Facial skeletal expansion: treatment strategies and rationale.

Forty-three nonconsecutive patients presenting with dentofacial deformity underwent surgical procedures designed intentionally to create skeletal disproportion in the sagittal and/or vertical dimensions. This was accomplished through expansion (enlargement) of the facial skeleton beyond normative standards. At the time of follow-up, which ranged from 14 to 36 months (mean 18.4 months), soft-tissue cephalometric analyses documented facial disproportion to exist in 37 of the 43 patients treated. Thirty-two patients had excessive anterior divergence (facial protrusion) at pogonion, and 17 patients had excessive lower face height as measured from subnasale to menton. All patients were judged to have had a favorable aesthetic outcome. This philosophy of facial skeletal expansion is predicated on two concepts: The first of these is that facial proportions and dimensions beyond those which are considered normal may be extremely attractive in a given individual. Second, the soft-tissue response to skeletal expansion is more favorable and predictable than it is to skeletal contraction in providing for well-supported soft tissues. This treatment planning approach is based on the dynamic interrelationship between the skeletal foundation and the soft-tissue facial mask. It relies on physical examination as the major determinant of aesthetic surgical options.     

Branchial innervation

Inspection of the dorsal end of fish gills reveals an impressive set of nerve trunks, connecting the gills to the brain. These trunks are branches of cranial nerves VII (the facial) and especially IX (the glossopharyngeal) and X (the vagus). The nerve trunks carry a variety of nervous pathways to and from the gills. A substantial fraction of the nerves running in the branchial trunks carry afferent (sensory) information from receptors within the gills. There are also efferent (motor) pathways, which control muscles within the gills, blood flow patterns and possibly secretory functions. Undertaking a more careful survey of the gills, it becomes evident that the arrangement of the microanatomy (particularly the blood vessels) and its innervation are strikingly complex. The complexity not only reflects the many functions of the gills but also illustrates that the control of blood flow patterns in the gills is of crucial importance in modifying the efficiency of its chief functions: gas transfer and salt balance. The "respiratory-osmoregulatory compromise" is maintained by minimizing the blood/water exchange (functional surface area of the gills) to a level where excessive water loss (marine teleosts) or gain (freshwater teleosts) is kept low while ensuring sufficient gas exchange. This review describes the arrangement and mechanisms of known nervous pathways, both afferent and efferent, of fish (notably teleosts) gills. Emphasis is placed primarily on the autonomic nervous system and mechanisms of blood flow control, together with an outline of the afferent (sensory) pathways of the gill arches.     

Effects of retinoic acid on the development of the facial skeleton in hamsters: early changes involving cranial neural crest cells

Treatment of gravid hamsters with 60/mg of retinoic acid on the 8th day of pregnancy resulted in facial skeleton defects in 100% of the survivors examined by alizarin staining at term. An investigation of the early stages in the development of these malformations indicated that the teratogen induced delayed and disorganized patterns of cranial neural crest cell migration as well as extensive death and damage of crest cells. The results demonstrate that retinoic acid provides a useful tool for studies in the pathogenesis of facial skeletal abnormalities in vivo. Moreover, the extensive defects seen in the teratogen-treated litters at term, together with the results of the microscopical analyses, support the hypothesis that cranial neural crest cells make an important contribution to the development of the mammalian facial skeleton.     

Roentgencephalometric measurements in trisomy 8 mosaicism: report of three cases

Roentgencephalometric anomalies in three cases of Warkany syndrome (trisomy 8 mosaicism) are described. These include asymmetry of the mandible with a wide gonial angle and a high and narrow symphysis; SNA (anteroposterior position of maxilla) and SNB (anteroposterior position of mandible) values indicate a backward position of the mandible. Other findings point to a disturbance in the vertical growth of the facial skeleton. These measurements may explain at least part of the facial phenotype and may aid in diagnosis, especially in those cases with an uncertain clinical diagnosis and "normal" karyotype in peripheral blood lymphocytes.     

