Faculty Bibliography

OBJECTIVE:To examine the therapeutic effects of an attenuated, replication-competent vaccinia virus (GLV-1h68) against a panel of 5 human salivary gland carcinoma cell lines. DESIGN/METHODS:The susceptibility of 5 salivary gland carcinoma cell lines to infection and oncolysis by GLV-1h68 was assessed in vitro and in vivo. RESULTS:All 5 cell lines were susceptible to viral infection, transgene expression, and cytotoxic reactions. Three cell lines were exquisitely sensitive to infection by very low doses of GLV-1h68. Orthotopic parotid tumors exhibited more aggressive behavior compared with flank tumors. A single intratumoral injection of GLV-1h68 induced significant tumor regression without observed toxic effects in flank and parotid tumor models; controls demonstrated rapid tumor progression. CONCLUSION/CONCLUSIONS:These promising results demonstrate significant oncolytic activity by an attenuated vaccinia virus for infecting and lysing salivary gland carcinomas, supporting future clinical trials.

Cellular communities in living tissues act in concert to establish intricate microenvironments, with complexity difficult to recapitulate in vitro. We report a method for docking numerous cellularized hydrogel shapes (100-1,000 µm in size) into hydrogel templates to construct 3D cellular microenvironments. Each shape can be uniquely designed to contain customizable concentrations of cells and molecular species, and can be placed into any spatial configuration, providing extensive compositional and geometric tunability of shape-coded patterns using a highly biocompatible hydrogel material. Using precisely arranged hydrogel shapes, we investigated migratory patterns of human mesenchymal stem cells and endothelial cells. We then developed a finite element gradient model predicting chemotactic directions of cell migration in micropatterned cocultures that were validated by tracking ∼2,500 individual cell trajectories. This simple yet robust hydrogel platform provides a comprehensive approach to the assembly of 3D cell environments.

OBJECT/OBJECTIVE:This study was designed to determine if the "keyhole concept," proposed by Perneczky's group, can be verified quantitatively. METHODS:Fourteen (3 bilateral and 8 unilateral) sides of embalmed latex-injected cadaveric heads were dissected via 3 sequential craniotomy approaches: supraorbital keyhole, frontotemporal pterional, and supraorbital. Three-dimensional cartesian coordinates were recorded using a stereotactic localizer. The orthocenter of the ipsilateral anterior clinoid process, the posterior clinoid process, and the contralateral anterior clinoid process are expressed as a center point (the apex). Seven vectors project from the apex to their corresponding target points in a radiating manner on the parasellar skull base. Each 2 neighboring vectors border what could be considered a triangle, and the total area of the 7 triangles sharing the same apex was geometrically expressed as the area of exposure in the parasellar region. RESULTS:Values are expressed as the mean ± SD (mm(2)). The total area of exposure was as follows: supraorbital keyhole 1733.1 ± 336.0, pterional 1699.3 ± 361.9, and supraorbital 1691.4 ± 342.4. The area of exposure on the contralateral side was as follows: supraorbital keyhole 602.2 ± 194.7, pterional 595.2 ± 228.0, and supraorbital 553.3 ± 227.2. The supraorbital keyhole skull flap was 2.0 cm(2), and the skull flap size ratio was 1:5:6.5 (supraorbital keyhole/pterional/supraorbital). CONCLUSIONS:The area of exposure of the parasellar region through the smaller supraorbital keyhole approach is as adequate as the larger pterional and supraorbital approaches. The keyhole concept can be verified quantitatively as follows: 1) a wide area of exposure on the skull base can be obtained through a small keyhole skull opening, and 2) the side opposite the opening can also be visualized.

BACKGROUND:Paragangliomas are rare, vascular, and predominantly benign neoplasms of neural crest origin. They typically arise in the head and neck from the carotid body, jugulotympanic, or vagal paraganglia. Rarely, paragangliomas occur in the larynx. Only 2 cases of hypopharyngeal paraganglioma have been reported. We discuss the case of a hypopharyngeal paraganglioma and review the literature concerning laryngopharyngeal paragangliomas. METHODS AND RESULTS/RESULTS:We present the case of a woman with 2 months of dysphagia and hoarseness that was found to have a hypopharyngeal paraganglioma. The patient underwent embolization and resection of the mass via a lateral thyrotomy approach. Pathologic analysis and selective staining confirmed the presence of a paraganglioma. CONCLUSIONS:Proper histopathologic identification of these tumors is tantamount to guiding treatment. The preferred operative approach is a lateral thyrotomy to minimize patient morbidity. We present the third documented case of a hypopharyngeal paraganglioma and the first in the English-language literature.

