Current and Emerging Treatments for Postsurgical Cleft Lip Scarring: Effectiveness and Mechanisms.

Cleft lip with or without cleft palate is the most common congenital malformation of the head and the third-most common birth defect. Surgical repair of the lip is the only treatment and is usually performed during the first year of life. Hypertrophic scar (HTS) formation is a frequent postoperative complication that impairs soft tissue form, function, or movement. Multiple lip revision operations are often required throughout childhood, attempting to optimize aesthetics and function. The mechanisms guiding HTS formation are multifactorial and complex. HTS is the result of dysregulated wound healing, where excessive collagen and extracellular matrix proteins are deposited within the wound area, resulting in persistent inflammation and resultant fibrosis. Many studies support the contribution of dysregulated, exaggerated inflammation in scar formation. Fibrosis and scarring result from chronic inflammation that interrupts tissue remodeling in normal wound healing. Failure of active resolution of inflammation pathways has been implicated. The management of HTS has been challenging for clinicians, since current therapies are minimally effective. Emerging evidence that specialized proresolving mediators of inflammation accelerate wound healing by preventing chronic inflammation and allowing natural uninterrupted tissue remodeling suggests new therapeutic opportunities in the prevention and management of HTS.

The effects of lip revision surgery on nasolabial esthetics in patients with cleft lip.

OBJECTIVES: 1) To determine the concordance among surgeons on subjective assessments of nasolabial esthetics in children with repaired cleft lip; and 2) to evaluate longitudinal changes in nasolabial esthetics in relation to cleft lip revision surgery. SETTING AND SAMPLE POPULATION: School of Dentistry at University of North Carolina, Chapel Hill. Children with repaired unilateral cleft lip: 32 had lip revision surgery and 27 did not have surgery. MATERIALS AND METHODS: Retrospective observational study from a non-randomized clinical trial. Ratings of nasolabial esthetics performed by six surgeons using the Asher-McDade scale at baseline and 12-month follow-up. RESULTS: Concordance among surgeons ranged from poor to acceptable. Nasolabial ratings at follow-up were better in the Revision group than in the Non-Revision group, although differences were small. The most prevalent change in the Revision Group was improvement in one or more units on the scale, while 'no change' was most prevalent in the Non-Revision group. Participants in the Revision group were more likely to receive a 'no' in relation to the need for lip or nose revision at the follow-up visit. CONCLUSION: There were mild esthetic improvements observed in relation to lip revision surgery, which should be interpreted with caution given the subjectivity of the rating method used.

Effects of lip revision surgery in cleft lip/palate patients.

The decision for lip revision surgery in patients with repaired cleft lip/palate is based on surgeons' subjective evaluation of lip disability. An objective evaluation would be highly beneficial for the assessment of surgical outcomes. In this study, the effects of lip revision on circumoral movements were objectively quantified. The hypothesis was that lip revision increases scarring and impairment. The study was a non-randomized clinical trial that included patients with cleft lip who had revision, patients with cleft lip who did not, and non-cleft control individuals. Three-dimensional facial movements were measured. Revision patients were measured before and after surgery. Other individuals were measured at similar intervals. Regression models were fit to summary measurements, and changes were modeled. Patients with repaired cleft lip/palate had fewer mean movements than control individuals. Lip revision did not worsen mean movements; however, individual patients' movements varied from 'improvement' to 'no change' to 'worse' relative to those of control individuals.

HIV seroprevalence among male prison inmates in the six countries of the organization of eastern Caribbean States in the Caribbean / Seroprevalencia del VIH entre los reclusos varones en los seis países de la organización de Estados del Caribe Oriental (OECO) del Caribe

OBJETIVE: To determine HIV prevalence among male prison inmates in the six OECS countries in the Caribbean. SUBJECTS AND METHODS: Six unlinked, anonymous point prevalence surveys of a total of 1288 male inmates were conducted during a one-year period, August 2004 - August 2005. An oral fluid sample was collected and an interviewer-administered questionnaire and consent form was completed for each survey participant. RESULTS: The overall HIV prevalence was 2.8% (range 2.0% - 4.1%). Only 39% of all inmates had previously been tested, compared to 67% of the HIV-positive inmates. Of all inmates who previously tested, 61% had their last test less than two years ago, 45% had done so while in prison and 39% had done so in a hospital. Most of those who had not previously been tested had no particular reason for not doing so (57%); 24% of them felt it was not necessary or they were not at risk. CONCLUSION: HIV prevalence among male prison inmates was three times higher than the estimated OECS population prevalence in 2003, slightly higher than the prevalence among incarcerated males in the United States of America and Canada, and lower than that in other Caribbean countries in earlier years. Health information on prison populations is important as this is a vulnerable group, with frequent movement in and out of the general population. Preventative services, voluntary counselling and testing, and appropriate care and treatment should be available to all inmates as this is an opportunity for many who may not otherwise access these services.

