[Stereotactic lung radiotherapy: Technical setting up on Novalis Tx® and single centre prospective study of the 100 first malignant pulmonary nodules treated at centre Jean-Perrin].

PubMed

Bellière-Calandry, A; Dupic, G; Magnier, F; Chassin, V; Dedieu, V; Lapeyre, M

2017-06-01

Description of the treatment technique of stereotactic lung radiotherapy on Novalis Tx ® and prospective study of the first 100 pulmonary nodules treated at centre Jean-Perrin (France). From October 2012 to December 2015, 100 inoperable pulmonary nodules (62 stage I non-small-cell lung cancer and 38 metastases) of 90 patients with a mean age of 68.2 years (range: 46-89 years) were prospectively treated with dynamic arctherapy on Novalis Tx ® . Mean gross tumour and planning target volumes were respectively 6.9 cm 3 (range: 0.2-31.4 cm 3 ) and 38.7 cm 3 (range: 1.7-131 cm 3 ), which correspond to diameters equal to 2.3cm and 4.2cm. Prescribed doses to the 80% isodose line were 54Gy in three fractions for peripheral non-small-cell lung cancer, 50Gy in five fractions for central non-small-cell lung cancer and 45Gy in three fractions for lung metastases. Clinical and radiological follow-up was done every three months with RECIST criteria for efficacy and NCI-CTCAE v4 scale for toxicity. Median follow-up was 12.5 months. Complete response was observed in 23.8% of cases. Local control rates were 100% and 90.7% respectively at 12 and 24 months, with 96% at 24 months for stage I non-small-cell lung cancer. Overall survival rates of patients with stage I non-small-cell lung cancer were 77.4% and 73.5% at 12 and 24 months (median overall survival was 32 months). Diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume below 40% was significantly associated to a poor prognostic factor on univariate analysis (P=0.00013). At least three deaths were due to an acute respiratory failure, which correspond to about 4.8% of grade 5 radiation pneumonitis. Overall survival rate for metastatic patients were 95.2% and 59.5% respectively at 12 and 24 months (median overall survival was 25 months); 23.3% of grade 2 or less radiation pneumonitis, 7.8% of grade 2 or less radiation dermatitis, 2.2% of asymptomatic ribs fracture and 3.3% of chest pains were observed. Stereotactic lung radiotherapy is an effective treatment for inoperable stage I non-small-cell lung cancer and lung oligometastases of well informed and selected patients. Initial respiratory state, and especially the diffusing capacity of the lungs for carbon monoxide corrected for alveolar volume, seems to be important for tolerance. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Stereotactic Body Radiotherapy for Medically Inoperable Lung Cancer: Prospective, Single-Center Study of 108 Consecutive Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taremi, Mojgan, E-mail: mojgan.taremi@rmp.uhn.on.ca; Department of Radiation Oncology, University Health Network, Toronto, ON; Department of Radiation Oncology, VU University Medical Center, Amsterdam

2012-02-01

Purpose: To present the results of stereotactic body radiotherapy (SBRT) for medically inoperable patients with Stage I non-small-cell lung cancer (NSCLC) and contrast outcomes in patients with and without a pathologic diagnosis. Methods and Materials: Between December 2004 and October 2008, 108 patients (114 tumors) underwent treatment according to the prospective research ethics board-approved SBRT protocols at our cancer center. Of the 108 patients, 88 (81.5%) had undergone pretreatment whole-body [18F]-fluorodeoxyglucose positron emission tomography/computed tomography. A pathologic diagnosis was unavailable for 33 (28.9%) of the 114 lesions. The SBRT schedules included 48 Gy in 4 fractions or 54-60 Gy inmore » 3 fractions for peripheral lesions and 50-60 Gy in 8-10 fractions for central lesions. Toxicity and radiologic response were assessed at the 3-6-month follow-up visits using conventional criteria. Results: The mean tumor diameter was 2.4-cm (range, 0.9-5.7). The median follow-up was 19.1 months (range, 1-55.7). The estimated local control rate at 1 and 4 years was 92% (95% confidence interval [CI], 86-97%) and 89% (95% CI, 81-96%). The cause-specific survival rate at 1 and 4 years was 92% (95% CI, 87-98%) and 77% (95% CI, 64-89%), respectively. No statistically significant difference was found in the local, regional, and distant control between patients with and without pathologically confirmed NSCLC. The most common acute toxicity was Grade 1 or 2 fatigue (53 of 108 patients). No toxicities of Grade 4 or greater were identified. Conclusions: Lung SBRT for early-stage NSCLC resulted in excellent local control and cause-specific survival with minimal toxicity. The disease-specific outcomes were comparable for patients with and without a pathologic diagnosis. SBRT can be considered an option for selected patients with proven or presumed early-stage NSCLC.« less

Radiofrequency ablation of stage IA non-small cell lung cancer in medically inoperable patients: Results from the American College of Surgeons Oncology Group Z4033 (Alliance) trial.

PubMed

Dupuy, Damian E; Fernando, Hiran C; Hillman, Shauna; Ng, Thomas; Tan, Angelina D; Sharma, Amita; Rilling, William S; Hong, Kelvin; Putnam, Joe B

2015-10-01

This study evaluated the 2-year overall survival rate, adverse event rate, local control rate, and impact on pulmonary function tests for medically inoperable patients with stage IA non-small cell lung cancer (NSCLC) undergoing computed tomography (CT)-guided radiofrequency ablation (RFA) in a prospective, multicenter trial. Fifty-four patients (25 men and 29 women) with a median age of 76 years (range, 60-89 years) were enrolled from 16 US centers; 51 patients were eligible for evaluation (they had biopsy-proven stage IA NSCLC and were deemed medically inoperable by a board-certified thoracic surgeon). Pulmonary function tests were performed within the 60 days before RFA and 3 and 24 months after RFA. Adverse events were recorded and categorized. Patients were followed with CT and fludeoxyglucose positron emission tomography. Local control rate and recurrence patterns were analyzed. The overall survival rate was 86.3% at 1 year and 69.8% at 2 years. The local tumor recurrence-free rate was 68.9% at 1 year and 59.8% at 2 years and was worse for tumors > 2 cm. In the 19 patients with local recurrence, 11 were re-treated with RFA, 9 underwent radiation, and 3 underwent chemotherapy. There were 21 grade 3 adverse events, 2 grade 4 adverse events, and 1 grade 5 adverse event in 12 patients within the first 90 days after RFA. None of the grade 4 or 5 adverse events were attributable to RFA. There was no significant change in the forced expiratory volume in the first second of expiration or the diffusing capacity of lung for carbon monoxide after RFA. A tumor size less than 2.0 cm and a performance status of 0 or 1 were associated with statistically significant improved survival of 83% and 78%, respectively, at 2 years. RFA is a single, minimally invasive procedure that is well tolerated in medically inoperable patients, does not adversely affect pulmonary function tests, and provides a 2-year overall survival rate that is comparable to the rate reported after stereotactic body radiotherapy in similar patients. © 2015 American Cancer Society.

Acute toxicity of definitive chemoradiation in patients with inoperable or irresectable esophageal carcinoma

PubMed Central

2014-01-01

Background Definitive chemoradiation (dCRT) is considered curative intent treatment for patients with inoperable or irresectable esophageal cancer. Acute toxicity data focussing on dCRT are lacking. Methods A retrospective analysis of patients treated with dCRT consisting of 6 cycles of paclitaxel 50 mg/m2 and carboplatin AUC2 concomitant with radiotherapy (50.4 Gy\\1.8Gy) from 2006 through 2011 at a single tertiary center was performed. Toxicity, hospital admissions and survival were analysed. Results 127 patients were treated with definitive chemoradiation. 33 patients were medically inoperable, 94 patients were irresectable, Despite of a significantly smaller tumor length in inoperable patients grade ≥3 toxicity was significantly recorded more often in the inoperable patients (44%) than in irresectable patients (20%) (p < 0.05) Hospital admission occurred more often in the inoperable patients (39%) than in the irresectable patients (22%) (p < 0.05) Median number of cycles of chemotherapy was five for inoperable patients (p = 0.01), while six cycles could be administered to patients with irresectable disease. Recurrence and survival were not significantly different. The odds ratio for developing toxicity ≥ grade 3 was 2.6 (95% CI 1.0-6.4 p < 0.05) for being an inoperable patient and 1.2 (95% CI 1.0-1.4 p = 0.02) per 10 extra micromol/l creatinine. Conclusions Our data show that acute toxicity of definitive chemoradiation is worse in patients with medically inoperable esophageal carcinoma compared to patients with irresectable esophageal cancer and mainly occurs in the 5th cycle of treatment. Improvement of supportive care should be undertaken in this more fragile group. PMID:24485047

Survival after Radiofrequency Ablation in 122 Patients with Inoperable Colorectal Lung Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gillams, Alice, E-mail: alliesorting@gmail.com; Khan, Zahid; Osborn, Peter

2013-06-15

Purpose. To analyze the factors associated with favorable survival in patients with inoperable colorectal lung metastases treated with percutaneous image-guided radiofrequency ablation. Methods. Between 2002 and 2011, a total of 398 metastases were ablated in 122 patients (87 male, median age 68 years, range 29-90 years) at 256 procedures. Percutaneous CT-guided cool-tip radiofrequency ablation was performed under sedation/general anesthesia. Maximum tumor size, number of tumors ablated, number of procedures, concurrent/prior liver ablation, previous liver or lung resection, systemic chemotherapy, disease-free interval from primary resection to lung metastasis, and survival from first ablation were recorded prospectively. Kaplan-Meier analysis was performed, andmore » factors were compared by log rank test. Results. The initial number of metastases ablated was 2.3 (range 1-8); the total number was 3.3 (range 1-15). The maximum tumor diameter was 1.7 (range 0.5-4) cm, and the number of procedures was 2 (range 1-10). The major complication rate was 3.9 %. Overall median and 3-year survival rate were 41 months and 57 %. Survival was better in patients with smaller tumors-a median of 51 months, with 3-year survival of 64 % for tumors 2 cm or smaller versus 31 months and 44 % for tumors 2.1-4 cm (p = 0.08). The number of metastases ablated and whether the tumors were unilateral or bilateral did not affect survival. The presence of treated liver metastases, systemic chemotherapy, or prior lung resection did not affect survival. Conclusion. Three-year survival of 57 % in patients with inoperable colorectal lung metastases is better than would be expected with chemotherapy alone. Patients with inoperable but small-volume colorectal lung metastases should be referred for ablation.« less

The spatial and temporal `cost' of volcanic eruptions: assessing economic impact, business inoperability, and spatial distribution of risk in the Auckland region, New Zealand

NASA Astrophysics Data System (ADS)

McDonald, Garry W.; Smith, Nicola J.; Kim, Joon-hwan; Cronin, Shane J.; Proctor, Jon N.

2017-07-01

Volcanic risk assessment has historically concentrated on quantifying the frequency, magnitude, and potential diversity of physical processes of eruptions and their consequent impacts on life and property. A realistic socio-economic assessment of volcanic impact must however take into account dynamic properties of businesses and extend beyond only measuring direct infrastructure/property loss. The inoperability input-output model, heralded as one of the 10 most important accomplishments in risk analysis over the last 30 years (Kujawaski Syst Eng. 9:281-295, 2006), has become prominent over the last decade in the economic impact assessment of business disruptions. We develop a dynamic inoperability input-output model to assess the economic impacts of a hypothetical volcanic event occurring at each of 7270 unique spatial locations throughout the Auckland Volcanic Field, New Zealand. This field of at least 53 volcanoes underlies the country's largest urban area, the Auckland region, which is home to 1.4 million people and responsible for 35.3% (NZ201481.2 billion) of the nation's GDP (Statistics New Zealand 2015). We apply volcanic event characteristics for a small-medium-scale volcanic eruption scenario and assess the economic impacts of an `average' eruption in the Auckland region. Economic losses are quantified both with, and without, business mitigation and intervention responses in place. We combine this information with a recent spatial hazard probability map (Bebbington and Cronin Bull Volcanol. 73(1):55-72, 2011) to produce novel spatial economic activity `at risk' maps. Our approach demonstrates how business inoperability losses sit alongside potential life and property damage assessment in enhancing our understanding of volcanic risk mitigation.

Impact of tumor size on outcome after stereotactic body radiation therapy for inoperable hepatocellular carcinoma

PubMed Central

Kuo, Hsing-Tao; Que, Jenny; Lin, Li-Ching; Yang, Ching-Chieh; Koay, Lok-Beng; Lin, Chia-Hui

2017-01-01

Abstract Stereotactic body radiation therapy (SBRT) for inoperable hepatocellular carcinoma (HCC) offers excellent local control rates. This study retrospectively analyzed the influence of different tumor size on treatment outcomes after SBRT. Between December 2008 and February 2014, 141 HCC patients were treated with Cyberknife SBRT. Patients were divided into 3 groups namely small tumors (≤4 cm), intermediate-sized (>4–<10 cm), and large (≥10 cm) tumors. Treatment outcomes, prognoses, and safety at each tumor size were compared and analyzed. A total of 52 patients with small tumors, 55 with intermediate tumors, and 34 patients with large tumors were retrospectively analyzed with a median follow-up of 16 months. Objective responses were achieved at 96.15%, 90.90%, and 76.47% for small, intermediate, and large tumors, respectively (P ≤ .0001) and the 3-year local control rates were 97.85%, 71.99%, and 82.14%, respectively (P = .0035). The 3-year overall survival rates were 50.26%, 45.29%, and 33.38% for small, intermediate, and large tumors, respectively (P = .3757). No significant differences were found in overall-survival, intra-hepatic recurrence free survival, disease-progression free survival, or distant metastasis-free survival. SBRT offers the best effective local control rate and response rate for small HCCs. However, tumor size did not significantly affect the overall survival rate, intra-hepatic recurrence free rate, or disease-progression free rate. PMID:29390360

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hatton, Matthew; Nankivell, Matthew, E-mail: mn@ctu.mrc.ac.uk; Lyn, Ethan

Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result ofmore » poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.« less

Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study.

PubMed

Ghofrani, Hossein-Ardeschir; Simonneau, Gérald; D'Armini, Andrea M; Fedullo, Peter; Howard, Luke S; Jaïs, Xavier; Jenkins, David P; Jing, Zhi-Cheng; Madani, Michael M; Martin, Nicolas; Mayer, Eckhard; Papadakis, Kelly; Richard, Dominik; Kim, Nick H

2017-10-01

Macitentan is beneficial for long-term treatment of pulmonary arterial hypertension. The microvasculopathy of chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension are similar. The phase 2, double-blind, randomised, placebo-controlled MERIT-1 trial assessed macitentan in 80 patients with CTEPH adjudicated as inoperable. Patients identified as WHO functional class II-IV with a pulmonary vascular resistance (PVR) of at least 400 dyn·s/cm 5 and a walk distance of 150-450 m in 6 min were randomly assigned (1:1), via an interactive voice/web response system, to receive oral macitentan (10 mg once a day) or placebo. Treatment with phosphodiesterase type-5 inhibitors and oral or inhaled prostanoids was permitted for WHO functional class III/IV patients. The primary endpoint was resting PVR at week 16, expressed as percentage of PVR measured at baseline. Analyses were done in all patients who were randomly assigned to treatment; safety analyses were done in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02021292. Between April 3, 2014, and March 17, 2016, we screened 186 patients for eligibility at 48 hospitals across 20 countries. Of these, 80 patients in 36 hospitals were randomly assigned to treatment (40 patients to macitentan, 40 patients to placebo). At week 16, geometric mean PVR decreased to 73·0% of baseline in the macitentan group and to 87·2% in the placebo group (geometric means ratio 0·84, 95% CI 0·70-0·99, p=0·041). The most common adverse events in the macitentan group were peripheral oedema (9 [23%] of 40 patients) and decreased haemoglobin (6 [15%]). In MERIT-1, macitentan significantly improved PVR in patients with inoperable CTEPH and was well tolerated. Actelion Pharmaceuticals Ltd. Copyright © 2017 Elsevier Ltd. All rights reserved.

International trade inoperability input-output model (IT-IIM): theory and application.

PubMed

Jung, Jeesang; Santos, Joost R; Haimes, Yacov Y

2009-01-01

The inoperability input-output model (IIM) has been used for analyzing disruptions due to man-made or natural disasters that can adversely affect the operation of economic systems or critical infrastructures. Taking economic perturbation for each sector as inputs, the IIM provides the degree of economic production impacts on all industry sectors as the outputs for the model. The current version of the IIM does not provide a separate analysis for the international trade component of the inoperability. If an important port of entry (e.g., Port of Los Angeles) is disrupted, then international trade inoperability becomes a highly relevant subject for analysis. To complement the current IIM, this article develops the International Trade-IIM (IT-IIM). The IT-IIM investigates the resulting international trade inoperability for all industry sectors resulting from disruptions to a major port of entry. Similar to traditional IIM analysis, the inoperability metrics that the IT-IIM provides can be used to prioritize economic sectors based on the losses they could potentially incur. The IT-IIM is used to analyze two types of direct perturbations: (1) the reduced capacity of ports of entry, including harbors and airports (e.g., a shutdown of any port of entry); and (2) restrictions on commercial goods that foreign countries trade with the base nation (e.g., embargo).

Pandemic recovery analysis using the dynamic inoperability input-output model.

PubMed

Santos, Joost R; Orsi, Mark J; Bond, Erik J

2009-12-01

Economists have long conceptualized and modeled the inherent interdependent relationships among different sectors of the economy. This concept paved the way for input-output modeling, a methodology that accounts for sector interdependencies governing the magnitude and extent of ripple effects due to changes in the economic structure of a region or nation. Recent extensions to input-output modeling have enhanced the model's capabilities to account for the impact of an economic perturbation; two such examples are the inoperability input-output model((1,2)) and the dynamic inoperability input-output model (DIIM).((3)) These models introduced sector inoperability, or the inability to satisfy as-planned production levels, into input-output modeling. While these models provide insights for understanding the impacts of inoperability, there are several aspects of the current formulation that do not account for complexities associated with certain disasters, such as a pandemic. This article proposes further enhancements to the DIIM to account for economic productivity losses resulting primarily from workforce disruptions. A pandemic is a unique disaster because the majority of its direct impacts are workforce related. The article develops a modeling framework to account for workforce inoperability and recovery factors. The proposed workforce-explicit enhancements to the DIIM are demonstrated in a case study to simulate a pandemic scenario in the Commonwealth of Virginia.

Exercise physiological responses to drug treatments in chronic thromboembolic pulmonary hypertension.

PubMed

Charalampopoulos, Athanasios; Gibbs, J Simon R; Davies, Rachel J; Gin-Sing, Wendy; Murphy, Kevin; Sheares, Karen K; Pepke-Zaba, Joanna; Jenkins, David P; Howard, Luke S

2016-09-01

We tested the hypothesis that patients with chronic thromboembolic pulmonary hypertension (CTEPH) that was deemed to be inoperable were more likely to respond to drugs for treating pulmonary arterial hypertension (PAH) by using cardiopulmonary exercise (CPX) testing than those with CTEPH that was deemed to be operable. We analyzed CPX testing data of all patients with CTEPH who were treated with PAH drugs and had undergone CPX testing before and after treatment at a single pulmonary hypertension center between February 2009 and March 2013. Suitability for pulmonary endarterectomy (PEA) was decided by experts in PEA who were associated with a treatment center. The group with inoperable CTEPH included 16 patients, the operable group included 26 patients. There were no differences in demographics and baseline hemodynamic data between the groups. Unlike patients in the operable group, after drug treatment patients with inoperable CTEPH had a significantly higher peak V̇o2 (P < 0.001), work load (P = 0.002), and oxygen pulse (P < 0.001). In terms of gas exchange, there was an overall net trend toward improved V̇e/V̇co2 in the group with inoperable CTEPH, with an increased PaCO2 (P = 0.01), suggesting reduced hyperventilation. No changes were observed in patients with operable CTEPH. In conclusion, treatment with PAH drug therapy reveals important pathophysiological differences between inoperable and operable CTEPH, with significant pulmonary vascular and cardiac responses in inoperable disease. Drug effects on exercise function observed in inoperable CTEPH cannot be translated to all forms of CTEPH. Copyright © 2016 the American Physiological Society.

Induction gemcitabine in standard dose or prolonged low-dose with cisplatin followed by concurrent radiochemotherapy in locally advanced non-small cell lung cancer: a randomized phase II clinical trial

PubMed Central

Vrankar, Martina; Zwitter, Matjaz; Bavcar, Tanja; Milic, Ana; Kovac, Viljem

2014-01-01

Background The optimal combination of chemotherapy with radiation therapy for treatment locally advanced non-small cell lung cancer (NSCLC) remains an open issue. This randomized phase II study compared gemcitabine in two different schedules and cisplatin - as induction chemotherapy, followed by radiation therapy concurrent with cisplatin and etoposid. Patients and methods. Eligible patients had microscopically confirmed inoperable non-metastatic non-small cell lung cancer; fulfilled the standard criteria for platin-based chemotherapy; and signed informed consent. Patients were treated with 3 cycles of induction chemotherapy with gemcitabine and cisplatin. Two different aplications of gemcitabine were compared: patients in arm A received gemcitabine at 1250 mg/m2 in a standard half hour i.v. infusion on days 1 and 8; patients in arm B received gemcitabine at 250 mg/m2 in prolonged 6-hours i.v. infusion on days 1 and 8. In both arms, cisplatin 75 mg/m2 on day 2 was administered. All patients continued treatment with radiation therapy with 60–66 Gy concurrent with cisplatin 50 mg/m2 on days 1, 8, 29 and 36 and etoposid 50 mg/m2 on days 1–5 and 29–33. The primary endpoint was response rate (RR) after induction chemotherapy; secondary endpoints were toxicity, progression-free survival (PFS) and overall survival (OS). Results From September 2005 to November 2010, 106 patients were recruited to this study. No statistically signifficant differences were found in RR after induction chemotherapy between the two arms (48.1% and 57.4%, p = 0.34). Toxicity profile was comparable and mild with grade 3/4 neutropenia as primary toxicity in both arms. One patient in arm B suffered from acute peripheral ischemia grade 4 and an amputation of lower limb was needed. With a median follow-up of 69.3 months, progression-free survival and median survival in arm A were 15.7 and 24.8 months compared to 18.9 and 28.6 months in arm B. The figures for 1- and 3-year overall survival were 73.1% and 30.8% in arm A, and 81.5 % and 44.4% in arm B, respectively. Conclusions Among the two cisplatin-based doublets of induction chemotherapy for inoperable NSCLC, both schedules of gemcitabine have a comparable toxicity profile. Figures for RR, PFS and OS are among the best reported in current literature. While there is a trend towards better efficacy of the treament with prolonged infusion of gemcitabine, the difference between the two arms did not reach statistical significance. PMID:25435850

Interdicting an Adversary’s Economy Viewed As a Trade Sanction Inoperability Input Output Model

DTIC Science & Technology

2017-03-01

set of sectors. The design of an economic sanction, in the context of this thesis, is the selection of the sector or set of sectors to sanction...We propose two optimization models. The first, the Trade Sanction Inoperability Input-output Model (TS-IIM), selects the sector or set of sectors that...Interdependency analysis: Extensions to demand reduction inoperability input-output modeling and portfolio selection . Unpublished doctoral dissertation

Long-term outcome of phase I/II prospective study of dose-escalated proton therapy for early-stage non-small cell lung cancer.

PubMed

Chang, Joe Y; Zhang, Wencheng; Komaki, Ritsuko; Choi, Noah C; Chan, Shen; Gomez, Daniel; O'Reilly, Michael; Jeter, Melenda; Gillin, Michael; Zhu, Xiaorong; Zhang, Xiaodong; Mohan, Radhe; Swisher, Stephen; Hahn, Stephen; Cox, James D

2017-02-01

The aim of this phase I/II study was to assess the long-term clinical benefits and toxicities of proton beam therapy for medically inoperable early-stage non-small cell lung cancer (NSCLC). From June 2006 to September 2011, 35 patients with medically inoperable T1N0M0 (central or superior location, 12 patients) or T2-3N0M0 (any location, 23 patients) NSCLC were treated with 87.5Gy at 2.5Gy/fraction of proton therapy. Toxicities were scored according to the Common Terminology Criteria for Adverse Events, version 4.0. The median follow-up time was 83.1months (95% CI: 69.2-97.1months). For all 35 patients, the 1, 3, and 5-year overall survival rates were 85.7%, 42.9%, and 28.1%, respectively. The 5-year local recurrence-free, regional recurrence-free, and distant metastasis-free survival rates were 85.0%, 89.2%, and 54.4%, respectively. Different T stages had no effect on local and regional recurrence (p=0.499, p=1.00). However, with the increase in T stages, the distant metastasis rate increased significantly (p=0.006). The most common adverse effects were dermatitis (grade 2, 51.4%; grade 3, 2.9%) and radiation pneumonitis (grade 2, 11.4%; grade 3, 2.9%). Other grade 2 toxicities included esophagitis (2.9%), rib fracture (2.9%), heart toxicities (5.7%), and chest wall pain (2.9%). According to our long-term follow-up data, proton therapy with ablative doses is well tolerated and effective in medically inoperable early-stage NSCLC. Systemic therapy should be considered to reduce the rate of distant metastasis in cases of T2 and T3 lesions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

HI-CHART: a phase I/II study on the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer.

PubMed

De Ruysscher, Dirk; Wanders, Rinus; van Haren, Erik; Hochstenbag, Monique; Geraedts, Wiel; Pitz, Cordula; Simons, Jean; Boersma, Liesbeth; Verschueren, Tom; Minken, Andre; Bentzen, Søren M; Lambin, Philippe

2008-05-01

To determine the feasibility of high-dose continuous hyperfractionated accelerated radiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). In a prospective, Phase I/II study, according to the risk for radiation pneumonitis, three risk groups were defined: V(20) <25%, V(20) 25-37%, and V(20) >37%. The dose was administered in three steps from 61.2 Gy/34 fractions/23 days to 64.8 Gy/36 fractions/24 days to 68.40 Gy/38 fractions/25 days (1.8 Gy b.i.d. with 8-h interval), using a three-dimensional conformal technique. Only the mediastinal lymph node areas that were positive on the pretreatment (18)F-deoxy-D-glucose positron emission tomography scan were included in the target volume. The primary endpoint was toxicity. A total of 48 Stage I-IIIB patients were included. In all risk groups, 68.40 Gy/38 fractions/25 days could be administered. Maximal toxicity according to the risk groups was as follows: V(20) <25% (n = 35): 1 Grade 4 (G4) lung and 1 G3 reversible esophageal toxicity; V(20) 35-37% (n = 12): 1 G5 lung and 1 G3 reversible esophageal toxicity. For the whole group, local tumor recurrence occurred in 25% (95% confidence interval 14%-40%) of the patients, with 1 of 48 (2.1%; upper one-sided 95% confidence limit 9.5%) having an isolated nodal recurrence. The median actuarial overall survival was 20 months, with a 2-year survival rate of 36%. High-dose continuous hyperfractionated accelerated radiotherapy up to a dose of 68.40 Gy/38 fractions/25 days (a biologic equivalent of approximately 80 Gy when delivered in conventional fractionation) in patients with inoperable NSCLC and a V(20) up to 37% is feasible.

Safety and effectiveness of eribulin in Japanese patients with locally advanced or metastatic breast cancer: a post-marketing observational study.

PubMed

Watanabe, Junichiro; Ito, Yoshinori; Ohsumi, Shozo; Mizutani, Mitsuhiro; Tashiro, Hideya; Sakurai, Kenichi; Takahashi, Masato; Saito, Tsuyoshi; Tsurutani, Junji; Mukai, Hirofumi; Yoshinami, Tetsuhiro; Takao, Shintaro; Yamamoto, Yasuhisa; Matsuoka, Toshiyuki; Iwase, Hirotaka; Iwata, Hiroji; Nakamura, Seigo; Saeki, Toshiaki

2017-12-01

Background This large-scale study was conducted to evaluate the safety and effectiveness of eribulin for the treatment of inoperable or recurrent breast cancer in real-world settings in Japan. Methods Between July and December 2011, eligible patients with inoperable or recurrent breast cancer receiving eribulin for the first time were centrally registered and observed for 1 year. Eribulin was administered intravenously (1.4 mg/m 2 ) on days 1 and 8 of every 3-week cycle. The primary endpoint was the frequency and intensity of adverse drug reactions (ADRs). Secondary endpoints included overall response rate (ORR) and time to treatment failure (TTF). Results Of 968 patients registered at 325 institutions, 951 and 671 were included in the safety and effectiveness analyses, respectively. In the safety population, ADRs were observed in 841 patients (88.4%). The most common (≥15% incidence) were neutropenia (66.6%), leukopenia (62.4%), lymphopenia (18.4%), and peripheral neuropathy (16.8%). The most common grade ≥ 3 ADRs (>5% incidence) were neutropenia (59.8%), leukopenia (50.5%), lymphopenia (16.1%), and febrile neutropenia (7.7%). In the effectiveness population, ORR was 16.5% (95% confidence interval: 13.7, 19.4). The median TTF was 127 days (95% confidence interval: 120, 134). Conclusions The safety and effectiveness profile of eribulin was consistent with prior studies. Eribulin had a favorable risk-benefit balance when used in real-world clinical settings.

Clinical trial will investigate targeted radionuclide therapy for inoperable rare tumors | Center for Cancer Research

Cancer.gov

In an upcoming phase II clinical trial, Center for Cancer Research investigators will explore the ability of a targeted radioactive drug to treat inoperable pheochromocytoma and paraganglioma, both rare tumors.  Learn more...

New Principles In Operating Gastro-Intestinal Tract With CO2 Laser

NASA Astrophysics Data System (ADS)

Skobelkin, O. K.; Litwin, G. D.; Smoljaninov, M. V.; Brehov, E. I.; Rjabov, V. I.; Kirpitchev, A. G.

1988-06-01

Laser devicea are becoming morn popular in surgery. They are mainly used for controling hemorrages through an endoscope, for radicalevaporating benign and small malignant tumors in esophagus, stomach, colon, and for palliative destruction of inoperable tumors to recanalize the lumen. According, to literature operations on abdominal parenchymal organs with laser are rather seldom. And the operations with laser on hollow organs of digestive tract are being mainly performed in the USSR, and they being rather effective.

Percutaneous thermal ablation for stage IA non-small cell lung cancer: long-term follow-up.

PubMed

Narsule, Chaitan K; Sridhar, Praveen; Nair, Divya; Gupta, Avneesh; Oommen, Roy G; Ebright, Michael I; Litle, Virginia R; Fernando, Hiran C

2017-10-01

Surgical resection is the most effective curative therapy for non-small cell lung cancer (NSCLC). However, many patients are unable to tolerate resection secondary to poor reserve or comorbid disease. Radiofrequency ablation (RFA) and microwave ablation (MWA) are methods of percutaneous thermal ablation that can be used to treat medically inoperable patients with NSCLC. We present long-term outcomes following thermal ablation of stage IA NSCLC from a single center. Patients with stage IA NSCLC and factors precluding resection who underwent RFA or MWA from July 2005 to September 2009 were studied. CT and PET-CT scans were performed at 3 and 6 month intervals, respectively, for first 24 months of follow-up. Factors associated with local progression (LP) and overall survival (OS) were analyzed. Twenty-one patients underwent 21 RFA and 4 MWA for a total of 25 ablations. Fifteen patients had T1a and six patients had T1b tumors. Mean follow-up was 42 months, median survival was 39 months, and OS at three years was 52%. There was no significant difference in median survival between T1a nodules and T1b nodules (36 vs . 39 months, P=0.29) or for RFA and MWA (36 vs . 50 months, P=0.80). Ten patients had LP (47.6%), at a median time of 35 months. There was no significant difference in LP between T1a and T1b tumors (22 vs . 35 months, P=0.94) or RFA and MWA (35 vs . 17 months, P=0.18). Median OS with LP was 32 months compared to 39 months without LP (P=0.68). Three patients underwent repeat ablations. Mean time to LP following repeat ablation was 14.75 months. One patient had two repeat ablations and was disease free at 40-month follow-up. Thermal ablation effectively treated or controlled stage IA NSCLC in medically inoperable patients. Three-year OS exceeded 50%, and LP did not affect OS. Therefore, thermal ablation is a viable option for medically inoperable patients with early stage NSCLC.

SU-E-T-625: Potential for Reduced Radiation Induced Toxicity for the Treatment of Inoperable Non-Small-Cell Lung Cancer Using RapidArc Planning

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pokhrel, D; Sood, S; Badkul, R

2015-06-15

Purpose: To investigate the feasibility of using RapidArc (RA) treatment planning to reduce irradiation volume of normal lung and other organs at risk (OARs) in the treatment of inoperable non-small-cell lung cancer (NSCLC) patients. Methods: A retrospective treatment planning and delivery study was performed to compare target coverage and the volumes of the normal lung, spinal cord, heart and esophagus on 4D-CT scan above their dose tolerances delivered by RA vs. IMRT for ten inoperable NSCLC patients (Stage I-IIIB). RA plans consisted of either one-full or two-partial co-planar arcs used to treat 95% of the planning target volume (PTV) withmore » 6MV beam to a prescription of 66Gy in 33 fractions. IMRT plans were generated using 5–7 co-planar fields with 6MV beam. PTV coverage, dose-volume histograms, homogeneity/conformity indices (CI), total number of monitor units(MUs), beam-on time and delivery accuracy were compared between the two treatment plans. Results: Similar target coverage was obtained between the two techniques. RA (CI=1.02) provided more conformal plans without loss of homogeneity compared to IMRT plans (CI=1.12). Compared to IMRT, RA achieved a significant median dose reduction in V10 (3%), V20 (8%), and mean lung dose (3%) on average, respectively. On average, V5 was comparable between the two treatment plans. RA reduced mean esophagus (6%), mean heart (18%), and maximum spinal cord dose (7%), on average, respectively. Total number of MUs and beam-on time were each reduced almost by a factor of 2 when compared to IMRT-patient comfort, reduced intra-fraction-motion and leakage dose. The average IMRT and RA QA pass rate was about 98% for both types of plans for 3%/3mm criterion. Conclusion: Compared to IMRT plans, RA provided not only comparable target coverage, but also improved conformity, treatment time, and significant reduction in irradiation of OARs. This may potentially allow for target dose escalation without increase in normal tissue toxicity.« less

Incidental Prophylactic Nodal Irradiation and Patterns of Nodal Relapse in Inoperable Early Stage NSCLC Patients Treated With SBRT: A Case-Matched Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lao, Louis; Department of Radiation Oncology, Auckland City Hospital, Auckland; Hope, Andrew J.

2014-09-01

Purpose: Reported rates of non-small cell lung cancer (NSCLC) nodal failure following stereotactic body radiation therapy (SBRT) are lower than those reported in the surgical series when matched for stage. We hypothesized that this effect was due to incidental prophylactic nodal irradiation. Methods and Materials: A prospectively collected group of medically inoperable early stage NSCLC patients from 2004 to 2010 was used to identify cases with nodal relapses. Controls were matched to cases, 2:1, controlling for tumor volume (ie, same or greater) and tumor location (ie, same lobe). Reference (normalized to equivalent dose for 2-Gy fractions [EQD2]) point doses atmore » the ipsilateral hilum and carina, demographic data, and clinical outcomes were extracted from the medical records. Univariate conditional logistical regression analyses were performed with variables of interest. Results: Cases and controls were well matched except for size. The controls, as expected, had larger gross tumor volumes (P=.02). The mean ipsilateral hilar doses were 9.6 Gy and 22.4 Gy for cases and controls, respectively (P=.014). The mean carinal doses were 7.0 Gy and 9.2 Gy, respectively (P=.13). Mediastinal nodal relapses, with and without ipsilateral hilar relapse, were associated with mean ipsilateral hilar doses of 3.6 Gy and 19.8 Gy, respectively (P=.01). The conditional density plot appears to demonstrate an inverse dose-effect relationship between ipsilateral hilar normalized total dose and risk of ipsilateral hilar relapse. Conclusions: Incidental hilar dose greater than 20 Gy is significantly associated with fewer ipsilateral hilar relapses in inoperable early stage NSCLC patients treated with SBRT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Joe Y., E-mail: jychang@mdanderson.org; Komaki, Ritsuko; Wen, Hong Y.

Purpose: To analyze the toxicity and patterns of failure of proton therapy given in ablative doses for medically inoperable early-stage non-small cell lung cancer (NSCLC). Methods and Materials: Eighteen patients with medically inoperable T1N0M0 (central location) or T2-3N0M0 (any location) NSCLC were treated with proton therapy at 87.5 Gy (relative biological effectiveness) at 2.5 Gy /fraction in this Phase I/II study. All patients underwent treatment simulation with four-dimensional CT; internal gross tumor volumes were delineated on maximal intensity projection images and modified by visual verification of the target volume in 10 breathing phases. The internal gross tumor volumes with maximalmore » intensity projection density was used to design compensators and apertures to account for tumor motion. Therapy consisted of passively scattered protons. All patients underwent repeat four-dimensional CT simulations during treatment to assess the need for adaptive replanning. Results: At a median follow-up time of 16.3 months (range, 4.8-36.3 months), no patient had experienced Grade 4 or 5 toxicity. The most common adverse effect was dermatitis (Grade 2, 67%; Grade 3, 17%), followed by Grade 2 fatigue (44%), Grade 2 pneumonitis (11%), Grade 2 esophagitis (6%), and Grade 2 chest wall pain (6%). Rates of local control were 88.9%, regional lymph node failure 11.1%, and distant metastasis 27.8%. Twelve patients (67%) were still alive at the last follow-up; five had died of metastatic disease and one of preexisting cardiac disease. Conclusions: Proton therapy to ablative doses is well tolerated and produces promising local control rates for medically inoperable early-stage NSCLC.« less

Clinical outcome of fiducial-less CyberKnife radiosurgery for stage I non-small cell lung cancer

PubMed Central

Jung, In-Hye; Jung, Jinhong; Cho, Byungchul; Kwak, Jungwon; Je, Hyoung Uk; Choi, Wonsik; Jung, Nuri Hyun; Kim, Su Ssan; Choi, Eun Kyung

2015-01-01

Purpose To evaluate the treatment results in early stage non-small cell lung cancer patients who have undergone fiducial-less CyberKnife radiosurgery (CKRS). Materials and Methods From June 2011 to November 2013, 58 patients underwent CKRS at Asan Medical Center for stage I lung cancer. After excluding 14 patients, we retrospectively reviewed the records of the remaining 44 patients. All analyses were performed using SPSS ver. 21. Results The median age at diagnosis was 75 years. Most patients had inoperable primary lung cancer with a poor pulmonary function test with comorbidity or old age. The clinical stage was IA in 30 patients (68.2%), IB in 14 (31.8%). The mean tumor size was 2.6 cm (range, 1.2 to 4.8 cm), and the tumor was smaller than 2 cm in 12 patients (27.3%). The radiation dose given was 48-60 Gy in 3-4 fractions. In a median follow-up of 23.1 months, local recurrence occurred in three patients (2-year local recurrence-free survival rate, 90.4%) and distant metastasis occurred in 13 patients. All patients tolerated the radiosurgery well, only two patients developing grade 3 dyspnea. The most common complications were radiation-induced fibrosis and pneumonitis. Eight patients died due to cancer progression. Conclusion The results showed that fiducial-less CKRS shows comparable local tumor control and survival rates to those of LINAC-based SABR or CKRS with a fiducial marker. Thus, fiducial-less CKRS using Xsight lung tracking system can be effectively and safely performed for patients with medically inoperable stage I non-small cell lung cancer without any risk of procedure-related complication. PMID:26157678

Treatment of early non-small cell lung cancer, stage IA, by image-guided robotic stereotactic radioablation--CyberKnife.

PubMed

Brown, William T; Wu, Xiaodong; Amendola, Beatriz; Perman, Mark; Han, Hoke; Fayad, Fahed; Garcia, Silvio; Lewin, Alan; Abitbol, Andre; de la Zerda, Alberto; Schwade, James G

2007-01-01

To evaluate the efficacy of using image-guided robotic stereotactic radioablation as an alternative treatment modality for patients with surgically resectable, but medically inoperable, T1 N0 M0, stage IA non-small cell lung cancer. Between January 2004 and May 2006, 19 patients, 11 women and 8 men ranging in age from 52 to 88 years, with stage IA non-small cell lung cancer were treated. Tumor volume ranged from 1.7 to 13 mL. Total doses ranged from 24 to 60 Gy delivered in 3 fractions. Eleven patients received 60 Gy. Real-time target localization was accomplished by radiographic detection of fiducial marker(s) implanted within the tumor combined with respiratory motion tracking. All patients tolerated radioablation well with fatigue as the main side effect. Fourteen patients are alive from 1 to 25 months posttreatment. Four patients died: 2 of comorbid disease and 2 of cancer progression (status post 60 and 55.5 Gy). Three patients developed grade I radiation pneumonitis. Two patients have stable disease. In 3 patients, cancer recurred in the planning treatment volume: in 2 patients after treatment with 60 Gy and in 1 patient after treatment with 55.5 Gy. One patient had local control in the target volume but developed metastasis to the ipsilateral hilum. Nine patients had a complete response and show no evidence of disease. In our early experience, stereotactic radioablation using the CyberKnife system appears to be a safe, minimally invasive, and effective modality for treating early stage lung cancer in patients with medically inoperable disease. Dose escalation and/or increasing the treatment volumes, with the aid of the high conformality of this technique, may help to achieve further improvements in these promising results.

77 FR 60146 - Biweekly Notice: Applications and Amendments to Facility Operating Licenses and Combined Licenses...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-02

... support unlisted software, and the NRC Meta System Help Desk will not be able to offer assistance in using... supported Technical Specification (TS) systems inoperable when the associated snubber(s) cannot perform its... allowed before declaring a TS supported system inoperable and taking its Conditions and Required Actions...

Electrochemical treatment of lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xin, Y.L.; Xue, F.Z.; Ge, B.S.

1997-03-01

A pilot study of electrochemical treatment (ECT) as a therapy for 386 patients with nonsmall cell lung cancer was undertaken. There were 103 stage 2 cases, 89 stage 3a cases, 122 stage 3b cases, and 72 stage 4 cases. Two ECT methods were used. For peripherally located lung cancer, platinum electrodes were inserted transcutaneously into the tumor under x-ray or CT guidance. For central type lung cancer or for those inoperable during thoracotomy, electrodes were inserted intraoperatively directly into the cancer. Voltage was 6--8 V, current was 40--100 mA, and electric charge was 100 coulombs per cm of tumor diameter.more » The number of electrodes was determined from the size of cancer mass, because the diameter of effective area around each electrode is approximately 3 cm. The short-term (6 months after ECT) results of the 386 lung cancer cases were: complete response (CR), 25.6% (99/386); partial response (PR), 46.4% (179/386); no change (NC), 15.3% (59/386); and progressive disease (PD), 12.7% (49/386). The total effective rate (CR + PR) was 72% (278/386). The 1, 3, and 5 year overall survival rates were 86.3% (333/386), 58.8% (227/386), and 29.5% (114/386), respectively. The main complication was traumatic pneumothorax, with an incidence rate of 14.8% (57/386). These clinical results show that ECT is simple, safe, effective, and minimally traumatic. ECT provides an alternative method for treating lung cancers that are conventionally inoperable, that are not responsive to chemotherapy or radiotherapy, or that cannot be resected after thoracotomy. Long-term survival rates suggest that ECT warrants further investigation.« less

Internal stenting in malignant biliary obstruction.

PubMed

Cowling, M G; Adam, A N

2001-03-01

Internal stenting in inoperable malignant biliary obstruction plays an important role in patient management. Surgical bypass may still be undertaken where there is also duodenal obstruction, though the need for gastroenterostomy may be reduced with the increasing use of metallic stents for the relief of malignant gastric outlet obstruction. Stents may be placed endoscopically or percutaneously, though in most centers the endoscopic route is usually tried first, with the percutaneous route being reserved for endoscopic failures. Plastic and self-expanding metallic biliary stents are available, each with its own advantages and disadvantages. In general, longer periods of patency are observed with metallic stents, though they are more expensive. Plastic stents can be changed endoscopically relatively easily when they have blocked, and in practice it is common for plastic stents to be inserted via this route for initial biliary drainage. If there is prolonged survival thereafter, many workers insert a metallic stent in an attempt to reduce the number of interventions required. If the percutaneous route is being employed, the histologic diagnosis has been confirmed, and the malignancy is inoperable, our practice is to use a self-expanding metallic stent, as the delivery system is relatively small and subsequent occlusion less likely.

Apparatus for rendering at least a portion of a device inoperable and related methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daniels, Michael A.; Steffler, Eric D.; Hartenstein, Steven D.

2016-11-08

Apparatus for rendering at least a portion of a device inoperable may include a containment structure having a first compartment that is configured to receive a device therein and a movable member configured to receive a cartridge having reactant material therein. The movable member is configured to be inserted into the first compartment of the containment structure and to ignite the reactant material within the cartridge. Methods of rendering at least a portion of a device inoperable may include disposing the device into the first compartment of the containment structure, inserting the movable member into the first compartment of themore » containment structure, igniting the reactant material in the cartridge, and expelling molten metal onto the device.« less

A Phase I Trial of an Immune Checkpoint Inhibitor Plus Stereotactic Ablative Radiotherapy in Patients with Inoperable Stage I Non-Small Cell Lung Cancer

DTIC Science & Technology

2016-10-01

contained in this report are those of the author(s) and should not be construed as an official Department of the Army position, policy or decision ...14. ABSTRACT This clinical trial is the first to evaluate the synergy between radiation, a well-known immune modulator, with the novel immune...proposed clinical /translational trial seeks to provide the first human evidence for combining SAR with an immune checkpoint inhibitor, with the goal of

Locking mechanism for orthopedic braces

NASA Technical Reports Server (NTRS)

Chao, J. I.; Epps, C. H., Jr.

1981-01-01

An orthopedic brace locking mechanism is described which under standing or walking conditions cannot be unlocked, however under sitting conditions the mechanism can be simply unlocked so as to permit bending of the patient's knee. Other features of the device include: (1) the mechanism is rendered operable, and inoperable, dependent upon the relative inclination of the brace with respect to the ground; (2) the mechanism is automatically locked under standing or walking conditions and is manually unlocked under sitting conditions; and (3) the mechanism is light in weight and is relatively small in size.

Continuous subcutaneous infusion of hyoscine butylbromide reduces secretions in patients with gastrointestinal obstruction.

PubMed

De Conno, F; Caraceni, A; Zecca, E; Spoldi, E; Ventafridda, V

1991-11-01

We describe the use of hyoscine butylbromide as a subcutaneous infusion in 3 patients with inoperable malignant bowel obstruction. An objective reduction of drainage from the gastrointestinal tract was observed with the hyoscine butylbromide infusion (60-120 mg/day). We suggest that this effect can be useful in the palliative treatment of vomiting in inoperable bowel obstruction.

Genetics Home Reference: small fiber neuropathy

MedlinePlus

... Small fiber neuropathy is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which ... Page National Institute of Neurological Disorders and Stroke: Peripheral Neuropathy Information Page Educational Resources (4 links) Johns Hopkins ...

Randomised phase III trial of concurrent chemoradiotherapy with extended nodal irradiation and erlotinib in patients with inoperable oesophageal squamous cell cancer.

PubMed

Wu, Shi-Xiu; Wang, Lv-Hua; Luo, Hong-Lei; Xie, Cong-Ying; Zhang, Xue-Bang; Hu, Wei; Zheng, An-Ping; Li, Duo-Jie; Zhang, Hong-Yan; Xie, Cong-Hua; Lian, Xi-Long; Du, De-Xi; Chen, Ming; Bian, Xiu-Hua; Tan, Bang-Xian; Jiang, Hao; Zhang, Hong-Bo; Wang, Jian-Hua; Jing, Zhao; Xia, Bing; Zhang, Ni; Zhang, Ping; Li, Wen-Feng; Zhao, Fu-Jun; Tian, Zhi-Feng; Liu, Hui; Huang, Ke-Wei; Hu, Jin; Xie, Rui-Fei; Du, Lin; Li, Gang

2018-04-01

This randomised phase III study was conducted to investigate the efficacy of extended nodal irradiation (ENI) and/or erlotinib in inoperable oesophageal squamous cell cancer (ESCC). Patients with histologically confirmed locally advanced ESCC or medically inoperable disease were randomly assigned (ratio 1:1:1:1) to one of four treatment groups: group A, radiotherapy adoption of ENI with two cycles of concurrent TP chemotherapy (paclitaxel 135 mg/m 2  day 1 and cisplatin 20 mg/m 2 days 1-3, every 4 weeks) plus erlotinib (150 mg per day during chemoradiotherapy); group B, radiotherapy adoption of ENI with two cycles of concurrent TP; group C, radiotherapy adoption of conventional field irradiation (CFI) with two cycles of concurrent TP plus erlotinib; group D, radiotherapy adoption of CFI with two cycles of concurrent TP. A total of 352 patients (88 assigned to each treatment group) were enrolled. The 2-year overall survival rates of group A, B, C and D were 57.8%, 49.9%, 44.9% and 38.7%, respectively (P = 0.015). Group A significantly improved 2-year overall survival compared with group D. The ENI significantly improved overall survival in patients with inoperable ESCC (P = 0.014). The addition of erlotinib significantly decreased loco-regional recurrence (P = 0.042). Aside from rash and radiation oesophagitis, the incidence of grade 3 or greater toxicities did not differ among 4 groups. Chemoradiotherapy with ENI and erlotinib might represent a substantial improvement on the standard of care for inoperable ESCC. ENI alone should be adopted in concurrent chemoradiotherapy for ESCC patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cardiopulmonary exercise testing to evaluate the exercise capacity of patients with inoperable chronic thromboembolic pulmonary hypertension: an endothelin receptor antagonist improves the peak PETCO2.

PubMed

Hirashiki, Akihiro; Adachi, Shiro; Nakano, Yoshihisa; Kono, Yuji; Shimazu, Shuzo; Shimizu, Shinya; Morimoto, Ryota; Okumura, Takahiro; Takeshita, Kyosuke; Yamada, Sumio; Murohara, Toyoaki; Kondo, Takahisa

2014-11-24

The 6-min walking distance is often used for assessing the exercise capacity under the treatment with an endothelin receptor antagonist (ERA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH). The cardiopulmonary exercise testing (CPX) was reported to be more useful for the patients with pulmonary arterial hypertension (PAH), however, few reports exist in patients with inoperable CTEPH. The aim of this study was to investigate the effects of an oral dual ERA, bosentan, on exercise capacity using CPX in patients with PAH and inoperable CTEPH. This study included all patients diagnosed with 17 PAH and 12 CTEPH in the World Health Organization functional classes II-IV who started treatment with bosentan therapy. They underwent CPX, which was performed before bosentan therapy and at 3 to 6 months of the treatment. In PAH patients, peak VO2 significantly increased after the bosentan treatment (p=0.009). On the other hand, in CTEPH patients, there were no significant differences in the peak VO2. However, the peak PETCO2 was significantly increased from 23.9±5.2 mm Hg at baseline to 29.3±10.7 mm Hg after the bosentan treatment (p=0.040). In addition, peak heart rate during exercise tended to decrease after the bosentan therapy (p=0.089). Bosentan therapy improved peak PETCO2 but not peak VO2 in patients with inoperable CTEPH. These findings demonstrated that CPX is useful for assessing the exercise capacity of patients with PAH and inoperable CTEPH under the treatment with an ERA. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Operability assessment in CTEPH: Lessons from the CHEST-1 study.

PubMed

Jenkins, David P; Biederman, Andrzej; D'Armini, Andrea M; Dartevelle, Philippe G; Gan, Hui-Li; Klepetko, Walter; Lindner, Jaroslav; Mayer, Eckhard; Madani, Michael M

2016-09-01

Pulmonary endarterectomy is the gold standard treatment for chronic thromboembolic pulmonary hypertension and is potentially curative, although some patients are unsuitable for pulmonary endarterectomy and require alternative management. Lack of standardized assessment of pulmonary endarterectomy eligibility risks suboptimal treatment in some patients. We discuss the implications for future clinical trials and practice of a unique operability assessment in patients who have chronic thromboembolic pulmonary hypertension and were initially screened for inclusion in the CHEST-1 (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase Stimulator Trial-1) study. The CHEST-1 study evaluated riociguat for the treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy. Screened patients who were initially considered "inoperable" underwent central independent adjudication by a committee of experienced surgeons, or local adjudication in collaboration with an experienced surgeon. Operability decisions were based on accessibility of thrombi and the association between pulmonary vascular resistance (PVR) and the extent of obstruction, using pulmonary angiography/computed tomography with ventilation/perfusion scintigraphy as the minimum diagnostic tests. Of 446 patients screened for CHEST-1, a total of 188 and 124 underwent central and local adjudication, respectively, after being initially considered to be "inoperable." After a second assessment by an experienced surgeon, 69 of these 312 "inoperable" patients were deemed operable. Rigorous measures in CHEST-1 guaranteed that only technically inoperable patients, or patients who had persistent/recurrent pulmonary hypertension, were enrolled, thus ensuring that only patients for whom surgery was not an option were enrolled. This study design sets new standards for future clinical trials and practice in CTEPH, helping to ensure that patients who have CTEPH receive optimal treatment. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

30 Gy or 34 Gy? Comparing 2 Single-Fraction SBRT Dose Schedules for Stage I Medically Inoperable Non-Small Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Videtic, Gregory M.M., E-mail: videtig@ccf.org; Stephans, Kevin L.; Woody, Neil M.

2014-09-01

Purpose: To review outcomes of 2 single-fraction lung stereotactic body radiation therapy (SBRT) schedules used for medically inoperable early stage lung cancer. Methods and Materials: Patients in our institution have been treated on and off protocols using single-fraction SBRT (30 Gy and 34 Gy, respectively). All patients had node-negative lung cancer measuring ≤5 cm and lying ≥2 cm beyond the trachea-bronchial tree and were treated on a Novalis/BrainLAB system with the ExactTrac positioning system for daily image guidance. Results: For the interval from 2009 to 2012, 80 patients with 82 lesions were treated with single-fraction lung SBRT. Fifty-five patients (69%) and 25 patients (31%) received 30 Gymore » and 34 Gy, respectively. In a comparison of 30 Gy and 34 Gy cohorts, patient and tumor characteristics were balanced and median follow-up in months was 18.7 and 17.8, respectively. The average heterogeneity-corrected mean doses to the target were 33.75 Gy and 37.94 Gy for the 30-Gy and 34-Gy prescriptions, respectively. Comparing 30-Gy and 34-Gy cohorts, 92.7% and 84.0% of patients, respectively, experienced no toxicity (P was not significant), and had neither grade 3 nor higher toxicities. For the 30-Gy and 34-Gy patients, rates of 1-year local failure, overall survival, and lung cancer-specific mortality were 2.0% versus 13.8%, 75.0% versus 64.0%, and 2. 1% versus 16.0%, respectively (P values for differences were not significant). Conclusions: This is the largest single-fraction lung SBRT series yet reported. and it confirms the safety, efficacy, and minimal toxicity of this schedule for inoperable early stage lung cancer.« less

[Comparison of treatments in patients with inoperable stage IV advanced esophageal cancer].

PubMed

Lee, Gyu Jin; Park, Moo In; Gwoo, Sangeon; Jung, Hyun Joo; Kim, Joo Hoon; Park, Seun Ja; Moon, Won; Kim, Hyung Hun; Kim, Yang Soo; Park, Sung Dal; Jeong, Tae Sig

2012-04-01

The aim of this study was to compare palliative treatments such as chemotherapy, chemoradiotherapy or radiotherapy with best supportive care in patients with inoperable advanced esophageal cancer. A total of 67 patients with inoperable advanced esophageal cancer visiting Kosin University Gospel Hospital between January 2000 and July 2010 were included in a retrospective analysis. Patients were categorized as having palliative treatment or best supportive care to compare their prognosis. The median survival was 6.4 months in 67 patients. There was significant difference in median survival between the palliative and best supportive treatment (9.8 months vs. 4.5 months, p=0.01). The patients who underwent palliative treatment had superior 1-year and 3-year overall survival rate than those with best supportive treatment (27%, 10% vs. 5%, 5%, respectively). The 1-year and 3-year overall survival rate of palliative treatment was 18% (1-year overall survival rate) in chemotherapy, 33% (1-year overall survival rate) in radiotherapy, 45% and 9% in concurrent chemoradiotherapy, and 20% and 20% in sequential chemoradiotherapy, respectively. These results may suggest that palliative treatments are more effective than best supportive care. Further prospective studies are still needed to elucidate beneficial effect of palliative treatments on inoperable advanced esophageal cancer.

Sources of emergency water supplies in Santa Clara County, California

USGS Publications Warehouse

Akers, J.P.

1977-01-01

Water distribution systems in Santa Clara County, Calif., may be damaged and rendered inoperable by a large earthquake or other disaster. In such an event, individual agencies may have to implement emergency measures to supply water for drinking, firefighting, decontamination, or other purposes. In Santa Clara County, 128 wells have been identified as potential water-supply sources in emergencies. The criteria used to select the wells are: yield of at least 3 liters per second (50 gallons per minute), good water quality, ready accessibility, and available emergency power. Purification methods of small water supplies are described. (Woodard-USGS)

Palliative percutaneous transhepatic drainage for inoperable obstructive jaundice.

PubMed Central

Baxter-Smith, D. C.; Temple, J. G.; Howarth, F.

1982-01-01

A technique of percutaneous transhepatic drainage under local anaesthesia is described for the relief of intractable pruritus in patients with obstructive jaundice due to inoperable carcinoma. After standard percutaneous transhepatic cholangiography a polyethylene catheter is introduced into one of the large dilated bile ducts and left in situ, thereby establishing external retrograde biliary drainage. The technique has been used successfully in 6 cases with reduction in serum bilirubin levels and relief of pruritus. PMID:6182832

Baseline Cardiopulmonary Function as an Independent Prognostic Factor for Survival of Inoperable Non-Small-Cell Lung Cancer After Concurrent Chemoradiotherapy: A Single-Center Analysis of 161 Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Semrau, Sabine, E-mail: sabine.semrau@uk-erlangen.d; Department of Radiation Therapy, University of Rostock, Suedring, Rostock; Klautke, Gunther

2011-01-01

Purpose: Little is known about the effects of cardiopulmonary function on the prognosis of concurrent chemoradiotherapy in patients with inoperable non-small-cell lung cancer (NSCLC). Methods and Materials: A retrospective analysis of the effects of tumor- and patient-related factors and parameters of cardiopulmonary function and heart morphology on the feasibility, toxicity, and prognosis was performed. Results: Cardiopulmonary function had no effect on the toxicity or feasibility of treatment; effects on survival were observed in the univariate analysis. Median survival varied as follows: cardiac function: 13.0 {+-} 1.6 months for left ventricular ejection fraction (LVEF) > 50% vs. 10.0 {+-} 1.9 monthsmore » for LVEF {<=} 50% (p = 0.003); pulmonary function: 16.0 {+-} 0.6 months for no lung function deficits (vital capacity [VC]{>=} 60%, forced expiratory volume in 1 s {>=} 80%, and diffusing capacity of the lung for carbon monoxide (DLCO) {>=}60%) vs. 14.0 {+-} 1.5 months for one or two function deficits vs. 8.0 {+-} 1.5 months for three lung function deficits (p = 0.001); T stage: 19.0 {+-} 3.1 months for rcT0/cT1/cT2 vs. 12.0 {+-} 0.8 months for cT3/cT4 (p = 0.039); and age: 11.0 {+-} 1.5 months for <60 years vs. 18.0 {+-} 2.5 months for 60-69 years vs. 12.0 {+-} 1.2 months for {>=}70 years (p = 0.008). Prognostic factors identified in the multivariate analysis were LVEF {<=}50% (p = 0.043; hazard ratio [HR], 1.74), reduced pulmonary function (p = 0.001; HR, 1.71 or 5.05) and T stage (p = 0.026; HR: 1.71). Conclusions: In addition to T-stage, cardiac and pulmonary function variables affected the survival of non-small-cell lung cancer patients after chemoradiotherapy.« less

Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours

PubMed Central

Nakratzas, G.; Wagenaar, J. P. M.; Reintjes, M.; Scheffer, E.; Swierenga, J.

1974-01-01

Nakratzas, G., Wagenaar, J. P. M., Reintjes, M., Scheffer, E., and Swierenga, J. (1974).Thorax, 29, 125-131. Repeated partial endoscopic resections as treatment for two patients with inoperable tracheal tumours. Two cases of tracheal tumour are described, one a carcinoid and the other an adenoid cystic carcinoma (cylindroma). Both patients were treated by repeated partial bronchoscopic resections. The patients are in good health nine and three years respectively after treatment. Images PMID:4363463

Modeling uncertainties in workforce disruptions from influenza pandemics using dynamic input-output analysis.

PubMed

El Haimar, Amine; Santos, Joost R

2014-03-01

Influenza pandemic is a serious disaster that can pose significant disruptions to the workforce and associated economic sectors. This article examines the impact of influenza pandemic on workforce availability within an interdependent set of economic sectors. We introduce a simulation model based on the dynamic input-output model to capture the propagation of pandemic consequences through the National Capital Region (NCR). The analysis conducted in this article is based on the 2009 H1N1 pandemic data. Two metrics were used to assess the impacts of the influenza pandemic on the economic sectors: (i) inoperability, which measures the percentage gap between the as-planned output and the actual output of a sector, and (ii) economic loss, which quantifies the associated monetary value of the degraded output. The inoperability and economic loss metrics generate two different rankings of the critical economic sectors. Results show that most of the critical sectors in terms of inoperability are sectors that are related to hospitals and health-care providers. On the other hand, most of the sectors that are critically ranked in terms of economic loss are sectors with significant total production outputs in the NCR such as federal government agencies. Therefore, policy recommendations relating to potential mitigation and recovery strategies should take into account the balance between the inoperability and economic loss metrics. © 2013 Society for Risk Analysis.

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer.

PubMed

Kasahara, Kazuo; Kimura, Hideharu; Shibata, Kazuhiko; Araya, Tomoyuki; Sone, Takashi; Oribe, Yoshitaka; Furusho, Shiho; Kita, Toshiyuki; Shirasaki, Hiroki; Oribe, Yoshitaka; Yoshimi, Yuzo; Ueda, Akihito; Tachibana, Hideki; Shintani, Hiromoto; Mizuguchi, Masayuki; Nishi, Kohichi; Fujimura, Masaki; Nakao, Shinji

2006-01-01

The aim of this phase II study was to evaluate the efficacy of combination chemotherapy consisting of docetaxel and carboplatin in patients with inoperable non-small cell lung cancer (NSCLC). For this multicenter phase II study, the eligibility criteria included histologically or cytologically proven inoperable NSCLC, measurable lesions, Eastern Cooperative Oncology Group performance status (PS) 0-2, adequate organ and bone marrow functions, and written informed consent. Patients received 60 mg/m2 of docetaxel and carboplatin (target AUC 5.5) on day 1 every 3 weeks until disease progression. The primary end-point of this study was response rate and the secondary end-points were toxicities, time to progression and overall survival. A total of 40 patients were enrolled and 39 patients were eligible. A complete response and partial response were observed in 1 and 13 patients, respectively. An objective response rate was 35.9% (95% confidential interval [CI] 20.8-51.0%). The median time to progression was 5.2 months and the median overall survival was 12.0 months. The 1- and 2-year survival rates were 53.8% and 25.1%, respectively. The major toxicities were leukocytopenia and neutropenia. Grade 3 or 4 thrombocytopenia was rare and non-hematological toxicities were generally mild. Grade 3 non-hematological toxicities were observed in 6 patients (2 with nausea and vomiting, 1 with diarrhea, 1 with elevated transaminase levels, 1 with allergic reaction and 1 with edema). No grade 4 non-hematological toxicities were observed. Docetaxel and carboplatin combination chemotherapy was well tolerated and active in Japanese patients with advanced or metastatic NSCLC.

Comparison of the Effectiveness of Radiofrequency Ablation With Stereotactic Body Radiation Therapy in Inoperable Stage I Non-Small Cell Lung Cancer: A Systemic Review and Pooled Analysis.

PubMed

Bi, Nan; Shedden, Kerby; Zheng, Xiangpeng; Kong, Feng-Ming Spring

2016-08-01

To performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95% confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparison of the Effectiveness of Radiofrequency Ablation With Stereotactic Body Radiation Therapy in Inoperable Stage I Non-Small Cell Lung Cancer: A Systemic Review and Pooled Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bi, Nan; Department of Radiation Oncology, Cancer Hospital and Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing; Shedden, Kerby

Purpose: To performed a systematic review and pooled analysis to compare clinical outcomes of stereotactic body radiation therapy (SBRT) and radiofrequency ablation (RFA) for the treatment of medically inoperable stage I non-small cell lung cancer. Methods and Materials: A comprehensive literature search for published trials from 2001 to 2012 was undertaken. Pooled analyses were performed to obtain overall survival (OS) and local tumor control rates (LCRs) and adverse events. Regression analysis was conducted considering each study's proportions of stage IA and age. Results: Thirty-one studies on SBRT (2767 patients) and 13 studies on RFA (328 patients) were eligible. The LCR (95%more » confidence interval) at 1, 2, 3, and 5 years for RFA was 77% (70%-85%), 48% (37%-58%), 55% (47%-62%), and 42% (30%-54%) respectively, which was significantly lower than that for SBRT: 97% (96%-98%), 92% (91%-94%), 88% (86%-90%), and 86% (85%-88%) (P<.001). These differences remained significant after correcting for stage IA and age (P<.001 at 1 year, 2 years, and 3 years; P=.04 at 5 years). The effect of RFA was not different from that of SBRT on OS (P>.05). The most frequent complication of RFA was pneumothorax, occurring in 31% of patients, whereas that for SBRT (grade ≥3) was radiation pneumonitis, occurring in 2% of patients. Conclusions: Compared with RFA, SBRT seems to have a higher LCR but similar OS. More studies with larger sample sizes are warranted to validate such findings.« less

Advances in radiotherapy techniques and delivery for non-small cell lung cancer: benefits of intensity-modulated radiation therapy, proton therapy, and stereotactic body radiation therapy

PubMed Central

Diwanji, Tejan P.; Mohindra, Pranshu; Vyfhuis, Melissa; Snider, James W.; Kalavagunta, Chaitanya; Mossahebi, Sina; Yu, Jen; Feigenberg, Steven

2017-01-01

The 21st century has seen several paradigm shifts in the treatment of non-small cell lung cancer (NSCLC) in early-stage inoperable disease, definitive locally advanced disease, and the postoperative setting. A key driver in improvement of local disease control has been the significant evolution of radiation therapy techniques in the last three decades, allowing for delivery of definitive radiation doses while limiting exposure of normal tissues. For patients with locally-advanced NSCLC, the advent of volumetric imaging techniques has allowed a shift from 2-dimensional approaches to 3-dimensional conformal radiation therapy (3DCRT). The next generation of 3DCRT, intensity-modulated radiation therapy and volumetric-modulated arc therapy (VMAT), have enabled even more conformal radiation delivery. Clinical evidence has shown that this can improve the quality of life for patients undergoing definitive management of lung cancer. In the early-stage setting, conventional fractionation led to poor outcomes. Evaluation of altered dose fractionation with the previously noted technology advances led to advent of stereotactic body radiation therapy (SBRT). This technique has dramatically improved local control and expanded treatment options for inoperable, early-stage patients. The recent development of proton therapy has opened new avenues for improving conformity and the therapeutic ratio. Evolution of newer proton therapy techniques, such as pencil-beam scanning (PBS), could improve tolerability and possibly allow reexamination of dose escalation. These new progresses, along with significant advances in systemic therapies, have improved survival for lung cancer patients across the spectrum of non-metastatic disease. They have also brought to light new challenges and avenues for further research and improvement. PMID:28529896

Does immunohistochemistry affect response to therapy and survival of inoperable non-small cell lung carcinoma patients? A survey of 145 stage III-IV consecutive cases.

