[Infantile swallowing]. / Frühkindliches Schlucken.

BACKGROUND: Increasing numbers of preterm infants 1 and ever-improving potentials in neonatal medicine will lead to a rising incidence in infantile feeding problems. Profound knowledge regarding the development and anatomy of pre- and postnatal swallowing functions is essential for the assessment and therapy of infantile feeding and swallowing problems. METHOD: For this systematic review a selective literature research in PubMed has been carried out. RESULTS: Oropharyngeal structures and oral-motor skills for sucking and swallowing develop during embryonic and foetal stages and enable postnatal oral feeding. Knowledge of pre- and postnatal developmental stages of oral-motor development and swallowing serves as a base for the assessment of preterm infants' abilities and tolerance for feeding. A direct comparison of the swallowing process between infants, children and adults is not possible due to different anatomical characteristics. Developmental processes and neurologically triggered coordination procedures of early feeding skills are complex and very susceptible to faults. Disruption can cause severe disorders of swallowing coordination. Feeding problems are a common problem in preterm infants. Differentiated assessments on the basis of these results and early intervention facilitating oral-motor skills can accelerate the transition from tube to oral feeding and prevent further feeding issues.

Evolution of oropharyngeal patterning mechanisms involving Dlx and endothelins in vertebrates.

In jawed vertebrates, the Dlx code, or nested expression patterns of Dlx genes, specify the dorsoventral polarity of pharyngeal arches, downstream of endothelin-1 (Edn-1) and its effectors, Bapx1 (Nkx3.2) and dHand (Hand2). To elucidate the evolution of the specification mechanism of the oropharyngeal skeletal system, lamprey homologs of Dlx, Edn, endothelin receptor (Ednr), Bapx1, and dHand were identified. Our analysis suggested that the Edn gene family emerged at the advent of vertebrates, and that gene duplications leading to the different Edn gnathostome subtypes (Edn1-3) occurred before the cyclostome-gnathostome split. This timing of gene duplications, giving rise to multiple subtypes, was also implied for Dlx, Ednr, Hand, and Bapx. In lamprey embryos, nested expressions of Dlx genes were not observed in pharyngeal arches, nor was any focal expression of Bapx1, known in gnathostomes to specify the jaw joint. The dHand homolog, however, was expressed more intensively ventrally, as in gnathostomes. Lamprey homologs of Edn-1 and EdnrA were also shown to be expressed as described in mice, indicating involvement of this signaling pathway in the craniofacial patterning early in vertebrate evolution. These results suggest that the last common ancestor of all the extant vertebrates would have possessed basic gene repertoires involved in oropharyngeal patterning in gnathostomes, but the elaborate genetic program leading to the Dlx code is likely to have been acquired uniquely in gnathostomes.

Sex differences in prenatal oral-motor function and development.

The aim of this study was to investigate sex-related differences in the prenatal development of early oral, lingual, pharyngeal, and laryngeal motor activities. Sonographic images of oral-upper airway regions were observed in 85 healthy fetuses (43 males, 42 females; mean gestational age 24wks 3d [SD 0.69]; range 15-38wks). Biometric data on morphologic development and associated motor patterns were compared across second and third trimesters. Results showed that while males and females demonstrated statistically similar patterns of general physical growth (p>0.05), significant differences in development of specific lingual and pharyngeal structures were present (p<0.05). Significant differences were found for laryngeal and pharyngeal motor activity, and oral-lingual movements (p<0.05). Complex oral-motor and upper airway skills emerged earlier in females, suggesting a sex-specific trajectory of motor development. It was concluded that differential patterns of prenatal motor development may be important in defining sex-specific indices of oral skill maturation.

Persistent buccopharyngeal membrane in an adult.

Persistence of the buccopharyngeal membrane (BPM) also called the oropharyngeal membrane is a rare congenital oropharyngeal anomaly. We report a case of an adult aboriginal male patient with a membrane that closed his oropharyngeal isthmus except for a 2 cm diameter central perforation. The patient had no symptoms related to this membrane and no other congenital anomalies were found. This finding has not previously been reported in an adult. The embryology and management of this rare condition is discussed.

