Cleft palate is a common human birth defect caused by any process which interferes with palatogenesis. Studies in Hoxa2 mutant (Hoxa2-/-) mice which exhibit a secondary cleft palate were reported to be due to an abnormal positioning of the tongue which prevents normal palatal shelf fusion to occur. To obtain direct evidence for the importance of Hoxa2 in murine palate development, an in vitro whole organ palatal culture model was developed, eliminating any influences from the tongue. A retroviral gene delivery system was employed, containing either Hoxa2 sense or Hoxa2 antisense cDNA, to respectively enhance or knockdown the expression of Hoxa2 mRNA in the developing palate. <p>Our results show that palatal cultures infected with the lowest titer of Hoxa2 sense virus induce a fusion rate of 72.7%, which is similar to palatal cultures treated with the control virus (81.8%), although fusion rates of 41.2% to 50.0% were observed in palates infected with higher titers. With the antisense virus treated group, a more profound inhibition of the fusion rate was observed (27.7% - 46.1%), which is comparable with the frequency of palatal fusion in Hoxa2-/- mice (44.4%). Additionally, the palatal shelves in both sense and antisense virus treated groups appear to be relatively shorter in length, than those measured in the control group. Interestingly, in the antisense virus treated group, the ratio of the length of the fused portion to the length of palatal shelves appears to be relatively large compared to the control group. Verification and quantification of Hoxa2 mRNA in the developing palate between E12.5 and E15.5 was performed by real-time RT-PCR. Hoxa2 gene expression was observed at all stages studied, with expression being the highest at E12.5 and declining from E13.5. The expression level remained constant from E13.5 through E15.5. These findings demonstrate for the first time that Hoxa2 may play a direct role in murine palate development. Results suggest that both factors (the absence of Hoxa2 gene in the palate causing delayed palatal development, as well as the position of the tongue) appear to act in unison to produce cleft palate in Hoxa2 knockout mice.

The purpose of this study was to evaluate the burden of care (BOC) of two presurgical infant orthopedic (PSIO) protocols used for complete unilateral cleft lip and palate (CUCLP), and to compare aesthetic outcomes with centres not utilizing PSIO. Four samples were collected. Two from the same centre that underwent either traditional infant orthopedics (TIO) or nasoalveolar molding (NAM) and two from centres not employing PSIO. BOC data were collected for the PSIO groups and photos at age 5 were collected for ratings of nasolabial aesthetics. The BOC of NAM was found to be significantly greater than IO for number of visits (9.9 vs. 6.6, (p<0.001)) and days wearing the appliance (127 vs. 112, (p<0.05)). Significant differences in aesthetic ratings were noted amongst the three centres but not between the NAM and TIO groups. Overall, an increased burden of NAM over TIO was detected, without an observable aesthetic improvement.

The purpose of this study was to evaluate the burden of care (BOC) of two presurgical infant orthopedic (PSIO) protocols used for complete unilateral cleft lip and palate (CUCLP), and to compare aesthetic outcomes with centres not utilizing PSIO. Four samples were collected. Two from the same centre that underwent either traditional infant orthopedics (TIO) or nasoalveolar molding (NAM) and two from centres not employing PSIO. BOC data were collected for the PSIO groups and photos at age 5 were collected for ratings of nasolabial aesthetics. The BOC of NAM was found to be significantly greater than IO for number of visits (9.9 vs. 6.6, (p<0.001)) and days wearing the appliance (127 vs. 112, (p<0.05)). Significant differences in aesthetic ratings were noted amongst the three centres but not between the NAM and TIO groups. Overall, an increased burden of NAM over TIO was detected, without an observable aesthetic improvement.

Cleft palate is a common human birth defect caused by any process which interferes with palatogenesis. Studies in Hoxa2 mutant (Hoxa2-/-) mice which exhibit a secondary cleft palate were reported to be due to an abnormal positioning of the tongue which prevents normal palatal shelf fusion to occur. To obtain direct evidence for the importance of Hoxa2 in murine palate development, an in vitro whole organ palatal culture model was developed, eliminating any influences from the tongue. A retroviral gene delivery system was employed, containing either Hoxa2 sense or Hoxa2 antisense cDNA, to respectively enhance or knockdown the expression of Hoxa2 mRNA in the developing palate. <p>Our results show that palatal cultures infected with the lowest titer of Hoxa2 sense virus induce a fusion rate of 72.7%, which is similar to palatal cultures treated with the control virus (81.8%), although fusion rates of 41.2% to 50.0% were observed in palates infected with higher titers. With the antisense virus treated group, a more profound inhibition of the fusion rate was observed (27.7% - 46.1%), which is comparable with the frequency of palatal fusion in Hoxa2-/- mice (44.4%). Additionally, the palatal shelves in both sense and antisense virus treated groups appear to be relatively shorter in length, than those measured in the control group. Interestingly, in the antisense virus treated group, the ratio of the length of the fused portion to the length of palatal shelves appears to be relatively large compared to the control group. Verification and quantification of Hoxa2 mRNA in the developing palate between E12.5 and E15.5 was performed by real-time RT-PCR. Hoxa2 gene expression was observed at all stages studied, with expression being the highest at E12.5 and declining from E13.5. The expression level remained constant from E13.5 through E15.5. These findings demonstrate for the first time that Hoxa2 may play a direct role in murine palate development. Results suggest that both factors (the absence of Hoxa2 gene in the palate causing delayed palatal development, as well as the position of the tongue) appear to act in unison to produce cleft palate in Hoxa2 knockout mice.