PubMed

Pelosi, Giuseppe; Haspinger, Eva Regina; Bimbatti, Manuela; Leone, Giorgia; Paolini, Biagio; Fabbri, Alessandra; Tamborini, Elena; Perrone, Federica; Testi, Adele; Garassino, Marina; Maisonneuve, Patrick; de Braud, Filippo; Pilotti, Silvana; Pastorino, Ugo

2014-04-01

Whether non-small cell lung carcinoma (NSCLC) unveiled by immunohistochemistry (IHC) has the same clinical outcome as those typed by morphology is still matter of debate. A total of 145 stage III-IV, consecutive inoperable NSCLC patients treated by chemotherapy (133 cases) or EGFR tyrosine kinase inhibitor (12 cases) and including 100 biopsies, 11 surgical specimens, and 34 cytological samples had originally accounted for 120 adenocarcinomas (ADs), 19 squamous cell carcinomas (SQCs), and 6 adenosquamous carcinomas (ADSQCs) by integrating morphology and thyroid transcription factor-1 (TTF1)/p40 IHC. Thirty-two NSCLC-not otherwise specified (NSCLC-NOS) cases were identified by morphology revision of the original diagnoses, which showed solid growth pattern (P < .001), 22 ADs, 5 SQCs, and 5 ADSQCs by IHC profiling (P < .001), and 10 gene-altered tumors (3 EGFR, 5 KRAS, and 2 ALK). While no significant relationships were observed between response to therapy and original, morphology or IHC diagnoses, driver mutations and tumor differentiation by TTF1 expression, AD run better progression-free survival (PFS) or overall survival (OS) than other tumor types by morphology (P = .010 and P = .047) and IHC (P = .033 and P = .046), respectively. Furthermore, patients with NSCLC-NOS confirmed as AD by IHC tended to have poorer OS (P = .179) and PFS (P = .193) similar to that of ADSQC and SQC (P = .702 and P = .540, respectively). A category of less differentiated AD with poorer prognosis on therapy could be identified by IHC, while there were no differences for SQC or ADSQC. The terminology of "NSCLC-NOS, favor by IHC" is appropriate to alert clinicians toward more aggressive tumors.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer.

PubMed

Crumley, A B C; McMillan, D C; McKernan, M; McDonald, A C; Stuart, R C

2006-03-13

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied (n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l(-1)) and hypoalbuminaemia (<35 g l(-1)) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02-1.46, P<0.05), stage (HR 1.55, 95% CI 1.30-1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22-1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80-3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.

Therapeutic options for intractable hematuria in advanced bladder cancer.

PubMed

Abt, Dominik; Bywater, Mirjam; Engeler, Daniel Stephan; Schmid, Hans-Peter

2013-07-01

Intractable hematuria is a common and severe complication in patients with inoperable bladder carcinoma. The aim was to provide an overview of therapeutic options for such cases, and analyze their effectiveness and risk profile, so a systematic literature search of peer-reviewed papers published up to September 2012 was carried out. Various options are available to treat hematuria in patients with inoperable bladder cancer; these include orally administered epsilon-aminocaproic acid, intravesical formalin, alum or prostaglandin irrigation, hydrostatic pressure, urinary diversion, radiotherapy, embolization and intraarterial mitoxantrone perfusion. These treatment options are associated with different prospects of success, risks and side-effects. Well-designed and large studies comparing options are completely lacking. Despite various treatment options, management of intractable hematuria in patients with inoperable bladder cancer remains a challenge, and most of the reported methods should be seen as experimental. Interventional radiology and alum instillation seem to be suitable alternative options for patients who, after critical consideration, cannot be treated by irrigation, transurethral resection or palliative cystectomy. © 2013 The Japanese Urological Association.

Clinical outcomes using carbon-ion radiotherapy and dose-volume histogram comparison between carbon-ion radiotherapy and photon therapy for T2b-4N0M0 non-small cell lung cancer-A pilot study.

PubMed

Shirai, Katsuyuki; Kawashima, Motohiro; Saitoh, Jun-Ichi; Abe, Takanori; Fukata, Kyohei; Shigeta, Yuka; Irie, Daisuke; Shiba, Shintaro; Okano, Naoko; Ohno, Tatsuya; Nakano, Takashi

2017-01-01

The safety and efficacy of carbon-ion radiotherapy for advanced non-small cell lung cancer have not been established. We evaluated the clinical outcomes and dose-volume histogram parameters of carbon-ion radiotherapy compared with photon therapy in T2b-4N0M0 non-small cell lung cancer. Twenty-three patients were treated with carbon-ion radiotherapy between May 2011 and December 2015. Seven, 14, and 2 patients had T2b, T3, and T4, respectively. The median age was 78 (range, 53-91) years, with 22 male patients. There were 12 adenocarcinomas, 8 squamous cell carcinomas, 1 non-small cell lung carcinoma, and 2 clinically diagnosed lung cancers. Eleven patients were operable, and 12 patients were inoperable. Most patients (91%) were treated with carbon-ion radiotherapy of 60.0 Gy relative biological effectiveness (RBE) in 4 fractions or 64.0 Gy (RBE) in 16 fractions. Local control and overall survival rates were calculated. Dose-volume histogram parameters of normal lung and tumor coverages were compared between carbon-ion radiotherapy and photon therapies, including three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT). The median follow-up of surviving patients was 25 months. Three patients experienced local recurrence, and the 2-year local control rate was 81%. During follow-up, 5 patients died of lung cancer, and 1 died of intercurrent disease. The 2-year overall survival rate was 70%. Operable patients had a better overall survival rate compared with inoperable patients (100% vs. 43%; P = 0.04). There was no grade ≥2 radiation pneumonitis. In dose-volume histogram analysis, carbon-ion radiotherapy had a significantly lower dose to normal lung and greater tumor coverage compared with photon therapies. Carbon-ion radiotherapy was effectively and safely performed for T2b-4N0M0 non-small cell lung cancer, and the dose distribution was superior compared with those for photon therapies. A Japanese multi-institutional study is ongoing to prospectively evaluate these patients and establish the use of carbon-ion radiotherapy.

Therapeutic Trial for Patients With Ewing Sarcoma Family of Tumor and Desmoplastic Small Round Cell Tumors

ClinicalTrials.gov

2017-09-18

Desmoplastic Small Round Cell Tumor; Ewing Sarcoma of Bone or Soft Tissue; Localized Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Smoothing-Based Relative Navigation and Coded Aperture Imaging

NASA Technical Reports Server (NTRS)

Saenz-Otero, Alvar; Liebe, Carl Christian; Hunter, Roger C.; Baker, Christopher

2017-01-01

This project will develop an efficient smoothing software for incremental estimation of the relative poses and velocities between multiple, small spacecraft in a formation, and a small, long range depth sensor based on coded aperture imaging that is capable of identifying other spacecraft in the formation. The smoothing algorithm will obtain the maximum a posteriori estimate of the relative poses between the spacecraft by using all available sensor information in the spacecraft formation.This algorithm will be portable between different satellite platforms that possess different sensor suites and computational capabilities, and will be adaptable in the case that one or more satellites in the formation become inoperable. It will obtain a solution that will approach an exact solution, as opposed to one with linearization approximation that is typical of filtering algorithms. Thus, the algorithms developed and demonstrated as part of this program will enhance the applicability of small spacecraft to multi-platform operations, such as precisely aligned constellations and fractionated satellite systems.

Evaluation of Shape and Textural Features from CT as Prognostic Biomarkers in Non-small Cell Lung Cancer.

PubMed

Bianconi, Francesco; Fravolini, Mario Luca; Bello-Cerezo, Raquel; Minestrini, Matteo; Scialpi, Michele; Palumbo, Barbara

2018-04-01

We retrospectively investigated the prognostic potential (correlation with overall survival) of 9 shape and 21 textural features from non-contrast-enhanced computed tomography (CT) in patients with non-small-cell lung cancer. We considered a public dataset of 203 individuals with inoperable, histologically- or cytologically-confirmed NSCLC. Three-dimensional shape and textural features from CT were computed using proprietary code and their prognostic potential evaluated through four different statistical protocols. Volume and grey-level run length matrix (GLRLM) run length non-uniformity were the only two features to pass all four protocols. Both features correlated negatively with overall survival. The results also showed a strong dependence on the evaluation protocol used. Tumour volume and GLRLM run-length non-uniformity from CT were the best predictor of survival in patients with non-small-cell lung cancer. We did not find enough evidence to claim a relationship with survival for the other features. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Medical Therapy Versus Balloon Angioplasty for CTEPH: A Systematic Review and Meta-Analysis.

PubMed

Phan, Kevin; Jo, Helen E; Xu, Joshua; Lau, Edmund M

2018-01-01

A significant number of chronic thromboembolic pulmonary hypertension (CTEPH) patients will have an inoperable disease. Medical therapy and balloon pulmonary angioplasty (BPA) have provided alternate therapeutic options for patients with inoperable CTEPH, although there are a limited number of published studies examining the outcomes. Thus, our study aims to evaluate and compare the efficacy of medical therapy and BPA in patients with inoperable CTEPH. An electronic search of six databases was performed and the search results were screened against established criteria for inclusion into this study. Data was extracted and meta-analytical techniques were used to analyse the data. Pooled data from RCTs revealed that medical therapy, compared with a placebo, was associated with a significant improvement of at least one functional class (p=0.038). With regards to pulmonary haemodynamics, medical therapy also resulted in a significant reduction in both mean pulmonary arterial pressure (mPAP) (p=0.002) and pulmonary vascular resistance (PVR) (p<0.001). From the included observational studies, the 6-minute walk distance (6MWD) significantly increased following medical therapy by an average of 22.8% (p<0.001). The pooled improvement in 6MWD was found to be significantly higher in the BPA group when compared to medical therapy for CTEPH (p=0.001). Pooled data from available observational studies of medical therapy or BPA all demonstrated significant improvements in mPAP and PVR for pre versus post intervention comparisons. The improvement in mPAP (p=0.002) and PVR (p=0.002) were significantly greater for BPA intervention when compared to medical therapy. High-quality evidence supports the use of targeted medical therapy in improving haemodynamics in patients with inoperable CTEPH. There is only moderate-quality evidence from observational studies supporting the efficacy of BPA in improving both haemodynamics and exercise capacity. Further RCTs and prospective observational studies comparing medical therapy and BPA in patients with inoperable CTEPH are required. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

Liquid nitrogen spray cryotherapy for dysphagia palliation in patients with inoperable esophageal cancer.

PubMed

Kachaamy, Toufic; Prakash, Ravi; Kundranda, Madappa; Batish, Raman; Weber, Jeffrey; Hendrickson, Scott; Yoder, Leon; Do, Hannah; Magat, Theresa; Nayar, Rajeev; Gupta, Digant; DaSilva, Trisha; Sangal, Ashish; Kothari, Shivangi; Kaul, Vivek; Vashi, Pankaj

2018-05-08

Dysphagia is a debilitating symptom in patients with inoperable esophageal cancer contributing to poor quality of life and worsening nutritional status. The 2 most commonly used palliative modalities for dysphagia are radiation therapy (RT) and esophageal stent placement. However, RT is limited by adverse events (AEs) and total dose, and stent placement has a high rate of AEs including reflux, migration, and chest pain. A relatively new modality of liquid nitrogen endoscopic spray cryotherapy has been described as salvage when other options have been exhausted and when patients are no longer receiving systemic therapy. We evaluated the safety and efficacy of cryotherapy as the primary modality for relieving dysphagia in inoperable esophageal cancer including patients receiving systemic cancer therapy. This is a retrospective multicenter consecutive case series of 49 inoperable esophageal cancer patients undergoing palliative endoscopic cryotherapy at 4 specialized cancer centers from May 2014 to May 2016. The primary outcomes were change in dysphagia scores between pre- and post-cryotherapy and AE. Dysphagia was measured using a 4-point Likert scale: 0, no dysphagia; 1, dysphagia to solids; 2, dysphagia to semi-solids; 3, dysphagia to liquids; 4, dysphagia to saliva. There were 39 males and 10 females with a mean age of 58 years who underwent a total of 120 cryotherapy treatments. The mean dysphagia score improved significantly from 2.4 pre-cryotherapy to 1.7 post-cryotherapy (improvement of 0.7 points; p<0.001). Minor AE were seen in 6/120 (5.0%) cryotherapy treatments (1 intra-procedural and 5 post-procedural). In addition, one patient developed a severe intra-procedural AE of dilation-related perforation whereas another patient developed a benign stricture requiring dilation. This preliminary retrospective study suggests that liquid nitrogen spray cryotherapy may be safe and effective for dysphagia palliation in inoperable esophageal cancer. Large prospective studies are needed to confirm these findings and identify patient and procedure characteristics associated with the greatest benefit. Copyright © 2018 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

Risk-based input-output analysis of influenza epidemic consequences on interdependent workforce sectors.

PubMed

Santos, Joost R; May, Larissa; Haimar, Amine El

2013-09-01

Outbreaks of contagious diseases underscore the ever-looming threat of new epidemics. Compared to other disasters that inflict physical damage to infrastructure systems, epidemics can have more devastating and prolonged impacts on the population. This article investigates the interdependent economic and productivity risks resulting from epidemic-induced workforce absenteeism. In particular, we develop a dynamic input-output model capable of generating sector-disaggregated economic losses based on different magnitudes of workforce disruptions. An ex post analysis of the 2009 H1N1 pandemic in the national capital region (NCR) reveals the distribution of consequences across different economic sectors. Consequences are categorized into two metrics: (i) economic loss, which measures the magnitude of monetary losses incurred in each sector, and (ii) inoperability, which measures the normalized monetary losses incurred in each sector relative to the total economic output of that sector. For a simulated mild pandemic scenario in NCR, two distinct rankings are generated using the economic loss and inoperability metrics. Results indicate that the majority of the critical sectors ranked according to the economic loss metric comprise of sectors that contribute the most to the NCR's gross domestic product (e.g., federal government enterprises). In contrast, the majority of the critical sectors generated by the inoperability metric include sectors that are involved with epidemic management (e.g., hospitals). Hence, prioritizing sectors for recovery necessitates consideration of the balance between economic loss, inoperability, and other objectives. Although applied specifically to the NCR, the proposed methodology can be customized for other regions. © 2012 Society for Risk Analysis.

Balloon Pulmonary Angioplasty for Inoperable Patients With Chronic Thromboembolic Pulmonary Hypertension. Observational Study in a Referral Unit.

PubMed

Velázquez, Maite; Albarrán, Agustín; Hernández, Ignacio; López-Gude, M Jesús; Sarnago, Fernando; Martín, Roberto; Arribas, Fernando; Escribano, Pilar

2018-05-29

Balloon pulmonary angioplasty (BPA) for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) is becoming widely accepted. Procedural refinement has reduced complications. Our primary objective was to analyze the results and complications of the first national BPA program. Observational, prospective series that included all consecutive BPA procedures in inoperable CTEPH patients between May 2013 and February 2017 performed at a single institution. We analyzed clinical and hemodynamic improvement, reperfusion pulmonary edema, and mortality. We performed 156 BPA sessions in 46 patients. Pulmonary vascular resistance was reduced by 44% (10.1 ± 4.9 vs 5.6 ± 2.2 WU; P < .001) and mean pulmonary arterial pressure by 23.6% (49.5 ± 12 vs 37.8 ± 9mmHg; P < .001); cardiac index rose by 17.1% (2.3 vs 2.7 L/min/m 2 ; P = .002), N-terminal pro-B-type natriuretic peptide levels were reduced by 79.2% (1233 ± 1327 vs 255.5 ± 318 pg/dL; P < .001) and the 6-minute walk test distance improved by 74 meters (394 vs 468 m; P = .001). Reperfusion pulmonary edema developed after 9 interventions (5.8%) and 1 patient died (mortality 2.1%). Due to its current refinement, BPA has become a safe and effective treatment for inoperable CTEPH that improves hemodynamics, functional status, and biomarkers with a low rate of severe periprocedural complications and mortality. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

Long-term outcome of concurrent chemoradiotherapy with elective nodal irradiation for inoperable esophageal cancer.

PubMed

Jing, Zhao; Chen, Tian; Zhang, Xuebang; Wu, Shixiu

2017-09-01

Elective nodal irradiation (ENI) might improve overall survival in patients with inoperable esophageal cancer. We conducted a retrospective analysis to assess the long-term survival and toxicity of esophageal cancer patients treated with ENI versus conventional-field irradiation (CFI). All data in the present study were based on our institutional experience from 2000 to 2005 of patients with inoperable esophageal cancer treated with ENI or CFI plus two concurrent cycles of paclitaxel/cisplatin. Based on the inclusion and exclusion criteria, 89 patients were included in the analysis. Of these patients, 51 were treated with ENI, whereas 38 were treated with CFI. For the per-protocol population, the patients in the ENI group significantly improved in terms of their 10-year disease-specific overall survival (43.1% vs 10.5%, P = 0.019), 10-year disease-free survival (36.7% vs 10.2%, P = 0.040) and 10-year local recurrence-free survival (47.2% vs 17.2%, P = 0.018) compared with the CFI group. Aside from radiation esophagitis, the incidence of grade 3 or greater acute toxicities did not differ between the two groups. Multivariate analysis showed that radiation field, tumor length and clinical stage were independent prognostic factors associated with OS. Concurrent chemoradiotherapy with ENI improves both disease-specific overall survival and loco-regional control in patients with inoperable esophageal cancer receiving per-protocol treatment. The regimen has a manageable tolerability profile. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Risk-Based Input-Output Analysis of Influenza Epidemic Consequences on Interdependent Workforce Sectors

PubMed Central

Santos, Joost R.; May, Larissa; Haimar, Amine El

2013-01-01

Outbreaks of contagious diseases underscore the ever-looming threat of new epidemics. Compared to other disasters that inflict physical damage to infrastructure systems, epidemics can have more devastating and prolonged impacts on the population. This paper investigates the interdependent economic and productivity risks resulting from epidemic-induced workforce absenteeism. In particular, we develop a dynamic input-output model capable of generating sector-disaggregated economic losses based on different magnitudes of workforce disruptions. An ex post analysis of the 2009 H1N1 pandemic in the National Capital Region (NCR) reveals the distribution of consequences across different economic sectors. Consequences are categorized into two metrics: (i) economic loss, which measures the magnitude of monetary losses incurred in each sector, and (ii) inoperability, which measures the normalized monetary losses incurred in each sector relative to the total economic output of that sector. For a simulated mild pandemic scenario in NCR, two distinct rankings are generated using the economic loss and inoperability metrics. Results indicate that the majority of the critical sectors ranked according to the economic loss metric comprise of sectors that contribute the most to the NCR's gross domestic product (e.g., federal government enterprises). In contrast, the majority of the critical sectors generated by the inoperability metric include sectors that are involved with epidemic management (e.g., hospitals). Hence, prioritizing sectors for recovery necessitates consideration of the balance between economic loss, inoperability, and other objectives. Although applied specifically to the NCR region, the proposed methodology can be customized for other regions. PMID:23278756

Early diagnosis of peripheral nervous system involvement in Fabry disease and treatment of neuropathic pain: the report of an expert panel

PubMed Central

2011-01-01

Background Fabry disease is an inherited metabolic disorder characterized by progressive lysosomal accumulation of lipids in a variety of cell types, including neural cells. Small, unmyelinated nerve fibers are particularly affected and small fiber peripheral neuropathy often clinically manifests at young age. Peripheral pain can be chronic and/or occur as provoked attacks of excruciating pain. Manifestations of dysfunction of small autonomic fibers may include, among others, impaired sweating, gastrointestinal dysmotility, and abnormal pain perception. Patients with Fabry disease often remain undiagnosed until severe complications involving the kidney, heart, peripheral nerves and/or brain have arisen. Methods An international expert panel convened with the goal to provide guidance to clinicians who may encounter unrecognized patients with Fabry disease on how to diagnose these patients early using simple diagnostic tests. A further aim was to offer recommendations to control neuropathic pain. Results We describe the neuropathy in Fabry disease, focusing on peripheral small fiber dysfunction - the hallmark of early neurologic involvement in this disorder. The clinical course of peripheral pain is summarized, and the importance of medical history-taking, including family history, is highlighted. A thorough physical examination (e.g., angiokeratoma, corneal opacities) and simple non-invasive sensory perception tests could provide clues to the diagnosis of Fabry disease. Reported early clinical benefits of enzyme replacement therapy include reduction of neuropathic pain, and adequate management of residual pain to a tolerable and functional level can substantially improve the quality of life for patients. Conclusions Our recommendations can assist in diagnosing Fabry small fiber neuropathy early, and offer clinicians guidance in controlling peripheral pain. This is particularly important since management of pain in young patients with Fabry disease appears to be inadequate. PMID:21619592

End results of radiation therapy, alone and combination with 5-fluorouracil in colorectal cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vongtama, V.; Douglass, H.O.; Moore, R.H.

The authors retrospectively analyzed the results of irradiation in 148 cases of primary inoperable and recurrent adenocarcinoma of the colon and rectum treated at the Department of Radiation Therapy, Roswell Park Memorial Institute between 1962 and 1970. This group includes 95 recurrences and 53 inoperable primaries. Uninterrupted radiotherapy was used in 118 cases and split-course technique in 30 cases. Eleven patients received combined radiotherapy and surgery. Seventy-eight patients received a combination of 5-fluorouracil (5-FU) and irradiation. The response rate and survival of individual groups is discussed in detail. This study indicated that perineal recurrences should receive whole pelvic irradiation inmore » addition to perineum field. Split-course technique appeared to yield a better survival than the uninterrupted course. The best 5-year survival rate (64 percent) is found in the group treated with a combination of radiation and surgery. For locally advanced, inoperable cancers, split-course technique, combined 5-FU and irradiation gave the best results, achieving longer palliation with improved quality of life and sometimes yielding cure (5-year survival). (auth)« less

TAMOXIFEN RETINOPATHY DURING TREATMENT OF AN INOPERABLE DESMOID TUMOR.

PubMed

Furst, Meredith; Somogyi, Marie B; Wong, Robert W; Araujo, Dejka; Harper, Clio A

2017-12-08

To evaluate the clinical significance and rarity of tamoxifen retinopathy after a long-term tamoxifen treatment for an inoperable desmoid tumor. Case report. Tamoxifen retinopathy is a condition rarely observed in clinical practice. Although tamoxifen is typically a treatment for breast cancer patients, we present a 68-year-old woman taking tamoxifen for an inoperable desmoid tumor, an equally rare condition. She presented with bilaterally deteriorating vision over the course of a year. Fundoscopic examination revealed parafoveal deposits bilaterally. Spectral domain optical coherence tomography exhibited hyperreflective deposits in all layers of the retina. She had a cumulative treatment dose of 292 g of tamoxifen, and the medication was subsequently stopped. Her vision remained stable 3 months after the cessation of tamoxifen. The development of tamoxifen retinopathy in the treatment of a desmoid tumor makes this case a rare entity, and this is the first reported case of these two concomitant conditions to our knowledge. With the use of long-term tamoxifen as a primary treatment, we recommend screening at regular intervals by an ophthalmologist as an integral part of treatment.

[High-intensity focused ultrasound (HIFU) for tumor pain relief in inoperable pancreatic cancer : Evaluation with the pain sensation scale (SES)].

PubMed

Marinova, M; Strunk, H M; Rauch, M; Henseler, J; Clarens, T; Brüx, L; Dolscheid-Pommerich, R; Conrad, R; Cuhls, H; Radbruch, L; Schild, H H; Mücke, M

2017-02-01

High-intensity focused ultrasound (HIFU) in combination with palliative standard therapy is an innovative and effective treatment option for pain reduction in patients with inoperable pancreatic cancer. Evaluation of the effects of additive ultrasound (US)-guided HIFU treatment in inoperable pancreatic cancer on the sensory and affective pain perception using validated questionnaries. In this study 20 patients with locally advanced inoperable pancreatic cancer and tumor-related pain were treated by US-guided HIFU (6 stage III, 12 stage IV according to UICC and 2 with local recurrence after surgery). Ablation was performed using the JC HIFU system (HAIFU, Chongqing, China) with an ultrasonic device for real-time imaging. Clinical assessment included evaluation of pain severity using validated questionnaires with particular attention to the pain sensation scale (SES) with its affective and sensory component and the numeric rating scale (NRS). The average pain reduction after HIFU was 2.87 points on the NRS scale and 57.3 % compared to the mean baseline score (n = 15, 75 %) in 19 of 20 treated patients. Four patients did not report pain relief, however, the previous opioid medication could be stopped (n = 2) or the analgesic dosage could be reduced (n = 2). No pain reduction was achieved in one patient. Furthermore, after HIFU emotional as well as sensory pain aspects were significantly reduced (before vs. 1 week after HIFU, p < 0.05 for all pain scales). US-guided HIFU can be used for effective and early pain relief and reduction of emotional and sensory pain sensation in patients with locally advanced pancreatic cancer.

Impact of wait times on the effectiveness of transcatheter aortic valve replacement in severe aortic valve disease: a discrete event simulation model.

PubMed

Wijeysundera, Harindra C; Wong, William W L; Bennell, Maria C; Fremes, Stephen E; Radhakrishnan, Sam; Peterson, Mark; Ko, Dennis T

2014-10-01

There is increasing demand for transcatheter aortic valve replacement (TAVR) as the primary treatment option for patients with severe aortic stenosis who are high-risk surgical candidates or inoperable. We used mathematical simulation models to estimate the hypothetical effectiveness of TAVR with increasing wait times. We applied discrete event modelling, using data from the Placement of Aortic Transcatheter Valves (PARTNER) trials. We compared TAVR with medical therapy in the inoperable cohort, and compared TAVR to conventional aortic valve surgery in the high-risk cohort. One-year mortality and wait-time deaths were calculated in different scenarios by varying TAVR wait times from 10 days to 180 days, while maintaining a constant wait time for surgery at a mean of 15.6 days. In the inoperable cohort, the 1-year mortality for medical therapy was 50%. When the TAVR wait time was 10 days, the TAVR wait-time mortality was 1.9% with a 1-year mortality of 31.5%. TAVR wait-time deaths increased to 28.9% with a 180-day wait, with a 1-year mortality of 41.4%. In the high-risk cohort, the wait-time deaths and 1-year mortality for the surgical patients were 2.5% and 27%, respectively. The TAVR wait-time deaths increased from 2.2% with a 10-day wait to 22.4% with a 180-day wait, and a corresponding increase in 1-year mortality from 24.5% to 32.6%. Mortality with TAVR exceeded surgery when TAVR wait times exceeded 60 days. Modest increases in TAVR wait times have a substantial effect on the effectiveness of TAVR in inoperable patients and high-risk surgical candidates. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

"What if I do nothing?" The natural history of operable cancer of the alimentary tract.

PubMed

Keshava, H B; Rosen, J E; DeLuzio, M R; Kim, A W; Detterbeck, F C; Boffa, D J

2017-04-01

"Natural history", or anticipated survival without treatment, is critical for patients weighing risks and benefits of cancer surgery. Current estimates concerning the natural history of cancer includes patients whose poor health precludes treatment; a cohort whose fate is likely distinctly worse than those eligible for surgery ("operable"). The study objective was to evaluate survival among patients recommended for cancer surgery but went untreated, to determine the natural history of "operable" alimentary tract cancer. The NCDB was queried for untreated patients with clinical stage I-III esophageal, gastric, colon, and rectal cancer diagnosed between 2003 and 2009. Untreated patients who were recommended for surgery were considered "operable," while patients coded as surgically ineligible for health reasons were "inoperable." 5-year survival of untreated, "operable" alimentary tract cancers varied by clinical stage: esophageal cI = 10.0%, cII = 9.8%, cIII = 4.6%; gastric cI = 9.2%, cII = 5.8%, cIII = 4.3%; colon cI = 18.4%, cII = 5.0%, cIII = 10.4; and rectal cI = 17.1%, cII = 14.0%, cIII = 19.9%. At every timepoint, stage-specific survival of "operable" patients was superior to inoperable patients (p < 0.05). Additionally, median survival among "operable" patients at least doubled "inoperable" patients for each tumor. Natural history of patients with "operable" alimentary tract cancer is superior to that of "inoperable" patients. Preoperative counseling should be refined to reflect this distinction. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Simultaneous integrated boost-intensity modulated radiation therapy for inoperable hepatocellular carcinoma.

PubMed

Kim, Tae Hyun; Park, Joong-Won; Kim, Yeon-Joo; Kim, Bo Hyun; Woo, Sang Myung; Moon, Sung Ho; Kim, Sang Soo; Lee, Woo Jin; Kim, Dae Yong; Kim, Chang-Min

2014-10-01

The aim of this work was to evaluate the clinical efficacy and safety of simultaneous integrated boost-intensity modulated radiation therapy (SIB-IMRT) in patients with inoperable hepatocellular carcinoma (HCC). A total of 53 patients with inoperable HCC underwent SIB-IMRT using two dose-fractionation schemes, depending on the proximity of gastrointestinal structures. The 41 patients in the low dose-fractionation (LD) group, with internal target volume (ITV) < 1 cm from gastrointestinal structures, received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 (PTV1) and 2 (PTV2), respectively. The 12 patients in the high dose-fractionation (HD) group, with ITV ≥ 1 cm from gastrointestinal structures, received total doses of 66 and 55 Gy in 22 fractions to the PTV1 and PTV2, respectively. Overall, treatment was well tolerated, with no grade > 3 toxicity. The LD group had larger sized tumors (median: 6 vs. 3.4 cm) and greater frequencies of vascular invasion (80.6 vs. 16.7 %) than patients in the HD group (p < 0.05 each). The median overall survival (OS) was 25.1 mKonzept ist machbar und sicheronths and the actuarial 2-year local progression-free survival (LPFS), relapse-free survival (RFS), and OS rates were 67.3, 14.7, and 54.7  %, respectively. The HD group tended to show better tumor response (100 vs. 62.2 %, p = 0.039) and 2-year LPFS (85.7 vs. 59  %, p = 0.119), RFS (38.1 vs. 7.3 %, p = 0.063), and OS (83.3 vs. 44.3 %, p = 0.037) rates than the LD group. Multivariate analysis showed that tumor response was significantly associated with OS. SIB-IMRT is feasible and safe for patients with inoperable HCC.

Endoscopic treatment of early bronchial cancer: our experience with photodynamic therapy (PDT)

NASA Astrophysics Data System (ADS)

Corti, Luigi; Toniolo, Lamberto; Boso, Caterina; Colaut, Flavio; Fiore, Davide; Muzzio, Pier-Carlo; Loreggian, Lucio; Sotti, Guido

2009-06-01

The role of photodynamic therapy (PDT) in the treatment of small cancers has been established in several clinical studies. Here, we report on the efficacy of PDT for early inoperable or recurrent non-small-cell lung cancer (NSCLC). Methods and Materials: From June 1989 to November 2004, 40 patients with 50 NSCLC were treated with PDT. Twelve cases were inoperable for medical reasons and were staged as T1N0M0, and 28 had recurrent in situ carcinoma. Patients with residual disease after PDT received definitive radiotherapy and/or brachytherapy. Follow-up ranged from 6 to 167 months (median 43.59). Twenty of the 40 patients received i.v. injections of hematoporphyrin derivative (5 mg/kg), the other 20 had injections of porfimer sodium (Photofrin, 2 mg/kg). An argon dye laser (630 nm wavelength, 200-300 J/cm2) was used for light irradiation in 24 of the 40 patients, a diode laser (Diomed, 630 nm wavelength, 100- 200 J/cm2) in the other 16. Results: PDT obtained a 72% complete response (CR) rate (36/50 treated lesions), that is 27 CR among the 37 Tis carcinomas and 9 among the 13 T1 cases. Kaplan-Meier curves showed a mean overall survival (OS) of 75.59 months (median 91.4 months). Two- and 5- year OS rates were 72.78% and 59.55%. The mean and median survival rates for patients with Tis stage were 86.5 and 120.4 months, respectively (standard error 9.50) and for patients with T1 disease they were 45.78 and 35.71 months, respectively; the difference was statistically significant (P< 0.03). No severe early or late PDT-related adverse events were recorded. Conclusions: PDT is effective in early primary or recurrent NSCLC, resulting in a CR rate of 72%. The incorporation of PDT in standard clinical practice, in combination with radiotherapy, warrants further investigation.

Comparison of Survival Rate in Primary Non-Small-Cell Lung Cancer Among Elderly Patients Treated With Radiofrequency Ablation, Surgery, or Chemotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Heon; Jin, Gong Yong, E-mail: gyjin@chonbuk.ac.kr; Han, Young Min

Purpose: We retrospectively compared the survival rate in patients with non-small-cell lung cancer (NSCLC) treated with radiofrequency ablation (RFA), surgery, or chemotherapy according to lung cancer staging. Materials and Methods: From 2000 to 2004, 77 NSCLC patients, all of whom had WHO performance status 0-2 and were >60 years old, were enrolled in a cancer registry and retrospectively evaluated. RFA was performed on patients who had medical contraindications to surgery/unsuitability for surgery, such as advanced lung cancer or refusal of surgery. In the RFA group, 40 patients with inoperable NSCLC underwent RFA under computed tomography (CT) guidance. These included 16more » patients with stage I to II cancer and 24 patients with stage III to IV cancer who underwent RFA in an adjuvant setting. In the comparison group (n = 37), 13 patients with stage I to II cancer underwent surgery; 18 patients with stage III to IV cancer underwent chemotherapy; and 6 patients with stage III to IV cancer were not actively treated. The survival curves for RFA, surgery, and chemotherapy in these patients were calculated using Kaplan-Meier method. Results: Median survival times for patients treated with (1) surgery alone and (2) RFA alone for stage I to II lung cancer were 33.8 and 28.2 months, respectively (P = 0.426). Median survival times for patients treated with (1) chemotherapy alone and (2) RFA with chemotherapy for stage III to IV cancer were 29 and 42 months, respectively (P = 0.03). Conclusion: RFA can be used as an alternative treatment to surgery for older NSCLC patients with stage I to II inoperable cancer and can play a role as adjuvant therapy with chemotherapy for patients with stage III to IV lung cancer.« less

Toxicity Profile and Pharmacokinetic Study of A Phase I Low-Dose Schedule-Dependent Radiosensitizing Paclitaxel Chemoradiation Regimen for Inoperable Non-Small-Cell Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Yuhchyau; Pandya, Kishan J.; Feins, Richard

Purpose: We report the toxicity profile and pharmacokinetic data of a schedule-dependent chemoradiation regimen using pulsed low-dose paclitaxel for radiosensitization in a Phase I study for inoperable non-small-cell lung cancer. Methods and Materials: Paclitaxel at escalating doses of 15 mg/m{sup 2}, 20 mg/m{sup 2}, and 25 mg/m{sup 2} were infused on Monday, Wednesday, and Friday with daily chest radiation in cohorts of 6 patients. Daily radiation was delayed for maximal G2/M arrest and apoptotic effect, an observation from preclinical investigations. Plasma paclitaxel concentration was determined by high-performance liquid chromatography. Results: Dose-limiting toxicities included 3 of 18 patients with Grade 3more » pneumonitis and 3 of 18 patients with Grade 3 esophagitis. There was no Grade 4 or 5 pneumonitis or esophagitis. There was also no Grade 3 or 4 neutropenia, thrombocytopenia, anemia or neuropathy. For Dose Levels I (15 mg/m{sup 2}), II (20 mg/m{sup 2}), and III (25 mg/m{sup 2}), the mean peak plasma level was 0.23 {+-} 0.06 {mu}mol/l, 0.32 {+-} 0.05 {mu}mol/l, and 0.52 {+-} 0.14 {mu}mol/l, respectively; AUC was 0.44 {+-} 0.09 {mu}mol/l, 0.61 {+-} 0.1 {mu}mol/l, and 0.96 {+-} 0.23 {mu}mol/l, respectively; and duration of drug concentration >0.05 {mu}mol/l (t > 0.05 {mu}mol/l) was 1.6 {+-} 0.3 h, 1.9 {+-} 0.2 h, and 3.0 {+-} 0.9 h, respectively. Conclusion: Pulsed low-dose paclitaxel chemoradiation is associated with low toxicity. Pharmacokinetic data showed that plasma paclitaxel concentration >0.05 {mu}mol/l for a minimum of 1.6 h was sufficient for effective radiosensitization.« less

High-Dose-Rate Brachytherapy for Non-Small-Cell Lung Carcinoma: A Retrospective Study of 226 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aumont-le Guilcher, Maud; Prevost, Bernard; Sunyach, Marie Pierre

Purpose: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma. Methods and Materials: We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis. Results: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed atmore » 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001). Conclusions: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma.« less

Drug Distribution into Peripheral Nerve.

PubMed

Liu, Houfu; Chen, Yan; Huang, Liang; Sun, Xueying; Fu, Tingting; Wu, Shengqian; Zhu, Xiaoyan; Zhen, Wei; Liu, Jihong; Lu, Gang; Cai, Wei; Yang, Ting; Zhang, Wandong; Yu, Xiaohong; Wan, Zehong; Wang, Jianfei; Summerfield, Scott G; Dong, Kelly; Terstappen, Georg C

2018-05-01

Little is known about the impact of the blood-nerve barrier (BNB) on drug distribution into peripheral nerves. In this study, we examined the peripheral nerve penetration in rats of 11 small-molecule drugs possessing diverse physicochemical and transport properties and ProTx-II, a tarantula venom peptide with molecular mass of 3826 Daltons. Each drug was administered as constant rate intravenous infusion for 6 hours (small molecules) or 24 hours (ProTx-II). Blood and tissues including brain, spinal cord, sciatic nerve, and dorsal root ganglion (DRG) were collected for drug concentration measurements. Unbound fractions of a set of compounds were determined by equilibrium dialysis method in rat blood, brains, spinal cords, sciatic nerves, and DRG. We also investigated the influence of N -[4-[2-(6,7-dimethoxy-3,4-dihydro-1 H -isoquinolin-2-yl)ethyl]phenyl]-5-methoxy-9-oxo-10 H -acridine-4-carboxamide (GF120918), a P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor, on the peripheral nerve and central nervous system (CNS) tissue penetration of imatinib. We found that: 1) the unbound fraction in brain tissue homogenate highly correlates with that in the spinal cord, sciatic nerve, and DRG for a set of compounds and thus provides a good surrogate for spinal cord and peripheral nerve tissues, 2) small-molecule drugs investigated can penetrate the DRG and sciatic nerve, 3) P-gp and BCRP have a limited impact on the distribution of small-molecule drugs into peripheral nerves, and 4) DRG is permeable to ProTx-II, but its distribution into sciatic nerve and CNS tissues is restricted. These results demonstrate that small-molecule drugs investigated can penetrate peripheral nerve tissues, and P-gp/BCRP may not be a limiting factor at the BNB. Biologics as large as ProTx-II can access the DRG but not sciatic nerve and CNS tissues. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

Radiotherapy in elderly patients with inoperable esophageal cancer. Is there a benefit?

PubMed

Semrau, R; Herzog, S L; Vallböhmer, D; Kocher, M; Hölscher, A; Müller, R-P

2012-03-01

Radiation oncologists increasingly face elderly cancer patients impaired by comorbidities and reduced performance status. As less data are available for this particular group of patients, the aim of the study was to assess the prognosis of inoperable esophageal cancer patients ≥ 70 years undergoing definitive radiotherapy or radiochemotherapy. PATIENTS AND TREATMENT PROTOCOL: Patients aged ≥ 70 with inoperable carcinoma of the esophagus undergoing definitive radio(chemo)therapy between 1995 and 2006 at the University of Cologne were included retrospectively. Maximal total dose of radiotherapy administered was 63 Gy (5 × 1.8 Gy/week). Chemotherapy consisted of cisplatin (20 mg/m(2) on days 1-5 and days 29-33) and 5-fluorouracil (650-1,000 mg/m(2) on days 1-5 and days 29-33). Efficacy was compared with a cohort of 152 patients < 70 years treated with the same protocol during the same time period. A total of 51 patients aged  ≥ 70 with inoperable cancer of the esophagus undergoing definitive therapy were identified (stage I/II 23.5%, stage III 56.9%, stage IV 9.8%; squamous cell carcinoma 74.5%, adenocarcinoma 25.5%). While 15 patients (29.4%) received combined radiochemotherapy (RCT), 40 patients (70.6%) were treated with radiotherapy alone (RT). Median progression-free survival (PFS) was 9.5 months; median overall survival (OS) was 13.9 months. Patients treated with RCT had a 2-year OS rate of 53.3% compared with 16.7% for RT patients (p = 0.039). The 2-year OS for clinically lymph node negative patients was 38.5% compared with 21.2% for lymph node positive patients (p = 0.072). Median OS was not significantly different between patients ≥ 70 years versus the patient cohort (n = 152) aged < 70 years (13.9 vs. 7.2 months, p = 0.072) but PFS showed a significant difference (4.9 vs. 9.5 months, p = 0.026) in favor of the > 70 years group. Prognosis in elderly patients with inoperable esophageal cancer undergoing definitive radiotherapy/radiochemotherapy is limited, although it is not inferior to patients < 70 years.

Toxicity evaluation of convection-enhanced delivery of small-molecule kinase inhibitors in naïve mouse brainstem.

PubMed

Zhou, Zhiping; Ho, Sharon L; Singh, Ranjodh; Pisapia, David J; Souweidane, Mark M

2015-04-01

Diffuse intrinsic pontine gliomas (DIPGs) are inoperable and lethal high-grade gliomas lacking definitive therapy. Platelet-derived growth factor receptor (PDGFR) and its downstream signaling molecules are the most commonly overexpressed oncogenes in DIPG. This study tested the effective concentration of PDGFR pathway inhibitors in cell culture and then toxicity of these small-molecule kinase inhibitors delivered to the mouse brainstem via convection-enhanced delivery (CED) for potential clinical application. Effective concentrations of small-molecule kinase inhibitors were first established in cell culture from a mouse brainstem glioma model. Sixteen mice underwent CED, a local drug delivery technique, of saline or of single and multidrug combinations of dasatinib (2 M), everolimus (20 M), and perifosine (0.63 mM) in the pons. Animals were kept alive for 3 days following the completion of infusion. No animals displayed any immediate or delayed neurological deficits postoperatively. Histological analysis revealed edema, microgliosis, acute inflammation, and/or axonal injury in the experimental animals consistent with mild acute drug toxicity. Brainstem CED of small-molecule kinase inhibitors in the mouse did not cause serious acute toxicities. Future studies will be necessary to evaluate longer-term safety to prepare for potential clinical application.

Commercial versus PARTNER study experience with the transfemoral Edwards SAPIEN valve for inoperable patients with severe aortic stenosis.

PubMed

Pendyala, Lakshmana K; Minha, Sa'ar; Barbash, Israel M; Torguson, Rebecca; Magalhaes, Marco A; Okubagzi, Petros; Loh, Joshua P; Chen, Fang; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

2014-01-15

In patients with aortic stenosis who cannot have surgery, transcatheter aortic valve replacement using the Edwards SAPIEN valve has been shown to improve survival rate and is approved for commercial use in the United States. This study aims to assess the clinical profile, procedural characteristics, and in-hospital complications in patients treated with a commercial SAPIEN valve outside the clinical trial context. We retrospectively analyzed 69 consecutive patients who underwent transcatheter aortic valve replacement with a commercial SAPIEN valve compared with 55 Placement of AoRTic traNscathetER valves (PARTNER) trial patients from cohort B enrolled in the same institution by the same Heart Team. Compared with the commercial group, patients in the PARTNER cohort B had higher mean Society of Thoracic Surgeons score (10 ± 5 vs 9 ± 4, p = 0.04) and a lower rate of peripheral arterial disease (19% vs 44%, p = 0.004). Most patients in the commercial group had the procedure under conscious sedation (83% vs 66%, p = 0.03). Planned surgical cut down for vascular access was rare in the commercial group (1.4% vs 46%, p <0.001). The overall rates of major vascular complications, life-threatening or major bleeding, and blood transfusions were lower in commercial group (7.2% vs 27%, p = 0.003; 2.9% vs 16%, p = 0.01; and 28% vs 60%, p <0.001, respectively). In-hospital all-cause mortality (5.8% vs 9.1%, p = 0.51) and stroke rates (7.2% vs 14.5%, p = 0.19) were not statistically different between groups. The median length of hospitalization (p <0.001) and postprocedural length of stay (p = 0.01) was shorter in the commercial group. In conclusion, transfemoral commercial use of the Edwards SAPIEN valve for inoperable patients shows similar in-hospital mortality and stroke rates compared with PARTNER cohort B. The refinements in the procedure such as more conscious sedation, experience of the operators, and careful vascular planning in the commercial group led to lesser vascular and bleeding complications and shorter length of stay. Copyright © 2014 Elsevier Inc. All rights reserved.

Intratumoral peripheral small papillary tufts: a diagnostic clue of renal tumors associated with Birt-Hogg-Dubé syndrome.

PubMed

Kuroda, Naoto; Furuya, Mitsuko; Nagashima, Yoji; Gotohda, Hiroko; Moritani, Suzuko; Kawakami, Fumi; Imamura, Yoshiaki; Bando, Yoshimi; Takahashi, Masayuki; Kanayama, Hiro-omi; Ota, Satoshi; Michal, Michal; Hes, Ondrej; Nakatani, Yukio

2014-06-01

In this article, we searched for the common histologic characteristic of renal tumors in patients with Birt-Hogg-Dubé syndrome (BHDS). We selected 6 patients with histologically confirmed renal tumor in BHDS. Germline FLCN gene mutation has been identified in 5 patients. Multifocality and bilaterality of the renal tumors were pathologically or radiologically confirmed in 5 and 2 cases, respectively. Histologic subtypes of the dominant tumor included 3 previously described hybrid oncocytic tumors, one composite chromophobe/papillary/clear cell renal cell carcinoma (RCC) and one unclassified RCC resembling hybrid chromophobe/clear cell RCC. In one case, chromophobe RCC and clear cell RCC were separately observed. Small papillary lesions located in the peripheral area of the tumor, which we designated as intratumoral peripheral small papillary tufts, were identified in all patients. In conclusion, multifocality/bilaterality of renal tumors, discordance of histologic subtypes, and the presence of intratumoral peripheral small papillary tufts may be important clues to identify BHDS-associated renal tumors. Copyright © 2014 Elsevier Inc. All rights reserved.

Charged-particle stereotactic radiosurgery

NASA Astrophysics Data System (ADS)

Lyman, John T.; Fabrikant, Jacob I.; Frankel, Kenneth A.

1985-05-01

Charged-particle stereotactic radiosurgery is the technique of using accelerated atomic nuclei for the irradiation of a small volume target to a high dose in a short time interval. This is contrasted with conventional radiotherapy where large volumes are treated with many small fractions of photon or electron radiation over a multi-week period. The helium-ion beam used for charged-particle stereotactic radiosurgery at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron is described. This beam is being used for the treatment of inoperable, deep, intracranial arteriovenous malformations (AVMs). Intracranial AVMs are collections of abnormal blood vessels in the brain that may represent a failure of vessels to mature properly and after a long period of slow growth they may produce clinically recognizable neurological symptoms. Based on our experience using narrow beams of helium ions for stereotactic radiosurgical treatment of AVM patients, the characteristics of the treatments are described. Improvements to the technique which are possible by the use of other charged particle beams are discussed.

Palliative treatment of inoperable patients with carcinoma of the cardia region.

PubMed

Seifert, E; Reinhard, A; Lütke, A; Gail, K

1983-02-01

Endoscopic palliative treatment of inoperable patients with carcinoma of the cardia region is superior to surgical procedures that allow the feeding of patients. After dilating the malignant stenosis with an Eder-Puestow dilator, a Celestin or Atkinson tube is inserted endoscopically by means of the Nottingham introducer. In 25 of 26 patients the inserted tube functioned well until the death of the patient for an average of 109 days. Six patients are still alive and one patient has had the tube for almost 3 years. Of the 19 patients who died, 18 retained the tube until they died. The complication rate of the procedure was 11.5% with a 3.8% mortality related to tube insertion.

Ras-Driven Transcriptome Analysis Identifies Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target

PubMed Central

Patel, Ami V.; Eaves, David; Jessen, Walter J.; Rizvi, Tilat A.; Ecsedy, Jeffrey A.; Qian, Mark G.; Aronow, Bruce J.; Perentesis, John P.; Serra, Eduard; Cripe, Timothy P.; Miller, Shyra J.; Ratner, Nancy

2013-01-01

Purpose Patients with Neurofibromatosis Type 1 (NF1) develop malignant peripheral nerve sheath tumors (MPNST) which are often inoperable and do not respond well to current chemotherapies or radiation. The goal of this study was to utilize comprehensive gene expression analysis to identify novel therapeutic targets. Experimental Design Nerve Schwann cells and/or their precursors are the tumorigenic cell types in MPNST due to the loss of the NF1 gene, which encodes the RasGAP protein neurofibromin. Therefore, we created a transgenic mouse model, CNP-HRas12V, expressing constitutively-active HRas in Schwann cells and defined a Ras-induced gene expression signature to drive a Bayesian factor regression model analysis of differentially expressed genes in mouse and human neurofibromas and MPNSTs. We tested functional significance of Aurora kinase over-expression in MPNST in vitro and in vivo using Aurora kinase shRNAs and compounds that inhibit Aurora kinase. Results We identified 2000 genes with probability of linkage to nerve Ras signaling of which 339 were significantly differentially expressed in mouse and human NF1-related tumor samples relative to normal nerves, including Aurora kinase A (AURKA). AURKA was dramatically over-expressed and genomically amplified in MPNSTs but not neurofibromas. Aurora kinase shRNAs and Aurora kinase inhibitors blocked MPNST cell growth in vitro. Furthermore, an AURKA selective inhibitor, MLN8237, stabilized tumor volume and significantly increased survival of mice with MPNST xenografts. Conclusion Integrative cross-species transcriptome analyses combined with preclinical testing has provided an effective method for identifying candidates for molecular-targeted therapeutics. Blocking Aurora kinases may be a viable treatment platform for MPNST. PMID:22811580

P-HPB-21: Isolated pancreatic tuberculosis mimicking inoperable pancreatic cancer

PubMed Central

Sahu, Manoj Kumar; Singh, Ayashkanta; Behera, Debasmita; Behera, Manas; Narayan, Jimmy

2017-01-01

Background: Pancreatic tuberculosis is an uncommon disease, presenting as hypoechoic mass on imaging mimicking malignancy. Consequently, it represents a diagnostic challenge necessitating a tissue diagnosis. Case Report: A 75-year-old female presented with progressive jaundice and weight loss; imaging with computed tomography (CT) showed a large (5.8 cm × 4.6 cm) pancreatic head mass with encasement of portal and superior mesenteric veins, peripancreatic nodes, atrophic pancreatic parenchyma, and dilated main pancreatic duct. Cancer antigen 19-9 was moderately elevated. With a diagnosis of inoperable pancreatic malignancy, she was planned for tissue diagnosis and palliative chemotherapy. Endoscopic ultrasonography (EUS) showed a heterogeneous mass with vascular invasion as in the CT. Fine needle aspiration (FNA) and biliary decompression with a plastic stent performed in the same sitting. Cytology demonstrated granuloma with caseous necrosis and presence of acid-fast bacilli. Antituberculosis treatment was started, and repeat CT after 6 months showed resolution of the mass. Discussion and Conclusion: A diagnosis of isolated pancreatic tuberculosis is rare and is difficult by clinical presentation alone; in India, it should be considered as a differential diagnosis of a pancreatic tumor. Benign lesions can also present with vascular invasions mimicking inoperable malignancy. EUS FNA is a very useful tool in accurate diagnosis of pancreatic head mass avoiding unnecessary surgeries.

Simple Clinical Score to Predict 24-Week Survival Times in Patients with Inoperable Malignant Distal Biliary Obstruction as a Tool for Selecting Palliative Metallic or Plastic Stents.

PubMed

Sripongpun, Pimsiri; Attasaranya, Siriboon; Chamroonkul, Naichaya; Sookpaisal, Theerapong; Khow-Ean, Uthai; Siripun, Aroon; Kongkamol, Chanon; Piratvisuth, Teerha; Ovartlarnporn, Bancha

2018-06-01

Endoscopic biliary drainage (EBD) is the mainstay treatment for inoperable malignant distal biliary obstruction (MDBO). Some authorities suggest that metallic stents are more cost-effective than plastic stents in patients with expected survival of at least 6 months. However, studies attempting to define the predictive factors for such survival times are limited. This study aims to develop a scoring system for predicting a survival time of <24 weeks in these patients. Patients with MDBO from inoperable periampullary cancers who underwent EBD at Songklanagarind Hospital during 2004-2009 were retrospectively analyzed. Baseline clinical, laboratory, and imaging data were retrieved. The survival time data were retrieved from the medical records and Thailand's civil registration database. Multivariate Cox regression model coefficients were used in the development of a survival time prediction scoring system. Ninety-eight patients were included. The overall median survival was 17.6 weeks. Fifty-seven (58.1%) survived <24 weeks. By multivariate analysis, cancer type and liver metastasis were significant predictive factors. The Simple Clinical Score (SCS) was calculated from (2× liver metastasis) + (1× pancreatic cancer) - (2× ampullary cancer) - (1× cholangiocarcinoma), when 1 and 0 were used for the presence and absence of each factor, respectively. The cutoff value of the score ≥0 had a sensitivity and specificity of 0.77 and 0.63, respectively, for predicting a survival time of <24 weeks, with AUC of 0.76. The median survival of patients with SCS <0 and ≥0 was 36.6 and 13.1 weeks, respectively. The scoring system from this study may be beneficial for clinicians to select the appropriate stents in endoscopic biliary drainage in inoperable MDBO patients.

Bronchoscopic drainage of a malignant lung abscess.

PubMed

Katsenos, Stamatis; Psathakis, Konstantinos; Chatzivasiloglou, Fotini; Antonogiannaki, Elvira-Markela; Psara, Anthoula; Tsintiris, Konstantinos

2015-04-01

Bronchoscopic drainage of a pyogenic lung abscess is an established therapeutic approach in selected patients in whom conventional antibiotic therapy fails. This intervention has also been undertaken in patients with abscess owing to underlying lung cancer and prior combined radiochemotherapy. However, this procedure has rarely been performed in cavitary lesions of advanced tumor origin before initiating any chemotherapy/radiotherapy scheme. Herein, we describe a case of a 68-year-old woman with lung adenocarcinoma stage IIIB, who underwent bronchoscopic drainage of necrotizing tumor lesion, thus improving her initial poor clinical condition and rendering other treatment modalities, such as radiotherapy, more effective and beneficial. Bronchoscopic drainage of a symptomatic cancerous lung abscess should be considered as an alternative and palliative treatment approach in patients with advanced inoperable non-small cell lung cancer.

Apparatus for stopping a vehicle

DOEpatents

Wattenburg, Willard H [Walnut Creek, CA; McCallen, David B [Livermore, CA

2007-03-20

An apparatus for externally controlling one or more brakes on a vehicle having a pressurized fluid braking system. The apparatus can include a pressurizable vessel that is adapted for fluid-tight coupling to the braking system. Impact to the rear of the vehicle by a pursuit vehicle, shooting a target mounted on the vehicle or sending a signal from a remote control can all result in the fluid pressures in the braking system of the vehicle being modified so that the vehicle is stopped and rendered temporarily inoperable. A control device can also be provided in the driver's compartment of the vehicle for similarly rendering the vehicle inoperable. A driver or hijacker of the vehicle preferably cannot overcome the stopping action from the driver's compartment.

Angioplasty and stent placement - peripheral arteries

MedlinePlus

... medlineplus.gov/ency/article/007393.htm Angioplasty and stent placement - peripheral arteries To use the sharing features ... inside the arteries and block blood flow. A stent is a small, metal mesh tube that keeps ...

Stereotactic body radiation therapy (SBRT) improves local control and overall survival compared to conventionally fractionated radiation for stage I non-small cell lung cancer (NSCLC).

PubMed

von Reibnitz, Donata; Shaikh, Fauzia; Wu, Abraham J; Treharne, Gregory C; Dick-Godfrey, Rosalind; Foster, Amanda; Woo, Kaitlin M; Shi, Weiji; Zhang, Zhigang; Din, Shaun U; Gelblum, Daphna Y; Yorke, Ellen D; Rosenzweig, Kenneth E; Rimner, Andreas

2018-06-06

Stereotactic body radiotherapy (SBRT) has been adopted as the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC), with local control rates consistently >90%. However, data directly comparing the outcomes of SBRT with those of conventionally fractionated radiotherapy (CONV) is lacking. Between 1990 and 2013, 497 patients (525 lesions) with early-stage NSCLC (T1-T2N0M0) were treated with CONV (n = 127) or SBRT (n = 398). In this retrospective analysis, five endpoints were compared, with and without adjusting for clinical and dosimetric factors. Competing risks analysis was performed to estimate and compare the cumulative incidence of local failure (LF), nodal failure (NF), distant failure (DF) and disease progression. Overall survival (OS) was estimated by the Kaplan-Meier method and compared by the Cox regression model. Propensity score (PS) matched analysis was performed based on seven patient and clinical variables: age, gender, Karnofsky performance status (KPS), histology, T stage, biologically equivalent dose (BED), and history of smoking. The median dose delivered for CONV was 75.6 Gy in 1.8-2.0 Gy fractions (range 60-90 Gy; median BED = 89.20 Gy) and for SBRT 48 Gy in four fractions (45-60 Gy in three to five fractions; median BED = 105.60 Gy). Median follow-up was 24.4 months, and 3-year LF rates were 34.1% with CONV and 13.6% with SBRT (p < .001). Three-year OS rates were 38.9 and 53.1%, respectively (p = .018). PS matching showed a significant improvement of OS (p = .0497) for SBRT. T stage was the only variable correlating with all five endpoints. SBRT compared to CONV is associated with improved LF rates and OS. Our data supports the continued use and expansion of SBRT as the standard of care treatment for inoperable early-stage NSCLC.

Cost-Effectiveness Analysis of Stereotactic Body Radiation Therapy Compared With Radiofrequency Ablation for Inoperable Colorectal Liver Metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Hayeon, E-mail: kimh2@upmc.edu; Gill, Beant; Beriwal, Sushil

Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account formore » model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.« less

Concurrent Chemotherapy and Radiation Therapy for Inoperable Locally Advanced Non-Small-Cell Lung Cancer.

PubMed

Rosenzweig, Kenneth E; Gomez, Jorge E

2017-01-01

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 72-year-old man with a 40-pack-year tobacco history developed a cough and decreased exercise tolerance. A chest x-ray demonstrated a right-upper-lobe opacity. Chest computed tomography (CT) scan revealed a 2.5-cm mass in the right upper lobe with multiple mediastinal lymph node disease ( Fig 1 ). A positron emission tomography (PET) scan confirmed the lung lesion and the mediastinal lymphadenopathy without distant metastases. Brain magnetic resonance imaging results were negative. The biopsy specimen revealed adenocarcinoma with no actionable mutations present. Cervical mediastinoscopy was positive for carcinoma in level 2, 3, 4R, and 7 lymph nodes; level 4L was negative. The patient's stage was T1bN2M0, stage IIIA. His medical history was significant for hyperlipidemia and hypothyroidism. He had smoked one pack a day for 40 years and had quit 15 years earlier. Physical examination was unrevealing, and the patient had an Eastern Cooperative Oncology Group performance status of 0. Because of the extent of lung cancer in the mediastinum, the patient's cancer was deemed inoperable, and he was referred for consideration of concurrent chemotherapy and radiation.

A new therapeutic proposal for inoperable osteosarcoma: Photodynamic therapy.

PubMed

de Miguel, Guilherme Chohfi; Abrantes, Ana Margarida; Laranjo, Mafalda; Grizotto, Ana Yoshie Kitagawa; Camporeze, Bruno; Pereira, José Aires; Brites, Gonçalo; Serra, Arménio; Pineiro, Marta; Rocha-Gonsalves, António; Botelho, Maria Filomena; Priolli, Denise Gonçalves

2018-03-01

Osteosarcoma, a malignant tumor characterized by bone or osteoid formation, is the second most common primary bone neoplasm. Clinical symptoms include local and surrounding pain, unrelieved by rest or anesthesia. Osteosarcoma has a poor chemotherapeutic response with prognosis dependent on complete tumor excision. Therefore, for inoperable osteosarcoma new therapeutic strategies are needed. The present study aimed to develop murine models of cranial and vertebral osteosarcoma that facilitate simple clinical monitoring and real-time imaging to evaluate the outcome of photodynamic therapy based on a previously developed photosensitizer. Balb/c nude mice were divided into two groups: the cranial and vertebral osteosarcoma groups. Each group was further subdivided into the photodynamic therapy-treated and untreated groups. Images were obtained by scintigraphy with 99m Tc-MIBI and radiography. Tumor growth, necrotic area, osteoid matrix area, and inflammatory infiltration were analyzed. Cranial and vertebral tumors could be macroscopically observed and measured. Radiographic and scintigraphic images showed tumor cells present at the inoculation sites. After photodynamic therapy, scintigraphy showed lower tumoral radiopharmaceutical uptake, which correlated histologically with increased necrosis. Osteoid matrix volume increased, and tumor size decreased in all photodynamic therapy-treated animals. Cranial and vertebral osteosarcoma models in athymic mice are feasible and facilitate in vivo monitoring for the development of new therapies. Photodynamic therapy is a potential antitumoral treatment for surgically inoperable osteosarcoma. Copyright © 2017 Elsevier B.V. All rights reserved.

Oral water soluble contrast for malignant bowel obstruction.

PubMed

Syrmis, William; Richard, Russell; Jenkins-Marsh, Sue; Chia, Siew C; Good, Phillip

2018-03-07

Malignant bowel obstruction (MBO) is a common problem in patients with intra-abdominal cancer. Oral water soluble contrast (OWSC) has been shown to be useful in the management of adhesive small bowel obstruction in identifying patients who will recover with conservative management alone and also in reducing the length of hospital stay. It is not clear whether the benefits of OWSC in adhesive small bowel obstruction are also seen in patients with MBO. To determine the reliability of OWSC media and follow-up abdominal radiographs in predicting the success of conservative treatment in resolving inoperable MBO with conservative management.To determine the efficacy and safety of OWSC media in reducing the duration of obstruction and reducing hospital stay in people with MBO. We identified studies from searching Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and MEDLINE in Process, Embase, CINAHL, Science Citation Index (Web of Science) and Conference Proceedings Citation Index - Science (Web of Science). We also searched registries of clinical trials and the CareSearch Grey Literature database. The date of the search was the 6 June 2017. Randomised controlled trials (RCTs), or prospective controlled studies, that evaluated the diagnostic potential of OWSC in predicting which malignant bowel obstructions will resolve with conservative treatment.RCTs, or prospective controlled studies, that assessed the therapeutic potential of OWSC in managing MBO at any level compared with placebo, no intervention or usual treatment or supportive care. We used standard methodological procedures expected by Cochrane. We assessed risk of bias and assessed the evidence using GRADE and created a 'Summary of findings' table. We found only one RCT meeting the selection criteria for the second objective (therapeutic potential) of this review. This study recruited nine participants. It compared the use of gastrografin versus placebo in adult patients with MBO with no indication for further intervention (surgery, endoscopy) apart from standardised conservative management.The overall risk of bias for the study was high due to issues with low numbers of participants, selective reporting of outcomes and a high attrition rate for the intervention arm.Primary outcomesThe included trial was a pilot study whose primary outcome was to test the feasibility for a large study. The authors reported specifically on the number of patients screened, the number recruited and reasons for exclusion; this was not the focus of our review.Due to the low number of participants, the authors of the study decided not to report on our primary outcome of assessing the ability of OWSC to predict the likelihood of malignant small bowel obstruction resolving with conservative treatment alone (diagnostic effect). It also did not report on our primary outcome of rate of resolution of MBO in patients receiving OWSC compared with those not receiving it (therapeutic effect).The study reported that no issues regarding safety or tolerability of either gastrografin or placebo were identified. The overall quality of the evidence for the incidence of adverse events with OWSC was very low, downgraded twice for serious limitations to study quality (high risk of selective reporting and attrition bias) and downgraded once for imprecision (sparse data).Secondary outcomesThe study planned to report on this review's secondary outcome measures of length of hospital stay and time from administration of OWSC to resolution of MBO. However the authors of the study decided not to do so due to the low numbers of patients recruited. The study did not report on our secondary outcome measure of survival times from onset of inoperable MBO until death. There is insufficient evidence from RCTs to determine the place of OWSC in predicting which patients with inoperable MBO will respond with conservative treatment alone. There is also insufficient evidence from RCTs to determine the therapeutic effects and safety of OWSC in patients with malignant small bowel obstruction.

High Intensity Focused Ultrasound Ablation of Pancreatic Neuroendocrine Tumours: Report of Two Cases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orgera, Gianluigi, E-mail: gianluigi.orgera@ieo.it; Krokidis, Miltiadis; Monfardini, Lorenzo

2011-04-15

We describe the use of ultrasound-guided high-intensity focused ultrasound (HIFU) for ablation of two pancreatic neuroendocrine tumours (NETs; insulinomas) in two inoperable young female patients. Both suffered from episodes of severe nightly hypoglycemia that was not efficiently controlled by medical treatment. After HIFU ablation, local disease control and symptom relief were achieved without postinterventional complications. The patients remained free of symptoms during 9-month follow-up. The lesions appeared to be decreased in volume, and there was decreased enhancing pattern in the multidetector computed tomography control (MDCT). HIFU is likely to be a valid alternative for symptoms control in patients with pancreaticmore » NETs. However, currently the procedure should be reserved for inoperable patients for whom symptoms cannot be controlled by medical therapy.« less

Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan.

PubMed

Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

2017-01-01

Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies.

Incidentally Detected Thyroid Follicular Neoplasm on Somatostatin Receptor Imaging and Post-therapy Scan

PubMed Central

Sood, Apurva; Singh, Harpreet; Sood, Ashwani; Basher, Rajender Kumar; Mittal, Bhagwant Rai

2017-01-01

Peptide receptor radionuclide therapy (PRRT) either using Lu-177 or Y-90 peptide radiopharmaceuticals has emerged as promising treatment modality in patients with inoperable metastatic neuroendocrine tumour (NET) including medullary thyroid cancer, because of overexpression of somatostatin receptor 2 (sstr-2) on these cells. The several investigators have used PRRT in non-iodine avid differentiated thyroid cancer patients with limited success, where other treatment modalities have failed, probably due to faint sstr-2 expression in these lesions. However Hurthle cell neoplasms being predominantly non-iodine avid lesions have shown sstr-2 over-expression. The present case of inoperable NET patient imaged and treated with radiolabelled somatostatin analogue showed incidentally detected thyroid lesion highlighting the its importance in imaging and treatment in these type of thyroid malignancies. PMID:28680210

Distinct Characteristics of Small Cell Lung Cancer Correlate With Central or Peripheral Origin: Subtyping Based on Location and Expression of Transcription Factor TTF-1.

