RESUMEN
Isolated oral clefts, including cleft lip with/without cleft palate (CL/P) and cleft palate (CP), have a complex and heterogeneous etiology. Case-parent trios from three populations were used to study genes spanning chromosome 2, where single nucleotide polymorphic (SNP) markers were analyzed individually and as haplotypes. Case-parent trios from three populations (74 from Maryland, 64 from Singapore and 95 from Taiwan) were genotyped for 962 SNPs in 104 genes on chromosome 2, including two well-recognized candidate genes: TGFA and SATB2. Individual SNPs and haplotypes (in sliding windows of 2-5 SNPs) were used to test for linkage and disequilibrium separately in CL/P and CP trios. A novel candidate gene (ZNF533) showed consistent evidence of linkage and disequilibrium in all three populations for both CL/P and CP. SNPs in key regions of ZNF533 showed considerable variability in estimated genotypic odds ratios and their significance, suggesting allelic heterogeneity. Haplotype frequencies for regions of ZNF533 were estimated and used to partition genetic variance into among-and within-population components. Wright's fixation index, a measure of genetic diversity, showed little difference between Singapore and Taiwan compared with Maryland. The tensin-1 gene (TNS1) also showed evidence of linkage and disequilibrium among both CL/P and CP trios in all three populations, albeit at a lower level of significance. Additional genes (VAX2, GLI2, ZHFX1B on 2p; WNT6-WNT10A and COL4A3-COL4A4 on 2q) showed consistent evidence of linkage and disequilibrium only among CL/P trios in all three populations, and TGFA showed significant evidence in two of three populations.
Asunto(s)
Cromosomas Humanos Par 2 , Labio Leporino/genética , Fisura del Paladar/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Mapeo Cromosómico , Salud de la Familia , Femenino , Frecuencia de los Genes , Ligamiento Genético , Genotipo , Haplotipos , Humanos , Desequilibrio de Ligamiento , Masculino , Maryland , Análisis Multivariante , Núcleo Familiar , Singapur , TaiwánRESUMEN
Markers in five candidate genes were examined on 269 case-parent trios ascertained through a child with an isolated, non-syndromic oral cleft (cleft lip, CL; cleft palate, CP; or cleft lip and palate, CLP). Cases and their parents were ascertained through treatment centers in Maryland. Markers at two of the five candidate genes, transforming growth factor beta3 (TGFbeta3) and MSX1, showed consistent evidence of linkage and disequilibrium due to linkage using several statistical tests (e.g., the global chi-square for TGFbeta3 was 21.1 with 12 df, P = 0.03; that for MSX1 was 8.7 with 3 df, P = 0.03). There was little evidence of heterogeneity in the role of TGFbeta3 between different types of oral clefts, but MSX1 did yield marginal evidence for such heterogeneity. MSX1 also showed evidence for interaction between infant's genotype and maternal smoking, giving a likelihood ratio test for heterogeneity between smoker and non-smoker mothers of 7.16 (2 df, P = 0.03). Using a conditional logistic model to test for gene-gene interaction showed no evidence of interaction between TGFbeta3 and MSX1, with both seeming to contribute independently to risk of isolated, non-syndromic oral clefts.
Asunto(s)
Labio Leporino/genética , Fisura del Paladar/genética , Desequilibrio de Ligamiento , Factores de Transcripción , Adulto , Alelos , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Femenino , Marcadores Genéticos , Genotipo , Proteínas de Homeodominio/genética , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Factor de Transcripción MSX1 , Masculino , Maryland/epidemiología , Núcleo Familiar , Proyectos de Investigación , Factor de Crecimiento Transformador beta/genéticaRESUMEN
PURPOSE: Isolated, nonsyndromic oral clefts cases (n = 171) and unaffected controls (n = 182) were used to identify both genetic and environmental risk factors. METHODS: Infants born in Maryland between 1992 to 1998 with an isolated, nonsyndromic oral cleft [cleft lip (CL), cleft lip and palate (CLP), or cleft palate (CP)] were recruited and exposure plus family history data were collected. Controls were unaffected infants. DNA was collected from all cases and their parents, plus controls. RESULTS: No statistically significant association was found between any of the following: maternal smoking, vitamin use, urinary tract infection, or recreational drug use in either univariate analysis or after adjusting for maternal age and education. More control mothers reported alcohol use during the critical time period of pregnancy (one month before conception through the first trimester) as compared to case mothers. There was a 10-fold increase in risk to siblings of cases as compared to siblings of controls. Markers at four candidate genes were examined: transforming growth factor alpha (TGF alpha), transforming growth factor beta 3 (TGF beta 3), MSX1, and BCL3. Only MSX1 showed significant differences in allele frequencies between CP cases and controls. MSX1 also showed significant evidence of linkage disequilibrium with a susceptibility gene controlling risk for CP. CONCLUSION: Most environmental risk factors examined here gave little evidence of association with risk to isolated, nonsyndromic oral clefts, although any alcohol consumption seemed protective. MSX1 showed evidence of linkage disequilibrium in both case-control and case-parent trio analysis.
