Analysis of fronto-orbital advancement for Apert, Crouzon, Pfeiffer, and Saethre-Chotzen syndromes

The purposes of this study were (1) to document outcome after primary fronto-orbital advancement for the four major eponymous craniosynostotic syndromes (Apert, Crouzon, Pfeiffer, and Saethre-Chotzen) and (2) to identify factors that might influence need for primary and secondary fronto-orbital advancement or foreheadplasty. Also tested was the hypothesis that coincident sagittal synostosis could modulate brachycephaly and affect whether a primary or secondary frontal operation was necessary. Data were collected on age and indications for initial operation, type of primary and secondary frontal procedures, and concomitant sagittal synostosis. Patients initially managed by subcranial Le Fort III were included in the study group but excluded from analysis of fronto-orbital advancement. Patients treated by monobloc advancement or Le Fort III osteotomies with frontal grafting or Anderl modification were assessed as having had primary fronto-orbital advancement. Minimum time to follow-up was 5 years. A total of 126 patients met inclusion criteria. Lateral photographs were examined to assess preoperative and postoperative sagittal position of supraorbital rims-to-globes. Frontal re-advancement was indicated if the corneal apex was anterior to the supraorbital rim. Foreheadplasty was indicated for unacceptable frontal contour and normal supraorbital rim-to-globe relationship. Primary correction for frontal retrusion was not required in 4 percent of Apert (1 of 25), 16 percent of Crouzon (7 of 44), 6 percent of Pfeiffer (2 of 31), and 19 percent of Saethre-Chotzen (5 of 26) patients. Of those infants who had a primary fronto-orbital advancement, reoperation for either supraorbital retrusion or frontal deformity was necessary in all 16 Apert patients and in 5 of 19 Crouzon (26 percent), 10 of 26 Pfeiffer (38 percent), and 13 of 20 Saethre-Chotzen (65 percent) patients (p < 0.001). Age at initial fronto-orbital advancement did not influence reoperative rate. No correlation was found between concomitant sagittal synostosis and necessity for primary or secondary frontal correction (p = 0.22). In summary, phenotypic diagnosis was determinant for outcome as defined by need for secondary fronto-orbital advancement, foreheadplasty, or both. Apert patients had the highest incidence of reoperation for frontal retrusion or forehead contour. Crouzon and Saethre-Chotzen patients were most likely to express a minor phenotype and not require fronto-orbital correction. Coincident sagittal synostosis did not influence frontal projection, as reflected in need for either primary or secondary frontal advancement.     

Soft-tissue refinements in the treatment of unicoronal craniosynostosis: the rotational forehead flap

Unicoronal craniosynostosis is characterized by ipsilateral superior and posterior displacement of the supraorbital rim and frontal bone, ipsilateral widening of the palpebral fissure, ipsilateral superior displacement of the brow, and contralateral brow depression. In the literature, surgical treatment has focused on bony anatomy, with little written about soft-tissue correction. Over the last 25 years, the senior author (L.A.W.) has incorporated soft-tissue refinements, including a rotational flap of the forehead, elevating the contralateral brow, depressing the ipsilateral brow, and equilibrating the supratarsal sulci in unicoronal craniosynostosis. This rotational forehead repositioning is a simple innovation that has provided for improved orbital and brow symmetry on long-term follow-up.     

Midface distraction following Le Fort III and monobloc osteotomies: problems and solutions

