Probing vocal fold fibroblast response to hyaluronan in 3D contexts.
Biotechnol Bioeng. 2009 Jun 8; Munoz-Pinto DJ, Jimenez-Vergara AC, Gelves LM, McMahon RE, Guiza-Arguello V, Hahn MSA number of treatments are being investigated for vocal fold (VF) scar, including designer implants. The aim of the present study was to validate a 3D model system for probing the effects of various bioactive moieties on VF fibroblast (VFF) behavior toward rational implant design. We selected poly(ethylene glycol) diacrylate (PEGDA) hydrogels as our base-scaffold due to their broadly tunable material properties. However, since cells encapsulated in PEGDA hydrogels are generally forced to take on rounded/stellate morphologies, validation of PEGDA gels as a 3D VFF model system required that the present work directly parallel previous studies involving more permissive scaffolds. We therefore chose to focus on hyaluronan (HA), a polysaccharide that has been a particular focus of the VF community. Toward this end, porcine VFFs were encapsulated in PEGDA hydrogels containing consistent levels of high M (w) HA (${rm HA}_{{rm H}{M}_{rm W} } $), intermediate M(w) HA (${rm HA}_{{rm I}{M}_{rm W} } $), or the control polysaccharide, alginate, and cultured for 7 and 21 days. ${rm HA}_{{rm H}{M}_{rm W} } $ promoted sustained increases in active ERK1/2 relative to ${rm HA}_{{rm I}{M}_{rm W} } $ . Furthermore, VFFs in ${rm HA}_{{rm I}{M}_{rm W} } $ gels displayed a more myofibroblast-like phenotype, higher elastin production, and greater protein kinase C (PkC) levels at day 21 than VFFs in ${rm HA}_{{rm H}{M}_{rm W} } $ and alginate gels. The present results are in agreement with a previous 3D study of VFF responses to ${rm HA}_{{rm I}{M}_{rm W} } $ relative to alginate in collagen-based scaffolds permissive of cell elongation, indicating that PEGDA hydrogels may serve as an effective 3D model system for probing at least certain aspects of VFF behavior. Biotechnol. Bioeng. (c) 2009 Wiley Periodicals, Inc.
Randomized Controlled Trial to Determine the Efficacy of Long-Term Growth Hormone Treatment in Severely Burned Children.
Ann Surg. 2009 Sep 2; Branski LK, Herndon DN, Barrow RE, Kulp GA, Klein GL, Suman OE, Przkora R, Meyer W, Huang T, Lee JO, Chinkes DL, Mlcak RP, Jeschke MGBACKGROUND:: Recovery from a massive burn is characterized by catabolic and hypermetabolic responses that persist up to 2 years and impair rehabilitation and reintegration. The objective of this study was to determine the effects of long-term treatment with recombinant human growth hormone (rhGH) on growth, hypermetabolism, body composition, bone metabolism, cardiac work, and scarring in a large prospective randomized single-center controlled clinical trial in pediatric patients with massive burns. PATIENTS AND METHODS:: A total of 205 pediatric patients with massive burns over 40% total body surface area were prospectively enrolled between 1998 and 2007 (clinicaltrials.gov ID NCT00675714). Patients were randomized to receive either placebo (n = 94) or long-term rhGH at 0.05, 0.1, or 0.2 mg/kg/d (n = 101). Changes in weight, body composition, bone metabolism, cardiac output, resting energy expenditure, hormones, and scar development were measured at patient discharge and at 6, 9, 12, 18, and 24 months postburn. Statistical analysis used Tukey t test or ANOVA followed by Bonferroni correction. Significance was accepted at P < 0.05. RESULTS:: RhGH administration markedly improved growth and lean body mass, whereas hypermetabolism was significantly attenuated. Serum growth hormone, insulin-like growth factor-I, and IGFBP-3 was significantly increased, whereas percent body fat content significantly decreased when compared with placebo, P < 0.05. A subset analysis revealed most lean body mass gain in the 0.2 mg/kg group, P < 0.05. Bone mineral content showed an unexpected decrease in the 0.2 mg/kg group, along with a decrease in PTH and increase in osteocalcin levels, P < 0.05. Resting energy expenditure improved with rhGH administration, most markedly in the 0.1 mg/kg/d rhGH group, P < 0.05. Cardiac output was decreased at 12 and 18 months postburn in the rhGH group. Long-term administration of 0.1 and 0.2 mg/kg/d rhGH significantly improved scarring at 12 months postburn, P < 0.05. CONCLUSION:: This large prospective clinical trial showed that long-term treatment with rhGH effectively enhances recovery of severely burned pediatric patients.