Sexual Dimorphism and Facial Growth Beyond Dental Maturity in Great Apes and Gibbons

The great apes and gibbons are characterized by extensive variation in degree of body size and cranial dimorphism, but although some studies have investigated how sexual dimorphism in body mass is attained in these species, for the majority of taxa concerned, no corresponding work has explored the full extent of how sexual dimorphism is attained in the facial skeleton. In addition, most studies of sexual dimorphism combine dentally mature individuals into a single “adult” category, thereby assuming that no substantial changes in size or dimorphism take place after dental maturity. We investigated degree and pattern of male and female facial growth in Pan troglodytes troglodytes, Pan paniscus, Gorilla gorilla gorilla, Pongo pygmaeus, and Hylobates lar after dental maturity through cross-sectional analyses of linear measurements and geometric mean values of the facial skeleton and age-ranking of individuals based on molar occlusal wear. Results show that overall facial size continues to increase after dental maturity is reached in males and females of Gorilla gorilla gorilla and Pongo pygmaeus, as well as in the females of Hylobates lar. In male Pongo pygmaeus, adult growth patterns imply the presence of a secondary growth spurt in craniofacial dimensions. There is suggestive evidence of growth beyond dental maturity in the females of Pan troglodytes troglodytes and Pan paniscus, but not in the males of those species. The results show the presence of statistically significant facial size dimorphism in young adults of Pan paniscus and Hylobates lar, and of near statistical significance in Pan troglodytes troglodytes, but not in older adults of those species; adults of Gorilla gorilla gorilla and Pongo pygmaeus are sexually dimorphic at all ages after dental maturity. The presence of sex-specific growth patterns in these hominoid taxa indicates a complex relationship between socioecological selective pressures and growth of the facial skeleton.     

Maxillary advancement for mandibular prognathism: indications and rationale

The surgical correction of mandibular prognathism has traditionally involved posterior repositioning of the mandibular body. This treatment approach corrects the skeletal disproportion at the expense of reducing facial skeletal volume and can unpredictably result in inadequately supported soft tissues with loss of skeletal definition. In an effort to avoid these sequelae of mandibular reduction, 18 patients diagnosed as having mandibular prognathism were treated with maxillary advancement surgery at the Le Fort I level. Mean patient SNB angle was 85.2 degrees, as compared with a normal 79 +/- 3 degrees. Maxillae were documented to be in normal position relative to both cranial base and Frankfort horizontal. The mean maxillary advancement was 6.9 mm, with a range of 4.5 to 8.8 mm. All patients required genioplasty to reduce vertical chin height and/or to laterally shift the chin. At the time of follow-up (mean 16.2 months), all patients retained cephalometric data suggestive of enlarged mandibles and excessive anterior facial divergence. However, maxillomandibular harmony and facial convexity had been restored without sacrificing skeletal volume. Treatment results demonstrated these faces to be skeletally well proportioned despite lower face protrusion that was beyond "normal." Postoperative appearances were characterized by a well-supported soft-tissue envelope and a highlighted skeletal foundation, creating angular, well-defined lower faces. These findings support the credibility of maxillary advancement as the procedure of choice in selected individuals with mandibular prognathism. Indications and an aesthetic rationale for this surgical approach are presented.     

The role of GDNF/Ret signaling in ureteric bud cell fate and branching morphogenesis

While GDNF signaling through the Ret receptor is critical for kidney development, its specific role in branching morphogenesis of the epithelial ureteric bud (UB) is unclear. Ret expression defines a population of UB "tip cells" distinct from cells of the tubular "trunks," but how these cells contribute to UB growth is unknown. We have used time-lapse mosaic analysis to investigate normal cell fates within the growing UB and the developmental potential of cells lacking Ret. We found that normal tip cells are bipotential, contributing to both tips and trunks. Cells lacking Ret are specifically excluded from the tips, although they contribute to the trunks, revealing that the tips form and expand by GDNF-driven cell proliferation. Surprisingly, the mutant cells assumed an asymmetric distribution in the UB trunks, suggesting a model of branching in which the epithelium of the tip and the adjacent trunk is remodeled to form new branches.     