Distraction osteogenesis has been used increasingly for midfacial advancement in patients with syndromic craniosynostosis and in severe developmental hypoplasia of the midface. In these patients, the degree of advancement required is often so great that restriction of the adjacent soft tissues may preclude stable advancement in one stage. Whereas distraction is an ideal solution by which to gradually lengthen both the bones and the soft tissues, potential problems remain in translating the distraction forces to the midface. In these patients, severe developmental hypoplasia may be associated with weak union between the zygoma and the maxilla, increasing the chance of zygomaticomaxillary dysjunction when using internal devices that translate distraction force to the maxilla through the zygoma. Eight cases are reported in which either internal or external distraction systems were used for midface advancement following Le Fort III (n = 7) or monobloc (n = 1) osteotomies. Cases of patients in whom hypoplasia at the zygomaticomaxillary junction altered or impaired plans for midface distraction were reported from three host institutions. Seven patients had midface hypoplasia associated with syndromic craniosynostosis, and one patient had severe developmental midface hypoplasia. The distraction protocol was modified to successfully complete midface advancement in light of weakness at the zygomaticomaxillary junction in seven patients. Modifications included change from an internal to an external distraction system in two patients, rigid fixation and bone graft stabilization of the midface in one patient, and plate stabilization of a fractured or unstable zygomaticomaxillary junction followed by resumption of internal distraction in four patients. Previous infection and bone loss involving both malar complexes precluded one patient from being a candidate for an internal distraction system. Using a problem-based approach, successful advancement of the midface ranging from 9 to 26 mm at the occlusal level as measured by preoperative and postoperative cephalograms was undergone by all patients. Advantages and disadvantages of the respective distraction systems are reviewed to better understand unique patient characteristics leading to the successful use of these devices for correction of severe midface hypoplasia.     

Facial infiltrating lipomatosis.

Facial infiltrating lipomatosis is a rare congenital disorder in which mature lipocytes invade adjacent tissue. The phenotypic features include soft-tissue and skeletal hypertrophy, premature dental eruption, and regional macrodontia. There is a high risk for regrowth after resection that is, perforce, subtotal. The etiology, natural history, optimal management, and relationship to other disorders of fatty overgrowth are unclear. In this study, the clinical features, radiographic findings, histopathology, and postoperative results were analyzed in 13 patients with facial infiltrating lipomatosis. The condition was diagnosed in infancy (eight male subjects, five female subjects) and characterized by enlargement of the cheek (n = 12) or chin (n = 1). Other findings included cutaneous capillary blush (n = 9), ipsilateral macroglossia (n = 8), and mucosal neuromas (n = 6). Most patients had early eruption of ipsilateral deciduous and permanent teeth (n = 12). Computed tomography and magnetic resonance imaging showed an infiltrated soft-tissue mass of fatty density (n = 13) and skeletal overgrowth (n = 9). Multiple resection was performed on six patients (mean number of operations per patient, 2.5; range, one to six operations); regrowth and/or worsening of the capillary stain occurred in all six patients. Because surgical removal of the mass is usually unsuccessful, specific management of this condition will require insight into its etiopathogenesis. Given the presence of mucosal neuromas and lipomatosis, this study included testing for the known mutations in three entities that are associated with these soft-tissue findings (Cowden syndrome, Bannayan-Riley-Ruvalcava syndrome, and multiple endocrine neoplasia type 2B). Results of DNA analyses for these germline mutations were negative. It is more likely that this disorder is caused by a somatic mutation involving a local increase in growth factor(s).     

Anthropometric study of synostotic frontal plagiocephaly: before and after fronto-orbital advancement with correction of nasal angulation

Surgical correction of synostotic frontal plagiocephaly (unilateral coronal synostosis) focuses on the asymmetry of the forehead and orbits. However, there is controversy regarding whether nasal angulation should be addressed during primary fronto-orbital advancement in infancy. This prospective study was undertaken to answer that question. Preoperative and postoperative anthropometric measurements were obtained for 19 infants with nonsyndromic synostotic frontal plagiocephaly. The measurements included nasal angulation, nasion-to-endocanthion distance, nasion-to-exocanthion distance, and exocanthion-to-tragion distance. All patients underwent bilateral parallelogrammatic fronto-orbital correction. Closing wedge nasal ostectomy was performed for group I (n = 14) and was not performed for group II (n = 5). The average age at the time of follow-up assessments was 3 years 8 months (range, 1 to 14 years) in group I and 5 years 5 months (range, 2 to 15 years) in group II. A statistically significant change was observed for patients who underwent primary correction of nasal angulation; the change correlated with improved naso-orbital symmetry, as judged with nasion-to-endocanthion and nasion-to-exocanthion measurements (p < 0.01 and p < 0.05, respectively). Group I patients exhibited an average preoperative nasal angulation of 9.15 +/- 0.8 degrees that decreased to 3.1 +/- 0.6 degrees postoperatively (p < 0.01). Group II patients exhibited an average preoperative nasal angulation of 6.4 +/- 0.7 degrees that was unchanged postoperatively at 7.2 +/- 1 degrees. The improvement in nasal angulation in group I was particularly striking because the patients in group II exhibited, on average, a lesser degree of preoperative nasal deviation (p < 0.01). This prospective comparison of fronto-orbital correction of synostotic frontal plagiocephaly with and without nasal correction confirmed an earlier study and demonstrated that angulation of the nasal pyramid does not self-correct within 5 years after traditional bilateral fronto-orbital repair. Closing wedge nasal ostectomy results in improved nasal angulation and naso-orbital symmetry, without evidence of distortion or inhibition of nasal growth.     

