Botulinum toxin A for mentalis muscle dysfunction.

OBJECTIVE: To describe the use of botulinum toxin A for treatment of mentalis muscle dysfunction secondary to failed augmentation mentoplasty. DESIGN: Clinical observations were made in the treatment of mentalis muscle dysfunction. Patients with the postmentoplasty signs of mental skin dimpling and soft tissue ptosis were injected with 20 U of botulinum toxin A and observed for visual and functional improvement. Photographs were taken for documentation. SETTING: Private facial plastic surgery practice. PATIENTS: Three patients with a history of failed augmentation mentoplasty were identified and signs/symptoms recorded. Each patient was treated with 20 U of botulinum toxin A and observed for clinical improvement. MAIN OUTCOME MEASURES: Pretreatment and posttreatment photographs of active and passive mentalis function together with patient satisfaction surveys. RESULTS: Of the 3 patients treated, all reported alleviation of the mentalis dysfunction and improved appearance. The symptoms began to return as the botulinum toxin A effects subsided. CONCLUSIONS: Botulinum toxin A is a safe and effective treatment of mentalis dysfunction secondary to failed augmentation mentoplasty. The effects are predictable, although temporary.

Detection and quantitation of human papillomavirus (HPV) DNA in the sera of patients with HPV-associated head and neck squamous cell carcinoma.

The human papillomavirus (HPV) has been implicated as an etiological factor in a subset of head and neck squamous cell carcinoma (HNSCC). Because circulating tumor DNA has previously been detected in the sera of patients with advanced HNSCC (stage III or IV), we hypothesized that HPV DNA might be present in the sera of HPV-positive HNSCC patients. Serum DNA extracts from 70 patients with HNSCC were screened for HPV using conventional PCR and a real-time quantitative assay. All samples subjected to conventional PCR were further tested by dot blot hybridization, and positives were confirmed by Southern blotting. Paired tumor DNA from archived tissues was then similarly screened for HPV genomic material (n = 51) or tested by in situ hybridization (n = 19). HPV-16 DNA was detected with L1 primers in 0 of 65 sera and in 15 of 70 (21%) tumors. Conventional PCR with E7 primers and Southern blot hybridization detected HPV-16 DNA in four (6%) sera. Using real-time quantitative PCR, six samples were found to contain various levels of circulating HPV DNA (mean, 12 copies/ml; range, <1-35.) All six serum-positive patients had corresponding tumors positive for E7. Four of these patients with HPV-positive tumors later developed distant metastases, suggesting that HPV DNA in serum may represent occult hematogenous spread of cancer cells in this subset of patients. Although a much larger prospective trial is required, the presence of HPV genomic material in serum DNA of HPV-positive HNSCC patients may serve as a useful marker of early metastatic disease.

Evidence for a causal association between human papillomavirus and a subset of head and neck cancers.

BACKGROUND: High-risk human papillomaviruses (HPVs) are etiologic agents for anogenital tract cancers and have been detected in head and neck squamous cell carcinomas (HNSCCs). We investigated, retrospectively, an etiologic role for HPVs in a large series of patients with HNSCC. METHODS: Tumor tissues from 253 patients with newly diagnosed or recurrent HNSCC were tested for the presence of HPV genome by use of polymerase chain reaction (PCR)-based assays, Southern blot hybridization, and in situ hybridization. The viral E6 coding region was sequenced to confirm the presence of tumor-specific viral isolates. Exons 5-9 of the TP53 gene were sequenced from 166 specimens. The hazard of death from HNSCC in patients with and without HPV-positive tumors was determined by proportional hazards regression analysis. RESULTS: HPV was detected in 62 (25%) of 253 cases (95% confidence interval [CI] = 19%-30%). High-risk, tumorigenic type HPV16 was identified in 90% of the HPV-positive tumors. HPV16 was localized specifically by in situ hybridization within the nuclei of cancer cells in preinvasive, invasive, and lymph node disease. Southern blot hybridization patterns were consistent with viral integration. Poor tumor grade (odds ratio [OR] = 2.4; 95% CI = 1.2- 4.9) and oropharyngeal site (OR = 6.2; 95% CI = 3.1-12.1) independently increased the probability of HPV presence. As compared with HPV-negative oropharyngeal cancers, HPV-positive oropharyngeal cancers were less likely to occur among moderate to heavy drinkers (OR = 0.17; 95% CI = 0.05-0.61) and smokers (OR = 0.16; 95% CI = 0.02-1.4), had a characteristic basaloid morphology (OR = 18.7; 95% CI = 2.1-167), were less likely to have TP53 mutations (OR = 0.06; 95% CI = 0.01-0. 36), and had improved disease-specific survival (hazard ratio [HR] = 0.26; 95% CI = 0.07-0.98). After adjustment for the presence of lymph node disease (HR = 2.3; 95% CI = 1.4- 3.8), heavy alcohol consumption (HR = 2.6; 95% CI = 1.4-4.7), and age greater than 60 years old (HR = 1.4; 95% CI = 0.8-2.3), all patients with HPV-positive tumors had a 59% reduction in risk of death from cancer when compared with HPV-negative HNSCC patients (HR = 0.41; 95% CI = 0.20-0.88). CONCLUSIONS: These data extend recent molecular and epidemiologic studies and strongly suggest that HPV-positive oropharyngeal cancers comprise a distinct molecular, clinical, and pathologic disease entity that is likely causally associated with HPV infection and that has a markedly improved prognosis.