Asunto(s)
Labio Leporino/epidemiología , Fisura del Paladar/epidemiología , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Labio Leporino/etiología , Labio Leporino/genética , Fisura del Paladar/etiología , Fisura del Paladar/genética , Genotipo , Humanos , Recién Nacido , Modelos Logísticos , Maryland/epidemiología , Método de Montecarlo , Factores de RiesgoRESUMEN
An assistive device (AD) was used to treat 122 infants with moderate-to-severe positional plagiocephaly. Clinical evaluations indicate that the AD provided the most benefit when applied to 2- to 8-month-old children. Our results suggest that the AD may join molding helmets and physical therapy as a treatment for moderate-to-severe positional plagiocephaly in infants under the age of 1 year.
Asunto(s)
Craneosinostosis/terapia , Hueso Occipital/patología , Posición Supina , Craneosinostosis/etiología , Femenino , Humanos , Lactante , Masculino , Hueso Occipital/crecimiento & desarrollo , Modalidades de Fisioterapia/instrumentación , SueñoRESUMEN
Morphological differences were quantified in three-dimensions among individuals with untreated isolated metopic synostosis and between those individuals and similar aged-matched normal dry skulls to test two hypotheses: first, that the dysmorphology is a self-correcting condition; and second, that a lack of vertical growth of the skull produces this dysmorphology. Three-dimensional (3D) coordinates were recorded for 22 craniofacial landmarks from CT scans of 15 metopic patients, ranging from 5- to 32-months-old, and of four normal dry skulls, ranging in age from 6- to 36-months-old. The patient population was diagnosed with isolated metopic synostosis at The Johns Hopkins Medical Institutions in Baltimore, Maryland or Children's Hospital in St. Louis, Missouri. Comparisons between the metopic age groups indicate that the trigonocephalic phenotype worsens through time. Between 5 and 14 months, the neurocranium displays an increase in vertical growth. This was followed by a lack of vertical growth between 14 and 32 months. The face displays a lack of vertical growth from 5 to 14 months and an increase in vertical growth after 14 months. Comparisons between the metopic age groups and the normal skulls indicate that the trigonocephalic head is taller superoinferiorly and longer anteroposteriorly. Relative to the normal phenotype, the inferior temporal region in the metopic phenotype is narrow. These findings enabled the rejection of both hypotheses and localized form differences between normal and metopic phenotypes. Based on these results, we suggest that the trigonocephalic phenotype worsens with age and the amount of vertical growth that produces the trigonocephalic phenotype varies throughout growth with respect to location within the skull and age.
Asunto(s)
Craneosinostosis/patología , Factores de Edad , Estudios de Casos y Controles , Preescolar , Femenino , Humanos , Lactante , Masculino , Modelos Biológicos , Fenotipo , Intensificación de Imagen Radiográfica , Cráneo/anatomía & histología , Cráneo/crecimiento & desarrollo , Cráneo/patología , Tomografía Computarizada por Rayos XRESUMEN
The cellular response to a wide variety of stresses results in the synthesis of a family of stress response proteins termed heat shock proteins. Recent studies have demonstrated that heat shock proteins produced in response to an initial stress seem to protect against subsequent unrelated stresses. Importantly, hyperthermia-induced heat shock proteins provided protection from ischemia/reperfusion injury in several organ transplantation models. We hypothesized that free musculocutaneous flap survival could be improved by enhancing the flap's tolerance to relative ischemia by the prior induction of heat shock proteins. Accordingly, we determined the heat shock protein response in skin and muscle after systemic or local heating and examined the effect on free musculocutaneous flap survival in a rat model. Free musculocutaneous flaps incorporating thigh adductor muscles and a 2 x 6-cm2 skin paddle were transplanted to the ipsilateral groin in three groups of male Wistar rats. Systemically heated rats (n = 6) were anesthetized and incubated for 30 minutes at 42 degrees C 6 hours before free musculocutaneous tissue transfer. Locally heated rats (n = 6) were anesthetized, and their donor site anterior thigh was placed for 30 minutes on a heating block set at 44 degrees C 6 hours before free tissue transfer. Control rats (n = 5) did not have heating pretreatment but underwent identical anesthesia. Animals were sacrificed on postoperative day 3, at which time skin loss (cm2) and muscle viability, quantified by nitroblue tetrazolium staining time, were assessed in a blinded fashion. The skin and muscle from the free flap were analyzed for HSP72 mRNA and protein using quantitative Northern and Western blot techniques. All free musculocutaneous flaps were viable. However, the locally and systemically heated rats demonstrated a marked improvement of skin survival, which correlated with increased skin levels of HSP72. There were no differences in nitroblue tetrazolium muscle staining times or muscle levels of HSP72 among the three groups. These findings suggest that prior heat-induced heat shock proteins result in improvement in musculocutaneous flap survival, which may have direct clinical applications, especially in high-risk patients.