PubMed

Miyauchi, Eisaku; Motoi, Noriko; Ono, Hiroshi; Ninomiya, Hironori; Ohyanagi, Fumiyoshi; Nishio, Makoto; Okumura, Sakae; Ichinose, Masakazu; Ishikawa, Yuichi

2015-12-01

Small-cell lung carcinoma (SCLC) is a type of lung cancer with neuroendocrine differentiation and a poor prognosis that is widely believed to arise in the central lung. Thyroid transcription factor-1 (TTF-1) is a peripheral marker of lung adenocarcinoma that is also highly expressed in SCLC. In this study, we examined whether SCLC is really a central-type tumor and the relationship between tumor location, TTF-1 expression and prognosis of SCLC.Ninety six SCLCs, diagnosed from biopsies or surgical materials, for which detailed computed tomography (CT) images were available, were collected consecutively from Japanese patients between 2004 and 2011. We examined the location of the primary tumor (central or peripheral) using thin-sliced CT, a TTF-1 immunohistochemical expression, and clinicopathology including prognosis.Of the 96 SCLCs, 74% (71/96) were of the peripheral type and found to have a significantly worse prognosis than central-type tumors. TTF-1 immunoreactivity was identified in 79 tumors (82%), 78% of which (62/79) were of the peripheral type and 22% of which were central. TTF-1 expression was significantly correlated with peripheral location (P = 0.030). Multivariate analysis revealed that high TNM stages and the peripheral location were independent markers for poor survival.The majority of SCLCs were of the peripheral type. The peripheral-type SCLC expressed TTF-1 more frequently and had a poorer prognosis than central-type tumors did. Further analysis on original sites of SCLC, using molecular methodology, or based on another ethnicity, should be warranted.

Brachytherapy Is Associated With Improved Survival in Inoperable Stage I Endometrial Adenocarcinoma: A Population-Based Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Acharya, Sahaja; Perkins, Stephanie M.; DeWees, Todd

2015-11-01

Purpose: To assess the use of brachytherapy (BT) with or without external beam radiation (EBRT) in inoperable stage I endometrial adenocarcinoma in the United States and to determine the effect of BT on overall survival (OS) and cause-specific survival (CSS). Methods and Materials: Data between 1998 and 2011 from the National Cancer Institute's Surveillance, Epidemiology and End Results database were analyzed. Coarsened exact matching was used to adjust for differences in age and grade between patients who received BT and those who did not. Prognostic factors affecting OS and CSS were evaluated using the Kaplan-Meier product-limit method and a Coxmore » proportional hazards regression model. Results: A total of 460 patients with inoperable stage I endometrial adenocarcinoma treated with radiation therapy were identified. Radiation consisted of either EBRT (n=260) or BT with or without EBRT (n=200). The only factor associated with BT use was younger patient age (median age, 72 vs 76 years, P=.001). Patients who received BT had a higher 3-year OS (60% vs 47%, P<.001) and CSS (82% vs 74%, P=.032) compared with those who did not. On multivariate analysis, BT use was independently associated with an improved OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.52-0.87) and CSS (HR 0.61, 95% CI 0.39-0.93). When patients were matched on age, BT use remained significant on multivariate analysis for OS (HR 0.65, 95% CI 0.48-0.87) and CSS (HR 0.52, 95% CI 0.31-0.84). When matched on age and grade, BT remained independently associated with improved OS and CSS (OS HR 0.62, 95% CI 0.46-0.83; CSS HR 0.57, 95% CI 0.34-0.92). Conclusion: Brachytherapy is independently associated with improved OS and CSS. It should be considered as part of the treatment regimen for stage I inoperable endometrial cancer patients undergoing radiation.« less

[Diagnosis and treatment of peripheral neuropathy induced by ANCA-associated vasculitis].

PubMed

Hattori, Naoki

2014-07-01

ANCA-associated vasculitis is induced by necrotizing angiitis of small vessels supplying the peripheral nervous system. Ischemic processes induce neuronal damage and axonal degeneration in the peripheral nerve. Motor dysfunction as well as sensory disturbance and allodynia caused by neuropathic symptoms may influence an individual's activities of daily living and quality of life. Notably, the peripheral nerve is predominantly affected in ANCA-associated vasculitis. We suggest that early diagnosis and appropriate treatment are important to improve survival in and functional prognosis of ANCA-associated vasculitis.

46 CFR 28.65 - Termination of unsafe operations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... freeboard; (6) Inoperable bilge system; (7) Intoxication of the master or individual in charge of a..., disposition, speech, muscular movement, general appearance or behavior is apparent by observation; (8) A lack...

46 CFR 28.65 - Termination of unsafe operations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... freeboard; (6) Inoperable bilge system; (7) Intoxication of the master or individual in charge of a..., disposition, speech, muscular movement, general appearance or behavior is apparent by observation; (8) A lack...

Modality-specific peripheral antinociceptive effects of μ-opioid agonists on heat and mechanical stimuli: Contribution of sigma-1 receptors.

PubMed

Montilla-García, Ángeles; Perazzoli, Gloria; Tejada, Miguel Á; González-Cano, Rafael; Sánchez-Fernández, Cristina; Cobos, Enrique J; Baeyens, José M

2018-06-01

Morphine induces peripherally μ-opioid-mediated antinociception to heat but not to mechanical stimulation. Peripheral sigma-1 receptors tonically inhibit μ-opioid antinociception to mechanical stimuli, but it is unknown whether they modulate μ-opioid heat antinociception. We hypothesized that sigma-1 receptors might play a role in the modality-specific peripheral antinociceptive effects of morphine and other clinically relevant μ-opioid agonists. Mechanical nociception was assessed in mice with the paw pressure test (450 g), and heat nociception with the unilateral hot plate (55 °C) test. Local peripheral (intraplantar) administration of morphine, buprenorphine or oxycodone did not induce antinociception to mechanical stimulation but had dose-dependent antinociceptive effects on heat stimuli. Local sigma-1 antagonism unmasked peripheral antinociception by μ-opioid agonists to mechanical stimuli, but did not modify their effects on heat stimulation. TRPV1+ and IB4+ cells are segregated populations of small neurons in the dorsal root ganglia (DRG) and the density of sigma-1 receptors was higher in IB4+ cells than in the rest of small nociceptive neurons. The in vivo ablation of TRPV1-expressing neurons with resiniferatoxin did not alter IB4+ neurons in the DRG, mechanical nociception, or the effects of sigma-1 antagonism on local morphine antinociception in this type of stimulus. However, it impaired the responses to heat stimuli and the effect of local morphine on heat nociception. In conclusion, peripheral opioid antinociception to mechanical stimuli is limited by sigma-1 tonic inhibitory actions, whereas peripheral opioid antinociception to heat stimuli (produced in TRPV1-expressing neurons) is not. Therefore, sigma-1 receptors contribute to the modality-specific peripheral effects of opioid analgesics. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evidence-Based Recommendations on Upper Gastrointestinal Tract Stenting: A Report from the Stent Study Group of the Korean Society of Gastrointestinal Endoscopy

PubMed Central

Jee, Sam Ryong; Kim, Kyung Ho; Kim, Sang Gyun; Cho, Jun-Hyung

2013-01-01

Endoscopic stents have evolved dramatically over the past 20 years. With the introduction of uncovered self-expanding metal stents in the early 1990s, they are primarily used to palliate symptoms of malignant obstruction in patients with inoperable gastrointestinal (GI) cancer. At present, stents have emerged as an effective, safe, and less invasive alternative for the treatment of malignant GI obstruction. Clinical decisions about stent placement should be made based on the exact understanding of the patient's condition. These recommendations based on a critical review of the available data and expert consensus are made for the purpose of providing endoscopists with information about stent placement. These can be helpful for management of patients with inoperable cancer or various nonmalignant conditions in the upper GI tract. PMID:23964331

Overview of HPM Effects in Electronics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holloway, Michael A.

2012-06-04

The following presentation contains an overview of HPM effects in modern electronics. HPM effects can be categorized into two basic level of effects, which are damaging and non-damaging. Damaging effects include junction breakdowns, dielectric breakdowns, and latch-up. These types of effects render a system inoperable until repaired. With non-damaging effects, HPM signals couple to into system components generating circuit responses that can overwhelm normal operation. Non-damaging effects can temporarily render a system inoperable or cause a system to lock and require a restart. Since modern systems are so complex, fundamental mechanisms of upset in circuit primitives are studied. All topicsmore » covered and all figured contained within are found in open literature. All data plots presented were obtained from experimental measurements conducted at the University of Maryland College Park and are also found in the open literature.« less

Hypofractionated accelerated CT-guided interstitial ¹⁹²Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer.

PubMed

Tselis, Nikolaos; Ratka, Markus; Vogt, Hans-Georg; Kolotas, Christos; Baghi, Mehran; Baltas, Dimos; Fountzilas, George; Georgoulias, Vassilios; Ackermann, Hanns; Zamboglou, Nikolaos

2011-01-01

Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC. From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0-36.0 Gy) in twice-daily fractions of 2.0-5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0-36.0 Gy) in once-daily fractions of 6.0-10.0 Gy in three patients. The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III-IV complications occurred in 13% of patients. In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effect of perioperative parecoxib sodium on postoperative pain control for transcatheter arterial chemoembolization for inoperable hepatocellular carcinoma: a prospective randomized trial.

PubMed

Lv, Ning; Kong, Yanan; Mu, Luwen; Pan, Tao; Xie, Qiankun; Zhao, Ming

2016-10-01

Pain is one of the most common side effects of transcatheter arterial chemoembolization (TACE) treatment. This study aimed to assess the analgesic effect of parecoxib sodium for postoperative pain control in patients with inoperable hepatocellular carcinoma (HCC) undergoing TACE. This randomized placebo-controlled prospective clinical study was conducted at a single cancer centre. Patients were randomly assigned to receive parecoxib sodium (experimental group; n = 60) or 0.9 % sodium chloride (control group; n = 60) 1 h before TACE and once every 12 h for 2 days after TACE. Pain level, morphine consumption, adverse events, and quality of life were evaluated and compared between the two groups. Pain scores, percentage distribution of pain categories, and morphine consumption were significantly lower in the experimental group than in the control group (P < 0.05). Fever score comparisons revealed significantly better body temperature balance in the experimental group than in the control group (P = 0.024). Quality-of-life scores in the experimental group were significantly better than those in the control group (P < 0.05). Our results demonstrate that the perioperative administration of parecoxib significantly improved its effectiveness in the control of postoperative pain after TACE. • Perioperative administration of parecoxib is effective for control of pain after TACE. • COX-2 inhibitors provide effective and safe pain control. • Parecoxib helps improve quality-of-life after TACE for patients with inoperable hepatocellular carcinoma.

Clinical, physiological and pathological characterisation of the sensory predominant peripheral neuropathy in copper deficiency.

PubMed

Taylor, Sean W; Laughlin, Ruple S; Kumar, Neeraj; Goodman, Brent; Klein, Christopher J; Dyck, Peter J; Dyck, P James B

2017-10-01

Myelopathy is considered the most common neurological complication of copper deficiency. Concurrent peripheral neuropathy has been recognised in association with copper deficiency but has not been well characterised. To characterise the clinical, physiological and pathological features of copper-deficient peripheral neuropathy. Patients with simultaneous copper deficiency (<0.78 μg/mL) and peripheral neuropathy seen at the Mayo Clinic from 1985 to 2005 were identified. 34 patients were identified (median age 55 years, range 36-78) including 24 women and 10 men. Myelopathy was found in 21 patients. Median serum copper level was 0.11 μg/mL (range 0-0.58). The most frequent clinical and electrophysiological pattern of neuropathy was a sensory predominant length-dependent peripheral neuropathy (71%). Somatosensory evoked potentials demonstrated central slowing supporting myelopathy (96%). Quantitative sensory testing demonstrated both small and large fibre involvement (100%). Autonomic reflex screens (77%) and thermoregulatory sweat test (67%) confirmed sudomotor dysfunction. 14 cutaneous nerve biopsies revealed loss of myelinated nerve fibres (86%), increased regenerative clusters (50%), increased rates of axonal degeneration (91%) and increased numbers of empty nerve strands (73%). 71% of biopsies demonstrated epineurial perivascular inflammation. An axonal, length-dependent sensory predominant peripheral neuropathy causing sensory ataxia is characteristic of copper deficiency usually co-occurring with myelopathy. Neurophysiological testing confirms involvement of large, greater than small fibres. The pathological findings suggest axonal degeneration and repair. Inflammatory infiltrates are common but are small and of doubtful pathological significance. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Vaccine Therapy for Unresectable Chordoma

Cancer.gov

In this phase II clinical trial, adult patients with inoperable chordoma who are scheduled to undergo radiation therapy will be randomly assigned to receive a yeast-based vaccine that targets a protein called brachyury or a placebo injection.

A schematic eye model for the effects of translation and rotation of ocular components on peripheral astigmatism.

PubMed

Barnes, D A; Dunne, M C; Clement, R A

1987-01-01

The relative contributions of translation and rotation of the cornea and lens to peripheral astigmatic asymmetry have been investigated using a linear algebraic ray tracing method. It is believed that lenticular rotation is responsible for angle alpha, so bringing about peripheral astigmatic asymmetry, as normally occurs in human eyes over the temporal and nasal retina. Rotation of the cornea may be responsible for the small numbers of eyes which exhibit large amounts of peripheral astigmatic asymmetry. The effects of corneal rotation and translation on the dimensions of the entrance pupil are illustrated.

AmeriFlux BR-Sa1 Santarem-Km67-Primary Forest

DOE Data Explorer

Saleska, Scott [University of Arizona

2016-01-01

This is the AmeriFlux version of the carbon flux data for the site BR-Sa1 Santarem-Km67-Primary Forest. Site Description - The LBA Tapajos KM67 Mature Forest site is located in the Tapajos National Forest, a 450,000 ha closed-canopy upland forest in Amazonian Brazil. Bounded by the Tapajos River in the west and highway BR-163 to the east, the tower is located on a flat plateau (or planalto) that extends up to 150 km to the north, south, and east. Within the confines of the National Forest, anthropogenic disturbances are limited to a few small hunting trails. The surrounding stand is classified as primary or "old-growth"" predominantly by its uneven age distribution, emergent trees, numerous epiphytes and abundant large logs. In 2007 falling trees hit the tower guy wires rendering all instrumentation in-operational. After a complete restoration tower measurements resumed in August of 2008.

Simple Radiowave-Based Method For Measuring Peripheral Blood Flow Project

NASA Technical Reports Server (NTRS)

Oliva-Buisson, Yvette J.

2014-01-01

Project objective is to design small radio frequency based flow probes for the measurement of blood flow velocity in peripheral arteries such as the femoral artery and middle cerebral artery. The result will be the technological capability to measure peripheral blood flow rates and flow changes during various environmental stressors such as microgravity without contact to the individual being monitored. This technology may also lead to an easier method of detecting venous gas emboli during extravehicular activities.

Fracture mechanics modeling of popping event during daughter cell separation.

PubMed

Jiang, Yuxuan; Liang, Xudong; Guo, Ming; Cao, Yanping; Cai, Shengqiang

2018-05-10

Most bacteria cells divide by binary fission which is part of a bacteria cell cycle and requires tight regulations and precise coordination. Fast separation of Staphylococcus Aureus (S. Aureus) daughter cells, named as popping event, has been observed in recent experiments. The popping event was proposed to be driven by mechanical crack propagation in the peripheral ring which connected two daughter cells before their separation. It has also been shown that after the fast separation, a small portion of the peripheral ring was left as a hinge. In the article, we develop a fracture mechanics model for the crack growth in the peripheral ring during S. Aureus daughter cell separation. In particular, using finite element analysis, we calculate the energy release rate associated with the crack growth in the peripheral ring, when daughter cells are inflated by a uniform turgor pressure inside. Our results show that with a fixed inflation of daughter cells, the energy release rate depends on the crack length non-monotonically. The energy release rate reaches a maximum value for a crack of an intermediate length. The non-monotonic relationship between the energy release rate and crack length clearly indicates that the crack propagation in the peripheral ring can be unstable. The computed energy release rate as a function of crack length can also be used to explain the existence of a small portion of peripheral ring remained as hinge after the popping event.

Chronic ETA antagonist reverses hypertension and impairment of structure and function of peripheral small arteries in aortic stiffening.

PubMed

Guo, Xiaomei; Chen, Huan; Han, Ling; Haulon, Stephan; Kassab, Ghassan S

2018-02-15

Arterial stiffness may contribute to the pathogenesis of hypertension. The goal of this study is to elucidate the role of Endothelin-1 (ET-1) in aortic stiffening-induced hypertension through ET A receptor activation. An increase in aortic stiffness was created by use of a non-constrictive restraint, NCR on the abdominal aortic surface. A group of rats underwent aortic NCR or sham operation for 12 weeks and were then treated with ET A receptor antagonist BQ-123 for 3 weeks. We found that 12 weeks of aortic NCR significantly increased pulse and mean pressure and altered peripheral flow pattern, accompanied by an increased serum ET-1 level (p < 0.05). The increase in aortic stiffness (evidenced by an elevated pulse wave velocity) caused hypertrophic structural remodeling and decreased arterial compliance, along with an impaired endothelial function in peripheral small arteries. BQ-123 treatment only partially attenuated peripheral arterial hypertrophy and restored arterial compliance, but completely recovered endothelium function, and consequently restored local flow and lowered blood pressure. Our findings underscore the hemodynamic coupling between aortic stiffening and peripheral arterial vessels and flow dynamics through an ET A -dependent mechanism. ET A receptor blockade may have therapeutic potential for improving peripheral vessel structure and function in the treatment of aortic stiffness-induced hypertension.

31 CFR 341.8 - Payment or redemption during lifetime of owner.

Code of Federal Regulations, 2014 CFR

2014-07-01

... chores. (4) Cancer which is inoperable and progressive. (5) Damage to the brain or brain abnormality...) Certain progressive diseases which have resulted in the physical loss or atrophy of a limb, such as...

27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

Code of Federal Regulations, 2010 CFR

2010-04-01

..., or slide action; (ii) Has been rendered permanently inoperable; or (iii) Is an antique firearm; (4... manufacturer stating that sales will only be made to law enforcement agencies, law enforcement officers, or...

27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., or slide action; (ii) Has been rendered permanently inoperable; or (iii) Is an antique firearm; (4... manufacturer stating that sales will only be made to law enforcement agencies, law enforcement officers, or...

27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., or slide action; (ii) Has been rendered permanently inoperable; or (iii) Is an antique firearm; (4... manufacturer stating that sales will only be made to law enforcement agencies, law enforcement officers, or...

27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., or slide action; (ii) Has been rendered permanently inoperable; or (iii) Is an antique firearm; (4... manufacturer stating that sales will only be made to law enforcement agencies, law enforcement officers, or...

27 CFR 478.40 - Manufacture, transfer, and possession of semiautomatic assault weapons.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., or slide action; (ii) Has been rendered permanently inoperable; or (iii) Is an antique firearm; (4... manufacturer stating that sales will only be made to law enforcement agencies, law enforcement officers, or...

Modeling and simulation of emergent behavior in transportation infrastructure restoration

USGS Publications Warehouse

Ojha, Akhilesh; Corns, Steven; Shoberg, Thomas G.; Qin, Ruwen; Long, Suzanna K.

2018-01-01

The objective of this chapter is to create a methodology to model the emergent behavior during a disruption in the transportation system and that calculates economic losses due to such a disruption, and to understand how an extreme event affects the road transportation network. The chapter discusses a system dynamics approach which is used to model the transportation road infrastructure system to evaluate the different factors that render road segments inoperable and calculate economic consequences of such inoperability. System dynamics models have been integrated with business process simulation model to evaluate, design, and optimize the business process. The chapter also explains how different factors affect the road capacity. After identifying the various factors affecting the available road capacity, a causal loop diagram (CLD) is created to visually represent the causes leading to a change in the available road capacity and the effects on travel costs when the available road capacity changes.

Endoscopic Management of Tumor Bleeding from Inoperable Gastric Cancer

PubMed Central

Kim, Young-Il

2015-01-01

Tumor bleeding is not a rare complication in patients with inoperable gastric cancer. Endoscopy has important roles in the diagnosis and primary treatment of tumor bleeding, similar to its roles in other non-variceal upper gastrointestinal bleeding cases. Although limited studies have been performed, endoscopic therapy has been highly successful in achieving initial hemostasis. One or a combination of endoscopic therapy modalities, such as injection therapy, mechanical therapy, or ablative therapy, can be used for hemostasis in patients with endoscopic stigmata of recent hemorrhage. However, rebleeding after successful hemostasis with endoscopic therapy frequently occurs. Endoscopic therapy may be a treatment option for successfully controlling this rebleeding. Transarterial embolization or palliative surgery should be considered when endoscopic therapy fails. For primary and secondary prevention of tumor bleeding, proton pump inhibitors can be prescribed, although their effectiveness to prevent bleeding remains to be investigated. PMID:25844339

CANCER OF THE LUNG IN WOMEN

PubMed Central

Ottoman, Richard E.; Stein, Justin J.

1960-01-01

Cancer of the lung in women has the same signs and symptoms as in men, but the disease seems to advance more rapidly. Of 35 female patients, half were under radiation therapy (for inoperable tumor) within four months after the first manifestation. In three of the five who had no symptoms, the cancer when diagnosed was inoperable. Scalene node biopsy confirmed metastasis in nine of the eleven cases in which it was used, and this procedure should be used after diagnosis whenever metastasis is not evident. Of the 35 women, two received only chemotherapy, 32 radiotherapy. Only four were alive at the time of report—one without evidence of disease at 20 months, one with symptoms of disease at 11 months, two under chemotherapy at two months, For 29 who received palliative or radical irradiation to the primary tumor site, the median survival time was 26 weeks. PMID:14429438

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis.

PubMed

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity.

Can involved-field irradiation replace elective nodal irradiation in chemoradiotherapy for esophageal cancer? A systematic review and meta-analysis

PubMed Central

Wang, Xiaoyue; Miao, Chuanwang; Chen, Zhen; Li, Wanhu; Yuan, Shuanghu; Yu, Jinming; Hu, Xudong

2017-01-01

Chemoradiotherapy is the most common treatment for inoperable esophageal cancer. However, there is no consensus on the delineation of the clinical target volume. Elective nodal irradiation (ENI) is recommended for inoperable esophageal cancer. A few studies have reported a decrease in the incidence of radiation-related toxicity of involved-field irradiation (IFI) for esophageal cancer. A systematic review and pooled analysis were performed to determine whether IFI in definitive chemoradiotherapy was more beneficial than ENI for esophageal cancer. The results showed no significant differences in the overall survival and local control rates between the IFI and ENI arms. Meanwhile, the incidences of esophageal and lung toxicities were significantly decreased in the IFI arm. These results suggest that IFI is a feasible treatment option for locally advanced esophageal cancer, especially to minimize irradiation-related toxicity. PMID:28442917

The role of active muscle mass in determining the magnitude of peripheral fatigue during dynamic exercise.

PubMed

Rossman, Matthew J; Garten, Ryan S; Venturelli, Massimo; Amann, Markus; Richardson, Russell S

2014-06-15

Greater peripheral quadriceps fatigue at the voluntary termination of single-leg knee-extensor exercise (KE), compared with whole-body cycling, has been attributed to confining group III and IV skeletal muscle afferent feedback to a small muscle mass, enabling the central nervous system (CNS) to tolerate greater peripheral fatigue. However, as task specificity and vastly differing systemic challenges may have complicated this interpretation, eight males were studied during constant workload trials to exhaustion at 85% of peak workload during single-leg and double-leg KE. It was hypothesized that because of the smaller muscle mass engaged during single-leg KE, a greater magnitude of peripheral quadriceps fatigue would be present at exhaustion. Vastus lateralis integrated electromyogram (iEMG) signal relative to the first minute of exercise, preexercise to postexercise maximal voluntary contractions (MVCs) of the quadriceps, and twitch-force evoked by supramaximal magnetic femoral nerve stimulation (Qtw,pot) quantified peripheral quadriceps fatigue. Trials performed with single-leg KE (8.1 ± 1.2 min; 45 ± 4 W) resulted in significantly greater peripheral quadriceps fatigue than double-leg KE (10 ± 1.3 min; 83 ± 7 W), as documented by changes in the iEMG signal (147 ± 24 vs. 85 ± 13%), MVC (-25 ± 3 vs. -12 ± 3%), and Qtw,pot (-44 ± 6 vs. -33 ± 7%), for single-leg and double-leg KE, respectively. Therefore, avoiding concerns over task specificity and cardiorespiratory limitations, this study reveals that a reduction in muscle mass permits the development of greater peripheral muscle fatigue and supports the concept that the CNS tolerates a greater magnitude of peripheral fatigue when the source of group III/IV afferent feedback is limited to a small muscle mass.

Use of small gap anastomosis for the repair of peripheral nerve injury by cutting and sleeve jointing the epineurium.

PubMed

Wang, Peiji; Zhao, Jiaju; Jiang, Bo; Zhang, Yong

2015-05-01

Although epineurium neurorrhaphy is the most reliable and conventional method for the repair of peripheral nerve injury and is accepted as the gold standard, it is still far from ideal. Many attempts have been made to develop nerve anastomosis techniques. The aim of this study was to investigate the use of small gap anastomosis performed by cutting and sleeve jointing the epineurium for nerve repair. A 12-week study was performed using small gap anastomosis via cutting and sleeve jointing the epineurium, compared with epineurium neurorrhaphy in situ, to repair a rat sciatic nerve rupture. Three experimental groups were included: sham control (n = 8), small gap anastomosis (n = 16), and epineurium neurorrhaphy (n = 16). About 12 weeks after surgery, recovery was assessed with walking track analysis, electrophysiology, hematoxylin and eosin staining, immunohistochemistry, and electron microscopy. The sciatic nerve functional index observed in the small gap anastomosis group was significantly higher than that in the epineurium neurorrhaphy group (p < 0.05). In vivo electrophysiological analysis confirmed that the small gap anastomosis group showed a significantly higher conduction velocity than the epineurium neurorrhaphy group (p < 0.05). Postoperative morphometric analysis revealed better results after small gap anastomosis compared with epineurium neurorrhaphy. Small gap anastomosis via cutting and sleeve jointing the epineurium could be an alternative to epineurium neurorrhaphy for the repair of peripheral nerve injury, particularly, considering that the epineurium originates from native tissue that provides a suitable microenvironment for the selective regeneration of axons. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Implications of the Index Cholecystectomy and Timing of Referral for Radical Resection of Advanced Incidental Gallbladder Cancer

PubMed Central

Ausania, F; White, SA; French, JJ; Jaques, BC; Charnley, RM; Manas, DM

2015-01-01

Introduction Advanced (pT2/T3) incidental gallbladder cancer is often deemed unresectable after restaging. This study assesses the impact of the primary operation, tumour characteristics and timing of management on re-resection. Methods The records of 60 consecutive referrals for incidental gallbladder cancer in a single tertiary centre from 2003 to 2011 were reviewed retrospectively. Decision on re-resection of incidental gallbladder cancer was based on delayed interval restaging at three months following cholecystectomy. Demographics, index cholecystectomy data, primary pathology, CA19–9 tumour marker levels at referral and time from cholecystectomy to referral as well as from referral to restaging were analysed. Results Thirty-seven patients with pT2 and twelve patients with pT3 incidental gallbladder cancer were candidates for radical re-resection. Following interval restaging, 24 patients (49%) underwent radical resection and 25 (51%) were deemed inoperable. The inoperable group had significantly more patients with positive resection margins at cholecystectomy (p=0.002), significantly higher median CA19–9 levels at referral (p=0.018) and were referred significantly earlier (p=0.004) than the patients who had resectable tumours. On multivariate analysis, urgent referral (p=0.036) and incomplete cholecystectomy (p=0.048) were associated significantly with inoperable disease following restaging. Conclusions In patients with incidental, potentially resectable, pT2/T3 gallbladder cancer, inappropriate index cholecystectomy may have a significant impact on tumour dissemination. Early referral of breached tumours is not associated with resectability. PMID:25723690

Vismodegib and Gamma-Secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced or Metastatic Sarcoma

ClinicalTrials.gov

2016-06-09

Adult Alveolar Soft Part Sarcoma; Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Hemangioendothelioma; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Unclassified Pleomorphic Sarcoma; Chondrosarcoma; Clear Cell Sarcoma of the Kidney; Conjunctival Kaposi Sarcoma; Dermatofibrosarcoma Protuberans; Gastrointestinal Stromal Tumor; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Ovarian Sarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult Unclassified Pleomorphic Sarcoma of Bone; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Kaposi Sarcoma; Recurrent Osteosarcoma; Recurrent Uterine Corpus Sarcoma; Small Intestine Leiomyosarcoma; Stage III Adult Soft Tissue Sarcoma; Stage III Uterine Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Uterine Sarcoma; Unclassified Pleomorphic Sarcoma of Bone

77 FR 5743 - Special Anchorage Areas; Port of New York, NY

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... inoperable bilge pumps, which could in turn result in vessels taking on water and sinking, disrupting other... areas in Sheepshead Bay, NY at all times. During times of high winds, vessels moored near the edge of...

[Localizating and Extracting Small Peripheral Nodules of Lung with Simulating 
Radiaotherapy Combining Methylene Blue Staining].

PubMed

Mao, Feng; Zhang, Liang; Gu, Hengle; Zhang, Hui; Lv, Changxing; Shen-Tu, Yang

2016-09-20

With the extensively application of HRCT (high resolution CT) and the popularization of early lung cancer screening, the proportion of small nodullar lung cancer to be operated increases rapidly. Identifying the focus lesions quickly and accurately in operation has shown to be a challenge. We carried out this research trying to make use of and evaluate a new method that localizaes and extracts small peripheral pulmonary nodules by way of simulating radiaotherapy combining methylene blue staining. From February 2012 to January 2015, 97 patients with 100 peripheral pulmonary nodules ≤10 mm in size were simulated puncturing using a radiotherapy planning. When the anaesthesia came into use, methylene blue dye was injected to the virtually identified point corresponding to the surface point, according to the angle and depth previously computed by the radiotherapy planning. The video-assisted thoracoscopic surgery (VATS) wedge resections of the marked lesions were undertaken and the specimens were sent for frozen pathologic examination. The interval time from anesthesia-completing to puncture and injection, The interval time from methylene blue injection to identifying the stained area and the distances between the centre point of the stains and edge of coloured lesion were recorded. Our preoperative localization procedure was successful in 96 of 100 (96%) nodules. The interval time from anesthesia-completing to puncture and injection of methylene blue were (4.85±1.25) min. The interval time from methylene blue injection to identifying the stained area was (16.36±2.36) min. The distances between the centre point of the stains and edge of coloured lesion were (4.78±2.51) mm. No complication was observed in all participants. The new method of locating peripheral pulmonary nodules by simulating simulating radiaotherapy combining methylene blue staining has a high success rate and no complication for localizing small peripheral pulmonary lesions, avoiding the fear and pain of the patients untaken puncture without anaesthesia reducing radial damage.

Navigation bronchoscopy for diagnosis and small nodule location

PubMed Central

Muñoz-Largacha, Juan A.; Litle, Virginia R.

2017-01-01

Lung cancer continues to be the most common cause of cancer death. Screening programs for high risk patients with the use of low-dose computed tomography (CT) has led to the identification of small lung lesions that were difficult to identify using previous imaging modalities. Electromagnetic navigational bronchoscopy (ENB) is a novel technique that has shown to be of great utility during the evaluation of small, peripheral lesions, that would otherwise be challenging to evaluate with conventional bronchoscopy. The diagnostic yield of navigational bronchoscopy however is highly variable, with reports ranging from 59% to 94%. This variability suggests that well-defined selection criteria and standardized protocols for the use of ENB are lacking. Despite this variability, we believe that this technique is a useful tool evaluating small peripheral lung lesions when patients are properly selected. PMID:28446971

Full-Thickness Astigmatic Keratotomy Combined With Small-Incision Lenticule Extraction to Treat High-Level and Mixed Astigmatism.

PubMed

Kim, Bu Ki; Mun, Su Joung; Lee, Dae Gyu; Kim, Jae Ryun; Kim, Hyun Seung; Chung, Young Taek

2015-12-01

To explore the clinical effects of combined full-thickness astigmatic keratotomy and small-incision lenticule extraction (SMILE) in patients who are inoperable using SMILE alone. We included 13 eyes of 9 patients with high-level or mixed astigmatism who underwent full-thickness astigmatic keratotomy followed by SMILE (secondarily) to correct the residual refractive error. Six months after SMILE, the spherical equivalent was reduced from -4.83 ± 3.26 D to -0.17 ± 0.38 D (P < 0.001), and the astigmatism was reduced from 5.12 ± 0.96 D to 0.21 ± 0.22 D (P < 0.001). The uncorrected and corrected (CDVA) distance visual acuities improved from 1.07 ± 0.62 to 0.02 ± 0.13 (P < 0.001) and from 0.08 ± 0.14 to -0.01 ± 0.14 (P = 0.002), respectively. The CDVA improved by 1 or 2 Snellen lines in 8 cases (61.5%), and there was no loss in CDVA. All procedures were completed without intraoperative or postoperative complications. This combined procedure was effective and safe for the treatment of high-level or mixed astigmatism.

Stereotactic radiotherapy for early lung cancer: Evidence-based approach and future directions

PubMed Central

Chehade, Samer; Palma, David A.

2015-01-01

Aim To review key studies evaluating stereotactic radiotherapy in the setting of early-stage non-small cell lung cancer (NSCLC) for inoperable or high-risk patients, and discuss areas of ongoing research and clinical trials. Background The use of stereotactic radiotherapy for the treatment of early stage non-small cell lung cancer (NSCLC) has increased rapidly over the past decade. Numerous studies have reported outcomes for patients treated with SBRT who are unfit for surgical resection, or at high risk of surgical complications. Materials and methods A narrative review. Results The preponderance of evidence suggests that SBRT is associated with excellent local control (∼90% at 3 years) and a favorable toxicity profile. In patients with higher operative risks, such as the elderly and patients with severe COPD, SBRT may provide a less-toxic treatment than surgery with similar oncologic outcomes. Ongoing studies are evaluating the use of SBRT for locally advanced or oligometastatic NSCLC. Conclusions A large body of evidence now exists to support the use of SBRT for early-stage NSCLC. Decisions regarding the optimal choice of treatment should be individualized, and made in the context of a multidisciplinary team. PMID:26696779

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

ClinicalTrials.gov

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Peripheral neuroblastoma in a young Beagle dog.

PubMed

Matsushima, S; Maruyama, T; Torii, M

1998-01-01

A peripheral neuroblastoma was found in the abdominal cavity of a young male beagle dog. The large tumor mass involved the left kidney and both adrenal glands. Histologically, a major portion of the neoplasm consisted of lobulated sheets of small round cells with hyperchromatic nuclei mixed with polygonal cells and neuropil. Small clusters of polygonal cells with abundant eosinophilic cytoplasm and a trabecular growth pattern were observed adjacent to some of the tumor lobules. Small, round neoplastic cells metastasized to lumbar lymph nodes and also to the adrenal glands. The neoplastic cells were positive for neuron-specific enolase, synaptophysin, and neurofilament protein. Electron micrographs revealed intracytoplasmic dense core granules, microtubules, intermediate filaments, and desmosomes in the cytoplasm of the neoplastic cells.

Cisplatin and Fluorouracil Compared With Carboplatin and Paclitaxel in Treating Patients With Inoperable Locally Recurrent or Metastatic Anal Cancer

ClinicalTrials.gov

2017-12-07

Anal Basaloid Carcinoma; Anal Canal Cloacogenic Carcinoma; Anal Squamous Cell Carcinoma; Metastatic Anal Canal Carcinoma; Recurrent Anal Canal Carcinoma; Stage IIIB Anal Canal Cancer; Stage IV Anal Canal Cancer

75 FR 21349 - Notice of Lodging of Consent Decree Under the Clean Air Act and the Emergency Planning and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-23

... Community Right-To-Know Act. The Complaint alleges violations including the burning of diesel fuel with excessive sulfur; operating three diesel generators while air pollution control devices were inoperable...

Gallbladder Cancer Presenting with Jaundice: Uniformly Fatal or Still Potentially Curable?

PubMed

Tran, Thuy B; Norton, Jeffrey A; Ethun, Cecilia G; Pawlik, Timothy M; Buettner, Stefan; Schmidt, Carl; Beal, Eliza W; Hawkins, William G; Fields, Ryan C; Krasnick, Bradley A; Weber, Sharon M; Salem, Ahmed; Martin, Robert C G; Scoggins, Charles R; Shen, Perry; Mogal, Harveshp D; Idrees, Kamran; Isom, Chelsea A; Hatzaras, Ioannis; Shenoy, Rivfka; Maithel, Shishir K; Poultsides, George A

2017-08-01

Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.

Impulse Oscillometry and Spirometry Small-Airway Parameters in Mild to Moderate Bronchiectasis.

PubMed

Guan, Wei-Jie; Yuan, Jing-Jing; Gao, Yong-Hua; Li, Hui-Min; Zheng, Jin-Ping; Chen, Rong-Chang; Zhong, Nan-Shan

2016-11-01

Both impulse oscillometry and spirometry can reflect small-airway disorders. The objective of this work was to investigate the diagnostic value of impulse oscillometry and spirometry small-airway parameters and their correlation with radiology, disease severity, and sputum bacteriology in mild to moderate bronchiectasis (bronchiectasis severity index <9) and to validate these findings in sensitivity analyses (mild bronchiectasis). We recruited 94 subjects with mild to moderate bronchiectasis and 26 healthy subjects. The diagnostic value of small-airway parameters was compared using the receiver operating characteristic curve. Chest high-resolution computed tomography (HRCT), impulse oscillometry measurement, spirometry, and sputum culture were performed. Correlation between small-airway parameters and clinical indices was determined, adjusting for age, sex, body mass index, and smoking history. Sensitivity analyses were repeated when excluding subjects with bronchiectasis severity index ≥9 or HRCT score ≥13. Impulse oscillometry and spirometry small-airway parameters could discriminate mild to moderate bronchiectasis from healthy subjects and correlated significantly with HRCT score and the number of bronchiectatic lobes and the bronchiectasis severity index (all P < .01). Small-airway parameters were more aberrant in subjects with dyshomogeneity and cystic bronchiectasis but were independent of Pseudomonas aeruginosa isolation or the location of predominant bronchiectatic lobes. Spirometry, but not impulse oscillometry, small-airway parameters differed statistically between subjects with isolated peripheral-airway bronchiectasis and those with peripheral plus central-airway bronchiectasis (all P < .01). Subgroup analyses yielded similar findings, except for the lack of correlation between small-airway parameters and clinical parameters in subjects with HRCT score ≤6. Impulse oscillometry and spirometry small-airway parameters have similar diagnostic value in reflecting peripheral-airway disorders and correlate with the HRCT scores, the bronchiectasis severity index, and the number of bronchiectatic lobes in mild to moderate bronchiectasis. Assessment of small-airway parameters should be incorporated in future lung function investigations in bronchiectasis. Copyright © 2016 by Daedalus Enterprises.

Electromagnetic navigational bronchoscopy with dye marking for identification of small peripheral lung nodules during minimally invasive surgical resection

PubMed Central

Muñoz-Largacha, Juan A.; Ebright, Michael I.; Litle, Virginia R.

2017-01-01

Background Identification of small peripheral lung nodules during minimally invasive resection can be challenging. Electromagnetic navigational bronchoscopy (ENB) with injection of dye to identify nodules can be performed by the surgeon immediately prior to resection. We evaluated the effectiveness of ENB with dye marking to aid minimally invasive resection. Methods Patients with peripheral pulmonary nodules underwent ENB before planned thoracoscopic or robotic-assisted thoracoscopic resection. Methylene blue was injected directly into the lesion for pleural-based lesions or peripherally for lesions deep to the pleural surface. Surgical resection was then immediately performed. Technical success was defined as identification of the dye marking within/close to the lesion with pathological confirmation after minimally invasive surgical resection. Results Seventeen patients (19 nodules) underwent ENB with dye marking followed by minimally invasive resection. Median lesion size was 9 mm (4–32 mm) and the median distance from the pleura was 9.5 mm (1–40 mm). Overall success rate was 79% (15/19). In two cases the dye was not visualized and in the remaining two there was extravasation of dye into the pleural space. There were trends favoring technical success for nodules that were larger or closer to the pleural surface. Five patients required adhesiolysis to visualize the target lesion and all were successful. There were no significant adverse events and a definitive diagnosis was ultimately accomplished in all patients. Conclusions ENB with dye marking is useful for guiding minimally invasive resection of small peripheral lung nodules. ENB can be undertaken immediately before performing resection in the operating room. This improves workflow and avoids the need for a separate localization procedure. PMID:28449489

PHOX2B reliably distinguishes neuroblastoma among small round blue cell tumours.

PubMed

Hung, Yin P; Lee, John P; Bellizzi, Andrew M; Hornick, Jason L

2017-11-01

Neuroblastoma shows considerable histological overlap with other small round blue cell tumours. PHOX2B, a transcription factor that is essential for autonomic nervous system development, has been reported as an immunohistochemical marker for neuroblastoma. The aim of this study was to validate the specificity and diagnostic utility of PHOX2B for peripheral neuroblastic tumours. We evaluated 240 cases (133 in whole-tissue sections; 107 in tissue microarrays), including 76 peripheral neuroblastic tumours (median age 2 years; including four adults) and 164 other tumours: 44 Wilms tumours; 20 Ewing sarcomas; 10 each of CIC-rearranged round cell sarcomas, poorly differentiated synovial sarcomas, lymphoblastic lymphomas, alveolar rhabdomyosarcomas, embryonal rhabdomyosarcomas, mesenchymal chondrosarcomas, Merkel cell carcinomas, olfactory neuroblastomas, and melanomas; and five each of NUT midline carcinomas and desmoplastic small round cell tumours. Immunohistochemistry for PHOX2B was performed with a rabbit monoclonal antibody. PHOX2B positivity was defined as the presence of nuclear immunoreactivity in ≥5% of cells. PHOX2B was positive in 70 (92%) peripheral neuroblastic tumours, including 68 of 72 (94%) paediatric and two of four (50%) adult cases. Furthermore, PHOX2B was consistently negative in all non-peripheral neuroblastic tumours, with staining being absent in 160 cases and limited in four cases. PHOX2B is a highly sensitive and specific immunohistochemical marker for peripheral neuroblastic tumours, including neuroblastoma. PHOX2B reliably distinguishes neuroblastoma from histological mimics such as Wilms tumour, Ewing sarcoma, and CIC-rearranged round cell sarcoma. PHOX2B negativity in two of four adult neuroblastoma cases raises the possibility that some adult neuroblastomas are of a different lineage than paediatric cases. © 2017 John Wiley & Sons Ltd.

[Peripheral lymphadenopathy in childhood--recommendations for diagnostic evaluation].

PubMed

Benesch, M; Kerbl, R; Wirnsberger, A; Stünzner, D; Mangge, H; Schenkeli, R; Deutsch, J

2000-01-01

Enlargement of peripheral lymph nodes most commonly caused by a local inflammatory process is frequently seen in childhood. The aim of the present study was to analyze the most common causes of peripheral lymphadenopathy and to develop a simple algorithm for the primary diagnostic evaluation of peripheral lymph node enlargement in this age group. Between April and September 1999 87 unselected children (median age: 5 1/2 years) with peripheral lymphadenopathy were referred to the Department of Pediatrics, University of Graz, for further investigation. EBV infection was diagnosed in 20 (23.0%) children. 19 (21.8%) patients had acute bacterial lymphadenitis. In 21 (24.1%) patients lymph node enlargement was classified as "post/parainfectious (viral)". Four patients each had toxoplasmosis and cat scratch disease. In 11 (12.6%) patients neither physical nor laboratory examinations revealed pathologic results. Among the remaining 8 children sarcoidosis and Hodgkin disease was diagnosed in one patient each. Small, soft, mobile, nontender, cervical, axillary or inguinal lymph nodes do not require further investigations. In case of enlarged, tender lymph nodes with overlying skin erythema and fever diagnostic evaluation should include complete blood count, erythrocyte sedimentation rate and/or c-reactive protein level, supplemented by appropriate antibody testing (EBV, CMV, Toxoplasma gondii, Bartonella henselae). Firm, enlarged, painless lymph nodes which are matted together and fixed to the skin or underlying tissues necessitate a more detailed diagnostic evaluation in order to exclude malignant or granulomatous diseases. Our study demonstrated that primary diagnostic evaluation of childhood peripheral lymphadenopathy is mainly based on clinical grounds. In most cases a small number of additionally performed laboratory tests allow to correctly identify the cause of the peripheral lymph node enlargement.

Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures.

PubMed

Lee, T H; Moon, J H; Kim, J H; Park, D H; Lee, S S; Choi, H J; Cho, Y D; Park, S H; Kim, S J

2013-01-01

Endoscopic bilateral drainage for inoperable malignant hilar biliary strictures (HBS) using metal stents is considered to be technically difficult. Furthermore, endoscopic revision of bilateral stenting after occlusion can be challenging. This study was performed to evaluate the long-term efficacy of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents in high-grade malignant HBS and planned endoscopic bilateral revision. A total of 84 patients with inoperable high-grade malignant HBS were enrolled from three academic tertiary referral centers. Two cross-wired metal stents were inserted using a bilateral stent-in-stent placement method. Bilateral endoscopic revision was also performed during follow-up using either identical metal stents or plastic stents. The main outcome measurements were technical and functional success, complications, stent patency, and endoscopic revision efficacy. The technical and clinical success rates of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents were 95.2% (80/84) and 92.9% (78/84), respectively. Median patency (range) and survival were 238 days (10-429) and 256 days (10-1130), respectively. Obstruction of primary bilateral stents occurred in 30.8% (24/78) of patients with functionally successful stent placement. The technical and clinical success rates of planned bilateral endoscopic revision for occluded stents were 83.3% (20/24) and 79.2% (19/24), respectively. For revision, bilateral metallic stents were placed in 11 patients (55.0%); the remaining patients received plastic stents. Palliative endoscopic bilateral stent-in-stent placement of cross-wired metallic stents was effective in patients with inoperable HBS. Revision endoscopic bilateral stenting may be feasible and successful in cases where the primary deployed metal stents are occluded. © Georg Thieme Verlag KG Stuttgart · New York.

Prospective Multicenter Study on the Challenges Inherent to Using Large Cell-Type Stents for Bilateral Stent-in-Stent Placement in Patients with Inoperable Malignant Hilar Biliary Obstruction.

PubMed

Yang, Min Jae; Kim, Jin Hong; Hwang, Jae Chul; Yoo, Byung Moo; Lee, Sang Hyub; Ryu, Ji Kon; Kim, Yong-Tae; Woo, Sang Myung; Lee, Woo Jin; Jeong, Seok; Lee, Don Haeng

2018-06-22

Although endoscopic bilateral stent-in-stent placement is challenging, many recent studies have reported promising outcomes regarding technical success and endoscopic reintervention. This study aimed to evaluate the technical feasibility of stent-in-stent placement using large cell-type stents in patients with inoperable malignant hilar biliary obstruction. Forty-three patients with inoperable malignant hilar biliary obstruction from four academic centers were prospectively enrolled from March 2013 to June 2015. Bilateral stent-in-stent placement using two large cell-type stents was successfully performed in 88.4% of the patients (38/43). In four of the five cases with technical failure, the delivery sheath of the second stent became caught in the hook-cross-type vertex of the large cell of the first stent, and subsequent attempts to pass a guidewire and stent assembly through the mesh failed. Functional success was achieved in all cases with technical success. Stent occlusion occurred in 63.2% of patients (24/38), with a median patient survival of 300 days. The median stent patency was 198 days. The stent patency rate was 82.9%, 63.1%, and 32.1% at 3, 6, and 12 months, respectively. Endoscopic re-intervention was performed in 14 patients, whereas 10 underwent percutaneous drainage. Large cell-type stents for endoscopic bilateral stent-in-stent placement showed acceptable functional success and stent patency when technically successful. However, the technical difficulty associated with the entanglement of the second stent delivery sheath in the hook-cross-type vertex of the first stent may preclude large cell-type stents from being considered as a dedicated standard tool for stent-in-stent placement.

Variation in palliative care of esophageal cancer in clinical practice: factors associated with treatment decisions.

PubMed

Opstelten, Jorrit L; de Wijkerslooth, Laetitia R H; Leenders, Max; Bac, Dirk Jan; Brink, Menno A; Loffeld, Boudewijn C A J; Meijnen-Bult, Mariëlle J F; Minderhoud, Itta M; Verhagen, Marc A M T; van Oijen, Martijn G H; Siersema, Peter D

2017-02-01

Various treatments are available for the palliation of esophageal cancer, but the optimal therapeutic approach is unclear. This study aimed to assess the palliative treatment modalities used in patients with inoperable esophageal cancer and to identify factors associated with treatment decisions. A population-based, retrospective cohort study was conducted using data from the nationwide Netherlands Cancer Registry and medical records of seven participating hospitals. Patients diagnosed with stage III-IV inoperable esophageal or gastric cardia cancer in the central part of the Netherlands between 2001 and 2010 were included. Logistic regression analyses were performed to identify determinants of treatment choices. In total, 736 patients were initially treated with best supportive care (21%), stent placement (19%), chemotherapy (18%), external beam radiotherapy (EBRT) (16%), brachytherapy (6%), a combination of EBRT and brachytherapy (6%), a combination of chemotherapy and EBRT (5%) or another treatment (9%). The palliative approach varied for disease stage (P < 0.01) and hospital of diagnosis (P < 0.01). Independent factors affecting treatment decisions were age, degree of dysphagia, tumor histology, tumor localization, disease stage, and hospital of diagnosis. For example, patients diagnosed in one hospital were less likely to be treated with EBRT than with stent placement compared to patients in another hospital (odds ratio 0.20, 95% confidence interval 0.07-0.59). In conclusion, the initial palliative approach of patients with inoperable esophageal cancer varies widely and is not only associated with patient- and disease-related factors, but also with hospital of diagnosis. These findings suggest a lack of therapeutic guidance and highlight the need for more evidence on palliative care strategies for esophageal cancer. © 2016 International Society for Diseases of the Esophagus.

Interventional bronchoscopy for treatment of tracheal obstruction secondary to benign or malignant thyroid disease.

PubMed

Noppen, Marc; Poppe, Kris; D'Haese, Jan; Meysman, Marc; Velkeniers, Brigitte; Vincken, Walter

2004-02-01

Surgery is the treatment of choice for symptomatic tracheal obstruction due to benign or malignant thyroid disease. In case of inoperability, or when surgery is refused, few therapeutic alternatives are available. Interventional bronchoscopic procedures have only been reported anecdotally. The objective of this study is to evaluate the results of interventional bronchoscopic procedures in the treatment of severe tracheal obstruction due to thyroid disease. Retrospective cohort analysis. University hospital, tertiary referral center. Thirty consecutive patients referred for bronchoscopic treatment of benign (n = 17) or malignant (n = 13) thyroid-related upper airway obstruction due to tracheomalacia, extrinsic compression, and/or tracheal ingrowth. Indications for bronchoscopic treatment were medical or surgical inoperability, prevention or treatment of tracheomalacia, and refusal of surgery. There were no procedure-related complications. Rigid bronchoscopy with dilatation, stenting and/or Nd-YAG laser treatment, and clinical follow-up. Subjective improvement, pulmonary function tests, early and late complications, and survival. In the benign group, immediate (100% relief of dyspnea) and long-term (88% relief of dyspnea) results were excellent after airway stenting (21 stents used in 17 patients). There was one unrelated death 1 week after stenting in a 98-year-old patient. There were 6% and 30% short-term and long-term complications, respectively, that could be managed endoscopically. In the malignant group, Nd-YAG laser treatment (n = 3) and stenting (n = 13) yielded immediate and long-term success in 92% of patients. There were 15% short-term and 8% long-term complications. Median survival time was 540 days. Interventional bronchoscopic procedures including Nd-YAG laser treatment and stenting are valuable alternatives to surgery in inoperable thyroid-induced tracheal obstruction, or when surgery is refused.

Using binary statistics in Taurus-Auriga to distinguish between brown dwarf formation processes

NASA Astrophysics Data System (ADS)

Marks, M.; Martín, E. L.; Béjar, V. J. S.; Lodieu, N.; Kroupa, P.; Manjavacas, E.; Thies, I.; Rebolo López, R.; Velasco, S.

2017-08-01

Context. One of the key questions of the star formation problem is whether brown dwarfs (BDs) form in the manner of stars directly from the gravitational collapse of a molecular cloud core (star-like) or whether BDs and some very low-mass stars (VLMSs) constitute a separate population that forms alongside stars comparable to the population of planets, for example through circumstellar disk (peripheral) fragmentation. Aims: For young stars in Taurus-Auriga the binary fraction has been shown to be large with little dependence on primary mass above ≈ 0.2 M⊙, while for BDs the binary fraction is < 10%. Here we investigate a case in which BDs in Taurus formed dominantly, but not exclusively, through peripheral fragmentation, which naturally results in small binary fractions. The decline of the binary frequency in the transition region between star-like formation and peripheral formation is modelled. Methods: We employed a dynamical population synthesis model in which stellar binary formation is universal with a large binary fraction close to unity. Peripheral objects form separately in circumstellar disks with a distinctive initial mass function (IMF), their own orbital parameter distributions for binaries, and small binary fractions, according to observations and expectations from smoothed particle hydrodynamics (SPH) and grid-based computations. A small amount of dynamical processing of the stellar component was accounted for as appropriate for the low-density Taurus-Auriga embedded clusters. Results: The binary fraction declines strongly in the transition region between star-like and peripheral formation, exhibiting characteristic features. The location of these features and the steepness of this trend depend on the mass limits for star-like and peripheral formation. Such a trend might be unique to low density regions, such as Taurus, which host binary populations that are largely unprocessed dynamically in which the binary fraction is large for stars down to M-dwarfs and small for BDs. Conclusions: The existence of a strong decline in the binary fraction - primary mass diagram will become verifiable in future surveys on BD and VLMS binarity in the Taurus-Auriga star-forming region. The binary fraction - primary mass diagram is a diagnostic of the (non-)continuity of star formation along the mass scale, the separateness of the stellar and BD populations, and the dominant formation channel for BDs and BD binaries in regions of low stellar density hosting dynamically unprocessed populations.

SU-E-T-538: Does Abdominal Compression Through Prone Patient Position Reduce Respiratory Motion in Lung Cancer Radiotherapy?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Catron, T; Rosu, M; Weiss, E

2014-06-01

Purpose: This study assesses the effect of physiological abdominal compression from prone positioning by comparing respiratory-induced tumor movements in supine and prone positions. Methods: 19 lung cancer patients underwent repeated supine and prone free-breathing 4DCT scans. The effect of patient position on motion magnitude was investigated for tumors, lymph nodes (9 cases), and subgroups of central (11 cases), peripheral (8 cases) and small peripheral tumors (5 cases), by evaluating the population average excursions, absolute and relative to a carina-point. Results: Absolute motion analysis: In prone, motion increased by ~20% for tumors and ~25% for lymph nodes. Central tumors moved moremore » compared to peripheral tumors in both supine and prone (~22%, and ~4% respectively). Central tumors movement increased by ~12% in prone. For peripheral tumors the increase in prone position was ~25% (~40% and 29% changes on along RL and AP directions). Motion relative to carina-point analysis: Overall, tumor excursions relative to carina-point increased by ~17% in prone. Lymph node relative magnitudes were lower by ~4%. Likewise, the central tumors moved ~7% less in prone. The subgroup of peripheral tumors exhibited increased amplitudes by ~44%; the small peripheral tumors had even larger relative displacements in prone (~46%). Conclusion: Tumor and lymph node movement in the patient population from this study averaged to be higher in prone than in supine position. Results from carina analysis also suggest that peripheral tissues have more physiologic freedom of motility when placed in the prone position, regardless of size. From these observations we should continue to avoid prone positioning for all types of primary lung tumor, suggesting that patients should receive radiotherapy for primary lung cancer in supine position to minimize target tissue mobility during normal respiratory effort. Further investigation will include more patients with peripheral tumors to validate our observations.« less

Identification and isolation from either adult human bone marrow or G-CSF-mobilized peripheral blood of CD34(+)/CD133(+)/CXCR4(+)/ Lin(-)CD45(-) cells, featuring morphological, molecular, and phenotypic characteristics of very small embryonic-like (VSEL) stem cells.

PubMed

Sovalat, Hanna; Scrofani, Maurice; Eidenschenk, Antoinette; Pasquet, Stéphanie; Rimelen, Valérie; Hénon, Philippe

2011-04-01

Recently, we demonstrated that normal human bone marrow (hBM)-derived CD34(+) cells, released into the peripheral blood after granulocyte colony-stimulating factor mobilization, contain cell subpopulations committed along endothelial and cardiac differentiation pathways. These subpopulations could play a key role in the regeneration of post-ischemic myocardial lesion after their direct intracardiac delivery. We hypothesized that these relevant cells might be issued from very small embryonic-like stem cells deposited in the BM during ontogenesis and reside lifelong in the adult BM, and that they could be mobilized into peripheral blood by granulocyte colony-stimulating factor. Samples of normal hBM and leukapheresis products harvested from cancer patients after granulocyte colony-stimulating factor mobilization were analyzed and sorted by multiparameter flow cytometry strategy. Immunofluorescence and reverse transcription quantitative polymerase chain reaction assays were performed to analyze the expression of typical pluripotent stem cells markers. A population of CD34(+)/CD133(+)/CXCR4(+)/Lin(-) CD45(-) immature cells was first isolated from the hBM or from leukapheresis products. Among this population, very small (2-5 μm) cells expressing Oct-4, Nanog, and stage-specific embryonic antigen-4 at protein and messenger RNA levels were identified. Our study supports the hypothesis that very small embryonic-like stem cells constitute a "mobile" pool of primitive/pluripotent stem cells that could be released from the BM into the peripheral blood under the influence of various physiological or pathological stimuli. In order to fully support that hBM- and leukapheresis product-derived very small embryonic-like stem cells are actually pluripotent, we are currently testing their ability to differentiate in vitro into cells from all three germ layers. Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.

50 CFR 697.22 - Exempted fishing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... American lobster, weakfish, Atlantic red drum, Atlantic striped bass, Atlantic sturgeon, or horseshoe crab... the exemption will not: (1) Have a detrimental effect on the American lobster, weakfish, Atlantic red..., may authorize a substitute vessel to haul ashore the lobster trap gear of an inoperable or...

50 CFR 697.22 - Exempted fishing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... American lobster, weakfish, Atlantic red drum, Atlantic striped bass, Atlantic sturgeon, or horseshoe crab... the exemption will not: (1) Have a detrimental effect on the American lobster, weakfish, Atlantic red..., may authorize a substitute vessel to haul ashore the lobster trap gear of an inoperable or...

Killing Cancer Cells with the Help of Infrared Light – Photoimmunotherapy

Cancer.gov

Near-infrared photoimmunotherapy uses an antibody–photoabsorber conjugate that binds to cancer cells. When near-infrared light is applied, the cells swell and then burst, causing the cancer cell to die. Photoimmunotherapy is in clinical trials in patients with inoperable tumors.

9 CFR 86.4 - Official identification.

Code of Federal Regulations, 2014 CFR

2014-01-01

... the ear); (iii) Malfunction of the electronic component of a radio frequency identification (RFID) device; or (iv) Incompatibility or inoperability of the electronic component of an RFID device with the management system or unacceptable functionality of the management system due to use of an RFID device. (2...

Special Operations Forces--Responsive, Capable, and Ready

DTIC Science & Technology

1990-05-01

communication Planning Criticisms of poor communications that hammeted mission success rangea from radio inoperability amorng raid force elements to strict...ons, an armory. and a means of rapid escape are also face the Unenviable choice of rushing light and inad- normally part of the complex. equate

29 CFR 1917.116 - Elevators and escalators.

Code of Federal Regulations, 2010 CFR

2010-07-01

... or more floors of a structure. The term excludes such devices as conveyors, tiering or piling... devices shall not be overridden or made inoperable. (e) Elevators and escalators shall be thoroughly... shall be conducted by designated persons. Records of the results of the latest annual elevator...

Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

ClinicalTrials.gov

2017-12-05

B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

76 FR 73727 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... Detection Instrumentation,'' to define a new time limit for restoring inoperable RCS leakage detection... Specifications Section 3.4.15 regarding reactor coolant leakage detection instrumentation to be consistent with... amendments revised the Technical Specifications (TSs) ``RCS [reactor coolant system] Leakage Detection...

Measuring Global Position Using the Sun

ERIC Educational Resources Information Center

Murphy, Evan; Hughes, Stephen

2014-01-01

The determination of latitude and longitude on Earth has always been of interest to explorers and cartographers alike. Accurate positional information is often needed for rescue purposes in locations where satellite navigational systems are inoperable. The activity described in this paper demonstrates a simple procedure to determine latitude and…

Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.

Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{submore » 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.« less

Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

ClinicalTrials.gov

2013-06-03

Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

36 CFR 1002.4 - Weapons, traps and nets.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Weapons, traps and nets. 1002.4 Section 1002.4 Parks, Forests, and Public Property PRESIDIO TRUST RESOURCE PROTECTION, PUBLIC USE... temporary lodging or mechanical mode of conveyance when such implements are rendered temporarily inoperable...

36 CFR 1002.4 - Weapons, traps and nets.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Weapons, traps and nets. 1002.4 Section 1002.4 Parks, Forests, and Public Property PRESIDIO TRUST RESOURCE PROTECTION, PUBLIC USE... temporary lodging or mechanical mode of conveyance when such implements are rendered temporarily inoperable...

77 FR 13369 - Biweekly Notice Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-06

...] Leakage Detection Systems,'' to define a new time limit for restoring inoperable RCS leakage detection instrumentation to operable status, establish alternate methods of monitoring RCS leakage when monitors are... design bases related to the operability of the RCS leakage detection instrumentation. Date of issuance...

75 FR 79048 - Notice of Availability of the Models for Plant-Specific Adoption of Technical Specifications Task...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-17

... Specifications (STS) to define a new time limit for restoring inoperable RCS leakage detection instrumentation to... operability of the RCS leakage detection instrumentation. The CLIIP model SE will facilitate expedited... Operability Requirements and Actions for RCS Leakage Instrumentation'' AGENCY: Nuclear Regulatory Commission...

76 FR 37845 - Biweekly Notice; Applications and Amendments to Facility Operating Licenses Involving No...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... define a new time limit for restoring inoperable Reactor Coolant System (RCS) leakage detection... RCS leakage detection instrumentation. These changes are consistent with NRC-approved Revision 3 to...? Response: No. The proposed change clarifies the operability requirements for the RCS leakage detection...

76 FR 23801 - North American Electric Reliability Corporation; Order Approving Reliability Standard

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-28

... primary control functionality. Nonetheless, until data from drills, exercises and tests can support a... control center becomes inoperable and to conduct reviews and tests, at least annually, to ensure viability... Preparedness and Operations (EOP) Reliability Standard EOP- 008-1 (Loss of Control Center Functionality). The...

Correction to: Real-World Switching to Riociguat: Management and Practicalities in Patients with PAH and CTEPH.

PubMed

Gall, Henning; Vachiéry, Jean-Luc; Tanabe, Nobuhiro; Halank, Michael; Orozco-Levi, Mauricio; Mielniczuk, Lisa; Chang, MiKyung; Vogtländer, Kai; Grünig, Ekkehard

2018-06-01

The original version of this article unfortunately contained a mistake. In the "Results" section, the percentage of patients with inoperable or persistent/recurrent CTEPH included in the study was reported as 85%. This has been corrected to 68% with this erratum.

A Teachable Moment

ERIC Educational Resources Information Center

Bigelow, Terry Patrick; Ried, C. A.

2006-01-01

The first part of this article recounts the experiences of a language arts teacher, Terry Patrick Bigelow, and his former student, Cynthia (Noyes) Ried, who suffers from Fahr's Syndrome, a neurodegenerative congenital disease that forms calcium deposits deep inside the brain. It is irreversible, inoperable, and incurable. In the first part of the…

Lung Carcinoma Predictive Biomarker Testing by Immunoperoxidase Stains in Cytology and Small Biopsy Specimens: Advantages and Limitations.

PubMed

Zhou, Fang; Moreira, Andre L

2016-12-01

- In the burgeoning era of molecular genomics, immunoperoxidase (IPOX) testing grows increasingly relevant as an efficient and effective molecular screening tool. Patients with lung carcinoma may especially benefit from the use of IPOX because most lung carcinomas are inoperable at diagnosis and only diagnosed by small tissue biopsy or fine-needle sampling. When such small specimens are at times inadequate for molecular testing, positive IPOX results still provide actionable information. - To describe the benefits and pitfalls of IPOX in the detection of biomarkers in lung carcinoma cytology specimens and small biopsies by summarizing the currently available commercial antibodies, preanalytic variables, and analytic considerations. - PubMed. - Commercial antibodies exist for IPOX detection of aberrant protein expression due to EGFR L858R mutation, EGFR E746_A750 deletion, ALK rearrangement, ROS1 rearrangement, and BRAF V600E mutation, as well as PD-L1 expression in tumor cells. Automated IPOX protocols for ALK and PD-L1 detection were recently approved by the Food and Drug Administration as companion diagnostics for targeted therapies, but consistent interpretive criteria remain to be elucidated, and such protocols do not yet exist for other biomarkers. The inclusion of cytology specimens in clinical trials would expand patients' access to testing and treatment, yet there is a scarcity of clinical trial data regarding the application of IPOX to cytology, which can be attributed to trial designers' lack of familiarity with the advantages and limitations of cytology. The content of this review may be used to inform clinical trial design and advance IPOX validation studies.

Prognostic value of fluorine-18 fludeoxyglucose positron emission tomography parameters differs according to primary tumour location in small-cell lung cancer.

PubMed

Nobashi, Tomomi; Koyasu, Sho; Nakamoto, Yuji; Kubo, Takeshi; Ishimori, Takayoshi; Kim, Young H; Yoshizawa, Akihiko; Togashi, Kaori

2016-01-01

To investigate the prognostic value of fluorine-18 fludeoxyglucose (FDG) positron emission tomography (PET) parameters for small-cell lung cancer (SCLC), according to the primary tumour location, adjusted by conventional prognostic factors. From 2008 to 2013, we enrolled consecutive patients with histologically proven SCLC, who had undergone FDG-PET/CT prior to initial therapy. The primary tumour location was categorized into central or peripheral types. PET parameters and clinical variables were evaluated using univariate and multivariate analysis. A total of 69 patients were enrolled in this study; 28 of these patients were categorized as having the central type and 41 patients as having the peripheral type. In univariate analysis, stage, serum neuron-specific enolase, whole-body metabolic tumour volume (WB-MTV) and whole-body total lesion glycolysis (WB-TLG) were found to be significant in both types of patients. In multivariate analysis, the independent prognostic factor was found to be stage in the central type, but WB-MTV and WB-TLG in the peripheral type. Kaplan-Meier analysis demonstrated that patients with peripheral type with limited disease and low WB-MTV or WB-TLG showed significantly better overall survival than all of the other groups (p < 0.0083). The FDG-PET volumetric parameters were demonstrated to be significant and independent prognostic factors in patients with peripheral type of SCLC, while stage was the only independent prognostic factor in patients with central type of SCLC. FDG-PET is a non-invasive method that could potentially be used to estimate the prognosis of patients, especially those with peripheral-type SCLC.

Epidermal growth factor receptor gene mutation defines distinct subsets among small adenocarcinomas of the lung.

PubMed

Haneda, Hiroshi; Sasaki, Hidefumi; Shimizu, Shigeki; Endo, Katsuhiko; Suzuki, Eriko; Yukiue, Haruhiro; Kobayashi, Yoshihiro; Yano, Motoki; Fujii, Yoshitaka

2006-04-01

Epidermal growth factor receptor (EGFR) gene mutations are frequently detected in lung cancer, especially in adenocarcinoma, in females, and non-smoking patients. EGFR mutations are closely associated with clinical response to EGFR tyrosine kinase inhibitor. Bronchioloalveolar carcinoma (BAC) appearance is a good predictor of response to this agent. Noguchi et al. subdivided small peripheral adenocarcinoma of the lung into two groups. One group was characterized with tumor cell growth replacing the normal alveolar cells with varying degree of fibrosis (types A-C), and the other shows non-replacing and destructive growth (types D-F). Using probes for the 13 mutations which have been previously described, we have genotyped the EGFR gene status in surgically resected atypical adenomatous hyperplasias (AAH) and small peripheral adenocarcinomas up to 2 cm in diameter using TaqMan PCR assay. In 95 small-sized adenocarcinomas, the EGFR mutations were detected in 37 patients (38.9%), and no mutations were found in five AAHs. In small peripheral adenocarcinomas, EGFR mutations were found 47.1% of types A, B, or C adenocarcinomas; it was less frequent (16%) in Noguchi's types D, E or F adenocarcinomas. These results suggest that type D, F adenocarcinomas are not derived from the less malignant types A-C adenocarcinomas; rather, they have arisen de novo by distinct mechanisms. Although types A and B adenocarcinomas are almost 100% cured by surgery, some type C adenocarcinoma show lymph node metastasis and relapse. EGFR mutation analysis may help identify patients who will respond to treatment with tyrosine kinase inhibitors, e.g., gefitinib.

