OBJECTIVES/HYPOTHESIS:: Choline transporter-like protein 2 (CTL2), a 68-72 kDa inner-ear membrane glycoprotein, is a candidate target antigen in autoimmune hearing loss (AIHL). The objective of this study was to test recombinant human CTL2 as a potential target for the detection of human autoantibodies in patients with AIHL. STUDY DESIGN:: In vitro assay development. METHODS:: Human inner ear CTL2 mRNA was cloned into baculovirus and used to infect insect cells. Immunofluorescence and western blotting were used to determine optimal expression of recombinant human CTL2 (rHuCTL2) in insect cells. AIHL patient sera of known reactivity with guinea pig inner ear were tested for antibodies to purified rHuCTL2 on western blots. Sera from normal hearing donors were used as controls. RESULTS:: The rHuCTL2 protein migrated as three bands: a core protein of 62kDa and two N-glycosylated bands at 66 and 70 kDa. Sera from 6/12 (50%) of AIHL patients with antibody to the 68-72 kDa inner-ear protein or to supporting cells also have antibody to rHuCTL2. Four of the four patients with antibody to rHuCTL2 responded to corticosteroids, whereas 4/8 that lacked antibody to rHuCTL2 did not. Among normal human sera, 80% were negative; binding was barely detectable in 3/15 (20%). CONCLUSIONS:: The rHuCTL2 protein can be produced efficiently and used as a substrate for testing human sera. Antibodies to rHuCTL2 were detected in 50% of inner-ear-reactive AIHL sera. Additionally, circulating antibody to rHuCTL2 is with associated response to corticosteroids in some AIHL patients. Laryngoscope, 2009.

CONTEXT: Individuals suffering from patellofemoral pain have previously been reported to have decreased isometric strength of the hip musculature; however, no researchers have investigated concentric and eccentric torque of the hip musculature in individuals with patellofemoral pain. OBJECTIVE: To compare concentric and eccentric torque of the hip musculature in individuals with and without patellofemoral pain. DESIGN: Case control. SETTING: Research laboratory. PATIENTS OR OTHER PARTICIPANTS: Twenty participants with patellofemoral pain (age = 26.8 +/- 4.5 years, height = 171.8 +/- 8.4 cm, mass = 72.4 +/- 16.8 kg) and 20 control participants (age = 25.6 +/- 2.8 years, height = 169.5 +/- 8.9 cm, mass = 70.0 +/- 16.9 kg) were tested. Volunteers with patellofemoral pain met the following criteria: knee pain greater than or equal to 3 cm on a 10-cm visual analog scale, insidious onset of symptoms not related to trauma, pain with palpation of the patellar facets, and knee pain during 2 of the following activities: stair climbing, jumping or running, squatting, kneeling, or prolonged sitting. Control participants were excluded if they had a prior history of patellofemoral pain, knee surgery in the past 2 years, or current lower extremity injury that limited participation in physical activity. INTERVENTION(S): Concentric and eccentric torque of the hip musculature was measured on an isokinetic dynamometer. All volunteers performed 5 repetitions of each strength test. Separate multivariate analyses of variance were performed to compare concentric and eccentric torque of the hip extensors, abductors, and external rotators between groups. MAIN OUTCOME MEASURE(S): Average and peak concentric and eccentric torque of the hip extensors, abductors, and external rotators. Torque measures were normalized to the participant's body weight multiplied by height. RESULTS: The patellofemoral pain group was weaker than the control group for peak eccentric hip abduction torque (F(1,38)= 6.630, P =.014), and average concentric (F(1,38)= 4.156, P =.048) and eccentric (F(1,38)= 4.963, P =.032) hip external rotation torque. CONCLUSIONS: The patellofemoral pain group displayed weakness in eccentric hip abduction and hip external rotation, which may allow for increased hip adduction and internal rotation during functional movements.

