Development of the movement of the epiglottis in infant and juvenile pigs

Although backward folding of the epiglottis is one of the signal events of the mammalian adult swallow, the epiglottis does not fold during the infant swallow. How this functional change occurs is unknown, but we hypothesize that a change in swallow mechanism occurs with maturation, prior to weaning. Using videofluoroscopy, we found three characteristic patterns of swallowing movement at different ages in the pig: an infant swallow, a transitional swallow and a post-weaning (juvenile or adult) swallow. In animals of all ages, the dorsal region of the epiglottis and larynx was held in an intranarial position by a muscular sphincter formed by the palatopharyngeal arch. In the infant swallow, increasing pressure in the oropharynx forced a liquid bolus through the piriform recesses on either side of a relatively stationary epiglottis into the esophagus. As the infant matured, the palatopharyngeal arch and the soft palate elevated at the beginning of the swallow, so exposing a larger area of the epiglottis to bolus pressure. In transitional swallows, the epiglottis was tilted backward relatively slowly by a combination of bolus pressure and squeezing of the epiglottis by closure of the palatopharyngeal sphincter. The bolus, however, traveled alongside but never over the tip of the epiglottis. In the juvenile swallow, the bolus always passed over the tip of the epiglottis. The tilting of the epiglottis resulted from several factors, including the action of the palatopharyngeal sphincter, higher bolus pressure exerted on the epiglottis and the allometry of increased size. In both transitional and juvenile swallows, the subsequent relaxation of the palatopharyngeal sphincter released the epiglottis, which sprang back to its original intranarial position.     

Mechanisms of swallowing and airway protection in infant mammals (Sus domesticus and Macaca fascicularis)

Protection of the airway, necessary for continued respiration, is a problem for mammals because of the relative positions of the oesophageal and laryngeal openings in the pharynx. In human infants, and all other mammals, infant and adult, the epiglottis contacts the posterior surface of the soft palate, providing a continuous passage from the nasopharynx to larynx. The function and movements of the epiglottis during swallows are debated as to whether the epiglottis bends to protect the airway or remains erect and leaves the airway open during the swallow. Using high-speed cineradiography, we examined swallows in detail for a precocious infant, Sus domesticus , the miniature pig, and the more altrical primate, Macaca fascicularis. Infant pigs swallowed in two different ways: down the midline of the oropharynx, over a bent epiglottis, and laterally, around an erect epiglottis, and presumably open airway. The epiglottis of infant macaques never bent, and milk always travelled laterally, through the pyriform recesses and around the larynx. The macaque airway was closed superiorily, however, when the soft palate sealed against the posterior pharyngeal wall. A hypothesis that could account for this pattern of swallowing involves an ontogenetic change from swallows travelling laterally through the pyriform recesses in young infants to swallows travelling over a bent epiglottis in more mature infants. This change would accompany maturation associated with weaning and the need to protect the airway from the larger and less fluid boluses of masticated solid food.     

The Function of the Epiglottis in Monkey and Man

In stumptail monkeys from birth to adulthood, and in very young human infants, the epiglottis serves to guide the larynx upwardly behind the soft palate so it can lock into the nasopharynx and remain there during respiration. After early infancy in man the attainment of a larynx-nasopharynx connection is uniquely lost, causing the epiglottis to have no essential function.     

Movement of the epiglottis in mammals

In contrast to adult humans, the epiglottis of other mammals and infant humans is situated close to the soft palate. It has been argued that this posture is maintained during swallowing, with food passing laterally around an intact airway. To test this supposition, the movement of the epiglottis in two contrasting mammalian species, pigs and ferrets, was studied by placing radiopaque markers on the epiglottis and soft palate. Swallowing was observed with videofluoroscopy while the animals were feeding on hard and soft foods, liquids, and food mixed with barium sulfate. Analysis of the images showed that bolus formation and downward movement of the epiglottis away from the soft palate were unvarying phenomena in both animals for all tested foods. The duration of the epiglottic movement was approximately 0.3 s for liquids and slightly longer for solids. Because swallowing never occurred past an upright epiglottis, the results of this study do not support the hypothesis that adult animals maintain a patent airway during swallowing. Instead, the epiglottis in nonhuman mammals downfolds similarly to that of adult humans during swallowing. © 1996 Wiley-Liss, Inc.     

