David W. Low

Myosin gene mutation correlates with anatomical changes in the human lineage

Powerful masticatory muscles are found in most primates, including chimpanzees and gorillas, and were part of a prominent adaptation of Australopithecus and Paranthropus, extinct genera of the family Hominidae. In contrast, masticatory muscles are considerably smaller in both modern and fossil members of Homo. The evolving hominid masticatory apparatus—traceable to a Late Miocene, chimpanzee-like morphology—shifted towards a pattern of gracilization nearly simultaneously with accelerated encephalization in early Homo. Here, we show that the gene encoding the predominant myosin heavy chain (MYH) expressed in these muscles was inactivated by a frameshifting mutation after the lineages leading to humans and chimpanzees diverged. Loss of this protein isoform is associated with marked size reductions in individual muscle fibres and entire masticatory muscles. Using the coding sequence for the myosin rod domains as a molecular clock, we estimate that this mutation appeared approximately 2.4 million years ago, predating the appearance of modern human body size and emigration of Homo from Africa. This represents the first proteomic distinction between humans and chimpanzees that can be correlated with a traceable anatomic imprint in the fossil record.

Surgical Airway Management in Pierre Robin Sequence: Is There a Role for Tongue-Lip Adhesion?

OBJECTIVE The purpose of this study was to examine the efficacy of tongue-lip adhesion (TLA) in the management of clinically significant airway obstruction associated with Pierre Robin sequence. DESIGN The records of all children admitted to The Childrens Hospital of Philadelphia with a diagnosis of Pierre Robin sequence were reviewed. Charts were reviewed for birth data, diagnosis, preoperative airway management methods, and surgical intervention. Records of infants undergoing TLA were analyzed for timing of surgery, operative technique, postoperative complications, length of hospital stay, and treatment outcome. RESULTS Over the 28-year period 1971 to 1999, 107 patients (47 boys, 60 girls) meeting the criteria for Pierre Robin sequence were admitted for treatment. Of these, 74 (69.2%) were successfully managed by positioning alone. Surgical management of the airway was performed in the remaining 33 (30.8%) patients, 29 of whom underwent TLA and 4 of whom underwent tracheostomy. Dehiscence of the adhesion occurred in five patients (17.2%), two of whom subsequently required tracheostomy. Within the group of patients who underwent mucosal adhesion alone, the dehiscence rate was 41.6%. When the adhesion included muscular sutures, however, dehiscence was not observed in any patient. Of the 24 patients in whom primary TLA healed uneventfully, airway obstruction was successfully relieved in 20 (83.3%). Failure of a healed TLA to relieve the airway obstruction resulted in conversion to a tracheostomy in four patients. Six patients who underwent TLA (20.7%) ultimately required a tracheostomy; five of these patients (83.3%) were syndromic. Of patients requiring preoperative intubation, 42.9% ultimately required tracheostomy. CONCLUSION TLA successfully relieves airway obstruction that is unresponsive to positioning alone in the majority of patients with Pierre Robin sequence and should therefore play an important role in the management of these infants.

Body image concerns of breast augmentation patients

This study investigated the body image concerns of women who sought cosmetic breast augmentation. Thirty breast augmentation candidates completed several measures of body image before their initial surgical consultation. Thirty physically similar women who were not interested in breast augmentation were recruited from the medical center and university community and also completed the measures. Breast augmentation candidates, as compared with women not seeking augmentation, reported greater dissatisfaction with their breasts. Augmentation candidates rated their ideal breast size, as well as the breast size preferred by women, as significantly larger than did controls. In addition, women interested in breast augmentation reported greater investment in their appearance, greater distress about their appearance in a variety of situations, and more frequent teasing about their appearance. Finally, breast augmentation candidates also reported more frequent use of psychotherapy in the year before the operation as compared with women not seeking augmentation. These results replicate and extend previous studies of body image in cosmetic surgery patients.

Uniform Scale-Independent Gene Transfer to Striated Muscle After Transvenular Extravasation of Vector

Background—The muscular dystrophies exemplify a class of systemic disorders for which widespread protein replacement in situ is essential for treatment of the underlying genetic disorder. Somatic gene therapy will require efficient, scale-independent transport of DNA-containing macromolecular complexes too large to cross the continuous endothelia under physiological conditions. Previous studies in large-animal models have revealed a trade-off between the efficiency of gene transfer and the inherent safety of the required surgical and pharmacological interventions to achieve this. Methods and Results—Rats and dogs underwent limb or hemibody isolation via atraumatic tourniquet placement or myocardial isolation via heterotopic transplantation. Recombinant adenovirus (1013 particles per kilogram) or recombinant adeno-associated virus (1014 genome copies/kg) encoding the lacZ transgene was delivered through pressurized venous infusion without pharmacological mediators. Muscle exhibited almost 100% myofiber transduction in rats and dogs by X-galactosidase staining and significantly higher &bgr;-galactosidase levels compared with nonpressurized delivery. No significant difference was seen in &bgr;-galactosidase levels between 100- or 400-mm Hg groups. The <50-mm Hg group yielded inhomogeneous and significantly lower transgene expression. Conclusions—Uniform scale- and vector-independent skeletal and cardiac myofiber transduction is facilitated by pressurized venous infusion in anatomic domains isolated from the central circulation without pharmacological interference with cardiovascular homeostasis. We provide the first demonstration of uniform gene transfer to muscle fibers of an entire extremity in the dog, providing a firm foundation for further translational studies of efficacy in canine models for human diseases.