PURPOSE: Over the past 60 years, cytotoxic chemotherapy has targeted the cancer cell. Despite this, there have been few cancer cures. A new approach to cancer therapy is to target the multicellular biological entity of the tumor microenvironment. EXPERIMENTAL DESIGN: Lenalidomide, an immunomodulatory drug, sunitinib, a tyrosine kinase inhibitor, and low-dose metronomic cyclophosphamide, were tested alone and in combination for their abilities to inhibit endothelial cell tube formation, rat aortic ring outgrowth, tumor growth, and metastatic development in mice. In addition, ectopic tumor lysates were evaluated for the presence of proangiogenic proteins. RESULTS: The three agents alone were shown to significantly inhibit endothelial cells' ability to form tubes and significantly inhibit the multicellular microenvironment in the rat aortic ring assay (P < 0.01 and P < 0.001). This effect was also significantly augmented when the agents were combined. Furthermore, the three-drug combination was able halt the progression of tumor growth almost completely in xenograft models of ocular melanoma, colon cancer, pancreatic cancer, and cutaneous melanoma. These agents significantly decrease the number of proliferating cells in tumors, significantly increase the number of cells undergoing active cell death in tumors, and significantly decrease the number of blood vessels in treated tumors (P < 0.05). Combination therapy shows a decrease in the compensatory up-regulation of proangiogenic proteins after treatment when compared with single-agent therapy. CONCLUSIONS: This combination of agents causes an inhospitable microenvironment for tumor cells and shows great promise for use in the clinic.

The monoclonal antibody against HER2, trastuzumab (Herceptin((R))), has become an important player in the treatment of patients with HER2-positive breast cancer. Both in the metastatic and adjuvant setting, the addition of trastuzumab to other systemic treatments has led to a striking increase in tumor response and survival. The downside with the use of this agent, however, is its inherent cardiotoxicity, which is particularly common when anthracyclines are used concurrently. This review will focus on all aspects of the cardiac side-effects of trastuzumab, ranging from epidemiology and pathophysiology to cardiac monitoring, and treatment and prevention.

BACKGROUND: In 2000, Delaware instituted a trauma system that included establishing four Level III trauma centers in counties previously without trauma centers. The purpose of this study was to analyze whether implementation of this inclusive trauma system reduced the injury-related mortality rates in these counties. METHODS: Using the state trauma registry, patients with trauma admitted to all acute care hospitals in Delaware from January 1, 1995 through December 31, 2004 were identified and categorized into two groups: preimplementation of an inclusive trauma system (1995-1999), and postimplementation (2000-2004). These groups were compared in aggregate and by individual counties for age, sex, mechanism of injury, Abbreviated Injury Score, injury-related mortality rate, mean Injury Severity Score (ISS), acute transfers out, and acute transfers in (Level I only). chi test and Mann-Whitney U test were used where indicated. Significance was determined to be p < or = 0.05. RESULTS: After implementation, mortality rates significantly decreased (5.3%-2.8%) and rate of acute transfers out increased (14.7%-19.5%) in the counties served by the Level III centers. The ISS of patients in the Level I trauma center significantly increased (mean ISS = 10) when compared with the Level III trauma centers (mean ISS = 6), reflecting increased transfers of patients with severe injuries. CONCLUSION: An inclusive state trauma system that included the establishment of Level III trauma centers in previously underserved counties led to a decrease in trauma-related mortality rates in these counties. In the county served by the Level I trauma center, mortality remained unchanged despite an increase in admissions and the injury severity of these admissions.

INTRODUCTION: The aim of this study is to report an update of the surgical experience at a single institution with these unusual tumors. METHODS: Sixteen consecutive patients who underwent surgery for a pathologically confirmed solid pseudopapillary neoplasm (SPPN) were retrospectively reviewed. RESULTS: Fifteen of the patients were female and the median age at diagnosis was 30 years (range, 14-53 years). Abdominal and back pain were the most common presenting symptoms. The tumors appeared on cross-sectional imaging as solid and cystic (n = 14) or cystic (n = 2) masses. The median tumor size was 9.5 cm (range, 5.0-24.0 cm). All 16 patients had curative resections including 3 pancreaticoduodenectomies and 13 distal pancreatectomies. Three patients required extended resections including pancreaticoduodenectomy with portal vein resection, distal pancreatectomy with tranverse colectomy, and distal pancreactomy with omentectomy. Two of the resections were R1 whereas 14 were R0. All patients were alive and disease-free at a median follow-up of 43 months (range, 3-186 months). CONCLUSION: SPPNs should be considered in young women presenting with a large solid-cystic pancreatic mass. Aggressive en bloc resection should always be attempted including resection of concomitant metastases as patients demonstrate excellent long-term survival even in the presence of distant spread. J. Surg. Oncol.(c) 2007 Wiley-Liss, Inc.