An analysis of Le Fort I maxillary advancement in cleft lip and palate patients.

We present a series of 24 consecutive cleft lip and palate patients aged 16 to 46 years (mean age 27 years) who underwent Le Fort I maxillary advancement by the senior author over the past 8 years. Two groups, one of 12 patients with wire fixation and one of 12 patients with miniplate fixation, were evaluated. Each group had 10 unilateral and 2 bilateral clefts. All patients were grafted with autogenous bone (8 cranial, 14 iliac, and 2 mandibular). Horizontal advancement was 3 mm to 2 cm (with a mean of 7.8 mm). Vertical movement ranged from a shortening of 5 mm to a lengthening of 1.3 cm (mean 2.3 mm of lengthening). The amount and timing of relapse were compared in both the horizontal and vertical dimensions. The plated group was more stable in both the horizontal and vertical dimensions (p < 0.05). No significant skeletal relapses occurred after the first year. Statistically significant dental relapse occurred only in the wired group. Three patients developed transverse collapse of the small maxillary cleft segment, and four developed incisor angulation to compensate for maxillary skeletal relapse. The presence of a pharyngeal flap at the time of advancement appeared to increase relapse in both horizontal and vertical dimensions (p < 0.03), but there were too few patients (7 of 24) with pharyngeal flaps to prove this conclusively. We also concluded that pterygomandibular grafting is not necessary to achieve excellent results using miniplate fixation; autogenous grafting of the anterior maxillary osteotomy alone provides the necessary stability.     

Modifications in the surgical correction of trigonocephaly

A modified technique for the surgical correction of trigonocephaly is presented. The technical modifications are designed both to increase the stability of fixation of the supraorbital bar and lateral canthal advancements and to increase interorbital distance and anterior cranial fossa volume when utilized in those patients who exhibit the full expression of trigonocephaly, including midline ridging, bifrontal recession, hypotelorbitism, shortened anterior cranial fossa, deficient projection of lateral orbit, and bitemporal narrowing. It is a modification of the supraorbital bar remodeling/advancement procedure as originally described by Marchac with the introduction of a nasofrontal osteotomy and superior osteotomy bone graft and midline miniplate fixation of the supraorbital bar to the nasofrontal junction. Its use in 20 patients has been favorable.     