Non-Small Cell Carcinoma of the Lung With Osteoclast-Like Giant Cells.

PubMed

Dahm, Hans Helmut

2017-05-01

Carcinomas of the lung with benign osteoclast-like giant cells are rare. A literature search showed only 8 previously reported examples. These tumors resemble a giant cell tumor of bone. Many of these tumors, which occur in most epithelium-containing organs, are composed of an undifferentiated, sarcomatoid component that contains benign osteoclast-like giant cells and a conventional carcinoma. In some tumors the epithelial origin may be revealed by immunohistochemistry only; others lack any evidence of an epithelial component. A 59-year-old man had an inoperable tumor in the upper lobe of the left lung. The tumor did not respond to radiation therapy, and chemotherapy resulted in minimal relief of symptoms. Light microscopy of biopsy samples showed benign osteoclast-like giant cells distributed irregularly between proliferations of undifferentiated medium-sized tumor cells. Approximately one third of the undifferentiated tumor cells were cytokeratin AE1/AE3-positive, and a minor alveolar clear cell component of the tumor was cytokeratin 7-positive. The osteoclast-like giant cells were strongly CD68-positive. The clinical and histologic findings supported the diagnosis of a non-small cell carcinoma of the lung with benign osteoclast-like giant cells. The differential diagnosis is composed of giant cell carcinoma, carcinosarcoma, and mesenchymal tumors of the lung.

CD200-expressing human basal cell carcinoma cells initiate tumor growth.

PubMed

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

PubMed

He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

2010-04-26

Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

Electrotherapy for the treatment of painful diabetic peripheral neuropathy: a review.

PubMed

Pieber, Karin; Herceg, Malvina; Paternostro-Sluga, Tatjana

2010-04-01

To review different types of electrotherapy for the treatment of painful diabetic peripheral neuropathy. A structured search of the electronic database MEDLINE was performed from the time of its initiation to July 2009. Articles in English and German were selected. The efficacy of different types of electrotherapy for painful diabetic peripheral neuropathy has been evaluated in 15 studies; the effects of transcutaneous electrical nerve stimulation are consistent. The beneficial effects of prolonged use have been reported in three large studies and one small study. The effects of frequency-modulated electromagnetic neural stimulation were assessed in one large study, and a significant reduction in pain was reported. Treatment with pulsed and static electromagnetic fields has been investigated in two small and three large studies, and analgesic benefits have been reported. In one large study focusing on pulsed electromagnetic fields, no beneficial effect on pain was registered. Only small studies were found concerning other types of electrotherapy, such as pulsed-dose electrical stimulation, high-frequency external muscle stimulation or high-tone external muscle stimulation. The conclusions drawn in these articles are diverse. Shortcomings and problems, including a poor study design, were observed in some. Further randomized, double-blind, placebo-controlled studies comprising larger sample sizes, a longer duration of treatment, and longer follow-up assessments are required.

Electromagnetic Navigational Bronchoscopy

PubMed Central

Port, Jeffrey; Harrison, Sebron

2013-01-01

Despite advances in technology and treatment options, lung cancer remains a deadly disease. National screening programs are being instituted in an attempt to discover lung cancer in high-risk individuals at an earlier stage. Such screening programs invariably discover small peripheral nodules that previously would not have been clinically apparent; the management of such lesions can be challenging. Current diagnostic options such as percutaneous biopsy are effective; however, they are hindered by their risk of morbidity such as pneumothorax. Electromagnetic bronchoscopy (ENB) is an emerging technology that allows the practitioner the ability to both sample and treat small peripheral pulmonary lesions. In experienced centers, ENB provides high rates of diagnostic yield for small lesions and a complication rate significantly lower than that of more conventional diagnostic modalities. Although there are current barriers to its widespread utilization (cost, specialized imaging, technical training), these obstacles will handled similarly to any other emerging technology and will likely not be long-term impediments to its use. PMID:24436528

Influence of blood flow occlusion on the development of peripheral and central fatigue during small muscle mass handgrip exercise

PubMed Central

Broxterman, R M; Craig, J C; Smith, J R; Wilcox, S L; Jia, C; Warren, S; Barstow, T J

2015-01-01

Abstract The influence of the muscle metabolic milieu on peripheral and central fatigue is currently unclear. Moreover, the relationships between peripheral and central fatigue and the curvature constant (W ′) have not been investigated. Six men (age: 25 ± 4 years, body mass: 82 ± 10 kg, height: 179 ± 4 cm) completed four constant power handgrip tests to exhaustion under conditions of control exercise (Con), blood flow occlusion exercise (Occ), Con with 5 min post-exercise blood flow occlusion (Con + Occ), and Occ with 5 min post-exercise blood flow occlusion (Occ + Occ). Neuromuscular fatigue measurements and W ′ were obtained for each subject. Each trial resulted in significant peripheral and central fatigue. Significantly greater peripheral (79.7 ± 5.1% vs. 22.7 ± 6.0%) and central (42.6 ± 3.9% vs. 4.9 ± 2.0%) fatigue occurred for Occ than for Con. In addition, significantly greater peripheral (83.0 ± 4.2% vs. 69.0 ± 6.2%) and central (65.5 ± 14.6% vs. 18.6 ± 4.1%) fatigue occurred for Occ + Occ than for Con + Occ. W ′ was significantly related to the magnitude of global (r = 0.91) and peripheral (r = 0.83) fatigue. The current findings demonstrate that blood flow occlusion exacerbated the development of both peripheral and central fatigue and that post-exercise blood flow occlusion prevented the recovery of both peripheral and central fatigue. Moreover, the current findings suggest that W ′ may be determined by the magnitude of fatigue accrued during exercise. Key points Critical power represents an important threshold for neuromuscular fatigue development and may, therefore, dictate intensities for which exercise tolerance is determined by the magnitude of fatigue accrued. Peripheral fatigue appears to be constant across O2 delivery conditions for large muscle mass exercise, but this consistency is equivocal for smaller muscle mass exercise. We sought to determine the influence of blood flow occlusion during handgrip exercise on neuromuscular fatigue development and to examine the relationship between neuromuscular fatigue development and W ′. Blood flow occlusion influenced the development of both peripheral and central fatigue, thus providing further evidence that the magnitude of peripheral fatigue is not constant across O2 delivery conditions for small muscle mass exercise. W ′ appears to be related to the magnitude of fatigue accrued during exercise, which may explain the reported consistency of intramuscular metabolic perturbations and work performed for severe-intensity exercise. PMID:26104881

WE-AB-207B-10: On Spinal Nerve Toxicity from Single-Session SAbR in Pigs and the Translation of Small Animal NTCP Models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hrycushko, B; Medin, P

Purpose: The incidence of peripheral neuropathy has risen with increased utilization of SAbR. There is no consensus regarding the dose-tolerance of the peripheral nervous system. In 2015, we commenced an investigation to test the hypotheses that single-session irradiation to the pig spinal nerves exhibit a similar dose-tolerance as that of the spinal cord and that a dose-length effect exists. This work evaluates the direct application of small animal NTCP models to both large animal spinal cord and preliminary peripheral nerve data. Methods: To date, 16 of 25 Yucatan minipigs have received single-session SAbR to a 1.5cm length and 4 ofmore » 25 have received irradiation to a 0.5cm length of left-sided C6-C8 spinal nerves. Toxicity related gait change has been observed in 13 animals (9 from the long length group and 4 from the short). This preliminary data is overlaid on several dose-response models which have been fit to rodent spinal cord tolerance experiments. Model parameters define a toxicity profile between a completely serial or parallel behaving organ. Adequacy of model application, including how length effects are handled, to published minipig spinal cord dose-response data and to preliminary peripheral nerve response data was evaluated through residual analysis. Results: No rodent-derived dose-response models were directly applicable to all pig data for the different lengths irradiated. Several models fit the long-length irradiated spinal cord data well, with the more serial-like models fitting best. Preliminary data on the short-length irradiation suggests no length effect exists, disproving our hypothesis. Conclusion: Direct application of small-animal NTCP models to pig data suggests dose-length effect predictions from small animal data may not translate clinically. However, the small animal models used have not considered dose heterogeneity and it is expected that including the low-to-mid dose levels in the penumbral region will improve this match. This work was funded by the Cancer Prevention Research Institute of Texas (CPRIT).« less

76 FR 189 - Notice of Availability of the Models for Plant-Specific Adoption of Technical Specifications Task...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-03

... Specifications (STS) to define a new time limit for restoring inoperable RCS leakage detection instrumentation to... operability of the RCS leakage detection instrumentation. The CLIIP model SE will facilitate expedited... Operability Requirements and Actions for RCS Leakage Instrumentation'' AGENCY: U.S. Nuclear Regulatory...

75 FR 18907 - Notice of Opportunity for Public Comment on the Proposed Model Safety Evaluation for Plant...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-13

... Specifications (STS) to define a new time limit for restoring inoperable RCS leakage detection instrumentation to... contents of the facility design bases related to the operability of the RCS leakage detection... leakage detection instrumentation to operable status and establish alternate methods of monitoring RCS...

Potential Applicability of Just-In-Time Inventory Management Within the Navy.

DTIC Science & Technology

1995-12-01

Naval Postgraduate School, Monterey, CA, 1992. 7. Heizer & Render , PRODUCTION AND OPERATION MANAGEMENT (3rd ED), Massachusetts, Simon & Schuster, Inc...applicable end item. If the failure of an item would render the end item inoperable, the item is assigned a Military Essentiality Code (MEC) of ŕ." If the

Primary pulmonary lymphoma mimicking a refractory lung abscess: A case report.

PubMed

Matsumoto, Takeshi; Otsuka, Kojiro; Funayama, Yuki; Imai, Yukihiro; Tomii, Keisuke

2015-04-01

The current study presents a case of primary pulmonary lymphoma (PPL) mimicking refractory lung abscess that was diagnosed at autopsy. An 80-year-old male with clinically inapparent aspiration presented with a large cavitated mass and pleural effusion. A lung abscess and empyema was diagnosed, therefore, antibiotics were administered and the pleural effusion was drained. Various examinations, including a biopsy, yielded no specific diagnosis. The lesion was considered inoperable due to the poor general condition of the patient. Subsequently, the mass that had been diagnosed as a refractory lung abscess became enlarged and a repeat biopsy resulted in a diagnosis of diffuse large B-cell lymphoma. The patient succumbed to sudden respiratory failure, and the final diagnosis of PPL was confirmed at autopsy. PPL is a rare disease that accounts for 0.45% of all pulmonary malignant tumors and is difficult to diagnose in inoperable cases. Therefore, patients with PPL who do not undergo surgery can be misdiagnosed and consequently treated inappropriately. PPL should therefore be considered in the differential diagnosis of a refractory lung abscess.

Studies On Endoscopic Local Hyperthermia Using Nd-YAG Laser

NASA Astrophysics Data System (ADS)

Tsunekawa, H.; Kanemaki, N.; Furusawa, A.; Hotta, M.; Kuroiwa, A.; Nishida, M.; Mori, N.; Watanabe, Y.; Morise, K.; Iizuka, A.

1987-03-01

Attempting a new method of laser irradiation for depressed gastric carcinoma, using a newly developed interstitial probe and laser attenuator, we applied local hyperthermia with prolonged low watt contact irradiation. Experimental studies were performed with this probe, using BDF1 mice injected hypodermically with Lewis lung carcinoma. A laser power of 2.0 w at the tip of fiber produced the most desirable temperature curve, about 43 - 60°C at the irradiation site. Clinical applications were carried out on 15 patients with early gastric carcinoma (mainly depressed), 10 preoperative pilot cases and 5 inoperable cases. In follow-up operations and biopsies gastric carcinoma was found to have completely dis-appeared in 2 of the preoperative and 4 of the inoperable cases. In the remaining 8 preoperative cases residual traces of carcinoma were found at the margin of the laser ulcer, but not at the bottom of it. We propose that endoscopic local hyperthermia using interstitial probe and low power irradiation (2.0 W) is the safest and most suitable method of dealing with depressed carcinoma.

[Blood-nerve barrier and peripheral nerve regeneration].

PubMed

Kanda, Takashi

2013-01-01

Blood-nerve barrier (BNB) restricts the movement of soluble mediators and leukocytes from the blood contents to the peripheral nervous system (PNS) parenchyma and thus maintains the endoneurial homeostasis. However, it interferes the supply of various neurotrophic factors from the blood constituents and stops the drainage of toxic substances out of the PNS parenchyma, resulting in the inhibition of peripheral nerve regeneration. If the manipulation of BNB function is possible, regeneration of peripheral nerve may be facilitated via the alteration of peripheral nerve microenvironment and ample supply of neurotrophic substances. A possible method to manipulate the BNB for therapeutic purposes is to modify the endothelial function using siRNAs, oligonucleotides and virus vectors. Another possible method is to modify BNB pericytes: small hydrophobic substances that can reach the pericyte membrane through the endothelial monolayer and strengthen the pericytic activity, including the release of various cytokines/chemokines that influence endothelial function, may also be useful as drug candidates to control the BNB function.

A finite element simulation of sound attenuation in a finite duct with a peripherally variable liner

NASA Technical Reports Server (NTRS)

Watson, W. R.

1977-01-01

Using multimodal analysis, a variational finite element method is presented for analyzing sound attenuation in a three-dimensional finite duct with a peripherally variable liner in the absence of flow. A rectangular element, with cubic shaped functions, is employed. Once a small portion of a peripheral liner is removed, the attenuation rate near the frequency where maximum attenuation occurs drops significantly. The positioning of the liner segments affects the attenuation characteristics of the liner. Effects of the duct termination are important in the low frequency ranges. The main effect of peripheral variation of the liner is a broadening of the attenuation characteristics in the midfrequency range. Because of matrix size limitations of the presently available computer program, the eigenvalue equations should be solved out of core in order to handle realistic sources.

Carbon Ion Radiotherapy for Peripheral Stage I Non-Small Cell Lung Cancer

NASA Astrophysics Data System (ADS)

Kamada, Tadashi; Yamamoto, Naoyoshi; Baba, Masayuki

The National Institute of Radiological Sciences in Chiba, Japan (NIRS) has the highest number of patients with lung cancer treated with carbon ion beams in the world. This report describes the techniques and clinical trials that have been undertaken at NIRS and preliminary results of a current study on single-fraction irradiation. The data are compared to recent results for the treatment of peripheral stage I lung cancer from the literature.

Optimum dose of radiotherapy for chemodectomas of the middle ear

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, J.A.; Elkon, D.; Lim, M.L.

Forty patients with chemodectomas of the middle ear were seen at the University of Virginia Hospital from 1932 to 1978. Surgery, post-operative radiotherapy or radiotherapy alone were the treatment modalities employed depending on the extent of the disease. These have been reviewed with regard to the clinical presentation and results of treatment with long term follow-up of 1 to 30 years. An attempt was made to determine the optimum dose of radiotherapy based on our data and reported cases in the literature. The majority of patients complaining of tinnitus, otalgia and pulsation obtained significant if not complete relief of symptoms.more » Cranial nerve defects, however, ofter persisted after therapy. Tumor was considered to be controlled if there was no increase in its size or progression of symptoms. Tumor control was obtained in eight of 10 early patients but only in two of seven more patients with advanced disease with total resection. Control rate with post-operative radiotherapy after subtotal resection was 85%. Radiotherapy alone was used for inoperable or recurrent tumors and control was obtained in 88% of them. In addition to our data, the radiation dose used in over 200 patients reported in the literature was analyzed. There was only a 2% recurrence rate in patients who received 4000 rad/4 weeks or higher. Twenty-two percent of patients treated with less than 4000 rad developed recurrence. The tendency is to use a lower dose of postoperative treatment and a higher dose for gross inoperable tumors. 4000 rad/4 weeks seems to be adequate for control of postoperative residual disease and no more than 5000 rad/5 weeks are required even for advanced inoperable cases. By keeping the dose below 5000 rad/5 weeks, the incidence of complications such as brain necrosis is greatly decreased.« less

Cost-effectiveness of Stereotactic Body Radiation Therapy versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Markov Modeling Study.

PubMed

Pollom, Erqi L; Lee, Kyueun; Durkee, Ben Y; Grade, Madeline; Mokhtari, Daniel A; Wahl, Daniel R; Feng, Mary; Kothary, Nishita; Koong, Albert C; Owens, Douglas K; Goldhaber-Fiebert, Jeremy; Chang, Daniel T

2017-05-01

Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. © RSNA, 2017 Online supplemental material is available for this article.

Cost-effectiveness of Stereotactic Body Radiation Therapy versus Radiofrequency Ablation for Hepatocellular Carcinoma: A Markov Modeling Study

PubMed Central

Lee, Kyueun; Durkee, Ben Y.; Grade, Madeline; Mokhtari, Daniel A.; Wahl, Daniel R.; Feng, Mary; Kothary, Nishita; Koong, Albert C.; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy; Chang, Daniel T.

2017-01-01

Purpose To assess the cost-effectiveness of stereotactic body radiation therapy (SBRT) versus radiofrequency ablation (RFA) for patients with inoperable localized hepatocellular carcinoma (HCC) who are eligible for both SBRT and RFA. Materials and Methods A decision-analytic Markov model was developed for patients with inoperable, localized HCC who were eligible for both RFA and SBRT to evaluate the cost-effectiveness of the following treatment strategies: (a) SBRT as initial treatment followed by SBRT for local progression (SBRT-SBRT), (b) RFA followed by RFA for local progression (RFA-RFA), (c) SBRT followed by RFA for local progression (SBRT-RFA), and (d) RFA followed by SBRT for local progression (RFA-SBRT). Probabilities of disease progression, treatment characteristics, and mortality were derived from published studies. Outcomes included health benefits expressed as discounted quality-adjusted life years (QALYs), costs in U.S. dollars, and cost-effectiveness expressed as an incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analysis was performed to assess the robustness of the findings. Results In the base case, SBRT-SBRT yielded the most QALYs (1.565) and cost $197 557. RFA-SBRT yielded 1.558 QALYs and cost $193 288. SBRT-SBRT was not cost-effective, at $558 679 per QALY gained relative to RFA-SBRT. RFA-SBRT was the preferred strategy, because RFA-RFA and SBRT-RFA were less effective and more costly. In all evaluated scenarios, SBRT was preferred as salvage therapy for local progression after RFA. Probabilistic sensitivity analysis showed that at a willingness-to-pay threshold of $100 000 per QALY gained, RFA-SBRT was preferred in 65.8% of simulations. Conclusion SBRT for initial treatment of localized, inoperable HCC is not cost-effective. However, SBRT is the preferred salvage therapy for local progression after RFA. © RSNA, 2017 Online supplemental material is available for this article. PMID:28045603

A randomized study of involved-field irradiation versus elective nodal irradiation in combination with concurrent chemotherapy for inoperable stage III nonsmall cell lung cancer.

PubMed

Yuan, Shuanghu; Sun, Xindong; Li, Minghuan; Yu, Jinming; Ren, Ruimei; Yu, Yonghu; Li, Jianbin; Liu, Xiuqing; Wang, Renben; Li, Baosheng; Kong, Li; Yin, Yong

2007-06-01

Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC). A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI. Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048). IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Advanced Epithelial Cancer, Malignant Lymphoma, or Sarcoma

ClinicalTrials.gov

2013-02-06

AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Primary CNS Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Chondrosarcoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Nodal Marginal Zone B-cell Lymphoma; Ovarian Sarcoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Osteosarcoma; Recurrent Small Lymphocytic Lymphoma; Recurrent Uterine Sarcoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult Soft Tissue Sarcoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Stage IV Uterine Sarcoma; Unspecified Adult Solid Tumor, Protocol Specific

Eye movement perimetry in glaucoma.

PubMed

Trope, G E; Eizenman, M; Coyle, E

1989-08-01

Present-day computerized perimetry is often inaccurate and unreliable owing to the need to maintain central fixation over long periods while repressing the normal response to presentation of peripheral stimuli. We tested a new method of perimetry that does not require prolonged central fixation. During this test eye movements were encouraged on presentation of a peripheral target. Twenty-three eyes were studied with an Octopus perimeter, with a technician monitoring eye movements. The sensitivity was 100% and the specificity 23%. The low specificity was due to the technician's inability to accurately monitor small eye movements in the central 6 degrees field. If small eye movements are monitored accurately with an eye tracker, eye movement perimetry could become an alternative method to standard perimetry.

Stereotactic hypofractionated radiation therapy for stage I non-small cell lung cancer.

PubMed

Zimmermann, Frank B; Geinitz, Hans; Schill, Sabine; Grosu, Anca; Schratzenstaller, Ulrich; Molls, Michael; Jeremic, Branislav

2005-04-01

We reviewed our initial institutional experience with the use of stereotactic hypofractionated radiation therapy (SFRT) in patients with stage I non-small cell lung cancer (NSCLC). Thirty patients with inoperable stage I non-small cell lung cancer due to a severe chronic obstructive pulmonary disease (COPD) and/or chronic heart disease (Eastern Cooperative Oncology Group (ECOG) performance status of 0-2) were treated between December 2000 and October 2003 with SFRT in curative intent. Infiltration of locoregional lymph nodes and distant metastases were ruled out by computerized tomography (CT) scan of the brain, thorax, and abdomen, and by whole body FDG-positron emission tomography scan in all patients. Total RT doses ranged from 24.0 to 37.5 Gy, given in 3-5 fractions to the 60% isodose encompassing the planning target volume. Immobilization was carried out by a vacuum couch and a low-pressure foil. The clinical target volume was the tumor as it appeared in lung windowing on lung CT scan. Organ movements (caused by breathing; range, 6-22 mm) and reproducibility of patient positioning in the couch (range, 3-12 mm) were calculated by sequential CT and orthogonal films. The individual values were taken into account as a safety margin for the definition of the planning target volume (PTV). The median follow-up of living patients is 18 months (range, 6-38 months). As maximum response, there were 10 (33%) complete responses (CRs) and 14 (47%) partial responses (PRs), resulting in a total response rate of 80%. Stable disease was observed in 6 (20%) patients, while no patient experienced progressive disease. During follow-up, 2 (7%) local recurrences were observed (after 17 and 18 months, respectively). Of 5 (17%) patients who developed distant metastasis, 1 patient developed it in liver (3 months), another one in brain (6 months), and another one in the lung (36 months), while 2 patients developed it in mediastinal lymph nodes (after 8, and 11 months, respectively) only. Of 9 (30%) patients who have died, only 3 (10%) died of cancer, while 6 (20%) died of cancer-unrelated or unknown causes. Acute side effects were mild and affected 9 (33%) patients during the RT course (fatigue being the most frequent one in 6 patients). There were 22 acute events occurring in 19 (63%) patients during the first 3 months post-SFRT, the most frequent one being pneumonitis observed in 14 (46%) patients. However, there was only one (3%) grade 3 acute toxicity and no patient experienced greater than grade 3 toxicity during this study. One (3%) patient experienced rib fracture as the late event. SFRT is a feasible and safe treatment method in inoperable patients with stage I NSCLC having reduced lung capacity. Longer follow-up is necessary to get robust data on late toxicity as well as survival.

Peripheral primitive neuroectodermal tumor of the vulva: report of a case with imprint cytology.

PubMed

Takeshima, N; Tabata, T; Nishida, H; Furuta, N; Tsuzuku, M; Hirai, Y; Hasumi, K

2001-01-01

Peripheral primitive neuroectodermal tumor (PNET) of the vulva is an extremely rare disease, and, to our knowledge, only two cases have been previously reported. A 45-year-old woman presented with a mass in the right labium major. Three years after removal of the tumor, she noticed a new lesion in the same place and underwent a partial vulvectomy. The imprint cytology of the recurrent tumor showed a monomorphic appearance, composed of small round cells with scant cytoplasm against a hemorrhagic background. These tumor cells were loosely connective, but rosettelike structures were observed focally. On pathologic examination, the neoplasm was composed of small round tumor cells showing sinusoidal, diffuse or micropapillary growth. Immunohistochemically, the neoplastic cells stained positively for neuron-specific enolase, vimentin and HBA 71 and negatively for cytokeratin, HBA 45 and muscle-specific actin. The morphologic characteristics of the disease were well expressed in the imprint cytology, and this influenced the selection of immunohistochemical studies. Cytologic examination for vulvar tumors, even imprint cytology, can be a useful tool in obtaining an accurate pathologic diagnosis of a rare disease, such as peripheral PNET.

Binocular summation and peripheral visual response time

NASA Technical Reports Server (NTRS)

Gilliland, K.; Haines, R. F.

1975-01-01

Six males were administered a peripheral visual response time test to the onset of brief small stimuli imaged in 10-deg arc separation intervals across the dark adapted horizontal retinal meridian under both binocular and monocular viewing conditions. This was done in an attempt to verify the existence of peripheral binocular summation using a response time measure. The results indicated that from 50-deg arc right to 50-deg arc left of the line of sight binocular summation is a reasonable explanation for the significantly faster binocular data. The stimulus position by viewing eye interaction was also significant. A discussion of these and other analyses is presented along with a review of related literature.

A histone deacetylase 3–dependent pathway delimits peripheral myelin growth and functional regeneration

PubMed Central

He, Xuelian; Zhang, Liguo; Queme, Luis F; Liu, Xuezhao; Lu, Andrew; Waclaw, Ronald R; Dong, Xinran; Zhou, Wenhao; Kidd, Grahame; Yoon, Sung-Ok; Buonanno, Andres; Rubin, Joshua B; Xin, Mei; Nave, Klaus-Armin; Trapp, Bruce D; Jankowski, Michael P; Lu, Q Richard

2018-01-01

Deficits in Schwann cell–mediated remyelination impair functional restoration after nerve damage, contributing to peripheral neuropathies. The mechanisms mediating block of remyelination remain elusive. Here, through small-molecule screening focusing on epigenetic modulators, we identified histone deacetylase 3 (HDAC3; a histone-modifying enzyme) as a potent inhibitor of peripheral myelinogenesis. Inhibition of HDAC3 enhanced myelin growth and regeneration and improved functional recovery after peripheral nerve injury in mice. HDAC3 antagonizes the myelinogenic neuregulin–PI3K–AKT signaling axis. Moreover, genome-wide profiling analyses revealed that HDAC3 represses promyelinating programs through epigenetic silencing while coordinating with p300 histone acetyltransferase to activate myelination-inhibitory programs that include the HIPPO signaling effector TEAD4 to inhibit myelin growth. Schwann cell–specific deletion of either Hdac3 or Tead4 in mice resulted in an elevation of myelin thickness in sciatic nerves. Thus, our findings identify the HDAC3–TEAD4 network as a dual-function switch of cell-intrinsic inhibitory machinery that counters myelinogenic signals and maintains peripheral myelin homeostasis, highlighting the therapeutic potential of transient HDAC3 inhibition for improving peripheral myelin repair. PMID:29431744

Role of Schwann cells in the regeneration of penile and peripheral nerves

PubMed Central

Wang, Lin; Sanford, Melissa T; Xin, Zhongcheng; Lin, Guiting; Lue, Tom F

2015-01-01

Schwann cells (SCs) are the principal glia of the peripheral nervous system. The end point of SC development is the formation of myelinating and nonmyelinating cells which ensheath large and small diameter axons, respectively. They play an important role in axon regeneration after injury, including cavernous nerve injury that leads to erectile dysfunction (ED). Despite improvement in radical prostatectomy surgical techniques, many patients still suffer from ED postoperatively as surgical trauma causes traction injuries and local inflammatory changes in the neuronal microenvironment of the autonomic fibers innervating the penis resulting in pathophysiological alterations in the end organ. The aim of this review is to summarize contemporary evidence regarding: (1) the origin and development of SCs in the peripheral and penile nerve system; (2) Wallerian degeneration and SC plastic change following peripheral and penile nerve injury; (3) how SCs promote peripheral and penile nerve regeneration by secreting neurotrophic factors; (4) and strategies targeting SCs to accelerate peripheral nerve regeneration. We searched PubMed for articles related to these topics in both animal models and human research and found numerous studies suggesting that SCs could be a novel target for treatment of nerve injury-induced ED. PMID:25999359

Better Contract Oversight Could Have Prevented Deficiencies in the Detention Facility in Parwan, Afghanistan

DTIC Science & Technology

2012-05-17

a visitation center, a water treatment plant, and vocational buildings where detainees can learn carpentry and culinary skills. The facility also...room not connected MHU PPI 69 DCID HVAC unit is inoperable Ml DAB PPI has o rdered p arts and w ill fix w hen it arrives 70 Access broken to VCD

40 CFR 122.41 - Conditions applicable to all permits (applicable to State programs, see § 123.25).

Code of Federal Regulations, 2013 CFR

2013-07-01

... become inoperable, or substantial and permanent loss of natural resources which can reasonably be... disposal in violation of this permit which has a reasonable likelihood of adversely affecting human health... permit using test procedures approved under 40 CFR Part 136, or another method required for an industry...

40 CFR 122.41 - Conditions applicable to all permits (applicable to State programs, see § 123.25).

Code of Federal Regulations, 2014 CFR

2014-07-01

... become inoperable, or substantial and permanent loss of natural resources which can reasonably be... disposal in violation of this permit which has a reasonable likelihood of adversely affecting human health... permit using test procedures approved under 40 CFR Part 136, or another method required for an industry...

40 CFR 122.41 - Conditions applicable to all permits (applicable to State programs, see § 123.25).

Code of Federal Regulations, 2012 CFR

2012-07-01

... become inoperable, or substantial and permanent loss of natural resources which can reasonably be... disposal in violation of this permit which has a reasonable likelihood of adversely affecting human health... permit using test procedures approved under 40 CFR Part 136, or another method required for an industry...

Electromagnetic Navigation Bronchoscopy-directed Pleural Tattoo to Aid Surgical Resection of Peripheral Pulmonary Lesions.

PubMed

Tay, Jun H; Wallbridge, Peter D; Larobina, Marco; Russell, Prudence A; Irving, Louis B; Steinfort, Daniel P

2016-07-01

Limited (wedge) resection of pulmonary lesions is frequently performed as a diagnostic/therapeutic procedure. Some lesions may be difficult to locate thoracoscopically with conversion to open thoracotomy or incomplete resection being potential limitations to this approach. Multiple methods have been described to aid video-assisted thoracoscopic surgical (VATS) wedge resection of pulmonary nodules, including hookwire localization, percutaneous tattoo, or intraoperative ultrasound. We report on our experience using electromagnetic navigation bronchoscopic dye marking of small subpleural lesions to aid VATS wedge resection. A retrospective cohort study of consecutive patients undergoing VATS wedge resection of peripheral lesions. Preoperative bronchoscopy with electromagnetic navigation was utilized to guide a 25 G needle to within/adjacent to the target lesion with injection of 1 mL of methylene blue or indigo carmine under fluoroscopic vision. Six patients underwent bronchoscopic marking of peripheral pulmonary lesions, navigation deemed successful in all patients, with no procedural complications. Surgery was performed within 24 hours of bronchoscopic marking. Pleural staining by dye was visible thoracoscopically in all 6 lesions either adjacent to or overlying the lesion. All lesions were fully excised with wedge resection. Pathologic examination confirmed accuracy of dye staining. Electromagnetic navigation bronchoscopic dye marking of peripheral lesions is feasible, without complications commonly associated with percutaneous marking procedures. Further experience is required but early findings suggest that this method may have utility in aiding minimally invasive resection of small subpleural lesions.

Action video game players and deaf observers have larger Goldmann visual fields.

PubMed

Buckley, David; Codina, Charlotte; Bhardwaj, Palvi; Pascalis, Olivier

2010-03-05

We used Goldmann kinetic perimetry to compare how training and congenital auditory deprivation may affect the size of the visual field. We measured the ability of action video game players and deaf observers to detect small moving lights at various locations in the central (around 30 degrees from fixation) and peripheral (around 60 degrees ) visual fields. Experiment 1 found that 10 habitual video game players showed significantly larger central and peripheral field areas than 10 controls. In Experiment 2 we found that 13 congenitally deaf observers had significantly larger visual fields than 13 hearing controls for both the peripheral and central fields. Here the greatest differences were found in the lower parts of the fields. Comparison of the two groups showed that whereas VGP players have a more uniform increase in field size in both central and peripheral fields deaf observers show non-uniform increases with greatest increases in lower parts of the visual field.

High-throughput deep screening and identification of four peripheral leucocyte microRNAs as novel potential combination biomarkers for preeclampsia

PubMed Central

Wang, Yonghong; Yang, Xukui; Yang, Yuanyuan; Wang, Wenjun; Zhao, Meiling; Liu, Huiqiang; Li, Dongyan; Hao, Min

2016-01-01

Objective: To identify the specific microRNA (miRNA) biomarkers of preeclampsia (PE), the miRNA profiles analysis were performed. Study Design: The blood samples were obtained from five PE patients and five normal healthy pregnant women. The small RNA profiles were analyzed to identify miRNA expression levels and find out miRNAs that may associate with PE. The quantitative reverse transcriptase–PCR (qRT-PCR) assay was used to validate differentially expressed peripheral leucocyte miRNAs in a new cohort. Result: The data analysis showed that 10 peripheral leucocyte miRNAs were significantly differently expressed in severe PE patients. Four differently expressed miRNAs were successfully validated using qRT-PCR method. Conclusion: We successfully constructed a model with high accuracy to predict PE. A combination of four peripheral leucocyte miRNAs has great potential to serve as diagnostic biomarkers of PE. PMID:26675000

Rheumatological manifestations in inflammatory bowel disease

PubMed Central

Voulgari, Paraskevi V.

2011-01-01

Rheumatological manifestations in inflammatory bowel disease (IBD) are frequent and include peripheral arthritis, axial involvement and peripheral enthesitis. Secondary osteoporosis and hypertrophic osteoarthropathy may also occur. Complications of IBD (e.g. septic arthritis) must be distinguished from sterile inflammation. Adverse effects of corticosteroid treatment, such as osteonecrosis, may also affect joints. Axial involvement ranges from low back pain to true ankylosing spondylitis. Human leukocyte antigen B27 is associated with axial involvement of IBD. Peripheral arthritis has been classified into two types. Type I is a pauciarticular, asymmetric usually non destructive arthritis affecting large joints and is usually associated with active bowel disease. Type II is a polyarthritis affecting small joints and tends to run a course independent of the bowel disease. Treatment of joint symptoms in IBD include sulphasalazine, azathioprine, methotrexate and glucocorticoids. Anti-tumor necrosis factor antibodies are effective in treating resistant or complicated Crohn’s disease as well as peripheral arthritis and axial involvement. PMID:24713717

Diagnostic utility of cyclin D1 in the diagnosis of small round blue cell tumors in children and adolescents.

PubMed

Magro, Gaetano; Salvatorelli, Lucia; Alaggio, Rita; D'Agata, Velia; Nicoletti, Ferdinando; Di Cataldo, Andrea; Parenti, Rosalba

2017-02-01

Small round blue cell tumors (SRBCTs) of children and adolescents are often diagnostically challenging lesions. With the increasing diagnostic approach based on small biopsies, there is the need of specific immunomarkers that can help in the differential diagnosis among the different tumor histotypes to assure the patient a correct diagnosis for proper treatment. Based on our recent studies showing cyclin D1 overexpression in both Ewing sarcoma/primitive peripheral neuroectodermal tumor (EWS/pPNET) and peripheral neuroblastic tumors (neuroblastoma and ganglioneuroblastoma), we immunohistochemically assessed cyclin D1 immunoreactivity in 128 cases of SRBCTs in children and adolescents to establish its potential utility in the differential diagnosis. All cases of EWS/pPNET and the undifferentiated/poorly differentiated neuroblastomatous component of all peripheral neuroblastic tumors exhibited strong and diffuse nuclear staining (>50% of neoplastic cells) for cyclin D1. In contrast, this marker was absent from rhabdomyosarcoma (regardless of subtype) and lymphoblastic lymphoma (either B- or T-cell precursors), whereas it was only focally detected (<5% of neoplastic cells) in some cases of Wilms tumor (blastemal component) and desmoplastic small round cell tumor. Our findings suggest that cyclin D1 can be exploitable as a diagnostic adjunct to conventional markers in confirming the diagnosis of EWS/pPNET or neuroblastoma/ganglioneuroblastoma. Its use in routine practice may also be helpful for those cases of SRBCT with undifferentiated morphology that are difficult to diagnose after application of the conventional markers. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of tachykinins in small human airways.

PubMed

Frossard, N; Barnes, J

1991-07-01

We have compared the contractile responses of substance P (SP) and neurokinin A (NKA) to that of the non degradable muscarinic agonist, carbachol, in small and large human airways in vitro. We have also investigated the effects of the neutral endopeptidase (NEP) inhibitor, thiorphan (100 microM) on these responses. NKA contracted large and small airways to a different extent (56% vs 92% of carbachol maximal contraction, respectively). NKA was significantly less potent in large vs small bronchi (EC50 = 150 +/- 15 vs 12 +/- 5 nM respectively, p less than 0.05). SP had a lower contractile effect in large (26% carbachol maximum) and small airways (59%) with EC50 values higher than 0.5 microM. The enkephalinase inhibitor thiorphan shifted the concentration-response curve to NKA to the left in large (EC50 = 35.2 +/- 8.2 nM) and small bronchi (EC50 = 2.8 +/- 1.3 nM, p less than 0.02). This shift was associated with an increase in the maximal contraction to NKA (75% in large vs 123% in small bronchi). The amplitude of contraction to SP was also potentiated in large (45%) and in smaller bronchi (101%). In conclusion, we have demonstrated that NKA has a significantly greater constrictor effect than a cholinergic agent in more peripheral human airways in vitro. This suggests that non cholinergic constrictor pathways are more likely to be important in more peripheral airways.

Clinical data, clinicopathologic findings and outcome in dogs with amegakaryocytic thrombocytopenia and primary immune-mediated thrombocytopenia.

PubMed

Cooper, S A; Huang, A A; Raskin, R E; Weng, H-Y; Scott-Moncrieff, J C

2016-03-01

The aim of this study was to identify distinguishing characteristics between dogs diagnosed with amegakaryocytic thrombocytopenia and those diagnosed with presumed primary peripheral immune-mediated thrombocytopenia. Presenting clinical and clinicopathologic data and outcomes were compared between the two groups. Retrospective study performed on seven client-owned dogs diagnosed with amegakaryocytic thrombocytopenia and 34 client-owned dogs with primary peripheral immune-mediated thrombocytopenia. All dogs in the amegakaryocytic thrombocytopenia group were anaemic on presentation with a median haematocrit of 23% (range 9·4 to 36), while the primary peripheral immune-mediated thrombocytopoenia group had a median presenting haematocrit of 35% (range 10 to 53). Dogs with amegakaryocytic thrombocytopenia had a median of five (range 4 to 7) clinical signs of bleeding compared to a median of three (range 0 to 6) in the primary peripheral immune-mediated thrombocytopenia group with 86% (6 of 7) of amegakaryocytic thrombocytopenia dogs requiring a blood transfusion compared to 41% (14 of 34) of primary peripheral immune-mediated thrombocytopenia dogs. Six of the seven amegakaryocytic thrombocytopenia dogs did not survive to discharge, while only five of the 34 primary peripheral immune-mediated thrombocytopenia dogs did not survive to discharge. The clinical presentation of dogs with amegakaryocytic thrombocytopenia and primary peripheral immune-mediated thrombocytopenia is similar, but dogs with amegakaryocytic thrombocytopenia had a more severe clinical course compared to primary peripheral immune-mediated thrombocytopenia dogs. The prognosis for dogs with amegakaryocytic thrombocytopenia is poor. © 2016 British Small Animal Veterinary Association.

Comparing the fixational and functional preferred retinal location in a pointing task

PubMed Central

Sullivan, Brian; Walker, Laura

2016-01-01

Patients with central vision loss (CVL) typically adopt eccentric viewing strategies using a preferred retinal locus (PRL) in peripheral retina. Clinically, the PRL is defined monocularly as the area of peripheral retina used to fixate small stimuli. It is not clear if this fixational PRL describes the same portion of peripheral retina used during dynamic binocular eye-hand coordination tasks. We studied this question with four participants each with a unique CVL history. Using a scanning laser ophthalmoscope, we measured participants’ monocular visual fields and the location and stability of their fixational PRLs. Participants’ monocular and binocular visual fields were also evaluated using a computer monitor and eye tracker. Lastly, eye-hand coordination was tested over several trials where participants pointed to and touched a small target on a touchscreen monitor. Trials were blocked and carried out monocularly and binocularly, with a target appearing at 5° or 15° from screen center, in one of 8 locations. During pointing, our participants often exhibited long movement durations, an increased number of eye movements and impaired accuracy, especially in monocular conditions. However, these compensatory changes in behavior did not consistently worsen when loci beyond the fixational PRL were used. While fixational PRL size, location and fixation stability provide a necessary description of behavior, they are not sufficient to capture the pointing PRL used in this task. Generally, patients use a larger portion of peripheral retina than one might expect from measures of the fixational PRL alone, when pointing to a salient target without time constraints. While the fixational and pointing PRLs often overlap, the fixational PRL does not predict the large area of peripheral retina that can be used. PMID:26440864

Ultrastructure of cardiac muscle in reptiles and birds: optimizing and/or reducing the probability of transmission between calcium release units.

PubMed

Perni, Stefano; Iyer, V Ramesh; Franzini-Armstrong, Clara

2012-06-01

It is known that cardiac myocytes contain three categories of calcium release units (CRUs) all bearing arrays of RyR2: peripheral couplings, constituted of an association of the junctional SR (jSR) with the plasmalemma; dyads, associations between jSR and T tubules; internal extended junctional jSR (EjSR)/corbular jSR that is not associated with plasmalemma/T tubules. The bird hearts, even if fast beating (e.g., in finch and hummingbird) have no T tubules, despite fiber sizes comparable to those of mammalian ventricle, but are rich in EjSR/corbular SR. The heart of small lizard also lacks T tubule, but it has only peripheral couplings and compensates for lack of internal CRUs by the small diameter of its cells. We have extended previous information on chicken heart to finch and lizard by establishing a spatial relationship between RyR2 clusters in jSR of peripheral couplings and clusters of intra-membrane particles identifiable as voltage sensitive calcium channels (CaV1.2) in the adjacent plasmalemma. This provides the structural basis for initiation of the heart beat in all three species. Further we evaluated the distances separating peripheral couplings from each other and between EjSR/corbular SR sites within the bird muscles in all three hearts. The distances suggest that peripheral coupling sites are most likely to act independently of each other and that a calcium wave-front propagation from one internal CRU site to the other across the level of the Z line, may be marginally successful in the chicken, but certainly very effective in the finch.

Bendamustine Hydrochloride, Etoposide, Dexamethasone, and Filgrastim For Peripheral Blood Stem Cell Mobilization in Treating Patients With Refractory or Recurrent Lymphoma or Multiple Myeloma

ClinicalTrials.gov

2017-04-14

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

The incidental finding of elevated anti GQ1B antibodies in a patient with selective small fiber neuropathy.

PubMed

Favoni, Valentina; Liguori, Rocco; Incensi, Alex; Fileccia, Enrico; Donadio, Vincenzo

2018-05-15

Small fiber neuropathy (SFN) selectively affects small diameter sensory and/or autonomic axons. Pain and autonomic dysfunctions are the most common symptoms. SFN occurs in several autoimmune diseases and autoantibodies against neuronal proteins may play a role in SFN pathophysiology. Anti-GQ1b antibody has been associated with Miller Fisher syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoplegia, pharyngeal-cervical-brachial weakness and peripheral neuropathy involving large fibers. Isolated SFN associated with anti-GQ1b antibodies has not been previously reported. Here we report a 45-year-old woman presenting with highly positive anti-GQ1b titer and selective SFN without central nervous system or peripheral large nerve involvement. She improved upon administration of adalizumab. Further studies will clarify a possible pathogenetic role of antiganglioside antibodies in SFN. Moreover, the recognition of antiganglioside antibodies in SFN may have therapeutic consequences with patients who would benefit from immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

[Best practice guide for radiation therapy of non-small cell bronchial cancers].

PubMed

Martel-Lafay, I; Fourneret, P; Ayadi, M; Brun, O; Buatois, F; Carrie, C; Chilles, A; Claude, L; Cottin-Durrleman, G; Farsi, F; Fournel, P; Mongodin, B; Pouchard, I; Balestrière, V; Suchaud, J P

2009-01-01

The objective was the drafting of a practical document intended for radiotherapists and radiophysicists, describing the technique of irradiation of a non small cell bronchial cancer. The good practices concern the care of patients affected by bronchial cancer localized in the thorax and inoperable or patients who must undergo postoperative irradiation. The document has been developed according to a methodology aiming to join the current scientific data from an analysis of the literature on the subject and the assessment of radiotherapists, radiophysicists, lung specialists and methodologists from Rhône-Alpes area. From the stages necessary for the good progress of a radiotherapy, the writers of this document proposed common definitions concerning the centering and the location of the zone to be treated, the calculation of the dose distribution, the preparation of the patient for the treatment, the treatment and the surveillance during the treatment. The recommendations of this guide took into account the peculiarities bound to the nature of the treated region and more particularly the lung heterogeneity, respiratory movements and the radiosensibility of healthy lung tissue. Even if the technical aspect of the radiotherapy was particularly developed, the interest accorded to patient information takes on all its importance for a therapeutic coverage of quality. The authors of the document wished that this Guide of Good Practices, which will be regularly updated, helps the radiotherapists and allows them to harmonize their practices.

Three dimensional structure of the distal condyles of the third metacarpal bone of the horse.

PubMed

Boyde, A; Haroon, Y; Jones, S J; Riggs, C M

1999-03-01

This study examined the three-dimensional (3D) microarchitecture of regions of the equine third metacarpal bone (McIII) commonly involved in distal condylar fractures. Limbs were obtained from Thoroughbred horses (neonates to age 24 years) destroyed for inoperable fractures and a variety of other conditions. Beams, blocks and sections were cut in the principal axes, some embedded in PMMA and others examined unembedded. Several methods were used to study the 3D structure, including conventional and confocal optical microscopy, scanning electron microscopy (SEM) and radiography. The mineralised articular cartilage tends to cleave in the sagittal plane. Proximal to the subchondral bone, the main trabeculae are robust plates running in the sagittal direction with less significant mediolateral connections. Small blood vessel canals lie inside the sagittal plates. This structure gives maximum strength and protection in the sagittal plane in which the bone rotates, but offers minimal resistance to fracture propagation in this plane. The anatomical course of the common distal condylar fractures of the third metacarpal bones can be explained by underlying anisotropic structural features of the mineralised tissues.

Early-stage central lung cancer and volumetric modulated arc therapy: a dosimetric case study with literature review.

PubMed

Valakh, Vladimir; Chan, Philip; D'Adamo, Karen; Micaily, Bizhan

2013-10-01

In the present article we review on the use of Volumetric Modulated Arc Therapy (VMAT) for a small lung nodule that was centrally located in close proximity to the mediastinal structures. An inoperable patient with central, clinical stage IA adenocarcinoma of the right lung was treated with external-beam radiation therapy of 52.5 Gy in 15 factions. A single 360° coplanar arc VMAT plan (360-VMAT) was used for treatment and compared to step-and-shoot Intensity Modulation Radiotherapy (IMRT) and a single 180° ipsilateral partial arc VMAT plan (180-VMAT). Planning Target Volume (PTV) coverage was not different, and 360-VMAT had the highest dose homogeneity. Both 360-VMAT and 180-VMAT reduced esophageal dose compared to IMRT. While IMRT had the lowest lung dose, all 3 plans achieved acceptable sparing of the lung. 180-VMAT had the highest dose conformity. Both 360-VMAT and 180-VMAT improved esophageal sparing compared to IMRT. Use of VMAT in early-stage, centrally located NSCLC is a promising treatment approach and merits additional investigation.

Prevention and treatment of the chronic thromboembolic pulmonary hypertension.

PubMed

Pesavento, Raffaele; Prandoni, Paolo

2018-04-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon and late complication of pulmonary embolism resulting from misguided remodelling of residual pulmonary thromboembolic material and small-vessel arteriopathy. CTEPH is the only form of pulmonary hypertension (PH) potentially curable by pulmonary endarterectomy (PEA). Unfortunately, several patients have either an unacceptable risk-benefit ratio for undergoing the surgical intervention or develop persistent PH after PEA. Novel medical and endovascular therapies can be considered for them. The soluble guanylate cyclase stimulator riociguat is recommended for the treatment of patients with inoperable disease or with recurrent/persistent PH after PEA. Other drugs developed for the treatment of other forms of PH, as prostanoids, phosphodiesterase-5 inhibitors and endothelin receptor antagonists have been used in the treatment of CTEPH, with limited benefit. Balloon pulmonary angioplasty is a novel and promising technique and is progressively emerging from the pioneering phase. Highly specialized training level and complex protocols of postoperative care are mandatory to consolidate the technical success of the surgical and endovascular intervention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of a constant-level lighting control system on small offices with windows. Final technical report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edgar, L.

To reduce energy consumption stemming from lighting, some of the fixtures in Army office buildings have been delamped and building energy managers have instituted the policy of turning lights off when not in use. Even with these measures, lighting is still one of the largest consumers of electricity. The current problem is to find ways to reduce the energy consumption of lighting systems when they are in use. The objectives of this research was to provide information on the performance and energy savings potential of constant level lighting (CLL) controls. Based on a review of product information, researchers selected themore » Conservolite Plus 20 for testing and installed it in 10 office spaces. After 4 months of operation, a survey of the office occupants revealed that they were satisfied with the CLL system. Although electrical cost savings were realized, the payback period varied greatly, depending on the cost of replacing old or inoperable lamps and ballasts. Before large scale installation of CLL systems, it is recommended that the power factor and harmonic distortion be monitored at a large facility.« less

Mini-review: Far peripheral vision.

PubMed

Simpson, Michael J

2017-11-01

The region of far peripheral vision, beyond 60 degrees of visual angle, is important to the evaluation of peripheral dark shadows (negative dysphotopsia) seen by some intraocular lens (IOL) patients. Theoretical calculations show that the limited diameter of an IOL affects ray paths at large angles, leading to a dimming of the main image for small pupils, and to peripheral illumination by light bypassing the IOL for larger pupils. These effects are rarely bothersome, and cataract surgery is highly successful, but there is a need to improve the characterization of far peripheral vision, for both pseudophakic and phakic eyes. Perimetry is the main quantitative test, but the purpose is to evaluate pathologies rather than characterize vision (and object and image regions are no longer uniquely related in the pseudophakic eye). The maximum visual angle is approximately 105 0 , but there is limited information about variations with age, race, or refractive error (in case there is an unexpected link with the development of myopia), or about how clear cornea, iris location, and the limiting retina are related. Also, the detection of peripheral motion is widely recognized to be important, yet rarely evaluated. Overall, people rarely complain specifically about this visual region, but with "normal" vision including an IOL for >5% of people, and increasing interest in virtual reality and augmented reality, there are new reasons to characterize peripheral vision more completely. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sirolimus for progressive neurofibromatosis type 1-associated plexiform neurofibromas: a neurofibromatosis Clinical Trials Consortium phase II study.

PubMed

Weiss, Brian; Widemann, Brigitte C; Wolters, Pamela; Dombi, Eva; Vinks, Alexander; Cantor, Alan; Perentesis, John; Schorry, Elizabeth; Ullrich, Nicole; Gutmann, David H; Tonsgard, James; Viskochil, David; Korf, Bruce; Packer, Roger J; Fisher, Michael J

2015-04-01

Plexiform neurofibromas (PNs) are benign peripheral nerve sheath tumors that arise in one-third of individuals with neurofibromatosis type 1 (NF1). They may cause significant disfigurement, compression of vital structures, neurologic dysfunction, and/or pain. Currently, the only effective management strategy is surgical resection. Converging evidence has demonstrated that the NF1 tumor suppressor protein, neurofibromin, negatively regulates activity in the mammalian Target of Rapamycin pathway. We employed a 2-strata clinical trial design. Stratum 1 included subjects with inoperable, NF1-associated progressive PN and sought to determine whether sirolimus safely and tolerably increases time to progression (TTP). Volumetric MRI analysis conducted at regular intervals was used to determine TTP relative to baseline imaging. The estimated median TTP of subjects receiving sirolimus was 15.4 months (95% CI: 14.3-23.7 mo), which was significantly longer than 11.9 months (P < .001), the median TTP of the placebo arm of a previous PN clinical trial with similar eligibility criteria. This study demonstrated that sirolimus prolongs TTP by almost 4 months in patients with NF1-associated progressive PN. Although the improvement in TTP is modest, given the lack of significant or frequent toxicity and the availability of few other treatment options, the use of sirolimus to slow the growth of progressive PN could be considered in select patients. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Ultrasound-Guided Cryoanalgesia of Peripheral Nerve Lesions.

PubMed

Djebbar, Sahlya; Rossi, Ignacio M; Adler, Ronald S

2016-11-01

The real-time nature of ultrasound makes it ideally suited to provide guidance for a variety of musculoskeletal interventional procedures involving peripheral nerves. Continuous observation of the needle ensures proper placement and allows continuous monitoring when performing localized ablative therapy and therefore more accurate positioning of a cryoprobe, use of smaller needles, as well as access to small structures. We describe our experience performing cryoablative procedures. Patients undergoing cryoneurolysis have largely reported varying degrees of long-term pain relief and improvement in function; no serious complications have yet been identified. Ultrasound-guided cryoneurolysis can provide a useful, safe alternative to other ablative techniques to achieve long-term analgesia from painful peripheral nerve lesions. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Review of Matters Related to the Death of Corporal Patrick Tillman, U.S. Army

DTIC Science & Technology

2007-03-26

34 or " jingle " truck). The jinga truck, driven by a local Afghan, was towing a fifth (inoperable) U.S. vehicle. After the split, Serial 1 traveled down...vehicle, with the assistance of a local " jingle " truck, to a pre-designated location for pick up. After the two Serials separated, and due to terrain

Implementing Emergency Online Schools on the Fly as a Means of Responding to School Closures after Disaster Strikes

ERIC Educational Resources Information Center

Rush, S. Craig; Partridge, Ashley; Wheeler, Joanna

2016-01-01

One means of sustaining school operations when a disaster makes school buildings inaccessible or inoperable for an extended period of time is to use online and other communication technology to temporarily provide online schooling, also known as emergency online schools. However, the current literature on emergency online schools suggests that…

National ESPC Committee Support

DTIC Science & Technology

2015-09-30

to the physical parameterization driver software at Navy, NOAA , NASA , and AFWA. This interoperability capability will allow for more...core from another system. Under NUOPC funding, ESMF development will be completed, maintained and evolved to address DoD and NOAA requirements. In...operational NWP centers; however, it also involves collaboration with other primary NWP development centers such as NASA , NCAR, and DOE and will

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction.

PubMed

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-08-14

To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization's scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure.

High intensity focused ultrasound ablation for patients with inoperable liver cancer.

PubMed

Chen, Lianyu; Wang, Kun; Chen, Zhen; Meng, Zhiqiang; Chen, Hao; Gao, Huifeng; Wang, Peng; Zhu, Huili; Lin, Junhua; Liu, Luming

2015-01-01

To analyses the feasibility and efficacy of high intensity focused ultrasound (HIFU) treatment in patients with inoperable liver cancer. 187 patients were treated with HIFU, of all these patients 116 cases were Primary Liver Cancer (PLC) and 71 cases were Metastatic Liver Cancer (MLC). According to some parameters, such as clinical symptoms, the basis of main organs functional tests, imaging examinations, and progression-free survival (PFS) time to assess the safety and efficacy of HIFU in the treatment of liver cancer. 55 patients (29.4%) achieved CR and 73 patients (39.0%) achieved PR, 32 patients (17.1%) had responses of SD, and 27 patients (14.4%) were PD, respectively. Response rates were 90.5% (32 CR + 6 PR/42) in left lobe cancer and 64.1% (22 CR + 62 PR/131) in right lobe cancer. The median PFS for those CR case was 7 months, of PLC was 8 months, of MLC was 5 months. HIFU is effective and feasible in the treatment of liver cancer. It offer a significant noninvasive therapy for local treatment of liver cancer. For those right lobe liver cancers or with poor ultrasonic window, increasing treatment time or repeated treatment may improve the efficiency of HIFU ablation.

Understanding and managing the effects of battery charger and inverter aging

NASA Astrophysics Data System (ADS)

Gunther, W.; Aggarwal, S.

An aging assessment of battery chargers and inverters was conducted under the auspices of the NRC's Nuclear Plant Aging Research (NPAR) Program. The intentions of this program are to resolve issues related to the aging and service wear of equipment and systems at operating reactor facilities and to assess their impact on safety. Inverters and battery chargers are used in nuclear power plants to perform significant functions related to plant safety and availability. The specific impact of a battery charger or inverter failure varies with plant configuration. Operating experience data have demonstrated that reactor trips, safety injection system actuations, and inoperable emergency core cooling systems have resulted from inverter failures; and dc bus degradation leading to diesel generator inoperability or loss of control room annunication and indication have resulted from battery and battery charger failures. For the battery charger and inverter, the aging and service wear of subcomponents have contributed significantly to equipment failures. This paper summarizes the data and then describes methods that can be used to detect battery charger and inverter degradation prior to failure, as well as methods to minimize the failure effects. In both cases, the managing of battery charger and inverter aging is emphasized.

Peripheral artery disease - legs

MedlinePlus

... flow, which can injure nerves and other tissues. Causes PAD is caused by "hardening of the arteries." ... small arteries Coronary artery disease Impotence Open sores (ischemic ulcers on the lower legs) Tissue death (gangrene) ...

What is the Best Strategy on Detection of Cornea Neuropathy in People with Diabetes? Recent Advances in Potential Measurements.

PubMed

Lv, Ying; Zhao, Shaozhen

2018-03-26

There are well-acknowledged clinical or pre-clinical measurements concerning diabetic peripheral neuropathy(DPN). The current gold standard for diagnosis of diabetic peripheral neuropathy is nerve conduction suitable for detecting large nerve fiber function[1] and intraepidermal nerve fiber density assessment for small fiber damage evaluation[2]. The lack of a sensitive, non-invasive, and repeatable endpoint to measure changes in small nerve fibers is a major factor holding back clinical trials for the treatment of diabetic peripheral neuropathy. As cornea is the most densely innerved tissue, assessing corneal nerves' structure and function will be promising to predict and assess the degree of DPN [3]. In the diabetic micro-environment, damaged corneal nerves lead to decreased corneal sensitivity, both of which resulting in abnormal tear function. According to this theory, the measurements of nerve structure, corneal sensitivity, tear secretion and tear components, to some extent, can reveal and assess the state of corneal neuropathy. This review focuses on summarizing the knowledge of the latest detective methods of diabetic corneal neuropathy, popular in use or possible to further in study and be applied into clinical practice. Copyright © 2018 Elsevier B.V. All rights reserved.

Clinical Outcomes and Prognostic Factors of High-Dose Proton Beam Therapy for Peripheral Stage I Non-Small-Cell Lung Cancer.

PubMed

Hatayama, Yoshiomi; Nakamura, Tatsuya; Suzuki, Motohisa; Azami, Yusuke; Ono, Takashi; Yabuuchi, Tomonori; Hayashi, Yuichiro; Kimura, Kanako; Hirose, Katsumi; Wada, Hitoshi; Hareyama, Masato; Kikuchi, Yasuhiro; Takai, Yoshihiro

2016-09-01

The efficacy, toxicity, and prognostic factors of high-dose proton beam therapy (PBT) for peripheral stage I non-small-cell lung cancer were assessed in this retrospective study. Fifty patients with peripheral stage I non-small-cell lung cancer, two of whom had heterochronic multiple lung cancers, underwent high-dose PBT between January 2009 and September 2014. The relative biological effectiveness of the proton beam was defined as 1.1. The beam energy and spread-out Bragg peak were fine-tuned for the 90% isodose volume of the prescribed dosage to encompass the planning target volume. The cumulative survival curves were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 4 of the Common Terminology Criteria for Adverse Events, version 4. The study included 35 males and 15 females with a median age of 72.5 years. The median follow-up period was 22.8 months. The clinical stage was IA in 44 (85%) and IB in eight (15%) tumors. The total dose of PBT was 66 GyE in 10 fractions in all tumors. Three-year overall survival rate among all patients was 87.9% (95% confidence interval [CI], 94.8%-73.2%). Forty-five patients were alive, and 5 were dead. Three-year local control and progression-free survival rates were 95.7% (95% CI, 98.9%-83.8%) and 76.3% (95% CI, 86.9%-59.3%), respectively. Only one patient experienced Grade 2 pneumonitis. High-dose PBT may be an effective and safe treatment option for patients with stage I non-small-cell lung cancer. Copyright © 2015 Elsevier Inc. All rights reserved.

AKAP localizes in a specific subset of TRPV1 and CaV1.2 positive nociceptive rat DRG neurons

PubMed Central

Brandao, Katherine E.; Dell’Acqua, Mark L.; Levinson, Simon R.

2016-01-01

Modulation of phosphorylation states of ion channels is a critical step in the development of hyperalgesia during inflammation. Modulatory enhancement of channel activity may increase neuronal excitability and affect downstream targets such as gene transcription. The specificity required for such regulation of ion channels quickly occurs via targeting of protein kinases and phosphatases by the scaffolding A-kinase anchoring protein 79/150 (AKAP79/150). AKAP79/150 has been implicated in inflammatory pain by targeting PKA and PKC to the TRPV1 channel in peripheral sensory neurons, thus lowering threshold for activation by multiple inflammatory reagents. However, the expression pattern of AKAP79/150 in peripheral sensory neurons is unknown. In this study we use immunofluorescence microscopy to identify in DRG sections the peripheral neuron subtypes that express the rodent isoform AKAP150, as well as the subcellular distribution of AKAP150 and its potential target ion channels. We found that AKAP150 is predominantly expressed in a subset of small DRG sensory neurons where it is localized at the plasma membrane of the soma, axon initial segment and small fibers. The majority of these neurons is peripherin positive and produces c-fibers, though a small portion produces Aδ-fibers. Furthermore, we demonstrate that AKAP79/150 colocalizes with TRPV1 and CaV1.2 in the soma and axon initial segment. Thus AKAP150 is expressed in small, nociceptive DRG neurons where it is targeted to membrane regions and where it may play a role in the modulation of ion channel phosphorylation states required for hyperalgesia. PMID:21674494

Effects of intravenous propranolol on heat pain sensitivity in healthy men.

PubMed

Schweinhardt, P; Abulhasan, Y B; Koeva, V; Balderi, T; Kim, D J; Alhujairi, M; Carli, F

2013-05-01

Clinical studies have shown opioid-sparing effects of β-adrenergic antagonists perioperatively and β-blockers are being investigated for chronic musculoskeletal pain. However, the direct analgesic effects of β-blockers have rarely been examined in healthy humans. In a randomized, counter-balanced, double-blind, within-subject crossover design, we tested the effect of the lipophilic β-blocker propranolol (0.035 mg/kg body weight i.v.) on heat pain sensitivity in 39 healthy males, compared with placebo. To test for peripheral versus central effects, the peripherally acting β-blocker sotalol was also examined. Experimental stimuli were brief superficial noxious heat stimuli applied to the volar forearm. Non-painful cold stimuli were included to test for specificity. Sedation, mood and anxiety were assessed to investigate potential mechanisms underlying any analgesic effect. β-blocker effects on blood pressure were incorporated into the analysis because of a known inverse relationship between pain sensitivity and systolic blood pressure. Propranolol significantly decreased perceived intensity of heat pain stimuli but only in participants with small propranolol-induced blood pressure decreases. Even in this group, the effect was small (4%). Propranolol did not influence perceived intensity of non-noxious stimuli and had no effect on sedation, anxiety or mood. Sotalol did not influence heat pain sensitivity. Propranolol decreased pain sensitivity but its analgesic effects were small and counteracted by blood pressure decreases. The analgesic effects were not mediated by peripheral β-receptor blockade, sedation, mood or anxiety. The small effect indicates that the utility of β-blockers for clinical pain must be related to factors that do not play a significant role for experimental pain. © 2012 European Federation of International Association for the Study of Pain Chapters.

Teaching by Simulation with Personal Computers.

ERIC Educational Resources Information Center

Randall, James E.

1978-01-01

Describes the use of a small digital computer to simulate a peripheral nerve demonstration in which the action potential responses to pairs of stimuli are used to illustrate the properties of excitable membranes. (Author/MA)

Peripherally inserted central catheter - dressing change

MedlinePlus

... chlorhexidine) in a single-use small applicator Special sponges or wipes that contain a cleaning agent, such ... Clean your skin around the site with the sponge and cleaning solution for 30 seconds. Let the ...

Intravenous Chemotherapy or Oral Chemotherapy in Treating Patients With Previously Untreated Stage III-IV HIV-Associated Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-06-20

AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma

The Celtic fringe of Britain: insights from small mammal phylogeography

PubMed Central

Searle, Jeremy B.; Kotlík, Petr; Rambau, Ramugondo V.; Marková, Silvia; Herman, Jeremy S.; McDevitt, Allan D.

2009-01-01

Recent genetic studies have challenged the traditional view that the ancestors of British Celtic people spread from central Europe during the Iron Age and have suggested a much earlier origin for them as part of the human recolonization of Britain at the end of the last glaciation. Here we propose that small mammals provide an analogue to help resolve this controversy. Previous studies have shown that common shrews (Sorex araneus) with particular chromosomal characteristics and water voles (Arvicola terrestris) of a specific mitochondrial (mt) DNA lineage have peripheral western/northern distributions with striking similarities to that of Celtic people. We show that mtDNA lineages of three other small mammal species (bank vole Myodes glareolus, field vole Microtus agrestis and pygmy shrew Sorex minutus) also form a ‘Celtic fringe’. We argue that these small mammals most reasonably colonized Britain in a two-phase process following the last glacial maximum (LGM), with climatically driven partial replacement of the first colonists by the second colonists, leaving a peripheral geographical distribution for the first colonists. We suggest that these natural Celtic fringes provide insight into the same phenomenon in humans and support its origin in processes following the end of the LGM. PMID:19793757

Cixutumumab and Doxorubicin Hydrochloride in Treating Patients With Unresectable, Locally Advanced, or Metastatic Soft Tissue Sarcoma

ClinicalTrials.gov

2016-05-16

Adult Angiosarcoma; Adult Desmoplastic Small Round Cell Tumor; Adult Epithelioid Sarcoma; Adult Extraskeletal Myxoid Chondrosarcoma; Adult Extraskeletal Osteosarcoma; Adult Fibrosarcoma; Adult Leiomyosarcoma; Adult Liposarcoma; Adult Malignant Mesenchymoma; Adult Malignant Peripheral Nerve Sheath Tumor; Adult Rhabdomyosarcoma; Adult Synovial Sarcoma; Adult Undifferentiated High Grade Pleomorphic Sarcoma of Bone; Childhood Angiosarcoma; Childhood Desmoplastic Small Round Cell Tumor; Childhood Epithelioid Sarcoma; Childhood Fibrosarcoma; Childhood Leiomyosarcoma; Childhood Liposarcoma; Childhood Malignant Mesenchymoma; Childhood Malignant Peripheral Nerve Sheath Tumor; Childhood Pleomorphic Rhabdomyosarcoma; Childhood Rhabdomyosarcoma With Mixed Embryonal and Alveolar Features; Childhood Synovial Sarcoma; Dermatofibrosarcoma Protuberans; Malignant Adult Hemangiopericytoma; Malignant Childhood Hemangiopericytoma; Metastatic Childhood Soft Tissue Sarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Adult Soft Tissue Sarcoma; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma; Untreated Childhood Rhabdomyosarcoma

Quasi-planar elemental clusters in pair interactions approximation

NASA Astrophysics Data System (ADS)

Chkhartishvili, Levan

2016-01-01

The pair-interactions approximation, when applied to describe elemental clusters, only takes into account bonding between neighboring atoms. According to this approach, isomers of wrapped forms of 2D clusters - nanotubular and fullerene-like structures - and truly 3D clusters, are generally expected to be more stable than their quasi-planar counterparts. This is because quasi-planar clusters contain more peripheral atoms with dangling bonds and, correspondingly, fewer atoms with saturated bonds. However, the differences in coordination numbers between central and peripheral atoms lead to the polarization of bonds. The related corrections to the molar binding energy can make small, quasi-planar clusters more stable than their 2D wrapped allotropes and 3D isomers. The present work provides a general theoretical frame for studying the relative stability of small elemental clusters within the pair interactions approximation.

