Alteration in volumetric bone mineralization density gradation patterns in mandibular distraction osteogenesis following radiation therapy.

BACKGROUND: The use of mandibular distraction osteogenesis for tissue replacement after oncologic resection or for deformations secondary to radiotherapy could have immense therapeutic ramifications. Radiotherapy, however, drastically impairs bone healing, potentially precluding the use of mandibular distraction osteogenesis as a durable reconstructive option. The authors have previously demonstrated significantly decreased mechanical and histologic metrics of the mandibular distraction osteogenesis regenerate after 36 Gy. The authors' goal is to now investigate the effect of these same radiation dosages on bone densitometrics using micro-computed tomographic scanning. METHODS: Six Sprague-Dawley rats received 36-Gy fractionated radiotherapy sessions to the left mandible; six received none. All animals had external fixators placed, creation of osteotomies, distraction, and consolidation. Mandibles were scanned with micro-computed tomographic scanning. Volumetric density and microdensitometric measurements were analyzed. RESULTS: There was a significant difference in volumetric bone mineralization patterns in irradiated animals. Bone volume fraction and bone mineral density, however, demonstrated no significant differences. CONCLUSIONS: The authors discovered a significant increase of low mineralized, immature bone and a significant decrease of highly mineralized, mature bone in the irradiated regenerate. These findings corroborate the authors' hypothesis that radiation induces a diminution in cell function, impairing optimal bone regeneration. Overall densitometrics, however, were unchanged according to micro-computed tomographic measurements, despite documented significant changes in biomechanical and histologic metrics. An optimal radiation dose must now be sought that demonstrates a higher degree of reproducible degradation, but not irreversible destruction, in all three outcomes. Such an approach will allow formulation of therapeutic interventions designed to enhance mandibular distraction osteogenesis so that it may be used as a viable reconstructive option.

Botulinum toxin type A: a treatment option for digital ischemia in patients with Raynaud's phenomenon.

PURPOSE: Raynaud's phenomenon is an exaggerated vasospastic response that causes pallor and cyanosis. In the hand, it results in pain, disability, and the need for amputation. Current accepted medical and surgical treatments are not uniformly successful and have their inherent morbidities. Reports in the literature describe the use of botulinum toxin type A (BTX-A) for the treatment of vasospastic ischemia of the digits. We report the results of the treatment of recalcitrant digital ischemia with BTX-A in our institution. METHODS: We performed a retrospective chart review between January 2003 and February 2007. All patients presented with a diagnosis of Raynaud's phenomenon with worsening pain, discoloration, or nonhealing wound of the hand. Patients received BTX-A injections into the perineurovascular tissue of the wrist or the distal palm, or along the digit. Outcomes measured included pain rating, digit color and appearance, transcutaneous oxygen saturation, and healing of chronic ulcers. RESULTS: Twenty-six patients were treated, with a total of 55 treatment encounters. Patients were observed for an average of 18 months. Statistically significant improvements were noted for pain score and digit transcutaneous oxygen saturation measurements after treatment (p < .05). We found smokers and women were more likely to have improved coloration and appearance after injections. Complications included localized injection-related pain and transient intrinsic muscle weakness. CONCLUSIONS: Botulinum toxin type A significantly improves pain and improves healing in Raynaud's patients with few complications. BTX-A was found to be a safe and useful treatment option for vasospastic digital ischemia.

Biomechanical assessment of regenerate integrity in irradiated mandibular distraction osteogenesis.

BACKGROUND: The role of mandibular distraction osteogenesis for reconstructing mandibular defects following radiation therapy depends on the quality of attenuated bone healing in the regenerate. This study investigated the regenerate properties after radiation therapy using yield and breaking load. The authors hypothesized that both would be significantly reduced in mandibular distraction osteogenesis following radiation therapy compared with mandibular distraction osteogenesis alone. METHODS: Male Sprague-Dawley rats underwent left mandibular fractionated 36-Gy preoperative external beam radiation therapy and then 2 weeks of recovery (n = 7) or no radiation therapy (n = 10) before surgery. External fixators were secured and unilateral osteotomies were created behind the third molar, followed by 4 days of latency and then mandibular distraction osteogenesis: 0.3 mm every 12 hours for 8 days (5.1 mm) and 4 weeks of consolidation. Unoperated controls received no radiation therapy (n = 13). Mandibles were tension tested at 0.5 mm/second to failure, and yield and breaking load were determined. RESULTS: There was a significantly lower breaking load for mandibular distraction osteogenesis following radiation therapy compared with mandibular distraction osteogenesis, alone, but there was no significant difference in yield between the groups. Both groups had significantly lower breaking load and yield when compared with unoperated controls. CONCLUSIONS: The lowered breaking load in mandibular distraction osteogenesis following radiation therapy reflects the reduced biomechanical quality of the regenerate, despite evidence of radiographic union. These data show that radiographic union is not an adequate outcome measure for regenerate healing and support the need to define quantitative bone-healing metrics in mandibular distraction osteogenesis following radiation therapy before implementation in head and neck reconstruction.

Breast cancer in sub-Saharan Africa: how does it relate to breast cancer in African-American women?

BACKGROUND: African-American women have had a lower incidence, yet higher mortality rate from breast cancer compared with White-American women. African-American women also have had a higher risk for early-onset, high-grade, node-positive, and hormone receptor-negative disease. Similar features have characterized hereditary breast cancer, prompting speculation that risk factors could be genetically transmitted. Further evaluation of this theory required the study of breast cancer among women from sub-Saharan Africa because of their shared ancestry with African-American women. METHODS: Publications from 1988 to 2004 of English-language literature on breast cancer in Africa were reviewed. RESULTS: Women from sub-Saharan Africa were found to have a low incidence of breast cancer. This was partly explained by a largely protective reproductive history, including late menarche, early menopause, high parity with prolonged breastfeeding, irregular menses, and fewer ovulatory cycles. The average age at diagnosis, however, was approximately 10 years younger than breast cancer patients of western nations, and disease stage distribution was shifted toward more advanced disease, which resulted in higher mortality rates. These features were found to be similar to data on breast cancer in African-American women. Mutations in BRCA1 and BRCA2 have been reported in African-American women, but the extent of the contribution of BRCA1 and BRCA2 to breast cancer burden in Africa was uncertain. Limited financial resources lead to suboptimal cancer data collection, as well as delayed diagnosis and treatment of many African breast cancer patients. CONCLUSIONS: Parallels between breast cancer burdens of African-American and sub-Saharan-African women were provocative, indicating the need for further exploration of possible genetically transmitted features related to estrogen metabolism and/or breast cancer risk.