Acute adipocyte viability after third-generation ultrasound-assisted liposuction.

BACKGROUND: Although clinical evidence of successful autologous fat transfer (AFT) using third-generation ultrasound-assisted liposuction (UAL) is readily available, no study has quantified adipocyte viability using standardized methods. OBJECTIVES: The authors assess acute adipocyte viability following fat aspiration as a first step in determining the overall efficacy of using third-generation UAL for AFT. METHODS: Lipoaspirate samples were collected from patients who underwent elective liposuction procedures at multiple surgery centers. Patients with a history of bleeding disorders, diabetes, human immunodeficiency virus, or lipoatrophy disorders were excluded. The UAL system (VASER; Sound Surgical Technologies, Inc, Louisville, Colorado) was set at 60% amplitude in pulsed mode with vacuum aspiration of 15 in Hg or less. Laboratory analysis included free lipid volume, viability via lipolysis and propidium iodide staining, and cytological analysis, including cell surface protein examination and hematoxylin and eosin staining. RESULTS: The lipolysis assay revealed metabolically active adipocytes with a mean (SD) correlative viability of 85.1% (11%). Direct measures of acute viability via propidium iodide staining resulted in a mean (SD) viability measure of 88.7% (3.5%). Both mean values are within the historical range reported from syringe and vacuum-assisted lipoaspiration. Aqueous and lipid contents were favorably reduced after washing and filtering (Puregraft system; Cytori Therapeutics, Inc, San Diego, California). Cellular phenotypes identified were primarily white blood cells or vascular endothelial and vascular associated cells. CONCLUSIONS: Adipose tissue acquired via third-generation UAL is viable at harvest and is potentially a suitable source for autologous fat grafts. These results confirm reported clinical successes utilizing third-generation ultrasound lipoaspirate for AFT.

Imaging of Plasmodium liver stages to drive next-generation antimalarial drug discovery.

Most malaria drug development focuses on parasite stages detected in red blood cells, even though, to achieve eradication, next-generation drugs active against both erythrocytic and exo-erythrocytic forms would be preferable. We applied a multifactorial approach to a set of >4000 commercially available compounds with previously demonstrated blood-stage activity (median inhibitory concentration < 1 micromolar) and identified chemical scaffolds with potent activity against both forms. From this screen, we identified an imidazolopiperazine scaffold series that was highly enriched among compounds active against Plasmodium liver stages. The orally bioavailable lead imidazolopiperazine confers complete causal prophylactic protection (15 milligrams/kilogram) in rodent models of malaria and shows potent in vivo blood-stage therapeutic activity. The open-source chemical tools resulting from our effort provide starting points for future drug discovery programs, as well as opportunities for researchers to investigate the biology of exo-erythrocytic forms.

Review of bone substitutes.

Bone substitutes are being increasingly used in craniofacial surgery and craniomaxillofacial trauma. We will review the history of the biomaterials and describe the ideal characteristics of bone substitutes, with a specific emphasis on craniofacial reconstruction. Some of the most commonly used bone substitutes are discussed in more depth, such as calcium phosphate and hydroxyapatite ceramics and cements, bioactive glass, and polymer products. Areas of active research and future directions include tissue engineering, with an increasing emphasis on bioactivity of the implant.

Laparoscopic Roux-en-Y gastric bypass surgery on morbidly obese patients with hypothyroidism.

BACKGROUND: It is well known that obesity is accompanied by changes in thyroid function. Hypothyroidism is associated with increased body weight. The aim of this study was to evaluate the operative outcomes, weight loss, and the effect of weight loss on thyroid function in morbidly obese patients with hypothyroidism who undergo laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. METHODS: A retrospective review of 20 morbidly obese female patients with hypothyroidism and on thyroid replacement therapy who underwent LRYGB between January 2003 and August 2006. RESULTS: Mean preoperative body mass index (BMI) was 47.6 kg/m2 (range 38-58.5 kg/m2). Average patient age was 44.5 years (range 21-66 years). There was one early complication (pneumonia). Late complications included one death, three anastomotic strictures, and one small bowel obstruction. The patients were followed for a mean of 13.5 months (range 3-24 months). Their mean excess body weight loss was 13 kg (22%), 24.4 kg (39.4%), 33.2 kg (63.3%), 38.4 kg (65%), 41.7 kg (70%), and 43 kg (73%) at 1, 3, 6, 9, 12, and 24 months, respectively. Change in a mean BMI was the same regardless of the patient preoperative and postoperative thyroxine dose. Hypothyroidism resolved in 5(25%) patients, improved in 2(10%) patients, unchanged in 8(40%) patients, and worsened in 5 (25%) patients. Most of the five whose hypothyroidism worsened had thyroid autoimmune disease. CONCLUSIONS: Hypothyroidism appears to improve in the vast majority of morbidly obese patients who undergo LRYGB, except for those whose thyroid disease is autoimmune in nature.

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer.

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.