Craniofacial embryology and postnatal development of relevant parts of the upper respiratory system.

OBJECTIVES: To compare historical and current knowledge relating to the development of the paranasal sinuses, the nose and face, the Eustachian tube and temporal bones, particularly with respect to chronic inflammation during childhood. METHODOLOGY: Traditional literature data, mainly emanating from text books, were supplemented with information based on a non-structured PubMed search covering the last two decades. RESULTS: Historical knowledge has most often been confirmed, sometimes supplemented and only rarely challenged by present-day studies. Recent studies focus mainly on the clinical application of modern imaging techniques. CONCLUSIONS: Interest in the development of relevant parts of the upper respiratory system remains as lively as ever. Imaging techniques with low or absent radiation exposure may give rise to a novel field of research, especially with respect to paediatric rhinosinusitis.

Human evolutionary history: consequences for the pathogenesis of otitis media.

The pathogenesis of otitis media is multifactorial, but the role of evolution on its development has not been addressed. We posit that the high prevalence of middle-ear disease is most likely restricted to humans, in contrast to other wild species, because the associated hearing loss would have reduced the fitness of affected individuals as a result of predation. We present here the possible consequences of two human adaptations that may have resulted in ubiquitous otitis media: the interaction of bipedalism and increased brain size, and the loss of facial prognathism resulting from speech or cooking. As a consequence of our adaptation for bipedalism, the female pelvic outlet is constricted, which, in the context of a rapidly enlarging brain, results in humans being born 12 months too soon. Significantly, immature eustachian tube structure and function, in conjunction with an immature immune system, helps to explain the high incidence of otitis media in the first year of life. But the persistence of middle-ear disease beyond this stage is not explained by "immaturity." The morphology of the palate changed with the adaptations that produced facial flattening, with concomitant effects on eustachian tube function. These changes resulted in relatively poor human physiologic tubal function in comparison to the nonhuman primate.

Relevance of the pharyngotympanic tube.

The auditory (Eustachian) tube connects the middle ear with the nasopharynx. This conduit permits equalisation of pressure between the middle ear and the throat. Balanced pressure allows the eardrum to vibrate freely as sound waves strike it. The auditory tube is also a potential anatomical route whereby opportunistic pathogens may migrate from the nose and throat to the middle ear. Eustachian tube (ET) function is disturbed in children with cleft palate, thereby rendering them susceptible to chronic otitis media with effusion (OME) and temporary conductive deafness. ET obstruction follows in these patients, and is thought to be related to the inability of the tensor veli palatini (TVP) to function properly. This anatomical overview reviews the clinical importance of the ET in the normal population and children with cleft palate.

Temporal bone morphometric study on the eustachian tube and its associated structures in patients with chromosomal aberrations.

This study characterized phenotypic anomalies of the eustachian tube (ET) and its associated structures in individuals with various chromosomal aberrations (trisomies 13, 18, 21, and 22 and inversion of chromosome 1). The morphological characteristics of the ET and its accessory structures from 10 temporal bone-ET specimens, obtained from 10 individuals with chromosomal aberrations who ranged from the 26th gestational week to 1 year in age, were compared with the same structures from 21 age-matched control subjects without anomalies. The subjects with chromosomal aberrations had a significantly smaller volume of the lateral lamina (LL) of the ET cartilage, a reduced attachment of the tensor veli palatini muscle (TVPM), and, in some cases, a reduced volume of the lumen of the cartilaginous ET. The volume of the medial lamina (ML) of the ET cartilage was normal at birth, but smaller in specimens more than 2 months of age; this finding suggests that the prenatal development was normal, but that the postnatal growth was retarded. The subjects with chromosomal aberrations also displayed a smaller ratio of the volume of the LL to that of the ML (LL/ML ratio). Our results suggest that individuals with various chromosomal aberrations have rather similar anomalies of the ET and its associated structures. We speculate that these anomalies might be closely related to ET dysfunction in these patients.

Resonance imaging of the eustachian tube cartilage in microtia.

OBJECTIVE: The purpose of this study was to determine whether external and internal defects in microtia are related. METHOD: Magnetic resonance images of the eustachian tube cartilage were evaluated for 20 patients who had unilateral microtia. Nineteen patients were classified as Grade 2, and one was classified as Grade 3. The Grade 3 patient also had unilateral facial palsy. RESULTS: On T1-, T2-, and proton-density-weighted images, the eustachian tube cartilage was clearly identified as a pair of straight lines with low signal intensity. There was no evidence of hypoplasia of the eustachian tube cartilage on the microtic side in any Grade 2 patient, but hypoplasia was evident on the microtic side of the patient classified as Grade 3. CONCLUSION: These findings are consistent with the view that impairment of embryonic development before 6 weeks results in injury to the immature primordium and malformation of both the external and middle ear. In contrast, injuries that occur at a later fetal age (i.e., after 3 months) do not appear to cause middle ear malformations.