OBJECTIVE:To assess the long-term occurrence of hydroceles and varicocele recurrence in patients receiving lymphatic sparing laparoscopic varicocelectomy (LSLV) compared to those receiving plain laparoscopic varicocelectomy (PLV), and also to assess the growth of testicular volume postoperatively. METHODS:We employed a standard three-trocar configuration. The spermatic vessels were identified in the retroperitoneum above the internal inguinal ring. Lymphatics were dissected free from the spermatic artery and veins based on laparoscopic appearance. The spermatic artery and veins were divided between plastic locking clips. We performed a retrospective chart review of all pediatric patients who underwent laparoscopic varicocelectomy between June 2003 and January 2009. RESULTS:Of a total of 97 patients, 67 underwent LSLV with mean follow-up of 45.8 ± 20.7 months and 30 underwent PLV with mean follow-up of 40.8 ± 25.3 months (p = 15). There was a 4.5% hydrocele rate in the LSLV group compared to 43.3% in the PLV group. Of the patients who underwent a PLV and subsequently developed a hydrocele, 31% (n = 4) required a hydrocelectomy, vs none of those who developed a hydrocele after LSLV. Varicocele rate was 6% in the LSLV group vs 3.3% in the PLV group. However, when the artery was not preserved, the probability of recurrence in the LSLV group was 1.3%. Time to hydrocele formation was 16 months in the LSLV group vs 37 months in the PLV group. There was catch-up testicular growth in both groups. CONCLUSIONS:There appears to be increased risk of need for a hydrocelectomy after a PLV as compared to LSLV. Performing a lymphatic sparing, non-artery preserving, laparoscopic varicocelectomy has success and complication rates comparable with those of subinguinal microsurgical varicocelectomy. There appears to be excellent catch-up testicular growth with either laparoscopic varicocelectomy technique.

BACKGROUND:Current immunosuppressive therapy after heart transplantation either generally suppresses the recipient's entire immune system or is mainly targeting T-lymphocytes. Monocytes/macrophages are recognized as a hallmark of acute allograft rejection, but the roles that they play are not well characterized in vivo, because the tools for accessing in situ macrophage infiltration are lacking. In this study, we used MRI to investigate the role of macrophages in acute heart allograft rejection by cellular and functional MRI with selectively depleted systemic macrophages without affecting other leukocyte population, as well as to explore the possibility that macrophages could be an alternative therapeutic target. METHODS AND RESULTS/RESULTS:A rodent heterotopic working heart-lung transplantation model was used for studying acute allograft rejection. Systemic macrophages were selectively depleted by treating recipient animals with clodronate-liposomes. Macrophage infiltration in the graft hearts was monitored by cellular MRI with in vivo ultrasmall superparamagnetic iron oxide particles labeling. Graft heart function was evaluated by tagging MRI followed by strain analysis. Clodronate-liposome treatment depletes circulating monocytes/macrophages in transplant recipients, and both cellular MRI and pathological examinations indicate a significant reduction in macrophage accumulation in the rejecting allograft hearts. In clodronate-liposome-treated group, allograft hearts exhibited preserved tissue integrity, partially reversed functional deterioration, and prolonged graft survival, compared with untreated controls. CONCLUSIONS:Cardiac cellular and functional MRI is a powerful tool to explore the roles of targeted immune cells in vivo. Our results indicate that macrophages are essential in acute cardiac allograft rejection, and selective depletion of macrophages with clodronate-liposomes protects hearts against allograft rejection, suggesting a potential therapeutic avenue. Our findings show that there is a finite risk of forming an intraventricular mass, presumably from the cellular debris or lipid material. Further optimization of the dosing protocol is necessary before clinical applications.

Neurogenic compromise of vocal fold function exists along a continuum encompassing vocal cord hypomobility (paresis) to vocal fold immobility (paralysis) with varying degrees and patterns of reinnervation. Vocal fold paralysis (VFP) may result from injury to the vagus or the recurrent laryngeal nerves anywhere along their course from the brainstem to the larynx. In this article, we review the anatomy of the vagus and recurrent laryngeal nerves and examine the various etiologies of VFP. Selected cases are presented with discussion of key imaging features of VFP including radiologic findings specific to central vagal neuropathy and peripheral recurrent nerve paralysis.

The current 'gold standard' for clinical evaluation of freezing of gait (FOG) in Parkinson's disease (PD) is determination of the number of FOG episodes from video by independent raters. We have previously described a robust technique for objective FOG assessment from lower-limb acceleration. However, there is no existing method for validation of autonomous FOG measures in the absence of video documentation. In this study we compared the results of clinical evaluation of FOG from computer-generated animations (derived from body-mounted inertial sensors) during a timed up and go test with the 'gold standard' of clinical video assessment, utilizing a cohort of 10 experienced raters from four PD centers. Agreement between the 10 clinical observers for scoring of FOG from computer animations was more robust for the relative duration of freeze events (percent time frozen; intraclass correlation coefficient of 0.65) than number of FOG episodes, and was comparable with clinical evaluation of the patient from video (intraclass correlation coefficient 0.73). This result suggests that percent time frozen should be considered (along with number of FOG events) to better convey FOG severity. The ability of clinical observers to quantify FOG from computer-generated animation derived from lower-limb motion data provides a potential approach to validation of accelerometry-based FOG identification outside of the clinic.