OBJETIVO: Determinar la prevalencia del VIH entre los reclusos varones en los seis países de la OECO del Caribe. SUBJETOS Y MÉTODOS: Se realizaron seis encuestas de seroprevalencia puntual del VIH anónimas no relacionadas a un total de 1288 reclusos varones por un período de un año, de agosto 2004 a agosto 2005. Se recogió una muestra de fluido oral, y un cuestionario aplicado por un entrevistador y una planilla de consentimiento fueron llenados por cada participante de la encuesta. RESULTADOS: La prevalencia general de VIH fue de 2.8%, (rango 2.0% - 4.1%). Sólo el 39% de todos los recursos habían sido sometidos a pruebas con anterioridad, en comparación con el 67% de reclusos VIH positivos. De todos los reclusos que habían sido previamente sometidos a prueba, al 61% le había sido aplicada la prueba hacía menos de dos años, el 45% la habían recibido mientras estaban en prisión, y el 39% la habían recibido en algún hospital. La mayor parte de los que no habían recibido la prueba previamente, no tenían una razón en particular para no hacerlo (57%), en tanto que el 24% sentía que no era necesario, o no corrían riesgo. CONCLUSIONES: La prevalencia del virus de la inmunodeficiencia humana entre los reclusos varones, fue tres veces mayor que la prevalencia estimada para la población de la OECO en el año 2003, ligeramente más alta que la prevalencia entre los encarcelados hombres en los Estados Unidos de Norteamérica y Canadá, y más baja que la existente en cualquiera de los países del Caribe en años anteriores. La información sobre la salud en las poblaciones de las prisiones es importante ya que tales poblaciones constituyen un grupo vulnerable, que con frecuencia entran y salen de la población general. Los servicios preventivos, asesoramiento voluntario y prueba, así como tratamiento y cuidado adecuados, debe estar disponibles para todos los reclusos, ya que se tata de una oportunidad para que muchos que, de lo contrario, no tendrían acceso a estos servicios.

HIV seroprevalence among male prison inmates in the six countries of the Organization of Eastern Caribbean states in the Caribbean (OECS).

OBJECTIVE: To determine HIV prevalence among male prison inmates in the six OECS countries in the Caribbean. SUBJECTS AND METHODS: Six unlinked, anonymous point prevalence surveys of a total of 1288 male inmates were conducted during a one-year period, August 2004 - August 2005. An oral fluid sample was collected and an interviewer-administered questionnaire and consent form was completed for each survey participant. RESULTS: The overall HIV prevalence was 2.8% (range 2.0-4.1%). Only 39% of all inmates had previously been tested, compared to 67% of the HIV-positive inmates. Of all inmates who previously tested, 61% had their last test less than two years ago, 45% had done so while in prison and 39% had done so in a hospital. Most of those who had not previously been tested had no particular reason for not doing so (57%); 24% of them felt it was not necessary or they were not at risk. CONCLUSION: HIV prevalence among male prison inmates was three times higher than the estimated OECS population prevalence in 2003, slightly higher than the prevalence among incarcerated males in the United States of America and Canada, and lower than that in other Caribbean countries in earlier years. Health information on prison populations is important as this is a vulnerable group, with frequent movement in and out of the general population. Preventative services, voluntary counselling and testing, and appropriate care and treatment should be available to all inmates as this is an opportunity for many who may not otherwise access these services.

Three dimensional analysis of facial movement in normal adults: influence of sex and facial shape.

