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Biomedical subjects

Thomas A Mustoe

Publications and source records attributed to Thomas A Mustoe.

29 records · Page 2Linked to original sources

Why change a good thing? Revisiting the fleur-de-lis reconstruction of the breast.

Although the latissimus flap is known for its simplicity and reliability, use of the fleur-de-lis pattern was plagued by undesirable T-shaped donor sites and small breast volumes in thin patients. We report a modified technique for optimal shaping of the standard latissimus with the successful application of a modified fleur-de-lis pattern. Because a "wet" tumescent infiltration was utilized and large amounts of subcutaneous fat were harvested, these changes permitted application to a wide variety of patients, with generous breast volumes reducing the size of the implant placed and resulting in excellent donor-site scars. This is a retrospective cohort study of 53 delayed or immediate reconstructions performed consecutively by the principal author (M.E.A.) on 48 patients at a university-based, urban hospital. Each case was analyzed between April of 1995 and February of 1999, with a follow-up from 2.5 to 44 months. All patients underwent injection of tumescent solution into the subcutaneous plane and harvest of large amounts of subcutaneous fat with the neurologically intact latissimus muscle. The last 25 reconstructions utilized the modified fleur-de-lis skin pattern, an inferiorly based vertical limb and replacement of skin deficiency in both axes. Of 11 perioperatively irradiated patients, none required skin grafting, whereas 6 percent of all native mastectomy flaps were grafted. There was one instance of minor distal tip flap necrosis in a nonirradiated patient. No implants became infected or were extruded. Donor sites were without wound complications and unveiled a 16 percent overall seroma rate.Through selective addition of harvested tissue, this modified technique, particularly the fleur-de-lis pattern, permits improved volume and projection in the inferior pole. The T-shaped donor-site closure is not only acceptable, but is also desirable, with reduced wound tension and minimization of dog-ear formation. With a relative paucity of complications, this conceptually ideal modification is technically simple and aesthetically comparable to our transverse rectus abdominis muscle flap results.

Adult↗

Simplified technique for creating a youthful umbilicus in abdominoplasty.

Reimplantation of the umbilicus remains a critical aesthetic component in abdominoplasty and transverse rectus abdominis musculocutaneous breast reconstruction. Although the ideal shape of the umbilicus has been debated, recent studies have shown the young, thin female with an attractive abdomen tends to have a small, vertically oriented umbilicus. The aesthetic considerations for reimplantation include position, depth, shape, and location of scar. The authors present a technique that is expedient and reliable and that addresses each of these variables. The umbilicus is sutured to the rectus fascia and reimplanted through a vertical incision in the abdominal flap. Subdermal sutures are placed from the umbilicus to the linea alba superiorly and inferiorly. These sutures create a vertically oriented shape and place the umbilicus in the midline. Shortening the umbilical stalk establishes depth and hides the closure of the umbilicus and abdominal flap within the stalk. The stalk length is easily varied, depending on the thickness of the panniculus. Defatting is performed through the vertical incision to allow easy visualization of the umbilicus. This technique creates depth, ensures optimal position, pulls the scar deep in the umbilicus, and produces a vertically oriented, youthful umbilicus. More importantly, a questionnaire given to patients who have undergone abdominoplasty with this procedure (n = 21) confirms that patients have a high level of satisfaction with the resulting shape, position, and overall appearance.

Abdomen↗

The prevention of emesis in plastic surgery: a randomized, prospective study.