The cardiac mutant gene c in axolotls: cellular, developmental, and molecular studies.

The cardiac mutant axolotl is an interesting model for studying heart development. The mutant gene results in a failure of heart cells to form organized myofibrils and as a consequence the heart fails to beat. Experiments have shown that mutant hearts can be "rescued" (i.e., turned into normally contracting organs) by the addition of RNA purified from conditioned media produced by normal embryonic anterior endoderm-mesoderm cultures. These corrected hearts form myofibrils of normal morphology. New advances in recombinant DNA technology applied to this system should provide significant insights into the regulatory mechanisms of myofibrillogenesis as well as the inductive processes related to the control of gene expression during embryonic heart development. In a broader biological sense, the use of gene c in axolotls is potentially capable of helping to solve major unanswered questions in modern biology related to the genetic regulation of differentiation in vertebrates.

Detection nonuniformity measurements and corrections for cone beam transmission CT on a gamma camera.

Cone beam transmission CT (CB-CT) improves SPECT imaging by providing high-quality attenuation maps for attenuation compensation and for correlated SPECT and CT imaging. The present work measures the detection nonuniformity for CB-CT implemented with a gamma camera, and applies nonuniformity corrections to make CB-CT more uniform and accurate. Two cone beam collimators were investigated, as well as the uncollimated cone beam geometry, using both uniformity images and CB-CT reconstructions of a uniform circular cylinder. Uniformity images were acquired as a function of point source position relative to the nominal focal point. The uniformity images for both collimators were highly nonuniform, with some regions differing by more than 15% from the average image counts per pixel, indicating that the holes do not focus to the same point. The most uniform images were obtained with the point source located at or near the nominal focal point. Radiographs estimated the misfocusing of the holes to be about 0.6 degrees in some regions. There were no indications that the hole size was nonuniform. The CB-CT reconstructions of data acquired with collimator showed no obvious signs of image artifact from the detection nonuniformities. However, low-noise simulated data with well-localized detection defects produced readily-apparent circular artifacts. The nonuniformity correction was accurate and easy to apply, and should be used whenever quantitative accuracy is required. The uniformity images acquired without collimator lacked the collimator-produced nonuniformities, but had decreased counts near the detector edge. The decrease was predictable, using simple geometric considerations. Uniform cylinder reconstructions of "without collimator" data showed a corresponding decrease in center density relative to the edge (edge-to-center ratio = 1.25), which was improved by the nonuniformity correction (ratio = 0.21). Accurate CB-CT without collimator will require further correction for photon scatter.

Attenuation compensation of cone beam SPECT images using maximum likelihood reconstruction.

Attenuation compensation for cone beam single-photon emission computed tomography (SPECT) imaging is performed by cone beam maximum likelihood reconstruction with attenuation included in the transition matrix. Since the transition matrix is too large to be stored in conventional computers, the E-M maximum likelihood estimator is implemented with a ray-tracing algorithm, efficiently recalculating each matrix element as needed. The method was applied and tested in both uniform and nonuniform density phantoms. Test projections sets were obtained from Monte Carlo simulations and experiments using a commercially available cone beam collimator. For representative regions of interest. reconstruction of a uniform sphere is accurate to within 3% throughout, in comparison to a reference image simulated and reconstructed without attenuation. High- and low-activity regions in a uniform density are reconstructed accurately, except that low-activity regions in a more active background have a small error. This error is explainable by the nonnegativity constraints of the E-M estimator and the image statistical noise.