Effect of systemic parathyroid hormone (1-34) and a beta-tricalcium phosphate biomaterial on local bone formation in a critical-size rat calvarial defect model.

OBJECTIVE: The objective of this study was to evaluate local bone formation following systemic administration of parathyroid hormone (1-34) (PTH), a surgically implanted synthetic beta-tricalcium phosphate (beta-TCP) bone biomaterial serving as a matrix to support new bone formation. MATERIALS AND METHODS: Critical-size, 8 mm, calvarial through-and-through osteotomy defects were surgically created in 100 adult male Sprague-Dawley rats. The animals were randomized into five groups of 20 animals each to receive one of the following treatments: PTH (15 microg PTH/kg/day; subcutaneously), PTH/beta-TCP, beta-TCP, or particulate human demineralized freeze-dried bone (DFDB), and sham-surgery controls. Ten animals/group were euthanized at 4 and 8 weeks post-surgery for radiographic and histometric analysis. RESULTS: The histometric analysis showed that systemic PTH significantly enhanced local bone formation, bone fill averaging (+/-SE) 32.2+/-4.0% compared with PTH/beta-TCP (15.7+/-2.4%), beta-TCP (12.5+/-2.3%), DFDB (14.5+/-2.3%), and sham-surgery control (10.0+/-1.5%) at 4 weeks (p<0.014). Systemic PTH showed significantly enhanced bone formation (41.5+/-4.0%) compared with PTH/beta-TCP (22.4+/-3.0%), beta-TCP (21.3+/-4.4%), and with the sham-surgery control (23.8+/-4.2%) at 8 weeks (p<0.025). The DFDB group showed significantly increased bone formation from 4 (14.5+/-2.3%) to 8 weeks (32.0+/-3.2%) (p<0.006). The PTH/beta-TCP and beta-TCP groups both showed limited biomaterials resorption. The radiographic analysis was not diagnostic to distinguish local bone formation from the radiopaque beta-TCP biomaterial. CONCLUSIONS: Systemic administration of PTH significantly stimulates local bone formation. Bone formation was significantly limited by the beta-TCP biomaterial.

Effect of intermittent systemic administration of recombinant parathyroid hormone (1-34) on mandibular fracture healing in rats.

PURPOSE: To establish a rat mandibular fracture model and investigate the short- and long-term effects of recombinant parathyroid hormone (PTH 1-34) on mandibular fracture healing in rats. MATERIALS AND METHODS: A controlled unilateral mandibular fracture was created surgically in 29 male Sprague-Dawley rats and then stabilized using an external fixation device. The rats were divided into 2 groups: 1 group received daily subcutaneous injections of 10 microg/kg of PTH(1-34) and 1 group served as the vehicle control. The rats were killed on postoperative days 7 and 21, and radiographic densitometry and histologic evaluation of new bone formation were performed. RESULTS: A novel unilateral mandibular fracture model was established that has significant differences from previously published models, both in the location of the osteotomy site and in the rigid external stabilization device. The PTH(1-34) treated rats showed a statistically significant difference (P < .05) in callous formation compared with the control animals. Radiographic densitometry evaluation of the injury site revealed an increase in bone density, apparent at day 7 in the experimental group. Visual inspection of the histologic sections stained with Masson's trichrome blue showed an apparent increase in new bone formation at 21 days in the PTH-treated group compared with the control group. CONCLUSIONS: Intermittent systemic administration of PTH(1-34) might enhance the healing of mandibular fractures in the early phase (7-day period). Long-term administration (21-day period) showed no statistically significant differences between the control and experimental group by radiographic densitometry.

Mobile health applications enhance weight loss efficacy following bariatric surgery.