The Children's Hospital of Philadelphia modification of the Furlow double-opposing z-palatoplasty: Long-term speech and growth results

Of the 261 nonsyndromic patients we studied, over 90% had minimal or absent hypernasality, almost 86% had inconsistent or no nasal emission, and 95% had no articulation errors related to velar function. The patients with a Pittsburgh score indicating an incompetent velopharyngeal mechanism comprised only about 6% of the group. Ninety-four percent had a socially functional speech quality. Secondary surgery was done in 6.5% of patients and was done or was recommended in about 8% of patients. Patients with isolated cleft palate seemed to do less well, although their outcomes were not statistically different from those with complete unilateral and bilateral clefts. Relaxing incisions have kept our fistula rate to an acceptably low rate of 6.8%. No major soft palate dehiscences or hard palate flap losses have occurred. The speech outcomes we are achieving are improved over our historical results and compared with published reports using nondouble reversing z-palatoplasty techniques. Similar outcomes with the Furlow repair have been confirmed. Maxillary growth, occlusion, and the need for orthognathic surgery do not seem to be influenced by the CHOP modification of the Furlow double-opposing z-palatoplasty. These modifications facilitate a tension free-closure and a low fistula rate.

Bigger Is Not Always Better: Body Image Dissatisfaction in Breast Reduction and Breast Augmentation Patients

This study investigated body image dissatisfaction in breast reduction and breast augmentation patients. Thirty breast reduction and 30 breast augmentation patients completed two body image measures preoperatively. Breast reduction patients reported greater dissatisfaction with their overall body image as compared with breast augmentation patients, part of which can be understood as a function of their increased body weight. When asked specifically about their breasts, reduction patients displayed increased body image dysphoria and maladaptive behavioral change, including embarrassment about their breasts in public areas and social settings and avoidance of physical activity. Results are discussed in the context of ideal body weight cutoffs by third-party payers for reimbursement for breast reduction. Recommendations for reimbursement criteria that de-emphasize the role of body weight are made.

A Comparison between DIEP and Muscle-Sparing Free TRAM Flaps in Breast Reconstruction: A Single Surgeon's Recent Experience

Background: Discussions of abdominal donor-site morbidity and risk of flap loss continue to surround free flap breast reconstruction. The authors performed a head-to-head comparison of deep inferior epigastric perforator (DIEP) and muscle-sparing free transverse rectus abdominis musculocutaneous (TRAM) flaps performed by a single senior surgeon at a single institution. Methods: The senior authors (J.M.S.) recent experience with DIEP and muscle-sparing free TRAM flaps between July of 2006 and July of 2008 was reviewed retrospectively. The choice of flap was dictated by an intraoperative algorithm based on number, size, and location of perforator vessels. Variables assessed included intraoperative and postoperative complications. Three groups were analyzed: DIEP reconstructions, muscle-sparing free TRAM reconstructions, and bilateral reconstructions in which one of each flap type was performed. Results: Ninety-one patients underwent 123 muscle-sparing free TRAM flap reconstructions, 53 patients underwent 71 DIEP flap reconstructions, and 31 patients underwent bilateral reconstruction with one DIEP and one muscle-sparing free TRAM flap. There were no significant differences in intraoperative complications or in minor postoperative complications. There was, however, a significant increase in total major postoperative complications in the DIEP study group (DIEP = 3.9 percent, muscle-sparing free TRAM = 0 percent, p = 0.03). No significant difference was noted in hernia formation (DIEP = 0, muscle-sparing free TRAM = 4, p = 0.15). Conclusions: This study demonstrates that both of these flaps may be reliably performed with an extremely low risk of complications. The choice of flap should be made intraoperatively, based on anatomic findings on a patient-by-patient basis, so as to optimize flap survivability while minimizing donor-site morbidity to the greatest extent possible.

The pediatric mandible: II. Management of traumatic injury or fracture.