Gustatory neurons derived from epibranchial placodes are attracted to, and trophically supported by, taste bud-bearing endoderm in vitro.

Taste buds are multicellular receptor organs innervated by the VIIth, IXth, and Xth cranial nerves. In most vertebrates, taste buds differentiate after nerve fibers have reached the lingual epithelium, suggesting that nerves induce taste buds. However, under experimental conditions, taste buds of amphibians develop independently of innervation. Thus, rather than being induced by nerves, the developing taste periphery likely regulates ingrowing nerve fibers. To test this idea, we devised a culture approach using axolotl embryos. Gustatory neurons were generated from cultured epibranchial placodes, and when cultured alone, axon outgrowth was random over 4 days, a time period coincident with axon growth to the periphery in vivo. In contrast, cocultures of placodal neurons with oropharyngeal endoderm (OPE), the normal taste bud-containing target for these neurons, resulted in neurite growth toward the target tissue. Unexpectedly, placodal neurons also grew toward flank ectoderm (FE), which these neurons do not encounter in vivo. To compare further the impact of OPE and FE explants on gustatory neurons, cocultures were extended and examined at 6, 8, and 10 days, when, in vivo, placodal fibers have innervated the epithelium but prior to taste bud formation, when taste buds have differentiated and are innervated, and when the mouth has opened and larvae have begun to feed, respectively. The behavior of placodal axons with respect to target type did not differ between OPE and FE cocultures at 6 days. However, by 8 days, differences in axonal outgrowth were observed with respect to target type, and these differences were enhanced by 10 days in vitro. Most clearly, exuberant placodal fibers grew in 10-day OPE cocultures, and numerous neurites had invaded OPE explants by this time, whereas gustatory neurites were sparse in FE cocultures, and rarely approached and almost never contacted FE explants. Thus, embryonic endoderm destined to give rise to taste buds specifically attracts its innervation early in development, as placodal neurons send out axons. Later, when gustatory axons synapse with differentiated taste buds in vivo, the OPE provides trophic support for cultured gustatory neurons.

Emergence of oropharyngeal, laryngeal and swallowing activity in the developing fetal upper aerodigestive tract: an ultrasound evaluation.

The developing fetal upper aerodigestive system provides the structural support for respiratory and ingestive functions necessary to sustain life at birth. This study investigated prenatal development of upper aerodigestive anatomy and the association of emerging functions as predictors of postnatal feeding skills. Biometric measures of oral, lingual, pharyngeal and laryngeal structures were obtained in fetuses 15-38 weeks gestational age using a four-plane sonographic technique. Accompanying ingestive behaviors were tallied across development. The data from 62 healthy controls were compared to seven cases at risk for postnatal feeding and swallowing dysfunction (Type II Arnold Chiari Malformation, trisomy 18, polyhydramnios, intrauterine growth restriction, Brachmann-de Lange Syndrome). Significant (p<0.001) linear regressions occurred in pharyngeal and lingual growth across gestation while ingestive behavior such as suckling emerged in a sequence of basic to complex movement patterns. Jaw and lip movements progressed from simple mouth opening to repetitive open-close movements important for postnatal suckling. Lingual movements increased in complexity from simple forward thrusting and cupping to anterior-posterior motions necessary for successful suckling at term. Laryngeal movements varied from shallow flutter-like movements along the lumen to more complex and complete adduction-abduction patterns. Fetal swallowing primarily occurred in the presence of concomitant oral-facial stimulatory activity. Significant variations (p<0.01) in the form and function of the ingestive system occurred in comparisons of gestational age-matched controls to at-risk cases. We postulate that prenatal developmental indices of emerging aerodigestive skills may guide postnatal decisions for feeding readiness and, ultimately, advance the care of the premature, medically fragile neonate.

Widespread expression of tartrate-resistant acid phosphatase (Acp 5) in the mouse embryo.

