Biomedical subjects

James Chang

Publications and source records attributed to James Chang.

At least 19 recordsLinked to original sources

PubMed2007

Optimization of microsurgery: improved coverage of the latissimus dorsi vascular pedicle with vascularized serratus fascia.

The latissimus dorsi free flap is a workhorse for extremity reconstruction. One of its benefits is a long vascular pedicle that spans the zone of injury. However, it may be difficult to adequately cover this pedicle. Direct closure may be too tight, and skin grafting over the pedicle risks exposure if graft take is poor. We report a technique in which the serratus branch of the thoracodorsal artery and its overlying fascia are harvested en bloc with the thoracodorsal artery and latissimus muscle. This provides 2 flaps on a common pedicle that can easily be rotated to allow positioning and insetting. We successfully used this technique in the reconstruction of both upper and lower extremities. The serratus fascia provides excellent padded covering and is a good bed for skin grafting. The versatility of this hybrid flap will allow its use in a range of complex reconstructive procedures.

Adult↗

PubMed2007

Requests for 692 transfers to an academic level I trauma center: implications of the emergency medical treatment and active labor act.

BACKGROUND: The Emergency Medical Treatment and Active Labor Act (EMTALA) effectively requires Level I trauma centers (TC) to accept all transfers for a higher level of care if capacity exists. We hypothesized that EMTALA would burden a Level I TC by a selective referral of a poor payer mix of primarily nonoperative patients. METHODS: All transfer calls (December 2003 and September 2005) to our Level I TC are handled by a dedicated transfer center. Calls were reviewed for age, surgical service requested, and outcome of request. The trauma registry was queried to compare Injury Severity Scale (ISS) score, hospital stay (LOS), operations, mortality, and payer status for transfer and primary catchment patients. RESULTS: In all, 821 calls were received; 77 calls were cancelled by the referring hospital and 52 were for consultation only. Of the 692 transfer requests, 534 (77%) were accepted, 134 (19%) were denied for no capacity, and only 24 (4%) were declined by TC as not clinically indicated. Transferred patients were younger (32.0 +/- 1.49 versus 38.9 +/- 0.51, p < 0.05), had similar ISS scores (13.6 +/- 0.62 versus 13.7 +/- 0.26) and LOS (7.0 +/- 0.70 versus 7.4 +/- 0.25), but were somewhat more likely to require an operation than direct admissions (58% versus 51%, p < 0.05). Although trauma (24%) and neurosurgery (24%) were the most commonly requested services, followed by orthopedics (20%), orthopedics accounted for 60% of operations on transferred patients compared with 10% to 13% for trauma and neurosurgery (mostly spine). There was no difference in the payer status of transfer and direct admit patients. CONCLUSIONS: Contrary to our assumptions, EMTALA patients had an identical payer mix and similar operative need compared with our primary catchment patients. They do represent a large additional patient load (20% of admissions) and differentially impact specialists, mostly operative for orthopedics and complex nonoperative care for trauma and neurosurgery. These data suggest that the primary motivations for transfer are specialist availability and complexity of care rather than financial concerns. As TCs provide backup specialty call coverage for a wide geographic area, this further supports the need for trauma systems development.

Adult↗

PubMed2006

Expression of a novel gene, MafB, in Dupuytren's disease.

PURPOSE: Dupuytren's disease (DD) is characterized by fibroblastic proliferation of the palmar fascia, often leading to flexion contracture in the hand. Although there is a strong genetic component the genome-wide expression of novel genes is not known. The purpose of this study was to use DNA microarray technology to identify upregulated genes in DD. METHODS: Human tissue samples were harvested from 3 patient sources: DD cord tissue (n = 20), normal-appearing adjacent control fascia (n = 15), and palmar fascia from patients having carpal tunnel release (n = 15). DNA microarray analysis was performed on amplified sample RNA. Novel genes were compared with known gene functions. A candidate gene of interest was studied further by using immunohistochemistry on DD tissue samples and controls. RESULTS: Several novel genes not described previously in the study of DD were upregulated significantly, including MafB, collagen type V, alpha-2 (COL5A2), collagen type VIII, alpha-1 (COL8A1), contactin I (CNTN1), and leucine-rich repeat containing 17 (LRRC17). These upregulated genes were compared with their known gene-expression profiles in other tissues and their purported functions. MafB was found to be of particular interest because of its prominent role in tissue development and cellular differentiation. MafB immunohistochemistry showed positive staining in 50% of the DD specimens but complete absence of MafB in all control tissues (adjacent control fascia, carpal tunnel fascia). Co-localization experiments with MafB and alpha-smooth muscle actin showed staining properties in similar regions but these 2 proteins were not confined solely to the same cells. CONCLUSIONS: Microarray analysis of DD tissue has identified significant upregulated gene expression of MafB. MafB protein also is found in Dupuytren's cords but not in control fascia. Co-localization data suggest that the association of MafB with DD is not related exclusively to myofibroblast proliferation. Because of its role in fibroblastic transformation in other models MafB and its relationship to the pathogenesis of DD deserves further study.