The Distribution of Transient Receptor Potential Melastatin-8 in the Rat Soft Palate, Epiglottis, and Pharynx

Immunohistochemistry for transient receptor potential melastatin-8 (TRPM8), the cold and menthol receptor, was performed on the rat soft palate, epiglottis and pharynx. TRPM8-immunoreactive (IR) nerve fibers were located beneath the mucous epithelium, and occasionally penetrated the epithelium. These nerve fibers were abundant in the posterior portion of the soft palate and at the border region of naso-oral and laryngeal parts of the pharynx. The epiglottis was free from such nerve fibers. The double immunofluorescence method demonstrated that TRPM8-IR nerve fibers in the pharynx and soft palate were mostly devoid of calcitonin gene-related peptide-immunoreactivity (CGRP-IR). The retrograde tracing method also demonstrated that 30.1 and 8.7 % of sensory neurons in the jugular and petrosal ganglia innervating the pharynx contained TRPM8-IR, respectively. Among these neurons, the co-expression of TRPM8 and CGRP-IR was very rare. In the nodose ganglion, however, pharyngeal neurons were devoid of TRPM8-IR. Taste bud-like structures in the soft palate and pharynx contained 4–9 TRPM8-IR cells. In the epiglottis, the mucous epithelium on the laryngeal side had numerous TRPM8-IR cells. The present study suggests that TRPM8 can respond to cold stimulation when food and drinks pass through oral and pharyngeal cavities.     

Position and growth of upper and lower tooth primordia in prenatal mouse--3D study

The secondary palate formation in mouse has been associated with the period of fast growth of the mandible from embryonic days (ED) 13.0 to 16.0. During that time, the incisors and first molars develop from the bud to the bell stage. We investigated the position and growth of the tooth during prenatal elongation of the lower and upper jaws, and searched for the developmental stage when alignment of opposing teeth was achieved. Computer-aided 3D representations allowed us to represent the position of incisors and molars in the embryonic head from ED 13.5 to 18.0 on the basis of data obtained from histological sections. The atlas-hypophysis connection exhibited minimum change in length and orientation during the prenatal period, and thus was used as a reference line. The length of the teeth was calculated from 3D data. The upper first and second molars were longer than the lower ones. When viewed from the upper side, the upper and lower molar primordia were parallel from ED 13.5 to 15.0. During this period, the upper molars had a more lateral position than the lower ones. This situation was maintained in the anterior extremity of the first molars at later stages, while the posterior part of the upper and lower molar epithelia reached opposition in the medio-lateral direction from ED 16.0. The lower incisors exhibited an apparently backward position when compared to the upper incisors at earlier stages. However, the distance between the prospective anterior tips of the opposing incisors gradually decreased. The part of Meckel's cartilage associated with the lower dental quadrant elongated more than 3-fold from ED 13.5 to 18.0, and the lower jaw grew faster than the upper one. This difference resulted from the fast growth of the lower diastema from ED 14.0 to 18.0. The different growth speeds of the upper and lower jaws did not change the relative antero-posterior adjustment of the upper and lower molars, but contributed to achieving the opposition of the gnawing ends of the incisors.     

The Distribution of TRPV1 and TRPV2 in the Rat Pharynx

Immunohistochemistry for two nociceptive transducers, the transient receptor potential cation channel subfamily V members 1 (TRPV1) and 2 (TRPV2), was performed on the pharynx and its adjacent regions. TRPV1-immunoreactivity (IR) was detected in nerve fibers beneath and within the epithelium and/or taste bud-like structure. In the pharynx, these nerve fibers were abundant in the naso-oral part and at the border region of naso-oral and laryngeal parts. They were also numerous on the laryngeal side of the epiglottis and in the soft palate. TRPV2-IR was expressed by dendritic cells in the pharynx and epiglottis, as well as in the root of the tongue and soft palate. These cells were located in the epithelium and lamina propria. TRPV2-immunoreactive (IR) dendritic cells were numerous in the naso-oral part of the pharynx, epiglottis, and tongue. Abundance of TRPV2-IR dendritic processes usually obscured the presence of TRPV2-IR nerve fibers in these portions. However, some TRPV2-IR nerve fibers could be observed in the epithelium of the soft palate. Retrograde tracing method also revealed that sensory neurons which innervate the pharynx or soft palate were abundant in the jugular–petrosal ganglion complex and relatively rare in the nodose ganglion. In the jugular–petrosal ganglion complex, TRPV1- and TRPV2-IR were expressed by one-third of pharyngeal and soft palate neurons. TRPV2-IR was also detected in 11.5 % pharyngeal and 30.9 % soft palate neurons in the complex. Coexpression of TRPV1 and CGRP was frequent among pharyngeal and soft palate neurons. The present study suggests that TRPV1- and TRPV2-IR jugular–petrosal neurons may be associated with the regulation of the swallowing reflex.     

