William C. Yao

Chemokine monokine induced by IFN-γ/CXC chemokine ligand 9 stimulates T lymphocyte proliferation and effector cytokine production

Monokine induced by IFN-γ (MIG; CXC chemokine ligand (CXCL)9) is important in T lymphocyte recruitment in organ transplantation. However, it is not known whether this chemokine, in addition to its chemotactic properties, exerts any effect on T lymphocyte effector functions. For in vivo studies, we used a previously characterized murine model of chronic rejection. The recipient mice were treated with anti-MIG/CXCL9 Ab; graft-infiltrating cells were analyzed for IFN-γ production. For in vitro studies, exogenous CXCR3 ligands were added to CD4 lymphocytes in MLRs, and the proliferative responses were measured. Separate experiments quantitated the number of IFN-γ-producing cells in MLRs by ELISPOT. Neutralization of MIG/CXCL9, in the in vivo model, resulted in significant reduction in the percentage of IFN-γ-producing graft-infiltrating T lymphocytes. In vitro experiments demonstrated that 1) exogenous MIG/CXCL9 stimulated CD4 lymphocyte proliferation in a MHC class II-mismatched MLR, 2) MIG/CXCL9 also increased the number of IFN-γ-producing CD4 lymphocytes in ELISPOT, 3) neutralization of MIG/CXCL9 in MLR reduced T lymphocyte proliferation, 4) IFN-γ-inducible protein 10/CXCL10 and IFN-inducible T cell α chemoattractant/CXCL11 had similar effects on T lymphocyte proliferation, 5) MIG/CXCL9 stimulated T lymphocyte proliferation in MHC class I- and total MHC-mismatched MLRs, 6) neutralization of CXCR3 reduced MIG/CXCL9-induced T lymphocyte proliferation and the number of IFN-γ-positive spots on ELISPOT, and 7) the proliferative effects of MIG/CXCL9 were mediated via an IL-2-independent pathway and were controlled by IFN-γ. This study demonstrates that MIG/CXCL9 stimulates T lymphocyte proliferation and effector cytokine production, in addition to its chemotactic effects. This novel observation expands our current understanding of MIG/CXCL9 biology beyond that of mediating T cell trafficking.

CD8 lymphocytes are sufficient for the development of chronic rejection

Background. The role of CD8 lymphocytes, in chronic rejection or cardiac allograft vasculopathy (CAV), is incompletely understood. The purposes of this study were to determine whether CD8 lymphocytes, in the absence of CD4 lymphocytes, are capable of causing the intimal lesions of CAV; and if so, to define the effector mechanism(s) of CD8 lymphocytes. Methods. We modified a previously characterized major histocompatibility complex class II mismatched murine model of CAV. Wild-type CD8 lymphocytes were transferred to nude mice followed by heterotopic heart transplantation. Recipient mice were then treated with a CD40 activating antibody, which is known to provide help for CD8 lymphocyte activation, in the absence of CD4 lymphocytes. Donor hearts were harvested on day 40 posttransplantation and analyzed for cellular infiltrates and intimal thickening. In separate experiments, isolated perforin −/−, Fas ligand (FasL) −/−, and interferon (IFN)-&ggr; −/− CD8 lymphocytes were transferred to nude mice followed by identical experimented protocol. Results. With adaptive transfer of wild-type CD8 lymphocytes, the donor hearts were infiltrated with activated CD8 lymphocytes and displayed significant intimal lesions. Adoptive transfer of perforin −/− and FasL −/− CD8 lymphocytes to nude mice resulted in similar patterns of CD8 lymphocyte infiltration and similar severity of intimal lesions. The donor hearts from IFN-&ggr; −/− CD8 lymphocyte reconstituted recipients displayed minimal intimal lesions, although CD8 lymphocytes were present in the allografts. Conclusions. Unprimed CD8 lymphocytes in the absence of CD4 lymphocytes can cause intimal lesions of CAV. CD8 lymphocytes production of IFN-&ggr;, but not the perforin or the FasL-mediated cytotoxicity, is the critical step in the development of intimal lesions.

Dry Eye Syndrome: An Update in Office Management

Dry eye syndrome is a multifactorial disease of the ocular surface and tear film that results in ocular discomfort, visual disturbances, and tear instability, with potential damage to the cornea and conjunctiva. Risk factors for dry eye syndrome include age (>50 years old), female sex, environments with low humidity, systemic medications, and autoimmune disorders. There are several treatment options that range from artificial tears to anti-inflammatory and immunosuppressant agents. Treatment of this highly prevalent condition can drastically improve the quality of life of individuals and prevent damage to the ocular surface.

Improved skin paddle survival in pectoralis major myocutaneous flap reconstruction of head and neck defects

OBJECTIVE To examine our outcomes with skin paddle survival using pectoralis myocutaneous flaps in reconstruction of the head and neck. The pectoralis major myocutaneous flap has been associated with a notable incidence of distal skin necrosis and flap loss. Our experience has been favorable compared with that reported in the literature. METHODS Retrospective medical record review of 81 cases of pectoralis major muscle flap reconstruction performed in 78 patients from 1995 to 2008 using a flap harvest technique that is slightly different from the classic descriptions. Data were obtained regarding coexisting health conditions and perioperative complications, which were divided into major and minor categories. Major complications were defined as total flap failure or greater than 25% skin paddle loss. Minor complications and donor site complications included fistulas that were managed conservatively, wound dehiscence not requiring additional surgery, local infections, seromas, and hematomas. RESULTS Of the 81 flaps performed, 22 complications were encountered. Total flap loss was not encountered in any patient. The overall major complication rate in myocutaneous flaps was 3 of 76 (4%), with these cases consisting of significant skin paddle loss. Minor complications occurred in 14 of 81 myofascial and myocutaneous flaps (17%). Donor site complications of the chest wall occurred in 5 of 81 flaps (6%). CONCLUSIONS Skin paddle necrosis may be minimized with modifications of the classic technique. We believe that extension of the skin flap over the rectus sheath is the cause of distal skin flap necrosis. The pectoralis major myocutaneous flap remains a valuable reconstructive option in the head and neck.

