Biomechanical Effects of e-PTFE Implant Structure on Soft Tissue Implantation Stability: A Study in the Porcine Model

Successful implantation of biocompatible materials depends on physical aspects of its structure. Meshed implants are stable but cannot be easily removed. Nonporous materials are easily removed, but subject to extrusion. We hypothesized that the microporous structure of expanded polytetrafluoroethylene(e-PTFE) would permit limited fibrous ingrowth into the substance of the material, and that tubular implant shape would increase tissue integration while preserving ease of removal. A two-tailed in vivo study was done comparing implant retention, strength of fixation, and removability between tubular and solid-strip e-PTFE implants. Differences in implant retention within tissues were assessed by implanting 396 implants subcutaneously in five swine for observation periods ranging from 3 weeks to 12 months. Strength of implant attachment to host soft tissues was measured at 52 sites by extraction with a tensiometer with forces both parallel and perpendicular to the implant used. Implant porosity was assessed with scanning electron micrography of tubular and solid-strip e-PTFE implants. Measurements of the force and stress tolerances of the implant-tissue interface demonstrated significantly stronger attachment in tubular than strip-shaped implants (P < 0.005). The 11 N (2.75 lb) force sustained by the tubular implant exceeded the 3.4 N(<1 lb) force for the e-PTFE strip by a statistically significant margin on two-tailed Student's t-test (P < 0.005). Even greater forces were tolerated when applied at right angles to the axis of the tubular implant, emulating tissue suspension (21 N, 5.25 lb). The forces and stresses tolerated by both e-PTFE implants far exceeded the fracture stress measured for the implants. Implant extrusion rates were significantly smaller in tubular (0.85%) than in strip-shaped (4.4%) e-PTFE implants (P< 0.05). Standard error of the mean (SEM) demonstrated lesser porosity in tubular than strip implants, suggesting lesser direct tissue attachment. Tubular e-PTFE implant structure facilitates ingrowth of soft tissue through the tube's lumen. This increases the attachment to surrounding soft tissues, increasing fixation strength, decreasing extrusion rate, but still allowing easy removal. These properties may improve clinical applications in facial implantation.     

Nasal Reconstruction Using a Combination of Alloplastic Materials and Autogenous Tissues: A Surgical Alternative

Re-creation of a functional and aesthetically acceptable nose after partial nasal defect requires accurate reproduction of nasal lining, support, and coverage. Most authors recommend an approach to reconstruction with cantilevered bone grafting and paramedian forehead flap placement. The authors propose an alternative approach for selected patients with total or near-total nasal defects combining both alloplastic and autogenous tissues. This method uses vitallium or titanium mesh for the dorsal framework formation, tissue-expanded paramedian forehead flap for soft tissue coverage, and composite chondrocutaneous auricular grafts for tip reconstruction. Nine individuals underwent nasal reconstruction using this method. The indications, details, and potential advantages of this technique are described with accompanying photographic results. A flexible approach using a combination of alloplastic materials and autogenous tissues provides additional reconstructive options for individuals with total or near-total nasal defects.     

Sex differences in response to red and blue light in human primary visual cortex: a bold fMRI study

Studies using a variety of investigative methods, including functional brain imaging and electroencephalography (EEG), have suggested that changes in central nervous system (CNS) dopamine function result in altered visual system processing. The discovery of abnormal retinal blue cone, but not red cone, electroretinogram in association with cocaine withdrawal and Parkinson's disease suggests that visual system response to blue light might be a marker for CNS dopamine tone. As there are numerous sex-related differences in central nervous system dopamine function, we predicted that blue and red light stimulation would produce sex-specific patterns of response in primary visual cortex when studied using the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) technique. We analyzed the BOLD response to red and blue light in male and female human volunteers (N=20). Red and blue light responses in primary visual cortex (V1) to stepped intensities of red and blue light were compared by sex for threshold to detectable BOLD signal increase and for stimulus intensity vs. BOLD signal response. Near threshold, males and females showed similar BOLD signal change to red light, but males showed a threefold greater increase (0.52%) to blue light stimulation when compared to females (0.14%). Log-linear regression modeling revealed that the slope coefficients for the red light stimulus intensity vs. signal change curve were not significantly different for males and females (z=0.995, P=0.320), whereas the slope coefficients for the blue light stimulus intensity vs. signal change curve were significantly larger in males (z=2.251, P=0.024). These findings support a sex and color-dependent differential pattern of primary visual cortical response to photic stimulation and suggest a method for assessing the influence of specific dopamine agonist/antagonist medications on visual function.     

Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS).

