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IMPROVED DIABETIC WOUND HEALING VIA TOPICAL GENE THERAPY: A VASCULAR MECHANISM [Meeting Abstract]

Tutela, JP; Nguyen, PD; Thanik, VD; Canizares, O; Varjabedian, L; Wagner, J; Lee, JW; Davidson, EH; Haberman, ID; Cohen, OD; Warren, SM; Levine, JP; Saadeh, PB
ISI:000264188600026
ISSN: 1067-1927
CID: 97660

Intracranial Microvascular Free Flaps

Levine, Steven; Garfein, Evan S; Weiner, Howard; Yaremchuk, Michael J; Saadeh, Pierre B; Gurtner, Geoffrey; Levine, Jamie P; Warren, Stephen M
Large acquired intracranial defects can result from trauma or surgery. When reoperation is required because of infection or tumor recurrence, management of the intracranial dead space can be challenging. By providing well-vascularized bulky tissue, intracranial microvascular free flaps offer potential solutions to these life-threatening complications. A multi-institutional retrospective chart and radiographic review was performed of all patients who underwent microvascular free-flap surgery for salvage treatment of postoperative intracranial infections between 1998 and 2006. A total of six patients were identified with large intracranial defects and postoperative intracranial infections. Four patients had parenchymal resections for tumor or seizure and two patients had posttraumatic encephalomalacia. All patients underwent operative debridement and intracranial free-flap reconstruction using the latissimus dorsi muscle ( N = 2), rectus abdominis muscle ( N = 2), or omentum ( N = 2). All patients had titanium ( N = 4) or Medpor ( N = 2) cranioplasties. We concluded that surgery or trauma can result in significant intracranial dead space. Treatment of postoperative intracranial infection can be challenging. Vascularized free tissue transfer not only fills the void, but also provides a delivery system for immune cells, antibodies, and systemically administered antibiotics. The early use of this technique when intracranial dead space and infection coexist is beneficial
PMID: 18925548
ISSN: 0743-684x
CID: 90063

Topical lineage-negative progenitor-cell therapy for diabetic wounds

Lin, Clarence D; Allori, Alexander C; Macklin, Jared E; Sailon, Alexander M; Tanaka, Rica; Levine, Jamie P; Saadeh, Pierre B; Warren, Stephen M
BACKGROUND: Impaired diabetic wound healing is due, in part, to defects in mesenchymal progenitor cell tracking. Theoretically, these defects may be overcome by administering purified progenitor cells directly to the diabetic wound. The authors hypothesize that these progenitor cells will differentiate into endothelial cells, increase wound vascularity, and improve wound healing. METHODS: Lineage-negative progenitor cells were isolated from wild-type murine bone marrow by magnetic cell sorting, suspended in a collagen matrix, and applied topically to full-thickness excisional dorsal cutaneous wounds in diabetic mice. Application of lineage-positive hematopoietic cells or acellular collagen matrix served as comparative controls (n = 16 for each group; n = 48 total). Time to closure and percentage closure were calculated by morphometry. Wounds were harvested at 7, 14, 21, and 28 days and then processed, sectioned, stained (lectin/DiI and CD31), and vascularity was quantified. RESULTS:: Wounds treated with lineage-negative cells demonstrated a significantly decreased time to closure (14 days) compared with lineage-positive (21 days, p = 0.013) and collagen controls (28 days, p = 0.004), and a significant improvement in percentage closure at 14 days compared with the lineage-positive group (p < 0.01) and the collagen control (p < 0.01). Fluorescently tagged lineage-negative cells remained viable in the wound for 28 days, whereas lineage-positive cells were not present after 7 days. Lineage-negative, but not lineage-positive, cells differentiated into endothelial cells. Vascular density and vessel cross-sectional area were significantly higher in lineage-negative wounds. CONCLUSION: Topical progenitor-cell therapy successfully accelerates diabetic wound closure and improves wound vascularity
PMID: 18971717
ISSN: 1529-4242
CID: 90061

Hedgehog signaling is essential for normal wound healing

Le, Huong; Kleinerman, Rebecca; Lerman, Oren Z; Brown, Daniel; Galiano, Robert; Gurtner, Geoffrey C; Warren, Stephen M; Levine, Jamie P; Saadeh, Pierre B
The hedgehog family of morphogens (sonic [Shh], Indian, and desert hedgehog) are central regulators of embryologic growth and tissue patterning. Although recent work implicates Shh in postnatal tissue repair and development, conclusive evidence is lacking. Here, we demonstrated the importance of Shh in wound repair, by examining the effects of cyclopamine, a specific inhibitor of the Shh signaling cascade, on tissue repair. Using a murine-splinted excisional wound model, which attenuates wound contraction in this loose-skinned rodent, we established that, by all measures (wound closure, epithelialization, granulation formation, vascularity, and proliferation), wound healing was profoundly impaired when Shh signaling was disrupted. Because embryonic disruption of Shh is associated with distinct phenotypic defects, our findings invite investigation of the potential role of Shh signaling under postnatal conditions associated with disregulated wound healing
PMID: 19128247
ISSN: 1524-475x
CID: 91870