Orbital Decompression in the Endoscopic Age The Modified Inferomedial Orbital Strut

Objective Postoperative diplopia occurs in up to 45% of patients following orbital decompression for exophthalmos associated with Graves’ orbitopathy. We sought to describe outcomes of our balanced orbital decompression strategy that includes the preservation of a modified inferomedial orbital strut (mIOS). Study Design Case series with chart review. Setting Academic medical center. Subjects and Methods A total of 115 consecutive orbital decompressions were performed on 73 patients (42 bilateral) with Graves’ orbitopathy. All patients underwent (1) a balanced decompression technique incorporating an endoscopic medial and external lateral decompression and (2) a mIOS technique with preservation of the anterior half of the inferomedial orbital strut. A periorbital periosteal (orbital) sling was utilized in patients (n = 54) without threatened vision loss, proptosis >28 mm, or periorbital disruption to prevent prolapse of the medial rectus muscle. Results Utilization of the mIOS technique with or without a sling did not adversely affect the reduction in proptosis (5.1 mm with sling vs 5.0 mm without sling; P = .85).The incidence of new-onset postoperative diplopia was 17% (n = 6). The sling was not associated with postoperative diplopia (odds ratio = 0.54, 95% confidence interval: 0.08-3.40, P = .51), while it was associated with resolution of preexisting diplopia (odds ratio = 6.67, 95% confidence interval: 1.06-42.06, P = .04). No intraoperative complications occurred, and no patients suffered a decrement in visual acuity. Conclusion Balanced orbital decompression utilizing a mIOS in patients with Graves’ orbitopathy provides a safe and effective reduction in proptosis with a low rate of new-onset diplopia as compared with historical values. Utilization of an orbital sling may be beneficial in reducing postoperative diplopia in select patients.

The need for intranasal packing in endoscopic endonasal surgery

Abstract Conclusion: The present findings indicate that conventional nasal packing is not required for endoscopic endonasal surgery. Objectives: To evaluate the routine use of packing in endoscopic endonasal surgery. Methods: From January 2006 through January 2009, 146 consecutive patients who underwent endoscopic endonasal surgery performed by the same surgeon in Kyoto University Hospital were evaluated. The surgical procedure was ended with conventional gauze packing in 70 consecutive patients from January 2006 through August 2007 (Packing group), and placing of oxidized cellulose on operative sites was performed in 76 consecutive patients from September 2007 to January 2009 (Non-packing group). We analyzed demographic characteristics, comorbidities, surgical procedures, incidence of packing the nose after excessive postoperative bleeding, and occurrence of postoperative adhesion. Results: No significant differences in the demographic characteristics, except for gender, and in comorbidities were found between the two groups. The number of endoscopic sinus surgery procedures with septoplasty and/or turbinoplasty, or tumor extirpation in the Non-packing group was significantly larger than that in the Packing group. There was no significant difference in the incidence of postoperative bleeding or postoperative adhesion between the two groups.

Three-dimensional sinus imaging as an adjunct to two-dimensional imaging to accelerate education and improve spatial orientation

Develop a novel three‐dimensional (3‐D) anatomical model to assist in improving spatial knowledge of the skull base, paranasal sinuses, and adjacent structures, and validate the utilization of 3‐D reconstruction to augment two‐dimensional (2‐D) computed tomography (CT) for the training of medical students and otolaryngology–head and neck surgery residents.

Staining intraoperative topical solutions with fluorescein: enhancing the safety of sinus surgery

Oxymetazoline HCl 0.05%, 1:100,000 lidocaine with epinephrine (lido+epi), and 1:1000 epinephrine are all colorless solutions employed in sinus surgery. Because lido+epi is injected whereas others are not, care must be taken to label all solutions to avoid inadvertent injection of oxymetazoline or concentrated epinephrine because of life‐threatening complications. Dyes have been used to color solutions for visual identification, but efficacy and cost have never been compared. We sought to determine the effectiveness of surgical marking pen (gentian violet) and fluorescein strips as coloring agents in mediums commonly used in sinus surgery.

Safety and efficacy of concentrated topical epinephrine use in endoscopic endonasal surgery

Effective topical decongestion is critical for the safe performance of endoscopic endonasal surgery (EES). Despite the vasoconstriction offered by topical concentrated (1:1000) epinephrine (CE), its use has not gained widespread acceptance because of concerns over systemic absorption and its effect on blood pressure and postoperative rebound epistaxis. The purpose of this study was to examine the physiological changes in blood pressure and rate of epistaxis with use of topical CE in a variety of endoscopic nasal procedures.

Endoscopic management of orbital tumors

Purpose of reviewOrbital tumors have been classically approached via external incision. The introduction of endoscopic surgery has revolutionized the management of sinus and skull base disorder. Similarly, endoscopic techniques have been increasingly utilized to access intraorbital tumors located in the medial and inferior orbit with excellent outcomes. The history of the procedure, surgical anatomy of the orbit, patient selection, surgical planning, and the surgical techniques are discussed in this article. Recent findingsAlthough the endoscopic management of orbital tumors is still in its infancy, it has already demonstrated enhanced access to the posterior orbit and orbital apex with decreased morbidity relative to external approaches. SummaryA multidisciplinary team approach, including an oculoplastic surgeon, is an essential component for the surgical planning and management. As the cumulative surgical experience increases, the indications for this approach will likely continue to expand.