Direct Excision of the Lower Eyelid: A Safe and Effective Method for Treating Dermatochalasis and Pigmentation.

The subciliary and skin pinch approaches are the most widely accepted techniques for treating dermatochalasis of the lower eyelid. Direct excision (DE) is an accepted method for treating festoons; however, it is not a popular technique for the treatment of dermatochalasis and pigment of the lower lid. DE of the lower lid offers a safe and excellent aesthetic result for dermatochalasis and pigment of the lower lid, without causing lower lid malposition, which can occur with more traditional methods. In addition to being able to remove significantly more skin without risking lower lid malposition, this procedure allows for removal of the most pigmented and poorly textured skin overlying the nasojugal groove. It is an effective alternative to the conventional subciliary and skin pinch approaches.

Long-term volumetric retention of autologous fat grafting processed with closed-membrane filtration.

BACKGROUND: Some practitioners have criticized the unpredictable retention associated with autologous fat transfer. Potential causes of variations in predictability include intrinsic (patient-related) or extrinsic factors, such as harvesting, processing, and graft-delivery technique. OBJECTIVES: The authors sought to determine the long-term retention of autologous fat graft processed with a closed-membrane filtration system, to compare this retention with centrifuge-processed fat, and to analyze factors that affect graft retention. METHODS: This was a prospective analysis of 26 female patients (representing 52 hemi-midfaces) who underwent autologous fat transfer to the midface via the closed-membrane filtration system. The Vectra 3D camera and software were employed for all photography, which was then analyzed to compare immediate preoperative images with long-term follow-up images (obtained at least 10 months postprocedure). The authors compared the findings with data from their previous study of centrifuge-processed fat grafts (historical controls). RESULTS: Mean values were as follows: age, 55 years; follow-up period, 17 months; amount of autologous fat injected, 8.88 mL; absolute volume augmentation measured at the last postoperative visit, 3.71 mL; and retention, 41.2%. Results of Welch's t test, in which the membrane-filtration data were compared with the previous centrifuge data (31.8% long-term retention), showed a significant difference (P=.03). Retention in this study was significantly higher in patients younger than 55 years (53.0% vs 31% for older patients; P=.001) and lower in patients who underwent rhytidectomy (23.8% vs 47.6% for nonrhytidectomy patients; P<.001). CONCLUSIONS: Autologous fat processed by closed-membrane filtration had a significantly higher long-term retention rate than did centrifuged-processed fat injected by the same surgeons. LEVEL OF EVIDENCE: 3.

Overlapping and enzyme-specific contributions of matrix metalloproteinases-9 and -12 in IL-13-induced inflammation and remodeling.

IL-13 potently stimulates eosinophilic and lymphocytic inflammation and alveolar remodeling in the lung, effects that depend on the induction of various matrix metalloproteinases (MMPs). Here, we compared the remodeling and inflammatory effects of an IL-13 transgene in lungs of wild-type, MMP-9-deficient, or MMP-12-deficient mice. IL-13-induced alveolar enlargement, lung enlargement, compliance alterations, and respiratory failure and death were markedly decreased in the absence of MMP-9 or MMP-12. Moreover, IL-13 potently induced MMPs-2, -12, -13, and -14 in the absence of MMP-9, while induction of MMPs-2, -9, -13, and -14 by IL-13 was diminished in the absence of MMP-12. A deficiency in MMP-9 did not alter eosinophil, macrophage, or lymphocyte recovery, but increased the recovery of total leukocytes and neutrophils in bronchoalveolar lavage (BAL) fluids from IL-13 transgenic mice. In contrast, a deficiency in MMP-12 decreased the recovery of leukocytes, eosinophils, and macrophages, but not lymphocytes or neutrophils. These studies demonstrate that IL-13 acts via MMPs-9 and -12 to induce alveolar remodeling, respiratory failure, and death and that IL-13 induction of MMPs-2, -9, -13, and -14 is mediated at least partially by an MMP-12-dependent pathway. The also demonstrate that MMPs-9 and -12 play different roles in the generation of IL-13-induced inflammation, with MMP-9 inhibiting neutrophil accumulation and MMP-12 contributing to the accumulation of eosinophils and macrophages.