The aim of this study was to quantify facial movements in a sample of normal adults and to investigate the influence of sex and facial shape on these movements. The study sample consisted of 50 healthy adult subjects, 25 males and 25 females (age: mean = 27.3 years; range = 23-39 years). A video-based tracking system was used to track small-diameter retroreflective markers positioned at specific facial sites. Subjects were instructed to make 7 maximum facial animations from rest, and the facial movements for each animation were characterized as the vectors of maximum displacement. Hotelling's T2 was used to test for significant sex differences in facial movements. In order to determine the effects of facial shape on facial movements, an index of facial shape was first calculated for each subject, and then a mixed-model ANOVA was used with facial shape (index), sex, and the interaction between facial shape and sex as fixed effects and subject as a random effect. The results demonstrated specific movement patterns for each animation. In general, males had larger movements than females and facial shape had a small but significant effect on facial movements. By comparing patient movements with the data from this large normative sample, the utility of this method to assess region-specific movement deficits was demonstrated.

Multimeric hemoglobin of the Australian brine shrimp Parartemia.

The hemoglobin molecule of the commercially important brine shrimp Artemia sp. has been used extensively as a model for the study of molecular evolution. It consists of nine globin domains joined by short linker sequences, and these domains are believed to have originated through a series of duplications from an original globin gene. In addition, in Artemia, two different polymers of hemoglobin, called C and T, are found which differ by 11.7% at the amino acid level and are believed to have diverged about 60 MYA. This provides a set of data of 18 globin domain sequences that have evolved in the same organism. The pattern of amino acid substitution between these two polymers is unusual, with pairs of equivalent domains displaying differences of up to 2.7-fold in total amino acid substitution. Such differences would reflect a similar range of molecular-clock rates in what appear to be duplicate, structurally equivalent domains. In order to provide a reference outgroup, we sequenced the cDNA for a nine-domain hemoglobin (P) from another genus of brine shrimp, Parartemia zietziana, which differs morphologically and ecologically from Artemia and is endemic to Australia. Parartemia produces only one hundredth the amount of hemoglobin that Artemia produces and does not upregulate production in response to low oxygen partial pressure. Comparison of the globin domains at the amino acid and DNA levels suggests that the Artemia globin T gene has accumulated substitutions differently from the Parartemia P and Artemia C globin genes. We discuss the questions of accelerated evolution after duplication and possible functions for the Parartemia globin.

Design and effectiveness of a computer-based continuing education program for orthodontists.

The design of computer-based continuing education for health professionals is an important consideration for Internet delivery because the size of graphic files greatly affects the speed with which information is delivered. Orthodontists who had indicated an interest in computer-based continuing education were shown via CD-ROM either a dynamic version of a computer continuing education program (with transitions and animations to liven up the content) or a plain version (identical content except that the transitions and animations were omitted). The program provided new information about superelastic arch wires for the initial stage of orthodontic treatment. For both versions, over 90% of the viewers thought the program was well done and provided useful information. Six of the orthodontists who received the dynamic version felt that the animations were distracting rather than helpful; only one who received the plain version felt that it was lifeless. A follow-up questionnaire showed that two-thirds of those who viewed the program had subsequently reviewed the performance data for the initial wire they were using and 20% had changed it, so the computer program was effective in changing clinical behavior. Those who saw the plain version also were more likely to have changed their clinical procedures. For Internet delivery of information to highly motivated professionals, it appears that transitions and animations are not necessary and may be more likely to decrease than increase the effectiveness of the teaching material.

Three-dimensional nasolabial displacement during movement in repaired cleft lip and palate patients.

The objective of this study was two-fold: (1) to explore the suitability of a novel modified Procrustes fit method to adjust data for head motion during instructed facial movements, and (2) to compare the adjusted data among repaired unilateral (n = 4) and bilateral (n = 5) cleft lip and palate patients and noncleft control subjects (n = 50). Using a video-based tracking system, three-dimensional displacement of 14 well-defined nasolabial landmarks was measured during four set facial animations without controlling for head motion. The modified Procrustes fit method eliminated the contributions of head motion by matching the most stable landmarks of each video-recorded frame of the face during function to frames at rest. Its effectiveness was found to approximate that of a previous method (i.e., use of a maxillary occlusal splint to which stable dentition-based markers were attached). Data from both the unilateral and bilateral cleft lip and palate patients fell outside the normal range of maximum displacements and of asymmetry, and individual patients demonstrated greater right-versus-left asymmetry in maximum displacement than did individual noncleft subjects. It is concluded that the modified Procrustes fit method is fast, is easy to apply, and allows subjects to move the head naturally without the inconvenience of a splint while facial movement data are being collected. Results obtained using this method support the view that facial movements in cleft patients may be severely hampered and that assessment of facial animation should be strongly considered when contemplating surgical lip revisions.