大鼠气管插管方法学概述

由于大鼠呼吸频率较快、口腔狭小、声门较高,医学实验中气管内插管操作具有较多困难,多年来很多学者对大鼠气管内插管方法进行了大量研究。本文主要对大鼠气管内插管时动物和气管导管的选择、麻醉方式、插管的体位以及各种插管工具和方法等作一简要的综述。     

Development of the supralaryngeal vocal tract in Japanese macaques: implications for the evolution of the descent of the larynx

The configuration of the supralaryngeal vocal tract depends on the nonuniform growth of the oral and pharyngeal portion. The human pharynx develops to form a unique configuration, with the epiglottis losing contact with the velum. This configuration develops from the great descent of the larynx relative to the palate, which is accomplished through both the descent of the laryngeal skeleton relative to the hyoid and the descent of the hyoid relative to the palate. Chimpanzees show both processes of laryngeal descent, as in humans, but the evolutionary path before the divergence of the human and chimpanzee lineages is unclear. The development of laryngeal descent in six living Japanese macaque monkeys, Macaca fuscata, was examined monthly during the first three years of life using magnetic resonance imaging, to delineate the present or absence of these two processes and their contributions to the development of the pharyngeal topology. The macaque shows descent of the hyoid relative to the palate, but lacks the descent of the laryngeal skeleton relative to the hyoid and that of the EG from the VL. We argue that the former descent is simply a morphological consequence of mandibular growth and that the latter pair of descents arose in a common ancestor of extant hominoids. Thus, the evolutionary path of the great descent of the larynx is likely to be explained by a model comprising multiple and mosaic evolutionary pathways, wherein these developmental phenomena may have contributed secondarily to the faculty of speech in the human lineage.     

Growth-related shape changes in the fetal craniofacial complex of humans (Homo sapiens) and pigtailed macaques (Macaca nemestrina): a 3D-CT comparative analysis

This study investigates whether macaques and humans possess a common pattern of relative growth during the fetal period. The fetal samples consist of 16 male pigtailed macaques (mean age, 20.5 gestational weeks) and 17 humans (9 males and 8 females; mean age, 29.5 gestational weeks). For each individual, three-dimensional coordinates of 18 landmarks on the skull were collected from three-dimensional computed tomographic (CT) reconstructed images and two-dimensional CT axial slices. Early and late groups were created from the human (early mean age, 24 weeks, N = 8; late mean age, 34 weeks, N = 9) and macaque samples (early mean age, 17.7 weeks, N = 7; late mean age, 23 weeks, N = 9). Inter- and intraspecific comparisons were made between the early and late groups. To determine if macaques and humans share a common fetal pattern of relative growth, human change in shape estimated from a comparison of early and late groups was compared to the pattern estimated between early and late macaque groups. Euclidean distance matrix analysis was used in all comparisons. Intraspecific comparisons indicate that the growing fetal skull displays the greatest amount of change along mediolateral dimensions. Changes during human growth are primarily localized to the basicranium and palate, while macaques experience localized change in the midface. Interspecific comparisons indicate that the two primate species do not share a common pattern of relative growth, and the macaque pattern is characterized by increased midfacial growth relative to humans. Our results suggest that morphological differences in the craniofacial skeleton of these species are in part established by differences in fetal growth patterns.     

