Genetics of the dentofacial variation in human malocclusion.

Malocclusions affect individuals worldwide, resulting in compromised function and esthetics. Understanding the etiological factors contributing to the variation in dentofacial morphology associated with malocclusions is the key to develop novel treatment approaches. Advances in dentofacial phenotyping, which is the comprehensive characterization of hard and soft tissue variation in the craniofacial complex, together with the acquisition of large-scale genomic data have started to unravel genetic mechanisms underlying facial variation. Knowledge on the genetics of human malocclusion is limited even though results attained thus far are encouraging, with promising opportunities for future research. This review summarizes the most common dentofacial variations associated with malocclusions and reviews the current knowledge of the roles of genes in the development of malocclusions. Lastly, this review will describe ways to advance malocclusion research, following examples from the expanding fields of phenomics and genomic medicine, which aim to better patient outcomes.

Candidate Gene Analyses of Skeletal Variation in Malocclusion.

This study evaluated associations between craniofacial candidate genes and skeletal variation in patients with malocclusion. Lateral cephalometric radiographs of 269 untreated adults with skeletal classes I, II, and III malocclusion were digitized with 14 landmarks. Two-dimensional coordinates were analyzed using Procrustes fit and principal component (PC) analysis to generate continuous malocclusion phenotypes. Skeletal class classifications (I, II, or III) were used as a categorical phenotype. Individuals were genotyped for 198 single-nucleotide polymorphisms (SNPs) in 71 craniofacial genes and loci. Phenotype-genotype associations were tested via multivariate linear regression for continuous phenotypes and multinomial logistic regression for skeletal malocclusion class. PC analysis resulted in 4 principal components (PCs) explaining 69% of the total skeletal facial variation. PC1 explained 32.7% of the variation and depicted vertical discrepancies ranging from skeletal deep to open bites. PC1 was associated with a SNP near PAX5 (P = 0.01). PC2 explained 21.7% and captured horizontal maxillomandibular discrepancies. PC2 was associated with SNPs upstream of SNAI3 (P = 0.0002) and MYO1H (P = 0.006). PC3 explained 8.2% and captured variation in ramus height, body length, and anterior cranial base orientation. PC3 was associated with TWIST1 (P = 0.000076). Finally, PC4 explained 6.6% and detected variation in condylar inclination as well as symphysis projection. PC4 was associated with PAX7 (P = 0.007). Furthermore, skeletal class II risk increased relative to class I with the minor alleles of SNPs in FGFR2 (odds ratio [OR] = 2.1, P = 0.004) and declined with SNPs in EDN1 (OR = 0.5, P = 0.007). Conversely, skeletal class III risk increased versus class I with SNPs in FGFR2 (OR 2.2, P = 0.005) and COL1A1 (OR = 2.1, P = 0.008) and declined with SNPs in TBX5 (OR = 0.5, P = 0.014). PAX5, SNAI3, MYO1H, TWIST1, and PAX7 are associated with craniofacial skeletal variation among patients with malocclusion, while FGFR2, EDN1, TBX5, and COL1A1 are associated with type of skeletal malocclusion.

An MRI scale for assessment of haemophilic arthropathy from the International Prophylaxis Study Group.

Evaluation of prophylactic treatment of haemophilia requires sensitive methods. To design and test a new magnetic resonance imaging (MRI) scale for haemophilic arthropathy, two scales of a combined MRI scoring scheme were merged into a single scale which includes soft tissue and osteochondral subscores. Sixty-one joint MRI's of 46 patients with haemophilia were evaluated by four radiologists using the new and older scales. Forty-six of the joints were evaluated using two X-ray scales. For all MRI scores, interreader agreement and correlations with X-ray scores and lifetime number of haemarthroses were analysed. The interreader agreement intraclass correlation coefficient was 0.82, 0.89 and 0.88 for the soft tissue and osteochondral subscores and the total score, as evaluated according to the new MRI scale, compared to 0.80 and 0.89 as for the older scales. The total score and osteochondral subscore according to the new scale, as well as scores according to the older scales were correlated (P < 0.01) with number of haemarthroses (Spearman correlation 0.35-0.68) and with the X-ray scores (Spearman correlation 0.40-0.76), but no correlation (P > 0.05) was found between the soft tissue subscore of the new MRI scale and the X-ray scores. The new MRI scale is simpler to apply than the older and has similar reader reliability and correlation with lifetime number of haemarthroses, and by separating soft tissue and osteochondral changes it gives additional information. The new scale is useful for analyses of early and moderate stages of arthropathy, and may help to evaluate prophylactic haemophilia treatment.