Tartrate-resistant acid phosphatase (TRAP, Acp 5) is considered to be a marker of the osteoclast and studies using 'knockout' mice have demonstrated that TRAP is critical for normal development of the skeleton. To investigate the distribution of TRAP in the mammalian embryo, cryostat sections of 18 d murine fetuses were examined by in situ hybridisation, immunohistochemistry and histochemical reactions in situ. Abundant expression of TRAP mRNA was observed in the skin and epithelial surfaces of the tongue, oropharynx and gastrointestinal tract including the colon, as well as the thymus, ossifying skeleton and dental papillae. TRAP protein was identified at the same sites, but the level of expression in the different tissues did not always correlate with apparent enzyme activity. The findings indicate that abundant TRAP expression is not confined to osteoclasts in bone, but occurs in diverse tissues harbouring cells of bone marrow origin, including dendritic cells and other cells belonging to the osteoclast/macrophage lineage.

Role of endothelin in the human craniofacial morphogenesis.

Human craniofacial morphogenesis is a complex biological event: it is mediated by several factors and different types tissue interaction. Recent studies on animal models have led to an improved understanding of human craniofacial malformations. In particular, the endothelins, peptides that are involved in various biological functions in many tissues and organs, have been shown to play a crucial role in the development of the first branchial-arch-derived structures in mice [Kurihara et al., Nature 368:703-710, 1994]. We previously reported the identification and localization of endothelin-1 (ET-1) and its receptors in human fetal jaw [Barni et al., Dev Biol 168:373-377, 1995]. In the present study, the gene expression of ET-1 and its receptors were demonstrated in human jaw from 11-12-week-old fetuses. By using in situ hybridization, mRNA for ET-1 was localized in the epithelial cells of the oral mucosa: mRNA for ET receptors (ETA and ETB subtypes) was expressed in the mesenchyme. In situ binding experiments confirmed the presence of ETA and ETB receptors in the cells involved in the osteogenesis of the mandible. Furthermore, ET-1 was able to stimulate thymidine uptake and the expression of the oncoprotein c-fos in the same cell types. Our results indicate that ET-1 may play a putative role in epithelium-mesenchyme interaction during human craniofacial morphogenesis. Our findings are in complete accord with those of the most recent works by Yanagisawa [Yanagisawa H et al., 1998] and Clouthier [Clouthier et al., Development 125:813-824, 1998]. They most probably confirm the primary role of ET-1 in the development of the pharyngeal arches.

Persistent oropharyngeal membrane in a Hereford calf.

Persistent oropharyngeal membrane was found in a 6-day-old Hereford calf. The calf was unable to nurse and had not passed feces since birth. Physical examination revealed a fold of tissue spanning the caudal oral cavity, and a barium study demonstrated that food remained within the oral cavity despite a swallowing reflex. A thickened epiglottis was demonstrated radiographically but was not confirmed on necropsy. Necropsy revealed a complete soft-tissue partition between oral cavity and oropharynx with a central blind-ended diverticulum. Only a few cases of persistent oropharyngeal membrane have been reported previously, all in humans. This is the first report of this defect in domestic animals. Possible similarities to the more common persistent anal membrane are discussed.

Assessment of fetal breathing movements using three different ultrasound modalities.

Twenty-five consecutive women in the third trimester of pregnancy were studied to determine the presence or absence of fetal breathing movements using three different ultrasound imaging techniques. Using real-time B-mode observation of the fetal trunk as the standard, image-directed pulsed wave Doppler insonation of the umbilical vein confirmed the presence of breathing movements with a sensitivity of 100% and the absence of breathing movements with a specificity of 100%. The sensitivity and specificity of color Doppler imaging of the fetal naso- and oropharynx for the presence or absence of fetal breathing movements were 96% and 100%, respectively. In the current study, the detection of fetal breathing movements by three different ultrasound modalities was virtually interchangeable.

[The development of the human lingual tonsil in the prenatal period]. / Razvitie iazychnoi mindaliny cheloveka v prenatal'nom periode.

