Four-bar linkage modelling in teleost pharyngeal jaws: computer simulations of bite kinetics

The pharyngeal arches of the red drum (Sciaenops ocellatus) possess large toothplates and a complex musculoskeletal design for biting and crushing hard prey. The morphology of the pharyngeal apparatus is described from dissections of six specimens, with a focus on the geometric conformation of contractile and rotational elements. Four major muscles operate the rotational 4th epibranchial (EB4) and 3rd pharyngobranchial (PB3) elements to create pharyngeal bite force, including the levator posterior (LP), levator externus 3/4 (LE), obliquus posterior (OP) and 3rd obliquus dorsalis (OD). A biomechanical model of upper pharyngeal jaw biting is developed using lever mechanics and four-bar linkage theory from mechanical engineering. A pharyngeal four-bar linkage is proposed that involves the posterior skull as the fixed link, the LP muscle as input link, the epibranchial bone as coupler link and the toothed pharyngobranchial as output link. We used a computer model to simulate contraction of the four major muscles, with the LP as the dominant muscle, the length of which determined the position of the linkage. When modelling lever mechanics, we found that the effective mechanical advantages of the pharyngeal elements were low, resulting in little resultant bite force. By contrast, the force advantage of the four-bar linkage was relatively high, transmitting approximately 50% of the total muscle force to the bite between the toothplates. Pharyngeal linkage modelling enables quantitative functional morphometry of a key component of the fish feeding system, and the model is now available for ontogenetic and comparative analyses of fishes with pharyngeal linkage mechanisms.     

Development of the pharyngeal arches

The oro-pharyngeal apparatus has its origin in a series of bulges that is found on the lateral surface of the embryonic head, the pharyngeal arches. The development of the pharyngeal arches is complex involving a number of disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose development must be co-ordinated to generate the functional adult apparatus. In the past, most studies have emphasised the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development, but it has also become apparent that the other tissues of the arches, most notably the endoderm, also plays a prominent role in directing arch development. Thus pharyngeal arch development is more complex, and more consensual, than was previously believed.     

咽癌患者调强适形放射治疗期间咽缩肌放射剂量对吞咽功能的影响

目的:观察咽癌患者调强适形放射治疗期间咽缩肌放射剂量与吞咽功能的关系。方法:选取80例咽癌患者作为研究对象,均实施调强适形放射治疗6个月,根据患者治疗需求选取咽缩肌放射剂量,分别于放疗1、3及6个月,记录患者吞咽功能评分,分析咽缩肌放射剂量与吞咽功能评分的相关性。并于放疗结束时,评估患者吞咽功能,将患者分为吞咽功能正常、吞咽障碍轻度、中度及重度障碍,比较无-轻度吞咽障碍组与中-重度吞咽障碍组咽缩肌放射剂量,采用回归分析检验咽缩肌放射剂量对吞咽功能的影响。结果:各时点中,放疗1个月时MDADI总分及各维度评分最高,后由高到低依次为放疗3个月时、放疗6个月时,不同时点MDADI评分比较差异均有统计学意义（P<0.05）;80例咽癌患者咽上缩肌放射剂量为（44.72±5.58） Gy,中咽缩肌放射剂量为（48.94±6.17） Gy,咽下缩肌放射剂量为（38.95±4.74） Gy,咽缩肌放射总剂量为（132.61±28.52） Gy;经一般线性双变量Pearson相关性分析结果显示,不同时点MDADI总分与咽缩肌总放射剂量呈负相关;80例咽癌患者放疗结束时,29例吞咽功能正常,18例轻度吞咽障碍,21例中度吞咽障碍,12例重度吞咽障碍;初步比较中-重度吞咽障碍组与无-轻度吞咽障碍组咽缩肌放射剂量后,经多元Logistic回归分析显示,咽缩肌放射剂量高是患者放疗结束时发生中-重度吞咽障碍的危险因素（OR>1, P<0.05）。结论:咽癌患者调强适形放射治疗期间咽缩肌放射剂量可影响吞咽功能,随剂量增加,患者吞咽功能降低,吞咽障碍发生风险增加。     