Learning Objectives: After studying this article, the participant should be able to: 1. Describe the changing epidemiology of mandibular fractures in children and adolescents. 2. Discuss the appropriate use of internal fixation in the treatment of pediatric mandibular fractures. 3. Describe the difficulties posed by the deciduous dentition in the use of interdental wiring. 4. Understand reasons why techniques specific to adult fractures may not be applicable to the growing mandible. 5. Understand the etiology and epidemiology of pediatric mandibular fractures. 6. Understand the reasons for conservative (closed) versus aggressive (open) treatment of mandibular injury. Background: Fractures of the pediatric mandible are complicated by the anatomic complexity of the developing mandible, particularly by the presence of tooth buds and the eruption of deciduous and permanent teeth. Traditional methods of fracture reduction and fixation employed in adults have little applicability in the pediatric population. Methods: The authors describe the surgical techniques that have been used at their institution and those that can be used safely in the pediatric setting. Results: In most cases, “conservative” management is the preferred option, especially in the treatment of condylar fractures. In cases requiring surgical intervention, interdental wiring, drop wires in combination with circummandibular wires, and acrylic splints are suited well to specific phases of dental maturation. Conclusion: Open reduction and internal fixation using monocortical screws and microplates or resorbable plates and screws are acceptable techniques in the pediatric patient, but they require special safeguards. Algorithms are presented to simplify management of these complicated injuries.

Breast reconstruction with free tissue transfer from the abdomen in the morbidly obese.

Background: There are national trends of increasing incidence of morbid obesity and autologous breast reconstruction with free tissue transfer from the abdomen. The purpose of this study was to assess the safety and efficacy of free flap breast reconstruction in the morbidly obese population. Methods: A retrospective review was conducted on all patients who underwent transverse rectus abdominis myocutaneous, deep inferior epigastric perforator, or superficial inferior epigastric artery flap breast reconstructions between July of 2006 and October of 2008. Data from all patients with a body mass index greater than 40 were compared with those of patients with a body mass index less than 40. A p value less than 0.05 was considered significant. Significant findings were then analyzed in a post hoc fashion to examine trends with increasing body mass index. Results: Four hundred four patients underwent 612 free flap breast reconstructions during the study period. Twenty-five of these patients (6 percent) had a body mass index greater than 40. The morbidly obese group had significantly higher rate of total flap loss (p = 0.02), total major postoperative complications (p = 0.05), and delayed wound healing (p = 0.006). Conclusions: Free flap breast reconstruction in the morbidly obese is associated with a higher risk of total flap loss, total major postoperative complications, and delayed abdominal wound healing. However, the overall incidence of complications is low, making free tissue transfer from the abdomen an acceptable method of breast reconstruction in this patient population.

Percutaneous sclerotherapy in neonatal and infant head and neck lymphatic malformations: a single center experience

PURPOSE To evaluate the clinical outcomes of percutaneous sclerotherapy for congenital head and neck lymphatic malformations in our institution. MATERIALS AND METHODS Over a 7-year period, 17 children (10 M, 7 F) mean age 5.8 months (5 days to 13 months) underwent 49 sclerotherapy procedures for congenital head and neck malformations. The imaging and clinical records were reviewed for each patient. Ten of 17 had macrocystic disease; 7 of 17 had microcystic disease. Imaging response was categorized by volume reductions of 0% to 25%, 25% to 50%, 50% to 75%, or 75% to 100%. A concentration of 10 mg/mL doxycycline was used routinely via catheter in 3 instillations with a dose range of 50 to 500 mg per session as per our standard protocol in 17 of 17 patients. In more recent patients, systemic doxycycline levels were obtained after instillations. Additional treatments included direct injection doxycycline (10/17), instillation of absolute ethanol (7/17) or sodium tetradecyl sulfate (4/17), or a combination of these methods. RESULTS Imaging improvement of ≥ 76% was noted in 11 of 17. Of these, 8 of 11 had macrocystic disease. Four of 17 had 51% to 75% resolution, of which 3/4 were mixed. Two of 17 children had 25% to 50% resolution with a mixed lesion. Seven of 49 peri-procedural complications: hemolytic anemia in 2 infants, hypoglycemic and metabolic acidosis in 3 neonates aged 7 to 10 days, transient hypotension during absolute alcohol instillation in 1 neonate, and self-limiting skin excoriation secondary to peri-catheter leakage of doxycycline in one neonate. Neonates prone to these systemic complications had doxycycline doses of greater than 250 mg and resulted in serum levels of >5 μg/mL but as high as 21 μg/mL. Delayed neural complications occurred in 7 of 49 procedures, Horners syndromes in 4 of 49 procedures, transient left lip weakness in 1 of 49 procedures, right facial nerve palsy in 1 of 49 procedures, and transient left hemidiaphragm paralysis in 1/49 procedures. CONCLUSION Our experience with catheter directed doxycycline sclerotherapy provides excellent results for large macrocystic head and neck lymphatic malformations. Microcystic and mixed lesions continue to provide a therapeutic challenge.