Simulation of turbulent airflow using a CT based upper airway model of a racehorse

Computational model for airflow through the upper airway of a horse was developed. Previous flow models for human airway do not hold true for horses due to significant differences in anatomy and the high Reynolds number of flow in the equine airway. Moreover, models that simulate the entire respiratory cycle and emphasize on pressures inside the airway in relation to various anatomical diseases are lacking. The geometry of the airway was created by reconstructing images obtained from computed tomography scans of a thoroughbred racehorse. Different geometries for inhalation and exhalation were used for the model based on the difference in the nasopharynx size during the two phases of respiration. The Reynolds averaged Navier-Stokes equations were solved for the isothermal flow with the standard k-epsilon model for turbulence. Transient pressure boundary conditions for the entire breathing cycle were obtained from past experimental studies on live horses. The flow equations were solved in a commercial finite volume solver. The flow rates, computed based on the applied pressure conditions, were compared to experimentally measured flow rates for model validation. Detailed analysis of velocity, pressure, and turbulence characteristics of the flow was done. Velocity magnitudes at various slices during inhalation were found to be higher than corresponding velocity magnitudes during exhalation. The front and middle parts of the nasopharynx were found to have minimum intraluminal pressure in the airway during inhalation. During exhalation, the pressures in the soft palate were higher compared to those in the larynx, epiglottis, and nasopharynx. Turbulent kinetic energy was found to be maximum at the entry to the airway and gradually decreased as the flow moved inside the airway. However, turbulent kinetic energy increased in regions of the airway with abrupt change in area. Based on the analysis of pressure distribution at different sections of the airway, it was concluded that the front part of the nasopharynx requires maximum muscular activity to support it during inhalation. During exhalation, the soft palate is susceptible to displacements due to presence of high pressures. These can serve as critical information for diagnosis and treatment planning of diseases known to affect the soft palate and nasopharynx in horses, and can potentially be useful for human beings.     

Development of the orbicularis oris muscle in normal and cleft lip and palate human fetuses using three-dimensional computer reconstruction

As part of an ongoing study of cleft lip and palate fetal morphology, normal and dysmorphic development of the human fetal orbicularis oris muscle was studied in a cross-sectional sample of 29 human fetuses (20 "normal" and 9 cleft lip and palate) ranging in age from 8 to 21 postmenstrual weeks. The specimens were embedded in celloidin and sectioned at 20 microns, and every tenth section was stained with hematoxylin and eosin. A computer reconstruction technique was applied to produce three-dimensional representations of the orbicularis oris muscle. The orbicularis oris muscle in the normal fetal sample with discernible lip fibers (N = 15) increased symmetrically in both fiber density and complexity from 12 to 21 weeks. Metrically, muscle volume and thickness growth curves were consistent with qualitative observations. In contrast, the unilateral cleft lip and palate fetal specimens with discernible lip fibers (N = 3) exhibited a 3.5-week delay in overall muscle development, asymmetrical fiber distribution, and abnormal fiber insertions. However, quantitatively, no significant (p greater than 0.05) differences were noted in orbicularis oris muscle thickness or volume between the normal and cleft lip and palate fetal specimens through 21 weeks. Findings suggest that orbicularis muscle deficiency, noted clinically in cleft lip and palate neonates, may be a result of perinatal functional dysmorphogenesis rather than congenital mesenchymal reduction or deficiency.     

A new intraoral flap: facial artery musculomucosal (FAMM) flap.

By combining the principles of nasolabial and buccal mucosal flaps, we have designed a new axial musculomucosal flap based on the facial artery. This flap has been designated the facial artery musculomucosal (FAMM) flap. The flap has proven to be reliable either superiorly based (retrograde flow) or inferiorly based (antegrade flow). It is versatile and has been used 18 times in 15 patients, with one failure and two partial losses. It has been used successfully to reconstruct a wide variety of difficult oronasal mucosal defects, including defects of the palate, alveolus, nasal septum, antrum, upper and lower lips, floor of the mouth, and soft palate.     