Actins↗

PubMed2006

Tissue engineering for the hand surgeon: a clinical perspective.

Hand surgeons may be faced with tissue shortages for reconstruction after trauma, tumor resection, or congenital deficiency. Tissue engineering is a developing scientific field that combines the principles of life sciences and engineering in developing biologic substitutes that will restore, maintain, or improve tissue function. This article reviews the general principles of tissue engineering as applied to musculoskeletal tissues including nerve, bone, tendon, skin, vessels, and cartilage and focuses on the application of tissue engineering that is relevant to clinical hand surgery.

Blood Vessel Prosthesis↗

PubMed2006

Tissue engineering of flexor tendons: optimization of tenocyte proliferation using growth factor supplementation.

A significant problem in flexor tendon repair is the lack of suitable graft material for reconstruction. The ex vivo production of flexor tendon graft constructs requires the expansion of primary cells. Growth factors, such as platelet-derived growth factor-BB (PDGF-BB), insulin-like growth factor-1 (IGF-1), and basic fibroblast growth factor (bFGF), are known to promote tendon healing and tendon cell proliferation. The purpose of these experiments was to optimize tenocyte proliferation in 3 tendon cell populations using growth factor supplementation. Cells of the synovial sheath, epitenon, and endotenon were isolated from rabbit flexor digitorum profundus tendons and maintained in culture. Cell cultures were supplemented with IGF-1, PDGF-BB, and bFGF alone and in combination. The conditions used for individual growth factor supplementation were IGF-1 (10, 50, and 100 ng/mL), PDGF-BB (1, 10, and 50 ng/mL), and bFGF (0.5, 1, and 5 ng/mL). The conditions used for combinations of growth factors were IGF-1 + PDGF-BB (50 + 10 and 100 + 50 ng/mL, respectively) and IGF-1 + PDGF-BB+ bFGF (50 + 10 + 1; 50 + 10 + 5; 100 + 50 + 1; and 100 + 50 + 5 ng/mL, respectively). For all 3 tendon cell populations, proliferation at 72 h was greater in the presence of individual growth factors as compared to controls. With PDGF-BB (50 ng/mL) supplementation, mean absorbance values increased 97% (0.57 to 1.13) in S cells, 37% (0.51 to 0.70) in E cells, and 33% (0.33 to 0.44) in T cells ( p < 0.001). In addition, a synergistic effect was observed. The combination of growth factors resulted in greater proliferation as compared to maximal doses of individual growth factors. In cultures supplemented with IGF-1 (100 ng/mL) +PDGF-BB (50 ng/mL), mean absorbance increased 114% (0.57 to 1.22) in S cells, 63% (0.51 to 0.831) in E cells, and 47% (0.33 to 0.48) in T cells ( p < 0.001). IGF-1 (100 ng/mL) + PDGF-BB (50 ng/mL) + bFGF (5 ng/mL) resulted in the greatest amount of cell proliferation for all 3 tendon cell populations. The mean absorbances increased 251% in S cells, 98% in E cells, and 106% in T cells ( p < 0.001). In summary, IGF-1, PDGF-BB, and bFGF can be used in combination to maximize tenocyte proliferation. Synergism among growth factors may provide a means to facilitate tendon engineering.

Animals↗

PubMed2006

Mannose-6-phosphate, an inhibitor of transforming growth factor-beta, improves range of motion after flexor tendon repair.