Radical resection of low-grade gliomas can decrease the incidence of recurrence, the time to tumor progression, and the incidence of malignant transformation. The authors present a series of 25 patients who underwent craniotomy and resection of low-grade tumor in an intraoperative magnetic resonance (MR) imager. This is an open configuration 0.5-tesla imager developed by The Brigham and Women's Hospital and General Electric, in which a patient can be placed to undergo surgery. Gross-total removal was accomplished under real-time image guidance. These intraoperative images allow definitive localization and targeting of the lesions and accommodate anatomical changes that may occur during surgery. The authors consistently found that the extent of abnormality seen on the intraoperatively obtained films of resection was larger than that apparent in the surgical field of view alone. Intraoperative imaging made accurate surgical identification of these abnormal areas and subsequent resection possible. Patients with tumors adjacent to or within motor or language cortex underwent resection while awake, with monitoring of neurological function. In these cases, an aggressive resection without increased neurological morbidity was accomplished using the image guidance in conjunction with serial testing. A 1-month postoperative MR image was obtained in all patients. These correlated with the final intraoperative images obtained after the resection was completed. Only one patient had a mild postoperative deficit that remained at the 1-month follow-up examination. As the long-term outcome in patients with low-grade gliomas has been shown to correspond to the degree of resection, surgical resection in which intraoperative MR imaging guidance is used can be an invaluable modality in the treatment of these tumors.

The mobile part of the light-harvesting chlorophyll (chl) a/b protein complex (LHCII), composed of the Lhcb1 and Lhcb2 proteins, is the basic unit of chloroplast state transitions-the short term tuning system in balancing the excitation energy between Photosystem (PS) II and PSI. State transitions are catalysed by the thylakoid associated STN7 kinase, and we show here that besides the phosphorylation of the Lhcb1 and Lhcb2 proteins, also the phosphorylation of Lhcb4.2 (CP29) is under the control of the STN7 kinase. Upon growth of Arabidopsis WT and stn7 mutant plants under low and moderate light conditions, the WT plants favoured state 2 whereas stn7 was locked in state 1. The lack of the STN7 kinase and state transitions in stn7 also modified the thylakoid protein contents upon long-term low light acclimation resulting, for example, in low Lhcb1 and in elevated Lhca1 and Lhca2 protein amounts as compared to WT. Adjustments of thylakoid protein contents probably occurred at post-transcriptional level since the DNA microarray experiments from each growth condition did not reveal any significant differences between stn7 and WT transcriptomes. The resulting high Lhcb2/Lhcb1 ratio in stn7 upon growth at low light was accompanied by lower capacity for NPQ than in WT. On the contrary, higher amounts of PsbS in stn7 under moderate and high light growth conditions resulted in higher NPQ compared to WT and consequently also in a protection of PSII against photoinhibition. STN7 kinase and the state transitions are suggested to have a physiological significance for dynamic acclimation to low but fluctuating growth light conditions. They are shown to function as a buffering system upon short high light illumination peaks by shifting the thylakoids from state 2 to state 1 and thereby down regulating the induction of stress-responsive genes, a likely result from transient over-reduction of PSI acceptors.

Object. Neurenteric cysts are infrequently reported congenital abnormalities believed to be derived from an abnormal connection between the primitive endoderm and ectoderm. The authors report a series of 13 patients treated over a 50-year period. Methods. Of the 13 patients, seven were female and six were male. Their ages at presentation ranged widely from 5 weeks to 52 years of age. Children presented more commonly with cutaneous stigmata of occult spinal dysraphism (OSD) whereas adults presented primarily with pain. Neurological deficit as a presenting symptom was less common in our series, a finding that reflects the slow growth of these lesions. In all but one patient some form of vertebral anomaly was associated with the cystic lesions, including two patients with Klippel-Feil abnormalities. There was a high incidence of associated forms of OSD including split cord malformation, lipoma, dermal sinus tract, and tethered spinal cord. In previous reports the authors have suggested that neurenteric cysts are more common in the cervical region and in a position ventral to the cord. In the present series these cysts most commonly occurred as intradural, extramedullary masses in the thoracolumbar region, situated dorsal to the spinal cord. The median follow-up period was 7.5 years, and postoperative outcome reflected a patient's preoperative neurological status; in no patient was outcome worsened due to surgery. Conclusions. Complete excision of the neurenteric cyst remains the treatment of choice, as subtotal excision is associated with recurrence.