Atypical/Nor98 Scrapie Infectivity in Sheep Peripheral Tissues

PubMed Central

Andréoletti, Olivier; Orge, Leonor; Benestad, Sylvie L.; Beringue, Vincent; Litaise, Claire; Simon, Stéphanie; Le Dur, Annick; Laude, Hubert; Simmons, Hugh; Lugan, Séverine; Corbière, Fabien; Costes, Pierrette; Morel, Nathalie; Schelcher, François; Lacroux, Caroline

2011-01-01

Atypical/Nor98 scrapie was first identified in 1998 in Norway. It is now considered as a worldwide disease of small ruminants and currently represents a significant part of the detected transmissible spongiform encephalopathies (TSE) cases in Europe. Atypical/Nor98 scrapie cases were reported in ARR/ARR sheep, which are highly resistant to BSE and other small ruminants TSE agents. The biology and pathogenesis of the Atypical/Nor98 scrapie agent in its natural host is still poorly understood. However, based on the absence of detectable abnormal PrP in peripheral tissues of affected individuals, human and animal exposure risk to this specific TSE agent has been considered low. In this study we demonstrate that infectivity can accumulate, even if no abnormal PrP is detectable, in lymphoid tissues, nerves, and muscles from natural and/or experimental Atypical/Nor98 scrapie cases. Evidence is provided that, in comparison to other TSE agents, samples containing Atypical/Nor98 scrapie infectivity could remain PrPSc negative. This feature will impact detection of Atypical/Nor98 scrapie cases in the field, and highlights the need to review current evaluations of the disease prevalence and potential transmissibility. Finally, an estimate is made of the infectivity loads accumulating in peripheral tissues in both Atypical/Nor98 and classical scrapie cases that currently enter the food chain. The results obtained indicate that dietary exposure risk to small ruminants TSE agents may be higher than commonly believed. PMID:21347349

Detection and significance of TregFoxP3+ and Th17 cells in peripheral blood of non-small cell lung cancer patients

PubMed Central

Li, Sha; Li, Yan; Qu, Xun; Liu, Xiaolin

2014-01-01

Introduction The aim of this study was to explore the relationships between TregFoxP3+ cells and Th17 cells and occurrence of lung cancer. Material and methods The proportions of TregFoxP3+ and Th17 cells, the expression of FoxP3 and RORγt mRNA, and the levels of related cell factors such as transforming growth factor-β (TGF-β), interleukin IL-17 (IL-17) and IL-23 were determined respectively by flow cytometry analysis, real-time-polymerase chain reaction (PCR), and ELISA in peripheral blood of 18 healthy people and 26 patients with non-small cell lung cancer (NSCLC). Results The levels of TregFoxP3+ and Th17, expression of FoxP3 and RORγt mRNA, and ratios of TregFoxP3+/Th17 and FoxP3/RORγt in peripheral blood with NSCLC were higher than those in healthy controls (p < 0.05). The proportion of Th17 cells from NSCLC patients was positively correlated with that of TregFoxP3+ (r = 0.81, p < 0.05). The receiver-operating characteristic (ROC) curve demonstrates that the increased level of TregFoxP3+/Th17 in the peripheral blood may be a useful indicator in early diagnosis of non-small cell lung carcinoma. The TregFoxP3+/Th17 and FoxP3/RORγt levels for patients in stage IV were higher than those of patients in stages I, II, and III (p < 0.05). The levels of TGF-β, IL-17, and IL-23 were higher in NSCLC patients than those in healthy controls. Conclusions The results suggest that ratios of Treg/Th17 correlate with the stage of NSCLC. PMID:24904654

Peripheral neuropathy in military aircraft maintenance workers in Australia.

PubMed

Guest, Maya; Attia, John R; D'este, Catherine A; Boggess, May M; Brown, Anthony M; Gibson, Richard E; Tavener, Meredith A; Ross, James; Gardner, Ian; Harrex, Warren

2011-04-01

This study aimed to examine possible persisting peripheral neuropathy in a group who undertook fuel tank repairs on F-111 aircraft, relative to two contemporaneous comparison groups. Vibration perception threshold (VPT) was tested using biothesiometry in 614 exposed personnel, compared with two unexposed groups (513 technical trades and 403 nontrades). Regression modeling was used to examine associations, adjusting for possible confounders. We observed that 26% of participants had chronic persistent increased VPT in the great toe. In contrast, statistically significant higher VPT of the great toe was observed in the comparison groups; however, the effect was small, about 1/4 the magnitude of diabetes. Age, height, and diabetes were all significant and strong predictors in most models. This study highlights chronic persisting peripheral neuropathy in a population of aircraft maintainers.

Generalised peripheral oedema associated with amlodipine therapy in two dogs.

PubMed

Creevy, K E; Scuderi, M A; Ellis, A E

2013-11-01

This report details two cases of adverse drug reactions to amlodipine. The first case presented with diffuse peripheral oedema and a history of amlodipine therapy. Haematology, clinical chemistry, endocrine testing, thoracic, abdominal and cardiac imaging revealed no cause for oedema. Amlodipine therapy was discontinued and oedema diminished markedly within 72 hours. The second case presented for bilateral retinal detachments secondary to systemic hypertension. Haematology, clinical chemistry, thoracic and abdominal imaging were unremarkable and amlodipine therapy was begun. Within 72 hours, diffuse peripheral oedema developed that was unresponsive to therapy and the dog was euthanised. Veterinarians should be aware of the potential serious adverse events associated with commonly used drugs; severe, diffuse oedema is a possible adverse drug event in dogs treated with amlodipine. © 2013 British Small Animal Veterinary Association.

Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast.

PubMed

Ikhwan, S M; Kenneth, V K T; Seoparjoo, A; Zin, A A M

2013-06-21

Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.

The Czechoslovak Legions in World War I

DTIC Science & Technology

2012-05-04

Army. The Legion’s efforts in Russia after Brest -Utovsk Peace Treaty prevented Central Powers from reinforcing the Western and Southem fronts with...Czechoslovak Republic. While operating in Russia after the Brest – Litovsk peace treaty, the Legionaries continued fighting the Central Powers in...Operations in East Russia after the Brest -Litovsk peace treaty. Support of anti-Bolshevik movement. Content: Introduction – Creation of

Boron Neutron Capture Therapy in the Treatment of Locally Recurred Head-and-Neck Cancer: Final Analysis of a Phase I/II Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kankaanranta, Leena; Seppaelae, Tiina; Koivunoro, Hanna

2012-01-01

Purpose: To investigate the efficacy and safety of boron neutron capture therapy (BNCT) in the treatment of inoperable head-and-neck cancers that recur locally after conventional photon radiation therapy. Methods and Materials: In this prospective, single-center Phase I/II study, 30 patients with inoperable, locally recurred head-and-neck cancer (29 carcinomas and 1 sarcoma) were treated with BNCT. Prior treatments consisted of surgery and conventionally fractionated photon irradiation to a cumulative dose of 50 to 98 Gy administered with or without concomitant chemotherapy. Tumor responses were assessed by use of the RECIST (Response Evaluation Criteria in Solid Tumors) and adverse effects by usemore » of the National Cancer Institute common terminology criteria version 3.0. Intravenously administered L-boronophenylalanine-fructose (400 mg/kg) was administered as the boron carrier. Each patient was scheduled to be treated twice with BNCT. Results: Twenty-six patients received BNCT twice; four were treated once. Of the 29 evaluable patients, 22 (76%) responded to BNCT, 6 (21%) had tumor growth stabilization for 5.1 and 20.3 months, and 1 (3%) progressed. The median progression-free survival time was 7.5 months (95% confidence interval, 5.4-9.6 months). Two-year progression-free survival and overall survival were 20% and 30%, respectively, and 27% of the patients survived for 2 years without locoregional recurrence. The most common acute Grade 3 adverse effects were mucositis (54% of patients), oral pain (54%), and fatigue (32%). Three patients were diagnosed with osteoradionecrosis (each Grade 3) and one patient with soft-tissue necrosis (Grade 4). Late Grade 3 xerostomia was present in 3 of the 15 evaluable patients (20%). Conclusions: Most patients who have inoperable, locally advanced head-and-neck carcinoma that has recurred at a previously irradiated site respond to boronophenylalanine-mediated BNCT, but cancer recurrence after BNCT remains frequent. Toxicity was acceptable. Further research on novel modifications of the method is warranted.« less

Effect of tricuspid regurgitation and the right heart on survival after transcatheter aortic valve replacement: insights from the Placement of Aortic Transcatheter Valves II inoperable cohort.

PubMed

Lindman, Brian R; Maniar, Hersh S; Jaber, Wael A; Lerakis, Stamatios; Mack, Michael J; Suri, Rakesh M; Thourani, Vinod H; Babaliaros, Vasilis; Kereiakes, Dean J; Whisenant, Brian; Miller, D Craig; Tuzcu, E Murat; Svensson, Lars G; Xu, Ke; Doshi, Darshan; Leon, Martin B; Zajarias, Alan

2015-04-01

Tricuspid regurgitation (TR) and right ventricular (RV) dysfunction adversely affect outcomes in patients with heart failure or mitral valve disease, but their impact on outcomes in patients with aortic stenosis treated with transcatheter aortic valve replacement has not been well characterized. Among 542 patients with symptomatic aortic stenosis treated in the Placement of Aortic Transcatheter Valves (PARTNER) II trial (inoperable cohort) with a Sapien or Sapien XT valve via a transfemoral approach, baseline TR severity, right atrial and RV size and RV function were evaluated by echocardiography according to established guidelines. One-year mortality was 16.9%, 17.2%, 32.6%, and 61.1% for patients with no/trace (n=167), mild (n=205), moderate (n=117), and severe (n=18) TR, respectively (P<0.001). Increasing severity of RV dysfunction as well as right atrial and RV enlargement were also associated with increased mortality (P<0.001). After multivariable adjustment, severe TR (hazard ratio, 3.20; 95% confidence interval, 1.50-6.82; P=0.003) and moderate TR (hazard ratio, 1.60; 95% confidence interval, 1.02-2.52; P=0.042) remained associated with increased mortality as did right atrial and RV enlargement, but not RV dysfunction. There was an interaction between TR and mitral regurgitation severity (P=0.04); the increased hazard of death associated with moderate/severe TR only occurred in those with no/trace/mild mitral regurgitation. In inoperable patients treated with transcatheter aortic valve replacement, moderate or severe TR and right heart enlargement are independently associated with increased 1-year mortality; however, the association between moderate or severe TR and an increased hazard of death was only found in those with minimal mitral regurgitation at baseline. These findings may improve our assessment of anticipated benefit from transcatheter aortic valve replacement and support the need for future studies on TR and the right heart, including whether concomitant treatment of TR in operable but high-risk patients with aortic stenosis is warranted. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01314313. © 2015 American Heart Association, Inc.

Riociguat in patients with chronic thromboembolic pulmonary hypertension: results from an early access study.

PubMed

McLaughlin, Vallerie V; Jansa, Pavel; Nielsen-Kudsk, Jens E; Halank, Michael; Simonneau, Gérald; Grünig, Ekkehard; Ulrich, Silvia; Rosenkranz, Stephan; Gómez Sánchez, Miguel A; Pulido, Tomás; Pepke-Zaba, Joanna; Barberá, Joan Albert; Hoeper, Marius M; Vachiéry, Jean-Luc; Lang, Irene; Carvalho, Francine; Meier, Christian; Mueller, Katharina; Nikkho, Sylvia; D'Armini, Andrea M

2017-12-28

Following positive results from the Phase III CHEST-1 study in patients with inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), the Phase IIIb CTEPH early access study (EAS) was designed to assess the safety and tolerability of riociguat in real-world clinical practice, as well as to provide patients with early access to riociguat before launch. Riociguat is approved for the treatment of inoperable and persistent/recurrent CTEPH. We performed an open-label, uncontrolled, single-arm, early access study in which 300 adult patients with inoperable or persistent/recurrent CTEPH received riociguat adjusted from 1 mg three times daily (tid) to a maximum of 2.5 mg tid. Patients switching from unsatisfactory prior pulmonary arterial hypertension (PAH)-targeted therapy (n = 84) underwent a washout period of at least 3 days before initiating riociguat. The primary aim was to assess the safety and tolerability of riociguat, with World Health Organization functional class and 6-min walking distance (6MWD) as exploratory efficacy endpoints. In total, 262 patients (87%) completed study treatment and entered the safety follow-up (median treatment duration 47 weeks). Adverse events were reported in 273 patients (91%). The most frequently reported serious adverse events were syncope (6%), right ventricular failure (3%), and pneumonia (2%). There were five deaths, none of which was considered related to study medication. The safety and tolerability of riociguat was similar in patients switched from other PAH-targeted therapies and those who were treatment naïve. In patients with data available, mean ± standard deviation 6MWD had increased by 33 ± 42 m at Week 12 with no clinically relevant differences between the switched and treatment-naïve subgroups. Riociguat was well tolerated in patients with CTEPH who were treatment naïve, and in those who were switched from other PAH-targeted therapies. No new safety signals were observed. ClinicalTrials.org NCT01784562 . Registered February 4, 2013.

Congenital Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor: A Case Report and Review of the Literature.

PubMed

Jin, Shu-Guang; Jiang, Xiao-Ping; Zhong, Lin

2016-10-01

Ewing's sarcoma (EWS) and peripheral primitive neuroectodermal tumor (pPNET) are small round cell malignancies that develop in soft tissue and bone. They very rarely affect newborns. A diagnosis of EWS/pPNET depends mainly on immunohistochemistry and molecular/genetic assays. Since these tumors are highly aggressive, patient prognosis is typically very poor, and treatment remains a challenge. Here, we report a 13-day-old newborn diagnosed with congenital EWS/pPNET and describe its treatment. Copyright © 2014. Published by Elsevier B.V.

Peripheral killer cells do not differentiate between asthma patients with or without fixed airway obstruction.

PubMed

Tubby, Carolyn; Negm, Ola H; Harrison, Timothy; Tighe, Patrick J; Todd, Ian; Fairclough, Lucy C

2017-06-01

The three main types of killer cells - CD8 + T cells, NK cells and NKT cells - have been linked to asthma and chronic obstructive pulmonary disease (COPD). However, their role in a small subset of asthma patients displaying fixed airway obstruction (FAO), similar to that seen in COPD, has not been explored. The objective of the present study was to investigate killer cell numbers, phenotype and function in peripheral blood from asthma patients with FAO, asthma patients without FAO, and healthy individuals. Peripheral CD8 + T cells (CD8 + CD3 + CD56 - ), NK cells (CD56 + CD3 - ) and NKT-like cells (CD56 + CD3 + ) of 14 asthma patients with FAO (post-bronchodilator FEV/FVC <0.7, despite clinician-optimised treatment), 7 asthma patients without FAO (post-bronchodilator FEV/FVC ≥ 0.7), and 9 healthy individuals were studied. No significant differences were seen between the number, receptor expression, MAPK signalling molecule expression, cytotoxic mediator expression, and functional cytotoxicity of peripheral killer cells from asthma patients with FAO, asthma patients without FAO and healthy individuals. Peripheral killer cell numbers or functions do not differentiate between asthma patients with or without fixed airway obstruction.

KCC3 axonopathy: neuropathological features in the central and peripheral nervous system.

PubMed

Auer, Roland N; Laganière, Janet L; Robitaille, Yves O; Richardson, John; Dion, Patrick A; Rouleau, Guy A; Shekarabi, Masoud

2016-09-01

Hereditary motor and sensory neuropathy associated with agenesis of the corpus callosum (HMSN/ACC) is an autosomal recessive disease of the central and peripheral nervous system that presents as early-onset polyneuropathy. Patients are hypotonic and areflexic from birth, with abnormal facial features and atrophic muscles. Progressive peripheral neuropathy eventually confines them to a wheelchair in the second decade of life, and death occurs by the fourth decade. We here define the neuropathologic features of the disease in autopsy tissues from eight cases. Both developmental and neurodegenerative features were found. Hypoplasia or absence of the major telencephalic commissures and a hypoplasia of corticospinal tracts to half the normal size, were the major neurodevelopmental defects we observed. Despite being a neurodegenerative disease, preservation of brain weight and a conspicuous absence of neuronal or glial cell death were signal features of this disease. Small tumor-like overgrowths of axons, termed axonomas, were found in the central and peripheral nervous system, indicating attempted axonal regeneration. We conclude that the neurodegenerative deficits in HMSN/ACC are primarily caused by an axonopathy superimposed upon abnormal development, affecting peripheral but also central nervous system axons, all ultimately because of a genetic defect in the axonal cotransporter KCC3.

Imatinib Mesylate in Treating Patients With Relapsed or Refractory Solid Tumors of Childhood

ClinicalTrials.gov

2015-04-14

Childhood Desmoplastic Small Round Cell Tumor; Childhood Synovial Sarcoma; Gastrointestinal Stromal Tumor; Lung Metastases; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

Characterizing Treatable Causes of Small Fiber Polyneuropathy in Gulf War Veterans

DTIC Science & Technology

2016-10-01

autoimmune thyroid disease . Clin Rheumatol 33(7):885–891 31. Ørstavik K, Norheim I, Jorum E (2006) Pain and small-fiber neu- ropathy in patients with ...neuronopathy associated with celiac disease : skin biopsy findings. Arch Neurol 62:1574–1578 38. Chin RL, Latov N (2005) Peripheral neuropathy and celiac dis...patients with biopsy-verified celiac disease . JAMA Neurol 72(7):806–811 40. Tavee J, Zhou L (2009) Small fiber neuropathy: a burning problem. Cleve Clin

Reproductive hormones in menstrual blood.

PubMed

Zhou, J P; Fraser, I S; Caterson, I; Grivas, A; McCarron, G; Norman, T; Tan, K

1989-08-01

Menstrual and peripheral blood samples were collected from 19 regularly cycling women on days 1-3 of the menstrual cycle. Menstrual samples were collected with a soft silicone rubber menstrual cup. Hematocrit, PRL, LH, FSH, estradiol (E2), and progesterone (P4) were measured in all samples. Validation studies were carried out for RIAs of PRL, LH, and FSH in menstrual plasma. The menstrual plasma PRL level was significantly higher than its peripheral blood level on day 1 (63.3 +/- 14.7 and 12.1 +/- 2.9 micrograms/L, respectively; t = 3.331; P less than 0.01), and menstrual PRL was significantly higher on day 1 than on day 2 (t = 3.340; P less than 0.01). There was a strong negative correlation between log menstrual PRL concentration and time of onset of menstruation (r = -0.596; P less than 0.01). Menstrual plasma FSH levels were significantly lower than peripheral levels on each of days 1-3 (day 1:t = 4.787; P less than 0.001), and there was a significant positive correlation between menstrual and peripheral levels (r = 0.607; P less than 0.01). By contrast, menstrual plasma LH was significantly higher than the peripheral level on days 1 and 2 (day 1:t = 3.105; day 2:t = 3.180; P less than 0.01), with no correlation between menstrual and peripheral levels. Menstrual E2 was slightly lower than and significantly positively correlated with peripheral E2 (r = 0.646; P less than 0.01). Menstrual P4 was lower than but showed no correlation with peripheral levels. As expected, the menstrual blood hematocrit was less than 0.20 and highly significantly lower than that of peripheral venous blood. These results suggest that PRL is released in substantial amounts from secretory endometrium into the menstrual flow during the first day of menstrual breakdown. LH may also be released in small amounts from menstrual endometrium, while menstrual FSH, E2, and P4 probably arise entirely from the peripheral circulation.

Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity

PubMed Central

Argueta, Donovan A.; DiPatrizio, Nicholas V.

2017-01-01

The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance. We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats. We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i.e., high fat and sucrose). Feeding patterns were assessed in male C57BL/6Tac mice maintained for 60 days on WD or a standard rodent chow (SD), and the role for peripheral endocannabinoid signaling at CB1Rs in controlling food intake was investigated via pharmacological interventions. In addition, levels of the endocannabinoids, 2-AG and anandamide, in the upper small intestine and circulation of mice were analyzed via liquid chromatography coupled to tandem mass spectrometry to evaluate diet-related changes in endocannabinoid signaling and the potential impact on food intake. Mice fed WD for 60 days exhibited large increases in body weight, daily caloric intake, average meal size, and rate of feeding when compared to control mice fed SD. Inhibiting peripheral CB1Rs with the peripherally-restricted neutral cannabinoid CB1 receptor antagonist, AM6545 (10mg/kg), significantly reduced intake of WD during a 6 h test, but failed to modify intake of SD in mice. AM6545 normalized intake of WD, average meal size, and rate of feeding to levels found in SD control mice. These results suggest that endogenous activity at peripheral CB1Rs in WD mice is critical for driving hyperphagia. In support of this hypothesis, levels of 2-AG and anandamide in both, jejunum mucosa and plasma, of ad-libitum fed WD mice increased when compared to SC mice. Furthermore, expression of genes for primary components of the endocannabinoid system (i.e., cannabinoid receptors, and endocannabinoid biosynthetic and degradative enzymes) was dysregulated in WD mice when compared to SC mice. Our results suggest that hyperphagia associated with WD-induced obesity is driven by enhanced endocannabinoid signaling at peripheral CB1Rs. PMID:28065722

Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity.

PubMed

Argueta, Donovan A; DiPatrizio, Nicholas V

2017-03-15

The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance. We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats. We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i.e., high fat and sucrose). Feeding patterns were assessed in male C57BL/6Tac mice maintained for 60days on WD or a standard rodent chow (SD), and the role for peripheral endocannabinoid signaling at CB 1 Rs in controlling food intake was investigated via pharmacological interventions. In addition, levels of the endocannabinoids, 2-AG and anandamide, in the upper small intestine and circulation of mice were analyzed via liquid chromatography coupled to tandem mass spectrometry to evaluate diet-related changes in endocannabinoid signaling and the potential impact on food intake. Mice fed WD for 60days exhibited large increases in body weight, daily caloric intake, average meal size, and rate of feeding when compared to control mice fed SD. Inhibiting peripheral CB 1 Rs with the peripherally-restricted neutral cannabinoid CB 1 receptor antagonist, AM6545 (10mg/kg), significantly reduced intake of WD during a 6h test, but failed to modify intake of SD in mice. AM6545 normalized intake of WD, average meal size, and rate of feeding to levels found in SD control mice. These results suggest that endogenous activity at peripheral CB 1 Rs in WD mice is critical for driving hyperphagia. In support of this hypothesis, levels of 2-AG and anandamide in both, jejunum mucosa and plasma, of ad-libitum fed WD mice increased when compared to SC mice. Furthermore, expression of genes for primary components of the endocannabinoid system (i.e., cannabinoid receptors, and endocannabinoid biosynthetic and degradative enzymes) was dysregulated in WD mice when compared to SC mice. Our results suggest that hyperphagia associated with WD-induced obesity is driven by enhanced endocannabinoid signaling at peripheral CB 1 Rs. Copyright © 2017 Elsevier Inc. All rights reserved.

Retinotopic patterns of functional connectivity between V1 and large-scale brain networks during resting fixation

PubMed Central

Griffis, Joseph C.; Elkhetali, Abdurahman S.; Burge, Wesley K.; Chen, Richard H.; Bowman, Anthony D.; Szaflarski, Jerzy P.; Visscher, Kristina M.

2016-01-01

Psychophysical and neurobiological evidence suggests that central and peripheral vision are specialized for different functions. This specialization of function might be expected to lead to differences in the large-scale functional interactions of early cortical areas that represent central and peripheral visual space. Here, we characterize differences in whole-brain functional connectivity among sectors in primary visual cortex (V1) corresponding to central, near-peripheral, and far-peripheral vision during resting fixation. Importantly, our analyses reveal that eccentricity sectors in V1 have different functional connectivity with non-visual areas associated with large-scale brain networks. Regions associated with the fronto-parietal control network are most strongly connected with central sectors of V1, regions associated with the cingulo-opercular control network are most strongly connected with near-peripheral sectors of V1, and regions associated with the default mode and auditory networks are most strongly connected with far-peripheral sectors of V1. Additional analyses suggest that similar patterns are present during eyes-closed rest. These results suggest that different types of visual information may be prioritized by large-scale brain networks with distinct functional profiles, and provide insights into how the small-scale functional specialization within early visual regions such as V1 relates to the large-scale organization of functionally distinct whole-brain networks. PMID:27554527

Clinical Characteristics and Treatment Response of Peripheral Neuropathy in the Presence of Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss Syndrome): Experience at a Single Tertiary Center.

PubMed

Cho, Hye Jin; Yune, Sehyo; Seok, Jin Myoung; Cho, Eun Bin; Min, Ju Hong; Seo, Yeon Lim; Lee, Byung Jae; Kim, Byoung Joon; Choi, Dong Chull

2017-01-01

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic small-vessel vasculitis accompanied by asthma, eosinophilia, and eosinophilic inflammation of various tissues including the peripheral nerves. This study investigated the clinical course and long-term outcomes of peripheral neuropathy in patients with EGPA. Seventy-one patients with physician-diagnosed EGPA were identified at Samsung Medical Center between January 1995 and April 2014. Sixty-one of these patients were followed-up for more than 1 year and received corticosteroid therapy with or without intravenous cyclophosphamide pulse therapy for 6 to 18 months. Medical records of the 61 patients including demographic data, clinical features, laboratory and pathological findings, treatments, and outcomes were reviewed. Peripheral neuropathy as a manifestation of EGPA was present in 46 (75%) of the 61 patients. The mean follow-up duration of the patients with neuropathy was 6.4 years (range 1.2-18.8 years). The scores on the neurological functional disability scale before and after the combination treatment with corticosteroid and cyclophosphamide were 2.43±0.86 and 0.54±0.95 (mean±SD; p<0.001), respectively. The peripheral neuropathy relapsed in one patient. The long-term clinical outcome of peripheral neuropathy in patients with EGPA receiving initial corticosteroid and cyclophosphamide combination therapy was favorable with a very low relapse rate.

A Little Similarity Goes a Long Way: The Effects of Peripheral but Self-Revealing Similarities on Improving and Sustaining Interracial Relationships

PubMed Central

West, Tessa V.; Magee, Joe C.; Gordon, Sarah H.; Gullett, Lindy

2017-01-01

Integrating theory on close relationships and intergroup relations, we construct a manipulation of similarity that we demonstrate can improve interracial interactions across different settings. We find that manipulating perceptions of similarity on self-revealing attributes that are peripheral to the interaction improves interactions in cross-race dyads and racially diverse task groups. In a getting-acquainted context, we demonstrate that the belief that one’s different-race partner is similar to oneself on self-revealing, peripheral attributes leads to less anticipatory anxiety than the belief that one’s partner is similar on peripheral, nonself-revealing attributes. In another dyadic context, we explore the range of benefits that perceptions of peripheral, self-revealing similarity can bring to different-race interaction partners and find (a) less anxiety during interaction, (b) greater interest in sustained contact with one’s partner, and (c) stronger accuracy in perceptions of one’s partners’ relationship intentions. By contrast, participants in same-race interactions were largely unaffected by these manipulations of perceived similarity. Our final experiment shows that among small task groups composed of racially diverse individuals, those whose members perceive peripheral, self-revealing similarity perform superior to those who perceive dissimilarity. Implications for using this approach to improve interracial interactions across different goal-driven contexts are discussed. PMID:24956315

Synoviorthesis with 32P-colloidal chromic phosphate in rheumatoid arthritis--clinical, histopathologic and arthrographic changes.

PubMed

Onetti, C M; Gutiérrez, E; Hliba, E; Aguirre, C R

1982-01-01

Synoviorthesis was performed in 217 joints from 111 patients suffering from different stages of rheumatoid arthritis (RA). 32P-colloidal chromic phosphate was employed, with an average dose from 6 mCi for large joints (knees) to 0.3 mCi for small peripheral joints such as average dose from 6 mCi for large joints (knees) to 0.3 mCi for small peripheral joints such as the MCP or PIP joints. Satisfactory clinical results were observed in 84% of the cases and no significant side effects resulted after a follow-up period from 1 to 10 years. Striking effects after treatment were observed through histopathological studies (light and electron microscopy) and the use of contrast arthrography. We concluded that radioactive synovectomy with 32P-chromate is a very useful method for the local treatment of RA.

A "live" biopsy in a small-cell lung cancer patient by detection of circulating tumor cells.

PubMed

Bevilacqua, Simona; Gallo, Marianna; Franco, Renato; Rossi, Antonio; De Luca, Antonella; Rocco, Gaetano; Botti, Gerardo; Gridelli, Cesare; Normanno, Nicola

2009-07-01

A 71-year-old patient with a pulmonary lesion was diagnosed with a low-grade neuroendocrine tumor following examination of a fine needle aspiration biopsy. Analysis of a peripheral blood sample with the CellSearch system revealed the presence of putative circulating tumor cells (CTC) that were positive for EpCAM and cytokeratin (CK) expression. Since EpCAM is not usually expressed in neuroendocrine tumors, we performed a biopsy of liver metastases. Morphological and immunophenotypical characterization revealed that the patient had an EpCAM and CK positive small-cell lung cancer (SCLC). By using the CellSearch apparatus, EpCAM/CK positive CTC were detected in peripheral blood samples from 3 out of 4 additional SCLC patients. This study is the first to demonstrate that CTC can be identified in SCLC patients by using the CellSearch system.

Gene mutation analysis in non-small cell lung cancer patients using bronchoalveolar lavage fluid and tumor tissue as diagnostic markers.

PubMed

Li, Jian; Hu, Yi-Ming; Wang, Yi; Tang, Xing-Ping; Shi, Wei-Lin; Du, Yong-Jie

2014-12-09

Non-small cell lung cancer (NSCLC) is one of the main causes of cancer death in the world. Early detection of NSCLC can improve its outcome. The aim of this study was to identify the mutations of the KRAS and p53 genes in bronchoalveoar lavage (BAL) fluid for the early detection of peripheral NSCLC. We examined the DNA obtained from the tumor, nearby normal lung tissue, and matched BAL fluid for mutations in the KRAS and p53 genes; the material was obtained from 48 patients with peripheral NSCLC, and was analyzed by PCR-single strand conformation polymorphism and DNA sequencing. BAL fluids from 26 patients with benign lung disease were used as controls. Positive rates of KRAS and p53 mutations were distributed as follows: in NSCLC tissue, 52% and 58%; in BAL fluid of NSCLC patients, 38% and 44%; in normal lung tissue, 6% and 4%; and in BAL fluid of patients with benign lung disease, 8% and 4%. The combined detection of both KRAS and p53 mutations yielded a sensitivity of 66% for the diagnosis of peripheral NSCLC, which is markedly higher than that of cytology plus histology by first bronchoscopy (38%, p=0.008). In each patient with the 2 gene mutations in BAL fluid, mutation type and location were the same as those of the primary tumor. Our study indicates that the detection of the KRAS and p53 mutations in BAL fluids could be a helpful addition to cytology and histology examination for the diagnosis of peripheral NSCLC.

HCV RNA Genomic sequences and HCV-E2 glycoprotein in sural nerve biopsies from HCV-infected patients with peripheral neuropathy.

PubMed

Russi, S; Sansonno, D; Monaco, S; Mariotto, S; Ferrari, S; Pavone, F; Lauletta, G; Dammacco, F

2018-06-01

Peripheral neuropathy (PN), the major neurological complication of chronic HCV infection, is frequently associated with mixed cryoglobulinaemia (MC) and small-vessel systemic vasculitis. While humoral and cell-mediated immune mechanisms are suspected to act together in an aberrant immune response that results in peripheral nerve damage, the role of HCV remains largely speculative. The possible demonstration of HCV in peripheral nerve tissue would obviously assume important pathogenic implications. We studied sural nerve biopsies from 11 HCV-positive patients with neuropathic symptoms: five with and six without MC. In situ hybridization (ISH) and immunofluorescence studies were carried out to detect genomic and antigenomic HCV RNA sequences and HCV-encoded E2-glycoprotein, respectively. Epineurial vascular deposits of E2-glycoprotein were found in four (80%) MC and in two (33.3%) non-MC patients, respectively. These findings were enhanced by the perivascular deposition of positive-, though not negative-strand replicative RNA, as also found in the nerve extracts of all patients. Mild inflammatory cell infiltrates with no deposits of immunoglobulins and/or complement proteins were revealed around small vessels, without distinct vasculitis changes between MC and non-MC patients. These results indicate that nerve vascular HCV RNA/E2 deposits associated to perivascular inflammatory infiltrates were similar in chronically HCV-infected patients, regardless of cryoglobulin occurrence. Given the failure to demonstrate HCV productive infection in the examined sural nerve biopsies, nerve damage is likely to result from virus-triggered immune-mediated mechanisms. © 2017 British Neuropathological Society.

USSR and Eastern Europe Scientific Abstracts, Cybernetics, Computers and Automation Technology, Number 31

DTIC Science & Technology

1978-02-09

incorporation of subsystems and tasks into systems are specified by state and industrial- sector standards. However, such rigid requirements interfere...construction of the step-down substation, without which the new sector is inoperable. The question of who will build the substation is still unresolved... economico -mathematical evaluation). Among such applications, program decks completed by the "Soyuzsistemprom" are those for data integra- tion and

Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

ClinicalTrials.gov

2018-03-28

Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

Passive cooling system for liquid metal cooled nuclear reactors with backup coolant flow path

DOEpatents

Hunsbedt, Anstein; Boardman, Charles E.

1993-01-01

A liquid metal cooled nuclear fission reactor plant having a passive auxiliary safety cooling system for removing residual heat resulting from fuel decay during reactor shutdown, or heat produced during a mishap. This reactor plant is enhanced by a backup or secondary passive safety cooling system which augments the primary passive auxiliary cooling system when in operation, and replaces the primary system when rendered inoperable.

Comparison of the viewing wand and the BRW stereotaxy systems

NASA Astrophysics Data System (ADS)

Heiferman, Kenneth S.; Cramer, Kevin E.

1993-09-01

Intracranial lesions are invisible and exploration can be hazardous to the patient's postoperative quality of life. The first generation of neurosurgeons relied on their knowledge of neurology and anatomy to try to locate the patient's lesion. In general, this did not produce satisfactory results. Improvements in neuroradiology, neuroanesthesia, and neurosurgical techniques have diminished the proportion of the brain viewed as inoperable. These improvements have significantly improved patient outcomes.

Vismodegib hedgehog-signaling inhibition and treatment of basal cell carcinomas as well as keratocystic odontogenic tumors in Gorlin syndrome.

PubMed

Booms, Patrick; Harth, Marc; Sader, Robert; Ghanaati, Shahram

2015-01-01

Vismodegib hedgehog signaling inhibition treatment has potential for reducing the burden of multiple skin basal cell carcinomas and jaw keratocystic odontogenic tumors. They are major criteria for the diagnosis of Gorlin syndrome, also called nevoid basal cell carcinoma syndrome. Clinical features of Gorlin syndrome are reported, and the relevance of hedgehog signaling pathway inhibition by oral vismodegib for maxillofacial surgeons is highlighted. In summary, progressed basal cell carcinoma lesions are virtually inoperable. Keratocystic odontogenic tumors have an aggressive behavior including rapid growth and extension into adjacent tissues. Interestingly, nearly complete regression of multiple Gorlin syndrome-associated keratocystic odontogenic tumors following treatment with vismodegib. Due to radio-hypersensitivity in Gorlin syndrome, avoidance of treatment by radiotherapy is strongly recommended for all affected individuals. Vismodegib can help in those instances where radiation is contra-indicated, or the lesions are inoperable. The effect of vismodegib on basal cell carcinomas was associated with a significant decrease in hedgehog-signaling and tumor proliferation. Vismodegib, a new and approved drug for the treatment of advanced basal cell carcinoma, is a specific oncogene inhibitor. It also seems to be effective for treatment of keratocystic odontogenic tumors and basal cell carcinomas in Gorlin syndrome, rendering the surgical resections less challenging.

Fully Covered Metallic Stents for the Treatment of Benign Airway Stenosis

PubMed Central

Ocak, Sebahat; Gourdin, Maximilien; d'Odémont, Jean-Paul

2016-01-01

Introduction. We herein report our experience with new fully covered self-expanding metallic stents in the setting of inoperable recurrent benign tracheobronchial stenosis. Methods. Between May 2010 and July 2014, 21 Micro-Tech® FC-SEMS (Nanjing Co., Republic of Korea) were placed in our hospital in 16 patients for inoperable, recurrent (after dilatation), and symptomatic benign airway stenosis. Their medical files were retrospectively reviewed in December 2014, with focus on stent's tolerance and durability data. Results. Twenty-one stents were inserted: 13 for posttransplant left main bronchus anastomotic stricture, seven for postintubation tracheal stenosis, and one for postlobectomy anastomotic stricture. Positioning was easy for all of them. Stents were in place for a mean duration of 282 days. The most common complications were granulation tissue development (35%), migration (30%), and sputum retention (15%). Fifty-five % of the stents (11/20) had to be removed because of various complications, without difficulty for all of them. None of the patients had life-threatening complications. Conclusion. Micro-Tech FC-SEMS were easy to position and to remove. While the rate of complications requiring stent removal was significant, no life-threatening complication occurred. Further studies are needed to better define their efficacy and safety in the treatment of benign airway disease. PMID:27777507

Fully Covered Metallic Stents for the Treatment of Benign Airway Stenosis.

PubMed

Dahlqvist, Caroline; Ocak, Sebahat; Gourdin, Maximilien; Dincq, Anne Sophie; Putz, Laurie; d'Odémont, Jean-Paul

2016-01-01

Introduction. We herein report our experience with new fully covered self-expanding metallic stents in the setting of inoperable recurrent benign tracheobronchial stenosis. Methods. Between May 2010 and July 2014, 21 Micro-Tech® FC-SEMS (Nanjing Co., Republic of Korea) were placed in our hospital in 16 patients for inoperable, recurrent (after dilatation), and symptomatic benign airway stenosis. Their medical files were retrospectively reviewed in December 2014, with focus on stent's tolerance and durability data. Results. Twenty-one stents were inserted: 13 for posttransplant left main bronchus anastomotic stricture, seven for postintubation tracheal stenosis, and one for postlobectomy anastomotic stricture. Positioning was easy for all of them. Stents were in place for a mean duration of 282 days. The most common complications were granulation tissue development (35%), migration (30%), and sputum retention (15%). Fifty-five % of the stents (11/20) had to be removed because of various complications, without difficulty for all of them. None of the patients had life-threatening complications. Conclusion. Micro-Tech FC-SEMS were easy to position and to remove. While the rate of complications requiring stent removal was significant, no life-threatening complication occurred. Further studies are needed to better define their efficacy and safety in the treatment of benign airway disease.

The Role of Mifepristone in Meningiomas Management: A Systematic Review of the Literature.

PubMed

Cossu, Giulia; Levivier, Marc; Daniel, Roy Thomas; Messerer, Mahmoud

2015-01-01

We performed a systematic literature review to analyze the clinical application and the safety of mifepristone, a prominent antiprogesterone agent, in meningioma patients. A systematic search was performed through Medline, Cochrane, and clinicaltrials.gov databases from 1960 to 2014. Study Selection. Studies were selected through a PICO approach. Population was meningioma patients, meningioma cells cultures, and animal models. Intervention was mifepristone administration. Control was placebo administration or any other drug tested. Outcomes were clinical and radiological responsiveness, safety profile, and cell growth inhibition. A total of 7 preclinical and 6 clinical studies and one abstract were included. Encouraging results were found in preclinical studies. Concerning clinical studies, the response rate to mifepristone in terms of radiological regression and symptomatic improvement/stability in patients with inoperable meningioma was low. In meningiomatosis, favorable preliminary results were recorded. The safety profile was good. Limitations were as follows. The tumoral expression of progesterone receptors was not analyzed systematically in every study considered. No clear evidence exists to recommend mifepristone in inoperable meningiomas. Preliminary encouraging results were found in diffuse meningiomatosis. Mifepristone is a well-tolerated treatment. Patients' selection and hormonal profile analysis in meningiomas are fundamental for a better understanding of its benefit. Multicenter placebo-controlled trials are required.

Self-expanding metal mesh stents and laser therapy: a complementary approach for the palliation of malignant dysphagia

NASA Astrophysics Data System (ADS)

Madhotra, Ravi; Raouf, A.; Sturgess, R.; Krasner, Neville

1997-12-01

Re-establishment of the oesophageal lumen is the main focus of care in patients with inoperable oesophageal carcinomas. The self-expanding metal mesh stents (MMS) are increasingly being used. 51 patients aged 44 - 89 with inoperable oesophago-gastric carcinomas were intubated with MMS. 18 of these patients had endoscopic laser therapy (ELT) as primary palliation. 25 patients required follow-up endoscopy at variable intervals after stent insertion. 17 patients were found to have significant tumor growth (9), overgrowth (4) and both (4). All these patients were treated with Nd:YAG or diode laser for maintenance of satisfactory swallowing. 4 patients being treated with Nd:YAG laser developed deformity of MMS. This complication was not encountered with diode laser. The reblockage of MMS due to ingrowth or overgrowth of tumor is a not uncommon complication. The timing of the stent insertion should be carefully chosen since the longer the stent is in situ, the greater is the likelihood of tumor ingrowth or overgrowth. ELT can effectively deal with tumor ingrowth and overgrowth. Nd:YAG laser can cause melting of MMS. Overall the combination of ELT and MMS may offer the best palliation, particularly when patient survival of several months is anticipated.

Efficacy and tolerance of a new silicone stent for the treatment of benign tracheal stenosis: preliminary results.

PubMed

Vergnon, J M; Costes, F; Polio, J C

2000-08-01

In inoperable patients with tracheal stenosis who are treated using silicone stents, stent migration occurs in 18.6% of cases. To decrease the migration rate, we have designed a new silicone stent with narrow central and larger distal parts. This study analyzes the stability and tolerance of this new stent. Preliminary prospective study conducted in two French university hospitals. Thirteen inoperable patients with benign complex tracheal stenosis due to intubation or tracheotomy. Tracheal stent insertion was performed under general anesthesia with a rigid bronchoscope. The patients were followed up clinically up to stent removal, which was planned at 18 months. Stent insertion or removal was very simple and did not differ from other silicone stents. No migration occurred after a mean follow-up of 22.8 months. Minimal granuloma formation occurred in only one patient (7.7%). Sputum retention remained similar to that with other silicone stents and could be improved by a smoother internal wall. Stents have been removed in seven patients after a mean duration of 19.6 months, with a complete stenosis cure in four cases. This new stent combines the excellent stability of the metallic stents and the tolerance and easy removal of straight silicone stents. This allows a prolonged use in order to obtain curative action.

Endocavitary Ir-192 radiation and laser treatment for palliation of obstructive rectal cancer.

PubMed

Mischinger, H J; Hauser, H; Cerwenka, H; Stücklschweiger, G; Geyer, E; Schweiger, W; Rosanelli, G; Kohek, P H; Werkgartner, G; Hackl, A

1997-10-01

Endoscopic laser therapy (ELT) either alone or combined with endocavitary Ir-192 radiation is performed for advanced, inoperable rectal cancer and when patients are ineligible for surgery due to severe concomitant medical illness. During the period from January 1984 to January 1997 we treated 81 patients (51 males, 30 females). Sixty-seven patients had ELT only using a ND-Yag Laser system. Twenty-five patients (average age: 80.5 years) were ineligible for surgery (Group I). Forty-two patients (74.1 years) had an advanced locally inoperable tumour (Group II). Fourteen patients (76.5 years) underwent a combined therapeutic regime with endocavitary Ir-192 afterloading following ELT (Group III). Adequate desobliteration was achieved in 100% (groups I and III) and 97% (group II) of the patients. The average interval to aftertreatment was 8.4 weeks in group I and 9.4 weeks in group II, compared to 11.5 weeks in group III. Serious complications (perianal abscess, rectovaginal fistula) occurred in 3.7%, minor complications (laser-induced bleedings, unclear fever) in 12.3%. All laser-induced bleedings could be dealt with using laser therapy. The frequency of treatment was governed by tumour mass and the patient's survival. The results suggest that additional endocavitary radiation significantly prolongs the maintenance of normal bowel function compared with laser therapy alone.

Predictors of the patency of self-expandable metallic stents in malignant gastroduodenal obstruction

PubMed Central

Kim, Seung Han; Chun, Hoon Jai; Yoo, In Kyung; Lee, Jae Min; Nam, Seung Joo; Choi, Hyuk Soon; Kim, Eun Sun; Keum, Bora; Seo, Yeon Seok; Jeen, Yoon Tae; Lee, Hong Sik; Um, Soon Ho; Kim, Chang Duck

2015-01-01

AIM: To investigate the predictive factors of self-expandable metallic stent patency after stent placement in patients with inoperable malignant gastroduodenal obstruction. METHODS: A total of 116 patients underwent stent placements for inoperable malignant gastroduodenal obstruction at a tertiary academic center. Clinical success was defined as acceptable decompression of the obstructive lesion within the malignant gastroduodenal neoplasm. We evaluated patient comorbidities and clinical statuses using the World Health Organization’s scoring system and categorized patient responses to chemotherapy using the Response Evaluation Criteria in Solid Tumors criteria. We analyzed the relationships between possible predictive factors and stent patency. RESULTS: Self-expandable metallic stent placement was technically successful in all patients (100%), and the clinical success rate was 84.2%. In a multivariate Cox proportional hazards model, carcinoembryonic antigen (CEA) levels were correlated with a reduction in stent patency [P = 0.006; adjusted hazard ratio (aHR) = 2.92, 95%CI: 1.36-6.25]. Palliative chemotherapy was statistically associated with an increase in stent patency (P = 0.009; aHR = 0.27, 95%CI: 0.10-0.72). CONCLUSION: CEA levels can easily be measured at the time of stent placement and may help clinicians to predict stent patency and determine the appropriate stent procedure. PMID:26290640

Cell-Free RNA Content in Peripheral Blood as Potential Biomarkers for Detecting Circulating Tumor Cells in Non-Small Cell Lung Carcinoma

PubMed Central

Yu, Xin-Min; Wu, Yi-Chen; Liu, Xiang; Huang, Xian-Cong; Hou, Xiu-Xiu; Wang, Jiu-Li; Cheng, Xiang-Liu; Mao, Wei-Min; Ling, Zhi-Qiang

2016-01-01

Circulating tumor cells (CTCs) have been implicated in tumor progression and prognosis. Techniques detecting CTCs in the peripheral blood of patients with non-small cell lung carcinoma (NSCLC) may help to identify individuals likely to benefit from early systemic treatment. However, the detection of CTCs with a single marker is challenging, owing to low specificity and sensitivity and due to the heterogeneity and rareness of CTCs. Herein, the probability of cell-free RNA content in the peripheral blood as a potential biomarker for detecting CTCs in cancer patients was investigated. An immunomagnetic enrichment of real-time reverse-transcription PCR (RT-PCR) technology for analysis of CTCs in NSCLC patients was also developed. The mRNA levels of four candidate genes, cytokeratin 7 (CK7), E74-like factor 3 (ELF3), epidermal growth factor receptor (EGFR), and erythropoietin-producing hepatocellular carcinoma receptor B4 (EphB4) that were significantly elevated in tumor tissues and peripheral blood mononuclear cells (PBMCs) were determined. The expression of CK7 and ELF3 in tumor tissues and EGFR in PBMCs was associated with lymph node metastasis (all p < 0.05). The expression of CK7 in PBMCs was correlated with age and EphB4 in PBMCs correlated with histopathological type, respectively (all p < 0.05). The expression of all four genes in tumor tissues and PBMCs was significantly correlated with the clinical stage (all p < 0.01). Survival analysis showed that the patients with enhanced expression of CK7, ELF3, EGFR, and EphB4 mRNA in PBMCs had poorer disease-free survival (DFS) and overall survival (OS) than those without (all p < 0.0001). The present study showed that this alteration of cell-free RNA content in peripheral blood might have clinical ramifications in the diagnosis and treatment of NSCLC patients. PMID:27827952

[Detection and prognostic significance of micrometastasis in peripheral blood of patients with non-small cell lung cancer treated by chemo-radiation therapy].

PubMed

Chen, Ting-feng; Jiang, Guo-liang; Zhang, Yi-qin; Wang, Li-juan; Fu, Xiao-long; Qian, Hao; Wu, Kai-liang; Zhao, Sen

2007-05-01

To investigate the prognostic significance of micrometastasis (MM) in peripheral blood of patients with non-small cell lung cancer (NSCLC) treated by chemo-radiation therapy. Peripheral blood was taken from 67 NSCLC patients before and after definitive chemo-radiation therapy. CK19 mRNA of the peripheral blood was measured by nested RT-PCR and both their relationship with clinicopathological features and prognostic significance were further investigated. The micrometastasis-positive rates were 65.7% (44/67) and 32.8% (22/67), respectively, before and after the treatment. The micrometastasis-positive rate before treatment was closely in correlation with N-stage (P = 0.014). In contrast, it turned out to be more closely related with histological types (P = 0.019), weight loss (P = 0.01), KPS status (P = 0.027) as well as N-stage (P = 0.032) after chemo-radiation therapy. 4-yr distant metastasis rates (DMR) for micrometastasis-positive and -negative patients were 78.3% and 70.4%, respectively, before the treatment (P = 0.544) while they were 100% and 62.9%, respectively, after the chemoradiation (P < 0.001). The median survival time (MST) and 4-yr overall survival rate (OSR) for pretreatment micrometastasis-positive and -negative patients were 13.8 months and 17.6 months, and 18.2% and 17.4%, respectively (P = 0.619), while for post-treatment micrometastasis-positive and -negative patients they were 7.8 months and 27.6 months and 0 and 26.4%, respectively (P < 0.001). Multivariate analysis showed that the post-treatment positive micrometastasis was an independent unfavorable prognostic factor (P = 0.000). Detection of micrometastasis in peripheral blood may possess a prognostic significance after definitive chemo-radiation therapy. Micrometastasis-negative patients have better prognosis compared to those with positive micrometastasis.

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

PubMed

Ziegler, Matthew A; Distasi, Matthew R; Bills, Randall G; Miller, Steven J; Alloosh, Mouhamad; Murphy, Michael P; Akingba, A George; Sturek, Michael; Dalsing, Michael C; Unthank, Joseph L

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery Occlusion

PubMed Central

ZIEGLER, MATTHEW A.; DISTASI, MATTHEW R.; BILLS, RANDALL G.; MILLER, STEVEN J.; ALLOOSH, MOUHAMAD; MURPHY, MICHAEL P.; AKINGBA, A. GEORGE; STUREK, MICHAEL; DALSING, MICHAEL C.; UNTHANK, JOSEPH L.

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. PMID:20141596

Retrospective Correction of Physiological Noise in DTI Using an Extended Tensor Model and Peripheral Measurements

PubMed Central

Mohammadi, Siawoosh; Hutton, Chloe; Nagy, Zoltan; Josephs, Oliver; Weiskopf, Nikolaus

2013-01-01

Diffusion tensor imaging is widely used in research and clinical applications, but this modality is highly sensitive to artefacts. We developed an easy-to-implement extension of the original diffusion tensor model to account for physiological noise in diffusion tensor imaging using measures of peripheral physiology (pulse and respiration), the so-called extended tensor model. Within the framework of the extended tensor model two types of regressors, which respectively modeled small (linear) and strong (nonlinear) variations in the diffusion signal, were derived from peripheral measures. We tested the performance of four extended tensor models with different physiological noise regressors on nongated and gated diffusion tensor imaging data, and compared it to an established data-driven robust fitting method. In the brainstem and cerebellum the extended tensor models reduced the noise in the tensor-fit by up to 23% in accordance with previous studies on physiological noise. The extended tensor model addresses both large-amplitude outliers and small-amplitude signal-changes. The framework of the extended tensor model also facilitates further investigation into physiological noise in diffusion tensor imaging. The proposed extended tensor model can be readily combined with other artefact correction methods such as robust fitting and eddy current correction. PMID:22936599

Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis.

PubMed

Maurer, Britta; Busch, Nicole; Jüngel, Astrid; Pileckyte, Margarita; Gay, Renate E; Michel, Beat A; Schett, Georg; Gay, Steffen; Distler, Jörg; Distler, Oliver

2009-12-08

Microvascular damage is one of the first pathological changes in systemic sclerosis. In this study, we investigated the role of Fos-related antigen-2 (Fra-2), a transcription factor of the activator protein-1 family, in the peripheral vasculopathy of systemic sclerosis and examined the underlying mechanisms. Expression of Fra-2 protein was significantly increased in skin biopsies of systemic sclerosis patients compared with healthy controls, especially in endothelial and vascular smooth muscle cells. Fra-2 transgenic mice developed a severe loss of small blood vessels in the skin that was paralleled by progressive skin fibrosis at 12 weeks of age. The reduction in capillary density was preceded by a significant increase in apoptosis in endothelial cells at week 9 as detected by immunohistochemistry. Similarly, suppression of Fra-2 by small interfering RNA prevented human microvascular endothelial cells from staurosporine-induced apoptosis and improved both the number of tubes and the cumulative tube lengths in the tube formation assay. In addition, cell migration in the scratch assay and vascular endothelial growth factor-dependent chemotaxis in a modified Boyden chamber assay were increased after transfection of human microvascular endothelial cells with Fra-2 small interfering RNA, whereas proliferation was not affected. Fra-2 is present in human systemic sclerosis and may contribute to the development of microvasculopathy by inducing endothelial cell apoptosis and by reducing endothelial cell migration and chemotaxis. Fra-2 transgenic mice are a promising preclinical model to study the mechanisms and therapeutic approaches of the peripheral vasculopathy in systemic sclerosis.

Factors predicting outcomes of microwave ablation of small hepatocellular carcinoma.

PubMed

Ierardi, Anna Maria; Giorlando, Francesca; Piacentino, Filippo; Fontana, Federico; Novario, Raffaele; Angileri, Salvatore Alessio; Duka, Ejona; Carrafiello, Gianpaolo

2017-02-01

The aim of our study was to evaluate factors influencing effectiveness of percutaneous microwave ablation (MWA) in patients with small hepatocellular carcinoma (HCC) (<3 cm). Between December 2007 and August 2015, 49 patients with 65 previously histological typed HCC were treated in a total of 61 sessions. Tumours were subdivided into central (>3 cm from the capsule) (n = 22) and peripheral (<3 cm from the capsule) (n = 43). Imaging follow-up was performed at 1, 3, 6, and 12 months after treatment, then annually. Mean follow-up period was 18 months (range 1-55). Location of the lesion, age, sex, and underlying disease of the patients was analyzed and related with efficacy. Technical success was obtained in all cases. Residual disease was registered in 21 lesions (32.3 %): 13 were peripheral and 8 were central. Twelve of them were retreated with percutaneous MWA. Local recurrence was recorded in 8 lesions (12.3 %): 5 were retreated with MWA. No significant difference in terms of effectiveness was observed in lesions located in a central position and those situated in the peripheral position. Age, sex, and underlying disease not influenced results. Only one major complication was observed. The rate of minor complications was 24.5 %. Mortality at 30 days was 0 %. Our results encourage the role of MWA in the treatment of small HCC. More numerous series and randomized studies are necessary to state the role of MWA and to select cases in which MWA may be more effective and safer than RFA.

Exercise and nutrition interventions in advanced lung cancer: a systematic review

PubMed Central

Payne, C.; Larkin, P.J.; McIlfatrick, S.; Dunwoody, L.; Gracey, J.H.

2013-01-01

In this systematic review, we sought to evaluate the effect of physical activity or nutrition interventions (or both) in adults with advanced non-small-cell lung cancer (nsclc). Methods A systematic search for relevant clinical trials was conducted in 6 electronic databases, by hand searching, and by contacting key investigators. No limits were placed on study language. Information about recruitment rates, protocol adherence, patient-reported and clinical outcome measures, and study conclusions was extracted. Methodologic quality and risk of bias in each study was assessed using validated tools. Main Results Six papers detailing five studies involving 203 participants met the inclusion criteria. Two of the studies were single-cohort physical activity studies (54 participants), and three were controlled nutrition studies (149 participants). All were conducted in an outpatient setting. None of the included studies combined physical activity with nutrition interventions. Conclusions Our systematic review suggests that exercise and nutrition interventions are not harmful and may have beneficial effects on unintentional weight loss, physical strength, and functional performance in patients with advanced nsclc. However, the observed improvements must be interpreted with caution, because findings were not consistent across the included studies. Moreover, the included studies were small and at significant risk of bias. More research is required to ascertain the optimal physical activity and nutrition interventions in advanced inoperable nsclc. Specifically, the potential benefits of combining physical activity with nutrition counselling have yet to be adequately explored in this population. PMID:23904771

Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

PubMed

Zhao, Xueying; Wang, Shiming; Wu, Junjie; Li, Xiaoying; Wang, Xun; Gao, Zhiqiang; Wu, Wenting; Wang, Haijian; Wang, Jiucun; Qian, Ji; Ma, Ke; Li, Hui; Han, Baohui; Bai, Chunxue; Li, Qiang; Liu, Wenbin; Lu, Daru

2015-01-01

TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC) patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS), overall survival (OS), and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype) to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4)). It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023). In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002). The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.

Phase I Study of Accelerated Conformal Radiotherapy for Stage I Non–Small-Cell Lung Cancer in Patients With Pulmonary Dysfunction: CALGB 39904

PubMed Central

Bogart, Jeffrey A.; Hodgson, Lydia; Seagren, Stephen L.; Blackstock, A. William; Wang, Xiaofei; Lenox, Robert; Turrisi, Andrew T.; Reilly, John; Gajra, Ajeet; Vokes, Everett E.; Green, Mark R.

2010-01-01

Purpose The optimal treatment for medically inoperable stage I non–small-cell lung cancer (NSCLC) has not been defined. Patients and Methods Cancer and Leukemia Group B trial 39904 prospectively assessed accelerated, once-daily, three-dimensional radiotherapy for early-stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 or T2N0 NSCLC (< 4 cm) and pulmonary dysfunction. The nominal total radiotherapy dose remained at 70 Gy, while the number of daily fractions in each successive cohort was reduced. Results Thirty-nine eligible patients were accrued (eight patients each on cohorts 1 to 4 and seven patients on cohort 5) between January 2001 and July 2005. One grade 3 nonhematologic toxicity was observed in both cohort 3 (dyspnea) and cohort 4 (pain). The major response rate was 77%. After a median follow-up time of 53 months, the actuarial median survival time of all eligible patients was 38.5 months. Local relapse was observed in three patients. Conclusion Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further investigation of this approach is warranted. PMID:19933904

Relative Peripheral Refractive Error and the Risk of Onset and Progression of Myopia in Children

PubMed Central

Sinnott, Loraine T.; Mitchell, G. Lynn; Jones-Jordan, Lisa A.; Moeschberger, Melvin L.; Cotter, Susan A.; Kleinstein, Robert N.; Manny, Ruth E.; Twelker, J. Daniel; Zadnik, Karla

2011-01-01

Purpose. To investigate whether relative peripheral hyperopia is a risk factor for either the onset of myopia in children or the rate of myopic progression. Methods. The risk of myopia onset was assessed in 2043 nonmyopic third-grade children (mean age ± SD = 8.8 ± 0.52 years) participating in the Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study between 1995 and 2007, 324 of whom became myopic by the eighth grade. Progression analyses used data from 774 myopic children in grades 1 to 8. Foveal and relative peripheral refractive error 30° in the nasal visual field was measured annually by using cycloplegic autorefraction. Axial length was measured by A-scan ultrasonography. Results. The association between more hyperopic relative peripheral refractive error in the third grade and the risk of the onset of myopia by the eighth grade varied by ethnic group (Asian children odds ratio [OR] = 1.56, 95% confidence interval [CI] = 1.06–2.30; African-American children OR = 0.75, 95% CI = 0.58–0.96; Hispanics, Native Americans, and whites showed no significant association). Myopia progression was greater per diopter of more hyperopic relative peripheral refractive error, but only by a small amount (−0.024 D per year; P = 0.02). Axial elongation was unrelated to the average relative peripheral refractive error (P = 0.77), regardless of ethnicity. Conclusions. Relative peripheral hyperopia appears to exert little consistent influence on the risk of the onset of myopic refractive error, on the rate of myopia progression, or on axial elongation. PMID:20739476

Beyond the five-year horizon: long-term outcome of high-risk and inoperable patients undergoing TAVR with first-generation devices.

PubMed

Deutsch, Marcus-André; Erlebach, Magdalena; Burri, Melchior; Hapfelmeier, Alexander; Witt, Olivia Ganga; Ziegelmueller, Johannes Amadeus; Wottke, Michael; Ruge, Hendrik; Krane, Markus; Piazza, Nicolo; Bleiziffer, Sabine; Lange, Rüdiger

2018-05-20

We sought to determine the long-term outcome of high-risk patients who underwent transcatheter aortic valve replacement (TAVR) with first-generation devices with a focus on the identification of predictors for mortality and valve durability. Consecutive patients in our prospective single-centre registry undergoing TAVR with first-generation devices (n=214 CoreValve; n=86 SAPIEN) between 06/2007 and 07/2009 were retrospectively analysed (n=300, mean age 81.43±6.55 years, mean STS score 6.5±4.5%). Kaplan-Meier estimates of survival and the Cox proportional hazards model were used to identify independent predictors of all-cause-mortality. At 1, 5, and 7 years, estimated survival rates were 76.0%, 40.2%, and 23.2%, respectively. Age-adjusted baseline predictors of mortality included atrial fibrillation, impaired kidney function, peripheral artery disease, and mitral regurgitation (≥moderate). Baseline risk-adjusted procedure-related predictors for all-cause mortality included acute kidney injury, neurological events, major vascular complications, and major/life-threatening bleeding. At both five and six years, 78.2% of surviving patients were in NYHA Class I or II. PVL was ≤mild in the majority of patients at discharge and throughout follow-up. At seven years, the overall crude cumulative incidence of structural valve deterioration according to the 2017 EAPCI/ESC/EACTS definition was 14.9% (CoreValve 11.8% vs. SAPIEN 22.6%; p=0.01). Seven years after TAVR, 23.2% of high-risk patients were still alive. Independent predictors of all-cause mortality included both patient- and procedure-related factors. With a cumulative incidence of 14.9% at seven years, there is some suggestion that SVD post TAVR may become increasingly relevant during longer-term follow-up.

[Vasculitic Peripheral Neuropathies: Clinical Features and Diagnostic Laboratory Tests].

PubMed

Ogata, Katsuhisa

2016-03-01

Vasculitic peripheral neuropathy (VPN) occurs due to ischemic changes of peripheral nerves, resulting from a deficit of vascular blood supply due to damaged vasa nervorum leading to vasculitis. VPN usually manifests as sensorimotor or sensory disturbances accompanied by pain, presenting as a type of multiple mononeuropathy, with a scattered distribution in distal limbs. VPN may also present as a mononeuropathy, distal symmetric polyneuropathy, plexopathy, or radiculopathy. The rapidity of VPN is variable, ranging from days to months, with symptoms occasionally changing with the appearance of new lesions. Careful history taking and neurological examination provides an exact diagnosis. The most common cause of VPN is primary vasculitis predominantly affecting small vessels, including vasa nervorum, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa. Similar vasculitic processes can also result from a systemic collagen disorder or secondary vasculitis. Electrophysiological studies and pathological investigation of biopsied peripheral nerves and muscles are important for diagnosis of vasculitis. Serological tests, including ANCA, are useful for diagnosis of vasculitis. Accurate neurological examinations are essential for diagnosis and evaluation of clinical course.

DNA content determination of micronucleated polychromatic erythrocytes induced by clastogens and spindle poisons in mouse bone marrow and peripheral blood

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grawe, J.; Amneus, H.; Zetterberg, G.

1993-01-01

The frequencies and DNA distributions of micronuclei in polychromatic erythrocytes from the bone marrow and peripheral blood of mice after four different treatments were determined by flow cytometry. Polychromatic erthrocytes were detected using the fluorescent RNA stain thiazole orange, while micronuclei were detected with the DNA stain Hoechst 33342. The treatments were X-irradiation (1 Gy), cyclophosphamide (30 mg/kg), vincristine sulfphate (0.08 mg/kg), and cochicine (1 mg/kg). All treatments showed increased frequencies of micronucleated polychromatic erythrocytes at 30h after treatment in the bone marrow (colchicine 50h) and at 50h in the peripheral blood. The clostogenic agents X-irradiation and cyclophosphamide and themore » spindle poisons vincristine sulphate and cochicine could be grouped according to the fluorescent characteristics of the induced micronuclei as well as the relative frequency of small (0.5-2% if the diploid G1 DNA content) and large (2-10%) micronuclei. In the peripheral blood the relative frequency of large micronuclei was lower than in the bone marrow, indicating that they were partly eliminated before entrance into the peripheral circulation. The nature of presumed micronuclei was verified by sorting. The potential of this approach to give information on the mechanism of induction of micronuclei is discussed.« less

Revisiting control establishments for emerging energy hubs

NASA Astrophysics Data System (ADS)

Nasirian, Vahidreza

Emerging small-scale energy systems, i.e., microgrids and smartgrids, rely on centralized controllers for voltage regulation, load sharing, and economic dispatch. However, the central controller is a single-point-of-failure in such a design as either the controller or attached communication links failure can render the entire system inoperable. This work seeks for alternative distributed control structures to improve system reliability and help to the scalability of the system. A cooperative distributed controller is proposed that uses a noise-resilient voltage estimator and handles global voltage regulation and load sharing across a DC microgrid. Distributed adaptive droop control is also investigated as an alternative solution. A droop-free distributed control is offered to handle voltage/frequency regulation and load sharing in AC systems. This solution does not require frequency measurement and, thus, features a fast frequency regulation. Distributed economic dispatch is also studied, where a distributed protocol is designed that controls generation units to merge their incremental costs into a consensus and, thus, push the entire system to generate with the minimum cost. Experimental verifications and Hardware-in-the-Loop (HIL) simulations are used to study efficacy of the proposed control protocols.

