Heat shock proteins modulate keloid formation.

OBJECTIVE: Heat shock proteins (HSPs) modulate the intensity of the inflammatory and synthetic response to stress in wound healing. Induction of HSPs at the site of wounds improves healing by acting as a molecular chaperone. However, the role of HSPs may augment the inflammatory response, leading to an uncontrolled synthetic process. Propensity for keloid development involves genetic predisposition, physical factors, and an aggressive inflammatory response. The aim of this study is to demonstrate the differential expressions of HSPs in keloid and normal tissues. METHODS: Twenty-five keloid and adjacent normal tissue samples were removed from 24 patients who were between 16 and 45 years of age. Western blot, enzyme-linked immunosorbent assay, and immunofluorescence studies were performed to examine hsp27, hsp47, hsp60, hsp70, and hsp90 levels in keloid and normal tissue. RESULTS: Our results demonstrated a significant overexpression of hsp27, hsp47, and hsp70 in keloid tissue compared to that of normal tissue. Statistical analysis using the Student t test revealed a significant difference between these 2 groups (P < .01), while the expression of hsp60 and hsp90 were not significantly different between the keloid and normal tissue samples. CONCLUSION: The overexpression of HSPs indicates that both a proliferative (hsp70) and a matrix synthesis (hsp47, hsp27) component are present in keloid tissue. From this point of view, it is probable that HSPs play a pivotal role in keloid formation. Unveiling HSP-keloid interactions may allow us to manipulate the inflammatory and proliferative phases of wound healing with the potential to control keloid formation.

A novel autologous scaffold for diced-cartilage grafts in dorsal augmentation rhinoplasty.

BACKGROUND: Diced-cartilage grafts have been used for dorsal nasal augmentation for several years with good results. However, compounds such as Surgicel and temporalis fascia used as a wrap have inherent problems associated with them, predominantly inflammation and graft resorption. An autologous carrier could provide stabilization of cartilage grafts while avoiding the complications seen with earlier techniques. METHODS: In our patients, a malleable construct was used for dorsal nasal augmentation in which autologous diced-cartilage grafts were stabilized with autologous tissue glue (ATG) created from platelet-rich plasma (platelet gel) and platelet-poor plasma (fibrin glue). RESULTS: A prospective analysis of 68 patients, who underwent dorsal nasal augmentation utilizing ATG and diced-cartilage grafts between 2005 and 2008, were included in the study. Although there was notable maintenance of the dorsal height, no complications occurred that required explantation over a mean follow-up of 15 months. CONCLUSION: The use of ATG to stabilize diced-cartilage grafts is a safe, reliable technique for dorsal nasal augmentation. The platelet gel provides growth factors while the fibrin glue creates a scaffold that allows stabilization and diffusion of nutrients to the cartilage graft.

The no-scar lip-lift: upper lip suspension technique.

BACKGROUND: Addressing the long upper lip has been a complex problem for some time. Methods such as the subnasal skin excision and the vermillion advancement technique have been described, but both leave a visible scar. A no-scar lip-lift technique is necessary for a subset of patients who have a long upper lip and will not accept a visible scar. METHODS: The upper lip is shortened via an intranasal incision and suspension suture that elevates the upper lip and anchors it to the anterior nasal spine. A retrospective review of 92 patients who had undergone upper lip-lift with the no-scar suspension technique was performed. Three plastic surgeons assessed the pre- and postoperative results and determined the presence of improvement in four categories: lip shortening, lip projection, incisor show, and vermillion show. RESULTS: The lip parameters improved, with 85% of the patients showing noticeable lip shortening, 79% showing increased sagittal projection, 74% exhibiting increased incisor show, and 25% exhibiting increased vermillion show. All the patients had improvement in at least one of the four categories. Complications were experienced by two patients with a suture abscess and one patient with an unraveled suture. CONCLUSION: The overall lip contours improved after the lip suspension technique, most noticeably in terms of lip height and sagittal projection, and the scar was hidden intranasally.

The dermal suspension sling: shaping the inferior pedicle during breast reduction.

BACKGROUND: Complaints following reduction mammaplasty using the inferior pedicle include the migration of the deep tissue, a lack of medial fullness, poor projection, and bottoming-out. These are attributed to the lack of deep tissue suspension and skin envelope relaxation. We address these issues through horizontal dermal suspension and plication of the inferior pedicle. METHODS: The inferior pedicle is designed with medial and lateral triangular flaps in the areas, which would normally be excised. These triangular flaps are deepithelialized and defatted. The flaps are attached to the chest wall above the inferior pedicle to create a dermal sling. The breast mound is further contoured by horizontally plicating the dermis below the nipple-areola complex (NAC), which creates projection and rotates the NAC into the desired position in relation to the chest wall. RESULTS: Sixty-six women have undergone breast reduction using the horizontal dermal suspension sling modification to the inferior pedicle breast reduction technique. Breast projection and shape were sustained during follow-up, of which the median interval was 16 months. CONCLUSION: Dermal suspension and horizontal dermal plication provides a structural foundation to the inferior pedicle. The sling-like effect from the dermal suspension maintains a defined inframammary fold and maintains medial and lateral borders of the breast. Horizontal dermal plication shortens the length of the inferior pedicle while generating improved breast projection by rotating the NAC anteriorly. The firmly shaped inferior pedicle breast mound allows the skin flap to drape over the breast mound with minimal tension.