BACKGROUND: Adhesion formation between the flexor tendon and its surrounding fibro-osseous sheath results in a decreased postoperative range of motion in the hand. Transforming growth factor-beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. In this study, the effects of two natural inhibitors of TGF-beta, decorin and mannose-6-phosphate, were investigated in vitro and in vivo. METHODS: In the in vitro investigation, primary cell cultures from rabbit flexor tendon sheath, epitenon, and endotenon were established and each was supplemented with TGF-beta along with increasing doses of decorin or mannose-6-phosphate. Collagen-I production was measured with enzyme-linked immunosorbent assay (ELISA). For the in vivo study, rabbit zone-II flexor tendons were transected and then immediately repaired. Single intraoperative graded doses of decorin, mannose-6-phosphate, or phosphate-buffered saline solution (control) were added to the repair sites, and the forepaws were tested for the range of motion and repair strength at eight weeks postoperatively. RESULTS: Decorin and mannose-6-phosphate both reduced TGF-beta upregulated collagen production. Intraoperative application of low-dose mannose-6-phosphate significantly improved the range of motion of the operatively treated digits. The effect on breaking strength of the tendon repair was inconclusive. CONCLUSIONS: Mannose-6-phosphate is effective in reducing TGF-beta upregulated collagen production in an in vitro model. This finding correlated with our in vivo finding that a single intraoperative dose of mannose-6-phosphate improved the postoperative range of motion.

Animals↗

PubMed2005

Vascular mapping of the leg with multi-detector row CT angiography prior to free-flap transplantation.

PURPOSE: To retrospectively evaluate multi-detector row computed tomographic (CT) angiography in determining donor- and recipient-site arterial suitability for successful vascularized free-flap transplantation. MATERIALS AND METHODS: The institutional review board granted approval; informed consent was waived, and the study was HIPAA compliant. Lower extremities of 20 (12 male, eight female; mean age, 51 years; range, 10-84 years) patients undergoing vascularized free-flap procedures were examined at multi-detector row CT angiography. In five patients, legs were assessed as potential fibular free-flap donors for mandibular, maxillary, or radial reconstruction. In 15 patients, legs were assessed as recipient sites for free flaps. Vascular maps obtained with volume rendering, maximum intensity projections, and curved planar reformations were generated, and assessment was made in the depiction of calf vessels and presence of stenosis, occlusion, and anatomic anomaly. Findings of CT angiography, physical examination, and surgery were compared, where applicable, and successful CT-based prediction of the surgical intervention was assessed. Immediate and long-term (>70 days) viability of the graft was assessed in all patients. RESULTS: CT angiography depicted the entirety of all four major calf arteries in 29 of 32 legs scanned. In three legs, external-fixation hardware obscured some segments. There were no discrepancies between CT findings and those identified at the time of surgery. Arterial abnormalities, including stenosis, occlusion, and variant anatomy, were seen in 12 lower extremities in 10 patients. Only two were suspected on the basis of physical examination findings. In five of 20 patients, CT findings resulted in changes to the surgical plan. There was a 100% immediate viability of all grafts, which remained well vascularized between 70 days and 37 months after the procedure. CONCLUSION: Multi-detector row CT angiography provides a noninvasive means of preoperatively assessing lower extremity arteries for abnormalities, which could jeopardize graft viability or pedal arterial supply after free-flap procedures.

Aged↗

PubMed2005

Novel therapies for rheumatoid arthritis.

Recent years have witnessed significant advancements in the therapeutic approach to rheumatoid arthritis. The introduction of biologic agents, in particular inhibitors of tumor necrosis factor (TNF), has ushered a new era in which the goal of therapy has become achieving very low levels of disease activity. Success achieved with the TNF inhibitors has reinvigorated research into targeting other componenets of the dysregulated immune system in RA. A number of approaches, targeting various cytokines, other inflammatory mediators, and populations of immunocompetent cells, seem promising.

Journal Article↗

PubMed2005

Microarray analysis of mechanical shear effects on flexor tendon cells.