Usefulness of Photodynamic Therapy as a Possible Therapeutic Alternative in the Treatment of Basal Cell Carcinoma

PubMed Central

Savoia, Paola; Deboli, Tommaso; Previgliano, Alberto; Broganelli, Paolo

2015-01-01

Basal cell carcinoma (BCC) is the most common cancer in individuals with fair skin type (I–II) and steadily increasing in incidence (70% of skin malignancy). It is locally invasive but metastasis is usually very rare, with an estimated incidence of 0.0028%–0.55%. Conventional therapy is surgery, especially for the H region of the face and infiltrative lesions; in case of inoperable tumors, radiotherapy is a valid option. Recently, topical photodynamic therapy (PDT) has become an effective treatment in the management of superficial and small nodular BCC. PDT is a minimally invasive procedure that involves the administration of a photo-sensibilizing agent followed by irradiation at a pre-defined wavelength; this determines the creation of reactive oxygen species that specifically destroy target cells. The only major side effect is pain, reported by some patients during the irradiation. The high cure rate and excellent cosmetic outcome requires considering this possibility for the management of patients with both sporadic and hereditary BCC. In this article, an extensive review of the recent literature was made, in order to clarify the role of PDT as a possible alternative therapeutic option in the treatment of BCC. PMID:26426005

Current progress in use of adipose derived stem cells in peripheral nerve regeneration

PubMed Central

Zack-Williams, Shomari DL; Butler, Peter E; Kalaskar, Deepak M

2015-01-01

Unlike central nervous system neurons; those in the peripheral nervous system have the potential for full regeneration after injury. Following injury, recovery is controlled by schwann cells which replicate and modulate the subsequent immune response. The level of nerve recovery is strongly linked to the severity of the initial injury despite the significant advancements in imaging and surgical techniques. Multiple experimental models have been used with varying successes to augment the natural regenerative processes which occur following nerve injury. Stem cell therapy in peripheral nerve injury may be an important future intervention to improve the best attainable clinical results. In particular adipose derived stem cells (ADSCs) are multipotent mesenchymal stem cells similar to bone marrow derived stem cells, which are thought to have neurotrophic properties and the ability to differentiate into multiple lineages. They are ubiquitous within adipose tissue; they can form many structures resembling the mature adult peripheral nervous system. Following early in vitro work; multiple small and large animal in vivo models have been used in conjunction with conduits, autografts and allografts to successfully bridge the peripheral nerve gap. Some of the ADSC related neuroprotective and regenerative properties have been elucidated however much work remains before a model can be used successfully in human peripheral nerve injury (PNI). This review aims to provide a detailed overview of progress made in the use of ADSC in PNI, with discussion on the role of a tissue engineered approach for PNI repair. PMID:25621105

Position of peripheral venous cannulae and the incidence of thrombophlebitis: an observational study.

PubMed

Cicolini, Giancarlo; Bonghi, Antonia Pollidoro; Di Labio, Luisa; Di Mascio, Rocco

2009-06-01

This paper is a report of a study conducted to investigate the most suitable location of peripheral venous cannulae to reduce the incidence of thrombophlebitis. Peripheral intravenous cannulae are used for vascular access, but the site of insertion and size of the cannula could expose patients to local and systemic infectious complications. Small cannula size is an important factor in reducing the incidence of thrombophlebitis, but cannula location has not yet been studied. Evidence-based knowledge on how to prevent these complications is needed. An observational survey carried out was carried out in 2007 with 427 patients in one Italian hospital. A structured observation protocol was used to survey the frequency of thrombophlebitis and the relationship of location and size of peripheral intravenous cannulae. The variables evaluated were age, gender, cannula size and site of cannula location. Chi-square or Student t tests were used, and the adjusted odds ratios and relative 95% confidence intervals are reported. The frequency of peripheral intravenous cannulae thrombophlebitis was higher in females (OR:1.91;CI:1.20-3.03;P < 0.006). The highest incidence was found in patients with cannulae inserted in the dorsal side of the hand veins compared to those with cannulae inserted in cubital fossa veins (OR:3.33;CI:1.37-8.07; P < 0.001). The use of cubital fossa veins rather than forearm and hand veins should be encouraged to reduce the risk of thrombophlebitis in patients with peripheral intravenous cannulae.

A peripheral governor regulates muscle contraction.

PubMed

MacIntosh, Brian R; Shahi, M Reza S

2011-02-01

Active skeletal muscles are capable of keeping the global [adenosine triphosphate (ATP)] reasonably constant during exercise, whether it is mild exercise, activating a few motor units, or all-out exercise using a substantial mass of muscle. This could only be accomplished if there were regulatory processes in place not only to replenish ATP as quickly as possible, but also to modulate the rate of ATP use when that rate threatens to exceed the rate of ATP replenishment, a situation that could lead to metabolic catastrophe. This paper proposes that there is a regulatory process or "peripheral governor" that can modulate activation of muscle to avoid metabolic catastrophe. A peripheral governor, working at the cellular level, should be able to reduce the cellular rate of ATP hydrolysis associated with muscle contraction by attenuating activation. This would necessarily cause something we call peripheral fatigue (i.e., reduced contractile response to a given stimulation). There is no doubt that peripheral fatigue occurs. It has been demonstrated in isolated muscles, in muscles in situ with no central nervous system input, and in intact human subjects performing voluntary exercise with small muscle groups or doing whole-body exercise. The regulation of muscle activation is achieved in at least 3 ways (decreasing membrane excitability, inhibiting Ca2+ release through ryanodine receptors, and decreasing the availability of Ca2+ in the sarcoplasmic reticulum), making this a highly redundant control system. The peripheral governor attenuates cellular activation to reduce the metabolic demand, thereby preserving ATP and the integrity of the cell.

The Future of Indigenous Security Force Training: Considerations for the Joint Operational Commander

DTIC Science & Technology

2007-11-06

FINAL 3. DATES COVERED (From - To) 4. TITLE AND SUBTITLE The Future of Indigenous Security Force Training: 5a. CONTRACT NUMBER...focus on indigenous security force training and development (ISFTD) is unique to OIF or if it foreshadows a requirement that must be addressed in...operational plans using ad hoc capabilities. This research paper seeks to demonstrate that the U.S. military has an increased need to train indigenous

[History and care of malignant wounds in breast cancer].

PubMed

Fromantin, Isabelle; Alran, Séverine; Cassoux, Nathalie

2013-11-01

The first descriptions of ulcerated breast cancer date back to ancient Egypt. From the Greek and Roman periods to the Renaissance, fungating wounds were described, excised, cauterized and necrotized using various techniques and unguents. The foundations of some of the therapeutic strategies we still use today were developed.Today the management of inoperable malignant wounds that are not amenable to anti-cancer treatment remains complex and the symptoms are difficult to control.

Industrial Relations (The National Shipbuilding Research Program)

DTIC Science & Technology

1981-01-01

permit- ting him so to do, he shall notify his supervisor promptly expost facto . 2. In case of non-attendance due to injury or illness, the mployees shall...this study possible. Special appreciation is due the following individuals who provided. their time and information in the conduct of this study . Aioi...The material contained herein was-developed from the study of the Industrial Relations programs and systems presently in-operation in the shipyards of

Safe Heavens. Military Strategy and Space Sanctuary Thought,

DTIC Science & Technology

1998-06-01

service proposed two ASAT solutions: a modified Nike Zeus antiballistic missile (ABM) and a "homing satellite" carrying a destructive charge.9...McNamara ordered the Army to modify the Nike Zeus ABM for a future ASAT role. The modified system, Program 505, was based at Kwajalein Atoll in...operational. President Carter’s 1978 Presidential Directive on Space Policy stated that "the United States finds itself under increasing pressure to

Repair, Evaluation, Maintenance, and Rehabilitation Research Program. Lubricants for Hydraulic Structures

DTIC Science & Technology

1989-08-01

machinery design , precision machining, proper maintenance, and proper lubrication. Ordinarily, wear is thought of only in terms of abrasive wear occurring in...operate under this principle. However, the design must allow the plates to lift and tilt properly and provide sufficient area to lift the load. 38. Another...friction and wear to a minimum. Boundary Lubrication 42. Lubrication designed to protect against frictional effects when asperities meet is called

Demonstration Program for Low-Cost, High-Energy-Saving Dynamic Windows

DTIC Science & Technology

2014-09-01

Design The scope of this project was to demonstrate the impact of dynamic windows via energy savings and HVAC peak-load reduction; to validate the...temperature and glare. While the installed dynamic window system does not directly control the HVAC or lighting of the facility, those systems are designed ...optimize energy efficiency and HVAC load management. The conversion to inoperable windows caused an unforeseen reluctance to accept the design and

Light emitting device having peripheral emissive region

DOEpatents

Forrest, Stephen R

2013-05-28

Light emitting devices are provided that include one or more OLEDs disposed only on a peripheral region of the substrate. An OLED may be disposed only on a peripheral region of a substantially transparent substrate and configured to emit light into the substrate. Another surface of the substrate may be roughened or include other features to outcouple light from the substrate. The edges of the substrate may be beveled and/or reflective. The area of the OLED(s) may be relatively small compared to the substrate surface area through which light is emitted from the device. One or more OLEDs also or alternatively may be disposed on an edge of the substrate about perpendicular to the surface of the substrate through which light is emitted, such that they emit light into the substrate. A mode expanding region may be included between each such OLED and the substrate.

Psychophysiological arousal and inter‐ and intraindividual differences in risk‐sensitive decision making

PubMed Central

Scheibehenne, Benjamin; Clark, Luke

2016-01-01

Abstract The current study assessed peripheral responses during decision making under explicit risk, and tested whether intraindividual variability in choice behavior can be explained by fluctuations in peripheral arousal. Electrodermal activity (EDA) and heart rate (HR) were monitored in healthy volunteers (N = 68) during the Roulette Betting Task. In this task, participants were presented with risky gambles to bet on, with the chances of winning varying across trials. Hierarchical Bayesian analyses demonstrated that EDA and HR acceleration responses during the decision phase were sensitive to the chances of winning. Interindividual differences in this peripheral reactivity during risky decision making were related to trait sensitivity to punishment and trait sensitivity to reward. Moreover, trial‐by‐trial variation in EDA and HR acceleration responses predicted a small portion of intraindividual variability in betting choices. Our results show that psychophysiological responses are sensitive to explicit risk and can help explain intraindividual heterogeneity in choice behavior. PMID:26927730

AlphaB-crystallin regulates remyelination after peripheral nerve injury

PubMed Central

Lim, Erin-Mai F.; Nakanishi, Stan T.; Hoghooghi, Vahid; Eaton, Shane E. A.; Palmer, Alexandra L.; Frederick, Ariana; Stratton, Jo A.; Stykel, Morgan G.; Zochodne, Douglas W.; Biernaskie, Jeffrey; Ousman, Shalina S.

2017-01-01

AlphaB-crystallin (αBC) is a small heat shock protein that is constitutively expressed by peripheral nervous system (PNS) axons and Schwann cells. To determine what role this crystallin plays after peripheral nerve damage, we found that loss of αBC impaired remyelination, which correlated with a reduced presence of myelinating Schwann cells and increased numbers of nonmyelinating Schwann cells. The heat shock protein also seems to regulate the cross-talk between Schwann cells and axons, because expected changes in neuregulin levels and ErbB2 receptor expression after PNS injury were disrupted in the absence of αBC. Such dysregulations led to defects in conduction velocity and motor and sensory functions that could be rescued with therapeutic application of the heat shock protein in vivo. Altogether, these findings show that αBC plays an important role in regulating Wallerian degeneration and remyelination after PNS injury. PMID:28137843

Hemodynamic response to fluid removal during hemodialysis: categorization of causes of intradialytic hypotension.

PubMed

Levin, Nathan W; de Abreu, Marcia H F G; Borges, Lucas E; Tavares Filho, Helcio A; Sarwar, Rabia; Gupta, Surendra; Hafeez, Tahir; Lev, Shaul; Williams, Caroline

2018-04-14

Intradialytic hypotension is a clinically significant problem, however, the hemodynamics that underlie ultrafiltration and consequent hypotensive episodes has not been studied comprehensively. Intradialytic cardiac output, cardiac power and peripheral resistance changes from pretreatment measurements were evaluated using a novel regional impedance cardiographic device (NICaS, NI Medical, Peta Tikva, Israel) in 263 hemodialysis sessions in 54 patients in dialysis units in the USA and Brazil with the goal of determining the various hemodynamic trends as blood pressure decreases. Hypotensive episodes occurred in 99 (13.5%) of 736 intra- and postdialytic evaluations. The hemodynamic profiles of the episodes were categorized: (i) The cardiac power index significantly decreased in 35% of episodes by 36%, from 0.66 [95% confidence interval (CI) 0.60-0.72] to 0.43 (95% CI 0.37-0.48) [w/m2] with a small reduction in the total peripheral resistance index. (ii) The total peripheral resistance index significantly decreased in 37.4% of episodes by 33%, from 3342 (95% CI 2824-3859) to 2251 (95% CI 1900-2602) [dyn × s/cm5 × m2] with a small reduction in the cardiac power index. (iii) Both the cardiac power index and total peripheral resistance index significantly decreased in 27.3% of episodes, the cardiac power index by 25% from 0.63 (95% CI 0.57-0.70) to 0.48 (95% CI 0.42-0.53) [w/m2] and the total peripheral resistance index by 23% from 2964 (95% CI 2428-3501) to 2266 (95% CI 1891-2642). The hemodynamic profiles clearly define specific hemodynamic mechanisms of cardiac power reduction and/or vasodilatation as underlying intradialytic hypotensive episodes. A reduction in cardiac power (reduction of both blood pressure and cardiac output) could be the result of preload reduction due to a high ultrafiltration rate with not enough refilling or low target weight. A reduction in peripheral resistance (reduction in blood pressure and increase in cardiac output) could be the result of relative vasodilatation as arteries do not contract to compensate for volume reduction due to autonomous dysfunction. As both phenomena are independent, they may appear at the same time. Based on these results, a reduction of ultrafiltration rate and an increase in target weight to improve preload or immediate therapeutic actions to increase peripheral resistance are rational measures that could be taken to maintain blood pressure and prevent hypotensive ischemic complications in dialysis patients.

Purposeful creation of a pneumothorax and chest tube placement to facilitate CT-guided coil localization of lung nodules before video-assisted thoracoscopic surgical wedge resection.

PubMed

Iqbal, Shams I; Molgaard, Christopher; Williamson, Christina; Flacke, Sebastian

2014-07-01

To evaluate the feasibility and efficacy of pneumothorax creation and chest tube insertion before computed tomography (CT)-guided coil localization of small peripheral lung nodules for video-assisted thoracoscopic surgical (VATS) wedge resection. From May 2011 to October 2013, 21 consecutive patients (seven men; mean age, 62 y; range, 42-76 y) scheduled for VATS wedge resection required CT-guided coil localization for small, likely nonpalpable peripheral lung lesions at a single institution. Outcomes were evaluated retrospectively for technical success and complications. There were 12 nodules and nine ground-glass opacities. Mean lesion distance from the pleural surface was 15 mm (range, 5-35 mm), and average size was 13 mm (range, 7-30 mm). A pneumothorax was successfully created in all patients with a Veress needle, and a chest tube was inserted. All target lesions were marked successfully, leaving one end of the coil within/beyond the lesion and the other end of the coil in the pleural space. The inserted chest tube was used to insufflate air to widen the pleural space during coil positioning and to aspirate any residual air before transfer of the patient to the operating room holding area. Intraparenchymal hemorrhages smaller than 7 cm in diameter developed in two patients during coil placement. All lesions were successfully resected with VATS. Histologic examinaiton revealed 13 primary adenocarcinomas, four metastases, and four benign lesions. Pneumothorax creation and chest tube placement before CT-guided coil localization of peripheral lung nodules for VATS wedge resection facilitates the deployment of the peripheral end of the coil in the pleural space and provides effective management of procedure-related pneumothorax until surgery. Copyright © 2014 SIR. Published by Elsevier Inc. All rights reserved.

Lung penetration and patient adherence considerations in the management of asthma: role of extra-fine formulations

PubMed Central

Scichilone, Nicola; Spatafora, Mario; Battaglia, Salvatore; Arrigo, Rita; Benfante, Alida; Bellia, Vincenzo

2013-01-01

The mainstay of management in asthma is inhalation therapy at the target site, with direct delivery of the aerosolized drug into the airways to treat inflammation and relieve obstruction. Abundant evidence is available to support the concept that inflammatory and functional changes at the level of the most peripheral airways strongly contribute to the complexity and heterogeneous manifestations of asthma. It is now largely accepted that there is a wide range of clinical phenotypes of the disease, characterized primarily by small airways involvement. Thus, an appropriate diagnostic algorithm cannot exclude biological and functional assessment of the peripheral airways. Similarly, achievement of optimal control of the disease and appropriate management of specific phenotypes of asthma should be based on drugs (and delivery options) able to distribute uniformly along the bronchial tree and to reach the most peripheral airways. Products developed with the Modulite® technology platform have been demonstrated to meet these aims. Recent real-life studies have shown clearly that extra-fine fixed-combination inhaled therapy provides better asthma control than non-extra-fine formulations, thus translating the activity of the drugs into greater effectiveness in clinical practice. We suggest that in patients with incomplete asthma control despite good lung function, involvement of the peripheral airways should always be suspected. When this is the case, treatments targeting both the large and small airways should be used to improve asthma control. Above all, it is emphasized that patient adherence with prescribed medications can contribute to clinical success, and clinicians should always be aware of the role played by patients themselves in determining the success or failure of treatment. PMID:23378776

Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-05-07

Hodgkin Lymphoma; Non-Hodgkin Lymphoma; Burkitt's Lymphoma; Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Marginal Zone; Waldenstrom's Macroglobulinaemia; Lymphoma,T-cell Cutaneous; Lymphoma, T-Cell, Peripheral

Genetically Engineered Lymphocyte Therapy After Peripheral Blood Stem Cell Transplant in Treating Patients With High-Risk, Intermediate-Grade, B-cell Non-Hodgkin Lymphoma

ClinicalTrials.gov

2018-02-09

Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma

Low-Dose Total Body Irradiation and Donor Peripheral Blood Stem Cell Transplant Followed by Donor Lymphocyte Infusion in Treating Patients With Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, or Multiple Myeloma

ClinicalTrials.gov

2017-10-23

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage II Multiple Myeloma; Stage III Multiple Myeloma; Testicular Lymphoma; Waldenström Macroglobulinemia

Chemical Structure and Morphology of Dorsal Root Ganglion Neurons from Naive and Inflamed Mice*

PubMed Central

Barabas, Marie E.; Mattson, Eric C.; Aboualizadeh, Ebrahim; Hirschmugl, Carol J.; Stucky, Cheryl L.

2014-01-01

Fourier transform infrared spectromicroscopy provides label-free imaging to detect the spatial distribution of the characteristic functional groups in proteins, lipids, phosphates, and carbohydrates simultaneously in individual DRG neurons. We have identified ring-shaped distributions of lipid and/or carbohydrate enrichment in subpopulations of neurons which has never before been reported. These distributions are ring-shaped within the cytoplasm and are likely representative of the endoplasmic reticulum. The prevalence of chemical ring subtypes differs between large- and small-diameter neurons. Peripheral inflammation increased the relative lipid content specifically in small-diameter neurons, many of which are nociceptive. Because many small-diameter neurons express an ion channel involved in inflammatory pain, transient receptor potential ankyrin 1 (TRPA1), we asked whether this increase in lipid content occurs in TRPA1-deficient (knock-out) neurons. No statistically significant change in lipid content occurred in TRPA1-deficient neurons, indicating that the inflammation-mediated increase in lipid content is largely dependent on TRPA1. Because TRPA1 is known to mediate mechanical and cold sensitization that accompanies peripheral inflammation, our findings may have important implications for a potential role of lipids in inflammatory pain. PMID:25271163

[Effect of Small Knife Needle on β-enorpin and Enkehalin Contents of Tansverse Process Syndrome of the Third Vertebra].

PubMed

Liu, Nai-gang; Guo, Chang-qing; Sun, Hong-mei; Li, Xiao-hong; Wu, Hai-xia; Xu, Hong

2016-04-01

To explore the analgesic mechanism of small knife needle for treating transverse process syndrome of the third vertebra (TPSTV) by observing peripheral and central changesof β-endorphin (β-EP) and enkephalin (ENK) contents. Totally 30 Japanese white big-ear rabbits of clean grade were divided into 5 groups according to random digit table, i.e., the normal control group, the model group, the small knife needle group, the electroacupunture (EA) group, and the small knife needle plus EA group, 6 in each group. The TPSTV model was established by inserting a piece of gelatin sponge into the left transverse process of 3rd lumbar vertebrae. Rabbits in the small knife needlegroup were intervened by small knife needle. Those in the EA group were intervened by EA at bilateralWeizhong (BL40). Those in the small knife needle plus EA group were intervened by small knife needleand EA at bilateral Weizhong (BL40). Contents of β-EP and ENK in plasma, muscle, spinal cord, and hypothalamus were determined after sample collection at day 28 after modeling. Compared with the normal control group, contents of β-EP and ENK in plasma and muscle increased significantly, and contents of β-EP and ENK in spinal cord and hypothalamus decreased significantly in the model group (P < 0.05, P < 0.01). Contents of β-EP and ENK approximated normal levels in the three treatment groups after respective treatment. Compared with the model group, the content of β-EP in muscle decreased, and contents of β-EP and ENK in hypothalamus increased in the three treatment groups after respective treatment (P < 0.05). There were no significant difference among the three treatment groups (P > 0.05). Small knife needle treatment and EA had benign regulation on peripheral and central β-EP and ENK in TPSTV rabbits. Small knife needle treatment showed better effect than that of EA.

Systemic Chemotherapy as Salvage Treatment for Locally Advanced Rectal Cancer Patients Who Fail to Respond to Standard Neoadjuvant Chemoradiotherapy.

PubMed

Sclafani, Francesco; Brown, Gina; Cunningham, David; Rao, Sheela; Tekkis, Paris; Tait, Diana; Morano, Federica; Baratelli, Chiara; Kalaitzaki, Eleftheria; Rasheed, Shahnawaz; Watkins, David; Starling, Naureen; Wotherspoon, Andrew; Chau, Ian

2017-06-01

The potential of chemotherapy as salvage treatment after failure of neoadjuvant chemoradiotherapy for locally advanced rectal cancer (LARC) has never been explored. We conducted a single-center, retrospective analysis to address this question. Patients with newly diagnosed LARC who were inoperable or candidates for extensive (i.e., beyond total mesorectal excision [TME]) surgery after long-course chemoradiotherapy and who received salvage chemotherapy were included. The primary objective was to estimate the proportion of patients who became suitable for TME after chemotherapy. Forty-five patients were eligible (39 candidates for extensive surgery and 6 unresectable). Previous radiotherapy was given concurrently with chemotherapy in 43 cases (median dose: 54.0 Gy). Oxaliplatin- and irinotecan-based salvage chemotherapy was administered in 40 (88.9%) and 5 (11.1%) cases, respectively. Eight patients (17.8%) became suitable for TME after chemotherapy, 10 (22.2%) ultimately underwent TME with clear margins, and 2 (4.4%) were managed with a watch and wait approach. Additionally, 13 patients had extensive surgery with curative intent. Three-year progression-free survival and 5-year overall survival in the entire population were 30.0% (95% confidence interval [CI]: 15.0-46.0) and 44.0% (95% CI: 26.0-61.0), respectively. For the curatively resected and "watch and wait" patients, these figures were 52.0% (95% CI: 27.0-73.0) and 67.0% (95% CI: 40.0-84.0), respectively. Systemic chemotherapy may be an effective salvage strategy for LARC patients who fail to respond to chemoradiotherapy and are inoperable or candidates for beyond TME surgery. According to our study, one out of five patients may become resectable or be spared from an extensive surgery after systemic chemotherapy. High-quality evidence to inform the optimal management of rectal cancer patients who are inoperable or candidates for beyond total mesorectal excision surgery following standard chemoradiotherapy is lacking. We show for the first time that systemic chemotherapy may be beneficial and result in one out of five poor prognosis patients becoming resectable or being spared from an extensive surgical approach. Although mores studies are needed to confirm these data, administering salvage systemic chemotherapy in this setting may have the potential to minimize morbidity associated with extensive surgical procedures and improve long-term oncological outcome. © AlphaMed Press 2017.

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas

PubMed Central

Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-01-01

Introduction Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. Aim The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. Materials and Methods This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn’t warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Results Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple’s procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Conclusion Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn’t predict vascular involvement and liver metastasis. PMID:27134925

The Role of CA19-9 in Predicting Tumour Resectability in Carcinoma Head of Pancreas.

PubMed

Pandiaraja, Jayabal; Viswanathan, Subramanian; Antomy, Thomas Babu; Thirumuruganand, Sathyamoorthy; Kumaresan, Dhandapani Subramanian

2016-03-01

Carbohydrate antigen 19-9 (CA 19-9) is a tumour associated antigen. Blood levels may be elevated in benign as well as malignant conditions. Its sensitivity (70-90%) and specificity (68-91%) are inadequate for accurate diagnosis. It can be used to predict the extent of disease and outcome after resection. The aim of the present study was to assess the role of CA 19-9 in predicting the resectability of the tumour in the head of pancreas. This was a prospective study which included 30 patients and study period was from May 2012 to October 2014. Data collected from all patients with carcinoma of the head of pancreas on the basis of contrast enhanced computed tomography/Magnetic resonance cholangiopancreaticography. CA 19-9 levels were measured and recorded. Patients who were medically unfit for surgery or those who didn't warrant palliative surgery were excluded from the study. During surgery the operative findings on operability were documented and tabulated against corresponding CA 19-9 levels. Of the 30 patients who were operated, 13(43.3%) patients had operable tumours and underwent Whipple's procedure and 17(56.7%) underwent palliative bypass procedure. Of the 30, CA 19-9 levels were elevated in 9(30.0%) and were normal in 21(70.0%). Among 13(43.3%) who had operable tumours, CA 19-9 was elevated in 4(13.3) and was normal in 9(30.0%). Of the 17(56.7%) who had inoperable tumours CA 19-9 was elevated in 5(16.7%) and was normal in 12(40.0%). Among the 17 who had inoperable tumours, 8(47.1%) were diagnosed preoperatively and of them CA 19-9 levels were raised in 2(11.8%) and normal in 6(35.3%). In the group of 9(52.9%) who had inoperable tumours diagnosed intraoperatively, CA 19-9 was raised in 3(17.6%) of them and was normal in the remaining 6(35.3%) of them. Based on the study findings, it can be stated that there is no significant correlation with resectability of pancreatic adenocarcinoma and CA 19-9 and it doesn't predict vascular involvement and liver metastasis.

Peripheral CD4+ naïve/memory ratio is an independent predictor of survival in non-small cell lung cancer

PubMed Central

Yang, Peng; Ma, Junhong; Yang, Xin; Li, Wei

2017-01-01

Background To investigate the clinical significance of naïve T cells, memory T cells, CD45RA+CD45RO+ T cells, and naïve/memory ratio in non-small cell lung cancer (NSCLC) patients. Methods Pretreatment peripheral blood samples from 76 NSCLC patients and 28 age- and sex-matched healthy volunteers were collected and tested for immune cells by flow cytometry. We compared the expression of these immune cells between patients and healthy controls and evaluated their predictive roles for survival in NSCLC by cox proportional hazards model. Results Decreased naïve CD4+ T cells, naïve CD8+ T cells, CD4+ naïve/memory ratios and CD4+CD45RA+CD45RO+ T cells, and increased memory CD4+ T cells, were observed in 76 NSCLC patients compared to healthy volunteers. Univariate analysis revealed that elevated CD4+ naïve/memory ratio correlated with prolonged progression-free survival (P=0.013). Multivariate analysis confirmed its predictive role with a hazard ratio of 0.35 (95% confidence interval, 0.19-0.75, P=0.012). Conclusions Peripheral CD4+ naïve/memory ratio can be used as a predictive biomarker in NSCLC patients and used to optimize personalized treatment strategies. PMID:29137371

Technical Note: Out‐of‐field dose measurement at near surface with plastic scintillator detector

PubMed Central

Bourgouin, Alexandra; Varfalvy, Nicolas

2016-01-01

Out‐of‐field dose depends on multiple factors, making peripheral dosimetry complex. Only a few dosimeters have the required features for measuring peripheral dose. Plastic scintillator dosimeters (PSDs) offer numerous dosimetric advantages as required for out‐of‐field dosimetry. The purpose of this study is to determine the potential of using PSD as a surface peripheral dosimeter. Measurements were performed with a parallel‐plate ion chamber, a small volume ion chamber, and with a PSD. Lateral‐dose measurements (LDM) at 0.5 cm depth and depth‐dose curve (PDD) were made and compared to the dose calculation provided by a treatment planning system (TPS). This study shows that a PSD can measure a dose as low as 0.51±0.17cGy for photon beam and 0.58±0.20cGy for electron beam with a difference of 0.2 and 0.1 cGy compared to a parallel‐plate ion chamber. This study demonstrates the potential of using PSD as an out‐of‐field dosimeter since measurements with PSD avoid averaging over a too‐large depth, at 1 mm diameter, and can make precise measurement at very low dose. Also, electronic equilibrium is easier to reach with PSD due to its small sensitive volume and its water equivalence. PACS number(s): 87.55.N, 87.55.km PMID:27685131

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adelstein, D.J.; Padhya, T.; Tomashefski, J.F. Jr.

We describe a patient with recurrent small cell undifferentiated lung carcinoma after chemotherapy and mediastinal radiation therapy who presented with peripheral pulmonary infiltrates on chest radiograph. At autopsy the patient was found to have carcinomatous pneumonia confined to the radiographically abnormal lung. The descriptive term reverse radiation pneumonitis is applied in view of the striking nonsegmental distribution of these pulmonary infiltrates, which occurred only outside the irradiated field. In this patient, radiation therapy successfully controlled disease in the treated lung parenchyma, thus accounting for this unusual radiologic and histologic picture. Pneumonia carcinomatosa, occurring after lung irradiation, can therefore be addedmore » to the differential diagnosis of radiographic peripheral pulmonary infiltrates.« less

Subarachnoid and Intracerebral Hemorrhage in Patients with Churg-Strauss Syndrome: Two Case Reports

PubMed Central

Go, Myeong Hoon; Park, Jeong Un; Kang, Jae Gyu

2012-01-01

Churg-Strauss syndrome (CSS) is a systemic necrotizing vasculitis of the small and medium vessels, associated with extravascular eosinophilic granulomas, peripheral eosinophilia, and asthma. The exact etiology of CSS is unknown. This syndrome commonly affects the lungs, peripheral nerves, skin, heart, and gastrointestinal tract, but rarely the central nervous system. Subarachnoid and intracerebral hemorrhage in CSS patients is extremely rare; however, clinicians should consider that CSS may be a cause of intracranial hemorrhage and its high rate of mortality and morbidity. The authors report on two cases of subarachnoid and intracerebral hemorrhage with CSS and discuss a brief review of CSS. PMID:23210058

Bidirectional peripheral nerve interface and applications.

PubMed

Thakor, Nitish V; Qihong Wang; Greenwald, Elliot

2016-08-01

Peripheral nerves, due to their small size and complex innervation to organs and complex physiology, pose particularly significant challenges towards interfacing electrodes and electronics to enable neuromodulation. Here, we present a review of the technology for building such interface, including recording and stimulating electrodes and low power electronics, as well as powering. Of particular advantage to building a miniature implanted device is a "bidirectional" system that both senses from the nerves or surrogate organs and stimulates the nerves to affect the organ function. This review and presentation will cover a range of electrodes, electronics, wireless power and data schemes and system integration, and will end with some examples and applications.

DNA ISOLATION FROM SMALL TISSUE SAMPLES USING SALT AND SPERMINE

EPA Science Inventory

Common DNA isolation methods rely upon protein denaturation by organic solvents such as phenol and chloroform. hese solvents pose some risk to the user and require special disposal procedures. e have previously reported a method for isolating DNA from peripheral blood lymphocytes...

Radiological interventions in malignant biliary obstruction

PubMed Central

Madhusudhan, Kumble Seetharama; Gamanagatti, Shivanand; Srivastava, Deep Narayan; Gupta, Arun Kumar

2016-01-01

Malignant biliary obstruction is commonly caused by gall bladder carcinoma, cholangiocarcinoma and metastatic nodes. Percutaneous interventions play an important role in managing these patients. Biliary drainage, which forms the major bulk of radiological interventions, can be palliative in inoperable patients or pre-operative to improve liver function prior to surgery. Other interventions include cholecystostomy and radiofrequency ablation. We present here the indications, contraindications, technique and complications of the radiological interventions performed in patients with malignant biliary obstruction. PMID:27247718

Beating the Red Gold Rush: Copper Theft and Homeland Security

DTIC Science & Technology

2015-12-01

with the bulk 52 of the copper wiring rendering each of the turbines inoperable.116 Electrical infrastructure is, of course, not the only kind of...resulted in significant speed restrictions and stop orders for the country’s premier TGV high- speed service.119 Aside from rail lines and wind turbines ... Wind Turbines ,” France 24, May 28, 2014, http://www.france24.com/en/20140528-france-metal-organised-thefts- wind - turbines -copper, accessed August 22

Excellent Result With the Use of Single-Dose OK-432 in Cervical Macrocystic Lymphangioma.

PubMed

Efe, Nihal; Altas, Enver; Mazlumoglu, Muhammet Recai; Aktan, Bulent; Ucuncu, Harun; Eren, Suat; Oner, Fatih

2016-10-01

Though the lymphangioma is a benign neoplasm, it may make an invasion to vital structures by progressively growing. For lymphangioma, which progressed in such a way, surgical treatment has high morbidity and recurrence risk. On these cases, OK-432 is a frequently used sclerotherapy agent. The authors report the result they obtained by the use of single-dose OK-432 on an inoperable pediatric cervical macrocystic lymphangioma case and also their experiences.

Stereotactic Injection of DTI-015 into Recurrent Malignant Gliomas: Phase I/II Trial

PubMed Central

Hassenbusch, Samuel J; Nardone, Emilio M; Levin, Victor A; Leeds, Norman; Pietronigro, Dennis

2003-01-01

Abstract DTI-015 (BCNU in 100% ethanol) utilizes solvent facilitated perfusion for the intratumoral treatment of gliomas. The ethanol solvent vehicle facilitates a rapid and thorough saturation of the tumor with the dissolved anticancer agent BCNU. We conducted a phase I/II dose escalation study of DTI-015 in 40 heavily pretreated patients with inoperable recurrent malignant glioma. The study goals were to establish a maximally tolerated dose (MTD) for DTI-015 and assess its safety and activity. Patients received stereotactic intratumoral injection of DTI-015 under magnetic resonance imaging guidance. Dose escalation was performed in two phases. First, DTI-015 volume was escalated at a set BCNU concentration of 12.5 mg/ml; second, BCNU mg dose was escalated by increasing BCNU concentration to 30, 45, 60, and 75 mg/ml. A MTD of 5 ml and 240 mg was established. Twenty-five of 28 DTI-015 treatments (89%) using ≤MTD were administered safely without producing high-grade drug-related adverse events. Median survival for GBM patients administered DTI-015 at ≤MTD was 55 weeks. Magnetic resonance imaging demonstrated stable disease in 72% of evaluable patients with a median of 10.5 weeks. The results suggest that DTI-015 administered at ≤MTD is well tolerated and active in patients with inoperable recurrent GBM. PMID:12659665

Spiritual Well-Being and Correlated Factors in Subjects With Advanced COPD or Lung Cancer.

PubMed

Hasegawa, Takaaki; Kawai, Momoko; Kuzuya, Nanori; Futamura, Yohei; Horiba, Akane; Ishiguro, Takashi; Yoshida, Tsutomu; Sawa, Toshiyuki; Sugiyama, Yasuyuki

2017-05-01

Spiritual care for patients with COPD has rarely been discussed, and thus much remains unknown about their needs. The aims of this study were to identify the factors associated with spiritual well-being and to compare the levels of spiritual well-being between subjects with advanced COPD and those with inoperable lung cancer. A total of 96 subjects with COPD or lung cancer participated in this study, which was conducted between December 2014 and April 2016. Measures included the Japanese version of the 12-item Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp-12) scale, the McGill Quality of Life Questionnaire (MQOL), the modified Medical Research Council (mMRC) dyspnea scale, and various other medico-social factors. No significant differences were found between subjects with COPD and those with lung cancer in median FACIT-Sp-12 scores (COPD, 27; lung cancer, 26; P = .81). However, significant differences were found in the 2 MQOL domains, suggesting that subjects with COPD had a better psychological state ( P = .01) and that subjects with lung cancer had a better support state ( P = .002). Multiple regression analysis revealed that mMRC was significantly associated with FACIT-Sp-12 scores in subjects with COPD. These results suggest that subjects with advanced COPD experience spiritual well-being similar to that of subjects with inoperable lung cancer. Copyright © 2017 by Daedalus Enterprises.

Cytological Sampling Versus Forceps Biopsy During Percutaneous Transhepatic Biliary Drainage and Analysis of Factors Predicting Success

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tapping, C. R.; Byass, O. R.; Cast, J. E. I., E-mail: james.cast@hey.nhs.uk

Purpose: To assess the accuracy of cytological sampling and forceps biopsy in obstructing biliary lesions and to identify factors predictive of success. Methods: Consecutive patients (n = 119) with suspected malignant inoperable obstructive jaundice treated with percutaneous transhepatic biliary drainage during 7 years were included (60 male; mean age 72.5 years). All patients underwent forceps biopsy plus cytological sampling by washing the forceps device in cytological solution. Patient history, procedural and pathological records, and clinical follow-up were reviewed. Statistical analysis included chi-square test and multivariate regression analysis. Results: Histological diagnosis after forceps biopsy was more successful than cytology: Sensitivity wasmore » 78 versus 61%, and negative predictive value was 30 versus 19%. Cytology results were never positive when the forceps biopsy was negative. The cytological sample was negative and forceps sample positive in 2 cases of cholangiocarcinoma, 16 cases of pancreatic carcinoma, and 1 case of benign disease. Diagnostic accuracy was predicted by low bilirubin (p < 0.001), aspartate transaminase (p < 0.05), and white cell count (p {<=} 0.05). Conclusions: This technique is safe and effective and is recommended for histological diagnosis during PTBD in patients with inoperable malignant biliary strictures. Diagnostic yield is greater when bilirubin levels are low and there is no sepsis; histological diagnosis by way of forceps biopsy renders cytological sampling unnecessary.« less

Re-Operative Pancreaticoduodenectomy: Challenges and Outcomes.

PubMed

Bhandare, Manish S; Mehta, Nikhil; Chaudhari, Vikram; Kumar, Naveena An; Pai, Esha; Goel, Mahesh; Shrikhande, Shailesh V

2018-05-23

Tata Memorial Centre (TMC) is a high-volume centre for pancreatic tumour resections. We found a continually increasing referral of pancreatic tumours for re-evaluation for surgery, after an initial unsuccessful attempt at resection. To evaluate reasons of initial in-operability, the feasibility of re-operative pancreatico-duodenectomy (R-PD) and short- and long-term outcomes after R-PD. Data was collected from a prospective database of GI and hepato-pancreato-biliary service, TMC, Mumbai from January 2008 to December 2016. Forty patients with periampullary/pancreatic head tumours were referred to us after exploration. Thirty were planned for re-exploration, of whom 25 patients underwent successful R-PD, either upfront (n = 12) or after neo-adjuvant therapy (n = 13). Twenty were adenocarcinomas, 5 had other histologies. Majority of the patients were deemed inoperable in view of suspected vascular involvement at the time of initial surgery (68%). R0 resection was achieved in 90% of adenocarcinoma cases (n = 18). Postoperative major morbidity was 20% and mortality was 4% (n = 1). The estimated 1-, 2- and 5-year survival for those with adenocarcinoma was 83, 71.2, and 29.9% respectively. R-PD is safe and should be performed in experienced centres and can achieve long-term outcomes, comparable to conventional PD. The most common reason for denying resection at initial surgery was suspected or perceived vascular involvement. © 2018 S. Karger AG, Basel.

Self-expanding stent made of polyester mesh with silicon coating (Polyflex) in the treatment of inoperable tracheal stenoses.

PubMed

Terra, Ricardo Mingarini; Minamoto, Helio; Tedde, Miguel Lia; Almeida, José Luiz Jesus de; Jatene, Fabio Biscegli

2007-01-01

To evaluate the Polyflex stent in terms of its efficacy, ease of implantation, and complications in patients with tracheobronchial affections. This was a prospective study, in which sixteen patients with inoperable tracheal stenosis secondary to orotracheal intubation (n = 12), neoplasia (n = 3), or Wegener's granulomatosis (n = 1) were monitored. Of these patients, eleven were women, and five were men. The mean age was 42.8 years (range, 21-72 years). Patients were submitted to implantation of a total of 21 Polyflex stents. All procedures were carried out in the operating room under general anesthesia, and the stents were implanted via suspension laryngoscopy using the stent applicator. Stents were implanted and symptoms were resolved in all cases. The stents remained in place for a mean period of 7.45 months, ranging from 2 to 18 months. The complications observed in the immediate postoperative period were dysphonia (in two patients, 12.5%) and odynophagia (in two patients, 12.5%). Late complications were cough (in ten patients, 62.5%), migration (in seven patients, 43.75%), granuloma formation (in two patients, 12.5%), and pneumonia (in one patient, 6.25%). The Polyflex stent is easily implanted, easily removed, well tolerated by patients and effective in resolving symptoms. However, its use is associated with a high rate of migration, especially in patients with post-orotracheal intubation stenosis.

Variety of RNAs in Peripheral Blood Cells, Plasma, and Plasma Fractions

PubMed Central

Kuligina, Elena V.; Bariakin, Dmitry N.; Kozlov, Vadim V.; Richter, Vladimir A.; Semenov, Dmitry V.

2017-01-01

Human peripheral blood contains RNA in cells and in extracellular membrane vesicles, microvesicles and exosomes, as well as in cell-free ribonucleoproteins. Circulating mRNAs and noncoding RNAs, being internalized, possess the ability to modulate vital processes in recipient cells. In this study, with SOLiD sequencing technology, we performed identification, classification, and quantification of RNAs from blood fractions: cells, plasma, plasma vesicles pelleted at 16,000g and 160,000g, and vesicle-depleted plasma supernatant of healthy donors and non-small cell lung cancer (NSCLC) patients. It was determined that 16,000g blood plasma vesicles were enriched with cell-free mitochondria and with a set of mitochondrial RNAs. The variable RNA set of blood plasma 160,000g pellets reflected the prominent contribution of U1, U5, and U6 small nuclear RNAs' fragments and at the same time was characterized by a remarkable depletion of small nucleolar RNAs. Besides microRNAs, the variety of fragments of mRNAs and snoRNAs dominated in the set of circulating RNAs differentially expressed in blood fractions of NSCLC patients. Taken together, our data emphasize that not only extracellular microRNAs but also circulating fragments of messenger and small nuclear/nucleolar RNAs represent prominent classes of circulating regulatory ncRNAs as well as promising circulating biomarkers for the development of disease diagnostic approaches. PMID:28127559

Metastatic pulmonary calcification: high-resolution computed tomography findings in 23 cases.

PubMed

Belém, Luciana Camara; Souza, Carolina A; Souza, Arthur Soares; Escuissato, Dante Luiz; Hochhegger, Bruno; Nobre, Luiz Felipe; Rodrigues, Rosana Souza; Gomes, Antônio Carlos Portugal; Silva, Claudio S; Guimarães, Marcos Duarte; Zanetti, Gláucia; Marchiori, Edson

2017-01-01

The aim of this study was to evaluate the high-resolution computed tomography (HRCT) findings in patients diagnosed with metastatic pulmonary calcification (MPC). We retrospectively reviewed the HRCT findings from 23 cases of MPC [14 men, 9 women; mean age, 54.3 (range, 26-89) years]. The patients were examined between 2000 and 2014 in nine tertiary hospitals in Brazil, Chile, and Canada. Diagnoses were established by histopathologic study in 18 patients and clinical-radiological correlation in 5 patients. Two chest radiologists analyzed the images and reached decisions by consensus. The predominant HRCT findings were centrilobular ground-glass nodules ( n = 14; 60.9%), consolidation with high attenuation ( n = 10; 43.5%), small dense nodules ( n = 9; 39.1%), peripheral reticular opacities associated with small calcified nodules ( n = 5; 21.7%), and ground-glass opacities without centrilobular ground-glass nodular opacity ( n = 5; 21.7%). Vascular calcification within the chest wall was found in four cases and pleural effusion was observed in five cases. The abnormalities were bilateral in 21 cases. MPC manifested with three main patterns on HRCT, most commonly centrilobular ground-glass nodules, often containing calcifications, followed by dense consolidation and small solid nodules, most of which were calcified. We also described another pattern of peripheral reticular opacities associated with small calcified nodules. These findings should suggest the diagnosis of MPC in the setting of hypercalcemia.

Peripheral refraction and image blur in four meridians in emmetropes and myopes.

PubMed

Shen, Jie; Spors, Frank; Egan, Donald; Liu, Chunming

2018-01-01

The peripheral refractive error of the human eye has been hypothesized to be a major stimulus for the development of its central refractive error. The purpose of this study was to investigate the changes in the peripheral refractive error across horizontal, vertical and two diagonal meridians in emmetropic and low, moderate and high myopic adults. Thirty-four adult subjects were recruited and aberration was measured using a modified commercial aberrometer. We then computed the refractive error in power vector notation from second-order Zernike terms. Statistical analysis was performed to evaluate the statistical differences in refractive error profiles between the subject groups and across all measured visual field meridians. Small amounts of relative myopic shift were observed in emmetropic and low myopic subjects. However, moderate and high myopic subjects exhibited a relative hyperopic shift in all four meridians. Astigmatism J 0 and J 45 had quadratic or linear changes dependent on the visual field meridians. Peripheral Sphero-Cylindrical Retinal Image Blur increased in emmetropic eyes in most of the measured visual fields. The findings indicate an overall emmetropic or slightly relative myopic periphery (spherical or oblate retinal shape) formed in emmetropes and low myopes, while moderate and high myopes form relative hyperopic periphery (prolate, or less oblate, retinal shape). In general, human emmetropic eyes demonstrate higher amount of peripheral retinal image blur.

Peripheral prism glasses: effects of moving and stationary backgrounds.

PubMed

Shen, Jieming; Peli, Eli; Bowers, Alex R

2015-04-01

Unilateral peripheral prisms for homonymous hemianopia (HH) expand the visual field through peripheral binocular visual confusion, a stimulus for binocular rivalry that could lead to reduced predominance and partial suppression of the prism image, thereby limiting device functionality. Using natural-scene images and motion videos, we evaluated whether detection was reduced in binocular compared with monocular viewing. Detection rates of nine participants with HH or quadranopia and normal binocularity wearing peripheral prisms were determined for static checkerboard perimetry targets briefly presented in the prism expansion area and the seeing hemifield. Perimetry was conducted under monocular and binocular viewing with targets presented over videos of real-world driving scenes and still frame images derived from those videos. With unilateral prisms, detection rates in the prism expansion area were significantly lower in binocular than in monocular (prism eye) viewing on the motion background (medians, 13 and 58%, respectively, p = 0.008) but not the still frame background (medians, 63 and 68%, p = 0.123). When the stimulus for binocular rivalry was reduced by fitting prisms bilaterally in one HH and one normally sighted subject with simulated HH, prism-area detection rates on the motion background were not significantly different (p > 0.6) in binocular and monocular viewing. Conflicting binocular motion appears to be a stimulus for reduced predominance of the prism image in binocular viewing when using unilateral peripheral prisms. However, the effect was only found for relatively small targets. Further testing is needed to determine the extent to which this phenomenon might affect the functionality of unilateral peripheral prisms in more real-world situations.

Peripheral Prism Glasses: Effects of Moving and Stationary Backgrounds

PubMed Central

Shen, Jieming; Peli, Eli; Bowers, Alex R.

2015-01-01

Purpose Unilateral peripheral prisms for homonymous hemianopia (HH) expand the visual field through peripheral binocular visual confusion, a stimulus for binocular rivalry that could lead to reduced predominance (partial local suppression) of the prism image and limit device functionality. Using natural-scene images and motion videos, we evaluated whether detection was reduced in binocular compared to monocular viewing. Methods Detection rates of nine participants with HH or quadranopia and normal binocularity wearing peripheral prisms were determined for static checkerboard perimetry targets briefly presented in the prism expansion area and the seeing hemifield. Perimetry was conducted under monocular and binocular viewing with targets presented over videos of real-world driving scenes and still frame images derived from those videos. Results With unilateral prisms, detection rates in the prism expansion area were significantly lower in binocular than monocular (prism eye) viewing on the motion background (medians 13% and 58%, respectively, p = 0.008), but not the still frame background (63% and 68%, p = 0.123). When the stimulus for binocular rivalry was reduced by fitting prisms bilaterally in 1 HH and 1 normally-sighted subject with simulated HH, prism-area detection rates on the motion background were not significantly different (p > 0.6) in binocular and monocular viewing. Conclusions Conflicting binocular motion appears to be a stimulus for reduced predominance of the prism image in binocular viewing when using unilateral peripheral prisms. However, the effect was only found for relatively small targets. Further testing is needed to determine the extent to which this phenomenon might affect the functionality of unilateral peripheral prisms in more real-world situations. PMID:25785533

Fondaparinux for intra and perioperative anticoagulation in patients with heparin-induced thrombocytopenia candidates for peripheral vascular surgery: Report of 4 cases.

PubMed

Illuminati, Giulio; Calio', Francesco G; Pizzardi, Giulia; Amatucci, Chiara; Masci, Federica; Palumbo, Piergaspare

2016-01-01

Intra and perioperative anticoagulation in patients with heparin induced thrombocytopenia (HIT), candidates for peripheral vascular surgery remains a challenge, as the best alternative to heparin has not yet been established. We evaluated the off-label use of fondaparinux in four patients with HIT, undergoing peripheral vascular surgery procedures. Four patients of whom 3 men of a mean age of 66 years, with proven heparin induced thrombocytopenia (HIT) underwent two axillo-femoral bypasses, one femoro-popliteal bypass and one resection of a splenic artery aneurysm under fondaparinux. No intra or perioperative bleeding or thrombosis of new onset was observed. In the absence of a valid alternative to heparin for intra and perioperative anticoagulation in HIT, several other anticoagulants can be used in an off-label setting. However, no general consensus exist on which should be the one of choice. In this small series fondaparinux appeared to be both safe and effective. These preliminary results seem to justify the off-label use of fondaparinux for intra and perioperative anticoagulation in patients with HIT, candidates for peripheral vascular surgery interventions. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Strategies to promote peripheral nerve regeneration: electrical stimulation and/or exercise

PubMed Central

Gordon, Tessa; English, Arthur W.

2015-01-01

Enhancing the regeneration of axons is often considered a therapeutic target for improving functional recovery after peripheral nerve injury. In this review, the evidence for the efficacy of electrical stimulation (ES), daily exercise, and their combination in promoting nerve regeneration after peripheral nerve injuries in both animal models and in human patients, is explored. The rationale, effectiveness, and molecular basis of ES and exercise in accelerating axon outgrowth are reviewed. In comparing the effects of ES and exercise in enhancing axon regeneration, increased neural activity, neurotrophins, and androgens are considered common requirements. Similar, gender-specific requirements are found for exercise to enhance axon regeneration in the periphery and for sustaining synaptic inputs onto injured motoneurons. ES promotes nerve regeneration after delayed nerve repair in humans and rats. The effectiveness of exercise is less clear. Although ES, but not exercise, results in a significant misdirection of regenerating motor axons to reinnervate different muscle targets, the loss of neuromuscular specificity encountered has only a very small impact on resulting functional recovery. Both ES and exercise are promising experimental treatments for peripheral nerve injury that seem ready to be translated to clinical use. PMID:26121368

Peripheral Ammonia as a Mediator of Methamphetamine Neurotoxicity

PubMed Central

Halpin, Laura E.; Yamamoto, Bryan K.

2012-01-01

Ammonia is metabolized by the liver and has established neurological effects. The current study examined the possibility that ammonia contributes to the neurotoxic effects of methamphetamine (METH). The results show that a binge dosing regimen of METH to the rat increased plasma and brain ammonia concentrations that were paralleled by evidence of hepatotoxicity. The role of peripheral ammonia in the neurotoxic effects of METH was further substantiated by the demonstration that the enhancement of peripheral ammonia excretion blocked the increases in brain and plasma ammonia and attenuated the long term depletions of dopamine and serotonin typically produced by METH. Conversely, the localized perfusion of ammonia in combination with METH, but not METH alone or ammonia alone, into the striatum recapitulated the neuronal damage produced by the systemic administration of METH. Furthermore, this damage produced by the local administration of ammonia and METH was blocked by the GYKI 52466, an AMPA receptor antagonist. These findings highlight the importance of ammonia derived from the periphery as a small molecule mediator of METH neurotoxicity and more broadly emphasize the importance of peripheral organ damage as a possible mechanism that mediates the neuropathology produced by drugs of abuse and other neuroactive molecules. PMID:22993432

Park size and disturbance: impact on soil heterogeneity - a case study Tel-Aviv- Jaffa.

NASA Astrophysics Data System (ADS)

Zhevelev, Helena; Sarah, Pariente; Oz, Atar

2015-04-01

Parks and gardens are poly-functional elements of great importance in urban areas, and can be used for optimization of physical and social components in these areas. This study aimed to investigate alteration of soil properties with land usages within urban park and with area size of park. Ten parks differed by size (2 - 50 acres) were chosen, in random, in Tel-Aviv- Jaffa city. Soil was sampled in four microenvironments ((lawn, path, picnic and peripheral area (unorganized area) of each the park)), in three points and three depth (0-2, 5-10 and 10-20 cm). Penetration depth was measured in all point of sampling. For each soil sample electrical conductivity and organic matter content were determined. Averages of penetration depth drastically increased from the most disturbed microenvironments (path and picnic) to the less disturbed ones (lawn and peripheral). The maximal heterogeneity (by variances and percentiles) of penetration depth was found in the peripheral area. In this area, penetration depth increased with increasing park size, i.e., from 2.6 cm to 3.7 cm in the small and large parks, respectively. Averages of organic matter content and electrical conductivity decreased with soil depth in all microenvironments and increased with decreasing disturbance of microenvironments. Maximal heterogeneity for both of these properties was found in the picnic area. Increase of park size was accompanied by increasing of organic matter content in the upper depth in the peripheral area, i.e., from 2.4% in the small parks to 4.5% in the large ones. In all microenvironments the increasing of averages of all studied soil properties was accompanied by increasing heterogeneity, i.e., variances and upper percentiles. The increase in the heterogeneity of the studied soil properties is attributed to improved ecological soil status in the peripheral area, on the one hand, and to the high anthropogenic pressure in the picnic area, on the other. This means that the urban park offers "islands" with better ecological conditions which improve the urban system.

Academic Inbreeding: Local Challenge, Global Problem

ERIC Educational Resources Information Center

Altbach, Philip G.; Yudkevich, Maria; Rumbley, Laura E.

2015-01-01

"Academic inbreeding"--involving the appointment of faculty members who graduated from the institution employing them--is considered a small and peripheral aspect of the academic profession but is quite widespread globally. This paper analyzes the nature of inbreeding and its impact on universities. Data from eight countries where…

Small heterodimer partner (NROB2) coordinates nutrient signaling and the circadian clock in mice

USDA-ARS?s Scientific Manuscript database

Circadian rhythm regulates multiple metabolic processes and in turn is readily entrained by feeding-fasting cycles. However, the molecular mechanisms by which the peripheral clock senses nutrition availability remain largely unknown. Bile acids are under circadian control and also increase postprand...

Renal Cell Carcinoma: Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review.

PubMed

Prins, Fieke M; Kerkmeijer, Linda G W; Pronk, Anne A; Vonken, Evert-Jan P A; Meijer, Richard P; Bex, Axel; Barendrecht, Maurits M

2017-10-01

The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery, alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA), microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance, radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future.

Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

PubMed

Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

2018-04-01

The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

An MRM-Based Cytokeratin Marker Assay as a Tool for Cancer Studies: Application to Lung Cancer Pleural Effusions.

PubMed

Perzanowska, Anna; Fatalska, Agnieszka; Wojtas, Grzegorz; Lewandowicz, Andrzej; Michalak, Agata; Krasowski, Grzegorz; Borchers, Christoph H; Dadlez, Michal; Domanski, Dominik

2018-03-01

The goal of this work was to develop an LC-MRM assay for the quantitative analysis of a set of established and diagnostically important cytokeratin (CK) markers used in cancer diagnosis, prognosis, and therapy monitoring. Second, the potential of this assay in lung cancer diagnosis through pleural effusion (PE) analysis was examined. A multiplexed MRM assay was developed for 17 CKs and their select caspase-cleaved fragments. Isotope-labeled standard peptides were used for high assay specificity and absolute peptide quantitation; with robust standard-flow LC coupled to a latest-generation triple-quadrupole instrument for high sensitivity. The potential clinical applicability was demonstrated by the analysis of 118 PE samples. The MRM assay was evaluated for endogenous detection, linearity, precision, upper and lower limits of quantification, selectivity, reproducibility and peptide stability, and is generally applicable to any epithelial cancer study. A set of 118 patients with known pathologies allowed us to define the range of CK levels in clinical PE samples. Specific CKs were able to differentiate cancer-related PEs from those caused by benign ailments. In addition, they allowed to differentiate between PEs from subjects with small cell lung cancer versus non-small cell lung carcinoma, and to further differentiate the latter into its two subtypes, adenocarcinoma and squamous cell carcinoma. An MRM-based CK assay for carcinoma studies can differentiate between the three lung cancer histological types using less-invasive PE sampling providing potential therapy-guiding information on patients that are inoperable. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Principles of radiotherapy of non-small cell lung cancer].

PubMed

Esik, Olga; Horváth, Akos; Bajcsay, András; Hideghéty, Katalin; Agócs, László; Pikó, Béla; Lengyel, Zsolt; Petrányi, Agota; Pisch, Julianna

2002-01-01

The long-term survival probability for Hungarian lung cancer patients is 10% worse than the best results published in the most highly developed countries (the mean 5-year survival probability in Hungary is 5%, in contrast with the 15% survival probability in the USA). On the basis of the international recommendations and personal experience, an attempt was made to formulate the guidelines for radiotherapy as one of the fundamental non-small cell lung cancer (NSCLC) treatment modalities for national use. An expert panel was set up comprising physicians from 6 radiotherapeutic centers (the National Institute of Oncology / Semmelweis University, Budapest; the Beth Israel Medical Center, New York; the University of Kaposvár; the University of Essen; the University of Debrecen; and the County Hospital of Gyula). Experts in two important medical fields closely related to radiotherapy (surgery and diagnostic imaging) were also engaged in the elaboration of the manuscript. Discussion of the most important principles of the radiotherapy and an overview of the prognostic factors was followed by a critical analysis of the protocols applied in the radiotherapy of Hungarian NSCLC patients during recent decades. The new guidelines suggested for the radiotherapy of NSCLC are presented separately for the postoperative period, marginally resectable tumors, and the aggressive or non-aggressive radiotherapy of inoperable tumors. Detailed accounts are given of the techniques of external irradiation and brachytherapy, and of the acute and late radiation-induced damage of normal tissues. The authors believe that this document may be instrumental in improving the survival index of Hungarian NSCLC patients in the near future.

Risk factors for disseminated intravascular coagulation in patients with lung cancer.

PubMed

Nakano, Kentaro; Sugiyama, Kumiya; Satoh, Hideyuki; Shiromori, Sadaaki; Sugitate, Kei; Arifuku, Hajime; Yoshida, Naruo; Watanabe, Hiroyoshi; Tokita, Shingo; Wakayama, Tomoshige; Tatewaki, Masamitsu; Souma, Ryosuke; Koyama, Kenya; Hirata, Hirokuni; Fukushima, Yasutsugu

2018-05-31

The mortality rate from disseminated intravascular coagulation (DIC) is higher in patients with lung cancer than in non-lung cancer patients. Moreover, the prevalence of DIC varies among the pathologic types of lung cancer. This study analyzed the relationship between coagulation factors and the pathologic types of lung cancer. Twenty-six patients with progressive, inoperable stage IIB or higher lung cancer (20 men, 6 women; mean age 71 years; 11 Adeno, 10 squamous cell carcinoma, and 5 small cell carcinoma) and five healthy volunteers without respiratory disease (3 men, 2 women; mean age 72 years) were enrolled in the study. Blood samples were collected at lung cancer diagnosis, before treatment. White blood cell count, platelet count, serum C-reactive protein, fibrin/fibrinogen degradation products, fibrinogen, thrombin-antithrombin complex, and D-dimer levels differed significantly between lung cancer patients and the control group, but not among the pathologic types of lung cancer. Thrombomodulin levels were significantly higher in patients with Adeno and squamous cell carcinoma than in those with small cell carcinoma (P < 0.05 and P < 0.01, respectively). Antithrombin levels were significantly lower in patients with squamous cell carcinoma than in those with Adeno (P < 0.05). Coagulation disorders may develop secondary to chronic inflammation in patients with progressive lung cancer. DIC in lung cancer may be attributed to changes in anticoagulation factors, such as thrombomodulin and antithrombin, but not in other coagulation factors. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Peripheral doses from pediatric IMRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klein, Eric E.; Maserang, Beth; Wood, Roy

Peripheral dose (PD) data exist for conventional fields ({>=}10 cm) and intensity-modulated radiotherapy (IMRT) delivery to standard adult-sized phantoms. Pediatric peripheral dose reports are limited to conventional therapy and are model based. Our goal was to ascertain whether data acquired from full phantom studies and/or pediatric models, with IMRT treatment times, could predict Organ at Risk (OAR) dose for pediatric IMRT. As monitor units (MUs) are greater for IMRT, it is expected IMRT PD will be higher; potentially compounded by decreased patient size (absorption). Baseline slab phantom peripheral dose measurements were conducted for very small field sizes (from 2 tomore » 10 cm). Data were collected at distances ranging from 5 to 72 cm away from the field edges. Collimation was either with the collimating jaws or the multileaf collimator (MLC) oriented either perpendicular or along the peripheral dose measurement plane. For the clinical tests, five patients with intracranial or base of skull lesions were chosen. IMRT and conventional three-dimensional (3D) plans for the same patient/target/dose (180 cGy), were optimized without limitation to the number of fields or wedge use. Six MV, 120-leaf MLC Varian axial beams were used. A phantom mimicking a 3-year-old was configured per Center for Disease Control data. Micro (0.125 cc) and cylindrical (0.6 cc) ionization chambers were appropriated for the thyroid, breast, ovaries, and testes. The PD was recorded by electrometers set to the 10{sup -10} scale. Each system set was uniquely calibrated. For the slab phantom studies, close peripheral points were found to have a higher dose for low energy and larger field size and when MLC was not deployed. For points more distant from the field edge, the PD was higher for high-energy beams. MLC orientation was found to be inconsequential for the small fields tested. The thyroid dose was lower for IMRT delivery than that predicted for conventional (ratio of IMRT/cnventional ranged from 0.47-0.94) doses {approx}[0.4-1.8 cGy]/[0.9-2.9 cGy]/fraction, respectively. Prior phantom reports are for fields 10 cm or greater, while pediatric central nervous system fields range from 4 to 7 cm, and effectively much smaller for IMRT (2-6 cm). Peripheral dose in close proximity (<10 cm from the field edge) is dominated by internal scatter; therefore, field-size differences overwhelm phantom size affects and increased MU. Distant peripheral dose, dominated by head leakage, was higher than predicted, even when accounting for MUs ({approx}factor of 3) likely due to the pediatric phantom size. The ratio of the testes dose ranged from 3.3-5.3 for IMRT/conventional. PD to OAR for pediatric IMRT cannot be predicted from large-field full phantom studies. For regional OAR, doses are likely lower than predicted by existing ''large field'' data, while the distant PD is higher.« less

Failure Mechanisms of High Temperature Semiconductor Lasers

DTIC Science & Technology

1993-12-01

91 V.3.2. Facet Degradation 92 V.3.3. Dark Defect Degradation 95 V.3.4. Lasers Inoperational at Elevated Tempatur 96 V.3.5. Degradation Mechanism...they will be fairly easy to incorporate into the business of communications and control applications. The Air Force has a few of its own proposed uses ...demands a ho data processing Af~t which could be handled by lasems. A &W[ proposed use is a pilot chum•t-mo ited laer prwoicr to higgtthe portant dam2

Vitamin B12 deficiency after irradiation for bladder carcinoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kinn, A.C.; Lantz, B.

1984-05-01

Vitamin B12 deficiency was found in 10 of 41 patients who underwent radiotherapy before cystectomy with Bricker urinary diversion for carcinoma of the bladder. Of 13 patients given full irradiation because of inoperable bladder cancer 5 had malabsorption of vitamin B12. Serum folic acid was normal in these patients, indicating predominantly ileal irradiation sequelae. Routine evaluation of serum vitamin B12 after radiotherapy is recommended so that appropriate medication can be given, if possible before neurological symptoms appear.

[TAVI in 2018 : new indications and open questions].

PubMed

Fournier, Stephane; Roguelov, Christan; Monney, Pierre; Kirsch, Mathias; Eeckhout, Eric; Antiochos, Panagiotis; Lamsidri, Sabine; Muller, Olivier

2018-05-23

The last years, various large randomized studies have demonstrated the benefit of TAVI (transcatheter aortic valve implantation) over medical therapy or over conventional surgical treatment in inoperable or very high risk patients with symptomatic severe aortic stenosis. More recently, new data has also shown that among patients at intermediate risk, TAVI is at least as beneficial as surgical valve replacement. In this article, we will focus on the new recommendations of the European society of cardiology but also on issues that remain open.

Advantages and disadvantages of using intravenous tissue Plasminogen activator as salvage therapy for inoperable HeartWare thrombosis.

PubMed

Basken, Robyn; Bazzell, Charles M; Smith, Richard; Janardhanan, Rajesh; Khalpey, Zain

2017-07-01

Device thrombosis is a devastating complication of left ventricular assist devices. The definitive treatment has been device exchange or explant. Evidence of increasing morbidity and mortality with device exchange has shifted strategies toward conservative management. In this report, we detail the use of thrombolytics as salvage therapy in a patient with an occlusive HeartWare ventricular assist device (HeartWare Inc., Framingham, MA) thrombus, resulting in long-term survival without further intervention. © 2017 Wiley Periodicals, Inc.

Multipath Routing of Fragmented Data Transfer in a Smart Grid Environment

NASA Astrophysics Data System (ADS)

Borgohain, Tuhin; Borgohain, Amardeep; Borgohain, Rajdeep; Sanyal, Sugata

2015-02-01

The purpose of this paper is to do a general survey on the existing communication modes inside a smart grid, the existing security loopholes and their countermeasures. Then we suggest a detailed countermeasure, building upon the Jigsaw based secure data transfer [8] for enhanced security of the data flow inside the communication system of a smart grid. The paper has been written without the consideration of any factor of inoperability between the various security techniques inside a smart grid

Climatic Atlas of the Outer Continental Shelf Waters and Coastal Regions of Alaska. Volume 3. Chukchi-Beaufort Sea

DTIC Science & Technology

1988-01-01

activities Joe D. Elms , for their editorial evaluation of the vironmental Assessmant Program. Additional depends to a large extent on weathcr cond...winds of 25 knots lower. icing causes slippery decks, renders moving (13 meters per second) or more, and air tempera- parts inoperable, and, in extreme...try to avoid foul weather an thereby bias the oceanic climatology towards fair weather. A recent study by Elms (1986), in which he compared the

Foreign Object Debris: FOD Prevention QS210LSK-REV

NASA Technical Reports Server (NTRS)

Randolph, Sherry; Seaman, John

2004-01-01

Housekeeping in the space industry? You may think the idea isn't technical enough for the shuttle program. Yet, eliminating Foreign Object Debris or FOD is an important goal for USA and NASA. The justification for this effort is based on data from the aeronautics industry. Experience has shown that if debris is not controlled, it may later cause a variety of in-flight issues. FOD can result in material damage, or make systems and equipment inoperable unsafe, or less efficient

External-beam irradiation of carcinoma of the penis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sagerman, R.H.; Yu, W.S.; Chung, C.T.