Systemic administration of interleukin-10 attenuates early ischemic response following spinal cord ischemia reperfusion injury in rats.

BACKGROUND: The aim of this experimental study was to investigate the early effects of interleukin-10 (IL-10) and interleukin-1beta antagonist (anti-IL-1beta) against cellular damage, inflammatory reactivity, lipid peroxidation (LPO), and myeloperoxidase (MPO) activity induced by spinal cord ischemia reperfusion injury (IRI). METHODS: Thirty-two single strain female Albino rats were divided into four groups: control (sham-operated), IRI-alone, IL-10-treated (100 mug/kg), and anti-IL-1beta-treated (1 mg/kg) groups after IRI. IRI was induced by balloon occlusion of the aorta and simultaneous hypovolemia during occlusion. The animals were sacrificed at 24 h. Histopathological and ultrastructural analyses, biochemical studies for determination of LPO and MPO activity and Comet assays (single cell electrophoresis for detecting DNA single strand breaks) were performed in all study groups. RESULTS: Compared with the levels of control (sham-operated) animals, IRI produced a significant increase in the levels of LPO and MPO activity, and prominent tissue damage characterized by leukocyte infiltration, edema and neuronal and glial damage in the affected spinal cord in 24 h. The administration of IL-10 decreased LPO and MPO activity, and suppressed initial inflammatory response in the first 24 h. The effects of anti-IL-1beta were limited to decrease in LPO activity without considerable evidence of cellular preservation. CONCLUSIONS: These data suggest that systemic administration of IL-10 attenuates the early ischemic response, and may restrict the tissue damage in the first 24 h after spinal cord ischemia reperfusion injury. Anti-IL-1beta has no considerable effect in this time window. The results of this preliminary study promote further studies with longer time windows on the effects of anti-inflammatory cytokines in spinal cord IRI.

Mycobacterium abscessus infection after breast augmentation: a case of contaminated implants?

Infections after breast augmentation are uncommon, occurring in 1-3% of cases. Treatment often requires additional surgeries and may yield a sub-optimal cosmetic result. For this reason, post implant infection remains a serious concern among plastic surgeons. A 48-year-old female presented to our clinic with bilateral breast implant infections 3 months after primary augmentation in China. Cultures grew Mycobacterium abscessus, a previously undescribed infectious aetiology after breast augmentation. The fastidious nature of the organism often results in a negative acid fast stain and initially sterile cultures. For these reasons, clinical signs of infection in the face of sterile cultures should raise suspicion of Mycobacterium infection among clinicians. While the overall incidence of Mycobacterium infection after breast augmentation is low, it remains an important and often overlooked aetiology for patients with a lack of systemic symptoms and initial sterile cultures.

Clinical effectiveness of nebulised budesonide in the treatment of acute asthma attacks.

Nebulized budesonide (NB) might offer topical anti-inflammatory activity and be an alternative to systemic corticosteroid (SC) in the treatment of acute asthma. The aim of this study was to compare the effect of NB with SC on lung function and clinical findings of adult patients with acute asthma. Thirty patients admitted to clinic with asthma attack (F/M: 26/4; mean age: 47.1 +/- 2.1 years) were enrolled to the study. The patients were randomized into three groups; Group I were treated with NB alone (4 mg/day), Group II SC alone (1 mg/kg/day methylprednisolone), Group III NB plus SC. Pulmonary functions and respiratory symptom scores were measured and recorded before and during 7 days of study. Spirometric parameters significantly improved in all groups at 7th day significantly (p< 0.05) without a difference among groups (p> 0.05). FEV(1) % levels increased significantly at the first day of study in Group I and III (p< 0.05), but didn't change in Group II until 5th day of study. The mean symptom scores decreased significantly at the second day in Group I (p< 0.05), and at the 4th day in other groups. NB with or without SC improved successfully airway obstruction and symptoms in patients hospitalized with acute asthma attack as the 1st treatment day in comparison with SC alone and this effect lasted for 7 days. Regarding the superior safety profile and comparable efficacy with SC, NB might be an alternative to the patients with moderate-severe asthma attacks.

Directed migration of smooth muscle cells to engineer plaque-resistant vein grafts.