Morphology of the accessory (pharyngeal) adenohypophysis and its relationship with the pharyngeal tonsil in the human fetus

The pharyngeal pituitary was examined in human fetuses during weeks 16 to 32 of development by light microscopy with routine and histochemical treatment of slices. All the fetuses examined possessed a pharyngeal pituitary, which develops from the epithelium of the upper pharyngeal wall, just like the main pituitary. Rathke's pouch becomes transformed into a cord and grows towards the midbrain forming the hypophysis cerebri, while some cells at the base of the cord remain in the integumentary epithelium of the pharynx and give rise to the pharyngeal pituitary. This organ represents a group of long epithelial cords under the integumentary epithelium within the connective tissue of the pharyngeal mucosa. The cords contain light and dark cells with signs of a secretory cycle. The pituitary cords grow into the lymphoid tissue of the pharyngeal tonsil. The integumentary epithelium does not contain protective structures at the site of origin of the pharyngeal pituitary. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 8, pp. 211–214, August, 1995 Presented by N. K. Permyakov, Member of the Russian Academy of Medical Sciences     

Modeling the pharyngeal anatomical effects on breathing resistance and aerodynamically generated sound

The objective of this study was to systematically assess the effects of pharyngeal anatomical details on breathing resistance and acoustic characteristics by means of computational modeling. A physiologically realistic nose-throat airway was reconstructed from medical images. Individual airway anatomy such as the uvula, pharynx, and larynx was then isolated for examination by gradually simplifying this image-based model geometry. Large eddy simulations with the FW-H acoustics model were used to simulate airflows and acoustic sound generation with constant flow inhalations in rigid-walled airway geometries. Results showed that pharyngeal anatomical details exerted a significant impact on breathing resistance and energy distribution of acoustic sound. The uvula constriction induced considerably increased levels of pressure drop and acoustic power in the pharynx, which could start and worsen snoring symptoms. Each source anatomy was observed to generate a unique spectrum with signature peak frequencies and energy distribution. Moreover, severe pharyngeal airway narrowing led to an upward shift of sound energy in the high-frequency range. Results indicated that computational aeroacoustic modeling appeared to be a practical tool to study breathing-related disorders. Specifically, high-frequency acoustic signals might disclose additional clues to the mechanism of apneic snoring and should be included in future acoustic studies.     

Variations of the pharyngeal raphe

The pharyngeal raphe is described traditionally as a straight, continuous, median, fibrous band that provides attachment for and separates each pair of the three constrictor muscles of the pharynx. The posterior wall of the pharynx was dissected in 236 adult human cadavers of the Mongoloid, Caucasoid, and Negroid races. The arrangement of the raphe in each specimen was recorded. The various arrangements of the raphe were then organized into three types (I, II, or III) and eight subtypes (a, b, or c). The raphe was most often (47%) located between the inferior constrictor muscles only (type I) where it was either a straight or a curved line or had a fusiform to oval shape. The second most frequent pattern (40%) was a raphe located between the superior and middle constrictor muscles only (type II) with a shape similar to type I. The middle constrictor muscles were sometimes well developed and attached superiorly to the pharyngeal tubercle by way of a strong raphe. The raphe extended from the pharyngeal tubercle through all the constrictor muscles to the esophagus (type III) in only 13% of the specimens and was more often interrupted rather than a continuous line. The type usually described in anatomy textbooks (type IIIa) was found in only 5% of the specimens.     

Bovine herpesvirus-1-induced pharyngeal tonsil lesions in neonatal and weanling calves.

The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by intranasal aerosol. Calves were monitored from days 1 to 5, and on day 6 (neonates) or 8 (weanlings) and, in a second trial at day 4.5, by histology, electron microscopy, immunocytochemistry and virus isolation. Mucosal lesions of neonates were similar to, but less extensive than, those of weanling calves. Loss of microvilli and goblet cells, with minimal epithelial erosions as early as day 1, progressed to necrosis of epithelium and adjacent lymphoid tissue, and leucocyte exudation. Lesions and clinical disease were progressive up to and including day 6 in neonates, but resolving in weanlings on days 5 and 8. By transmission electron microscopy, the physical characteristics of the phagocytic cells appeared similar in both age groups, and viral replication was not identified in leucocytes. Virus was isolated from, or found by immunocytochemistry in, the pharyngeal tonsil of all calves examined, except for two weanlings on days 1 and 8. Virus as detected by immunocytochemistry was restricted to epithelium and superficial lymphoid tissue in neonates, but was found in deep lymphoid tissue around germinal centres in weanlings. The study showed that the pharyngeal tonsil is readily infected with BHV-1 and may be an important lymphoid tissue for early anti-viral responses. The delayed inflammatory response and reduced viral clearance may contribute to the increased susceptibility of neonatal calves to fatal BHV-1 infections.     