Prenatal exposure to fluconazole: an identifiable dysmorphic phenotype

BACKGROUND: Fluconazole is a triazole antifungal used to treat mycotic infections. Fluconazole is reported to act as a teratogen when used continuously at a dosage of 400-800 mg daily. Fluconazole embryopathy was previously reported in 4 cases. The common features that were also seen in the current case include multiple synostosis (including craniosynostosis and digital synostosis), congenital heart defects, skeletal anomalies, and recognizable dysmorphic facial features. CASE: We report the case of a 9-month-old male born to a 30-year-old woman following a 37-week pregnancy. The pregnancy was complicated by maternal human immunodeficiency virus (HIV) infection and multiple drug exposures, including fluconazole (400 mg/day) until the fifth month and then from 6 months to term, efavirenz, nevirapine, methadone, dapsone, pentamidine, and trimethoprim-sulfamethoxazole. At birth the infant had seizures related to neonatal abstinence syndrome and was noted to have multiple congenital anomalies. On examination at age 9 months, he had craniosynostosis secondary to coronal and lambdoidal suture closures, shallow orbital region, hypoplastic supraorbital ridges, hypertelorism, and mild ptosis. He had radioulnar synostosis and metacarpophalangeal-proximal interphalangeal symphalangism of D2-D5 bilaterally. CONCLUSIONS: The findings of cranial synostosis, multiple symphalangism, and long-bone abnormalities in our case are typical of other reported cases of fluconazole embryopathy. Our patient showed no evidence of embryopathy due to efavirenz, and he did not have the features of Antley-Bixler or other craniosynostosis syndromes. We review the literature regarding the teratogenic effects of prenatal exposure to fluconazole and provide additional evidence that prenatal fluconazole exposure has a clearly identifiable phenotype.     

The innervation of head neuromast rows in eleotridine gobies (Teleostei: Gobioidei)

The innervation of free neuromast (sensory papillae) rows is described from Sihler wholemount preparations of four species of eleotridine gobies, one ( Perccottus glenii ) representing the 'longitudinal' type of neuromast arrangement, the others ( Butis buits, Bostrychus urophthalmus, B. marmoratus ) the 'transverse' arrangement. In the latter, the characteristic transverse cheek rows (1–7) are innervated from the infraorbital trunk of the anterior lateral-line nerve. Longitudinal cheek rows b and d , and the three opercular rows, ot, os and oi , common to all species, are innervated by rami of the hyomandibular trunk of the same nerve. Two neuromast groupings are shown to have a mixed nerve supply. For the median preorbital snout rows, there is innervation from the infraorbital ( s ³ and r ) as well as the supraorbital ( s ¹ and s ²) trunks of the anterior lateral line nerve. The anterior dorsal rows are supplied both by the posterior lateral-line supratemporal ramus (rows g and m ) and the anterior lateral-line supraorbital trunk (rows o and n ). The neuromast rows, under the designations of Sanzo, are tabulated according to innervation and their putative origin in the phyletic replacement of a complete head canal system seen in more generalized percomorph fishes.     

Postoperative mental and morphological outcome for nonsyndromic brachycephaly

Bilateral coronal synostosis causes functional and morphological problems that require fronto-orbital advancement in infancy to correct the brachycephalic deformity and to prevent mental impairment caused by the intracranial hypertension. In this study, 99 children with isolated cases of brachycephaly were prospectively followed to study their preoperative and postoperative mental outcome, which was evaluated using developmental or intelligence quotients. Several factors were analyzed: age before treatment, age at the time of surgery, and the correlation between mental assessments before and after surgery. In a subgroup or patients tested for the FGFR3 P250R mutation (n = 48), mental and morphological assessments were analyzed. Before surgery, mental status was better in the patients tested before 1 year of age (p < 0.001). The preoperative mental assessment always correlated with the postoperative assessment (p < 0.0001). The postoperative mental outcome was better when surgery was performed before the patient reached 1 year of age (p < 0.02). Although both the morphological and functional outcomes were better in the subgroup of noncarriers of the mutation, the differences were not statistically significant. Prominent bulging of the temporal fossae was frequently responsible for poor morphological outcome in carriers of the mutation. This study confirms the need for early corrective surgery before 1 year of age in brachycephalic patients to prevent impairment of their mental development. Suboptimal morphological and mental outcomes can be expected in patients with nonsyndromic brachycephaly who carry the FGFR3 P250R mutation. Primary correction of the temporal bulging should be performed in conjunction with fronto-orbital advancement to improve the morphological outcome in patients with the mutation.     