Morphofunctional regularities in the development of the lingual tonsil were examined in 120 human embryos and fetuses of gestation age of 5 weeks to 9 months with the use of a complex of histologic and injection methods and transmission electron microscopy. Lingual tonsil development was found to start at gestation age of 9 weeks. By the end of gestation period the lingual tonsil represents a complex of cryptolymphatic units, each of them consisting of cryptal epithelial wall, lymphoid parenchyma, and connective-tissue capsule. The role of postcapillary venules with parafollicular zone high endothelium of lingual tonsil follicles is discussed.

The development of the human brain, the closure of the caudal neuropore, and the beginning of secondary neurulation at stage 12.

Twenty-four embryos of stage 12 (26 days) were studied in detail and graphic reconstructions of five of them were prepared. The characteristic features of this stage are 21-29 pairs of somites, incipient or complete closure of the caudal neuropore, and the appearance of upper limb buds. The caudal neuropore closes during stage 12, generally when 25 somitic pairs are present. The site of final closure is at the level of future somite 31, which corresponds to the second sacral vertebral level. Non-closure of the neuropore may be important in the genesis of spina bifida aperta at low levels. The primitive streak probably persists until the caudal neuropore closes, when it is replaced by the caudal eminence or end-bud (Endwulst oder Rumpfknospe). The caudal eminence, which appears at stage 9, gives rise inter alia to hindgut, notochord, caudal somites, and the neural cord. The material for somites 30-34 (which appear in stage 13) is laid down during stage 12, and its absence would be expected to result in sacral agenesis. Aplasia of the caudal eminence results in cloacal deficiency and various degrees of symmelia. The junction of primary and secondary development (primäre und sekundäre Körperentwicklung) is probably at the site of final closure of the caudal neuropore. Secondary neurulation begins during stage 12. The cavity of the already formed spinal cord extends into the neural cord, and isolated spaces are not found within the neural cord. Primary and secondary neurulation are probably coextensive with primary and secondary development of the body, respectively. The telencephalon medium has enlarged, two mesencephalic segments (M1 and M2) are distinguishable, and rhombomere 4 is reduced. The sulcus limitans is detectable in the spinal cord and hindbrain (RhD), and in the mesencephalon and diencephalon, where it extends as far rostrally as the optic sulcus in D1. A marginal layer is appearing in the rhombencephalon and mesencephalon. The first nerve fibres are differentiating, chiefly within the hindbrain (from the nucleus of the lateral longitudinal tract). Optic neural crest is at its maximum, and the otic vesicle is giving crest cells to ganglion 7/8. Neural crest continues to develop in the brain and contributes to cranial ganglia 5, 7/8, and 10/11. The spinal crest extends as far caudally as somites 18-19 but shows no subdivision into ganglia yet. Placodal contribution to the trigeminal ganglion is not certain at stage 12. Such a contribution to ganglion 7/8 is not unlikely.(ABSTRACT TRUNCATED AT 400 WORDS)

The first appearance of the neural tube and optic primordium in the human embryo at stage 10.

Thirteen embryos of stage 10 (22 days) were studied in detail and graphic reconstructions of most of them were prepared. The characteristic feature of this stage is 4-12 pairs of somites. Constantly present are the prechordal and notochordal plates (the notochord sensu stricto is not yet apparent), the neurenteric canal or at least its site, the thyroid primordium, probably the mesencephalic and rhombencephalic neural crest and the adenohypophysial primordium. During this stage, the following features appear: terminal notch, optic sulcus, initial formation of neural tube, oropharyngeal membrane, pulmonary primordium, cardiac loop, aortic arches 1-3, intersegmental arteries, and laryngotracheal groove. The primitive streak is still an important feature. Graphic reconstructions have permitted the detection of the telencephalic portion of the forebrain, for the first time at such an early stage. It is proposed that the remainder of the forebrain comprises two subdivisions: D1, which becomes largely the optic primordium during stage 10, and D2, which is the future thalamic region. The optic sulcus is found in D1 but does not extent into D2, as has been claimed in the literature. An indication of invagination of the otic disc appears towards the end of the stage. As compared with the previous stage, the prosencephalon has increased in length, the mesencephalon has remained the same, the rhombencephalon has decreased, and the spinal part of the neural plate has increased fivefold in length. The site of the initial closure of the neural groove is rhombencephalic, upper cervical, or both. The neural plate extends caudally beyond the site of the neurenteric canal. Cytoplasmic inclusions believed to indicate locations of great activity were always detected in the forebrain (especially in the optic primordium), and also in the rhombencephalon, spinal part, and mesencephalon.