1984-07-01

Twenty-four patients with biopsy-proved squamous-cell carcinoma of the penis underwent external-beam radiation therapy between 1966 and 1980. Fifteen were treated for the primary tumor and 9 for metastatic inguinal lymphadenopathy; no patient received prophylactic nodal irradiation. Seven out of 9 tumors in stage I, 2/3 in stage II, and 1/3 in stage IV were controlled for three years. Control of fixed, inoperable groin nodes was poor, and none of these patients survived beyond 1 1/2 years.

Through-focus optical characteristics of monofocal and bifocal soft contact lenses across the peripheral visual field.

PubMed

Ji, Qiuzhi; Yoo, Young-Sik; Alam, Hira; Yoon, Geunyoung

2018-05-01

To characterise the impact of monofocal soft contact lens (SCL) and bifocal SCLs on refractive error, depth of focus (DoF) and orientation of blur in the peripheral visual field. Monofocal and two bifocal SCLs, Acuvue Bifocal (AVB, Johnson & Johnson) and Misight Dual Focus (DF, CooperVision) with +2.0 D add power were modelled using a ray tracing program (ZEMAX) based on their power maps. These SCLs were placed onto the anterior corneal surface of the simulated Atchison myopic eye model to correct for -3.0 D spherical refractive error at the fovea. To quantify through-focus retinal image quality, defocus from -3.5 D to 1.5 D in 0.5 D steps was induced at each horizontal eccentricity from 0 to 40° in 10° steps. Wavefront aberrations were computed for each visual eccentricity and defocus. The retinal images were simulated using a custom software program developed in Matlab (The MathWorks) by convolving the point spread function calculated from the aberration with a reference image. The convolved images were spatially filtered to match the spatial resolution limit of each peripheral eccentricity. Retinal image quality was then quantified by the 2-D cross-correlation between the filtered convolved retinal images and the reference image. Peripheral defocus, DoF and orientation of blur were also estimated. In comparison with the monofocal SCL, the bifocal SCLs degraded retinal image quality while DoF was increased at fovea. From 10 to 20°, a relatively small amount of myopic shift (less than 0.3 D) was induced by bifocal SCLs compared with monofocal. DoF was also increased with bifocal SCLs at peripheral vision of 10 and 20°. The trend of myopic shift became less consistent at larger eccentricity, where at 30° DF showed a 0.75 D myopic shift while AVB showed a 0.2 D hyperopic shift and both AVB and DF exhibited large relative hyperopic defocus at 40°. The anisotropy in orientation of blur was found to increase and change its direction through focus beyond central vision. This trend was found to be less dominant with bifocal SCLs compared to monofocal SCL. Bifocal SCLs have a relatively small impact on myopic shift in peripheral refractive error while DoF is increased significantly. We hypothetically suggest that a mechanism underlying myopia control with these bifocal or multifocal contact lenses is an increase in DoF and a decrease in anisotropy of peripheral optical blur. © 2018 The Authors Ophthalmic & Physiological Optics © 2018 The College of Optometrists.

Retinal Disease in Marfan Syndrome: From the Marfan Eye Consortium of Chicago.

PubMed

Rahmani, Safa; Lyon, Alice T; Fawzi, Amani A; Maumenee, Irene H; Mets, Marilyn B

2015-10-01

To study the prevalence of peripheral retinal disease in patients with Marfan Syndrome (MFS). In this observational, cross-sectional case series, patients with MFS were recruited by the Marfan Eye Consortium of Chicago during the National Marfan Foundation's annual conference. Patients underwent a fully dilated exam by vitreoretinal specialists in addition to ultra-widefield fundus photography using a scanning laser ophthalmoscope (Optos 200Tx; Optos PLC, Dunfermline, Scotland, United Kingdom). Clinical examination revealed posterior segment pathology in 18% of eyes with increased incidence to 70% in patients with a subluxed lens. In six out of 10 subjects in whom the clinical exam was suboptimal (young age, small pupil, and limited cooperation), the Optos provided a superior view of the peripheral retina compared to clinical exam alone. Clinical exam of MFS patients revealed similar posterior segment pathology as noted in previous literature, with improved detection of peripheral retinal disease with the use of ultra-widefield imaging. Copyright 2015, SLACK Incorporated.

Diagnosis of Churg-Strauss Syndrome Presented With Neuroendocrine Carcinoma: A Case Report.

PubMed

Park, Dayun; Lee, Ho Jun; Lee, Kwang Hoon; Kwon, Bum Sun; Park, Jin-Woo; Nam, Ki Yeun; Lee, Kyoung Hwan

2017-06-01

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis that affect small and medium-sized blood vessels and is accompanied by asthma, eosinophilia, and peripheral neuropathy. This report describes a case of a 52-year-old man who had a history of sinusitis, asthma, and thymus cancer and who had complained of bilateral lower extremity paresthesia and weakness for a month. Peripheral neuropathy was detected by electrodiagnostic studies. Resection of a mediastinal mass, which was diagnosed as thymic neuroendocrine carcinoma, was performed five months before his visit. After thymectomy, peripheral blood tests revealed a gradual increase in eosinophils. Two months after surgery, he was admitted to the hospital for dyspnea, and nodules of focal consolidation were found in his chest X-ray. One month later, pyoderma occurred in the right shin, and the skin biopsy showed extravascular eosinophilic infiltration. He was diagnosed with CSS after thymectomy, and we report a very rare case of CSS presented with thymic neuroendocrine carcinoma.

Different effects of astrocytes and Schwann cells on regenerating retinal axons.

PubMed

Campbell, Gregor; Kitching, Juliet; Anderson, Patrick N; Lieberman, A Robert

2003-11-14

Following a crush injury of the optic nerve in adult rats, the axons of retinal ganglion cells, stimulated to regenerate by a lens injury and growing within the optic nerve, are associated predominantly with astrocytes: they remain of small diameter (0.1-0.5 microm) and unmyelinated for > or = 2 months after the operation. In contrast, when the optic nerve is cut and a segment of a peripheral nerve is grafted to the ocular stump of the optic nerve, the regenerating retinal axons are associated predominantly with Schwann cells: they are of larger diameter than in the previous experiment and include unmyelinated axons (0.2-2.5 microm) and myelinated axons (mean diameter 2.3 microm). Thus, the grafted peripheral nerve, and presumably its Schwann cells, stimulate enlargement of the regenerating retinal axons leading to partial myelination, whereas the injured optic nerve itself, and presumably its astrocytes, does not. The result points to a marked difference of peripheral (Schwann cells) and central (astrocytes) glia in their effect on regenerating retinal axons.

Hsp42 is required for sequestration of protein aggregates into deposition sites in Saccharomyces cerevisiae

PubMed Central

Specht, Sebastian; Miller, Stephanie B.M.

2011-01-01

The aggregation of proteins inside cells is an organized process with cytoprotective function. In Saccharomyces cerevisiae, aggregating proteins are spatially sequestered to either juxtanuclear or peripheral sites, which target distinct quality control pathways for refolding and degradation. The cellular machinery driving the sequestration of misfolded proteins to these sites is unknown. In this paper, we show that one of the two small heat shock proteins of yeast, Hsp42, is essential for the formation of peripheral aggregates during physiological heat stress. Hsp42 preferentially localizes to peripheral aggregates but is largely absent from juxtanuclear aggregates, which still form in hsp42Δ cells. Transferring the amino-terminal domain of Hsp42 to Hsp26, which does not participate in aggregate sorting, enables Hsp26 to replace Hsp42 function. Our data suggest that Hsp42 acts via its amino-terminal domain to coaggregate with misfolded proteins and perhaps link such complexes to further sorting factors. PMID:22065637

Surgical resection of peripheral odontogenic fibromas in African pygmy hedgehog (Atelerix albiventris): a case study.

PubMed

Wozniak-Biel, Anna; Janeczek, Maciej; Janus, Izabela; Nowak, Marcin

2015-07-04

Neoplastic lesions of the mammary gland, lymph nodes, or oral cavity in African pygmy hedgehogs (Atelerix albiventris) are common in captive animals. Chemotherapy and radiotherapy protocols have not yet been established for the African pygmy hedgehog. Thus, surgical resection is the current treatment of choice in this species. A 5-year-old male African pygmy hedgehog showed multiple erythematous, round small tumors located in the oral cavity, on both sides of maxilla. The treatment of choice was surgical resection of tumors using a surgical knife under general anesthesia. Excised neoplastic lesions were diagnosed as peripheral odontogenic fibroma by histopathology. Six months after surgery relapse of tumors in the oral cavity was not observed. The treatment adopted in this case report is safe for the patient and provides the best solution for mild proliferative lesions of the oral cavity. To our knowledge this is the first report of surgical resection of oral tumors (peripheral odontogenic fibroma) in the African pygmy hedgehog.

Mesenchymal stem cell and derived exosome as small RNA carrier and Immunomodulator to improve islet transplantation.

PubMed

Wen, Di; Peng, Yang; Liu, Di; Weizmann, Yossi; Mahato, Ram I

2016-09-28

Human bone marrow mesenchymal stem cells (hBMSCs) and their exosomes can suppress immune reaction and deliver small RNAs. Thus, they may improve islet transplantation by delivering small RNAs for promoting islet function and inhibiting immune rejection. Here, we proposed an hBMSC and its exosome-based therapy to overcome immune rejection and poor islet function, both of which hinder the success of islet transplantation. We found overexpressed siFas and anti-miR-375 in plasmid encoding shFas and anti-miR-375 transfected hBMSC-derived exosomes, which silenced Fas and miR-375 of human islets and improved their viability and function against inflammatory cytokines. This plasmid transfected hBMSCs downregulated Fas and miR-375 of human islets in a humanized NOD scid gamma (NSG) mouse model, whose immune reaction was inhibited by injecting hBMSC and peripheral blood mononuclear cell (PBMC) co-cultured exosomes. These exosomes suppressed immune reaction by inhibiting PBMC proliferation and enhancing regulatory T cell (Treg) function. Collectively, our studies elucidated the mechanisms of RNA delivery from hBMSCs to human islets and the immunosuppressive effect of hBMSC and peripheral blood mononuclear cell co-cultured exosomes for improving islet transplantation. Copyright © 2016 Elsevier B.V. All rights reserved.

Nutritional value of protein hydrolysis products (oligopeptides and free amino acids) as a consequence of absorption and metabolism kinetics

NASA Technical Reports Server (NTRS)

Rerat, A.

1995-01-01

When pigs were submitted to duodenal infusion of solutions containing a large percentage of small peptides (PEP) or free amino acids with the same pattern (AAL) amino acids appear in the portal blood more rapidly and more uniformly after infusion of PEP then after infusion of AAL, with the notable exception of methionine for which the opposite was true. These differences were lowered when a carbohydrate (maltose dextrin) was present in the solution, but nevertheless remained significant for the first hour after the infusion. The long-term (8-hour) uptake of free amino acids into the liver and the peripheral tissues differed in profile according to the nature of the duodenal infusion. Peripheral uptake was appreciably less well balanced after infusion of free amino acids (deficiency of threonine and phenylalanine) than after infusion of small peptides (deficiency of methionine). Accordingly, in the rat, under conditions of discontinuous enteral nutrition the mixture of small peptides was of greater nutritive value than the mixture of free amino acids. It thus appears that the absorption kinetics which results in important variations in the temporal distribution of free amino acids in the tissues may be at the origin of transitory imbalances in tissue amino acid uptake, and as a result of a lower nutritive value.

Chemical structure and morphology of dorsal root ganglion neurons from naive and inflamed mice.

PubMed

Barabas, Marie E; Mattson, Eric C; Aboualizadeh, Ebrahim; Hirschmugl, Carol J; Stucky, Cheryl L

2014-12-05

Fourier transform infrared spectromicroscopy provides label-free imaging to detect the spatial distribution of the characteristic functional groups in proteins, lipids, phosphates, and carbohydrates simultaneously in individual DRG neurons. We have identified ring-shaped distributions of lipid and/or carbohydrate enrichment in subpopulations of neurons which has never before been reported. These distributions are ring-shaped within the cytoplasm and are likely representative of the endoplasmic reticulum. The prevalence of chemical ring subtypes differs between large- and small-diameter neurons. Peripheral inflammation increased the relative lipid content specifically in small-diameter neurons, many of which are nociceptive. Because many small-diameter neurons express an ion channel involved in inflammatory pain, transient receptor potential ankyrin 1 (TRPA1), we asked whether this increase in lipid content occurs in TRPA1-deficient (knock-out) neurons. No statistically significant change in lipid content occurred in TRPA1-deficient neurons, indicating that the inflammation-mediated increase in lipid content is largely dependent on TRPA1. Because TRPA1 is known to mediate mechanical and cold sensitization that accompanies peripheral inflammation, our findings may have important implications for a potential role of lipids in inflammatory pain. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Possible role of CD22, CD79b and CD20 expression in distinguishing small lymphocytic lymphoma from chronic lymphocytic leukemia.

PubMed

Jovanovic, Danijela; Djurdjevic, Predrag; Andjelkovic, Nebojsa; Zivic, Ljubica

2014-01-01

Flow cytometry has an important role in diagnosis and classification of B-cell lymphoproliferative disorders (BCLPDs). However, in distinguishing chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL) only clinical criteria are available so far. Aim of the study was to determine differences in the expression of common B cell markers (CD22, CD79b and CD20) on the malignant lymphocytes in the peripheral blood samples of CLL and SLL patients. Peripheral blood samples of 56 CLL and 11 SLL patients were analyzed by 5-color flow cytometry on the CD45/CD19/CD5 gate for CD22, CD79b and CD20. In the samples collected from the CLL patients, CD22 expression was detected in only 20% of patients in the low pattern, while in SLL patients the expression was medium and present in 90.9% of patients (p < 0.0001). For CD79b expression, statistical significance is reached both in the expression pattern, which was low/medium for CLL and high for SLL, and expression level (p = 0.006). The expression of CD20 was counted as the CD20/CD19 ratio. The average ratio was 0.512 in the CLL patients vs. 0.931 in the SLL patients (p = 0.0001). The pattern of expression and expression level of CD22, CD79b and CD20 in peripheral blood could be used for distinguishing SLL from CLL patients.

Doppler velocity measurements from large and small arteries of mice

PubMed Central

Reddy, Anilkumar K.; Madala, Sridhar; Entman, Mark L.; Michael, Lloyd H.; Taffet, George E.

2011-01-01

With the growth of genetic engineering, mice have become increasingly common as models of human diseases, and this has stimulated the development of techniques to assess the murine cardiovascular system. Our group has developed nonimaging and dedicated Doppler techniques for measuring blood velocity in the large and small peripheral arteries of anesthetized mice. We translated technology originally designed for human vessels for use in smaller mouse vessels at higher heart rates by using higher ultrasonic frequencies, smaller transducers, and higher-speed signal processing. With these methods one can measure cardiac filling and ejection velocities, velocity pulse arrival times for determining pulse wave velocity, peripheral blood velocity and vessel wall motion waveforms, jet velocities for the calculation of the pressure drop across stenoses, and left main coronary velocity for the estimation of coronary flow reserve. These noninvasive methods are convenient and easy to apply, but care must be taken in interpreting measurements due to Doppler sample volume size and angle of incidence. Doppler methods have been used to characterize and evaluate numerous cardiovascular phenotypes in mice and have been particularly useful in evaluating the cardiac and vascular remodeling that occur following transverse aortic constriction. Although duplex ultrasonic echo-Doppler instruments are being applied to mice, dedicated Doppler systems are more suitable for some applications. The magnitudes and waveforms of blood velocities from both cardiac and peripheral sites are similar in mice and humans, such that much of what is learned using Doppler technology in mice may be translated back to humans. PMID:21572013

Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

PubMed Central

Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

2014-01-01

Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

Peripheral nerve block in patients with Ehlers-Danlos syndrome, hypermobility type: a case series.

PubMed

Neice, Andrew E; Stubblefield, Eryn E; Woodworth, Glenn E; Aziz, Michael F

2016-09-01

Ehlers-Danlos syndrome (EDS) is an inherited disease characterized by defects in various collagens or their post translational modification, with an incidence estimated at 1 in 5000. Performance of peripheral nerve block in patients with EDS is controversial, due to easy bruising and hematoma formation after injections as well as reports of reduced block efficacy. The objective of this study was to review the charts of EDS patients who had received peripheral nerve block for any evidence of complications or reduced efficacy. Case series, chart review. Academic medical center. Patients with a confirmed or probable diagnosis of EDS who had received a peripheral nerve block in the last 3 years were identified by searching our institutions electronic medical record system. The patients were classified by their subtype of EDS. Patients with no diagnosed subtype were given a probable subtype based on a chart review of the patient's symptoms. Patient charts were reviewed for any evidence of complications or reduced block efficacy. A total of 21 regional anesthetics, on 16 unique patients were identified, 10 of which had a EDS subtype diagnosis. The majority of these patients had a diagnosis of hypermobility-type EDS. No block complications were noted in any patients. Two block failures requiring repeat block were noted, and four patients reported uncontrolled pain on postoperative day one despite successful placement of a peripheral nerve catheter. Additionally, blocks were performed without incident in patients with classical-type and vascular-type EDS although the number was so small that no conclusions can be drawn about relative safety of regional anesthesia in these groups. This series fails to show an increased risk of complications of peripheral nerve blockade in patients with hypermobility-type EDS. Copyright © 2016 Elsevier Inc. All rights reserved.

Regional assessment of energy-producing metabolic activity in the endothelium of donor corneas.

PubMed

Greiner, Mark A; Burckart, Kimberlee A; Wagoner, Michael D; Schmidt, Gregory A; Reed, Cynthia R; Liaboe, Chase A; Flamme-Wiese, Miles J; Zimmerman, M Bridget; Mullins, Robert F; Kardon, Randy H; Goins, Kenneth M; Aldrich, Benjamin T

2015-05-01

We characterized mitochondrial respiration and glycolysis activity of human corneal endothelium, and compared metabolic activity between central and peripheral regions. Endothelial keratoplasty-suitable corneas were obtained from donors aged 50 to 75 years. The endothelium-Descemet membrane complex (EDM) was isolated, and 3-mm punches were obtained from central and peripheral regions. Endothelium-Descemet membrane punches were assayed for mitochondrial respiration (oxygen consumption) and glycolysis (extracellular acidification) using an extracellular flux analyzer. Enzymatic (citrate synthase, glucose hexokinase) and mitochondrial density (MitoTracker) assays also were performed. Ten corneas were analyzed per assay. Metabolic activity for mitochondrial respiration and glycolysis showed expected changes to assay compounds (P < 0.01, all pairwise comparisons). Basal mitochondrial respiration and glycolysis activity did not differ between regions (P > 0.99). Similarly, central versus peripheral activity after assay compound treatment showed no significant differences (P > 0.99, all time points). The intracorneal coefficient of variation for basal readings between two and four peripheral punches was 18.5% of the mean. Although peripheral samples displayed greater enzymatic activity than central samples (P < 0.05), similar to extracellular flux results, mitochondrial density did not differ between regions (P = 0.78). Extracellular flux analysis of oxygen and pH is a valid technique for characterizing metabolic activity of human corneal endothelium. This technique demonstrates high reproducibility, allows quantification of metabolic parameters using small quantities of live cells, and permits estimation of overall metabolic output. Neither oxygen consumption nor extracellular acidification differed between central and peripheral regions of transplant suitable corneas in this series. Our results show that endothelial cell health can be quantified biochemically in transplant suitable corneas.

A tactile stimulus applied to the leg improves postural stability in young, old and neuropathic subjects.

PubMed

Menz, Hylton B; Lord, Stephen R; Fitzpatrick, Richard C

2006-10-02

The purpose of this study was to determine whether the application of passive tactile cues to the lower limb could improve postural stability in healthy young controls, older people and people with diabetic peripheral neuropathy. Antero-posterior sway was measured with eyes open and closed in 10 healthy young subjects (mean age 27 years, 5 male, 5 female), 10 older subjects without diabetic peripheral neuropathy (mean age 88 years, 2 male, 8 female) and 10 subjects with diabetic peripheral neuropathy (mean age 65 years, 6 male, 4 female) while a small piece of Velcro attached to a flexible mount was applied to three different sites on the leg (ankle, calf, and knee). Across all conditions, the mean sway of the neuropathic subjects was 93% greater than for the young subjects and 11% more than the older subjects. On average, subjects swayed 10% more with the eyes closed than with the eyes open. Each stimulus reduced sway, but the effect increased approximately in proportion to the height of the stimulus above the ankles (ankle 7.6%, calf 13.5%, knee 20.1% reduction compared to the no stimulus condition). This experiment demonstrates that a passive stimulus applied to the skin of the leg, which provides sensory information about body movement, significantly reduces body sway during standing. This applies to older subjects and subjects with peripheral neuropathy as well as healthy young subjects. These results have implications for novel approaches for improving stability in people with peripheral sensory loss.

Transplantation of autologous peripheral blood mononuclear cells in the subarachnoid space for amyotrophic lateral sclerosis: a safety analysis of 14 patients

PubMed Central

Li, Xiao-yan; Liang, Zhan-hua; Han, Chao; Wei, Wen-juan; Song, Chun-li; Zhou, Li-na; Liu, Yang; Li, Ying; Ji, Xiao-fei; Liu, Jing

2017-01-01

There is a small amount of clinical data regarding the safety and feasibility of autologous peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis. The objectives of this retrospective study were to assess the safety and efficacy of peripheral blood mononuclear cell transplantation in 14 amyotrophic lateral sclerosis patients to provide more objective data for future clinical trials. After stem cell mobilization and collection, autologous peripheral blood mononuclear cells (1 × 109) were isolated and directly transplanted into the subarachnoid space of amyotrophic lateral sclerosis patients. The primary outcome measure was incidence of adverse events. Secondary outcome measures were electromyography 1 week before operation and 4 weeks after operation, Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale 1 week preoperatively and 1, 2, 4 and 12 weeks postoperatively. There was no immediate or delayed transplant-related cytotoxicity. The number of leukocytes, serum alanine aminotransferase and creatinine levels, and body temperature were within the normal ranges. Radiographic evaluation showed no serious transplant-related adverse events. Muscle strength grade, results of Functional Independence Measurement, Berg Balance Scale, and Dysarthria Assessment Scale were not significantly different before and after treatment. These findings suggest that peripheral blood mononuclear cell transplantation into the subarachnoid space for the treatment of amyotrophic lateral sclerosis is safe, but its therapeutic effect is not remarkable. Thus, a large-sample investigation is needed to assess its efficacy further. PMID:28469667

Phenytoin: neuroprotection or neurotoxicity?

PubMed

Keppel Hesselink, Jan M; Kopsky, David J

2017-06-01

Phenytoin is an 80-year young molecule and new indications are still emerging. The neuroprotective potential of phenytoin has been evaluated for decades. Recently, a positive phase II trial supported its further development in the treatment of optic neuritis in multiple sclerosis. In 1942, however, peripheral neuritis was first reported to be an adverse event of phenytoin, and since then a small but steady stream of publications discussed peripheral polyneuropathy as being a possible adverse event of phenytoin. We have reviewed the literature and concluded there is some supportive evidence for a reversible polyneuropathy after the oral use of phenytoin, though with no evidence for clear neurotoxicity on the level of peripheral nerves. This is probably due to the fact that the pharmacological effects of phenytoin, based on the stabilizing effect of the voltage-gated sodium channels, make impairment of nerve conduction in asymptomatic and symptomatic reversible polyneuropathies plausible. Clear toxically-induced phenytoin-related polyneuropathies, however, are extremely rare and are always related to high dose or high plasma levels of phenytoin, mostly developing during many years of therapy. We could only find one case of a probable reversible chronic phenytoin intoxication resulting in a biopsy proven axonal atrophy with secondary demyelination and signs of remyelination. All case series and case reports published are insufficient in detail to prove a clear causal relation between phenytoin intake and the induction of a peripheral polyneuropathy. Phenytoin does not lead to irreversible toxicity of the peripheral nerves and might, on the other hand, have neuroprotective properties.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond.

PubMed

Bakshi, Anshika; Chaudhary, Sandeep C; Rana, Mehtab; Elmets, Craig A; Athar, Mohammad

2017-12-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10-100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. © 2017 Wiley Periodicals, Inc.

Basal cell carcinoma pathogenesis and therapy involving hedgehog signaling and beyond

PubMed Central

Bakshi, Anshika; Chaudhary, Sandeep C.; Rana, Mehtab; Elmets, Craig A.; Athar, Mohammad

2018-01-01

Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling-related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm. Some of these pathways could be regulated by noncoding microRNA. Altered microRNA expression profile is recognized with the progression of these lesions. Stopping treatment with Smoothened (SMO) inhibitors often leads to tumor reoccurrence in the patients with basal cell nevus syndrome, who develop 10–100 of BCCs. In addition, the initial effectiveness of these SMO inhibitors is impaired due to the onset of mutations in the drug-binding domain of SMO. These data point to a need to develop strategies to overcome tumor recurrence and resistance and to enhance efficacy by developing novel single agent-based or multiple agents-based combinatorial approaches. Immunotherapy and photodynamic therapy could be additional successful approaches particularly if developed in combination with chemotherapy for inoperable and metastatic BCCs. PMID:28574612

Pros, cons, and current indications of open craniotomy versus gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization.

PubMed

Surdell, Daniel L; Bhattacharjee, Sumon; Loftus, Christopher M

2002-06-01

The successful treatment of an intracranial arteriovenous malformation poses both technical and conceptual problems to the neurosurgeon. Treatment decisions are made in light of current understanding of the natural history of these lesions. It is important to understand the pros, cons and current indication of open craniotomy vs. gamma knife in the treatment of arteriovenous malformations and the role of endovascular embolization. Surgical removal of an arteriovenous malformation is indicated when the operative risk is less than the morbidity and mortality associated with its natural history. The treatment goal of complete angiographic obliteration of arteriovenous malformations is achieved most effectively by microneurosurgery in low-grade lesions. Large lesions frequently require a combination of embolization and microsurgery. Although recent advances in technology and medical management have allowed previously inoperable arteriovenous malformations to be surgically excised, there is still a small group of arteriovenous malformations that cannot be excised safely due to their size and location. Stereotactic radiosurgery is clearly an important adjunct in the multimodality treatment approach for large arteriovenous malformations. Endovascular embolization can potentially increase safety and efficacy in the treatment of arteriovenous malformations when applied to selective cases with well-defined treatment goals.

Primary radiotherapy for carcinoma of the endometrium using external beam radiotherapy and single line source brachytherapy.

PubMed

Churn, M; Jones, B

1999-01-01

A small proportion of patients with adenocarcinoma of the endometrium are inoperable by virtue of severe concurrent medical conditions, gross obesity or advanced stage disease. They can be treated with primary radiotherapy with either curative or palliative intent. We report 37 such patients treated mainly with a combination of external beam radiotherapy and intracavitary brachytherapy using a single line source technique. The 5-year disease-specific survival for nonsurgically staged patients was 68.4% for FIGO Stages I and II and 33.3% for Stages III and IV. The incidence of late morbidity was acceptably low. Using the Franco-Italian Glossary, there was 27.0% grade 1 but no grade 2-4 bladder toxicity. For the rectum the rates were 18.9% grade 1, 5.4% grade 2, 2.7% grade 3, and no grade 4 toxicity. Methods of optimizing the dose distribution of the brachytherapy by means of variation of treatment length, radioactive source positions, and prescription point according to tumour bulk and individual anatomy are discussed. The biologically equivalent doses (BED) for combined external beam radiotherapy and brachytherapy were calculated to be in the range of 78-107 Gy(3) or 57-75 Gy(10) at point 'A' and appear adequate for the control of Stage I cancers.

Socioeconomic deprivation and the incidence of 12 cardiovascular diseases in 1.9 million women and men: implications for risk prediction and prevention.

PubMed

Pujades-Rodriguez, Mar; Timmis, Adam; Stogiannis, Dimitris; Rapsomaniki, Eleni; Denaxas, Spiros; Shah, Anoop; Feder, Gene; Kivimaki, Mika; Hemingway, Harry

2014-01-01

Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking. Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used. During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83-1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42-1.70 for heart failure; I2 = 81.9%, τ2 = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75-1.06 for cardiac arrest to 1.85, 95%CI 1.67-2.04 for peripheral arterial disease; I2 = 96.0%, τ2 = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men. Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wei Xiong; Liu, H. Helen; Tucker, Susan L.

Purpose: To identify clinical and dosimetric factors influencing the risk of pericardial effusion (PCE) in patients with inoperable esophageal cancer treated with definitive concurrent chemotherapy and radiation therapy (RT). Methods and Materials: Data for 101 patients with inoperable esophageal cancer treated with concurrent chemotherapy and RT from 2000 to 2003 at our institution were analyzed. The PCE was confirmed from follow-up chest computed tomography scans and radiologic reports, with freedom from PCE computed from the end of RT. Log-rank tests were used to identify clinical and dosimetric factors influencing freedom from PCE. Dosimetric factors were calculated from the dose-volume histogrammore » for the whole heart and pericardium. Results: The crude rate of PCE was 27.7% (28 of 101). Median time to onset of PCE was 5.3 months (range, 1.0-16.7 months) after RT. None of the clinical factors investigated was found to significantly influence the risk of PCE. In univariate analysis, a wide range of dose-volume histogram parameters of the pericardium and heart were associated with risk of PCE, including mean dose to the pericardium, volume of pericardium receiving a dose greater than 3 Gy (V3) to greater than 50 Gy (V50), and heart volume treated to greater than 32-38 Gy. Multivariate analysis selected V30 as the only parameter significantly associated with risk of PCE. Conclusions: High-dose radiation to the pericardium may strongly increase the risk of PCE. Such a risk may be reduced by minimizing the dose-volume of the irradiated pericardium and heart.« less

Liver Resection for Colorectal Hepatic Metastases after Systemic Chemotherapy and Selective Internal Radiation Therapy with Yttrium-90 Microspheres: A Systematic Review.

PubMed

Baltatzis, Minas; Siriwardena, Ajith K

2018-06-08

Selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres has been used together with systemic chemotherapy to treat patients with unresectable liver metastases. This study undertook the first systematic pooled assessment of the case profile, treatment and outcome in patients with initially inoperable colorectal hepatic metastases undergoing resection after systemic chemotherapy and SIRT. A systematic review of the literature was performed using Medline and Embase for publications between January 1998 and August 2017. Keywords and MESH headings "SIRT", "Yttrium-99 radio embolization" and "liver metastases" were used. Reports on patients undergoing liver resection after SIRT for colorectal liver metastases were included. Case reports, reviews and papers without original data were excluded. The study protocol was registered with PROSPERO, (registration number: CRD42017072374). The study population comprised of 120 patients undergoing liver resection after chemotherapy and SIRT. The conversion rate to hepatectomy in previously unresectable patients was 13.6% (109 of 802). All studies report a single application of SIRT. The interval from SIRT to surgery ranged from 39 days to 9 months. Overall, there were 4 (3.3%) deaths after hepatectomy in patients treated by chemotherapy and SIRT. This large pooled report of patients undergoing hepatectomy for colorectal liver metastases after chemotherapy and SIRT shows that 13.6% of patients with initially inoperable disease undergo resection with low procedure-related mortality. © 2018 S. Karger AG, Basel.

A new score for screening of malnutrition in patients with inoperable gastric adenocarcinoma.

PubMed

Esfahani, Ali; Somi, Mohammad Hossein; Asghari Jafarabadi, Mohammad; Ostadrahimi, Alireza; Ghayour Nahand, Mousa; Fathifar, Zahra; Doostzadeh, Akram; Ghoreishi, Zohreh

2017-06-01

Malnutrition is common in patients with gastric cancer. Early identification of malnourished patients results in improving quality of life. We aimed to assess the nutritional status of patients with inoperable gastric adenocarcinoma (IGA) and finding a precise malnutrition screening score for these patients before the onset of chemotherapy. Nutritional status was assessed using patient generated subjective global assessment (PG-SGA), visceral proteins, and high-sensitivity C reactive protein. Tumor markers of carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA-125) and CA 19-9 and their association with nutritional status were assessed. Then a new score for malnutrition screening was defined. Seventy-one patients with IGA completed the study. Malnourished and well-nourished patients (based on PG-SGA) were statistically different regarding albumin, prealbumin and CA-125. The best cut-off value for prealbumin for prediction of malnutrition was determined at 0.20 mg/dl and using known cut-off values for albumin (3.5 g/dl) and CA-125 (35 U/ml), a new score was defined for malnutrition screening named MS-score. According to MS-score, 92% of the patients had malnutrition and it could predict malnutrition with 96.8% sensitivity, 50% specificity and accuracy of 91.4%. MS-score has been suggested as an available and easy-to-use tool for malnutrition screening in patients with IGA. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Alterations in inflammatory biomarkers and energy intake in cancer cachexia: a prospective study in patients with inoperable pancreatic cancer.

PubMed

Bye, Asta; Wesseltoft-Rao, Nima; Iversen, Per Ole; Skjegstad, Grete; Holven, Kirsten B; Ulven, Stine; Hjermstad, Marianne J

2016-06-01

Chronic systemic inflammatory response is proposed as an underlying mechanism for development of cancer cachexia. We conducted a prospective study to examine changes in inflammatory biomarkers during the disease course and the relationship between inflammatory biomarkers and cachexia in patients with inoperable pancreatic cancer. Twenty patients, median (range) age 67.5 (35-79) years, 5 females, were followed for median 5.5 (1-12) months. Cachexia was diagnosed according to the 2011 consensus-based classification system (weight loss >5 % past six months, BMI < 20 kg/m(2) and weight loss >2 %, or sarcopenia) and the modified Glasgow Prognostic score (mGPS) that combines CRP and albumin levels. Inflammatory biomarkers were measured by enzyme immunoassays. The patients had increased levels of most inflammatory biomarkers, albeit not all statistically significant, both at study entry and close to death, indicating ongoing inflammation. According to the consensus-based classification system, eleven (55 %) patients were classified as cachectic upon inclusion. They did not differ from non-cachectic patients with regard to inflammatory biomarkers or energy intake. According to the mGPS, seven (35 %) were defined as cachectic and had a higher IL-6 (p < 0.001) than the non-cachectic patients. They also had a slightly, but insignificantly longer survival than non-cachectic patients (p = 0.08). The mGPS should be considered as an additional framework for identification of cancer cachexia.

Efficacy and safety of balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension guided by cone-beam computed tomography and electrocardiogram-gated area detector computed tomography.

PubMed

Ogo, Takeshi; Fukuda, Tetsuya; Tsuji, Akihiro; Fukui, Shigefumi; Ueda, Jin; Sanda, Yoshihiro; Morita, Yoshiaki; Asano, Ryotaro; Konagai, Nao; Yasuda, Satoshi

2017-04-01

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease characterized by chronic obstructive thrombus and pulmonary hypertension. Balloon pulmonary angioplasty (BPA), an emerging alternative catheter-based treatment for inoperable patients with CTEPH, has not yet been standardised, especially for lesion assessment in distal pulmonary arteries. Recent advancement in computed tomography enables distal CTEPH lesions to be visualized. We retrospectively studied 80 consecutive patients with inoperable CTEPH who received BPA guided by cone-beam computed tomography (CT) (CBCT) or electrocardiogram (ECG)-gated area detector CT (ADCT) for target lesion assessment. We collected clinical and hemodynamic data, including procedural complications, before BPA and at 3 months and 1year after BPA. Three hundred eight-five BPA sessions (4.8 sessions/patient) were performed for the lesions of subsegmental arteries (1155 lesions), segmental arteries (738 lesions), and lobar arteries (4 lesions) identified by CBCT or ECG-gated ADCT. Significant improvements in the symptoms, 6-min walk distance, brain natriuretic peptide level, exercise capacity, and haemodynamics were observed 3 months and 1year after BPA. No cases of death or cardiogenic shock with a low rate of severe wire perforation (0.3%) and severe reperfusion oedema (0.3%) were observed. BPA guided by CBCT or ECG-gated ADCT is effective and remarkably safe in patients with CTEPH . These new advanced CT techniques may be useful in pre-BPA target lesion assessment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Autologous transplantation with fewer fibers repairs large peripheral nerve defects

PubMed Central

Deng, Jiu-xu; Zhang, Dian-yin; Li, Ming; Weng, Jian; Kou, Yu-hui; Zhang, Pei-xun; Han, Na; Chen, Bo; Yin, Xiao-feng; Jiang, Bao-guo

2017-01-01

Peripheral nerve injury is a serious disease and its repair is challenging. A cable-style autologous graft is the gold standard for repairing long peripheral nerve defects; however, ensuring that the minimum number of transplanted nerve attains maximum therapeutic effect remains poorly understood. In this study, a rat model of common peroneal nerve defect was established by resecting a 10-mm long right common peroneal nerve. Rats receiving transplantation of the common peroneal nerve in situ were designated as the in situ graft group. Ipsilateral sural nerves (10–30 mm long) were resected to establish the one sural nerve graft group, two sural nerves cable-style nerve graft group and three sural nerves cable-style nerve graft group. Each bundle of the peroneal nerve was 10 mm long. To reduce the barrier effect due to invasion by surrounding tissue and connective-tissue overgrowth between neural stumps, small gap sleeve suture was used in both proximal and distal terminals to allow repair of the injured common peroneal nerve. At three months postoperatively, recovery of nerve function and morphology was observed using osmium tetroxide staining and functional detection. The results showed that the number of regenerated nerve fibers, common peroneal nerve function index, motor nerve conduction velocity, recovery of myodynamia, and wet weight ratios of tibialis anterior muscle were not significantly different among the one sural nerve graft group, two sural nerves cable-style nerve graft group, and three sural nerves cable-style nerve graft group. These data suggest that the repair effect achieved using one sural nerve graft with a lower number of nerve fibers is the same as that achieved using the two sural nerves cable-style nerve graft and three sural nerves cable-style nerve graft. This indicates that according to the ‘multiple amplification’ phenomenon, one small nerve graft can provide a good therapeutic effect for a large peripheral nerve defect. PMID:29323049

Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

PubMed

Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

2016-01-01

The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves.

Paraesthesia and peripheral neuropathy.

PubMed

Beran, Roy

2015-03-01

Paraesthesia reflects an abnormality affecting the sensory pathways anywhere between the peripheral sensory nervous system and the sensory cortex. As with all neurology, the fundamental diagnostic tool is a concise history, devoid of potentially ambiguous jargon, which properly reflects the true nature of what the patient is experiencing, provocateurs, precipitating and relieving factors, concomitant illnesses, such as diabetes, and any treatments that could evoke neuropathies. Some localised neuropathies, such as carpal tunnel syndrome (CTS) or ulnar neuropathy, produce classical features, such as weakness of the 'LOAF' (lateral two lumbricals, opponens pollicis, abductor pollicis brevis and flexor pollicis brevis) median innervated muscles, thereby obviating need for further neurophysiology. Nerve conduction studies may be necessary to diagnose peripheral neuropathy, but they may also be normal with small fibre neuropathy. Even with a diagnosis of peripheral neuropathy, definition of the underlying cause may remain elusive in a significant proportion of cases, despite involvement of consultants. Treatment is based on the relevant diagnosis and mechanism to address the cause. This includes better glycaemic control for diabetes, night splint for CTS or elbow padding for ulnar neuropathy, modifying lifestyle with reduced alcohol consumption or replacing dietary deficiencies or changing medications where appropriate and practical. Should such intervention fail to relieve symptoms, consideration of intervention to relieve symptoms of neuropathic pain may be required.

The Influence of Nicotine on Lung Tumor Growth, Cancer Chemotherapy, and Chemotherapy-Induced Peripheral Neuropathy.

PubMed

Kyte, S Lauren; Gewirtz, David A

2018-06-04

Studies in animal models have suggested that nicotine, an agonist of nicotinic acetylcholine receptors (nAChRs), may have the potential to prevent and/or reverse the peripheral neuropathy induced by cancer chemotherapeutic drugs, such as paclitaxel and oxaliplatin. However, a large body of evidence suggests that nicotine may also stimulate lung tumor growth and/or interfere with the effectiveness of cancer chemotherapy. While the reported proliferative effects of nicotine are highly variable, the antagonism of antitumor drug efficacy is more consistent, although this latter effect has been demonstrated primarily in cell culture studies. In contrast, in vitro and in vivo studies from our own laboratory indicate that nicotine fails to enhance the growth of non-small cell lung cancer cells or attenuate the effects of chemotherapy (paclitaxel). Given the inconsistencies in the literature, coupled with our own findings, the weight of evidence suggests that caution may be warranted in proposing to utilize nicotine to mitigate chemotherapy-induced peripheral neuropathy in cancer patients receiving chemotherapy. Conversely, clinical trials could be performed in patients who have completed therapy and are considered to be disease-free to determine whether nicotine, in the form of commercially available patches or gum, is effective in alleviating peripheral neuropathy symptoms. The American Society for Pharmacology and Experimental Therapeutics.

Legitimate Peripheral Participation by Sandwich Year Interns in the National Health Service

ERIC Educational Resources Information Center

Davies, Helen Maria; Sandiford, Peter John

2014-01-01

Student internships are widely seen as a valuable part of education provision and there is a growing body of research into internship programmes from student, employer and educator perspectives. This paper explores the experiences of a group of information technology interns employed in a small organisation involved in health care business…

[Chronic complications of diabetes mellitus. Recommendations from the American Diabetes Association 2011. Prevention and management].

PubMed

Isla Pera, Pilar

2012-09-01

Diabetes mellitus (DM) is one of the diseases with greater impact public health, not only because of its high prevalence, but, above all, by the consequences of the chronic complications arising from this disease. Hyperglycemia generates damage both in the field of microcirculation and the great vessels causing injury, macroangiopathies and microangiopathies. Macroangiopathies complications are generated from alterations or injury in the great vessels of the arterial to the most important, being from the clinical point of view, ischemic heart disease, disease stroke and peripheral arterial disease. Microangiopathies complications are due to alterations or injury of small vessels being the most important, from a clinical point of view, nephropathy, retinopathy and diabetic neuropathy. Macroangiopathies complications are generated from alterations or injury in the great vessels of the arterial to the most important, being from the clinical point of view, ischemic heart disease, disease stroke and peripheral arterial disease. Microangiopathies complications are due to alterations or injury of small vessels being the most important, from a clinical point of view, nephropathy, retinopathy and diabetic neuropathy.

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle.

PubMed

Yim, Peter D; Gallos, George; Perez-Zoghbi, Jose F; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W

2013-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K(+) channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders.

Stereotactic Body Radiotherapy for Early-stage Non-small-cell Lung Cancer in Patients 80 Years and Older: A Multi-center Analysis.

PubMed

Cassidy, Richard J; Patel, Pretesh R; Zhang, Xinyan; Press, Robert H; Switchenko, Jeffrey M; Pillai, Rathi N; Owonikoko, Taofeek K; Ramalingam, Suresh S; Fernandez, Felix G; Force, Seth D; Curran, Walter J; Higgins, Kristin A

2017-09-01

Stereotactic body radiotherapy (SBRT) is the standard of care for medically inoperable early-stage non-small-cell lung cancer. Despite the limited number of octogenarians and nonagenarians on trials of SBRT, its use is increasingly being offered in these patients, given the aging cancer population, medical fragility, or patient preference. Our purpose was to investigate the efficacy, safety, and survival of patients ≥ 80 years old treated with definitive lung SBRT. Patients who underwent SBRT were reviewed from 2009 to 2015 at 4 academic centers. Patients diagnosed at ≥ 80 years old were included. Kaplan-Meier and multivariate logistic regression and Cox proportional hazard regression analyses were performed. Recursive partitioning analysis was done to determine a subgroup of patients most likely to benefit from therapy. A total of 58 patients were included, with a median age of 84.9 years (range, 80.1-95.2 years), a median follow-up time of 19.9 months (range, 6.9-64.9 months), a median fraction size of 10.0 Gy (range, 7.0-20.0 Gy), and a median number of fractions of 5.0 (range, 3.0-8.0 fractions). On multivariate analysis, higher Karnofsky performance status (KPS) was associated with higher local recurrence-free survival (hazard ratio [HR], 0.92; P < .01), regional recurrence-free survival (HR, 0.94; P < .01), and overall survival (HR, 0.91; P < .01). On recursive partitioning analysis, patients with KPS ≥ 75 had improved 3-year cancer-specific and overall survival (99.4% and 91.9%, respectively) compared with patients with KPS < 75 (47.8% and 23.6%, respectively; P < .01). Definitive lung SBRT for early-stage non-small-cell lung cancer was efficacious and safe in patients ≥ 80 years old. Patients with a KPS of ≥ 75 derived the most benefit from therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Intrafraction Motion in Stereotactic Body Radiation Therapy for Non-Small Cell Lung Cancer: Intensity Modulated Radiation Therapy Versus Volumetric Modulated Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rossi, Maddalena M.G.; Peulen, Heike M.U.; Belderbos, Josè S.A.

Purpose: Stereotactic body radiation therapy (SBRT) for early-stage inoperable non-small cell lung cancer (NSCLC) patients delivers high doses that require high-precision treatment. Typically, image guidance is used to minimize day-to-day target displacement, but intrafraction position variability is often not corrected. Currently, volumetric modulated arc therapy (VMAT) is replacing intensity modulated radiation therapy (IMRT) in many departments because of its shorter delivery time. This study aimed to evaluate whether intrafraction variation in VMAT patients is reduced in comparison with patients treated with IMRT. Methods and Materials: NSCLC patients (197 IMRT and 112 VMAT) treated with a frameless SBRT technique to amore » prescribed dose of 3 × 18 Gy were evaluated. Image guidance for both techniques was identical: pretreatment cone beam computed tomography (CBCT) (CBCT{sub precorr}) for setup correction followed immediately before treatment by postcorrection CBCT (CBCT{sub postcorr}) for verification. Then, after either a noncoplanar IMRT technique or a VMAT technique, a posttreatment (CBCT{sub postRT}) scan was acquired. The CBCT{sub postRT} and CBCT{sub postcorr} scans were then used to evaluate intrafraction motion. Treatment delivery times, systematic (Σ) and random (σ) intrafraction variations, and associated planning target volume (PTV) margins were calculated. Results: The median treatment delivery time was significantly reduced by 20 minutes (range, 32-12 minutes) using VMAT compared with noncoplanar IMRT. Intrafraction tumor motion was significantly larger for IMRT in all directions up to 0.5 mm systematic (Σ) and 0.7 mm random (σ). The required PTV margins for IMRT and VMAT differed by less than 0.3 mm. Conclusion: VMAT-based SBRT for NSCLC was associated with significantly shorter delivery times and correspondingly smaller intrafraction motion compared with noncoplanar IMRT. However, the impact on the required PTV margin was small.« less

Development and validation of a prognostic model using blood biomarker information for prediction of survival of non-small-cell lung cancer patients treated with combined chemotherapy and radiation or radiotherapy alone (NCT00181519, NCT00573040, and NCT00572325).

PubMed

Dehing-Oberije, Cary; Aerts, Hugo; Yu, Shipeng; De Ruysscher, Dirk; Menheere, Paul; Hilvo, Mika; van der Weide, Hiska; Rao, Bharat; Lambin, Philippe

2011-10-01

Currently, prediction of survival for non-small-cell lung cancer patients treated with (chemo)radiotherapy is mainly based on clinical factors. The hypothesis of this prospective study was that blood biomarkers related to hypoxia, inflammation, and tumor load would have an added prognostic value for predicting survival. Clinical data and blood samples were collected prospectively (NCT00181519, NCT00573040, and NCT00572325) from 106 inoperable non-small-cell lung cancer patients (Stages I-IIIB), treated with curative intent with radiotherapy alone or combined with chemotherapy. Blood biomarkers, including lactate dehydrogenase, C-reactive protein, osteopontin, carbonic anhydrase IX, interleukin (IL) 6, IL-8, carcinoembryonic antigen (CEA), and cytokeratin fragment 21-1, were measured. A multivariate model, built on a large patient population (N = 322) and externally validated, was used as a baseline model. An extended model was created by selecting additional biomarkers. The model's performance was expressed as the area under the curve (AUC) of the receiver operating characteristic and assessed by use of leave-one-out cross validation as well as a validation cohort (n = 52). The baseline model consisted of gender, World Health Organization performance status, forced expiratory volume, number of positive lymph node stations, and gross tumor volume and yielded an AUC of 0.72. The extended model included two additional blood biomarkers (CEA and IL-6) and resulted in a leave-one-out AUC of 0.81. The performance of the extended model was significantly better than the clinical model (p = 0.004). The AUC on the validation cohort was 0.66 and 0.76, respectively. The performance of the prognostic model for survival improved markedly by adding two blood biomarkers: CEA and IL-6. Copyright © 2011 Elsevier Inc. All rights reserved.

Individualized Radical Radiotherapy of Non-Small-Cell Lung Cancer Based on Normal Tissue Dose Constraints: A Feasibility Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth

2008-08-01

Purpose: Local recurrence is a major problem after (chemo-)radiation for non-small-cell lung cancer. We hypothesized that for each individual patient, the highest therapeutic ratio could be achieved by increasing total tumor dose (TTD) to the limits of normal tissues, delivered within 5 weeks. We report first results of a prospective feasibility trial. Methods and Materials: Twenty-eight patients with medically inoperable or locally advanced non-small-cell lung cancer, World Health Organization performance score of 0-1, and reasonable lung function (forced expiratory volume in 1 second > 50%) were analyzed. All patients underwent irradiation using an individualized prescribed TTD based on normal tissuemore » dose constraints (mean lung dose, 19 Gy; maximal spinal cord dose, 54 Gy) up to a maximal TTD of 79.2 Gy in 1.8-Gy fractions twice daily. No concurrent chemoradiation was administered. Toxicity was scored using the Common Terminology Criteria for Adverse Events criteria. An {sup 18}F-fluoro-2-deoxy-glucose-positron emission tomography-computed tomography scan was performed to evaluate (metabolic) response 3 months after treatment. Results: Mean delivered dose was 63.0 {+-} 9.8 Gy. The TTD was most often limited by the mean lung dose (32.1%) or spinal cord (28.6%). Acute toxicity generally was mild; only 1 patient experienced Grade 3 cough and 1 patient experienced Grade 3 dysphagia. One patient (3.6%) died of pneumonitis. For late toxicity, 2 patients (7.7%) had Grade 3 cough or dyspnea; none had severe dysphagia. Complete metabolic response was obtained in 44% (11 of 26 patients). With a median follow-up of 13 months, median overall survival was 19.6 months, with a 1-year survival rate of 57.1%. Conclusions: Individualized maximal tolerable dose irradiation based on normal tissue dose constraints is feasible, and initial results are promising.« less

Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth.

PubMed

Abe, Tomoyuki; Kato, Masayoshi; Miki, Hiroaki; Takenawa, Tadaomi; Endo, Takeshi

2003-01-01

Rho family small GTPases regulate multiple cellular functions through reorganization of the actin cytoskeleton. Among them, Cdc42 and Tc10 induce filopodia or peripheral processes in cultured cells. We have identified a member of the family, designated as RhoT, which is closely related to Tc10. Tc10 was highly expressed in muscular tissues and brain and remarkably induced during differentiation of C2 skeletal muscle cells and neuronal differentiation of PC12 and N1E-115 cells. On the other hand, RhoT was predominantly expressed in heart and uterus and induced during neuronal differentiation of N1E-115 cells. Tc10 exogenously expressed in fibroblasts generated actin-filament-containing peripheral processes longer than the Cdc42-formed filopodia, whereas RhoT produced much longer and thicker processes containing actin filaments. Furthermore, both Tc10 and RhoT induced neurite outgrowth in PC12 and N1E-115 cells, but Cdc42 did not do this by itself. Tc10 and RhoT as well as Cdc42 bound to the N-terminal CRIB-motif-containing portion of N-WASP and activated N-WASP to induce Arp2/3-complex-mediated actin polymerization. The formation of peripheral processes and neurites by Tc10 and RhoT was prevented by the coexpression of dominant-negative mutants of N-WASP. Thus, N-WASP is essential for the process formation and neurite outgrowth induced by Tc10 and RhoT. Neuronal differentiation of PC12 and N1E-115 cells induced by dibutyryl cyclic AMP and by serum starvation, respectively, was prevented by dominant-negative Cdc42, Tc10 and RhoT. Taken together, all these Rho family proteins are required for neuronal differentiation, but they exert their functions differentially in process formation and neurite extension. Consequently, N-WASP activated by these small GTPases mediates neuronal differentiation in addition to its recently identified role in glucose uptake.

Population size, center-periphery, and seed dispersers' effects on the genetic diversity and population structure of the Mediterranean relict shrub Cneorum tricoccon.

PubMed

Lázaro-Nogal, Ana; Matesanz, Silvia; García-Fernández, Alfredo; Traveset, Anna; Valladares, Fernando

2017-09-01

The effect of population size on population genetic diversity and structure has rarely been studied jointly with other factors such as the position of a population within the species' distribution range or the presence of mutualistic partners influencing dispersal. Understanding these determining factors for genetic variation is critical for conservation of relict plants that are generally suffering from genetic deterioration. Working with 16 populations of the vulnerable relict shrub Cneorum tricoccon throughout the majority of its western Mediterranean distribution range, and using nine polymorphic microsatellite markers, we examined the effects of periphery (peripheral vs. central), population size (large vs. small), and seed disperser (introduced carnivores vs. endemic lizards) on the genetic diversity and population structure of the species. Contrasting genetic variation ( H E : 0.04-0.476) was found across populations. Peripheral populations showed lower genetic diversity, but this was dependent on population size. Large peripheral populations showed high levels of genetic diversity, whereas small central populations were less diverse. Significant isolation by distance was detected, indicating that the effect of long-distance gene flow is limited relative to that of genetic drift, probably due to high selfing rates ( F IS  = 0.155-0.887), restricted pollen flow, and ineffective seed dispersal. Bayesian clustering also supported the strong population differentiation and highly fragmented structure. Contrary to expectations, the type of disperser showed no significant effect on either population genetic diversity or structure. Our results challenge the idea of an effect of periphery per se that can be mainly explained by population size, drawing attention to the need of integrative approaches considering different determinants of genetic variation. Furthermore, the very low genetic diversity observed in several small populations and the strong among-population differentiation highlight the conservation value of large populations throughout the species' range, particularly in light of climate change and direct human threats.

Gene Expression Patterns in Peripheral Blood Leukocytes in Patients with Recurrent Ciguatera Fish Poisoning: Preliminary Studies.

PubMed

Lopez, Maria-Cecilia; Ungaro, Ricardo F; Baker, Henry V; Moldawer, Lyle L; Robertson, Alison; Abbott, Margaret; Roberts, Sparkle M; Grattan, Lynn M; Morris, J Glenn

2016-07-01

Ciguatera fish poisoning (ciguatera) is a common clinical syndrome in areas where there is dependence on tropical reef fish for food. A subset of patients develops recurrent and, in some instances, chronic symptoms, which may result in substantial disability. To identify possible biomarkers for recurrent/chronic disease, and to explore correlations with immune gene expression, peripheral blood leukocyte gene expression in 10 ciguatera patients (7 recurrent, 3 acute) from the U.S. Virgin Islands, and 5 unexposed Florida controls were evaluated. Significant differences in gene expression were noted when comparing ciguatera patients and controls; however, it was not possible to differentiate between patients with acute and recurrent disease, possibly due to the small sample sizes involved.

Gene Expression Patterns in Peripheral Blood Leukocytes in Patients with Recurrent Ciguatera Fish Poisoning: Preliminary Studies

PubMed Central

Lopez, Maria-Cecilia; Ungaro, Ricardo F.; Baker, Henry V.; Moldawer, Lyle L.; Robertson, Alison; Abbott, Margaret; Roberts, Sparkle M.; Grattan, Lynn M.; Morris, J. Glenn

2016-01-01

Ciguatera fish poisoning (ciguatera) is a common clinical syndrome in areas where there is dependence on tropical reef fish for food. A subset of patients develops recurrent and, in some instances, chronic symptoms, which may result in substantial disability. To identify possible biomarkers for recurrent/chronic disease, and to explore correlations with immune gene expression, peripheral blood leukocyte gene expression in 10 ciguatera patients (7 recurrent, 3 acute) from the U.S. Virgin Islands, and 5 unexposed Florida controls were evaluated. Significant differences in gene expression were noted when comparing ciguatera patients and controls; however, it was not possible to differentiate between patients with acute and recurrent disease, possibly due to the small sample sizes involved. PMID:27594814

Electrical Characterization of Hughes HCMP 1852D and RCA CDP1852D 8-bit, CMOS, I/O Ports

NASA Technical Reports Server (NTRS)

Stokes, R. L.

1979-01-01

Twenty-five Hughes HCMP 1852D and 25 RCA CDP1852D 8-bit, CMOS, I/O port microcircuits underwent electrical characterization tests. All electrical measurements were performed on a Tektronix S-3260 Test System. Before electrical testing, the devices were subjected to a 168-hour burn-in at 125 C with the inputs biased at 10V. Four of the Hughes parts became inoperable during testing. They exhibited functional failures and out-of-range parametric measurements after a few runs of the test program.

A Phase II Trial on the Effect of Low Dose versus High Dose Vitamin D Supplementation on Bone Mass in Adults with Neurofibromatosis 1 (NF1)

DTIC Science & Technology

2016-10-01

USAMRMC ORP HRPO. Ethics board approval from UBC has been approved by HRPO, and U of Cincinnati is under review. The University of Hamburg is working...UBC ethics committee approval was established, and USAMRMC ORP HRPO approval was provided October 20, 2015. Additional continuing review approval in...operations, and once translated to German will be submitted to its ethics committee. The CRFs have been translated into German and will be submitted

Pacemaker failure associated with therapeutic radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brooks, C.; Mutter, M.

1988-11-01

A 48-year-old white man with a multiprogrammable Intramedics 259-01 pacemaker was treated for inoperable lung cancer with a course of cobalt-60 radiotherapy (total 3500 rad). Several weeks subsequent to his last radiation treatment, the patient presented to the emergency department with chest and abdominal pain, shortness of breath, hypotension, and tachycardia. A paced tachycardia was noted, and application of a magnet over the pacemaker completely inhibited its function, allowing a normal sinus rhythm to ensue and the patient's symptoms to be relieved. Pacemaker failure probably was a complication of radiotherapy.

A thermodynamic approach to the 'mitosis/apoptosis' ratio in cancer

NASA Astrophysics Data System (ADS)

Lucia, Umberto; Ponzetto, Antonio; Deisboeck, Thomas S.

2015-10-01

Cancer can be considered as an open, complex, (bio-thermo)dynamic and self-organizing system. Consequently, an entropy generation approach has been employed to analyze its mitosis/apoptosis ratio. Specifically, a novel thermodynamic anticancer strategy is suggested, based on the variation of entropy generation caused by the application of external fields, for example electro-magnetic fields, for therapeutic purposes. Eventually, this innovative approach could support conventional therapies, particularly for inoperable tumors or advanced stages of cancer, when larger tumor burden is diagnosed, and therapeutic options are often limited.

Focal brainstem gliomas

PubMed Central

Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

2015-01-01

Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

Endoscopic ultrasonography in the management of esophageal cancer

NASA Astrophysics Data System (ADS)

Trowers, Eugene A.

2000-05-01

Precise tumor-staging is critical in the management of early esophageal caner. Endoscopic ultrasound (EUS) allows the endoscopist a view beyond the esophageal wall which opens the door to a variety of new gastroenterologic techniques. Endoscopic mucosal resection, laser photoablation and photodynamic therapy may be successfully employed in early esophageal cancer management. Combination radiation therapy and chemotherapy have shown better responses in advanced cancer. Expandable metallic stents may also provide palliation with inoperable esophageal cancer. The efficacy of EUS in the management of esophageal cancer is critically reviewed.

Current Status of Interventional Radiology in the Management of Gastro-Entero-Pancreatic Neuroendocrine Tumours (GEP-NETs)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Orgera, Gianluigi; Krokidis, Miltiadis, E-mail: mkrokidis@hotmail.com; Cappucci, Matteo

2015-02-15

Within the group of Gastro-Entero-Pancreatic Neuroendocrine tumours (GEP-NETs), several heterogeneous malignancies are included with a variety of clinical manifestations and imaging characteristics. Often these cases are inoperable and minimal invasive treatment offered by image-guided procedures appears to be the only option. Interventional radiology offers a valid solution in the management of primary and metastatic GEP-NETs. The purpose of this review article is to describe the current status of the role of Interventional Radiology in the management of GEP-NETs.

Obstetrics in a small maternity hospital.

PubMed

Elliott, C E

1992-05-01

This paper presents the case for continuing to practise safe obstetrics in a small suburban hospital. Boothville Maternity Hospital, Brisbane, is a Salvation Army hospital of 20 beds. Seven thousand births during the years 1975 to 1989 are reported. Perinatal mortality rate was 4.9/1000 total births, forceps rate 7.1%, caesarean rate 9.3% and transfer rate to larger centres 1.6% for babies and 1.2% for mothers. Personalised family-centred care in congenial surroundings serves to maximise the factors that favour uncomplicated delivery. Large centralised and small peripheral hospitals should be seen not as competitive but as complementary. Boothville provides mutually satisfying co-operation for care-givers and care-receivers.

A review of stereotactic body radiotherapy – is volumetric modulated arc therapy the answer?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sapkaroski, Daniel, E-mail: daniel.sapkaroski@gmail.com; Osborne, Catherine; Knight, Kellie A

2015-06-15

Stereotactic body radiotherapy (SBRT) is a high precision radiotherapy technique used for the treatment of small to moderate extra-cranial tumours. Early studies utilising SBRT have shown favourable outcomes. However, major disadvantages of static field SBRT include long treatment times and toxicity complications. Volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) may potentially mitigate these disadvantages. This review aims to assess the feasibility of emerging VMAT and IMRT-based SBRT treatment techniques and qualify which offers the best outcome for patients, whilst identifying any emerging and advantageous SBRT planning trends. A review and synthesis of data from current literature upmore » to September 2013 was conducted on EMBASE, Medline, PubMed, Science Direct, Proquest central, Google Scholar and the Cochrane Database of Systematic reviews. Only full text papers comparing VMAT and or IMRT and or Static SBRT were included. Ten papers were identified that evaluated the results of VMAT/IMRT SBRT. Five related to medically inoperable stage 1 and 2 non-small-cell lung cancer (NSCLC), three to spinal metastasis, one related to abdominal lymph node malignancies, with the final one looking at pancreatic adenocarcinoma. Overall treatment times with VMAT were reduced by 66–70% for lung, 46–58% for spine, 42% and 21% for lymph node and pancreatic metastasis respectively, planning constraints were met with several studies showing improved organs at risk sparing with IMRT/VMAT to static SBRT. Both IMRT and VMAT were able to meet all planning constraints in the studies reviewed, with VMAT offering the greatest treatment efficiency. Early clinical outcomes with VMAT and IMRT SBRT have demonstrated excellent local control and favourable survival outcomes.« less

Stereotactic ablative radiotherapy after concomitant chemoradiotherapy in non-small cell lung cancer: A TITE-CRM phase 1 trial.

PubMed

Doyen, Jérôme; Poudenx, Michel; Gal, Jocelyn; Otto, Josiane; Guerder, Caroline; Naghavi, Arash O; Gérard, Anais; Leysalle, Axel; Cohen, Charlotte; Padovani, Bernard; Ianessi, Antoine; Schiappa, Renaud; Chamorey, Emmanuel; Bondiau, Pierre-Yves

2018-05-01

Platinum based chemoradiotherapy is the standard of care for inoperable non-small cell lung cancer (NSCLC). With evidence that NSCLC can have a dose dependent response with stereotactic ablative radiotherapy (SABR), we hypothesize that a SABR boost on residual tumor treated with chemoradiotherapy could increase treatment efficacy. The purpose of this study was to determine feasibility of such an approach. A prospective phase I trial was performed including 26 patients. Time-to-event continual reassessment method (TITE-CRM) was used for dose escalation which ranged from 3 × 7 to 3 × 12 Gy for the stereotactic boost, after 46 Gy (2 Gy per day) of chemoradiotherapy. Median follow-up was of 37.1 months (1.7-60.7), and 3, 4, 3, 3, 9 and 4 patients were included at the dose levels 1, 2, 3, 4, 5 and 6, respectively. During chemoradiotherapy, 9 patients experienced grade 3 toxicity. After stereotactic radiotherapy, 1 patient experienced an esophageal fistula (with local relapse) at the 3 × 11 Gy level, and 1 patient died from hemoptysis at the 3 × 12 Gy level. The 2-year rate of local control, locoregional free survival, metastasis-free survival, and overall survival was 70.3%, 55.5%, 44.5% and 50.8%, respectively. In the treatment of NSCLC with chemoradiotherapy followed by a stereotactic boost, the safe recommended dose in our protocol was a boost dose of 3 × 11 Gy. Copyright © 2018 Elsevier B.V. All rights reserved.

Dose escalation study of proton beam therapy with concurrent chemotherapy for stage III non-small cell lung cancer.

PubMed

Harada, Hideyuki; Fuji, Hiroshi; Ono, Akira; Kenmotsu, Hirotsugu; Naito, Tateaki; Yamashita, Haruo; Asakura, Hirofumi; Nishimura, Tetsuo; Takahashi, Toshiaki; Murayama, Shigeyuki

2016-07-01

The purpose of this study is to determine the recommended dose (RD) of proton beam therapy (PBT) for inoperable stage III non-small cell lung cancer (NSCLC). We tested two prescribed doses of PBT: 66 Gy (relative biological effectiveness [RBE]) in 33 fractions and 74 Gy (RBE) in 37 fractions in arms 1 and 2, respectively. The planning target volume (PTV) included the primary tumor and metastatic lymph nodes with adequate margins. Concurrent chemotherapy included intravenous cisplatin (60 mg/m(2) , day 1) and oral S-1 (80, 100 or 120 mg based on body surface area, days 1-14), repeated as four cycles every 4 weeks. Dose-limiting toxicity (DLT) was defined as grade 3 or severe toxicities related to PBT during days 1-90. Each dose level was performed in three patients, and then escalated to the next level if no DLT occurred. When one patient developed a DLT, three additional patients were enrolled. Overall, nine patients (five men, four women; median age, 72 years) were enrolled, including six in arm 1 and three in arm 2. The median follow-up time was 43 months, and the median progression-free survival was 15 months. In arm 1, grade 3 infection occurred in one of six patients, but no other DLT was reported. Similarly, no DLT occurred in arm 2. However, one patient in arm 2 developed grade 3 esophageal fistula at 9 months after the initiation of PBT. Therefore, we determined that 66 Gy (RBE) is the RD from a clinical viewpoints. (Clinical trial registration no. UMIN000005585). © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

A comparative study of the target volume definition in radiotherapy with «Slow CT Scan» vs. 4D PET/CT Scan in early stages non-small cell lung cancer.

PubMed

Molla, M; Anducas, N; Simó, M; Seoane, A; Ramos, M; Cuberas-Borros, G; Beltran, M; Castell, J; Giralt, J

To evaluate the use of 4D PET/CT to quantify tumor respiratory motion compared to the «Slow»-CT (CTs) in the radiotherapy planning process. A total of 25 patients with inoperable early stage non small cell lung cancer (NSCLC) were included in the study. Each patient was imaged with a CTs (4s/slice) and 4D PET/CT. The adequacy of each technique for respiratory motion capture was evaluated using the volume definition for each of the following: Internal target volume (ITV) 4D and ITVslow in relation with the volume defined by the encompassing volume of 4D PET/CT and CTs (ITVtotal). The maximum distance between the edges of the volume defined by each technique to that of the total volume was measured in orthogonal beam's eye view. The ITV4D showed less differences in relation with the ITVtotal in both the cranio-caudal and the antero-posterior axis compared to the ITVslow. The maximum differences were 0.36mm in 4D PET/CTand 0.57mm in CTs in the antero-posterior axis. 4D PET/CT resulted in the definition of more accurate (ITV4D/ITVtotal 0.78 vs. ITVs/ITVtotal 0.63), and larger ITVs (19.9 cc vs. 16.3 cc) than those obtained with CTs. Planning with 4D PET/CT in comparison with CTs, allows incorporating tumor respiratory motion and improving planning radiotherapy of patients in early stages of lung cancer. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Recurrence Patterns and Second Primary Lung Cancers After Stereotactic Body Radiation Therapy for Early-Stage Non-Small-Cell Lung Cancer: Implications for Surveillance.