Hydrofiber dressing with silver for the management of split-thickness donor sites: a randomized evaluation of two protocols of care.

BACKGROUND: This randomized, open-label study evaluated Aquacel Ag Hydrofiber dressing with silver (HDS; ConvaTec, Skillman, NJ, USA) with an adherent or gelled protocol in the management of split-thickness donor sites. METHODS: HDS was the primary dressing in the adherent group (gauze as secondary covering) and gelled group (transparent film as secondary covering). Dressings were changed on study day 1 or 2 and study days 5 (optional), 10 (optional), and 14. The primary outcome was healing (>or=90% re-epithelialization) at study day 14. RESULTS: Seventy subjects were treated (36 adherent, 34 gelled). By study day 14, 77% of donor sites had healed (67% adherent, 88% gelled). Pain scores decreased over time in both treatment groups. Investigators were "very satisfied" or "satisfied" with (adherent, gelled) time required to manage dressing change (89%, 79% of subjects), minimization of donor-site pain (64%, 82%), ease of application (97%, 94%), management of drainage (92%, 82%), ease of removal (77%, 85%), and ability of dressing to remain in place (69%, 76%). Thirty-nine (56%) subjects had adverse events, most commonly non-donor-site infection (11%) and gastrointestinal events (11%). CONCLUSION: In this randomized, open-label study, HDS was well-tolerated, versatile, and effective in the management of split-thickness donor sites.

Facial fractures in a level I trauma centre: the importance of protective devices and alcohol abuse.

Urban trauma centres have recently noted a shift in the causative mechanism of facial fractures away from motor vehicle crashes (MVC) to blunt assaults (BA). This study was conducted to examine the incidence and aetiology of facial fractures at our institution as well as the relationship with alcohol and protective device use. Trauma registry records of all patients admitted to a level I trauma centre from 1 January 1988 to 1 January 1999 were reviewed. There were 13594 trauma admissions during the 11-year period. Facial fractures were sustained by 1429 patients (10.5%) and this group forms the subject of this study. MVC was the predominant aetiology (59.9%) followed by BA (18.8%). Facial fractures were found in 9.5% of restrained MVC patients compared to 15.4% of unrestrained patients (P<0.00l). Non-helmeted motorcyclists were four times more likely to sustain facial fractures (4.3% vs. 18.4%) than helmeted patients (P<0.00l). 39.6% of patients in the MVC group were legally intoxicated compared to 73.5% in the BA group (P<0.00l). 45.4% of unrestrained patients with facial fractures were intoxicated compared to 11.8% of restrained MVC patients with facial fractures (P<0.001). MVC continue to be the primary aetiology of facial fractures in our trauma population. Protective devices decrease the incidence of facial fractures. Lack of protective device use and the consumption of alcohol correlate with sustaining facial fractures.

A comparison of total body water analyses: bioelectric impedance analysis versus the tritiated water method.

Bioelectric impedance analysis (BIA) is used to measure the body composition and total body water of normal subjects. The purpose of this study was to determine if the hydration of patients with burns could be assessed by BIA. Assessments of total body water as determined by BIA and the tritiated water method were prospectively compared. The 2 analyses were performed 48 hours after admission for 5 patients with acute burns to determine the correlation of the 2 methods. The patients had a mean age of 36.4+/-14.7 years (range, 20-56 years), a mean burn size of 39.4%+/-15.9% of the body surface area (range, 23%-65%), and a mean full-thickness burn size of 27.7% of the body surface area. The total body water was measured on admission and again at 48 hours postburn. There is an excellent relationship between BIA and tritiated-water-method determinations of the total body water of patients with severe burns (r = 0.958). This correlation suggests that BIA provides an accurate measure of total body water, and so it is a reliable means of monitoring fluid resuscitation in patients with burns.