INTRODUCTION: With the epidemic of obesity numerous mobile health (mHealth) applications have been designed with the goal of facilitating weight loss. This technology has the potential to focus behavioral modification in a manner that's effective for weight loss. We examined the use of this mHealth technology in our bariatric surgery population to evaluate effects on weight loss following surgery. METHODS: Single institution prospective randomized control trial performed at an academic center. 56 patients who recently underwent a laparoscopic sleeve gastrectomy (LSG) were enrolled into a control group with standard post-operative monitoring and a mHealth application group provided with iPad© minis with the MyFitnessPal© mHealth application. Participants were followed for 24 months. The primary outcomes were effect on weight loss as determined by excess body weight loss (%EWL) and excess BMI loss (%EBL). RESULTS: Statistically significant differences in weight loss outcomes between the groups were present throughout the duration of the study. At 12 months, %EWL was 74.41% (control) vs 81.41% (mHealth) p value 0.047 and at 24 months, it was 59.10% (control) vs 71.47% (mHealth) p value 0.0078. %EBL findings at 12 months was 28.02% (control) vs 32.15% (mHealth) p value 0.0007 and at 24 months, it was 25.39% (control) vs 27.87% (mHealth) p value 0.048. CONCLUSION: Our results demonstrate mHealth applications are a useful adjunct to improve and maintain weight loss following bariatric surgery. We suggest mHealth applications should be utilized following bariatric surgery for improved outcomes.

Evaluating the molecular basis for acute mountain sickness: hypoxia response gene expression patterns in warfighters and murine populations.

Acute mountain sickness (AMS) is an illness that affects many individuals at altitudes above 2,400 m (8,000 ft) resulting in decreased performance. Models that provide quantitative estimates of AMS risk are expanding, but predictive genetic models for AMS susceptibility are still under investigation. Thirty-four male U.S. Army Soldier volunteers were exposed to baseline, 3,000 m, 3,500 m, or 4,500 m altitude conditions in a hypobaric chamber and evaluated for onset of AMS symptoms. In addition, mice were evaluated at extreme hypoxia conditions equivalent to 7,600 m. Real-time polymerase chain reaction hypoxia response array was used to identify 15 genes that were activated in Soldiers and 46 genes that were activated in mice. We identified angiopoietin-like 4 (ANGPTL4) as a gene that is significantly activated in response to hypoxia (5.8-fold upregulated at 4,500 m in humans). The role of ANGPTL4 in high-altitude response has not been explored. Pretreatment of mice with fenofibrate, an ANGPTL4-activating pharmaceutical, had a considerable effect on overall hypoxia response gene expression and resulted in significantly decreased cerebral edema following exposure to hypoxia. Activation of ANGPTL4 may protect against cerebral edema by inhibiting vascular endothelial growth factor and therefore serve as a potential target for AMS prevention.

Thymic hyperplasia and Graves disease: management of anterior mediastinal masses in patients with Graves disease.

OBJECTIVE: To describe a case of an anterior mediastinal mass (AMM) in a patient with Graves disease. METHODS: We report the clinical presentation, diagnosis, management, and outcome of a 34-year-old man with dyspnea on exertion. RESULTS: Initial evaluation of the patient's complaints revealed a large AMM on chest radiography and then chest computed tomography. After occurrence of additional symptoms, the patient was diagnosed as having Graves disease and treated with antithyroid medications. Despite an appropriate biochemical response, he continued to experience severe dyspnea on exertion. A repeated computed tomographic scan 8 weeks after initiation of therapy showed no appreciable decrease in size of the AMM. He elected to undergo thymectomy. An intraoperative phrenic nerve injury resulted in a paralyzed left hemidiaphragm, leaving the patient with considerable difficulties in his career and profoundly decreased exercise tolerance. CONCLUSION: The differential diagnosis of an AMM includes several malignant lesions with a risk often warranting early surgical excision. In light of the association of benign thymic hyperplasia with Graves disease, thymectomy may be delayed in expectation of thymic regression with medical therapy. The timing of regression is variable, and very few reports exist in the literature. In our current case, the patient opted for thymectomy relatively early and had an unfortunate complication. The lack of clinical evidence regarding management of an enlarged thymus in patients with Graves disease, however, makes management decisions more difficult.