[Surgical management of primary bone cancer]
Bull Acad Natl Med. 2009 Jan; 193(1): 107-26Anract PPatients with primary bone malignancies must be treated by specialized multidisciplinary teams composed of pathologists, surgeons, orthopedists, oncologists, radiologists and radiotherapists, all with experience in the diagnosis and treatment of these tumors. If a malignancy is suspected, the biopsy must also be performed in such a center. Biopsy is part of the treatment and must be done by a senior surgeon, before starting specific treatment. Indeed, inappropriate biopsy can compromise the patient's functional prognosis and sometimes the vital outcome. The biopsy can be done percutaneously under radiological control with a True-cut needle or a trocart to obtain cores of pathological tissue. The pathologist must be well-versed in bone disorders. Open surgical biopsy is preferable for primary bone tumors, especially when a cartilaginous tumor is suspected. A short incision is used, situated on the same approach as that which will be used for surgical resection of the tumor, so that the biopsy scar is excised along with the tumor, in a single block. Surgical treatment of primary bone malignancies requires extensive resection, i.e. excision of the affected bone segment and any invaded soft tissues, as a single block, without breaching the tumor, and preserving a peripheral margin of healthy tissue. In most cases, reconstruction is necessary to preserve the function of the resected region. It is based on standard orthopedic techniques, namely osteosynthesis, bone grafts (autografts and allografts), prostheses of variable size, or a combination of prostheses and allografts (composite reconstruction). Amputation is only indicated if conservative resection is impossible. It has been shown that conservative resection, now possible in about 80% of cases, does not reduce the survival chances of patients with osteosarcoma. The indications for amputation include massive tumors invading vessels and nerves, resection of which would leave the limb non functional, as sell as tumor infection (often secondary to biopsy), inappropriate biopsy (infection of vessels or periarticular muscles, etc.), and local relapse. Amputation must respect the same oncologic principles as conservative resection.
Factors affecting willingness to undergo carpal tunnel release.
J Bone Joint Surg Am. 2009 Sep; 91(9): 2130-6Gong HS, Baek GH, Oh JH, Lee YH, Jeon SH, Chung MSBACKGROUND: Factors regarding patient willingness to undergo or avoid joint replacement have been studied; however, these factors have not been studied in patients with carpal tunnel syndrome. To further understand the aspects that are important for a patient with carpal tunnel syndrome in deciding whether to have surgery, we identified factors that affect this decision in women and that are not related to Workers' Compensation status. METHODS: We retrospectively reviewed 282 female patients with electrophysiologically confirmed carpal tunnel syndrome without a known cause who were recommended for carpal tunnel release by a single hand surgeon in a tertiary medical setting. Of those, thirty-six female patients who were not entitled to Workers' Compensation canceled the operation during the waiting period, which averaged four weeks. Thirty-three of them were surveyed with a questionnaire sent by mail, and eighteen completed surveys were reviewed at a mean follow-up of thirty-two months. Furthermore, seventy female patients who underwent carpal tunnel release were randomly sampled, and thirty-eight patients completed the survey. The operation and cancellation groups were compared with regard to the reasons for choosing or canceling surgery. RESULTS: The groups were similar with regard to age, sociodemographic variables, follow-up length, initial electrophysiological findings, and functional status. The highest-ranked reason for choosing surgery was symptom severity rather than fear of progression or a positive electrodiagnostic result. Those who canceled the operation rated symptom improvement during the waiting period as the leading reason for doing so, but they were also concerned about transient weakness, the financial burden, and a scar or pillar pain. Disease persistence or recurrence was the issue of most concern in both groups. At the time of the final review, the functional status was significantly improved in both groups and no significant difference between the groups was detected. CONCLUSIONS: Women with carpal tunnel syndrome report that subjective symptom severity is the most important reason for undergoing surgery. Understanding this and other patient concerns may help physicians during patient-oriented consultation and decision-making. In particular, recommendations for carpal tunnel release on the basis of symptoms are reasonable from the perspective of the patient who has carpal tunnel syndrome without a known cause.