Plasminogen-mediated group A streptococcal adherence to and pericellular invasion of human pharyngeal cells

Alpha-enolase (SEN) is a strong plasminogen-binding protein on the surface of group A streptococci (GAS). By flow cytometry and immunofluorescence analyses and using human enolase-specific antibody, human pharyngeal cells (Detroit 562) also were found to express enolase on their surface. Detroit 562 cells preferentially bound to Lys-plasminogen and this binding was inhibited in the presence of a lysine analog, epsilon-aminocaproic acid and by carboxypeptidase-B treatment suggesting that the C-terminal lysine residue of the putative pharyngeal cell receptor(s) may play an important role in plasminogen-binding. The increased plasminogen-binding in the presence of free enolase indicated the presence of an enolase/SEN-specific receptor on the pharyngeal cell surface. GAS, when precoated with Lys-plasminogen, adhered to pharyngeal cells significantly more in numbers than when precoated with fibronectin or laminin. Similarly, GAS adhered also significantly more in numbers to pharyngeal cells which were precoated with Lys-plasminogen. GAS adhered similarly in high numbers when incubated with pharyngeal cells in the presence of soluble plasminogen. The de novo pharyngeal cell-bound protease activity, created as a result of activation of bound plasminogen by t-PA, indicated its potential role in pericellular fibrinolytic activity. Further GAS with tPA-activated plasminogen bound on their surface penetrated through Transwell-grown pharyngeal cells in significantly higher numbers. Together, the results presented in this study highlight a novel function of plasminogen in streptococcal adherence to pharyngeal cells and a newly discovered streptococcal ability to pericellularly invade pharyngeal cells as a result of tPA/endogenous plasminogen activator-mediated proteolytic activity.     

Deficits in the posterior pharyngeal endoderm in the absence of retinoids.

Recent studies have shown that the pharyngeal endoderm plays a critically important role in directing the development of the pharyngeal region of the vertebrate embryo. We have, however, had few insights into how the pharyngeal endoderm itself is patterned. Recently, several studies have suggested that retinoic acid is required for the development of the pharyngeal endoderm. To study this proposal in greater depth, we have examined the development of the pharyngeal endoderm in the absence of retinoid signalling, by using the vitamin A- deficient (VAD) quail model system. We find in early stages that, in the absence of retinoids, this territory extends further caudally than normal. Furthermore, as development proceeds, we find that the first pouch invariably forms, that the second pouch is abnormal, and that the third and fourth pharyngeal pouches never form. We do find, however, that dorsoventral patterning of the pharyngeal endoderm is unaffected. Finally, we have examined the expression patterns of RALDH2 before and during early development of the pharyngeal pouches. We find that this enzyme is expressed adjacent to the pharyngeal endoderm in tissues around the regressing anterior intestinal portal and that from stage 12 onward its anterior limit of expression lies at the level of the second pouch. This finding helps explain why the first pouch always forms in the absence of retinoids, and why defects are seen starting with the second and most evidently in the caudal pouches.     

Oral and pharyngeal cancer in Ireland

Early diagnosis and treatment of cancer are essential to achieving a good prognosis. This is particularly true for oral and pharyngeal cancer (OPC) which accounts for over half a million new cases and 200,000 deaths worldwide per annum. Despite the high mortality and high morbidity associated with OPC, it remains a relatively unknown disease. The lack of public awareness and the low profile of this disease, even among health care professionals, are considered among the main reasons for late presentation, with 60% of cases presenting at an advanced stage. Due to the age and general medical profile of the average oral cancer patient, many attend their general physician on a regular basis. An opportunity therefore exists to increase the rate of detection of early asymptomatic lesions by opportunistic screening particularly of "high risk individuals". Furthermore, prompt recognition of symptomatic lesions has the potential to greatly enhance the outcome for these patients. The aim of this paper is to increase awareness of OPC and to highlight the need for closer interdisciplinary links between medical and dental professionals.     