Maxillary advancement for mandibular prognathism: indications and rationale

The surgical correction of mandibular prognathism has traditionally involved posterior repositioning of the mandibular body. This treatment approach corrects the skeletal disproportion at the expense of reducing facial skeletal volume and can unpredictably result in inadequately supported soft tissues with loss of skeletal definition. In an effort to avoid these sequelae of mandibular reduction, 18 patients diagnosed as having mandibular prognathism were treated with maxillary advancement surgery at the Le Fort I level. Mean patient SNB angle was 85.2 degrees, as compared with a normal 79 +/- 3 degrees. Maxillae were documented to be in normal position relative to both cranial base and Frankfort horizontal. The mean maxillary advancement was 6.9 mm, with a range of 4.5 to 8.8 mm. All patients required genioplasty to reduce vertical chin height and/or to laterally shift the chin. At the time of follow-up (mean 16.2 months), all patients retained cephalometric data suggestive of enlarged mandibles and excessive anterior facial divergence. However, maxillomandibular harmony and facial convexity had been restored without sacrificing skeletal volume. Treatment results demonstrated these faces to be skeletally well proportioned despite lower face protrusion that was beyond "normal." Postoperative appearances were characterized by a well-supported soft-tissue envelope and a highlighted skeletal foundation, creating angular, well-defined lower faces. These findings support the credibility of maxillary advancement as the procedure of choice in selected individuals with mandibular prognathism. Indications and an aesthetic rationale for this surgical approach are presented.     

Clinical and ultrastructural studies of Romberg's hemifacial atrophy

Romberg's disease is an uncommon and poorly understood condition manifested by progressive hemifacial atrophy of skin, soft tissue, and bone. In order to better define the natural history and anatomic variation of this disorder, we evaluated 41 patients by history, physical examination, and facial radiographs. Light microscopic studies were performed on tissue from 19 patients, and ultrastructural analysis was performed on specimens from 6 patients. The average age at inception of the disease was 8.8 years. Atrophy, within one or more trigeminal nerve dermatomes, progressed at a variable rate (mean period of active tissue dissolution = 8.9 +/- 6 years). In 26 patients with skeletal involvement, the mean age of onset was 5.4 years, versus 15.4 years for 15 patients without skeletal involvement, a statistically significant difference (p less than 0.01). However, there was no correlation between the severity of soft-tissue deformity and the age of onset. Electron microscopy demonstrated lymphocytic infiltrates in neurovascular bundles and abnormalities of vascular endothelium and basement membranes. We hypothesize that the pathogenesis of Romberg's disease involves chronic cell-mediated vascular injury and incomplete endothelial regeneration along branches of the trigeminal nerve (lymphocytic neurovasculitis).     

Mutations that cause osteoglophonic dysplasia define novel roles for FGFR1 in bone elongation

Activating mutations in the genes for fibroblast growth factor receptors 1-3 (FGFR1-3) are responsible for a diverse group of skeletal disorders. In general, mutations in FGFR1 and FGFR2 cause the majority of syndromes involving craniosynostosis, whereas the dwarfing syndromes are largely associated with FGFR3 mutations. Osteoglophonic dysplasia (OD) is a "crossover" disorder that has skeletal phenotypes associated with FGFR1, FGFR2, and FGFR3 mutations. Indeed, patients with OD present with craniosynostosis, prominent supraorbital ridge, and depressed nasal bridge, as well as the rhizomelic dwarfism and nonossifying bone lesions that are characteristic of the disorder. We demonstrate here that OD is caused by missense mutations in highly conserved residues comprising the ligand-binding and transmembrane domains of FGFR1, thus defining novel roles for this receptor as a negative regulator of long-bone growth.     

A triceps musculocutaneous flap for chest-wall defects

A posterior upper arm flap based on the profunda brachii vessels has been described to cover soft-tissue defects in the upper anterolateral chest. In our series, the posterior upper arm skin is elevated with the long head of the triceps muscle to cover seven chest-wall defects resulting from indolent postradiation open wounds following partial TRAM flap failure (n = 2), soft-tissue deficiencies following partial TRAM flap loss (n = 3), and primarily as an ancillary flap in TRAM flap breast reconstruction (n = 2). This flap also may be used to supply well-vascularized tissue in the regions of the shoulder, axilla, and posterolateral back. A prerequisite for this operation is redundant tissue of the upper arm often present in middle-aged women and in patients with lymphedema following mastectomy. In our series of seven patients, all donor sites were closed primarily, and there was no subjective functional deficit following transfer of the long head of the triceps muscle.     