A novel murine model of isolated skin radiation injury [Meeting Abstract]

Nguyen, PD; Zoumalan, RA; Chang, CC; Allen, RJ; Sailon, AM; Warren, SM; Levine, JP; Saadeh, PB
ISI:000259288500128
ISSN: 1072-7515
CID: 88543

Topically delivered siRNA for cutaneous gene suppression [Meeting Abstract]

Sailon, AM; Thanik, VD; Zoumalan, RA; Chang, CC; Levine, JP; Warren, SM; Saadeh, PB
ISI:000259288500229
ISSN: 1072-7515
CID: 88544

Less Is More: VRAM Inset Modification in Glossectomy Reconstruction

Haddock, Nicholas T; Delacure, Mark D; Saadeh, Pierre B
PMID: 18626322
ISSN: 1529-4242
CID: 94600

Functional reconstruction of glossectomy defects: the vertical rectus abdominus myocutaneous neotongue [Case Report]

Haddock, Nicholas T; DeLacure, Mark D; Saadeh, Pierre B
The vertical rectus abdominus myocutaneous (VRAM) flap is a valuable option for tongue reconstruction. However, the traditional inset (skin to remaining oral mucosa) obviates a more anatomic reconstruction. Eight patients underwent total or subtotal glossectomy with VRAM reconstruction. The muscle inset was supported at the inferior mandibular border attached to the remaining lingual mucosa or gingiva. The neotongue, consisting of skin and subcutaneous fat, was sutured posteriorly to the remaining tongue base, and the other surfaces were trimmed and left unsutured. Reconstruction was successful in all patients. The neotongue assumed palatal configuration, and within 2 weeks uniform granulation tissue followed by mucosalization occurred. One year postoperatively, all patients tolerated ad lib diets, spoke intelligibly, were gastrostomy tube and tracheotomy free and had no evidence of aspiration. This neotongue sits on the mandible under voluntary control, permitting effective obturation against the hard palate and providing successful speech and swallowing
PMID: 18597221
ISSN: 0743-684x
CID: 91434

Microsurgical correction of facial contour deformities in patients with craniofacial malformations: a 15-year experience

Saadeh, Pierre B; Chang, Christopher C; Warren, Stephen M; Reavey, Patrick; McCarthy, Joseph G; Siebert, John W
BACKGROUND: Since their first review of microsurgical correction of facial contour deformities in 19 patients with craniofacial malformations, the authors have treated an additional 74 patients (n = 93). The authors review indications, choices, safety, efficacy, complications, and technical refinements. A treatment algorithm is presented. METHODS: A retrospective chart review of all patients who underwent microvascular reconstruction of the face and all patients with craniofacial dysmorphology was performed. Between 1989 and 2004, a total of 93 patients with the following diagnoses were identified: craniofacial microsomia (n = 73), Treacher Collins syndrome (n = 8), and severe orbitofacial cleft (n = 12). All patients underwent microsurgical facial reconstruction with a superficial inferior epigastric, groin, or circumflex scapular flap. Flap revisions, complications, and non-free flap related surgery were reviewed. RESULTS: The mean age at microvascular reconstruction was 11 years (range, 4 to 27 years). Flap choices included the following: superficial inferior epigastric (n = 4), groin (n = 3), and circumflex scapular (n = 105). Seventy-six patients underwent unilateral and 17 patients underwent bilateral (one of 17 simultaneous) reconstructions. Postoperative complications included partial flap loss (n = 1), reexploration (n = 1), hematoma (n = 5), and cellulitis (n = 5). All patients had subjective improvement in facial contour, symmetry, skin tone, and color. Most patients underwent additional non-free flap procedures including mandibular distraction and ear reconstruction. CONCLUSIONS: Microsurgical flaps have markedly improved the authors' ability to restore craniofacial contour in patients with craniofacial malformations. In selected patients, the authors choose primary midface augmentation with free vascularized tissue to restore form and function. Microsurgical flaps in patients with craniofacial malformations are safe, effective, and reliable
PMID: 18520863
ISSN: 1529-4242
CID: 79461

Alveolar bone regeneration in a gingivoperiosteoplasty model [Meeting Abstract]

Nguyen, PD; Lin, CD; Allori, AC; Reisler, T; Levine, JP; Saadeh, PB; Warren, SM
ISI:000256239800356
ISSN: 1937-3341
CID: 86863