BACKGROUND: Adhesion formation after flexor tendon repair remains a clinical problem. Early postoperative motion after tendon repair has been demonstrated to reduce adhesion formation while increasing tendon strength. The authors hypothesized that during mobilization, tendon cells experience mechanical shear forces that alter their biology in a fashion that reduces scar formation but also activates key genes involved in tendon healing. METHODS: To test this hypothesis, primary intrinsic tenocyte cultures were established from flexor tendons of 20 Sprague-Dawley rats and sheared at 50 rpm (0.41 Pa) using a cone viscometer for 6 and 12 hours. Total RNA was harvested and compared with time-matched unsheared controls using cDNA microarrays and Northern blot analysis. RESULTS: Microarray analysis demonstrated that mechanical shear stress induced an overall "antifibrotic" expression pattern with decreased transcription of collagen type I and collagen type III. Shear stress down-regulated profibrotic molecules in the platelet-derived growth factor, insulin-like growth factor, and fibroblast growth factor signaling pathways. In addition, shear stress induced an overall decrease in transforming growth factor (TGF)-beta signaling pathway molecules with down-regulation of TGF-beta2, TGF-beta3, TGF-RI, and TGF-RII expression. Moreover, sheared tendon cells increased expression of matrix metalloproteinases and decreased expression of tissue inhibitors of metalloproteinase, an expression pattern consistent with an antifibrotic increase in extracellular matrix degradation. However, the authors also found up-regulation of genes implicated in tendon healing, specifically, vascular endothelial growth factor-A and several bone morphogenetic proteins. Interestingly, the known mechanoresponsive gene, TGF-beta1, also implicated in tendon healing, was differentially up-regulated by shear stress. Northern blot validation of our results for TGF-beta1, TGF-beta2, TGF-beta3, and collagen type I demonstrated direct correlation with the authors' microarray data. CONCLUSIONS: The authors demonstrate an overall antifibrotic expression pattern in response to shear stress in tendon cells that may provide insight into the mechanisms by which early mobilization decreases adhesion formation without impaired tendon healing.

Animals↗

PubMed2004

Preoperative CT angiography for free fibula transfer.

The role of preoperative imaging prior to free fibula flap harvest remains controversial. The standard method of preoperative imaging has been arteriography. However, arteriography is associated with known risks and potential complications to the patient. Alternatives to traditional angiography have been sought to attempt to reduce these risks. CT angiography is a noninvasive imaging modality that can accurately assess the arterial and venous circulation, while providing images equal to those of traditional angiography. CT angiography was used in 7 patients prior to free fibula flap harvest. There were no complications from the CT angiogram or the fibula harvest. We describe our use of CT angiography for vascular imaging of the lower extremity prior to free fibula harvest.

Angiography↗

PubMed2004

Inhibition of TGF-beta-induced collagen production in rabbit flexor tendons.

PURPOSE: Postoperative adhesions frequently compromise the success of flexor tendon repair. Manipulation of growth factors responsible for scar formation may be a method of decreasing adhesion formation. Transforming growth factor beta (TGF-beta) is a key cytokine in the pathogenesis of tissue fibrosis. The purpose of this study was to examine the effectiveness of TGF-beta neutralizing antibody in blocking TGF-beta-induced collagen I production in rabbit flexor tendons in vitro. METHODS: Sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were obtained from rabbit flexor tendons. Each cell culture was supplemented with 1 ng/mL of TGF-beta along with increasing doses of TGF-beta neutralizing antibody (0.1-2.0 microg/mL). Collagen I production was measured by enzyme-linked immunoabsorbent assay and TGF-beta bioactivity was measured by the luciferase assay. Results were compared with TGF-beta alone and unsupplemented controls. RESULTS: The addition of neutralizing antibody significantly reduced TGF-beta-induced collagen I production in a dose-dependent manner in all 3 cell cultures. TGF-beta bioactivity was also reduced by its neutralizing antibody. CONCLUSIONS: This study shows that TGF-beta inhibition through its neutralizing antibody was effective in cultured flexor tendon cells. The results encourage further experiments that use such agents to modulate flexor tendon wound healing in in vivo models in the hope of eventually blocking the effect of TGF-beta on flexor tendons clinically.

Animals↗

PubMed2004

Clinical implications of growth factors in flexor tendon wound healing.