Maxillary growth in patients with clefts following secondary alveolar bone grafting.

OBJECTIVE: This investigation evaluated the effects of secondary alveolar bone grafting on subsequent maxillary growth in cleft patients. DESIGN: This was a retrospective longitudinal cephalometric study. Nineteen patients who had received secondary alveolar bone grafts were matched to a control sample by sex, cleft, availability of longitudinal records, and presurgical cranial base dimensions and growth direction. All patients had at least two lateral cephalometric radiographs before surgery and two radiographs after surgery. SETTING: The records were obtained from the Longitudinal Growth Study of the Lancaster (Pennsylvania) Cleft Palate Clinic. INTERVENTIONS: All patients had received similar primary surgical procedures by the same surgeon, no orthopedics, and similar mixed-dentition orthodontics. Secondary alveolar bone grafting was the only surgical intervention different between the two groups. MAIN OUTCOME MEASURES: Six measures of maxillary sagittal and vertical growth were taken from 235 radiographs. Slopes of the regression lines for each growth dimension were compared between groups both pre- and postsurgically. RESULTS: There were no significant between-group differences in maxillary sagittal or vertical growth following the grafting procedure. Anterior maxillary vertical growth rates decreased in the grafted group when their pre- and postsurgical rates were compared. Several growth trends in the postsurgical period were found to be continuations of the rates documented presurgically and unrelated to the grafting procedure. CONCLUSIONS: When evaluated longitudinally, maxillary growth in patients having received secondary alveolar bone grafting did not differ from a group of matched controls.

Ancient and recent intron stability in the Artemia hemoglobin gene.

Artemia has evolved three distinct hemoglobins formed by the association of two nine-domain globin polymers. Sequence analysis of cDNA clones corresponding to two polymers, named T and C, indicates that their genes are the products of a duplication event some 60 million years ago. The present study indicates the presence of 22 introns in each of the T and C polymer genes. The 22 introns are classified into two groups: 17 correspond to positions within globin domains, and 5 correspond to interdomain linkers (or N- and C-terminal extensions). Intron position and reading frame phase are precisely conserved between T and C polymers for all 22 introns, but within each gene the position and phase are not always consistent from domain to domain or from linker to linker. The discordance of Artemia hemoglobin introns is discussed in terms of different model mechanisms and constraints: intron sliding, intron loss or gain, and the exon definition model of primary transcript RNA splicing. The results suggest that constraints of pre-mRNA processing should be considered when considering intron positional changes in homologous genes.

Gorlin-Goltz: what's in a name?

This paper describes the clinical features of two very distinct syndromes with similar names: Gorlin-Goltz and Goltz-Gorlin Syndromes. A case report is presented that highlights the differences between these syndromes. To avoid errors in diagnosis because of the similarity in names, the authors caution that, based on additional information now available, the preferred names should be Focal Dermal Hypoplasia syndrome for Goltz-Gorlin syndrome and Nevoid Basal Cell Carcinoma syndrome for Gorlin-Goltz syndrome.

Variable substitution rates of the 18 domain sequences in Artemia hemoglobin.

The Artemia hemoglobin is a dimer comprising two nine-domain covalent polymers in quaternary association. Each polymer is encoded by a gene representing nine successive globin domains which have different sequences and are presumed to have been copied originally from a single-domain gene. Two different polymers exist as the result of a complete duplication of the nine-domain gene, allowing the formation of either homodimers or the heterodimer. The total population size of 18 domains comprising nine corresponding pairs, coupled with the probability that they reflect several hundred million years of evolution in the same lineage, provides a unique model in which the process of gene multiplication can be analyzed. The outcome has important implications for the reliability of local molecular clocks. The two polymers differ from each other at 11.7% of amino acid sites; however when corresponding individual domains are compared between polymers, amino acid substitution fluctuates by a factor of 2.7-fold from lowest to highest. This variation is not obvious at the DNA level: Domain pair identity values fluctuate by 1. 3-fold. Identity values are, however, uncorrected for multiple substitutions, and both silent and nonsilent changes are pooled. Therefore, to determine the variability in relative substitution rates at the DNA level, we have used the method of Li (1993, J Mol Evol 36:96-99) to determine estimates of nonsynonymous (KA) and synonymous (KS) substitutions per site for the nine pairs of domains. As expected, the overall level of silent substitutions (KS of 56. 9%) far exceeded nonsilent substitutions (KA of 6.7%); however, for corresponding domain pairs, KA fluctuates by 2.3-fold and KS by 1. 7-fold. The large discrepancies reflected in the expressed protein have accrued within a single lineage and the implication is that divergence dates of different genera based on amino acid sequences, even with well-studied proteins of reasonable size, can be wrong by a factor well in excess of 2.