Diaphragmatic hernia seen as a late complication of laparoscopic cholecystectomy.

Laparoscopic surgery has emerged as the standard of care for the elective operative management of symptomatic gallbladder disease. The surgical literature is now beginning to accumulate sufficient case numbers that more clearly define the associated morbidity of this type of surgery. This article reports an instance of iatrogenic injury to the right muscular hemidiaphragm and subsequent hernia after laparoscopic cholecystectomy.

Directional variance in skin movement.

Skin tension is known to affect the amount of movement in normal skin and has been theorized to have a possible influence on burn scars. This study measured the directional variance in skin movement, which is related to this theory. Twenty adult female volunteers had 5 predetermined skin sites tested; these sites were on the ventral surface of the upper extremities (UE), from the shoulder to the wrist. A 1 kg axial traction force was randomly applied to each skin site in both proximal and distal directions. The skin was load-cycled 6 times before movement was measured with the use of a laser beam projection. Analysis was performed for each site, and pooled data was normalized for the entire UE. Distal skin movement was significantly greater than proximal movement at each of the 5 test sites and for the UE as a whole (P < .001). No significant differences were found among like-direction sites. Only subject height and length of UE correlated strongly (r = .88). This study demonstrates a difference in skin movement and discusses how these findings may relate to the theory that skin tension could be involved in burn scar contracture and hypertrophy.

Multicenter trial to evaluate the safety and potential efficacy of pooled human fibrin sealant for the treatment of burn wounds.

OBJECTIVE: The primary purpose of this multicenter study was to evaluate the safety and potential efficacy of a solvent/detergent-treated commercial fibrin sealant (human) for topical hemostasis in skin grafting. METHODS: The study involved a prospective evaluation of changes in viral titers in patients with burns less than 15% after treatment with fibrin sealant (human). Each patient served as his/her own control for an unblinded, randomized comparison of donor site hemostasis and healing. Preoperative serum was obtained to screen for viral titers. At autografting, the recipient site and one of two randomly chosen donor sites were treated with fibrin sealant (human). The use of other hemostatic agents, including epinephrine was prohibited. Each donor site was covered with gauze to collect blood for estimation of the relative amount of bleeding. The healing of the graft and donor sites was observed. Viral titers and wounds were checked monthly for 6 months, and at 9 and 12 months postoperatively. RESULTS: Viral titers for human immunodeficiency virus; hepatitis A, B, and C; Epstein-Barr virus; and cytomegalovirus were obtained before and after treatment. Of 47 patients, 34 completed the full year of observation. After treatment, there were no seroconversions to any of the aforementioned viruses. Bleeding at the recipient site appeared well controlled with fibrin sealant (human). Although investigators felt that fibrin sealant (human) improved donor site hemostasis, differences in hemoglobin measurements of blood-soaked dressings failed to reach significance. No differences were noted with regard to acceleration of donor site healing, graft take, or scar maturation at the two groups of donor sites. Anecdotally, the maturation of the recipient site appeared to be accelerated. CONCLUSION: Fibrin sealant (human) is safe for use during excision and grafting, and its topical hemostatic potential needs to be examined in patients with larger burns. Its role in scar maturation also needs to be investigated.

The effect of Wilms tumor chemotherapy on contralateral renal growth after nephrectomy.