Conotruncal cardiac anomalies and otitis media.

BACKGROUND: The neural crest influences the differentiation of the branchial arches, including the precursor tissue of the cardiac outflow tract and the eustachian tubes. Abnormal eustachian tubes are associated with otitis media. We hypothesized a relationship between conotruncal anomalies and eustachian tube anomalies. METHODS: We surveyed 115 nonsyndromic patients, aged 5 to 20 years, attending a state-run pediatric cardiology clinic. The cardiac anomalies were conotruncal (transposition of the great arteries, tetralogy of Fallot, or aortic stenosis) or nonconotruncal (atrial septal defect, tricuspid atresia, atrioventricular canal). Tympanic membrane photographs were categorized independently by two physicians as to normal, abnormal (scarred or other indication of otitis proneness), or indeterminate. RESULTS: For the 37 patients who had both ears categorized as normal or abnormal by both physicians, 20 of the 26 with a conotruncal anomaly had evidence of otitis media. In contrast, only 4 of 11 with nonconotruncal cardiac anomaly had evidence of otitis (p < 0.03; relative risk [conotruncal vs nonconotruncal], 5.83; 95% confidence interval, 1.26 to 26.95). CONCLUSION: The concept is supported that a neural crest determined branchial field defect influences the development of the cardiac outflow tract and the eustachian tubes. Children with congenital cardiac conotruncal anomalies are otitis media prone.

Desarrollo del oído medio humano entre la 5a y la 17a semana de gestación / Human middle ear development between the 5th and the 17th week of pregnancy

Se realizó un estudio de la embriogénesis del oído medio humano entre la 5a y la 17a semana de gestación, utilizando 50 individuos (9 embriones y 41 fetos), los cuales fueron fijados, realizándose técnicas de tinción corrientes (hematoxilina-eosina), histoquímicas, tricrómicas e inmunohistoquímicas (anticuerpos monoclonales antilaminina, anticolágeno IV, antineurofilamentos). Seis fetos fueron procesados para microscopía electrónica de barrido, intentando obtener la mayor información posible del material humano. El análisis de los resultados reveló que el desarrollo del oído medio humano es mas tardío que el de los animales, distinguimos un crecimiento interesante de la tuba auditiva y como esta recubre a los huesecillos formando sus mesos, describimos la fijación de la platina del estribo a la pared medial de la caja timpánica en un período específico del desarrollo y la posterior formación, por muerte celular programada de la ventana oval y un nuevo pericondrio, hecho llamativo en la embriogénesis. En los embriones y fetos estudiados se describe la formación de nudos epidérmicos en la membrana timpánica (en su capa epitelial), dentro del desarrollo normal de esta estructura. Este hallazgo, no ha sido comunicado en la literatura. Con el conocimiento actual y el avance en la tecnología, se puede utilizar técnicas mas avanzadas de tinciones histológicas, inmunohistoquímicas y el uso de microscopio de barrido, para esclarecer las interrogantes del desarrollo del oído medio humano, agregando nueva información a lo tradicionalmente conocido

[The ultrastructure of the Eustachian tube].

To observe the ultrastructure of mucous membrane of Eustachian tube in human being, ninteen human's Eustachian tube from various ages, were divided into tympanic segment, isthmus and pharyngeal segment and observed under SEM. The results showed that the epithelium of Eustachian tube consisted of ciliated cells, nonciliated cells and goblet cells. At the isthmus, the bone and cartilage junction, the cells got crowded, and there were more and more goblet cells from tympanic side to pharyngeal side, as well as the cilia of ciliated cell leaned towards the pharyngeal side. The upper one third part of Eustachian tube was covered mostly by nonciliated cells, the floor and lower parts were ciliated cells. It was concluded that the upper parts of Eustachian tube's wall played an important role in maintaining equation of pressure in middle ear, and the floor and lower parts in providing an active mucociliary mechnism. The defence system of the Eustachian tube mucous membrane had developed during the fetal stage and was well established at birth.

Development of secretory elements in murine tubotympanum: lysozyme and lactoferrin immunohistochemistry.