Recent research has focused on the role of growth factors in flexor tendon wound healing. These basic science reports have described the identification and quantification of various growth factors in in vitro and in vivo models. Although these reports have begun to piece together the cascade of events involved in flexor tendon wound healing, the clinical relevance for the practicing hand surgeon is unclear. Growth factors are cell-secreted proteins that regulate cellular functions. These growth factors are involved in cell differentiation and growth, including the normal processes of development and tissue repair. Several growth factors recently have been identified as playing roles in tendon healing including vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), and transforming growth factor beta (TGF-beta). In addition, the transcription factor NF-kappaB has been implicated in the signaling pathways of these growth factors. The purpose of this article is to describe what is known about the molecular basis of flexor tendon wound healing, to review the most commonly studied growth factors, and to summarize likely clinical applications of these growth factors to flexor tendon repair.

Animals↗

PubMed2004

Twelve simple maneuvers to optimize digital replantation and revascularization.

Trauma can result in either complete amputation of fingers or devascularization of parts. Microsurgical techniques have made the salvage of devascularized digits possible. Although algorithms for digital replantation and revascularization exist, these procedures remain technically difficult and tedious. In multiple digit injuries, the complexity of replantation and revascularization is significantly increased. From our combined experience, we have found many "tricks" that have optimized digital replantation. In this paper, the current indications and contraindications for digital replantation and the technique of replantation are presented with specific reference to 12 simple maneuvers designed to maximize simplicity and efficiency.

Journal Article↗

PubMed2004

Flexor tendon wound healing in vitro: lactate up-regulation of TGF-beta expression and functional activity.

Flexor tendon wound healing in zone II is complicated by adhesions to the surrounding fibro-osseous sheath. These adhesions can significantly alter tendon gliding and ultimately hand function. Lactate and transforming growth factor-beta (TGF-beta) are two important mediators of wound healing that have been demonstrated to independently increase collagen production by cells of the tendon sheath, epitenon, and endotenon. This study examined the effects of lactate on TGF-beta peptide and receptor production by flexor tendon cells. Tendon sheath fibroblasts, epitenon tenocytes, and endotenon tenocytes were isolated from rabbit flexor tendons and cultured separately. Cell cultures were supplemented with 50 mM lactate, and the expression of three TGF-beta peptide isoforms (beta1, beta2, and beta3) and three receptor isoforms (R1, R2, and R3) was quantified with enzyme-linked immunosorbent assays. TGF-beta functional activity was also assessed with the addition of tendon cell conditioned media to mink lung epithelial cells transfected with a luciferase reporter gene expression construct responsive to TGF-beta. Supplementation of the cell culture medium with lactate significantly (p < 0.05) increased the expression of all TGF-beta peptide and receptor isoforms in all three cell lines. Tendon sheath fibroblasts exhibited the greatest increases in beta1 and beta2 peptide isoform expression (30 and 23 percent, respectively), whereas endotenon tenocytes demonstrated the greatest increase in beta3 peptide expression (32 percent). Epitenon tenocytes exhibited the greatest increases in receptor isoform R1 and R2 expression (17 and 19 percent, respectively). All three tendon cell types demonstrated significant (p < 0.05) increases in TGF-beta functional activity when exposed to lactate. Epitenon tenocytes demonstrated the greatest increase in activity (>4 times control values), whereas tendon sheath fibroblasts demonstrated the highest overall levels of total TGF-beta functional activity. Lactate significantly increased TGF-beta peptide (beta1, beta2, and beta3) expression, receptor (R1, R2, and R3) expression, and functional activity, suggesting a common pathway regulating tendon cell collagen production. Modulation of lactate and TGF-beta levels may provide a means of modulating the effects of TGF-beta on adhesion formation in flexor tendon wound healing.

Animals↗

PubMed2004

AC133+ G0 cells from cord blood show a high incidence of long-term culture-initiating cells and a capacity for more than 100 million-fold amplification of colony-forming cells in vitro.