Asunto(s)
Proteínas de Choque Térmico/biosíntesis , Músculo Esquelético/trasplante , Trasplante de Piel/métodos , Colgajos Quirúrgicos/fisiología , Animales , Northern Blotting , Western Blotting , Temperatura Corporal , Modelos Animales de Enfermedad , Fiebre/metabolismo , Supervivencia de Injerto , Proteínas de Choque Térmico/análisis , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/fisiología , Calor/efectos adversos , Hipertermia Inducida , Hibridación in Situ , Indicadores y Reactivos , Isquemia/prevención & control , Masculino , Proteínas Musculares/análisis , Músculo Esquelético/metabolismo , Nitroazul de Tetrazolio , ARN Mensajero/análisis , Ratas , Ratas Wistar , Daño por Reperfusión/prevención & control , Factores de Riesgo , Método Simple Ciego , Piel/metabolismo , Temperatura Cutánea , Trasplante de Piel/fisiología , Estrés Fisiológico/metabolismo , MusloRESUMEN
OBJECTIVE: Infants born in Maryland between June 1992 and June 1996 were used in a case-control study of nonsyndromic oral clefts to test for effects of maternal smoking and a polymorphic genetic marker at the transforming growth factor alpha (TGFA) locus, both of which have been reported to be risk factors for these common birth defects. DESIGN AND SETTING: Cases were infants with an oral cleft ascertained through three comprehensive treatment centers, with additional ascertainment through a registry of birth defects maintained by the Maryland Health Department. Controls were healthy infants. Medical history information on infants and mothers were collected, along with DNA samples. PATIENTS, PARTICIPANTS: Among 286 cases contacted (72% ascertainment), there were 192 nonsyndromic isolated oral clefts (106 M; 86 F) available for this case-control study. MAIN OUTCOME MEASURES: The largest group of 149 Caucasian nonsyndromic cases and 86 controls was used to test for association with maternal smoking and genotype at the Taq1 polymorphism in TGFA. RESULTS: While this modest sample had limited statistical power to detect gene-environment interaction, there was a significant marginal increase in risk of having an oral cleft if the mother smoked (odds ratio = 1.75, 95% CI = 1.01 to 3.02). We could not demonstrate statistical interaction between maternal smoking and TGFA genotype in this study, however, and the observed increase in the C2 allele among cases was not statistically significant. CONCLUSIONS: We could not confirm either the reported association between oral clefts and TGFA genotype or its interaction with maternal smoking. However, these data do show an increased risk if the mother smoked during pregnancy, and this effect was greatest among infants with a bilateral cleft and no close family history of clefts.
Asunto(s)
Labio Leporino/etiología , Fisura del Paladar/etiología , Complicaciones del Embarazo , Fumar/efectos adversos , Factor de Crecimiento Transformador alfa/genética , Alelos , Estudios de Casos y Controles , Mapeo Cromosómico , Labio Leporino/genética , Fisura del Paladar/genética , ADN/genética , Ambiente , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Genotipo , Humanos , Lactante , Masculino , Maryland , Oportunidad Relativa , Polimorfismo Genético , Embarazo , Sistema de Registros , Factores de Riesgo , Polimerasa Taq/genéticaRESUMEN
Lambdoid craniosynostosis has been regarded as one of the least common categories of premature fusion of the cranial sutures, yet reports have suggested the incidence may be increasing. To guide treatment decisions, the authors describe a set of rules based on radiographic indicators and clinical assessment in the child. Experience suggests that children can have abnormal-appearing cranial sutures with normal neurological status and normal-appearing sutures with neurological deficits or marked cerebral compression. Early evaluation and follow-up treatment is essential for children with suspected craniosynostosis.