Reorganization of the nervous system during regeneration in Dugesia tigrina]

The normal structure of the nervous system in Dugesia tigrina Girard and the total morphodynamics of the nervous system during regeneration have been studied by means of choline esterase assay. The nervous system reacts to local damages of the planarian body; accumulations of nervous elements form in the wound region. Following the transverse cut of a planarian, the regeneration of the nervous system is not reduced to the completion of lacking parts. In this case (as well as in that of asexual reproduction) the nervous system manifests a considerable morphological lability and undergoes morphological rearrangements accompanied by the appearance of additional, frequently unpaired, nerve trunks. The data obtained are to be taken into account in neurobiological studies on planarians.     

FGF/FGFR signaling coordinates skull development by modulating magnitude of morphological integration: evidence from Apert syndrome mouse models

The fibroblast growth factor and receptor system (FGF/FGFR) mediates cell communication and pattern formation in many tissue types (e.g., osseous, nervous, vascular). In those craniosynostosis syndromes caused by FGFR1-3 mutations, alteration of signaling in the FGF/FGFR system leads to dysmorphology of the skull, brain and limbs, among other organs. Since this molecular pathway is widely expressed throughout head development, we explore whether and how two specific mutations on Fgfr2 causing Apert syndrome in humans affect the pattern and level of integration between the facial skeleton and the neurocranium using inbred Apert syndrome mouse models Fgfr2(+/S252W) and Fgfr2(+/P253R) and their non-mutant littermates at P0. Skull morphological integration (MI), which can reflect developmental interactions among traits by measuring the intensity of statistical associations among them, was assessed using data from microCT images of the skull of Apert syndrome mouse models and 3D geometric morphometric methods. Our results show that mutant Apert syndrome mice share the general pattern of MI with their non-mutant littermates, but the magnitude of integration between and within the facial skeleton and the neurocranium is increased, especially in Fgfr2(+/S252W) mice. This indicates that although Fgfr2 mutations do not disrupt skull MI, FGF/FGFR signaling is a covariance-generating process in skull development that acts as a global factor modulating the intensity of MI. As this pathway evolved early in vertebrate evolution, it may have played a significant role in establishing the patterns of skull MI and coordinating proper skull development.     

不同垂直骨面型错合畸形患者颈椎姿势差异的研究

目的:研究不同垂直骨面型错合畸形患者颈椎姿势的特点及差异,为正畸矫治错合畸形获得较好的临床效果及颅面、颈部生长发育的研究提供一定的参考依据。方法:采用计算机辅助X线头影测量技术,对226例不同垂直骨面型的儿童、成人在自然头位时拍摄的头颅定位侧位片进行测量研究,分别比较儿童以及成人不同垂直骨面型间颈椎姿势的差异。结果:儿童:CVT-OPT、SN-CP、SN-OPT及SN-CVT在低、均、高角各组间的差别均无统计学意义。成人:CVT-OPT在低角组与高角组间、均角组与高角组间的差别有统计学意义,高角组低于低角组和均角组,在低角组与均角组间的差别无统计学意义;SN-CP在低、均、高角各组间的差别有统计学意义,低角组<均角组<高角组;SN-OPT及SN-CVT在低角组与高角组间的差别有统计学意义,低角组<高角组,在低角组与均角组间、均角组与高角组间的差别无统计学意义。结论:不同垂直骨面型错合畸形患者的颈椎姿势在儿童无显著差异,在成人差异显著。     