[Oropharyngeal lymphoid tissue as a bursa-equivalent structure: embryological and clinical considerations]. / Il tessuto linfoide orofaringeo come struttura borsa-equivalente: considerazioni embriologiche e cliniche.

If we examine with an ontogenetic viewpoint the tissues giving origin to both thymus and avian bursa of Fabricius, we can't ignore that they are primary lymphoid organs connected to areas of ecto-entodermic junctions. They have a strong development in the embryonic life while tending to regress in the adult. The analysis of the organogenesis clarifies this affirmation. In the human cephalic district we know of various ectoentodermic stratification areas: the branchial pockets and the Remake pharyngeal membrane. The oral-pharyngeal lymphoid tissue is histogenetically linked to the stem-cells of the marrow which migrate to occupy an initially ecto-entodermic milieu. Structural and ontogenetic analogies of embryological nature lead to an identification of the oral-pharyngeal lymphoid tissue in man with the avian bursa of Fabricius. Therefore we deem it very indicative that a humoral immunological deficiency syndrome appears in subjects with the atrophy of the Waldeyer ring; above all considering that an experimental model of the humoral immunological deficit has been reproduced in chicken surgically or hormonally bursectomized.

Indirect immunofluorescent staining of fibronectin associated with the floor of the foregut during formation and rupture of the oral membrane in the chick embryo.

The distribution of the glycoprotein, fibronectin, within the cranial region of stage 8--16 chick embryos was examined by indirect immunofluorescence using paraffin sections exposed to affinity-purified rabbit anti-human CIG and FITC-conjugated goat anti-rabbit immunoglobulins. Fluorescence was present within the matrix surrounding the cranial mesenchyme, along the basal surfaces of all epithelia, and surrounding the notochord at all stages. Fluorescence associated with the floor of the foregut was particularly intense. The fluorescent layers beneath the ectoderm and endoderm of the oral (oropharyngeal) membrane at stage 8 merged into a single, continuous, intensely fluorescent line as the extracellular space within the oral membrane narrowed during stages 9--12. This line of uniform fluorescence parallels the previously described histological reorganization of the extracellular compartment of the oral membrane, but the ultrastructural localization of this fluorescent material remains unknown. Fluorescence was also intense beneath the foregut endoderm in the presumptive cardiac region caudal to the oral membrane and was continuous with strands of fluorescent material extending into the matrix of the dorsal mesocardium and cardiac jelly of the developing tubular heart. These observations indicate that the extracellular matrix associated with the floor of the entire foregut contains fibronectin during stages encompassing the formation and rupture of the oral membrane. The presence of fibronectin within the oral membrane and dorsal mesocardium, as well as between Rathke's pouch and infundibulum and within the closing plates between ectodermal clefts and endodermal pouches, is consistent with the possibility that this glycoprotein may play a role in adhesion at these sites.

[Odontostomatogenic focal disease; embryologic and clinical causes of autoimmune pathogenesis]. / La malattia focale odontostomatogena; motivazioni embriologiche e cliniche della patogenesi autoimmune.

The autoimmune pathogenesis of the focal odontostomatogenous disease is investigated and emphasis is laid on the different keys of interpretation: at embryologic, clinic and immunologic level. A special attention is paid to the primary meaning of structured or non structured lymphoid tissue of oropharynx, on account of embryologic identity with thymus and bursa of Fabricius, differentiating into sectors of ecto-entodermic stratification. The clinical evidence of the bursa-equivalent significance of Waldeyer ring, appears to lie in the ascertainment of the tonsillar atrophy in course of agammaglobulinaemia of Bruton type. The active chronic irritant phlogistic stimulus in a primary structure could excite the normal production of intolerant clones, so as to exceed the normal physiological homeostasis (giving rise to the autoimmune disease), or alter the mosiac self, inducing a production of autoantibodies.