Direct DNA probe assay for Neisseria gonorrhoeae in pharyngeal and rectal specimens.

The direct detection of gonococcal DNA in rectal and pharyngeal specimens was evaluated by using a DNA probe-based assay (Gen-Probe, Inc., San Diego, Calif.). Rectal (234) and pharyngeal (608) swab specimens were obtained from 249 men and 372 women attending sexually transmitted disease clinics in Las Vegas and Reno, Nevada. The prevalence of gonococcal infection by culture at the pharyngeal and rectal sites was 2.9% (16 of 548 specimens) in women and 2.7% (8 of 294 specimens) in men. No false-positive reactions were observed among the 234 rectal specimens tested. Two probe-positive, culture-negative specimens were detected among the 361 pharyngeal specimens obtained from women. Both of these samples were confirmed as Neisseria gonorrhoeae by a probe competition assay. The overall correlation of the DNA probe test with pharyngeal and rectal cultures was 99.4% (837 of 842 cultures), with a sensitivity of 87.5% (21 of 24 cultures) and specificity of 99.7% (816 of 818 cultures). The positive and negative predictive values of the DNA assay were 91.3 and 99.8%, respectively. The direct DNA probe assay provides an alternative to culture screening for rectal and/or pharyngeal gonococcal infections.     

咽升动脉分支的解剖分组及其临床意义

目的:探讨咽升动脉及其主要分支在颈部颅底区域走行规律及其在血管内外治疗中的临床意义。方法:选择以10%甲醛固定并用乳胶灌注的8具（16侧）成人颅颈部标本,自颈总动脉分叉水平向上解剖至颅底骨质,分离显露咽升动脉及周围相关结构,观察咽升动脉的起源部位及主要分支,测量相关解剖学参数。依据咽升动脉主要分支与颈动脉鞘的位置关系分...     

The relationship between the oral and pharyngeal phases of swallowing

OBJECTIVE:

This study was designed to investigate a possible relationship between the duration of the oral and pharyngeal phases of swallowing.

INTRODUCTION:

The oral and pharyngeal phases of swallowing are independent from each other but may be related.

METHODS:

We used videofluoroscopy to evaluate 30 healthy volunteers between 29 and 77 years of age who swallowed 5- and 10-ml liquid and paste boluses in duplicate. The duration of the oral phase, pharyngeal transit, and pharyngeal clearance were measured.

RESULTS:

There were no differences in oral or pharyngeal transit times between the liquid and paste boluses or between the volumes of 5 and 10 ml (p>0.40). The pharyngeal clearance time for the paste bolus (0.48±0.27 s) was longer than for the liquid bolus (0.38±0.11 s, p = 0.03) with no difference between the volumes of 5 and 10 ml. There was no significant correlation between the oral transit time and the duration of pharyngeal transit for the liquid (5 ml, Spearman''s coefficient ρ: −0.14; 10 ml, ρ: 0.18) or the paste (5 ml, ρ: 0.08; 10 ml, ρ: 0.10). The correlation between the oral transit time and the pharyngeal clearance time was not significant for the liquid bolus (5 ml, ρ: 0.31; 10 ml, ρ: 0.18), but it was significant for both the 5 ml (ρ: 0.71) and 10 ml (ρ: 0.64) paste boluses.

DISCUSSION:

The relationship between the oral and pharyngeal phases of swallowing can be affected by bolus consistency.

CONCLUSION:

There is a correlation between the duration of oral transit and the duration of pharyngeal clearance during the swallowing of paste boluses.     