PURPOSE: Our aim was to evaluate the effect of current Wilms tumor chemotherapy on renal growth and function after unilateral nephrectomy. MATERIALS AND METHODS: Yorkshire piglets were enrolled in 2 study groups: group 1--6 underwent unilateral nephrectomy and placebo infusion, and group 2--10 underwent nephrectomy, and infusion of 7.5 mcg/kg. actinomycin D and 0.75 mcg/m2 vincristine according to the National Wilms Tumor Study 4 protocol. Weekly measurements of renal size by ultrasound and gross specimens at sacrifice at age 11 weeks were examined and weekly laboratory studies were recorded. Growth rates of renal length and volume were evaluated by linear regression analysis. Terminal renal length and volume were compared between groups. RESULTS: Mean slope plus or minus standard deviation of the rate of growth in length in the control and chemotherapy groups was 0.067 +/- 0.004 and 0.074 +/- 0.011, respectively (p < or = 0.148, not statistically significant). Mean slope of growth in volume was 1.401 +/- 0.240 versus 1.642 +/- 0.456 (p < or = 0.252), average terminal renal length was 10.71 +/- 1.02 versus 11.58 +/- 1.03 cm (p < or = 0.13, not significant) and mean final volume was 128.67 +/- 32.41 versus 137 +/- 32.52 cc (p < or = 0.65). No differences in final serum creatinine levels were noted. CONCLUSIONS: Chemotherapy for Wilms tumor did not adversely affect contralateral renal growth or function in a nephrectomized piglet model.

Accuracy of renal ultrasound measurements for predicting actual kidney size.

PURPOSE: We attempted to evaluate the accuracy of renal ultrasound measurements for determining actual kidney size in a growing renal unit. MATERIALS AND METHODS: We evaluated 18 renal units in growing piglets weekly for 11 weeks on ultrasound. Measured parameters included length, transverse and anteroposterior dimensions, and volume. At 11 weeks final ultrasound measurements were obtained, animals were sacrificed and gross specimen measurements were made. Final ultrasound dimensions and serial measurements were correlated with actual size. Growth charts were constructed to evaluate variability between observations. RESULTS: Mean difference between final ultrasound renal length and actual size was 3.8 mm. (correlation coefficient 0.74). Serial length measurements were not more accurate than isolated measurements for predicting final length (correlation coefficient 0.34). Volume measurement was not more accurate than renal length. Analysis of individual growth charts revealed a significant week-to-week variation. CONCLUSIONS: Error in ultrasound measured kidney length can equal 1 or more years of growth in a child. Our results show that caution should be used when incorporating ultrasound measurements into surgical decision making.

Primary hyperparathyroidism in a paediatric hospital.

We retrospectively reviewed the presentation and management of children with primary hyperparathyroidism (PHPT) from 1973 to 1995 at a paediatric tertiary-care centre. There were 11 patients (6 females), aged 12.3-17.7 years at presentation, with sporadic PHPT confirmed by histopathology (single adenoma). Presentation consisted of renal colic, or non-specific gastrointestinal, musculoskeletal or neurological symptoms. Misdiagnosis was common until hypercalcaemia was identified, 0.5-24 months after onset of symptoms (mean 7.7 months). All patients had hypercalcaemia and low-normal serum phosphate. The parathyroid hormone (PTH) radioimmunoassay used before 1986 was elevated in 1/4 patients; the intact PTH assay used after 1986 was elevated in 7/7 patients. At presentation, six had end-organ damage: band keratopathy, renal lesions, and/or bone disease. Preoperative localization was accurate in 0/4 patients diagnosed before 1986, but 5/7 patients diagnosed after 1986: three by ultrasound or sestamibi scan alone, and two by ultrasound and technetium scan. Surgical outcome was not dependent upon the accuracy of pre-operative localization. PHPT is rare in children but usually associated with end-organ damage, presumably due to delayed diagnosis. It should be considered in the differential diagnosis of unexplained non-specific complaints. The intact PTH assay greatly assists pre-operative diagnosis. The usefulness of pre-operative localization requires further research.

Functional outcomes for the patient with burn injuries.

In health care, outcome measures have become important tools to assist with monitoring the efficacy of therapeutic interventions. This article defines functional outcomes and describes why therapists should begin monitoring the care of patients with burn injuries in terms of function. Suggestions are provided on the identification and documentation of functional outcomes for patients with burn injuries.