PURPOSE: To test the hypothesis that controlled perivascular release of tissue plasminogen activator (tPA) can generate cleaved extracellular matrix (ECM) chemotactic gradients to guide the migration of vascular smooth muscle cells (SMCs) away from the lumen, thereby limiting neointima formation. METHODS: This hypothesis was tested in rabbit models in which the perivascular surface of vein bypass grafts was treated with microspheres releasing tPA (MS-tPA), microspheres containing no drug (MS-blank), or phosphate buffered saline (PBS). Vein graft segments harvested after 7 days were then evaluated for elastin content, proliferating SMCs, intima-to-media (I/M) ratio, and inflammation; late impact on neointima formation was also examined. RESULTS: The 7-day results demonstrated cleaved elastin gradients and proliferating SMCs that assumed a more peripheral distribution in the MS-tPA group than MS-blank and PBS controls (p<0.05). At 28 days, vein grafts treated with MS-tPA showed a mean I/M ratio (0.35+/-0.04) that was 63.5% lower than PBS controls (0.96+/-0.07, p<0.005) and 43.5% lower than MS-blank specimens (0.62+/-0.08, p<0.05). CONCLUSIONS: Perivascular release of tPA modifies ECM gradients, directionally guides SMC migration away from the lumen, and limits neointima formation.

Circumferential negative-pressure dressing (VAC) to bolster skin grafts in the reconstruction of the penile shaft and scrotum.

This paper presents 4 consecutive cases using negative-pressure dressings (VAC) to bolster skin grafts in male genital reconstruction. In this series reconstruction followed 1 case of tumor ablation and 3 cases of debridement of abscesses or Fornier's gangrene. The VAC was applied circumferentially to the penis to secure skin grafts either directly to the penile shaft or to facilitate skin grafting to the scrotum. Graft areas ranged from 75 to 250 cm. All cases resulted in successful genital wound coverage; minor complications are described. Three practical points are brought forth. First, the VAC facilitates skin grafting to the complex contour of male genitalia. Second, the VAC can be applied circumferentially to the penis without the need for perfusion monitoring or fears of avascular necrosis. Third, with the use of the VAC, bolster use can likely be discontinued as early as 72 hours with good graft adherence and survival.

Local resistance to oxidative stress by overexpression of copper-zinc superoxide dismutase limits neointimal formation after angioplasty.

PURPOSE: To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD). METHODS: The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing beta-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation. RESULTS: At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation byproducts were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582+/-0.088 for the nonviral control group versus 0.565+/-0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259+/-0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05). CONCLUSIONS: Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.

Stent-based controlled release of intravascular angiostatin to limit plaque progression and in-stent restenosis.

PURPOSE: To evaluate the importance of angiogenesis in plaque progression after stent placement, this study examines stent-based controlled delivery of the antiangiogenic agent, angiostatin, in a rabbit model. MATERIALS AND METHODS: Controlled release biodegradable microspheres delivering angiostatin or polymer-only microspheres (polylactic-co-glycolic-acid-polyethylene glycol; PLGA/PEG) were loaded in channeled stents, anchored, and deployed in the aorta of adult New Zealand white rabbits (n = 6 animals per group, three each per time point). The stented aortas were harvested at 7 days and 28 days and evaluated for neovascularization, local inflammation, vascular smooth muscle cell proliferation, and in-stent plaque progression. RESULTS: At 7 days, neovascularization was significantly decreased in the angiostatin groups (1.6 +/- 1.6 neovessels per mm(2) plaque) versus the control group (15.4 +/- 2.6 neovessels per mm(2) plaque; P =.00081), as were local inflammation where angiostatin-treated groups demonstrated significantly lower macrophage recruitment per cross section (34.9 +/- 4.9 cells per cross section) relative to the control group (55.2 +/- 3.84 cells per cross section; P =.0037). And a significant decrease in the overall vascular smooth muscle cell proliferation (143.8 +/- 26.3 Ki-67 positive cells per mm(2)) relative to the control group (263.2 +/- 16.6 Ki-67 positive cells per mm(2); P =.00074). At both 7 and 28 days, in-stent plaque progression in the angiostatin groups was successfully limited relative to the control group by 54% (0.255 +/- 0.019% of cross section; P =.00016) and 19% (1.981 +/- 0.080; P =.0033) respectively and resulted in reduction of in-stent restenosis relative to the control group. CONCLUSION: Angiostatin-eluting stents may limit neovascularity after arterial implantation, offer insight into in-stent restenosis, and allow future refinement of bioactive stent designs and clinical strategies, particularly in light of evidence that intimal smooth muscle cells may in part be marrow-derived.

Topographic mapping of the superior transverse scapular ligament: a cadaver study to facilitate suprascapular nerve decompression.