PURPOSE: To evaluate the impact of patient, tumor, and treatment-related factors on outcome in unselected patients with recurrent osteosarcoma. PATIENTS AND METHODS: Five hundred seventy-six consecutive patients who had achieved a first complete surgical remission (CR) during combined-modality therapy on neoadjuvant Cooperative Osteosarcoma Study Group (COSS) protocols and then developed recurrent osteosarcoma were analyzed (median time from biopsy to relapse, 1.6 years; range, 0.1 to 14.3 years). There were 501 patients with metastases, 44 with local recurrences, and 31 with both. Metastases involved lungs (469 patients), bones (90 patients), and/or other sites (54 patients). RESULTS: After a median follow-up of 1.2 years for all patients and 4.2 years for survivors, actuarial overall survival (OS) rates at 2, 5, and 10 years were 0.38, 0.23, and 0.18, respectively. Five-year OS was 0.39 for 339 patients with and 0.00 for 229 patients without a second surgical CR (P < .0001). A long time to relapse, a solitary lesion, and, in the case of pulmonary metastases, unilateral disease and the absence of pleural disruption, were of positive prognostic value in uni- and multivariate analyses, as were a second surgical CR and the use of second-line chemotherapy. Radiotherapy was associated with moderately prolonged survival in patients without a second CR. The very limited prognostic differences associated with the use of second-line chemotherapy appeared to be more pronounced with polychemotherapy. CONCLUSION: Time to relapse and tumor burden correlate with postrelapse outcome in osteosarcoma. Complete surgery is an essential component of curative second-line therapy. Chemotherapy, particularly chemotherapy with more than one agent, may contribute to limited improvements in outcome.     

CYP1A2 and NAT2 genotype/phenotype relations and urinary excretion of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in a human dietary intervention study.

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking, and is subsequently metabolically activated by cytochrome P4501A2 (CYP1A2) and N-acetyltransferase 2 (NAT2). Respective genes encoding for these enzymes, display polymorphic distribution in the human population and are thus believed to cause interindividual differences in cancer risk susceptibility. The present study investigated the influence of dietary exposure and CYP1A2 and NAT2 genotypes and phenotypes on differential urinary PhIP excretion levels in 71 human volunteers after consumption of either a high (7.4 ng/g) or low (1.7 ng/g) dose of PhIP. Urinary PhIP excretion levels were found to reflect recent dietary exposure levels, with average levels of 174% (high dose group) and 127% (low dose group), as compared to pre-feed levels. Urinary caffeine metabolite ratios were significantly different between the two NAT2 genotypes, whereas for CYP1A2, the apparent difference in metabolic ratios between the genotypes was statistically non-significant. Significant correlations were firstly found between the CYP1A2-164A-->C (CYP1A2*1F) polymorphism and differential urinary PhIP excretion levels. Although the found correlations are driven primarily by a small number of subjects possessing the homozygous variant constellation, the strong influence of this genotype indicates that the CYP1A2*1F polymorphism could play an important role in human cancer risk susceptibility.     

No signs of subclinical atherosclerosis after risk-reducing salpingo-oophorectomy in BRCA1/2 mutation carriers

BackgroundBRCA1/2 mutation carriers are generally exposed to early menopause due to risk-reducing salpingo-oophorectomy (RRSO) around the age of 40 years. This risk-reducing intervention is based on a 10–40% life-time risk of ovarian cancer in this population. Although effective, premature and acute menopause induces non-cancer related morbidity in both the short and long term. Little is known about the impact of RRSO on the cardiovascular system.MethodsThis cross-sectional study explored the relationship between time since RRSO and signs of subclinical atherosclerosis, as measured by carotid intima-media thickness (CIMT) and pulse wave velocity (PWV), in 165 BRCA1/2 mutation carriers. All participants, aged 40 to 63 years, underwent RRSO before the age of 45 years, and at least 5 years ago. Cardiovascular risk factors were assessed by questionnaires and a single screening visit. Data were analyzed using linear regression models.ResultsMean CIMT was 692.7 μm (SD 87.0), and mean central PWV 6.40 m/s (SD 1.42). After adjustment for age and several relevant cardiovascular risk factors, time since RRSO was not associated with CIMT (β=0.68 μm; 95% CI –4.02, 5.38) and PWV (β=44 mm/s; 95% CI –32, 120). Compared to women of a reference group from the general population, lower systolic blood pressure [mean difference 12 mmHg; 95% confidence interval (CI) 10, 14] was found in BRCA1/2 mutation carriers.ConclusionsWe found that, in BRCA1/2 mutation carriers, at 5 to 24 years follow-up, time since RRSO is not related to development of subclinical atherosclerosis. However, the follow-up period in these relatively young women might have been too short.