Perhaps the most unpleasant experience following outpatient plastic surgery procedures is postoperative nausea and vomiting. Postoperative nausea and vomiting often results in delayed recovery time and unintended admission, and it can be a contributing factor to the formation of hematoma following rhytidectomy. Ondansetron (Zofran) has proven benefit in preventing postoperative nausea and vomiting if given before general anesthesia in a variety of surgical procedures. Its utility in cases performed under conscious sedation has not been determined. The purpose of this study was (1) to test the ability of prophylactic ondansetron to prevent postoperative nausea and vomiting in plastic surgery cases performed under conscious sedation, and (2) to determine relative risk factors for postoperative nausea and vomiting and a selection policy for the administration of antiemetic prophylaxis. This was a prospective, randomized, double-blind study. One hundred twenty patients were enrolled after giving informed consent. Patients received a single dose of either placebo or ondansetron (4 mg intravenously) before administration of sedation. Sedation administration followed a standardized institutional protocol, using midazolam and fentanyl. Data were recorded from a series of three questionnaires: preoperatively, immediately postoperatively, and at the time of the first office return. Data were confirmed by means of telephone interview, chart analysis, and nursing documentation. Multivariate analysis was conducted. Nausea and emesis occurred with an overall frequency of 33 percent and 22 percent, respectively. Postoperative nausea and vomiting was associated with statistically longer recovery periods. The incidence of emesis was statistically higher among women, among those undergoing facial rejuvenation, and among those with a history of opioid-induced emesis or postoperative nausea and vomiting following a previous operation (p < 0.05). The incidence of postoperative nausea and vomiting paralleled increases in case duration; the incidence of emesis was zero in cases less than 90 minutes in duration. Ondansetron significantly reduced the incidence of emesis overall (placebo, 30 percent; ondansetron, 13 percent; p < 0.05). Postoperative perception of nausea was significantly lower among those who had received ondansetron (p < 0.05). These results confirm the efficacy of ondansetron for the prevention of postoperative nausea and vomiting in plastic surgery cases under conscious sedation. In those who are at increased risk, prophylaxis should be considered. Such risks include female gender, facial rejuvenation procedures, and a patient history of opioid-induced emesis or postoperative nausea and vomiting following a prior operation. The zero incidence of emesis in cases less than 90 minutes does not support the routine use of prophylaxis in such cases. Patient satisfaction in plastic surgery is derived from the overall subjective experience of the event as much as by the final result. By remaining attentive to patient concerns and optimizing perioperative care, we can improve the subjective experience for our patients.

Analgesics, Opioid↗

Effect of Mederma on hypertrophic scarring in the rabbit ear model.

Currently accepted conservative treatments of hypertrophic scars are limited to steroid injections, radiation therapy, and silicone occlusive therapy. However, the use of Mederma for these problematic lesions has become quite prevalent in the clinical setting. Little scientific evidence exists to support the efficacy of this product in reducing hypertrophic scars. The aim of this study was to study the effects of Mederma on hypertrophic scars in the rabbit hypertrophic scar model, allowing the histologic quantification of scar elevation, dermal collagen organization, vascularity, and inflammation and the gross examination of scar erythema. Full-thickness wounds down to cartilage, four per ear, were created in four New Zealand White rabbits, for a total of 32 scars. Twenty-eight days after the initial wounding, the hypertrophic scars were photographed, and treatment of half of the scars on each ear was begun with Mederma three times per day for a total of 4 weeks. The untreated scars served as control scars and were left exposed to air. After 4 weeks of treatment, the scars were once again photographed. The rabbits were then killed, and the scars were analyzed histologically. The pretreatment and posttreatment photographs were compared by using computer quantification of magenta, yellow, and cyan expression within the scars. Histologic analysis demonstrated no significant reduction in scar hypertrophy or scar elevation index. However, a significant improvement in dermal collagen organization was noted on comparing Mederma-treated scars with untreated control scars (p < 0.05). No significant difference in dermal vascularity or inflammation was noted. Computer analysis of the scar photographs demonstrated no significant reduction in scar erythema with Mederma treatment. The active product in Mederma, allium cepa, has as its derivative quercetin, a bioflavonoid noted for its antiproliferative effects on both normal and malignant cells, and its antihistamine release effects. These properties could theoretically prove beneficial in reversing the inflammatory and proliferative responses noted in hypertrophic scars. Despite the authors' inability to demonstrate a reduction in scar hypertrophy, the improvement in collagen organization noted in the Mederma-treated scars suggests it may have an effect on the pathophysiology of hypertrophic scar formation.

Animals↗

International clinical recommendations on scar management.

Many techniques for management of hypertrophic scars and keloids have been proven through extensive use, but few have been supported by prospective studies with adequate control groups. Several new therapies showed good results in small-scale trials, but these have not been repeated in larger trials with long-term follow-up. This article reports a qualitative overview of the available clinical literature by an international panel of experts using standard methods of appraisal. The article provides evidence-based recommendations on prevention and treatment of abnormal scarring and, where studies are insufficient, consensus on best practice. The recommendations focus on the management of hypertrophic scars and keloids, and are internationally applicable in a range of clinical situations. These recommendations support a move to a more evidence-based approach in scar management. This approach highlights a primary role for silicone gel sheeting and intralesional corticosteroids in the management of a wide variety of abnormal scars. The authors concluded that these are the only treatments for which sufficient evidence exists to make evidence-based recommendations. A number of other therapies that are in common use have achieved acceptance by the authors as standard practice. However, it is highly desirable that many standard practices and new emerging therapies undergo large-scale studies with long-term follow-up before being recommended conclusively as alternative therapies for scar management.