RESUMEN
When large portions of the internal orbit are destroyed (two to four walls), standard bone-grafting techniques for immediate and late orbital reconstruction may not yield predictable eye position. Critical bone support is most often deficient inferomedially. CT analysis of orbital volume in cases where eye position was unsatisfactory reveals that displacement of bone grafts is one mechanism of the unsatisfactory result. Other mechanisms include undercorrection and bone-graft resorption. In order to minimize postoperative bone-graft displacement, titanium implants were used to span large defects in the internal orbit to provide a platform for bone-graft support. Twenty-six implants were placed in immediate and 12 were placed in late orbital reconstructions. More reliable bone-graft position resulted. Two late infections have occurred resulting in implant removal in a 3-year period.
Asunto(s)
Trasplante Óseo/métodos , Fijación Interna de Fracturas/métodos , Fijadores Internos , Fracturas Orbitales/cirugía , Titanio , Huesos Faciales/cirugía , Femenino , Humanos , Masculino , Fracturas Orbitales/complicaciones , Fracturas Craneales/complicaciones , Fracturas Craneales/cirugíaRESUMEN
Silicone tissue expanders were inserted subcutaneously in the buttocks of nine young pigs and gradually inflated to maximum capacity over 5 weeks. On the control side the expanders were left uninflated. Island buttock flaps were then raised, the expanders removed and the flaps spread into the same sites for 10 days. The tissue was harvested. Area measurements and full thickness skin biopsies were taken 10 days after flap inset in order to study the changes in collagen composition and isotypes in the skin layers. Ten days after inset of the flap the expanded skin had a mean 47% increase in surface area, was 9% thinner (from surface to implant), mostly due to thinning of the subcutaneous zone, but was not significantly different in water content, relative to the control skin. The expanded skin had a significant 9.3% increase (p less than 0.01, t test) in collagen content of the dermis. The relative proportions of Types I and III were not significantly changed by skin expansion in either the dermal/epidermal or subcutaneous/capsular zones. It is speculated that tensile factors during expansion stimulate the biosynthetic activity and/or mitotic activity of fibroblasts in the dermis to produce this gain in collagen in the expanded compared with unexpanded tissue.
Asunto(s)
Colágeno/análisis , Piel/metabolismo , Expansión de Tejido , Animales , Biometría , Hidroxiprolina/análisis , Piel/anatomía & histología , Colgajos Quirúrgicos , PorcinosRESUMEN
The pig buttock flap model was used firstly, to compare changes in expanded axial skin flap area with control flaps prior to flap elevation and 3 or 4 months post-flap inset and, secondly, to compare the thickness of expanded and control flaps at elevation and for 3 to 6 months post-flap inset. Following 5 weeks' expansion and prior to elevation, the expanded tissue had gained a significant 63.3% mean increase in area compared with the control tissue (p less than 0.01). Immediately post elevation and inset, the expanded flaps were still significantly larger than the control flaps by a mean 29.8% (p less than 0.01) but had lost 56% of the original area gained. Little change in area occurred in the 3 months post-flap inset as the expanded flaps were still a mean 23.4% larger than the control (p less than 0.01). Dermal and cellular non-keratinised epidermal layers thickened markedly in expanded skin compared to control skin. Following elevation and inset of the flaps, both dermis and epidermis thickened in expanded and control flaps.
Asunto(s)
Prótesis e Implantes , Fenómenos Fisiológicos de la Piel , Colgajos Quirúrgicos , Animales , Piel/citología , Trasplante de Piel , Porcinos , Factores de TiempoRESUMEN
A comparison of viable areas of axial pattern flaps post inset was made between expanded and non-expanded pig buttock island flaps. The deep circumflex iliac artery and vein supply approximately the proximal 14 x 10 cm area of this flap. Larger flaps were raised on expanded and control sides of eight pigs to determine if expansion increased the area of survival. In six of eight pigs whose initial tissue expansion did not create more than approximately a 50% increase in skin area, the expanded flaps had a statistically significant increase in viable skin area (proportionally) 10 days post inset than their control flaps (p less than 0.05). Two other pigs did not conform to this pattern. Their initial tissue expansion was greater than 50%, and the resulting area of flap viability was proportionally less in expanded flaps than the control flaps.
Asunto(s)
Prótesis e Implantes , Trasplante de Piel , Colgajos Quirúrgicos , Animales , Supervivencia de InjertoRESUMEN
Closure of the meningomyelocele wound requires stable coverage of the dural repair. In the case presented, multiple conventional attempts at reconstruction failed. A modification of the "reverse" latissimus dorsi flap is presented that successfully managed this low lumbar defect.