Molecular cloning and functional characterization of mouse chitotriosidase.

Mammalian chitinase and chitinase-like proteins are members of a recently discovered gene family. Thus far, neither chitin nor chitin synthase has been found in mammals. The existence of chitinase genes in mammals is intriguing and the physiologic functions of chitinases are not clear. Human chitotriosidase, also called chitinase 1 (chit1), has been cloned. It has been found that high levels of serum chitotriosidase are associated with several diseases, but the physiologic functions of this enzyme are still unclear. To facilitate the studies in animal models we cloned and characterized a cDNA that encodes the mouse chitotriosidase. The open reading frame of this cDNA predicts a protein of 464 amino acids with a typical chitinase structure, including a signal peptide, a highly conserved catalytic domain and a chitin-binding domain. The predicted amino acid sequence is highly homologous to that of human chitotriosidase and to that of mouse acidic mammalian chitinase. Sequence analysis indicates that the mouse chitotriosidase gene has 12 exons, spanning a 40-kb region in mouse chromosome 1. The constitutive expression of mouse chitotriosidase is restricted to brain, skin, bone marrow, kidney, tongue, stomach and testis. Recombinant expression of the cloned cDNA demonstrated that the encoded protein is secreted and has chitinolytic activity that is sensitive to the specific chitinase inhibitor allosamidin and has the ability to bind to chitin particles. Substitution mutations at the conserved catalytic site completely abolished the enzymatic activity of the recombinant protein. These studies illustrate that mouse chitotriosidase is a typical chitinase that belongs to the mammalian chitinase gene family.

Midface sculpting with autologous fat.

There is currently a major paradigm shift from excision-based surgery to strictly volume enhancement. Because there is still no perfect facial filler, development of synthetic facial injectables continue to advance at a remarkable pace. Each type of filler carries a specific characteristic that makes it more suitable for a certain clinical application. The continuing change in facial fillers offers the possibility for volume augmentation procedures with less downtime and without the need for harvesting fat. We predict that volume enhancement will continue to play an increasing role as both a complementary and as a stand-alone procedure in facial rejuvenation.

Use of the Blom Tracheotomy Tube with Suction Inner Cannula to Decontaminate Microorganisms from the Subglottic Space. A Proof of Concept.

RATIONALE: Preventing pulmonary complications during mechanical ventilation via tracheotomy is a high priority. OBJECTIVES: To investigate if the Blom tracheotomy tube with suction-above-the-cuff inner cannula reduced the quantity of normal flora and pathogens in supra- versus subglottic spaces. METHODS: We enrolled 20 consecutive medical ICU adults requiring tracheostomy for mechanical ventilation in this proof-of-concept, prospective, single-center study. All participants received a Blom tracheotomy tube with suction-above-the-cuff inner cannula to decontaminate microorganisms from the supra- and subglottic spaces. Supra- and subglottic sputum samples were obtained for microbiologic analysis while an endotracheal tube was in place before tracheotomy and once per week for up to 4 weeks of mechanical ventilation after tracheotomy. MEASUREMENTS AND MAIN RESULTS: Demographics, duration of endotracheal tube intubation, and duration of mechanical ventilation post-tracheotomy were recorded. There was a significant reduction for supraglottic (2.86 ± 1.11 [mean ± SD]) versus subglottic suction samples (2.48 ± 1.07) (paired t test, P = 0.048; Wilcoxon test, P = 0.045) when all data pairs for normal flora and pathogens were combined across times. There was a significant reduction of normal flora pooled across times in 19 data pairs for supraglottic (3.00 ± 1.05) versus subglottic suction samples (2.00 ± 0.94) (paired t test, P = 0.0004; Wilcoxon test, P = 0.0007). There was no significant reduction of pathogens pooled across times in 25 data pairs for supraglottic (2.76 ± 1.16) versus subglottic suction samples (2.84 ± 1.03) (paired t test, P = 0.75; Wilcoxon test, P = 0.83). CONCLUSIONS: Proof-of-concept was confirmed. The Blom tracheotomy tube with disposable suction-above-the-cuff inner cannula decontaminated microorganisms from the subglottic space when normal flora and pathogens were combined. Future research should investigate if decreased quantity of normal flora and pathogens in the subglottic space reduces the incidence of ventilator-associated pulmonary complications in critically ill patients requiring ongoing mechanical ventilation via tracheotomy.