Craniofacial suture stenosis: morphologic effects

Craniofacial anomalies, such as Apert's and Crouzon's syndromes, are presumed to be related to premature growth arrest of cranial base growth sites. However, premature growth arrest at cranial vault sutures in animals appears to play a causative role in the development of cranial deformities characteristic of single-suture, or simple, craniosynostosis in humans. To study the possible causative role of cranial vault and other (interface) suture stenoses on the development of craniofacial deformity, a vault suture and an interface suture between the cranial vault and facial skeleton were simultaneously immobilized. Thirty-one New Zealand White rabbits at 9 days of age underwent implantation of dental amalgam growth markers adjacent to cranial vault and facial sutures. In the experimental group (n = 15), methylcyanoacrylate adhesive was applied over the coronal (vault) and frontonasal (interface suture between vault and facial skeleton) sutures to immobilize them. The remaining 16 animals served as sham-treated controls. All animals underwent serial radiographic cephalometry to document growth effects in the cranial vault, cranial base, and facial skeleton. Application of adhesive resulted in statistically significant (p less than 0.05) reduction in growth at the coronal and frontonasal sutures. This was accompanied by an overall significant reduction in neurocranial vault length during the first 30 days of development.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pathogenesis of median facial clefts in mice treated with methotrexate

Methotrexate (MTX), administered as a single 20 mg/kg intraperitoneal dose to C57Bl/6J mice on their 9th day of pregnancy results in high incidences of median facial clefts in the surviving gestational-day-18 fetuses. We have shown the presence of dilated and congested blood vessels in the frontonasal prominences (FNP) of embryos from treated mothers as early as 3 hours following drug administration. Within 24 hours, large vascular blebs are located in the FNP and the neural tubes appear somewhat distended. By 32 hours after treatment, distention of the neural tube is marked while blebs have become less evident. Subsequent to these changes, FNP mesenchymal deficiency as well as neural tube distention lead to the formation of median facial clefts. It is hypothesized that, as with a number of other teratogenic agents (especially hypoxia), initial fluid imbalance is the primary teratogenic insult.     

Morphodynamics of the nervous system in the regenerative processes of Convoluta convoluta (Turbellaria, Acoela)]

By means of the method for revealing cholinesterases the alterations in the nervous system of Convoluta convoluta after mechanical lesion were studied. After a transversal transection of the animal into two pieces the anterior part of the body acquired the normal form within 3-4 days; the nervous system underwent inconsiderable transformations associated with a formation of a plexus in the injured area. The posterior parts of the body regenerated slowly. During the first days disintegration of the resting parts of the nervous system was observed. Later on the diffuse cholinesterase activity suggesting the beginning of the brain formation was manifested in the wound field. Plexus strands "grow" in the caudal direction from the brain in parallel with its development. Within three weeks the nervous system of the animals which had restored their mouth opening, body shape and normal behaviour consists of the brain and plexus not arranged in nervous trunks. The reaction of the nervous system to the ablation of a part of the brain and to a continuous mechanical injury were studied. The data obtained show a high morphological lability of the nervous system of Convoluta convoluta, its ability to radical structural rearrangements.     

Amidic modification of valproic acid reduces skeletal teratogenicity in mice

BACKGROUND: The antiepileptic drug valproic acid (VPA) is well known to cause neural tube and skeletal defects in both humans and animals. The amidic VPA analogues valpromide (VPD) and valnoctamide (VCD) have much lower teratogenicity than VPA inducing exencephaly in mice. The objective of this study was to investigate the teratogenic effects of VPA, VPD, and VCD on the skeleton of NMRI mice. METHODS: Pregnant NMRI mice were given a single subcutaneous injection of VPA (400 and 800 mg/kg), VPD (800 mg/kg), or VCD (800 mg/kg) on the morning of gestation day (GD) 8. Cesarean section was carried out on GD 18. Live fetuses were double‐stained for bone and cartilage and their skeletons were examined. RESULTS: Significant increases in fetal loss and exencephaly rate were observed with VPA at 800 mg/kg compared to the vehicle control. There were no significant differences between either VPD or VCD and the control groups for any parameter at cesarean section. A number of abnormalities were dose‐dependently induced at high incidences by VPA in both the cartilage and bone of vertebrae, ribs and sternum. In contrast, lower frequencies of abnormality were exhibited with VPD and VCD than VPA in all skeletons affected by VPA. CONCLUSIONS: These findings clearly indicate that VPD and VCD are distinctly less teratogenic than VPA in the induction of not only neural tube defects, but also skeletal abnormalities. A structure‐teratogenicity relationship of VPA on the skeleton is suspected. Birth Defects Res B 71:47–53, 2004. © 2004 Wiley‐Liss, Inc.     