Division of the superior transverse scapular ligament for decompression of suprascapular nerve entrapment can be curative. However, the superior transverse scapular ligament can be difficult to locate, and large incisions are often required. This study was designed to determine the topographic coordinates of the superior transverse scapular ligament to permit reproducible surgical localization and reduce incision size. In 20 cadavers, the superior transverse scapular ligament was identified through a superior approach. Measurements were obtained from the superior transverse scapular ligament to external landmarks. The superior transverse scapular ligament was located 1.3 +/- 0.3 cm (+/- SD) posterior to the posterior border of the clavicle and 2.9 +/- 0.8 cm from the acromioclavicular joint in a two-dimensional surface plane. The depth of the superior transverse scapular ligament from the skin surface was 3.9 +/- 0.7 cm. An incision (mean length, 6.3 +/- 0.7 cm) derived from a novel system of planning marks facilitated access to the superior transverse scapular ligament. The authors conclude that the superior transverse scapular ligament can be located consistently through an incision located on the superior aspect of the shoulder on the basis of palpable topographic landmarks. The superior approach permits small incision size and the maintenance of local muscle anatomic integrity.

In vivo vascular engineering of vein grafts: directed migration of smooth muscle cells by perivascular release of elastase limits neointimal proliferation.

PURPOSE: Saphenous vein bypass grafting for coronary revascularization procedures remains limited by accelerated neointima formation. It was hypothesized that creation of a modified chemotactic gradient in vivo could guide migration of smooth muscle cells (SMCs) peripherally instead of in a luminal direction and reduce intimal hyperplasia during vein graft arterialization. MATERIALS AND METHODS: Surgical bypass vein grafting to femoral arteries was performed in adult male New Zealand White rabbits (n = 8 per treatment group; five for 7 d and three for 28 d). Controlled-release microspheres delivering elastase or buffered polymer only were administered perivascularly at the vein graft site. At 7 days, five vein grafts per group were harvested and cross-sections were immunostained with anti-proliferating cell nuclear antigen (PCNA) to determine the number and distribution of proliferating SMCs. At 28 days, three vein grafts per group were harvested and intima-to-media (I/M) ratios were calculated after staining with Verhoeff von Gieson-Masson trichrome stain. RESULTS: Significant early outward-directed elastin degradation resulted from elastase treatment. Concurrently, proliferating SMCs migrated peripherally. PCNA(+) cells in the outer half of the wall increased 2.37 fold compared to procedural controls (P <.0001). Directional shifts in SMC migration underlie these results because overall SMC proliferation was not significantly different. At 28 days after vein graft surgery, a 38% reduction (P =.0008) in neointima was observed relative to procedural controls. CONCLUSION: Directional guidance of SMC responses through perivascular elastase release achieves favorable vein graft remodeling characteristics, including limited neointima development. This represents practical evidence that SMC migration can be directionally guided in vivo in a vein graft model and that plaque progression can be prevented by redistributing elastin without decreasing functional vein graft wall stability.

In vivo vascular engineering: directed migration of smooth muscle cells to limit neointima.

Pathologic neointima formation requires directional smooth muscle cell (SMC) migration from media to intima. The very direction of SMC migration thus becomes a potential therapeutic target. Here, we hypothesize that proliferating SMC after injury can be redirected using engineered chemotactic gradients of elastin degradation to limit late pathologic neointima formation. Buffered bioerodible polymeric microspheres (MS) were constructed to provide 4-week sustained release of elastase, heat-killed elastase, or polymer only. In vitro elastase function and timecourse of release at 37 degrees C, physiologic pH, and shear was determined. Curves revealed an initial bolus followed by sustained linear release for elastase MS, while controls exhibited baseline hydrolysis of substrate. We then employ controlled perivascular release of elastase after angioplasty to engineer modified in vivo gradients of elastin degradation in rabbit femoral arteries. NZW rabbits (n = 8 each) underwent balloon angioplasty of the common femoral artery followed by perivascular distribution of MS. Significant early perivascular elastin degradation resulted. Concurrently, proliferating SMC were guided peripherally (further from lumen) with treatment without significant changes in total proliferation or inflammation. At 28 days, treatment significantly reduces neointima by 42% relative to controls. These results confirm that directionally guiding SMC responses after injury achieves favorable arterial remodeling and limits development of pathologic neointima. Thus, a potential class of therapeutics and the paradigm of in vivo vascular engineering emerge from this work.

New research in breast reconstruction: adipose tissue engineering.

In the human species, a major function of the breast is aesthetic. The soft-tissue volume within the breast displaces the overlying skin to create the protuberant contour of the female thorax, that is solidly associated with, and to some extent, definitive of, femininity in modern culture. Adipose tissue is the major contributor to the volume of the breast.