Movement of the human upper airway during inspiration with and without inspiratory resistive loading

The electromyographic (EMG) activity of human upper airway muscles, particularly the genioglossus, has been widely measured, but the relationship between EMG activity and physical movement of the airway muscles remains unclear. We aimed to measure the motion of the soft tissues surrounding the airway during normal and loaded inspiration on the basis of the hypothesis that this motion would be affected by the addition of resistance to breathing during inspiration. Tagged MR imaging of seven healthy subjects was performed in a 3-T scanner. Tagged 8.6-mm-spaced grids were used, and complementary spatial modulation of magnetization images were acquired beginning ～200 ms before inspiratory airflow. Deformation of tag line intersections was measured. The genioglossus moved anteriorly during normal and loaded inspiration, with less movement during loaded inspiration. The motion of tissues at the anterior border of the upper airway was nonuniform, with larger motions inferiorly. At the level of the soft palate, the lateral dimension of the airway decreased significantly during loaded inspiration (-0.15 ± 0.09 and -0.48 ± 0.09 mm during unloaded and loaded inspiration, respectively, P < 0.05). When resistance to inspiratory flow was added, genioglossus motion and lateral dimensions of the airway at the level of the soft palate decreased. Our results suggest that genioglossus motion begins early to dilate the airway prior to airflow and that inspiratory loading reduces the anterior motion of the genioglossus and increases the collapse of the lateral airway walls at the level of the soft palate.     

A morphometric analysis of craniofacial growth and changes in spatial relations during secondary palatal development in human embryos and fetuses

Staged human embryos and fetuses in the Carnegie Embryological Collection were morphometrically analyzed to show craniofacial dimensions and changes in spatial relations, and to identify patterns that would reflect normal developmental events during palatal formation. Normal embryos aged 7-8 weeks postconception (Streeter-O'Rahilly stages 19-23) and fetuses aged 9-10 weeks postconception, in eight groups with mean crown-rump (CR) lengths of 18-49 mm, were studied with cephalometric methods developed for histologic sections. In the 4-week period studied, facial dimensions increased predominantly in the sagittal plane with extensive changes in length (depth) and height, but limited changes in width. Growth of the mandible was more rapid than the nasomaxillary complex, and the length of Meckel's cartilage exceeded the length of the oronasal cavity at the time of horizontal movement of the shelves during stage 23. Simultaneously with shelf elevation, the upper craniofacial complex lifted, and the tongue and Meckel's cartilage extended forward beneath the primary palate. Analysis of spatial relations in the oronasal cavity showed that the palatomaxillary processes became separated from the tongue--mandibular complex as the head extended, and the tongue became positioned forward with growth of Meckel's cartilage. As the head position extended by 35 degrees, the cranial base angulation was unchanged and the primary palate maintained a 90 degrees position to the posterior cranial base. However, the sagittal position of the maxilla relative to the anterior cranial base increased by 20 degrees between stages 19 and 23. In the late embryonic and early fetal periods, the mean cranial base angulation of approximately 128 degrees and the mean maxillary position angulation of approximately 84 degrees were similar to the angulations previously shown to be present later prenatally and post-natally. The results suggest that human patterns of cranial base angulation and maxillary position to the cranial base develop during the late embryonic period when the chondrocranium and Meckel's cartilage form the primary skeleton.     

OSAHS患者上气道和软腭的流固耦合有限元模型的建立

目的:重建OSAHS患者上气道和软腭的流固耦合有限元模型,研究OSAHS患者上气道及软腭气流动力学特征,为进一步探讨OSAHS的的发病机制奠定基础。方法:对一名中度OSAHS患者的上气道及周围组织进行MRI扫描,将以DICOM格式存储的扫描数据导入Mimics15.0软件中进行预处理,得到上气道和软腭的模型;再利用逆向工程软件Geomagic Studio 2013建立了2 mm气道壁;然后在3-D重建软件NX中,生成气道壁和气道以及软腭之间的组合模型;最后将该组合模型导入ANSYS Workbench13.0软件中,通过网格划分、定义材料属性、设定模型的边界条件操作建立了上气道和软腭的流固耦合有限元模型。结果:利用Mimics、Ansys等软件建立了完整的上气道和软腭的流固耦合有限元模型。共得到气道:2806835单元和529281个节点;气道壁:2304348单元和3487609个节点;软腭:131855单元和204784个节点。结论:本研究建立的上气道及软腭的流固耦合有限元模型符合人体的生物力学特点,为下一步的数值模拟实验提供了一个更真实、可靠的模型。     

Epidermal growth factor (EGF) influences DNA synthesis in human fetal kidneys maturing in serum-free organ culture