Cicatrix, Hypertrophic↗

Biomechanical and viscoelastic properties of skin, SMAS, and composite flaps as they pertain to rhytidectomy.

Previous studies have focused on biomechanical and viscoelastic properties of the superficial musculoaponeurotic system (SMAS) flap and the skin flap lifted in traditional rhytidectomy procedures. The authors compared these two layers with the composite rhytidectomy flap to explain their clinical observations that the composite dissection allows greater tension and lateral pull to be placed on the facial and cervical flaps, with less long-term stress-relaxation and tissue creep. Eight fresh cadavers were dissected by elevating flaps on one side of the face and neck as skin and SMAS flaps and on the other side as a standard composite rhytidectomy flap. The tissue samples were tested for breaking strength, tissue tearing force, stress-relaxation, and tissue creep. For breaking strength, uniform samples were pulled at a rate of 1 inch per minute, and the stress required to rupture the tissues was measured. Tissue tearing force was measured by attaching a 3-0 suture to the tissues and pulling at the same rate as that used for breaking strength. The force required to tear the suture out of the tissues was then measured. Stress-relaxation was assessed by tensing the uniformly sized strips of tissue to 80 percent of their breaking strength, and the amount of tissue relaxation was measured at 1-minute intervals for a total of 5 minutes. This measurement is expressed as the percentage of tissue relaxation per minute. Tissue creep was assessed by using a 3-0 suture and calibrated pressure gauge attached to the facial flaps. The constant tension applied to the flaps was 80 percent of the tissue tearing force. The distance crept was measured in millimeters after 2 and 3 minutes of constant tension. Breaking strength measurements demonstrated significantly greater breaking strength of skin and composite flaps as compared with SMAS flaps (p < 0.05). No significant difference was noted between skin and composite flaps. However, tissue tearing force demonstrated that the composite flaps were able to withstand a significantly greater force as compared with both skin and SMAS flaps (p < 0.05). Stress-relaxation analysis revealed the skin flaps to have the highest degree of stress-relaxation over each of five 1-minute intervals. In contrast, the SMAS and composite flaps demonstrated a significantly lower degree of stress-relaxation over the five 1-minute intervals (p < 0.05). There was no difference noted between the SMAS flaps and composite flaps with regard to stress-relaxation. Tissue creep correlated with the stress-relaxation data. The skin flaps demonstrated the greatest degree of tissue creep, which was significantly greater than that noted for the SMAS flaps or composite flaps (p < 0.05). Comparison of facial flaps with cervical flaps revealed that cervical skin, SMAS, and composite flaps tolerated significantly greater tissue tearing forces and demonstrated significantly greater tissue creep as compared with facial skin, SMAS, and composite flaps (p < 0.05). These biomechanical studies on facial and cervical rhytidectomy flaps indicate that the skin and composite flaps are substantially stronger than the SMAS flap, allowing significantly greater tension to be applied for repositioning of the flap and surrounding subcutaneous tissues. The authors confirmed that the SMAS layer exhibits significantly less stress-relaxation and creep as compared with the skin flap, a property that has led aesthetic surgeons to incorporate the SMAS into the face lift procedure. On the basis of the authors' findings in this study, it seems that that composite flap, although composed of both the skin and SMAS, acquires the viscoelastic properties of the SMAS layer, demonstrating significantly less stress-relaxation and tissue creep as compared with the skin flap. This finding may play a role in maintaining long-term results after rhytidectomy. In addition, it is noteworthy that the cervical flaps, despite their increased strength, demonstrate significantly greater tissue creep as compared with facial flaps, suggesting earlier relaxation of the neck as compared with the face after rhytidectomy.

Aged↗

Inhibition of prolyl 4-hydroxylase reduces scar hypertrophy in a rabbit model of cutaneous scarring.

Hypertrophic scars result from excessive collagen deposition at sights of healing dermal wounds and can be functionally and cosmetically problematic. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. We tested the ability of the phenanthrolinone derivative FG-1648 (in 0.5% Carbopol 971 PNF gel, pH 6.5), a prolyl 4-hydroxylase inhibitor, to reduce hypertrophic scar formation in a rabbit ear hypertrophic scar model. New Zealand White rabbits were divided into two treatment groups (n = 12 wounds per group with an equal number of controls): low-dose group: 0.5% FG-1648; high-dose group: 1% FG-1648. Left ears were used for treatment and right ear for control. Four 7-mm dermal ulcer wounds were made on each ear. The inhibitor was topically applied to the wound at the time of wounding and once daily up to postoperative day 7. Wounds were harvested at postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. All wounds showed complete healing. Treatment of wounds with 1% prolyl 4-hydroxylase inhibitor decreased the scar elevation index by 26% compared to control wounds (p < 0.01). Wounds treated with 0.5% FG-1648 inhibitor showed no difference in scar elevation compared to control wounds. These results suggest that inhibition of prolyl 4-hydroxylase may be a suitable agent for topical treatment for the prevention of hypertrophic scar tissue.

