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F Frank Isik

Publications and source records attributed to F Frank Isik.

9 recordsLinked to original sources

Histology of the thick scar on the female, red Duroc pig: final similarities to human hypertrophic scar.

The etiology and treatment of hypertrophic scar remain puzzles even after decades of research. A significant reason is the lack of an accepted animal model of the process. The female, red Duroc pig model was described long ago. Since the skin of the pig is similar to that of humans, we are attempting to validate this model and found it to be encouraging. In this project we quantified myofibroblasts, mast cells and collagen nodules in the thick scar of the Duroc pig and compared these to the values for human hypertrophic scar. We found the results to be quite similar and so further validated the model. In addition, we observed that soon after wounding an inflammatory cell layer forms. The thickness of the inflammatory layer approaches the thickness of the skin removed as if the remaining dermis "knows" how much dermis is gone. In deep wounds this inflammatory layer thickens and this thickness is predictive of the thickness of the ultimate scar.

Adolescent↗

Does the use of a flap during abdominoperineal resection decrease pelvic wound morbidity?

We hypothesized that the use of muscle flaps, known as tissue transfer (TT), at the time of abdominoperineal resection (APR) reduces perineal wound complications. A restrospective review of patients undergoing an APR at the University of Washington (1984-2003) was conducted. Perineal wound complications and eventual wound healing were compared in patients with and without TT. Ninety-two patients (mean age, 56.6 years) underwent APR; 23.9 per cent (n = 22) had concurrent TT. Patients undergoing TT were more likely to have cancer (91% vs. 77%, P = 0.05) and radiation therapy (86% vs. 52%, P < 0.01). Operative times were nearly 2 hours longer in patients having TT (7.4 hours +/- 2.5 hours vs. 5.6 hours +/- 1.8 hours, P = 0.03), but lengths of stay were similar (13 +/- 5.9 days vs. 12 +/- 7.6 days, P = 0.5). Patients undergoing TT had a higher rate of all wound-healing complications (59% vs. 40%, P = 0.1) and major wound-healing complications (32% vs. 26%, P = 0.6). However, these differences were not statistically significant. No differences in major complications were identified in patients with and without preoperative radiation therapy (26% vs. 28%, P = 0.8). Fifteen per cent (n = 14) of all patients failed to heal wounds at 6 months, but only 9 per cent (n = 2) of patients undergoing TT failed to heal their wounds at 6 months compared with 17 per cent (n = 12) in the non-TT group (P = 0.3). After controlling for important covariates, patients undergoing TT during an APR did not have a significantly lower rate of wound complications. The impact of TT on wound healing in patients with recurrent cancer and preoperative radiation therapy is suggestive of a benefit but requires prospective investigation.

Abdomen↗

Simplifying the vertical reduction mammaplasty.

The vertical reduction mammaplasty is an evolving technique. Its proponents report significantly decreased scarring, better breast shape, and more stable results compared with the standard inverted-T method, but the learning curve is long and cosmetic outcomes can be inconsistent. Many surgeons have experimented with the vertical closure before returning to methods more familiar to them. The authors present their modifications to the vertical reduction mammaplasty. Their changes simplify the preoperative markings and the intraoperative technique to shorten the learning curve while maintaining reliable aesthetic results. With the patient standing, only four preoperative marks are made: (1) the inframammary fold; (2) the breast axis; (3) the apex of the new nipple-areola complex; and (4) the medial and lateral limbs of the vertical incision. In the operating room, a medial or a superomedial pedicle is developed. Excess breast skin is resected with the inferior and lateral parenchyma as a C-shaped wedge. The lateral skin-adipose flap is redraped inferomedially and sutured to the chest wall. The inferior aspect of the breast is aggressively debulked and a gathering subcuticular stitch is started 2 cm below the nadir of the nipple-areola complex. Finally, a 38-mm to 42-mm nipple-areola complex marker is used to create a circular defect that is offset 0.5 cm medial to the vertical axis of the breast. In their series, 56 patients were treated and no major complications were noted. The median follow-up period was 17 months. The average reduction was 554.5 g per breast; however, the reduction was greater than 1000 g per breast in eight patients. The authors found that (1) chest wall anchoring improves lateral contour and minimizes axillary fullness; (2) aggressive debulking inferiorly avoids the persistent inferior bulge; and (3) starting the subcuticular gathering suture 2 cm below the nipple-areola complex followed by placement of a nipple-areola complex marker at the conclusion of the case prevents lateral deviation and corrects the nipple-areola complex teardrop deformity. These innovations accelerate the learning curve by simplifying the preoperative markings and lead to more consistent postoperative results and an improved cosmetic outcome. In conclusion, these modifications yield a simple, easily learned vertical reduction mammaplasty with aesthetically reliable results.

Adolescent↗

The female, red Duroc pig as an animal model of hypertrophic scarring and the potential role of the cones of skin.

Hypertrophic scarring occurs after deep dermal wounds. Our understanding of the etiology is poor; one reason is the lack of an animal model. In 1972, Silverstein described scarring in the Duroc pig but the model was never confirmed nor disproved. Another reason, as we previously suggested, is that hypertrophic scarring only occurs within regions of human skin that contain cones and the cones have not been studied in relation to hypertrophic scarring. We, therefore (i) explored healing in the female, red Duroc model for similarities to human hypertrophic scarring, studying wound thickness, appearance, healing status at 3 weeks, histology, and immunocytochemical localization of decorin, versican, TGFbeta1 and IGF-1; and (ii) examined Duroc skin for cones. We found that healing after deep wounds in Duroc pigs is similar, but not identical, to human hypertrophic scarring. We also found that Duroc skin contains cones. Healing in the female, red Duroc pig is sufficiently similar to human hypertrophic scarring to warrant further study so that it can be accepted or rejected as a model of human hypertrophic scarring. In addition, the relationship of the cones to hypertrophic scarring needs further detail and can be studied in this model.