Sensitivity of a method for the analysis of facial mobility. I. Vector of displacement.

OBJECTIVE: (1) To determine which facial landmarks show the greatest movement during specific facial animations and (2) to determine the sensitivity of our instrument in using these landmarks to detect putatively abnormal facial movements. DESIGN: Movements of an array of skin-based landmarks on five healthy human subjects (2 men and 3 women; mean age, 27.6 years; range, 26 to 29 years) were observed during the execution of specific facial animations. To investigate the instrument sensitivity, we analyzed facial movements during maximal smile animations in six patients with different types of functional problems. In parallel, a panel was asked to view video recordings of the patients and to rate the degree of motor impairment. Comparisons were made between the panel scores and those of the measurement instrument. RESULTS: Specific regions of the face display movement that is representative of specific animations. During the smile animation, landmarks on the mid- and lower facial regions demonstrated the greatest movement. A similar pattern of movement was seen during the cheek puff animation, except that the infraorbital and chin regions demonstrated minimal movement. For the grimace and eye closure animations, the upper, mid-facial, and upper-lip regions exhibited the greatest movement. During eye opening, the upper and mid-facial regions, excluding the upper lip and cheek, moved the most, and during lip purse, markers on the mid- and lower face demonstrated the most movement. We used the smile-sensitive landmarks to evaluate individuals with functional impairment and found good agreement between instrument rankings based on the data from these landmarks and the panel rankings. CONCLUSION: The present method of three-dimensional tracking has the potential to detect and characterize a range of clinically significant functional deficits.

Sensitivity of a method for the analysis of facial mobility. II. Interlandmark separation.

OBJECTIVE: This study demonstrates a method of quantifying facial movements based on distortions of the skin surface. DESIGN: Landmarks were identified on the faces of five healthy human subjects (2 men and 3 women; mean age, 27.6 years; range, 26 to 29 years), and the distortions were characterized by changes in the separation between 20 pairs of landmark distances during specific maximal facial animations: smile, lip purse, cheek puff, grimace, eye closure, and eye opening. Data were recorded with a video-based tracking system for a period of 3 seconds at a sampling rate of 60 Hz or frames per second. For each subject, we analyzed the change in the separation of 20 pairs of landmarks, of which the majority were bilaterally symmetrical and functionally active. RESULTS: Characteristic patterns of movement emerged for each animation. We found that smiling involved movements of the lateral orbital, circumoral, and chin regions; grimacing involved the inner orbital, lateral orbital, lateral nasal, and upper-lip regions; eye closure involved the inner orbital, lateral orbital, and, to a lesser degree, lateral nasal regions; eye opening involved the inner and lateral orbital regions; cheek puffing involved the cheek and lower-lip regions; and the lip purse animation involved the nasolabial, cheek, commissure, and lip regions. CONCLUSION: This measurement of distortion provided a quantitative estimate of facial movement, and this approach is especially applicable to patients with unilateral problems in which the patient can serve as his or her own control.

Measurement of facial soft tissue mobility in man.