Deep pelvic abscesses in children: transrectal drainage under radiologic guidance.

PURPOSE: To compare the effectiveness of radiologically guided transrectal drainage (TRD) of deep pelvic abscesses (DPAs) in children with that of percutaneous and surgical techniques. MATERIALS AND METHODS: Treatment results in 57 children with DPAs were retrospectively evaluated. The following procedures were performed: TRD alone (n = 21), TRD and percutaneous drainage (PD) of multiple abscesses (n = 5), PD alone (n = 19), and open surgical drainage (SD) (n = 8). Four patients were treated medically. Most abscesses were due to either perforated appendix or recent appendectomy. Patients believed to have a perforated appendix underwent interval appendectomy 4-6 weeks after TRD or PD. RESULTS: All patients recovered fully. TRD was tolerated better than PD or SD. Patients were usually ambulatory within 24 hours of the TRD procedure and required minimal analgesia. The average hospital stay was 4.2 days with TRD, 8 days with TRD and PD, 6 days with PD, and 10.5 days with SD. CONCLUSION: Radiologically guided TRD is effective in the treatment of DPAs.

Intussusception: ability of fluoroscopic images obtained during air enemas to depict lead points and other abnormalities.

PURPOSE: To evaluate the ability of fluoroscopic images obtained during air enemas to depict or exclude lead points of intussusceptions and other abnormalities that require surgical treatment in the absence of intussusception. MATERIALS AND METHODS: The clinical, radiologic, surgical, and pathologic findings were reviewed in 14 patients with lead points or other lesions. RESULTS: Fluoroscopic images failed to depict a lead point in 10 patients. The air enema easily reduced intussusceptions with benign lead points in seven patients. Fluoroscopic images depicted pathologic lead points in two patients and were normal in two patients with intussusception. Fluoroscopic images failed to depict an abnormality that required surgery in the absence of intussusception in two patients. CONCLUSION: Successful reduction of an intussusception does not always rule out a lead point. Other imaging studies, the patient's condition, and laparotomy may also be necessary to diagnose and treat lead points and other lesions.

Fabrication of total-contact burn masks by use of human body topography and computer-aided design and manufacturing.

Total-contact burn masks are used to treat scar tissue hypertrophy of the face. The mask should conform very closely to the contours of the face and provide evenly distributed pressure. The mask is worn continually throughout wound maturation. Lack of fit because of an inability to obtain exact facial contours by use of an alginate material diminishes the effectiveness of the mask. A multidisciplinary team representing physical therapy, CAD/CAM (computer-aided design and computer-aided manufacturing), biomedical engineering, and prosthetics has advanced the method of developing total-contact burn masks by use of human body electronic imaging, computer graphics, and numerically controlled milling processes. High-resolution surface scanning and CAD/CAM have been used successfully to accurately fabricate three such masks. The methodology and preliminary results from use of these state-of-the-art techniques are described in this article.

Posttraumatic arterial priapism in children: management with embolization.

PURPOSE: To evaluate selective embolization for management of posttraumatic priapism in preadolescent boys and color Doppler sonography for diagnosis of the causative lesion and for planning embolization. MATERIALS AND METHODS: Five preadolescent boys with posttraumatic priapism underwent selective angiography and embolization. Color Doppler sonography was performed in the last three patients. RESULTS: Selective angiography showed an intracavernosal arteriovenous fistula in two patients, pseudoaneurysm of the cavernosal artery in two patients, and asymmetric cavernosal arterial flow in the other patient. After successful embolization, detumescence was achieved in all patients. Color Doppler sonography enabled localization and characterization of the lesion causing the priapism in the three patients. CONCLUSION: Angiography with selective embolization is a safe and effective method to correct posttraumatic priapism in children. Color Doppler sonography is a valuable preangiographic study, as it allows for characterization and localization of the causative lesion and obviates diagnostic cavernosal aspiration.