Secretory activity, particularly of antibacterial agents such as lysozyme and lactoferrin, is an important aspect of the mucosal defense mechanism, and the development of these agents may have a direct bearing on the susceptibility of the ear to infection. In this study, the secretory cells of the murine tubal epithelium were first observed at gestational day 17. Although tubal glands began to develop on gestational day 18, their secretory activity was first shown on postnatal day 3. The number of secretory cells of the tubal epithelium increased rapidly immediately after birth, while that of the tubal glands showed a gradual increase from postnatal day 3. The epithelial secretory cells in the tubotympanum matured at birth, but the tubal glands matured gradually after birth. Lysozyme was first recognized in the epithelial secretory cells on postnatal day 1, while lactoferrin was first detected in the tubal glands on postnatal day 3. Both lysozyme and lactoferrin were co-localized in the serous cells of the tubal glands. The secretion of lysozyme and lactoferrin seemed to reflect the maturation of the secretory cells in the murine tubotympanum.

Luminal development of the eustachian tube and middle ear: murine model.

The purpose of this study was to describe the luminal development of the murine eustachian tube and middle ear. Thirty specimens, aging from gestational day 11 to postnatal day 21, were investigated through the light microscopic observations. The present study also used digitizer, computer, and serially sectioned temporal bone specimens for three-dimensional reconstruction to measure the volume of the eustachian tube and middle ear cavity at different gestational and postnatal ages. The first pharyngeal pouch elongated during gestational day 12 to form the tubotympanic recess. Between gestational day 13 and 14 this tubotympanic recess extended to the middle ear area. A rapid increment in the volume of the tubotympanic recess was noted between gestational day 15 and 16. At this age, a definite division of the tubotympanic recess into the eustachian tube and middle ear cavity was observed. During the postnatal period, the maximum change of the middle ear volume was noted on postnatal day 11 when the mesenchymal tissue in the middle ear cavity disappeared completely.

Development of the mucociliary system in the eustachian tube and middle ear: murine model.

In order to describe the developmental anatomy of the murine eustachian tube and its related structures, seventy six mice of ages ranging from gestational day 11 to postnatal day 21 were investigated through the light and electron microscopic observations. Development of the ciliated cells was seen concurrently in both the eustachian tube and middle ear on the 16 th gestation day, one day earlier than the epithelial secretory cells appeared in both the eustachian tube and middle ear. The number of ciliated cells and secretory cells increased rapidly after birth. Tubal glands were well identified with evidence of secretory activity around the time of birth. Thus, the findings of this study indicate that the mucociliary defense system starts to develop during the fetal stage and is well established immediately after birth.

Developmental anatomy of the eustachian tube and middle ear in mice.

PURPOSE: It is generally accepted that the development of the tubotympanum has significant bearing on the susceptibility to ear infection. A detailed study of the differentiation of ciliated cells in secretory elements will be useful in understanding both the normal physiology and the pathology of the tubotympanum. METHOD: Serially sectioned temporal bones of 76 mice ranging from gestational age day 11 to postnatal day 21 were examined microscopically. RESULTS: During the period of gestation, the tubotympanic recess was formed at the 12th day and began to extend to form the middle ear between the 13th and 14th days. A rapid increase in the volume of the tubotympanic recess was observed between the 15th and 16th days when a definitive division of the tubotympanic recess into the eustachian tube and middle ear cavity was observed. Postnatally the tubotympanum attained an adult form around day 9, and the maximum change of middle ear volume was noted on day 11, when the mesenchymal tissue in the middle ear cavity disappeared completely. Development of the ciliated cells was observed concurrently in both the eustachian tube and middle ear on the 16th gestational day, one day earlier than the appearance of the epithelial secretory cells in both the eustachian tube and middle ear. The number of ciliated cells and secretory cells increased rapidly after birth. Tubal glands were well developed with evidence of secretory activity around the time of birth. CONCLUSIONS: Based on these findings, one can conclude that the mucociliary defense system starts to develop during the fetal stage and is well established immediately after birth.

The embryologic development of the human external auditory meatus. Preliminary report.

During the final period of embryogenesis, a funnel-shaped tube continues medially into the mesenchymal tissue forming a curved path. Although this may sound simple, the development occurring during early fetal life is in fact very complex. At first, ectodermal cells proliferate to fill the lumen of the meatus, forming the meatal plug, and then at 10 weeks the bottom of the plug extends in a disc-like fashion, so that in the horizontal plane the meatus is boot-shaped with a narrow neck and the sole of the meatal plug spreading widely to form the future tympanic membrane medially. At the same time, the plug in the proximal portion of the neck starts to be resorbed. In the 13-week fetus, the disc-like plug begins to show signs of its final destiny; the innermost surface of the plug in contact with the anlage of the malleus is ready to contribute to the formation of the tympanic membrane. In the 15-week fetus, the innermost portion of the disc-like plug splits, leaving a thin ectodermal cell layer of immature tympanic membrane. The neck of the boot forms the border between the primary and secondary meatus, and is the last part to split. In the 16.5-week fetus, the meatus is fully patent throughout its entire length, although the lumen is still narrow and curved. In the 18-week fetus, the meatus is already fully expanded to its complete form.