AC133+ cells may provide an alternative to CD34+ cells as a target for cell expansion and gene therapy protocols. We examined the differences in proliferative potential between cord blood selected for AC133 or CD34 in serum-free, stroma cell-free culture for up to 30 weeks. Because most hemopoietic stem cells reside within the G0/G1 phase of the cell cycle, we combined enrichment according to AC133 or CD34 expression with G0 position in the cell cycle to identify populations enriched for putative stem cells. Our results show that AC133+ G0 cells demonstrated a long-term culture-initiating cell incidence of 1 in 4.2 cells, had a colony-forming cell incidence of 1 in 2.8 cells, were capable of producing 660 million-fold expansion of nucleated cells and 120 million-fold expansion of colony-forming units-granulocyte-macrophage over a period of 30 weeks, and were consistently superior to CD34+ G0 cells according to these parameters. Furthermore, we have shown that AC133+CD34- cells have the ability to generate CD34+ cells in culture, which suggests that at least some AC133+ cells are ancestral to CD34+ cells. We conclude that AC133 isolation provides a better means of selection for primitive hemopoietic cells than CD34 and that, in combination with isolation according to G0 phase of the cell cycle, AC133 isolation identifies a highly enriched population of putative stem cells.

AC133 Antigen↗

PubMed2003

Three-dimensional hyaluronic acid grafts promote healing and reduce scar formation in skin incision wounds.

Hyaluronic acid (HA) has been found to play important roles in tissue regeneration and wound-healing processes. Fetal tissue with a high concentration of HA heals rapidly without scarring. The present study employed HA formed into three-dimensional strands with or without keratinocytes to treat full-thickness skin incision wounds in rats. Wound closure rates of HA strand grafts both with and without keratinocytes were substantially enhanced. The closure times of both HA grafts were less than 1 day (average 16 h), about 1/7 that of the contralateral control incisions (114 h, p <.01). Average wound areas after 10 days were HA-only graft: 0.151 mm2 +/- 0.035; HA + cell grafts: 0.143 mm2 +/- 0.036 and controls: 14.434 mm2 +/- 1.175, experimental areas were 1% of the controls (p < 0.01). Transforming growth factor (TGF) beta1 measured by immunostaining was remarkably reduced in HA-treated wounds compared to the controls. In conclusion, HA grafts appeared to produce a fetal-like environment with reduced TGF-beta1, which is known to be elevated in incipient scars. The HA strands with or without cultured cells may potentially improve clinical wound healing as well as reduce scar formation.

Animals↗

PubMed2003

Tissue engineering of flexor tendons.

Despite technical advances in suture methods and rehabilitation protocols, challenges remain in the field of flexor tendon repair. This article reviews the state-of-the-art research in the tissue engineering of flexor tendons. These early published data will hopefully lay the foundation for molecular methods and materials that can be used to reconstruct tendons to restore normal form and function in the hand.

Humans↗

PubMed2003

Protective effects of superoxide dismutase against ischemia-reperfusion injury: development and application of a transgenic animal model.

Reperfusion of ischemic tissues can be associated with structural and functional injury, which is referred to as ischemia-reperfusion injury. Superoxide dismutase is an endogenous free radical scavenger that converts toxic oxygen derived free radicals to hydrogen peroxide. With the development of gene cloning technology, the potential of manipulating cells to overexpress endogenous proteins has been realized. Transgenic mice capable of overexpressing superoxide dismutase, and knockout mice in which the gene responsible for its production has been deleted, were used as a model to examine the protective effects of superoxide dismutase against ischemia-reperfusion injury. Epigastric island flaps were elevated in wild-type (control), transgenic superoxide dismutase 1, and knockout superoxide dismutase 1 mice and subjected to ischemic intervals of 0, 3, 6, 9, or 12 hours. Five animals were studied at each time point in each study group. Flap viability was assessed on postoperative day 7. Baseline wild-type flap survival was 100 percent after 3 hours of ischemia and subsequent reperfusion; survival decreased to 21 percent after 9 hours of ischemia. Transgenic mice had significantly higher flap survival than wild-type animals after 6 hours of ischemia and subsequent reperfusion (97.0 versus 85.2 percent) and after 9 hours of ischemia (82 versus 21 percent, p < 0.01). In knockout mice, there was complete flap necrosis after as little as 3 hours of ischemia. This study confirms the protective effects of superoxide dismutase against ischemia-reperfusion injury. In addition, its deficiency results in a dramatic susceptibility to ischemic injury.

Abdominal Wall↗