Human fetal kidney explants (13-17 weeks of gestation) were maintained in serum-free organ culture. The influence of epidermal growth factor (EGF) was determined after 2 and 5 days by evaluating DNA and protein synthesis as well as the activities of five brush border hydrolases. During the studied period the overall morphology was preserved and the analysed parameters remained constant. Only DNA synthesis decreased after 2 days. The addition of EGF to the medium did not change any of the cell activities, except DNA synthesis. In fact, the incorporation of [3H]thymidine was significantly stimulated by 105% in 5-day explants cultured in the presence of the growth factor. These results indicate that EGF directly influences proliferation but not maturation of brush border enzymes in fetal human kidneys in culture.     

The basicranium of Plio-Pleistocene hominids as an indicator of their upper respiratory systems

Our analyses of extant primates have shown that a relationship exists between the degree of flexion of the basicranium and the location of upper respiratory structures such as the larynx and pharynx (Laitman et al., 1978). Based upon these relationships, we have previously used the basicrania of late Pleistocene hominids as a guide to the reconstruction of their upper respiratory anatomy (Laitman et al., 1979). This study continues our approach by examining the basicrania of Plio-Pleistocene hominids and reconstructing their upper respiratory systems. Nine Plio-Pleistocene hominids had basicrania complete enough to be used in this study. These included the originals of Sts 5, MLD 37/38, SK 47, SK 48, SK 83, Taung, KNM-ER 406, OH 24, and a cast of OH 5. Craniometric analysis of the basicrania of these specimens showed that they had marked similarities to those of extant pongids. These basicranial similarities between Plio-Pleistocene hominids and extant apes suggest that the upper respiratory systems of these groups were also alike in appearance. As with living nonhuman primates, the early hominids probably exhibited a larynx and pharynx positioned high in the neck. This high position would have permitted an intranarial epiglottis to be present during both normal respiration and the ingestion of a liquid bolus of food. The high position of the larynx would have also greatly restricted the supralaryngeal portion of the pharynx available to modify laryngeal sounds. It is thus possible that the Plio-Pleistocene hominids exhibited modes of breathing, swallowing and vocalizing similar to those of living apes.     

天山东部西伯利亚落叶松树轮生长对气候要素的响应分析

天山东部西伯利亚落叶松的树木年轮学研究可以看出：森林上限树轮宽度年表之间相关性较高而下限年表间相关稍低,表明下限小生境要素对树木生长干扰较大。森林上下限树轮年表中样本的总解释量（ESP）和信噪比（SNR）都比较高,说明树木中都含有较多的环境信息;但标准年表中平均敏感度（M．S．）和轮宽指数的标准差（S．D．）都是森林上限数值低于下限,这表明森林上限树木生长对环境变化响应的敏感性降低;相关分析和响应分析也发现森林下限生长的树木对气候因子的响应较为显著。就温度而言,森林上限和下限表现基本一致,树木生长多与温度负相关,其中下限树木生长与春季均温和3．6月份均温显著负相关;降水表现出一定的差别,上限树木生长与春季、夏季及年降水量有较高的负相关,而对下限树木生长影响最大的则是冬季和3—6月份降水。湿润指数与降水基本一致即上限呈负相关而下限正相关,温暖指数全为负相关,寒冷指数下限负相关显著;显然该地区森林上下限树木生长的生态模式存在着一定的差异。研究发现,冬春季节的不同水热组合则是形成树木年轮宽窄的限制因素;同时,前期生长的滞后效应对年轮形成有重要的影响。     

Advances in understanding the relationship between the skull base and larynx with comments on the origins of speech

The position of upper respiratory structures, such as the larynx, has proven to be of great importance in determining an animal’s breathing, swallowing and vocalizing abilities. Studies on living mammals have also shown that the shape of the basicranium is related to the position of the larynx. This information has been of value in using the skull base as a means to reconstruct the upper respiratory tract of fossil hominids. Ongoing comparative and experimental studies of this region are adding new information on the mechanical relationship of the skull base to contiguous areas of the respiratory tract. For example, examination of the region in mammals disparate from humans, such as cetaceans, and experimental work on the region in rats, is adding new data on how the larynx and skull base may functionally interact.