Animals↗

Use of hypoxia-inducible factor signal transduction pathway to measure O2 levels and modulate growth factor pathways.

Tissue PO2 levels are known to directly modulate numerous processes involved in the reparative response to cutaneous tissue injury, including cell differentiation and migration, extracellular matrix synthesis and maturation, and effectiveness of endogenous and exogenous growth factors. Oxygen is therefore likely the critical variable determining the healing capabilities of any tissue. Significant advances in the understanding of cutaneous wound healing progressed with advances in the measurement of tissue PO2, which has advanced over the past several decades from implantable probes to now include molecular tools such as the transcription factor hypoxia inducible factor-1 (HIF-1). HIF-1 modulates the expression of genes that drive the cellular adaptive response to hypoxia and possess the HIF-1 binding sequence named hypoxia response element within their promoter sequence. Molecular biology techniques are now allowing exploitation of the HIF-1/hypoxia response element pathway to drive the expression of potential vulnerary ectopic genes. Here we show the utility of the hypoxia response element for hypoxia-driven expression of the transforming growth factor-beta-signaling component Smad3 in vitro and the in vivo detection of ischemic hypoxia using luciferase. Smad3 is a positive effector of transforming growth factor-beta superfamily signal transduction. Such approaches are the latest evolution of work championed by Hunt and colleagues over the past 4 decades.

Animals↗

Age-dependent response of primary human dermal fibroblasts to oxidative stress: cell survival, pro-survival kinases, and entrance into cellular senescence.

A central question in cell biology is how cells become senescent. After a finite number of cell divisions, normal cultured human cells enter a state of irreversible growth arrest, termed "replicative senescence." Alternatively, oxidative stress in the form of hydrogen peroxide (H(2)O(2)) can render human dermal fibroblasts (HDFs) nonproliferative and quiescent, a phenomenon known as stress-induced premature senescence (SIPS). Although critical to the understanding of the pathophysiological basis of many diseases, there is no research to date that has simultaneously examined the interactions between age, oxidative stress, and SIPS. Therefore, the goals of this study were to examine in concert the interactions between these three factors in primary HDFs, and to test our central hypothesis that aging lowers the ability of primary HDFs to respond to oxidative stress. Our data provide, for the first time, evidence that aging dramatically reduces the capacity of primary HDFs to respond to the challenge of hydrogen peroxide. Specifically, aged HDFs showed decreased cell viability, decreased phosphorylation (activation) of pro-survival kinases (Akt and ERK 1/2), and increased entrance into a senescent state when compared with their younger counterparts. Another important conclusion of this study is that blockade of transforming growth factor-beta1 had a pronounced "rescue effect" in the aged, preventing entrance of HDFs into cellular senescence.

Adolescent↗

Inhibition of procollagen C-proteinase reduces scar hypertrophy in a rabbit model of cutaneous scarring.

Hypertrophic scarring, which results from excessive collagen deposition at sites of dermal wound repair, can be functionally and cosmetically debilitating to the surgical patient. Pharmacological regulation of collagen synthesis and deposition is a direct approach to the control of scar tissue formation. One of the key steps in collagen stabilization is the cleavage of the C-terminal propeptide from the precursor molecule to form collagen fibrils, a reaction catalyzed by procollagen C-proteinase (PCP). We tested the ability of a PCP inhibitor to reduce hypertrophic scar formation in a rabbit ear model. After the placement of four, 7-mm dermal wounds on each ear, New Zealand white rabbits received PCP inhibitor subcutaneously in the left ear at four time points postwounding: days 7, 9, 11, 13 (early treatment; n=20 wounds) or days 11, 13, 15, 17 (late treatment; n=20 wounds). The right ear of each animal served as a control (vehicle alone). Wounds were harvested on postoperative day 28 and scar hypertrophy quantified by measurement of the scar elevation index. Early treatment of wounds with PCP inhibitor did not reduce scar formation compared with controls (p>0.05). However, late treatment resulted in a statistically significant reduction in the scar elevation index (p<0.01). Our results point not only to the potential use of PCP inhibitors to mitigate hypertrophic scarring but also to the temporal importance of drug delivery for antiscarring therapy.

Analysis of Variance↗