Animals↗

Human dermal microvascular endothelial cells produce nerve growth factor: implications for wound repair.

Following cutaneous injury, sensory nerves regenerate into the dermis and epidermis. Tissues that are innervated by sensory nerves synthesize neurotrophins such as nerve growth factor (NGF). The close anatomic proximity of nerves and capillaries throughout the skin suggests that mutual regulation may exist between nerve fibers and microvascular endothelial cells (MECs) during wound repair. Release of the neuropeptide substance P by sensory nerves induces endothelial cell rounding, capillary leak, and cytokine upregulation. We propose that dermal endothelial cells produce neurotrophins required for nerve fiber maintenance and regeneration. In this study, we demonstrate that substance P stimulates NGF messenger RNA expression by cultured human dermal MECs. Likewise, enzyme-linked immunosorbant assay demonstrated that conditioned medium from cultured dermal MECs contains NGF. NGF bioactivity in the supemates was verified by conditioned medium-induced clonal rat pheochromocytoma (PC-12) cell differentiation. This activity was inhibited by anti-NGF antibodies. Therefore, we have demonstrated that substance P, an inflammatory neuropeptide released by sensory nerve fibers, induces endothelial cells to produce NGF. Our data suggest that MECs may be unrecognized contributors to nerve regeneration after cutaneous injury.

Animals↗

Innovations to the vertical reduction mammaplasty: making the transition.

The vertical reduction mammaplasty can be challenging to learn. In addition, first attempts to perform the vertical reduction mammaplasty can lead to inconsistent aesthetic results. The authors describe their transition from a traditional inverted-T reduction mammaplasty to a modified vertical reduction mammaplasty based on a technique described by Elizabeth Hall-Findlay. In their early cases using the Hall-Findlay technique, they noted several aesthetic complications. These problems included a persistent vertical dog-ear deformity at the nadir of the incision, a teardrop deformity of the nipple-areola complex, lateral deviation of the nipple, and lateral axillary fullness. They developed several modifications to the Hall-Findlay technique to correct the aesthetic deficiencies and to simplify further the vertical reduction method. The authors think their innovations facilitate the transition from a traditional inverted-T breast reduction to a successful vertical reduction mammaplasty technique.

Adult↗

Diminished neuropeptide levels contribute to the impaired cutaneous healing response associated with diabetes mellitus.

Background. Patients with diabetic sensory neuropathy have significant risk of chronic ulcers. Insufficient nerve-derived mediators such as substance P (SP) may contribute to the impaired response to injury. Mutant diabetic mice (db/db), which develop neuropathy and have delayed healing, may provide a model to study the role of nerves in cutaneous injury.Methods. Skin from human chronic nonhealing ulcers and age-matched control skin was immunohistochemically evaluated for nerves. Nerve counts were also compared in murine diabetic (C57BL/KsJ-m+/+ Lepr(db); db/db) and nondiabetic (db/-) skin. Excisional wounds on the backs of db/db and db/- mice were grouped as: (a) untreated db/- mice; (b) untreated db/db mice; (c) db/db mice with polyethylene glycol (PEG); (d) db/db mice with PEG and SP 10(-9) M; or (e) db/db mice with PEG and SP 10(-6) M.Results. We demonstrated fewer nerves in the epidermis and papillary dermis of skin from human subjects with diabetes. Likewise, db/db murine skin had significantly fewer epidermal nerves than nondiabetic littermates. We confirmed increased healing times in db/db mice (51.7 days) compared to db/- littermates (19.8 days; P </= 0.001). SP 10(-6) M (44 days; P = 0.02) and SP 10(-9) M (45 days; P = 0.03) shortened time to closure compared to PEG treatment alone (68 days). Since there was no difference in the percentage contraction in these treatment groups, SP may favorably promote wound epithelization.Conclusions. Our data support the use of db/db murine excisional wounds to evaluate the role of nerves in healing. We have demonstrated that exogenous SP improves wound healing kinetics in an animal model.

Aged↗

Utility of the free deep inferior epigastric perforator flap in chest wall reconstruction.

Breast cancer chest wall recurrence is often treated with chemotherapy, radical surgery, and radiation. Extensive chest wall resection requires soft-tissue reconstruction with tissue that provides chest wall stability and durability for additional radiation. Local and regional muscle and musculocutaneous flaps are often used for reconstruction. Free flaps, such as the transverse rectus abdominis musculocutaneous flap, are used for large defects, although donor site morbidity can result. The free deep inferior epigastric perforator (DIEP) flap provides coverage for large defects and may have less donor site morbidity. We describe the use of the free DIEP flap to reconstruct large chest wall defects (mean, 501 cm2 defects) after the resection of recurrent breast cancer in two patients. One patient had 2% flap loss. No donor site morbidity occurred. The free DIEP flap is a durable and reliable flap that provided immediate and complete coverage of these large chest wall defects with no donor site morbidity and did not delay the administration of adjuvant therapy.

Breast Neoplasms↗