Soft-tissue artefact assessment during step-up using fluoroscopy and skin-mounted markers

When measuring knee kinematics with skin-mounted markers, soft tissue and structures surrounding the knee hide the actual underlying segment kinematics. Soft-tissue artefacts can be reduced when plate-mounted markers or marker trees are used instead of individual unconstrained mounted markers. The purpose of this study was to accurately quantify the soft-tissue artefacts and to compare two marker cluster fixation methods by using fluoroscopy of knee motion after total knee arthroplasty during a step-up task. Ten subjects participated 6 months after their total knee arthroplasty. The patients were randomised into (1) a plate-mounted marker group and (2) a strap-mounted marker group. Fluoroscopic data were collected during a step-up motion. A three-dimensional model fitting technique was used to reconstruct the in vivo 3-D positions of the markers and the implants representing the bones. The measurement errors associated with the thigh were generally larger (maximum translational error: 17mm; maximum rotational error 12 degrees ) than the measurement errors for the lower leg (maximum translational error: 11mm; maximum rotational error 10 degrees ). The strap-mounted group showed significant more translational errors than the plate-mounted group for both the shank (respectively, 3+/-2.2 and 0+/-2.0mm, p = 0.025) and the thigh (2+/-2.0 and 0+/-5.9mm, p = 0.031). The qualitative conclusions based on interpretation of the calculated estimates of effects within the longitudinal mixed-effects modelling evaluation of the data for the two groups (separately) were effectively identical. The soft-tissue artefacts across knee flexion angle could not be distinguished from zero for both groups. For all cases, recorded soft-tissue artefacts were less variable within subjects than between subjects. The large soft-tissue artefacts, when using clustered skin markers, irrespective of the fixation method, question the usefulness of parameters found with external movement registration and clinical interpretation of stair data in small patient groups.     

Oral transmission of Trypanosoma cruzi with opposing evidence for the theory of carnivory

We present the first demonstration of oral transmission of Trypanosoma cruzi to raccoons (Procyon lotor), a natural reservoir host in the United States, by ingestion of trypomastigotes and infected bugs, but not infected tissue. To investigate an alternative, non-vector-based transmission method, we tested the hypothesis that raccoons scavenging on infected hosts results in patent infection. Macerated tissue from selected organs infected with amastigote stages of T. cruzi was orally administered to experimental groups of raccoons (n = 2/group) at 2, 12, or 24 hr after collection of the tissue samples. Additionally, raccoons (n=1) in control groups were inoculated intravenously or per os with trypomastigotes. To further elucidate transmission routes of T. cruzi to raccoons, infected Rhodnius prolixus were fed to raccoons (n=2). Raccoons did not become infected after ingestion of amastigote-infected tissues as evidenced by negative polymerase chain reaction results from blood and tissue, lack of seroconversion, and negative parasitemias. However, per os transmission can occur by ingestion of the infective trypomastigote stage or infected reduviid bugs. We conclude from these findings that oral transmission of T. cruzi may be a route of infection for wildlife in sylvatic cycles, but the scavenging behavior of animals is not likely a significant transmission route.     

Microvascular free tissue transfer for treatment of osteoradionecrosis of the maxilla

Head and neck tumors often require radiotherapy as part of the treatment protocol. Although it improves the survival rate in cancer patients, it may cause osteoradionecrosis, especially in the mandible and maxilla. Twelve patients with osteoradionecrosis of the maxilla were treated with microsurgical free tissue transplantations between April of 1996 and August of 2002. There were 10 male and two female patients, with a mean age of 60.2 years. The mean radiotherapy dose was 6674 cGy. The radiation dose could not be traced in three patients because radiotherapy was performed elsewhere. Radical sequestrectomy, soft-tissue debridement, and pathologic proof of no tumor recurrence were performed before microsurgical reconstruction. Free flaps used included the following: anterolateral thigh (n = 7), radial forearm (n = 2), rectus femoris musculocutaneous (n = 2), and supracondylar chimeric (n = 1) flaps. All flaps survived completely and reconstruction succeeded. During a mean 25-month follow-up period, ectropion, plate exposure, and mild infection were encountered in three patients and treated successfully. Radical debridement and obliteration of dead space with well-vascularized tissue are essential for successful treatment of maxillary osteoradionecrosis. The anterolateral thigh flap is most versatile for almost all types of soft-tissue defect reconstruction in the head and neck region.     