Development of Some Elements of the Peripheral Nervous System of the Locust Locusta migratoria during Larval Ontogenesis

Using supravital Methylene blue staining, development of elements of the peripheral nervous system was traced in the 1st–5th instar larvae of the locust Locusta migratoria L. Data were obtained on sensory cells of the I and II types in larvae of different instars, as well as on character of their changes in the course of larval development of the insect. The studied elements of the peripheral nervous system have been shown to be essentially transformed in the course of larval ontogenesis. The data are presented about the sensory cells of the proximal parts of the nerve trunks; they indicate that in the course of larvae development the cell number in these trunks near the ganglia of the nerve chain decreases, which might be due to their partial degeneration. With growth of muscle, changes in their sensory innervation take place. Subepithelial nerve plexus in larvae is largely represented in areas with hard and soft cuticles.     

Histochemical study of jaw muscle fibers in the American alligator (Alligator mississippiensis)

The ontogenetic development of caudal vertebrae and associated skeletal elements of salmonids provides information about sequence of ossification and origin of bones that can be considered as a model for other teleosts. The ossification of elements forming the caudal skeleton follows the same sequence, independent of size and age at first appearance. Dermal bones like principal caudal rays ossify earlier than chondral bones; among dermal bones, the middle principal caudal rays ossify before the ventral and dorsal ones. Among chondral bones, the ventral hypural 1 and parhypural ossify first, followed by hypural 2 and by the ventral spine of preural centrum 2. The ossification of the dorsal chondral elements starts later than that of ventral ones. Three elements participate in the formation of a caudal vertebra: paired basidorsal and basiventral arcocentra, chordacentrum, and autocentrum; appearance of cartilaginous arcocentra precedes that of the mineralized basiventral chordacentrum, and that of the perichordal ossification of the autocentrum. Each ural centrum is mainly formed by arcocentral and chordacentrum. The autocentrum is irregularly present or absent. Some ural centra are formed only by a chordacentrum. This pattern of vertebral formation characterizes basal teleosts and primitive extant teleosts such as elopomorphs, osteoglossomorphs, and salmonids. The diural caudal skeleton is redefined as having two independent ural chordacentra plus their arcocentra, or two ural chordacentra plus their autocentra and arococentra, or only two ural chordacentra. A polyural caudal skeleton is identified by more than two ural centra, variably formed as given for the diural condition. The two ural centra of primitive teleosts may result from early fusion of ural centra 1 and 2 and of ural centra 3 and 4, or 3, 4, and 5 (e.g., elopomorphs), respectively. The two centra may corespond to ural centrum 2 and 4 only (e.g., salmonids). Additionally, ural centra 1 and 3 may be lost during the evolution of teleosts. Additional ural centra form late in ontogeny in advanced salmonids, resulting in a secondary polyural caudal skeleton. The hypural, which is a haemal spine of a ural centrum, results by growth and ossification of a single basiventral ural arococentrum and its haemal spine. The proximal part of the hypural always includes part of the ventral ural arcocentrum. The uroneural is a modification of a ural neural arch, which is demonstrated by a cartilaginous precursor. The stegural of salmonids and esocids originates from only one paired cartilaginous dorsal arcocentrum that grows anteriorly by a perichondral basal ossification and an anterodorsal membranous ossification. The true epurals of teleosts are detached neural spines of preural and ural neural arches as shown by developmental series; they are homologous to the neural spines of anterior vertebrae. Free epurals without any indication of connection with the dorsal arococentra are considered herein as an advanced state of the epural. Caudal distal radials originate from the cartilaginous distal portion of neural and haemal spines of preural and ural (epurals and hypurals) vertebrae. Therefore, they result from distal growth of the cartilaginous spines and hypurals. Cartilaginous plates that support rays are the result of modifications of the plates of connective tissue at the posterior end of hypurals (e.g., between hypurals 2 and 3 in salmonids) and first preural haemal spines, or from the distal growth of cartilaginous spines (e.g., epural plates in Thymallus). Among salmonids, conditions of the caudal skeleton such as the progressive loss of cartilaginous portions of the arcocentra, the progressive fusion between the perichondral ossification of arcocentra and autocentra, the broadening of the neural spines, the enlargement and interdigitation of the stegural, and other features provide evidence that Prosopium and Thymallus are the most primitive, and that Oncorhynchus and Salmo are the most advanced salmonids respectively. This interpretation supports the current hypothesis of phylogenetic relationships of salmonids. © 1992 Wiley-Liss, Inc.     