IL-11 receptor alpha in the pathogenesis of IL-13-induced inflammation and remodeling.

IL-13 is a major stimulator of inflammation and tissue remodeling at sites of Th2 inflammation. In Th2-dominant inflammatory disorders such as asthma, IL-11 is simultaneously induced. However, the relationship(s) between IL-11 and IL-13 in these responses has not been defined, and the role(s) of IL-11 in the genesis of the tissue effects of IL-13 has not been evaluated. We hypothesized that IL-11, signaling via the IL-11Ralpha-gp130 receptor complex, plays a key role in IL-13-induced tissue responses. To test this hypothesis we compared the expression of IL-11, IL-11Ralpha, and gp130 in lungs from wild-type mice and transgenic mice in which IL-13 was overexpressed in a lung-specific fashion. We simultaneously characterized the effects of a null mutation of IL-11Ralpha on the tissue effects of transgenic IL-13. These studies demonstrate that IL-13 is a potent stimulator of IL-11 and IL-11Ralpha. They also demonstrate that IL-13 is a potent stimulator of inflammation, fibrosis, hyaluronic acid accumulation, myofibroblast accumulation, alveolar remodeling, mucus metaplasia, and respiratory failure and death in mice with wild-type IL-11Ralpha loci and that these alterations are ameliorated in the absence of IL-11Ralpha. Lastly, they provide insight into the mechanisms of these processes by demonstrating that IL-13 stimulates CC chemokines, matrix metalloproteinases, mucin genes, and gob-5 and stimulates and activates TGF-beta1 via IL-11Ralpha-dependent pathways. When viewed in combination, these studies demonstrate that IL-11Ralpha plays a key role in the pathogenesis of IL-13-induced inflammation and remodeling.

Role of cathepsin S-dependent epithelial cell apoptosis in IFN-gamma-induced alveolar remodeling and pulmonary emphysema.

Th1/Tc1 inflammation and remodeling responses characterized by tissue atrophy and destruction frequently coexist in human diseases and disorders. However, the mechanisms that are used by Th1/Tc1 cytokines, like IFN-gamma, to induce these responses have not been defined. To elucidate the mechanism(s) of IFN-gamma-induced tissue remodeling and destruction, we characterized the pathway that lung-targeted, transgenic IFN-gamma uses to induce alveolar remodeling in a murine pulmonary emphysema modeling system. In these mice, transgenic IFN-gamma caused epithelial cell DNA injury and apoptosis detectable with TUNEL (Roche) and dual annexin V and propidium iodide staining. These responses were associated with death receptor and mitochondrial apoptosis pathway activation. Importantly, apoptosis inhibition with a caspase inhibitor (N-benzylcarboxy-Val-Ala-Asp-fluoromethyl-ketone) or a null mutation of caspase-3 blocked this DNA injury and apoptosis response and significantly ameliorated IFN-gamma-induced emphysema. These interventions also ameliorated IFN-gamma-induced inflammation and decreased pulmonary protease burden. Selective cathepsin S inhibition and a null mutation of cathepsin S also decreased IFN-gamma-induced DNA injury, apoptosis, emphysema, inflammation, and protease accumulation. These studies demonstrate that cathepsin S-dependent epithelial cell apoptosis is a critical event in the pathogenesis of IFN-gamma-induced alveolar remodeling and emphysema. They also link inflammation, protease/antiprotease alterations, and protease-dependent apoptosis in the pathogenesis of Th1/Tc1 cytokine-induced tissue remodeling and destructive responses.