Hemifacial microsomia: a multisystem classification

Variability of deformities in hemifacial microsomia has precluded the general acceptance of any classification based on one reference organ. We present a review of hemifacial microsomia classifications and propose a TNM-style multisystem classification. This alphanumeric coding system, SAT, provides cohesion to existing hemifacial microsomia classifications. The acronym SAT is derived as follows: S = skeletal, A = auricle, and T = soft tissue. There are five levels of skeletal deformity (S1 through S5), four levels of auricular deformity (A0 through A3), and three levels of soft-tissue deformity (T1 through T3). Hence a patient with minimal deformity would be classified S1A0T1, whereas a patient with the most severe deformity would be S5A3T3.     

Os acromiale: population differences and their etiological significance.

The os acromiale is an accessory bone resulting from failure of the acromial apophysis to fuse to the scapula. It is a relatively frequent defect affecting 4-18% of most large skeletal series. The etiology of os acromiale is poorly understood, and two competing hypotheses have been proposed: (1) that the accessory bone represents a genetic defect, and (2) that it results from mechanical stress on the developing acromion. In order to assess the evidence for these two hypotheses, os acromiale frequencies from a South African cadaver sample (n = 494) were compared to frequencies from a medieval Danish archaeological sample (n = 532). The South African frequency (18.2%) was significantly higher than the medieval Danish frequency (7.7%, p < 0.0001). These results mirror those of another study comparing African- and Euro-Americans, and tend to support the genetic hypothesis. However, a left side bias (72%) was also found among the South Africans (p = 0.013), lending some support to the mechanical stress hypothesis. Sex and age biases were also examined but were not found. In order to further test the mechanical hypothesis, the medieval Danes were divided into groups of higher and lower socioeconomic status based upon cemetery type. Lower status individuals were presumed to have engaged in strenuous labor activities more often and at a younger age than higher status individuals. However, comparison of these two groups failed to demonstrate a significant frequency difference (p = 0.105). Based on the results of this study, it is suggested that a third etiology combining a genetic predisposition for os acromiale with mechanical stress as the proximate cause should also be considered.     

Visfatin mRNA expression in human subcutaneous adipose tissue is regulated by exercise

Visfatin [pre-beta-cell colony-enhancing factor (PBEF)] is a novel adipokine that is produced by adipose tissue, skeletal muscle, and liver and has insulin-mimetic actions. Regular exercise enhances insulin sensitivity. In the present study, we therefore examined visfatin mRNA expression in abdominal subcutaneous adipose tissue and skeletal muscle biopsies obtained from healthy young men at time points 0, 3, 4.5, 6, 9, and 24 h in relation to either 3 h of ergometer cycle exercise at 60% of Vo(2 max) or rest. Adipose tissue visfatin mRNA expression increased threefold at the time points 3, 4.5, and 6 h in response to exercise (n = 8) compared with preexercise samples and compared with the resting control group (n = 7, P = 0.001). Visfatin mRNA expression in skeletal muscle was not influenced by exercise. The exercise-induced increase in adipose tissue visfatin was, however, not accompanied by elevated levels of plasma visfatin. Recombinant human IL-6 infusion to mimic the exercise-induced IL-6 response (n = 6) had no effect on visfatin mRNA expression in adipose tissue compared with the effect of placebo infusion (n = 6). The finding that exercise enhances subcutaneous adipose tissue visfatin mRNA expression suggests that visfatin has a local metabolic role in the recovery period following exercise.