Growth of the skull in the mutant dwarf mouse

By following the development of individual mice from birth to 200 days of age, it was found that the skull of the homozygous mutant (dwdw) was 5% shorter than that of the normal phenotype at birth and some 30% shorter at 200 days of age. During post-natal growth of the skull, the cranium was least altered but the facial skeleton was greatly affected. The differences seen in different parts of the skull are attributed to the peak growth velocities of the various parts occurring at different times.     

Experimental studies on reproductive toxicologic effects of lamotrigine in mice

BACKGROUND: Virtually all antiepileptic drugs (AED) tested so far have been found to be teratogenic. The second generation AED possess a number of therapeutic advantages over the older ones. There are, however, very little data on their effects on embryonic development. A recent report suggests that lamotrigine (LTG) can be teratogenic to human fetuses. With only a few cases of prenatal exposure to LTG in the record, however, it has not been possible to establish a recognizable pattern of malformations in the infants of LTG‐treated mothers. OBJECTIVES: The objectives of the present study were to evaluate the reproductive toxic effects of LTG RESULTS: Single (50–200 mg/kg) or multiple doses (25, 50, 75 mg/kg) of LTG were administered by intraperitoneal (i.p.) injection (note that the therapeutic administration is oral) to groups of TO mice on gestation day (GD) 7 or 8. Fetuses were collected on GD 18. Maternal toxic effects including a dose‐related mortality, a high incidence of abortion, embryo lethality, congenital malformations and intrauterine growth retardation (IUGR) were observed in the LTG‐treated group. Administration of LTG in multiple low doses resulted in a better maternal survival and increased incidence of embryonic resorption and malformations with increasing dose; IUGR was significant but not dose‐dependent. The malformations characteristic of the LTG multiple low dose group fetuses included maxillary‐mandibular hypoplasia, exencephaly, cleft palate, median facial cleft, urogenital anomalies and varying degrees of caudal regression. Skeletal malformations and developmental delay of the skeleton were observed both in single and multiple dose groups. CONCLUSIONS: The results of this study indicate that LTG administered i.p. at high doses can induce intrauterine growth retardation and at low multiple doses causes a dose‐dependent increase in embryonic resorption, craniofacial and caudal malformations as well as maternal toxicity in the mouse. Previous studies in other laboratories have used oral route of exposure and concluded that there are no teratogenic effects of LTG at dose levels that are not maternally toxic. Birth Defects Res B 68:428–438, 2003. © 2003 Wiley‐Liss, Inc.     

日本血吸虫胆碱酯酶的组织化学定位

血吸虫的胆碱酯酶(ChE)与血吸虫神经介质的传递、肌肉活动以及与其它物质代谢均有密切关系,也是抗血吸虫药物作用的靶子之一。1959年沈美玲等进行了药物对日本血吸虫乙酰胆碱酯酶(AChE)活力的研究。最近,姚民一等(1981)采用等电聚焦电泳分离出日本血吸虫胆碱酯酶的同功酶。然而有关血吸虫胆碱酯酶的组织化学定位研究主要限于曼氏血吸虫(Pepler,1958;Lewert等,1965;Fripp,1967;Bueding等,1967;Bruckner等,1974;Diconza等,1975)除Bueding简单述及日本血吸虫成虫的AChE外,迄今国内外尚无日本血吸虫CbE的组化资料,而且日本血吸虫的神经系统也未被专门观察。由于ChE的组化定位能细致地显示出血吸虫的神经系统构造,并能进一步提