OBJECTIVE: The assessment of facial mobility is a key element in the treatment of patients with facial motor deficits. In this study, we explored the utility of a three-dimensional tracking system in the measurement of facial movements. METHODS AND RESULTS: First, the three-dimensional movement of potentially stable facial soft-tissue, headcap, and dental landmarks was measured with respect to a fixed space frame. Based on the assumption that the dental landmarks are stable, their motion during a series of standardized facial animations was subtracted from that of the facial and headcap landmarks to estimate their movement within the face. This residual movement was used to determine which points are relatively stable (< or = 1.5 mm of movement) and which are not (> or = 1.5 mm of movement). Headcap landmarks were found to be suitable as references during smile, cheek puff, and lip purse animations, and during talking. In contrast, skin-based landmarks were unsuitable as references because of their considerable and highly variable movement during facial animation. Second, the facial movements of patients with obvious facial deformities were compared with those of matched controls to characterize the face validity of three-dimensional tracking. In all instances, pictures that appear to be characteristic of the various functional deficits emerged. CONCLUSIONS: Our results argue that tracking instrumentation is a potentially useful tool in the measurement of facial mobility.

Stability of bimaxillary osteotomy following surgical correction of class II skeletal deformities: a two-centre study.

This study compares the stability following bimaxillary osteotomy for correction of class II skeletal deformities between two groups of patients. One group (15 patients) were treated at Canniesburn Hospital, West of Scotland Regional Plastic and Maxillofacial Unit, UK. The other group (15 patients) were treated at Ann Arbor Michigan University Hospital, USA. All cases were treated by Le Fort I maxillary advancement/impaction and bilateral sagittal split advancement osteotomy. In all cases Le Fort I maxillary osteotomy was more stable than sagittal split advancement osteotomy. The maxilla stayed within 1 mm of its immediate postoperative position. The average mandibular advancement in Canniesburn cases was 6 mm and about 4 mm in Michigan cases. During surgery the condyles were displaced about 2 mm posteriorly in Canniesburn cases, but remain in their anatomic position in Michigan cases. At 6 months following surgery, Canniesburn patients showed a clockwise mandibular relapse. This increased both the mandibular plane angle and ramus angle by 2.7 degrees and 2.9 degrees respectively. The mandible settled posteriorly 1.7 mm and inferiorly 1.5 mm. In Michigan cases the mandible stayed within 1 mm of its immediate postoperative position. The difference in mandibular relapse between the two groups was statistically significant (P < 0.05). The differences in the stability between the two groups are investigated and the theories of mandibular relapse following sagittal split osteotomy are discussed.

Multiple linear regression as an analytical tool in cephalometric studies.

When the effect is studied of a factor like 'orthodontic therapy' on linear craniofacial growth, the concomitant consequence of age and gender on size cannot be ignored. The methodologically correct solution is division of the study group into smaller units, each of which is homogeneous with respect to age, gender, and therapy, and to compare these with matched controls. Yet, apart from matched controls being hard to find, this method of subdivision has the serious drawback that smaller groups decrease statistical power. A solution without the need to create sub-groups lies in the application of multiple linear regression analysis. It has been applied to biological data in other studies, but verification of the outcome has not been reported so far. Indeed, testing the mathematical assumptions underlying the regression model created unresolvable obstacles and, therefore, it was decided to perform verification by means of practical examples. Two separate tests for the applicability of the multiple linear regression method, on different data, with differing predictor sets, and with different control samples have been performed.

Association of lip posture and the dimensions of the tonsils and sagittal airway with facial morphology.

The specific contribution of enlarged tonsils or adenoids to craniofacial growth remains unknown, and there is no agreement in the literature as to the significance of lip posture. This study assessed the separate associations of lip posture, sagittal airway size, and tonsil size with selected cephalometric measures. Clinical and cephalometric data of 207 children who presented for evaluation of tonsil and/or adenoid problems were evaluated. Multiple linear regression was used to assess the linear relationship between each of the three parameters and the cephalometric dependent variables. Open lip posture, reduced sagittal airway, and large tonsils were each associated statistically with a characteristic but different skeletal configuration. This association was proportional. Specifically, a more open lip posture was associated with a more backwardly rotated face and larger lower facial height. Reduced sagittal airway size was associated with en bloc backward relocation of the maxilla and mandible. Because the sella-nasion dimension shortened proportionally, the SNA and SNB angles were not affected. Larger tonsils were associated with more forward relocation and rotation of the maxilla and mandible and increased SNA and SNB angles. Because each of the three parameters was associated proportionally with a different craniofacial morphology, it is concluded that lip posture, sagittal airway size, and tonsil size represent three different and unrelated phenomena with respect to their effects on craniofacial growth and form.