The development and evolution of the pharyngeal arches

A muscularised pharynx, with skeletal support, serving the dual functions of feeding and respiration, is a fundamental vertebrate characteristic. Embryologically, the pharyngeal apparatus has its origin in a series of bulges that form on the lateral surface of the embryonic head, the pharyngeal arches, whose development is complex. These structures are composed of a number of disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose development must be coordinated to generate the functional adult apparatus. In the past, most studies have emphasised the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development, but it has also become apparent that the endoderm plays a prominent role in directing arch development. Neural crest cells are not required for arch formation, their regionalisation nor to some extent their sense of identity. Furthermore, the endoderm is the major site of expression of a number of important signalling molecules, and this tissue has been shown to be responsible for promoting the formation of particular components of the arches. Thus vertebrate pharyngeal morphogenesis can now be seen to be a more complex process than was previously believed, and must result from an integration of both neural crest and endodermal patterning mechanisms. Interestingly, this also mirrors the fact that the evolutionary origin of pharyngeal segmentation predates that of the neural crest, which is an exclusively vertebrate characteristic. As such, the evolution of the vertebrate pharynx is also likely to have resulted from an integration between these 2 patterning systems. Alterations in the interplay between neural crest and endodermal patterning are also likely to be responsible for the evolutionary that occurred to the pharyngeal region during subsequent vertebrate evolution.     

Non-receptor tyrosine kinase CSK-1 controls pharyngeal muscle organization in Caenorhabditis elegans

C-terminal Src kinase (Csk) is a non-receptor type of tyrosine kinase, and serves as an essential negative regulator of Src family tyrosine kinases (SFKs) in vertebrates. However, analyses of Csk and SFKs from primitive animals suggest that the Csk-mediated mechanisms regulating SFK activity might diverge between evolutional branches, different tissues or SFK family members. We examined in vivo roles of CSK-1, a Caenorhabditis elegans orthologue of Csk, by generating animals lacking csk-1 function. Although some csk-1 mutants died during embryogenesis, the majority of mutants died during the first stage of larval development. In csk-1 mutants, the function of pharyngeal muscles, the major site of CSK-1 expression, was severely damaged. The pumping of pharyngeal grinder cells became arrhythmic, causing disabled feeding. Electron microscopy showed that pharyngeal muscle filaments were disorientated in the csk-1 mutants. These indicate that CSK-1 is crucial for proper organization of pharyngeal muscles. However, the growth arrest phenotype in csk-1 mutants could not be suppressed by src-1 and/or src-2 mutation, and SRC-1 was not significantly activated in the csk-1 mutants. These results suggest that CSK-1 has an essential function in organization of pharyngeal muscle filaments that does not require C. elegans SFKs.     

The development and evolution of the pharyngeal arches

A muscularised pharynx, with skeletal support, serving the dual functions of feeding and respiration, is a fundamental vertebrate characteristic. Embryologically, the pharyngeal apparatus has its origin in a series of bulges that form on the lateral surface of the embryonic head, the pharyngeal arches, whose development is complex. These structures are composed of a number of disparate embryonic cell types: ectoderm, endoderm, neural crest and mesoderm, whose development must be coordinated to generate the functional adult apparatus. In the past, most studies have emphasised the role played by the neural crest, which generates the skeletal elements of the arches, in directing pharyngeal arch development, but it has also become apparent that the endoderm plays a prominent role in directing arch development. Neural crest cells are not required for arch formation, their regionalisation nor to some extent their sense of identity. Furthermore, the endoderm is the major site of expression of a number of important signalling molecules, and this tissue has been shown to be responsible for promoting the formation of particular components of the arches. Thus vertebrate pharyngeal morphogenesis can now be seen to be a more complex process than was previously believed, and must result from an integration of both neural crest and endodermal patterning mechanisms. Interestingly, this also mirrors the fact that the evolutionary origin of pharyngeal segmentation predates that of the neural crest, which is an exclusively vertebrate characteristic. As such, the evolution of the vertebrate pharynx is also likely to have resulted from an integration between these 2 patterning systems. Alterations in the interplay between neural crest and endodermal patterning are also likely to be responsible for the evolutionary that occurred to the pharyngeal region during subsequent vertebrate evolution.     