Asunto(s)
Meningomielocele/cirugía , Colgajos Quirúrgicos , Femenino , Humanos , Recién Nacido , Región Lumbosacra , Reoperación , Cirugía Plástica/métodos , Dehiscencia de la Herida Operatoria/cirugíaRESUMEN
Osteoradionecrosis of the olecranon is an unusual pathologic entity, treated best by debridement and wound closure using vascularized tissue. Local skin is often unavailable for flap design and transposition. The radial forearm flap can be isolated on a proximal vascular pedicle and transposed to cover the wound. In the case presented, healing was brisk and complete, allowing early elbow mobilization. Although the donor site is not easily concealed, no functional impairment results from flap elevation and all full-thickness wounds are confined to the involved extremity.
Asunto(s)
Articulación del Codo/cirugía , Osteorradionecrosis/cirugía , Traumatismos por Radiación/cirugía , Colgajos Quirúrgicos , Cúbito/cirugía , Adulto , Desbridamiento , Humanos , Artropatías/cirugía , MasculinoRESUMEN
Obstructive lymphedema is a pathologic condition resulting in the accumulation and stagnation of serum proteins in the lymphatics and interstitial spaces. In a canine model of obstructive lymphedema, one limb was rendered lymphedematous, and various biochemical parameters were determined in this and an unaffected control limb. Both lymph and interstitial fluid had significantly decreased acid proteinase activity (comprising mostly cathepsin D-like enzymes) and neutral proteinase activity (comprising metallo, sulfhydryl, and serine proteinases, and collagenase). Possible reasons for these decreases could be: (1) saturation of macrophages and their surrounding environment with whole or partially digested proteins, or (2) elevation in the levels of circulating inhibitors like alpha 2-macroglobulin. The lymphedematous skin was significantly thicker than control skin and had elevated levels of collagen. However, unlike some fibrotic conditions, the relative proportions of types I, III, and V collagen, as determined by pepsin solubilization and neutral salt fractionation of the collagen fibrils, were similar to those found in normal skin. It is speculated that a decrease in the breakdown of collagen by collagenase and a continuing synthesis of collagen by fibroblasts led to an imbalance in favor of collagen deposition in the skin.
Asunto(s)
Sistema Linfático/patología , Linfedema/metabolismo , Colagenasa Microbiana/metabolismo , Péptido Hidrolasas/metabolismo , Proteínas/metabolismo , Animales , Colágeno/metabolismo , Modelos Animales de Enfermedad , Perros , Espacio Extracelular/enzimología , Fibrosis , Hidroxiprolina/análisis , Linfa/enzimología , Linfedema/patología , Piel/análisis , Piel/patología , alfa-Macroglobulinas/metabolismoRESUMEN
Three cases of palatal fistulae closed by microvascular transfer of radial forearm flaps are presented. Vascularised bone was included in one flap and all operations were free of complications. Facial scarring is minimal and the secondary deformity in the arm has not been significant. It is suggested that this procedure presents fewer difficulties than other techniques for treating the large palatal fistula and may prevent the collapse of the alveolar arch which follows the scarring associated with closure by local tissue.
Asunto(s)
Fisura del Paladar/cirugía , Colgajos Quirúrgicos , Adolescente , Adulto , Niño , Femenino , Fístula/cirugía , Antebrazo , Humanos , MasculinoRESUMEN
The gluteus maximus island musculocutaneous flap has been described using a variety of designs. We employ an island whose long axis is directed toward the pressure sore, minimizing tension in wound closure. Skin overlying the greater trochanter is avoided. Previously undermined skin can be included in the flap. Fifty patients with ischial or sacral pressure sores have been managed by this technique. Superficial dehiscence occurred in 13 percent of patients, and deep dehiscence occurred in 10 percent. The dehiscence closed spontaneously in all but one patient. Forty-nine of the 50 patients experienced complete wound healing at the pressure sore site. The patients have been observed for an average of 20 months (range 3 to 38 months), with one recurrent pressure sore seen at 28 months postoperatively. The gluteus maximus musculocutaneous island flap has proven to be both reliable in healing and durable over the observed interval.
Asunto(s)
Úlcera por Presión/cirugía , Colgajos Quirúrgicos , Nalgas , Estudios de Seguimiento , Humanos , Dehiscencia de la Herida Operatoria/etiología , Factores de Tiempo , Cicatrización de HeridasRESUMEN
Craniofacial surgery has evolved through an era of refinement and finesse, both in techniques and in results. Tissue expansion offers an opportunity to improve the quantity and quality of tissue available for these procedures. It may also be of benefit in long-term molding of the craniofacial skeleton during growth of the child, obviating the need for multiple revisions. This adjunct to craniofacial surgery is being performed with minimal complications and results in improved appearance for the patient.