Thesis--University of Oklahoma. / Includes bibliographical references (leaves 64-65).

Auditory impairment in patients with craniofacial clefts has been well studied for decades. However, most previous research has only focused on middle ear disorders and related auditory consequences in this group. Studies of higher level auditory status and central auditory processing abilities of this group—particularly in children—have been unsystematic and have significant limitations, while the potentially negative impact of central auditory impairment on children should not be ignored. One important area which needs further research is the status of the central auditory nervous system (CANS) in children with non-syndromic cleft lip and/or palate (NSCLP). In order to objectively investigate possible central auditory impairment in children with NSCLP, the present research programme was initiated. Firstly, two major studies aimed to provide anatomical structural analysis and functional evaluation of the auditory structures of CANS in a group of infants with NSCLP, and compare the results to those of normal controls (Studies 1 and 2). Secondly, a pilot study (Study 3) was conducted to provide preliminary data and suggest methodology to support a major, future research programme to comprehensively investigate central auditory processing abilities in children with NSCLP. A multi-disciplinary approach that included brain magnetic resonance image (MRI) scanning, auditory evoked potentials (AEP) recording, and a central behavioural auditory test battery assessment protocol, was applied in the present research programme. Based on the results of the studies and data analysis, it was concluded that: (1) Structural abnormalities of CANS in infants with NSCLP may be primarily located in the left cerebral hemisphere and cortical abnormalities were more marked compared with those in other subcortical locations. The development and maturation of the auditory cortex in infants with NSCLP may be abnormal, compared with that in normal children; (2) Infants with NSCLP might have normal auditory sensory function at brain stem and subcortical levels, yet this group may have significant impaired auditory discriminatory function at cortical level; (3) Children with NSCLP may show normal auditory processing abilities in a quiet listening environment. However, they may be more vulnerable to background noise and have impaired auditory processing abilities in areas such as monaural low redundancy and temporal resolution ability. In summary, combining the results of MRI, AEP and behavioural measurements in the present research programme, it is suggested that children with NSCLP are at potential risk of both structural abnormalities and functional disorders of the CANS, particularly at auditory cortical level. In addition, this group might also be at risk of auditory processing impairments to some degree, particularly in noisy environments. The present research programme has made a contribution to our understanding of the central auditory status of children with NSCLP, which was not systematically investigated in previous studies, and provided information on which to base further research. The research findings should draw the attention of researchers and clinicians to improving auditory assessment and intervention for patients with craniofacial cleft disorders. Further efforts in this field in the long-term may help to develop a more sophisticated audiological evaluation and intervention approach for this population. / published_or_final_version / Speech and Hearing Sciences / Doctoral / Doctor of Philosophy

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

In der vorliegenden Dissertation wurde anhand von 1042 extraoralen Fotos im Profil und en face untersucht, wie sich das Wachstum longitudinal bei 166 gesunden Kindern, je zehn Kindern mit isolierter Gaumenspalte, einseitiger Lippen-Kiefer-Gaumenspalte sowie doppelseitiger Lippen-Kiefer-Gaumenspalte operiert nach dem Leipziger Konzept entwickelt, sowie inwiefern sich die einzelnen Gruppen in verschiedenen Altersstufen voneinander unterscheiden. Dazu wurden pro Gruppe jeweils fünf Jungen und fünf Mädchen kaukasischer Herkunft, geboren in den Jahren 1994 bis 2001, mit einer nichtsyndromalen Spalte ausgewählt, die ab der Geburt über mehrere Jahre hinweg fotografiert wurden. Diese Fotos wurden digitalisiert und denen von Kontrollpatienten gegenüber gestellt. Anhand von Winkeln der klassischen Morphometrie und Grafiken und Statistiken der geometrischen Morphometrie wurden die Veränderungen im Wachstum analysiert und die Kontrollpatienten mit dem Leipziger OP-Konzept verglichen. Es konnte gezeigt werden, dass die geometrische Morphometrie durchaus geeignet ist, das Gesichtswachstum anhand von extraoralen Fotos zu beurteilen. Weiterhin konnte bestätigt werden, dass mit dem Leipziger Konzept zur funktionellen Rehabilitation von Patienten mit Lippen-Kiefer-Gaumenspalten sehr gute Operationsergebnisse und vor allem Langzeitergebnisse erzielt werden können.

No description available.

Thesis (Ph. D.)--Texas State University-San Marcos, 2007. / Vita. Includes bibliographical references (leaves 111-129).