatomical and neuroanatomical substrates upon which future studies of eustachian tube function in the guinea pig may be based.
Proper aeration is a prerequisite for normal middle ear function in all terrestrial mammals. Our previous studies in primates provided anatomic evidence of neural circuits between the middle ear, brain, and eustachian tube by which central respiratory neurons can control middle ear aeration. Yet mechanisms that regulate middle ear aeration remain poorly understood. This study extends our research by examining maturation of these neural circuits, and investigating their underlying physiology. Ultrastructural examination of tympanic nerves, the afferent limb of the neural circuit, in an age-graded series of cynomolgus monkeys (Macaca fascicularis) showed substantial differences between newborn, young, and adult animals. These included a twofold increase in average myelin thickness, and greater than threefold increase in the ratio of myelinated to unmyelinated fibers from newborn to adult animals. These marked developmental changes may translate into functional differences in regulation of middle ear aeration in young animals, and possibly explain the extraordinarily high incidence of middle ear disease in early childhood. In physiologic experiments, bilateral electromyographic responses were recorded from eustachian tube muscles, the efferent limb of the neural circuit, in adult monkeys after ipsilateral stimulation of the tympanic nerve. Response latencies were 9 to 28 msec, similar to those of other multisynaptic bilateral brainstem reflexes. These physiologic data strongly suggest a concept of active control of middle ear aeration by respiratory neurons in the brain.
Explore the source record for details and available documents.