Three-dimensional computer reconstruction of the eustachian tube and paratubal muscles.

A new method of anatomic dissection and image reconstruction using computer techniques for better understanding of eustachian tube (ET) functioning is presented. Coronal sections of two noncleft fetal skulls were photographed and projected on a graphic tablet. Contours of the pertinent structures were digitized using a mouse. Coordinates of all digitized points were entered into a special computer program. The data were transformed into three-dimensional representations of anatomic structures. The levator veli palatini muscle (M-LVP) was found to have a close relationship with the ET running underneath it and passing at the inside of the pharyngeal edge of the medial cartilage before entering the soft palate. On M-LVP contraction, this part of the medial ET cartilage appears to be the sole point of impact for ET opening. The tensor veli palatini muscle (M-TVP) is connected with the lateral cartilage of the ET and leaves the ET, rounding the pterygoid hamulus before entering the palatal aponeurosis. On this anatomic basis, action of the muscle by isotonic contraction appears to be more likely than isometric contraction.

Secondary cartilage in the auditory bulla of the hamster.

The auditory bulla, the bony capsule enclosing the middle ear, has been extensively studied in dry skulls and fossils, but detailed histological descriptions of the connective tissues involved are lacking. In rodents the membraneously ossified tympanic bone forms the major part of the enlarged auditory bulla. This study demonstrated fairly extensive secondary cartilage formation on the developing tympanic bone of the hamster. The first sign of the secondary cartilage was visible with Alcian blue staining on the 5th postnatal day. The amount of cartilage diminished after 15 days of age, but some cartilage was still present on the tympanic bone at the end of the observation period (25 days of age). While the secondary cartilage was present, a great amount of translative growth occurred in the bony coverage of the tympanic cavity, not only to accommodate the enchondrally growing cochlea within the cavity, but also to create space for the enlarged auditory bulla as an adaptation to low-frequency sensitivity in hearing. The tympanic bone is a derivative of the angular bone in the reptilian lower jaw. The mammalian mandible, a derivative of another membraneous bone of the reptilian lower jaw, the dentary, possesses secondary cartilages in the angular and condylar processes. Do the reptilian dentary and angular utilize secondary cartilage in the process of their transformation to the mammalian phylogenetic level?

Congenital cardiac outflow tract anomalies and otitis media.

The neural crest is involved in the differentiation of the cardiac outflow tract and branchial arches. Branchial arches one and two give rise to the eustachian tubes. Anatomically different eustachian tubes (e.g., short length) are found in persons prone to otitis media. We hypothesized a relationship between outflow tract anomalies and eustachian tube anomalies. The medical records of 238 children with a catheterization diagnosis of congenital heart disease were reviewed for otitis diagnoses. Children with syndromes known to be associated with recurring otitis media were excluded. Recurrent otitis media was recorded in 32.2% of those with outflow tract anomaly, significantly (P less than 0.03) higher than the 18.9% rate in children with a cardiac anomaly not involving the outflow tract. Neither race, sex, nor cyanosis seemed to account for the differing rates of otitis. These data may support the concept of a field defect arising from neural crest cells that influences the development of the cardiac outflow tract and eustachian tubes.

Evolution of the epidermoid formation and its role in the development of the middle ear and tympanic membrane during the first trimester.

In a study of 20 ears from embryos and early fetuses, 16 contained structures recognizable as precursors of the epidermoid formation (EF). The earliest were small, but later they took the form of a long epithelial bud which emanated from the tip of the tubotympanic recess or Eustachian tube. At a later stage still the EF protruded into the lumen of the Eustachian tube. The early formation of the tympanic membrane, the middle ear cavity and the osseous tympanic ring all take place in the vicinity of the EF precursor. It is possible that the EF precursor may act as an organizer, playing a prominent part in the migration of the first pharyngeal pouch towards the first branchial groove and the development of the middle ear and tympanic membrane.

Fetal development of the auditory tube and paratubal musculature.

The purpose of this study was to describe the prenatal development of the human auditory tube and paratubal musculature. Twenty prenatal specimens, 8 to 36 weeks of age postconception were embedded in celloidin, sectioned, and stained with hemotoxylin eosin. Qualitative data on the initial appearance and development were obtained using light microscopy (Plates I-VI). Linear and angular measurements were obtained from traced sections. The analysis showed the following: morphological differentiation of this area occurs between 8 and 16 weeks menstrual age; tubal structures develop in anterior-posterior and medial-lateral gradients; the tubal lumen of the perinatal fetus is cylindrical and lacks an isthmus; the allometric growth of the cartilaginous portion of the lumen between 16 and 28 weeks is responsible for the greatest increase in the tubal length during the fetal period.