增龄过程中咽食管管腔宽度的变化

目的 探讨增龄过程中咽食管(PES)管腔宽度的变化。方法 运用局部解剖技术,对60例成人尸体咽食管段标本管腔进行观测。结果 按形态将咽食管段管腔分紧缩型和平滑型,将咽食管段从上至下分为４个平面：环咽侧三角上缘平面、甲状软骨下角下缘平面、内腔最窄处平面和环状软骨下缘平面,从环咽侧三角上缘平面至内腔最窄处平面管腔逐渐缩窄(P<0.05),老年组管腔较中青年组及青少年组同平面管腔宽度增宽(P<0.05)。 结论 老年组咽食管段管腔比青少年组和中青年组均增宽,可能是老年化过程中的代偿性改变。     

Brain heterotopia in pharyngeal region. A morphological and immunohistochemical study

Pharyngeal brain heterotopia is a congenital and generally biologically benign lesion. In contrast to brain heterotopia in the nose, the most common site of this lesion, brain heterotopia in the pharynx is very rare. Pharyngeal heterotopic tissue can be composed of various components, i.e., astrocytes, neurons, ependyma or choroid plexus, oligodendrocytes, retina, and, occasionally, neoplastic nodules. In contrast, nasal lesions are often only composed of astrocytes. We report a case of brain heterotopia in the pharyngeal region, diagnosed in a newborn female infant, causing serious respiratory distress. The infant underwent surgical excision of the lesion, and after 1 year of follow-up, she is recurrence-free. The mass, about 3 cm in diameter and showing no connection with encephalic structures, was characterized by numerous papillary structures and areas containing stellate-like or spindle cells focally forming nodules. Moreover, there was inflammatory infiltration, whereas mitoses, hemorrhages, and necroses were absent. Immunohistochemistry revealed a choroid plexus nature of the papillary formations (S-100, cytokeratins, transthyretin and vimentin-positive) and the presence of glial and neuronal cells in the remaining areas (glial fibrillary acidic protein, neuron-specific enolase, neurofilaments, synaptophysin, and S-100 positive). This case report confirms that the presence of choroid plexus is not uncommon and that pharyngeal brain heterotopia is usually benign.     

扁桃体切除后伤口缝合方式对睡眠呼吸暂停患者咽腔结构影响的有限元方法研究

目的腭咽是阻塞性睡眠呼吸暂停(obstructive sleep apnea,OSA)患者中最为常见的阻塞部位,该类患者手术治疗多采用保留悬雍垂腭咽成形术(Han-uvulopalatopharyngoplasty,H-UPPP),切除扁桃体是该手术的重要组成部分,其目的是扩大咽腔,改善气道通气性能。手术后切口缝合时会引起组织中应力重新分布,从而直接影响术后咽腔壁的几何形态和手术效果。但目前尚无有效方法评估切口缝合方式对手术效果的影响。本研究提出利用有限元分析模型探究扁桃体窝不同缝合方式对咽腔结构的影响,以此对H-UPPP术式操作的选择提供理论依据。方法基于OSA患者头颈部磁共振图像,构建具有真实解剖结构的气道及周边组织的三维有限元模型。通过收缩扁桃体组织体积和限定其组织表面位移来模拟扁桃体切除手术及三种缝合方式。利用ADINA软件进行数值模拟,通过观察气道最小横截面面积和咽腔空间的变化等探讨不同缝合方式对咽腔尺度的影响。结果利用三维有限元模型模拟了对位、前拉、后拉三种缝合方式。数值模拟结果显示,前拉缝合扁桃体窝时气道最狭窄处横截面积变化最为显著,扩大了27.82%。而对位缝合和后拉缝合扁桃体窝的情况,该处横截面积增加量分别为24.76%和27.11%。对于对位和后拉缝合,悬雍垂游离端附近的咽腔横截面积变化更为明显,其平均值约为手术前的5倍。相比之下,前拉缝合后相同区域平均咽腔横截面积值约为手术前的4.3倍。结论腭咽成形术改良术式的伤口缝合方式会对周边软组织中应力分布和气道截面几何形态产生重要影响。本研究建立的方法可用于针对不同患者的个性化模拟,对于本研究所涉的患者上气道解剖结构类型,模型显示前拉缝合对改善患者咽腔最狭窄部位结构更为有利。