PubMed

Spratt, Daniel E; Wu, Abraham J; Adeseye, Victoria; Din, Shaun U; Shaikh, Fauzia; Woo, Kaitlin M; Zhang, Zhigang; Foster, Amanda; Rosenzweig, Kenneth E; Gewanter, Richard; Huang, James; Rimner, Andreas

2016-05-01

Patients treated with stereotactic body radiation therapy (SBRT) for early-stage non-small-cell lung cancer (NSCLC) are subject to locoregional and distant recurrence, as well as the formation of second primary lung cancers (SPLCs). The optimal surveillance regimen for patients treated with SBRT for early-stage NSCLC remains unclear; we therefore investigated the posttreatment recurrence patterns and development of SPLCs. Three hundred sixty-six patients with pathologically proven inoperable early-stage NSCLC treated with SBRT between 2006 and 2013 were assessed. Patients underwent a computed tomographic (CT) scan of the chest every 3 months during years 1 and 2, every 6 months during years 3 and 4, and annually thereafter. Competing risk analysis was used for all time-to-event analyses. With a median follow-up of 23 months, the 2-year cumulative incidence of local, nodal, and distant treatment failures were 12.2%, 16.1%, and 15.5%, respectively. In patients with disease progression after SBRT (n = 108), 84% (n = 91) of cases occurred within the first 2 years. Five percent (n = 19) of patients experienced SPLCs. The median time to development of an SPLC was 16.5 months (range, 6.5-71.1 months), with 33% (n = 6) of these patients experiencing SPLCs after 2 years. None of the never smokers, but 4% of former tobacco smokers and 15% of current tobacco smokers, experienced an SPLC (P = .005). Close monitoring with routine CT scans within the first 2 years after SBRT is effective in detecting early disease progression. In contrast, the risk for the development of an SPLC remains elevated beyond 2 years, particularly in former and current smokers. Copyright © 2015 Elsevier Inc. All rights reserved.

Design, development of water tank-type lung phantom and dosimetric verification in institutions participating in a phase I study of stereotactic body radiation therapy in patients with T2N0M0 non-small cell lung cancer: Japan Clinical Oncology Group trial (JCOG0702).

PubMed

Nishio, Teiji; Shirato, Hiroki; Ishikawa, Masayori; Miyabe, Yuki; Kito, Satoshi; Narita, Yuichirou; Onimaru, Rikiya; Ishikura, Satoshi; Ito, Yoshinori; Hiraoka, Masahiro

2014-05-01

A domestic multicenter phase I study of stereotactic body radiotherapy (SBRT) for T2N0M0 non-small cell lung cancer in inoperable patients or elderly patients who refused surgery was initiated as the Japan Clinical Oncology Group trial (JCOG0702) in Japan. Prior to the clinical study, the accuracy of dose calculation in radiation treatment-planning systems was surveyed in participating institutions, and differences in the irradiating dose between the institutions were investigated. We developed a water tank-type lung phantom appropriate for verification of the exposure dose in lung SBRT. Using this water tank-type lung phantom, the dose calculated in the radiation treatment-planning system and the measured dose using a free air ionization chamber and dosimetric film were compared in a visiting survey of the seven institutions participating in the clinical study. In all participating institutions, differences between the calculated and the measured dose in the irradiation plan were as follows: the accuracy of the absolute dose in the center of the simulated tumor measured using a free air ionization chamber was within 2%, the mean gamma value was ≤ 0.47 on gamma analysis following the local dose criteria, and the pass rate was >87% for 3%/3 mm from measurement of dose distribution with dosimetric film. These findings confirmed the accuracy of delivery doses in the institutions participating in the clinical study, so that a study with integration of the institutions could be initiated.

SUNSET: Stereotactic Radiation for Ultracentral Non-Small-Cell Lung Cancer-A Safety and Efficacy Trial.

PubMed

Giuliani, Meredith; Mathew, Ashwathy S; Bahig, Houda; Bratman, Scott V; Filion, Edith; Glick, Daniel; Louie, Alexander V; Raman, Srinivas; Swaminath, Anand; Warner, Andrew; Yau, Vivian; Palma, David

2018-04-18

Lung stereotactic body radiotherapy (SBRT) is considered a standard curative treatment for medically inoperable early stage non-small-cell lung cancer (NSCLC). Patients with ultracentral tumors (signifying tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, or pulmonary artery) may be at higher risk of serious toxicities such as bronchial stricture and collapse, esophageal strictures, tracheal-esophageal fistula, and hemorrhage. The primary objective of the study is to determine the maximum tolerated dose of radiotherapy for ultracentral NSCLC. This multicenter phase 1 dose-escalation study will use a time-to-event continual reassessment method (TITE-CRM). Accrual will start at level 1 (60 Gy in 8 fractions delivered daily). The model will use all available information from previously accrued patients to assign the highest dose with a predicted risk of grade 3-5 toxicity of 30% or less. All patients with newly diagnosed stage T1-3 N0M0 NSCLC (International Union Against Cancer, 8th edition) with tumor size ≤ 6 cm and meeting the criteria for ultracentral location (ie, tumors whose planning target volume touches or overlaps the central bronchial tree, esophagus, pulmonary vein, or pulmonary artery) will be eligible for this study. It is important to identify a safe dose-fractionation regimen for treating ultracentral tumors with SBRT. In addition, the data from this study may be informative in guiding future studies on the use of SBRT in treating malignancies within the mediastinum-for example, for salvage treatment of mediastinal lymph nodes for recurrent NSCLC or mediastinal oligometastases. Copyright © 2018 Elsevier Inc. All rights reserved.

Pattern of metastasis outside tumor-bearing segments in primary lung cancer: rationale for segmentectomy.

PubMed

Sakairi, Yuichi; Yoshino, Ichiro; Yoshida, Shigetoshi; Suzuki, Hidemi; Tagawa, Tetsuzo; Iwata, Takekazu; Mizobuchi, Teruaki

2014-05-01

Patterns of intrapulmonary metastasis, particularly metastasis outside tumor-bearing segments, were investigated in lung cancer patients to address the rationale for segmentectomy. In a consecutive series of patients who underwent resection of two or more pulmonary segments for primary lung cancer, intrapulmonary spread patterns, such as segmental/intersegmental node metastasis and pulmonary parenchymal metastasis, were pathologically examined. Eligible 244 lesions included 167 adenocarcinomas, 66 squamous cell carcinomas, and 11 large cell carcinomas. Pathologic stages included 0 to IA (n=111), IB (n=56), IIA (n=31), IIB (n=20), IIIA (n=23), and IIIB to IV (n=3); and N1 (n=26) and N2 (n=22). Intrapulmonary spread was observed in 24 cases (9.8%). Of these, metastasis outside tumor-bearing segments was only observed in 4 cases (1.6%), and such cancer spread was more frequently seen in cases with extrapulmonary (hilar to mediastinal) nodal metastasis (7.9%) than in cases without extrapulmonary metastasis (0.5%; p=0.01). Metastasis outside tumor-bearing segments was not observed in 64 tumors with pure or mixed ground glass opacity features on computed tomography. Although tumor location (peripheral or central/intermediate) was not related to the incidence of metastasis outside tumor-bearing segments, intrapulmonary spread was observed in only 1 of 52 peripheral small (≤20 mm) tumors. Metastasis outside tumor-bearing segments is rarely observed in cases with tumors (1) without extrapulmonary nodal metastasis and (2) with ground glass opacity or peripheral small (≤20 mm) features. Copyright © 2014 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles

PubMed Central

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B.; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S.; Freynhagen, Rainer; Kennedy, Jeffrey D.; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S.C.; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2016-01-01

Abstract Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders. PMID:27893485

Use of antigen-primed dendritic cells for inducing antitumor immune responses in vitro in patients with non-small cell lung cancer

PubMed Central

Obleukhova, Irina; Kiryishina, Nataliya; Falaleeva, Svetlana; Lopatnikova, Julia; Kurilin, Vasiliy; Kozlov, Vadim; Vitsin, Aleksander; Cherkasov, Andrey; Kulikova, Ekaterina; Sennikov, Sergey

2018-01-01

Cancer is associated with a reduction in immature and mature circulating dendritic cells (DCs), and with an impaired migratory capacity, compared with healthy donors. Therefore, modern approaches to the in vitro generation of DCs loaded with tumor antigens and their use for inducing antitumor immune responses in vivo are being investigated. The purpose of the present study was to investigate the phenotypic and functional characteristics of peripheral blood DC subsets in patients with non-small cell lung cancer (NSCLC), and the development of an antitumor cytotoxic response by mononuclear cells (MNCs) from patients using in vitro generated antigen-primed DCs. Heparinized peripheral venous blood samples were obtained from 10 healthy donors and 20 patients with a histologically verified diagnosis of NSCLC. The ability of antigen-activated DCs to stimulate the activity of MNCs against autologous tumor cells was evaluated using a cytotoxic test. Peripheral blood DC subsets from patients with NSCLC were identified to be decreased and to exhibit an impaired ability to mature, compared with healthy donors. Furthermore, DCs generated from MNCs from patients with NSCLC were able to stimulate a specific cytotoxic response when loaded with autologous tumor lysates or RNA and matured, in vitro. A perforin and granzyme B-dependent mode of cytotoxicity was primarily induced. The ability of DCs loaded with tumor antigens to increase the cytotoxic activity of MNCs against NSCLC cells in vitro indicates the effective induction and co-stimulation of T lymphocytes by the generated DCs. PMID:29399182

Morphological study of the prostate gland in viscacha (Lagostomus maximus maximus) during periods of maximal and minimal reproductive activity.

PubMed

Chaves, Maximiliano; Aguilera-Merlo, Claudia; Cruceño, Albana; Fogal, Teresa; Mohamed, Fabian

2015-11-01

The viscacha (Lagostomus maximus maximus) is a rodent with photoperiod-dependent seasonal reproduction. The aim of this work was to study the morphological variations of the prostate during periods of maximal (summer, long photoperiod) and minimal (winter, short photoperiod) reproductive activity. Prostates of adult male viscachas were studied by light and electron microscopy, immunohistochemistry for androgen receptor, and morphometric analysis. The prostate consisted of two regions: peripheral and central. The peripheral zone exhibited large adenomeres with a small number of folds and lined with a pseudostratified epithelium. The central zone had small adenomeres with pseudostratified epithelium and the mucosa showed numerous folds. The morphology of both zones showed variations during periods of maximal and minimal reproductive activity. The prostate weight, prostate-somatic index, luminal diameter of adenomeres, epithelial height and major nuclear diameter decreased during the period of minimal reproductive activity. Principal cells showed variations in their shape, size and ultrastructural characteristics during the period of minimal reproductive activity in comparison with the active period. The androgen receptor expression in epithelial and fibromuscular stromal cells was different between the studied periods. Our results suggest a reduced secretory activity of viscacha prostate during the period of minimal reproductive activity. Thus, the morphological variations observed in both the central and peripheral zones of the viscacha prostate agree with the results previously obtained in the gonads of this rodent of photoperiod-dependent reproduction. Additionally, the variations observed in the androgen receptors suggest a direct effect of the circulating testosterone on the gland. © 2015 Wiley Periodicals, Inc.

Temporal dissociation between the focal and orientation components of spatial attention in central and peripheral vision.

PubMed

Albonico, Andrea; Malaspina, Manuela; Bricolo, Emanuela; Martelli, Marialuisa; Daini, Roberta

2016-11-01

Selective attention, i.e. the ability to concentrate one's limited processing resources on one aspect of the environment, is a multifaceted concept that includes different processes like spatial attention and its subcomponents of orienting and focusing. Several studies, indeed, have shown that visual tasks performance is positively influenced not only by attracting attention to the target location (orientation component), but also by the adjustment of the size of the attentional window according to task demands (focal component). Nevertheless, the relative weight of the two components in central and peripheral vision has never been studied. We conducted two experiments to explore whether different components of spatial attention have different effects in central and peripheral vision. In order to do so, participants underwent either a detection (Experiment 1) or a discrimination (Experiment 2) task where different types of cues elicited different components of spatial attention: a red dot, a small square and a big square (an optimal stimulus for the orientation component, an optimal and a sub-optimal stimulus for the focal component respectively). Response times and cue-size effects indicated a stronger effect of the small square or of the dot in different conditions, suggesting the existence of a dissociation in terms of mechanisms between the focal and the orientation components of spatial attention. Specifically, we found that the orientation component was stronger in periphery, while the focal component was noticeable only in central vision and characterized by an exogenous nature. Copyright © 2016 Elsevier B.V. All rights reserved.

Peripheral neuropathic pain: a mechanism-related organizing principle based on sensory profiles.

PubMed

Baron, Ralf; Maier, Christoph; Attal, Nadine; Binder, Andreas; Bouhassira, Didier; Cruccu, Giorgio; Finnerup, Nanna B; Haanpää, Maija; Hansson, Per; Hüllemann, Philipp; Jensen, Troels S; Freynhagen, Rainer; Kennedy, Jeffrey D; Magerl, Walter; Mainka, Tina; Reimer, Maren; Rice, Andrew S C; Segerdahl, Märta; Serra, Jordi; Sindrup, Sören; Sommer, Claudia; Tölle, Thomas; Vollert, Jan; Treede, Rolf-Detlef

2017-02-01

Patients with neuropathic pain are heterogeneous in etiology, pathophysiology, and clinical appearance. They exhibit a variety of pain-related sensory symptoms and signs (sensory profile). Different sensory profiles might indicate different classes of neurobiological mechanisms, and hence subgroups with different sensory profiles might respond differently to treatment. The aim of the investigation was to identify subgroups in a large sample of patients with neuropathic pain using hypothesis-free statistical methods on the database of 3 large multinational research networks (German Research Network on Neuropathic Pain (DFNS), IMI-Europain, and Neuropain). Standardized quantitative sensory testing was used in 902 (test cohort) and 233 (validation cohort) patients with peripheral neuropathic pain of different etiologies. For subgrouping, we performed a cluster analysis using 13 quantitative sensory testing parameters. Three distinct subgroups with characteristic sensory profiles were identified and replicated. Cluster 1 (sensory loss, 42%) showed a loss of small and large fiber function in combination with paradoxical heat sensations. Cluster 2 (thermal hyperalgesia, 33%) was characterized by preserved sensory functions in combination with heat and cold hyperalgesia and mild dynamic mechanical allodynia. Cluster 3 (mechanical hyperalgesia, 24%) was characterized by a loss of small fiber function in combination with pinprick hyperalgesia and dynamic mechanical allodynia. All clusters occurred across etiologies but frequencies differed. We present a new approach of subgrouping patients with peripheral neuropathic pain of different etiologies according to intrinsic sensory profiles. These 3 profiles may be related to pathophysiological mechanisms and may be useful in clinical trial design to enrich the study population for treatment responders.

Expression of small cytoplasmic transcripts of the rat identifier element in vivo and in cultured cells.

PubMed Central

McKinnon, R D; Danielson, P; Brow, M A; Bloom, F E; Sutcliffe, J G

1987-01-01

We examined the level of expression of small RNA transcripts hybridizing to a rodent repetitive DNA element, the identifier (ID) sequence, in a variety of cell types in vivo and in cultured mammalian cells. A 160-nucleotide (160n) cytoplasmic poly(A)+ RNA (BC1) appeared in late embryonic and early postnatal rat brain development, was enriched in the cerebral cortex, and appeared to be restricted to neural tissue and the anterior pituitary gland. A 110n RNA (BC2) was specifically enriched in brain, especially the postnatal cortex, but was detectable at low levels in peripheral tissues. A third, related 75n poly(A)- RNA (T3) was found in rat brain and at lower levels in peripheral tissues but was very abundant in the testes. The BC RNAs were found in a variety of rat cell lines, and their level of expression was dependent upon cell culture conditions. A rat ID probe detected BC-like RNAs in mouse brain but not liver and detected a 200n RNA in monkey brain but not liver at lower hybridization stringencies. These RNAs were expressed by mouse and primate cell lines. Thus, tissue-specific expression of small ID-sequence-related transcripts is conserved among mammals, but the tight regulation found in vivo is lost by cells in culture. Images PMID:2439903

Novel Robotic Tools for Piping Inspection and Repair

DTIC Science & Technology

2015-01-14

was selected due to its small size, and peripheral capability. The SoM measures 50mm x 44mm. The SoM processor is an ARM Cortex -A8 running at720MHz...designing an embedded computing system from scratch. The SoM is a single integrated module which contains the processor , RAM, power management, and

The Role of Higher Education Centres in Research and Policy: A Case from a European Periphery

ERIC Educational Resources Information Center

Zgaga, Pavel

2014-01-01

This article focuses on higher education research and policies in small and/or peripheral countries that usually occupy a marginal position in contemporary international debates. The region discussed here is South-eastern Europe and especially the Western Balkans. First, an outline of emerging research centres and the developments in higher…

Churg-Strauss syndrome in childhood: a case report.

PubMed

Albahri, Ziad; Minxová, Lenka; Lukeš, Antonín; Mawiri, Abdul Al; Štefáčková, Šárka

2014-10-01

Churg-Strauss syndrome is a rare form of small-vessel vasculitis. In the current report, we describe the case of a 17-year-old Czech girl predominantly characterized by peripheral neuropathy, the presence of cardiac and pulmonary involvement, hypereosinophilia, asthma, and sinusitis that led to the diagnosis of Churg-Strauss syndrome. © The Author(s) 2013.

Adaptation to Leftward-Shifting Prisms Reduces the Global Processing Bias of Healthy Individuals

ERIC Educational Resources Information Center

Bultitude, Janet H.; Woods, Jill M.

2010-01-01

When healthy individuals are presented with peripheral figures in which small letters are arranged to form a large letter, they are faster to identify the global- than the local-level information, and have difficulty ignoring global information when identifying the local level. The global reaction time (RT) advantage and global interference effect…

Rescuing a Small Village School in the Context of Rural Change in Hungary

ERIC Educational Resources Information Center

Kovacs, Katalin

2012-01-01

The paper discusses local responses to schooling policy in the context of the uneven differentiation and sharp social polarisation of the Hungarian countryside. Counter-urbanisation, on the one hand, has brought affluent urban middle classes to suburban spaces, on the other hand, peripheral areas are becoming impoverished with high unemployment,…

Chinese Language Teaching in the UK: Present and Future

ERIC Educational Resources Information Center

Zhang, George X.; Li, Linda M.

2010-01-01

There has been a long history of Chinese learning and teaching (CLT) in the UK, but until recently CLT was predominantly confined to community schools for Chinese children at weekends and a small number of other schools and universities. Therefore, it had remained peripheral for a long time in terms of student numbers and its position in the…

Splenic marginal zone lymphoma.

PubMed

Piris, Miguel A; Onaindía, Arantza; Mollejo, Manuela

Splenic marginal zone lymphoma (SMZL) is an indolent small B-cell lymphoma involving the spleen and bone marrow characterized by a micronodular tumoral infiltration that replaces the preexisting lymphoid follicles and shows marginal zone differentiation as a distinctive finding. SMZL cases are characterized by prominent splenomegaly and bone marrow and peripheral blood infiltration. Cells in peripheral blood show a villous cytology. Bone marrow and peripheral blood characteristic features usually allow a diagnosis of SMZL to be performed. Mutational spectrum of SMZL identifies specific findings, such as 7q loss and NOTCH2 and KLF2 mutations, both genes related with marginal zone differentiation. There is a striking clinical variability in SMZL cases, dependent of the tumoral load and performance status. Specific molecular markers such as 7q loss, p53 loss/mutation, NOTCH2 and KLF2 mutations have been found to be associated with the clinical variability. Distinction from Monoclonal B-cell lymphocytosis with marginal zone phenotype is still an open issue that requires identification of precise and specific thresholds with clinical meaning. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

PubMed

Bauer, Joseph A; Frye, Gerald; Bahr, Anne; Gieg, Jennifer; Brofman, Peter

2010-10-01

Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer. (1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies. (1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment. We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

Behavioural, morphological and electrophysiological assessment of the effects of type 2 diabetes mellitus on large and small nerve fibres in Zucker diabetic fatty, Zucker lean and Wistar rats.

PubMed

Garcia-Perez, E; Schönberger, T; Sumalla, M; Stierstorfer, B; Solà, R; Doods, H; Serra, J; Gorodetskaya, N

2018-04-20

Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory-motor polyneuropathy that involves large and small nerve fibres in variable proportion. Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6- to 40-week-old rats. ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity-dependent slowing (ADS) of mechano-insensitive C-nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C-nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age-matched and apparently normoglycaemic ZL and WH rats fed with the same diet. ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C-fibres, clearly detected by microneurography SIGNIFICANCE: This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus. © 2018 European Pain Federation - EFIC®.

Heterogeneous living donor hepatic fat distribution on MRI chemical shift imaging.

PubMed

Choi, YoungRok; Lee, Jeong Min; Yi, Nam-Joon; Kim, Hyeyoung; Park, Min-Su; Hong, Geun; Yoo, Tae; Suh, Suk-Won; Lee, Hae Won; Lee, Kwang-Woong; Suh, Kyung-Suk

2015-07-01

We evaluated the heterogeneity of steatosis in living donor livers to determine its regional differences. Between June 2011 and February 2012, 81 liver donors were selected. Fat fraction was estimated using magnetic resonance triple-echo chemical shifting gradient imaging in 13 different regions: segment 1 (S1), S2, S3, and each peripheral and deep region of S4, S5, S6, S7, and S8. There were differences (range, 3.2%-5.3%) in fat fractions between each peripheral and deep region of S4, S6, S7, and S8 (P < 0.001, P = 0.004, P < 0.001, and P = 0.006). Fat deposit amount in S1, S2, S3 and deep regions of S4-S8 were significantly different from one another (F [4.003, 58.032] = 8.684, P < 0.001), while there were no differences among the peripheral regions of S4-S8 (F [2.9, 5.3] = 1.3, P = 0.272) by repeated measure analysis of variance method. And regional differences of the amount of fat deposit in the whole liver increased as a peripheral fat fraction of S5 increased (R(2) = 0.428, P < 0.001). Multifocal fat measurements for the whole liver are needed because a small regional evaluation might not represent the remaining liver completely, especially in patients with severe hepatic steatosis.

A comparison of phase imaging and quantitative susceptibility mapping in the imaging of multiple sclerosis lesions at ultrahigh field.

PubMed

Cronin, Matthew John; Wharton, Samuel; Al-Radaideh, Ali; Constantinescu, Cris; Evangelou, Nikos; Bowtell, Richard; Gowland, Penny Anne

2016-06-01

The aim of this study was to compare the use of high-resolution phase and QSM images acquired at ultra-high field in the investigation of multiple sclerosis (MS) lesions with peripheral rings, and to discuss their usefulness for drawing inferences about underlying tissue composition. Thirty-nine Subjects were scanned at 7 T, using 3D T 2*-weighted and T 1-weighted sequences. Phase images were then unwrapped and filtered, and quantitative susceptibility maps were generated using a thresholded k-space division method. Lesions were compared visually and using a 1D profiling algorithm. Lesions displaying peripheral rings in the phase images were identified in 10 of the 39 subjects. Dipolar projections were apparent in the phase images outside of the extent of several of these lesions; however, QSM images showed peripheral rings without such projections. These projections appeared ring-like in a small number of phase images where no ring was observed in QSM. 1D profiles of six well-isolated example lesions showed that QSM contrast corresponds more closely to the magnitude images than phase contrast. Phase images contain dipolar projections, which confounds their use in the investigation of tissue composition in MS lesions. Quantitative susceptibility maps correct these projections, providing insight into the composition of MS lesions showing peripheral rings.

Validation of the Italian Version of the Dizziness Handicap Inventory, the Situational Vertigo Questionnaire, and the Activity-Specific Balance Confidence Scale for Peripheral and Central Vestibular Symptoms.

PubMed

Colnaghi, Silvia; Rezzani, Cristiana; Gnesi, Marco; Manfrin, Marco; Quaglieri, Silvia; Nuti, Daniele; Mandalà, Marco; Monti, Maria Cristina; Versino, Maurizio

2017-01-01

Neurophysiological measurements of the vestibular function for diagnosis and follow-up evaluations provide an objective assessment, which, unfortunately, does not necessarily correlate with the patients' self-feeling. The literature provides many questionnaires to assess the outcome of rehabilitation programs for disequilibrium, but only for the Dizziness Handicap Inventory (DHI) is an Italian translation available, validated on a small group of patients suffering from a peripheral acute vertigo. We translated and validated the reliability and validity of the DHI, the Situational Vertigo Questionnaire (SVQ), and the Activities-Specific Balance Confidence Scale (ABC) in 316 Italian patients complaining of dizziness due either to a peripheral or to a central vestibular deficit, or in whom vestibular signs were undetectable by means of instrumental testing or clinical evaluation. Cronbach's coefficient alpha, the homogeneity index, and test-retest reproducibility, confirmed reliability of the Italian version of the three questionnaires. Validity was confirmed by correlation test between questionnaire scores. Correlations with clinical variables suggested that they can be used as a complementary tool for the assessment of vestibular symptoms. In conclusion, the Italian versions of DHI, SVQ, and ABC are reliable and valid questionnaires for assessing the impact of dizziness on the quality of life of Italian patients with peripheral or central vestibular deficit.

Validation of the Italian Version of the Dizziness Handicap Inventory, the Situational Vertigo Questionnaire, and the Activity-Specific Balance Confidence Scale for Peripheral and Central Vestibular Symptoms

PubMed Central

Colnaghi, Silvia; Rezzani, Cristiana; Gnesi, Marco; Manfrin, Marco; Quaglieri, Silvia; Nuti, Daniele; Mandalà, Marco; Monti, Maria Cristina; Versino, Maurizio

2017-01-01

Neurophysiological measurements of the vestibular function for diagnosis and follow-up evaluations provide an objective assessment, which, unfortunately, does not necessarily correlate with the patients’ self-feeling. The literature provides many questionnaires to assess the outcome of rehabilitation programs for disequilibrium, but only for the Dizziness Handicap Inventory (DHI) is an Italian translation available, validated on a small group of patients suffering from a peripheral acute vertigo. We translated and validated the reliability and validity of the DHI, the Situational Vertigo Questionnaire (SVQ), and the Activities-Specific Balance Confidence Scale (ABC) in 316 Italian patients complaining of dizziness due either to a peripheral or to a central vestibular deficit, or in whom vestibular signs were undetectable by means of instrumental testing or clinical evaluation. Cronbach’s coefficient alpha, the homogeneity index, and test–retest reproducibility, confirmed reliability of the Italian version of the three questionnaires. Validity was confirmed by correlation test between questionnaire scores. Correlations with clinical variables suggested that they can be used as a complementary tool for the assessment of vestibular symptoms. In conclusion, the Italian versions of DHI, SVQ, and ABC are reliable and valid questionnaires for assessing the impact of dizziness on the quality of life of Italian patients with peripheral or central vestibular deficit. PMID:29066999

Complaints to the Norwegian System of Patient Injury Compensation 2001-14 following nerve blockade.

PubMed

Kongsgaard, Ulf E; Fischer, Kristine; Pedersen, Tor Erlend; Bukholm, Ida Rashida Khan; Warncke, Torhild

2016-12-01

There has been a steady increase in cases reported to the Norwegian System of Patient Injury Compensation (NPE). We wished to look into what might characterise those cases of central and peripheral nerve blockade for anaesthesia that led to compensation claims. Cases with codes for central and peripheral blockade within the field of anaesthesiology were retrieved from the NPE database for the period 2001 – 14. The cases were evaluated on the basis of variables including sex, age, type of anaesthesia, diagnosis, type of injury, site of injury, damages received, and written descriptions of treatment and injury. The expert reports were anonymised and reviewed in detail. A total of 339 patient compensation claims relating to nerve blockade were identified, of which 149 concerned spinal anaesthesia, 142 epidural anaesthesia, 21 combined spinal and epidural anaesthesia and 27 peripheral nerve blockade. The group consisted of 236 women and 103 men, and the average age was 46 years. The 339 cases comprised 0.8 % of all cases reported to the NPE in this period. A total of 107 claims resulted in compensation. Eighty-two million Norwegian kroner were paid out in total. Peripheral and central nerve blockade accounts for only a small proportion of cases handled by the NPE. Only one in three applicants had their claim upheld, but when claims were upheld, the injuries were often severe and led to substantial pay-outs.

Atf3 mutant mice show reduced axon regeneration and impaired regeneration-associated gene induction after peripheral nerve injury

PubMed Central

Gey, Manuel; Wanner, Renate; Schilling, Corinna; Pedro, Maria T.; Sinske, Daniela

2016-01-01

Axon injury in the peripheral nervous system (PNS) induces a regeneration-associated gene (RAG) response. Atf3 (activating transcription factor 3) is such a RAG and ATF3's transcriptional activity might induce ‘effector’ RAGs (e.g. small proline rich protein 1a (Sprr1a), Galanin (Gal), growth-associated protein 43 (Gap43)) facilitating peripheral axon regeneration. We provide a first analysis of Atf3 mouse mutants in peripheral nerve regeneration. In Atf3 mutant mice, facial nerve regeneration and neurite outgrowth of adult ATF3-deficient primary dorsal root ganglia neurons was decreased. Using genome-wide transcriptomics, we identified a neuropeptide-encoding RAG cluster (vasoactive intestinal peptide (Vip), Ngf, Grp, Gal, Pacap) regulated by ATF3. Exogenous administration of neuropeptides enhanced neurite growth of Atf3 mutant mice suggesting that these molecules might be effector RAGs of ATF3's pro-regenerative function. In addition to the induction of growth-promoting molecules, we present data that ATF3 suppresses growth-inhibiting molecules such as chemokine (C-C motif) ligand 2. In summary, we show a pro-regenerative ATF3 function during PNS nerve regeneration involving transcriptional activation of a neuropeptide-encoding RAG cluster. ATF3 is a general injury-inducible factor, therefore ATF3-mediated mechanisms identified herein might apply to other cell and injury types. PMID:27581653

Peripheral axotomy of the rat mandibular trigeminal nerve leads to an increase in VIP and decrease of other primary afferent neuropeptides in the spinal trigeminal nucleus.

PubMed

Atkinson, M E; Shehab, S A

1986-12-01

In the vasoactive intestinal polypeptide (VIP)-rich lumbosacral spinal cord, VIP increases at the expense of other neuropeptides after primary sensory nerve axotomy. This study was undertaken to ascertain whether similar changes occur in peripherally axotomised cranial sensory nerves. VIP immunoreactivity increased in the terminal region of the mandibular nerve in the trigeminal nucleus caudalis following unilateral section of the sensory root of the mandibular trigeminal nerve at the foramen orale. Other primary afferent neuropeptides (substance P, cholecystokinin and somatostatin) were depleted and fluoride-resistant acid phosphatase activity was abolished in the same circumscribed areas of the nucleus caudalis. The rise in VIP and depletion of other markers began 4 days postoperatively and was maximal by 10 days, these levels remaining unchanged up to 1 year postoperatively. VIP-immunoreactive cell bodies were absent from trigeminal ganglia from the unoperated side but small and medium cells stained intensely in the ganglia of the operated side after axotomy. These observations indicate that increase of VIP in sensory nerve terminals is a general phenomenon occurring in both cranial and spinal sensory terminal areas. The intense VIP immunoreactivity in axotomised trigeminal ganglia suggests that the increased levels of VIP in the nucleus caudalis are of peripheral origin, indicating a change in expression of neuropeptides within primary afferent neurons following peripheral axotomy.

Partially covered versus uncovered self-expandable nitinol stents with anti-migration properties for the palliation of malignant distal biliary obstruction: A randomized controlled trial.

PubMed

Yang, Min Jae; Kim, Jin Hong; Yoo, Byung Moo; Hwang, Jae Chul; Yoo, Jun Hwan; Lee, Ki Seong; Kang, Joon Koo; Kim, Soon Sun; Lim, Sun Gyo; Shin, Sung Jae; Cheong, Jae Youn; Lee, Kee Myung; Lee, Kwang Jae; Cho, Sung Won

2015-01-01

Covered self-expandable metal stents (SEMSs) are increasingly used as alternatives to uncovered SEMSs for the palliation of inoperable malignant distal biliary obstruction to counteract tumor ingrowth. We aimed to compare the outcomes of partially covered and uncovered SEMSs with identical mesh structures and anti-migration properties, such as low axial force and flared ends. One hundred and three patients who were diagnosed with inoperable malignant distal biliary obstruction between January 2006 and August 2013 were randomly assigned to either the partially covered (n = 51) or uncovered (n = 52) SEMS group. There were no significant differences in the cumulative stent patency, overall patient survival, stent dysfunction-free survival and overall adverse events, including pancreatitis and cholecystitis, between the two groups. Compared to the uncovered group, stent migration (5.9% vs. 0%, p = 0.118) and tumor overgrowth (7.8% vs. 1.9%, p = 0.205) were non-significantly more frequent in the partially covered group, whereas tumor ingrowth showed a significantly higher incidence in the uncovered group (5.9% vs. 19.2%, p = 0.041). Stent migration in the partially covered group occurred only in patients with short stenosis of the utmost distal bile duct (two in ampullary cancer, one in bile duct cancer), and did not occur in any patients with pancreatic cancer. For the palliation of malignant distal biliary obstruction, endoscopic placement of partially covered SEMSs with anti-migration designs and identical mesh structures to uncovered SEMSs failed to prolong cumulative stent patency or reduce stent migration.

Automatic treatment planning facilitates fast generation of high-quality treatment plans for esophageal cancer.

PubMed

Hansen, Christian Rønn; Nielsen, Morten; Bertelsen, Anders Smedegaard; Hazell, Irene; Holtved, Eva; Zukauskaite, Ruta; Bjerregaard, Jon Kroll; Brink, Carsten; Bernchou, Uffe

2017-11-01

The quality of radiotherapy planning has improved substantially in the last decade with the introduction of intensity modulated radiotherapy. The purpose of this study was to analyze the plan quality and efficacy of automatically (AU) generated VMAT plans for inoperable esophageal cancer patients. Thirty-two consecutive inoperable patients with esophageal cancer originally treated with manually (MA) generated volumetric modulated arc therapy (VMAT) plans were retrospectively replanned using an auto-planning engine. All plans were optimized with one full 6MV VMAT arc giving 60 Gy to the primary target and 50 Gy to the elective target. The planning techniques were blinded before clinical evaluation by three specialized oncologists. To supplement the clinical evaluation, the optimization time for the AU plan was recorded along with DVH parameters for all plans. Upon clinical evaluation, the AU plan was preferred for 31/32 patients, and for one patient, there was no difference in the plans. In terms of DVH parameters, similar target coverage was obtained between the two planning methods. The mean dose for the spinal cord increased by 1.8 Gy using AU (p = .002), whereas the mean lung dose decreased by 1.9 Gy (p < .001). The AU plans were more modulated as seen by the increase of 12% in mean MUs (p = .001). The median optimization time for AU plans was 117 min. The AU plans were in general preferred and showed a lower mean dose to the lungs. The automation of the planning process generated esophageal cancer treatment plans quickly and with high quality.

Stereotactic body radiation therapy for palliative management of pancreatic adenocarcinoma in elderly and medically inoperable patients.

PubMed

Ryan, John F; Rosati, Lauren M; Groot, Vincent P; Le, Dung T; Zheng, Lei; Laheru, Daniel A; Shin, Eun J; Jackson, Juan; Moore, Joseph; Narang, Amol K; Herman, Joseph M

2018-03-27

Stereotactic body radiation therapy (SBRT) represents a promising treatment option for patients with localized pancreatic ductal adenocarcinoma (PDAC) who cannot tolerate surgical therapy. We retrospectively reviewed the records of patients with localized PDAC treated with SBRT at our institution between 2010 and 2016 to identify patients deemed medically inoperable due to poor performance status, advanced age, and/or comorbid conditions. Overall survival (OS), progression-free survival (PFS), and local progression-free survival (LPFS) were estimated using Kaplan-Meier curves. Twenty-nine patients were included. Median age was 74 (IQR 68-79). Thirteen patients (45%) had an Eastern Cooperative Oncology Group performance status of 2. Six patients (19%) had chronic obstructive pulmonary disease, 9 (31%) had cardiovascular disease, and 17 (58%) had diabetes mellitus. SBRT was delivered over 5 fractions to a median dose of 28 Gy (IQR, 25-33). Twenty-two patients (76%) received induction chemotherapy prior to SBRT, and 9 (31%) received maintenance chemotherapy after SBRT. Median OS was 13 months from diagnosis. Median OS and PFS were 8 and 6 months from SBRT, respectively. Six and 12-month LPFS rates were 91% and 78%, respectively. Patients receiving induction chemotherapy had superior survival from diagnosis than those who did not (14 vs. 7 months, p = 0.01). Three patients (10%) experienced acute grade ≥3 toxicity, and 1 patient (4%) experienced grade ≥3 late toxicity. Symptom relief was achieved at three-month follow-up in 8 of 11 patients (73%) experiencing abdominal pain. These results suggest SBRT may be safe and effective for patients who cannot tolerate surgery.

Peripheral venous catheter insertion simulation training: A randomized controlled trial comparing performance after instructor-led teaching versus peer-assisted learning.

PubMed

Pelloux, Sophie; Grégoire, Arnaud; Kirmizigul, Patrice; Maillot, Sandrine; Bui-Xuan, Bernard; Llorca, Guy; Boet, Sylvain; Lehot, Jean-Jacques; Rimmelé, Thomas

2017-12-01

Peripheral venous catheter insertion is a procedural skill that every medical student should master. Training is often limited to a small number of students and is poorly evaluated. The objective of this study was to evaluate the performance of peer-assisted learning in comparison to instructor-led teaching for peripheral venous catheter insertion training. Students were randomized to the control group attending a traditional instructor-led training session (slideshow and demonstration by an anesthetist instructor, followed by training on a procedural simulator) or to the test group attending a peer-assisted training session (slideshow and demonstration video-recorded by the same instructor, followed by training on a procedural simulator). The primary endpoint was the performance of peripheral venous catheter insertion, assessed on procedural simulator one week later by blinded experts using a standardized 20-item grid. Students self-evaluated their confidence levels using a numeric 10-point scale. Eighty-six students were included, 73 of whom attended the assessment session. The median performance score was 12/20 [8-15] in the instructor-led teaching group versus 13/20 [11-15] in the peer-assisted learning group (P=0.430). Confidence levels improved significantly after the assessment session and were significantly higher in the peer-assisted learning group (7.6/10 [7.0-8.0] versus 7.0/10 [5.0-8.0], P=0.026). Peer-assisted learning is effective for peripheral venous catheter insertion training and can be as effective as instructor-led teaching. Given the large number of students to train, this finding is important for optimizing the cost-effectiveness of peripheral venous catheter insertion training. Copyright © 2017 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy.

PubMed

Köşkderelioğlu, Aslı; Ortan, Pınar; Ari, Alpay; Gedizlioğlu, Muhteşem

2016-03-01

To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type.

Multimodal Retinal Imaging in Incontinentia Pigmenti Including Optical Coherence Tomography Angiography: Findings From an Older Cohort With Mild Phenotype.

PubMed

Liu, Tin Yan Alvin; Han, Ian C; Goldberg, Morton F; Linz, Marguerite O; Chen, Connie J; Scott, Adrienne W

2018-05-01

Incontinentia pigmenti (IP) is a rare, X-linked dominant disease with potentially severe ocular complications that predominantly affect the peripheral retina. However, little is known about its effects on the macula. To describe the structural and vascular abnormalities observed in the maculas of patients with IP and to correlate these findings with peripheral pathologies. Prospective, cross-sectional study at Wilmer Eye Institute, Johns Hopkins University. Five participants with a clinical diagnosis of IP were included and underwent multimodal imaging with ultra-wide-field fluorescein angiography (FA), spectral-domain optical coherence tomography (OCT), and OCT angiography. The structural and vascular abnormalities observed on spectral-domain OCT and OCT angiography and their correlation with peripheral pathologies seen on ultra-wide-field FA. A total of 9 eyes from 5 patients (median age, 20.5 years; range, 8.4-54.2 years) were included. Median Snellen visual acuity was 20/32 (range, 20/16 to 20/63). ultra-wide-field FA-identified retinal vascular abnormalities in all 7 eyes in which FA was obtained. These abnormalities included microaneurysms, areas of nonperfusion, and vascular anastomoses, most of which were peripheral to the standard view of 30° FA with peripheral sweeps. Structural abnormalities were observed in 6 eyes on spectral-domain OCT, including inner retinal thinning and irregularities in the outer plexiform layer. Optical coherence tomography angiography abnormalities were noted in all 9 eyes, including decreased vascular density, abnormal vascular loops, and flow loss in the superficial and deep plexuses, which corresponded to areas of retinal thinning on spectral-domain OCT. Although our study is limited by the small sample size, the findings suggest that multimodal imaging is useful for detecting structural and vascular abnormalities that may not be apparent on ophthalmoscopy in patients with IP. Macular pathologies, especially a decrease in vascular density on OCT angiography, are common. Further studies are needed to characterize further the association between macular and peripheral abnormalities in patients with IP.

Central or Peripheral Delivery of an Adenosine A1 Receptor Agonist Improves Mechanical Allodynia in a Mouse Model of Painful Diabetic Neuropathy

PubMed Central

Katz, N. K.; Ryals, J. M.; Wright, D. E.

2014-01-01

Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8-weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N6-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of painful diabetic neuropathy. Moreover, central and peripheral activation of A1R significantly improved mechanical sensitivity, warranting further investigation into this important antinociceptive pathway as a novel therapeutic option for the treatment of painful diabetic neuropathy. PMID:25451280

Screening for Electrophysiological Abnormalities in Chronic Hepatitis C Infection: Peripheral Neuropathy and Optic Neuropathy

PubMed Central

KÖŞKDERELİOĞLU, Aslı; ORTAN, Pınar; ARI, Alpay; GEDİZLİOĞLU, Muhteşem

2016-01-01

Introduction To investigate the existence of peripheral and optic neuropathies in asymptomatic individuals with hepatitis C infection. Methods Thirty consecutive patients who were followed in a hepatitis C outpatient clinic were recruited for electrophysiological evaluation together with 30 age- and gender-compatible healthy controls. All patients had a detailed neurological examination. The information regarding the disease duration and management with interferons were collected. Nerve conduction studies and visual evoked potentials (VEP) were recorded in all subjects. The results of the patient and control groups were statistically compared. Results Of the patients with hepatitis C infection, 16 were females and 14 males. The mean age was 57.5 years, and the average disease duration was 6.43 years. The P100 latencies in the patient group were within normal limits, while the amplitudes were meaningfully small by comparison with the controls. There were some abnormalities in the nerve conduction studies of 15 patients. Sensorial neuropathy was detected in two patients, sensorimotor polyneuropathy in four, carpal tunnel syndrome in seven, and carpal tunnel syndrome and sensorimotor polyneuropathy as comorbid states in another two patients. The nerve conduction studies and VEP parameters were entirely normal in the control group. Conclusion Hepatitis C-related neurological abnormalities may occur both in the central and peripheral nervous system. Mononeuritis multiplex, sensorial axonal neuropathy, and multiple mononeuropathies are some of the presentations of the peripheral nervous system involvement. The mode of infection is considered to be via vasculitic mechanisms. In addition, optic neuropathy is a known complication of interferon treatment. Autoantibodies, cytokines, chemokines, and cryoglobulins are accused to play roles in the pathogenesis. In this study, we investigated the involvement of the peripheral nervous system and optic nerves in a group of patients with hepatitis C. The results were in favor of peripheral nerve injury of various types and optic neuropathy of the axonal type. PMID:28360761

Gene expression patterns in peripheral blood leukocytes in patients with recurrent ciguatera fish poisoning: Preliminary studies.

PubMed

Lopez, Maria-Cecilia; Ungaro, Ricardo F; Baker, Henry V; Moldawer, Lyle L; Robertson, Alison; Abbott, Margaret; Roberts, Sparkle M; Grattan, Lynn M; Morris, J Glenn

2016-07-01

Ciguatera fish poisoning (ciguatera) is a common clinical syndrome in areas where there is dependence on tropical reef fish for food. A subset of patients develops recurrent and, in some instances, chronic symptoms, which may result in substantial disability. To identify possible biomarkers for recurrent/chronic disease, and to explore correlations with immune gene expression, peripheral blood leukocyte gene expression in 10 ciguatera patients (7 recurrent and 3 acute) from the U.S. Virgin Islands, and 5 unexposed Florida controls were evaluated. Significant differences in gene expression were noted when comparing ciguatera patients and controls; however, it was not possible to differentiate between patients with acute and recurrent disease, possibly due to the small sample sizes involved. Copyright © 2016 Elsevier B.V. All rights reserved.

Reversal learning enhanced by lysergic acid diethylamide (LSD)

PubMed Central

King, A.R.; Martin, I.L.; Arabella Melville, K.

1974-01-01

1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 μg/kg) consistently facilitated learning of a brightness discrimination reversal. 2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 μg/kg). 3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 μg/kg. PMID:4458849

Reversal learning enhanced by lysergic acid diethylamide (LSD): concomitant rise in brain 5-hydroxytryptamine levels.

PubMed

King, A R; Martin, I L; Melville, K A

1974-11-01

1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 mug/kg) consistently facilitated learning of a brightness discrimination reversal.2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 mug/kg).3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 mug/kg.

A new small molecule inhibitor of soluble guanylate cyclase

PubMed Central

Mota, Filipa; Gane, Paul; Hampden-Smith, Kathryn; Allerston, Charles K.; Garthwaite, John; Selwood, David L.

2015-01-01

Soluble guanylate cyclase (sGC) is a haem containing enzyme that regulates cardiovascular homeostasis and multiple mechanisms in the central and peripheral nervous system. Commonly used inhibitors of sGC activity act through oxidation of the haem moiety, however they also bind haemoglobin and this limits their bioavailability for in vivo studies. We have discovered a new class of small molecule inhibitors of sGC and have characterised a compound designated D12 (compound 10) which binds to the catalytic domain of the enzyme with a KD of 11 μM in a SPR assay. PMID:26264842

Analysis of the "endocannabinoidome" in peripheral tissues of obese Zucker rats.

PubMed

Iannotti, F A; Piscitelli, F; Martella, A; Mazzarella, E; Allarà, M; Palmieri, V; Parrella, C; Capasso, R; Di Marzo, V

2013-08-01

The endocannabinoid system (ECS) represents one of the major determinants of metabolic disorders. We investigated potential changes in the endogenous levels of anandamide (AEA), 2-arachidonoylglycerol (2-AG), N-oleoylethanolamine (OEA) and N-palmitoylethanolamine (PEA) in some peripheral organs and tissues of obese Zucker(fa/fa) and lean Zucker(fa/+) rats by qPCR, liquid chromatography mass spectrometry, western blot and enzymatic activity assays. At 10-12 weeks of age AEA levels were significantly lower in BAT, small intestine and heart and higher in soleus of Zucker(fa/fa) rats. In this tissue, also the expression of CB1 receptors was higher. By contrast in Zucker(fa/fa) rats, 2-AG levels were changed (and lower) solely in the small and large intestine. Finally, in Zucker(fa/fa), PEA levels were unchanged, whereas OEA was slightly lower in BAT, and higher in the large intestine. Interestingly, these differences were accompanied by differential alterations of the genes regulating ECS tone. In conclusion, the levels of endocannabinoids are altered during obesity in a way partly correlating with changes of the genes related to their metabolism and activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

Position-Specific HIV Risk in a Large Network of Homeless Youths

PubMed Central

Barman-Adhikari, Anamika; Milburn, Norweeta G.; Monro, William

2012-01-01

Objectives. We examined interconnections among runaway and homeless youths (RHYs) and how aggregated network structure position was associated with HIV risk in this population. Methods. We collected individual and social network data from 136 RHYs. On the basis of these data, we generated a sociomatrix, accomplished network visualization with a “spring embedder,” and examined k-cores. We used multivariate logistic regression models to assess associations between peripheral and nonperipheral network position and recent unprotected sexual intercourse. Results. Small numbers of nominations at the individual level aggregated into a large social network with a visible core, periphery, and small clusters. Female youths were more likely to be in the core, as were youths who had been homeless for 2 years or more. Youths at the periphery were less likely to report unprotected intercourse and had been homeless for a shorter duration. Conclusions. HIV risk was a function of risk-taking youths' connections with one another and was associated with position in the overall network structure. Social network–based prevention programs, young women's housing and health programs, and housing-first programs for peripheral youths could be effective strategies for preventing HIV among this population. PMID:22095350

Cytotoxic activity against human neuroblastoma and melanoma cells mediated by IgM antibodies derived from peripheral blood of healthy donors.

PubMed

Devarapu, Satish Kumar; Mamidi, Srinivas; Plöger, Frank; Dill, Othmar; Blixt, Ola; Kirschfink, Michael; Schwartz-Albiez, Reinhard

2016-06-15

A small percentage of healthy donors identified in the Western population carry antibodies in their peripheral blood which convey cytotoxic activity against certain human melanoma and neuroblastoma cell lines. We measured the cytotoxic activity of sera and plasmas from healthy donors on the human neuroblastoma cell line Kelly and various melanoma cell lines. Antibodies of IgM isotype, presumably belonging to the class of naturally occurring antibodies, exerted cytotoxic activity in a complement-dependent fashion. Apart from complement-dependent tumor cell lysis, we observed C3 opsonization in all tumor cell lines upon treatment with cytotoxic plasmas. Cell lines tested primarily expressed membrane complement regulatory proteins (mCRP) CD46, CD55 and CD59 to various extents. Blocking of mCRPs by monoclonal antibodies enhanced cell lysis and opsonization, though some melanoma cells remained resistant to complement attack. Epitopes recognized by cytotoxic antibodies were represented by gangliosides such as GD2 and GD3, as evidenced by cellular sialidase pretreatment and enhanced expression of distinct gangliosides. It remains to be clarified why only a small fraction of healthy persons carry these antitumor cytotoxic antibodies. © 2016 UICC.

Chloride channel blockers promote relaxation of TEA-induced contraction in airway smooth muscle

PubMed Central

Yim, Peter D.; Gallos, George; Perez-zoghbi, Jose F.; Trice, Jacquelyn; Zhang, Yi; Siviski, Matthew; Sonett, Joshua; Emala, Charles W.

2014-01-01

Enhanced airway smooth muscle (ASM) contraction is an important component in the pathophysiology of asthma. We have shown that ligand gated chloride channels modulate ASM contractile tone during the maintenance phase of an induced contraction, however the role of chloride flux in depolarization-induced contraction remains incompletely understood. To better understand the role of chloride flux under these conditions, muscle force (human ASM, guinea pig ASM), peripheral small airway luminal area (rat ASM) and airway smooth muscle plasma membrane electrical potentials (human cultured ASM) were measured. We found ex vivo guinea pig airway rings, human ASM strips and small peripheral airways in rat lungs slices relaxed in response to niflumic acid following depolarization-induced contraction induced by K+ channel blockade with tetraethylammonium chloride (TEA). In isolated human airway smooth muscle cells TEA induce depolarization as measured by a fluorescent indicator or whole cell patch clamp and this depolarization was reversed by niflumic acid. These findings demonstrate that ASM depolarization induced contraction is dependent on chloride channel activity. Targeting of chloride channels may be a novel approach to relax hypercontractile airway smooth muscle in bronchoconstrictive disorders. PMID:24662476

Brain Metastasis in Bone and Soft Tissue Cancers: A Review of Incidence, Interventions, and Outcomes

PubMed Central

Shweikeh, Faris; Bukavina, Laura; Saeed, Kashif; Sarkis, Reem; Suneja, Aarushi; Sweiss, Fadi; Drazin, Doniel

2014-01-01

Bone and soft tissue malignancies account for a small portion of brain metastases. In this review, we characterize their incidence, treatments, and prognosis. Most of the data in the literature is based on case reports and small case series. Less than 5% of brain metastases are from bone and soft tissue sarcomas, occurring most commonly in Ewing's sarcoma, malignant fibrous tumors, and osteosarcoma. Mean interval from initial cancer diagnosis to brain metastasis is in the range of 20–30 months, with most being detected before 24 months (osteosarcoma, Ewing sarcoma, chordoma, angiosarcoma, and rhabdomyosarcoma), some at 24–36 months (malignant fibrous tumors, malignant peripheral nerve sheath tumors, and alveolar soft part sarcoma), and a few after 36 months (chondrosarcoma and liposarcoma). Overall mean survival ranges between 7 and 16 months, with the majority surviving < 12 months (Ewing's sarcoma, liposarcoma, malignant fibrous tumors, malignant peripheral nerve sheath tumors, angiosarcoma and chordomas). Management is heterogeneous involving surgery, radiosurgery, radiotherapy, and chemotherapy. While a survival advantage may exist for those given aggressive treatment involving surgical resection, such patients tended to have a favorable preoperative performance status and minimal systemic disease. PMID:24757391

Donor Peripheral Stem Cell Transplant in Treating Patients With Hematolymphoid Malignancies

ClinicalTrials.gov

2016-11-17

Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Socioeconomic Deprivation and the Incidence of 12 Cardiovascular Diseases in 1.9 Million Women and Men: Implications for Risk Prediction and Prevention

PubMed Central

Pujades-Rodriguez, Mar; Timmis, Adam; Stogiannis, Dimitris; Rapsomaniki, Eleni; Denaxas, Spiros; Shah, Anoop; Feder, Gene; Kivimaki, Mika; Hemingway, Harry

2014-01-01

Background Recent experimental evidence suggests that socioeconomic characteristics of neighbourhoods influence cardiovascular health, but observational studies which examine deprivation across a wide range of cardiovascular diseases (CVDs) are lacking. Methods Record-linkage cohort study of 1.93 million people to examine the association between small-area socioeconomic deprivation and 12 CVDs. Health records covered primary care, hospital admissions, a myocardial infarction registry and cause-specific mortality in England (CALIBER). Patients were aged ≥30 years and were initially free of CVD. Cox proportional hazard models stratified by general practice were used. Findings During a median follow-up of 5.5 years 114,859 people had one of 12 initial CVD presentations. In women the hazards of all CVDs except abdominal aortic aneurysm increased linearly with higher small-area socioeconomic deprivation (adjusted HR for most vs. least deprived ranged from 1.05, 95%CI 0.83–1.32 for abdominal aortic aneurysm to 1.55, 95%CI 1.42–1.70 for heart failure; I2 = 81.9%, τ2 = 0.01). In men heterogeneity was higher (HR ranged from 0.89, 95%CI 0.75–1.06 for cardiac arrest to 1.85, 95%CI 1.67–2.04 for peripheral arterial disease; I2 = 96.0%, τ2 = 0.06) and no association was observed with stable angina, sudden cardiac death, subarachnoid haemorrhage, transient ischaemic attack and abdominal aortic aneurysm. Lifetime risk difference between least and most deprived quintiles was most marked for peripheral arterial disease in women (4.3% least deprived, 5.8% most deprived) and men (4.6% least deprived, 7.8% in most deprived); but it was small or negligible for sudden cardiac death, transient ischaemic attack, abdominal aortic aneurysm and ischaemic and intracerebral haemorrhage, in both women and men. Conclusions Associations of small-area socioeconomic deprivation with 12 types of CVDs were heterogeneous, and in men absent for several diseases. Findings suggest that policies to reduce deprivation may impact more strongly on heart failure and peripheral arterial disease, and might be more effective in women. PMID:25144739

Percutaneous Image-guided Radiofrequency Ablation of Tumors in Inoperable Patients - Immediate Complications and Overall Safety.

PubMed

Sahay, Anubha; Sahay, Nishant; Kapoor, Ashok; Kapoor, Jyoti; Chatterjee, Abhishek

2016-01-01

Percutaneous destruction of cancer cells using a radiofrequency energy source has become an accepted part of the modern armamentarium for managing malignancies. Radiofrequency ablation (RFA) is a relatively novel procedure for treating recurrent and metastatic tumors. It is used for debulking tumors and as adjuvant therapy for palliative care apart from its role as a pain management tool. Its use in the third world countries is limited by various factors such as cost and expertise. In the remotest parts of India, where economic development has been slow, abject poverty with poor health care facilities advanced malignancies present a challenge to health care providers. We undertook this study to assess the safety of the percutaneous RFA tumor ablation as a therapeutic or palliative measure in patients where surgery was not possible. We observed that RFA may be an effective, alternative therapeutic modality for some inoperable tumors where other therapeutic modalities cannot be considered. Palliative and therapeutic image-guided RFAs of tumors may be the only treatment option in patients who are inoperable for a variety of reasons. To assess the safety and complications of RFA in such a patient population is important before embarking upon any interventions given their physically, mentally, and socially compromised status in a country such as India. To assess the safety of percutaneous image-guided radiofrequency tumor ablation and to note the various immediate and early complications of the intervention. This was a prospective, observational study conducted in Tata Main Hospital, Jamshedpur, Jharkhand, India. After approval by the Hospital Approval Committee all patients who consented for percutaneous RFA of their tumor admitted in the hospital were included after taking fully informed consent from patient/close relative keeping the following criteria in view. Patients who were likely to derive a direct benefit in the survival or as a palliative measure for relief in their symptoms and patients who were inoperable because of any of the following reasons: (1) Exhausted conventional treatment options, (2) technical and anatomical contraindications to conventional treatment, (3) medical comorbidities precluding surgery, (4) patient refusal, (5) recurrent tumors, and (6) advanced tumor stage. Conventional Treatment has been defined as surgical resection, radiotherapy, and/or chemotherapy, although the patient eligibility for each treatment may vary. Patients with the following were excluded: (1) Severe coagulopathy, (2) heart, renal, or liver failure, (3) lesions within 1 cm of gall bladder, hilum, bowel wall, and major blood vessels, (4) patient with any metal implant, (5) patients in sepsis, and (6) tumor adjacent to structures at risk (main bile ducts, pericardium, stomach, or bowel). The duration of procedure as well as ablation of tumor free margin was significantly related to the size of the tumor. As the size of tumor increased, duration of procedure increased significantly. A good tumor-free margin also needs to be ablated for optimum results as it prevents residual tumors and recurrences in the future. We observed that tumors sized <3.1 cm were optimal in this regard. Most common adverse event in postprocedure period was pain in and around ablation site. Post-RFA syndrome is also a common and benign self-limiting side effect. Patient counseling and proper selection of patients in the early stages of malignancy can enhance the efficacy of the procedure and patient satisfaction. Percutaneous image-guided RFA is an option in patients where most other tumor management modalities have been exhausted or rejected. RFA may not be free from side effects such as postablation syndrome, pain, and there may be other serious complications such as bleeding, but based on our observations, percutaneous image-guided RFA of tumors is a safe palliative and therapeutic treatment option.

Ultrastructural study on the retinal pigment epithelium of human embryos, with special reference to quantitative study on the development of melanin granules.

PubMed

Oguni, M; Tanaka, O; Shinohara, H; Yoshioka, T; Setogawa, T

1991-01-01

The development of the retinal pigment epithelium (RPE) was studied ultrastructurally, using 13 externally normal human embryos, Carnegie stages ranging from 13 to 23 (4-8 week of gestation). Melanosomes in the peripheral and posterior RPE were classified according to Fitzpatrick et al. The melanosome of phase I is formed from the Golgi complex and parcelled off into small vesicles. The vesicle enlarges and elongates to form an oval organelle with membranous structures in it (phase II melanosome). Subsequently, melanin deposits on the membranous structures of the melanosomes (phase III melanosomes), and the completion of this process produces a uniformly electrondense granule without discernible internal structures (phase IV melanosome). Melanosomes of phases III and IV appeared in the RPE at stage 15. As the embryonic stage advanced, the ratio of phase II melanosomes decreased and that of phase IV melanosomes increased. The number of phase III melanosomes reached a peak in the peripheral and posterior RPE at stages 15 and 18, respectively. After stage 17, the increase in melanosomes and intracellular organelles was more prominent in the posterior than in the peripheral RPE. During stages 13 and 15, gap junctions were present not only in the apical but also basal plasma membranes of the RPE. At stage 20, gap junctions in the basal plasma membrane disappeared except for the transitional areas from the RPE to the neural retina (NR). In addition, gap junctions were observed between NR and RPE only in the peripheral region at stage 20. The morphological and quantitative differences in the peripheral and posterior RPE in the embryonic period are discussed.

A novel approach to 32-channel peripheral nervous system myelin imaging in vivo, with single axon resolution.

PubMed

Grochmal, Joey; Teo, Wulin; Gambhir, Hardeep; Kumar, Ranjan; Stratton, Jo Anne; Dhaliwal, Raveena; Brideau, Craig; Biernaskie, Jeff; Stys, Peter K; Midha, Rajiv

2018-01-19

OBJECTIVE Intravital spectral imaging of the large, deeply situated nerves in the rat peripheral nervous system (PNS) has not been well described. Here, the authors have developed a highly stable platform for performing imaging of the tibial nerve in live rodents, thus allowing the capture of high-resolution, high-magnification spectral images requiring long acquisition times. By further exploiting the qualities of the topically applied myelin dye Nile red, this technique is capable of visualizing the detailed microenvironment of peripheral nerve demyelination injury and recovery, while allowing us to obtain images of exogenous Schwann cell myelination in a living animal. METHODS The authors caused doxorubicin-induced focal demyelination in the tibial nerves of 25 Thy-1 GFP rats, of which 2 subsets (n = 10 each) received either BFP-labeled SKP-SCs or SCs to the zone of injury. Prior to acquiring images of myelin recovery in these nerves, a tibial nerve window was constructed using a silicone hemitube, a fast drying silicone polymer, and a small coverslip. This construct was then affixed to a 3D-printed nerve stage, which in turn was affixed to an external fixation/microscope stage device. Myelin visualization was facilitated by the topical application of Nile red. RESULTS The authors reliably demonstrated intravital peripheral nerve myelin imaging with micron-level resolution and magnification, and minimal movement artifact. The detailed microenvironment of nerve remyelination can be vividly observed, while exogenously applied Schwann cells and skin-derived precursor Schwann cells can be seen myelinating axons. CONCLUSIONS Topically applied Nile red enables intravital study of myelin in the living rat PNS. Furthermore, the use of a tibial nerve window facilitates stable intravital peripheral nerve imaging, making possible high-definition spectral imaging with long acquisition times.

Nervous System Sensitization as a Predictor of Outcome in the Treatment of Peripheral Musculoskeletal Conditions: A Systematic Review.

PubMed

O'Leary, Helen; Smart, Keith M; Moloney, Niamh A; Doody, Catherine M

2017-02-01

Research suggests that peripheral and central nervous system sensitization can contribute to the overall pain experience in peripheral musculoskeletal (MSK) conditions. It is unclear, however, whether sensitization of the nervous system results in poorer outcomes following the treatment. This systematic review investigated whether nervous system sensitization in peripheral MSK conditions predicts poorer clinical outcomes in response to a surgical or conservative intervention. Four electronic databases were searched to identify the relevant studies. Eligible studies had a prospective design, with a follow-up assessing the outcome in terms of pain or disability. Studies that used baseline indices of nervous system sensitization were included, such as quantitative sensory testing (QST) or questionnaires that measured centrally mediated symptoms. Thirteen studies met the inclusion criteria, of which six were at a high risk of bias. The peripheral MSK conditions investigated were knee and hip osteoarthritis, shoulder pain, and elbow tendinopathy. QST parameters indicative of sensitization (lower electrical pain thresholds, cold hyperalgesia, enhanced temporal summation, lower punctate sharpness thresholds) were associated with negative outcome (more pain or disability) in 5 small exploratory studies. Larger studies that accounted for multiple confounders in design and analysis did not support a predictive relationship between QST parameters and outcome. Two studies used self-report measures to capture comorbid centrally mediated symptoms, and found higher questionnaire scores were independently predictive of more persistent pain following a total joint arthroplasty. This systematic review found insufficient evidence to support an independent predictive relationship between QST measures of nervous system sensitization and treatment outcome. Self-report measures demonstrated better predictive ability. Further high-quality prognostic research is warranted. © 2016 World Institute of Pain.

Assessing the ability of the antiangiogenic and anticytokine agent thalidomide to modulate radiation-induced lung injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anscher, Mitchell S.; Garst, Jennifer; Marks, Lawrence B.

2006-10-01

Purpose: Thalidomide has broad anticytokine properties, which might protect normal tissues in patients undergoing chemoradiotherapy. The purpose of this study was to determine the maximal tolerated dose of thalidomide when used in combination with vinorelbine plus thoracic radiotherapy. Methods and Materials: Eligible patients had inoperable Stage III non-small-cell lung cancer, a Karnofsky Performance Status {>=}70, and life expectancy {>=}6 months. Patients underwent pretreatment evaluation of lung function. Radiotherapy consisted of 66 Gy in 6.5 weeks. Vinorelbine was administered i.v. (5 mg/m{sup 2}) 3 times per week just before radiotherapy. Thalidomide was begun at 50 mg, p.o., on day 1 ofmore » chemoradiotherapy and continued once daily for 6 months. Side effects were scored using National Cancer Institute Common Toxicity Criteria. Results: Ten patients were enrolled. Of the first 6 patients, 2 developed major thrombotic events that were believed to be possibly related to thalidomide. The study was suspended and modified to require prophylactic anticoagulation. Of the last 4 patients, 2 developed dose-limiting toxicity attributable to thalidomide; both patients required a dose reduction of thalidomide to <50 mg/day. Because the drug is not available in an oral product providing <50 mg/day, the study was closed. Conclusions: The combination of thalidomide concurrently with thoracic radiotherapy and vinorelbine resulted in excessive toxicity.« less

Advances in Wilms Tumor Treatment and Biology: Progress Through International Collaboration.

PubMed

Dome, Jeffrey S; Graf, Norbert; Geller, James I; Fernandez, Conrad V; Mullen, Elizabeth A; Spreafico, Filippo; Van den Heuvel-Eibrink, Marry; Pritchard-Jones, Kathy

2015-09-20

Clinical trials in Wilms tumor (WT) have resulted in overall survival rates of greater than 90%. This achievement is especially remarkable because improvements in disease-specific survival have occurred concurrently with a reduction of therapy for large patient subgroups. However, the outcomes for certain patient subgroups, including those with unfavorable histologic and molecular features, bilateral disease, and recurrent disease, remain well below the benchmark survival rate of 90%. Therapy for WT has been advanced in part by an increasingly complex risk-stratification system based on patient age; tumor stage, histology, and volume; response to chemotherapy; and loss of heterozygosity at chromosomes 1p and 16q. A consequence of this system has been the apportionment of patients into such small subgroups that only collaboration between large international WT study groups will support clinical trials that are sufficiently powered to answer challenging questions that move the field forward. This article gives an overview of the Children's Oncology Group and International Society of Pediatric Oncology approaches to WT and focuses on four subgroups (stage IV, initially inoperable, bilateral, and relapsed WT) for which international collaboration is pressing. In addition, biologic insights resulting from collaborative laboratory research are discussed. A coordinated expansion of international collaboration in both clinical trials and laboratory science will provide real opportunity to improve the treatment and outcomes for children with renal tumors on a global level. © 2015 by American Society of Clinical Oncology.

Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

PubMed Central

Blumenthal, Laura; VandenBoom, Timothy; Melian, Edward; Peterson, Anthony; Hutchens, Kelli A.

2015-01-01

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC. PMID:26594171

Quantification of incidental mediastinal and hilar irradiation delivered during definitive stereotactic body radiation therapy for peripheral non-small cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, Kate L.; Gomez, Jorge; Nazareth, Daryl P.

2012-07-01

To determine the amount of incidental radiation dose received by the mediastinal and hilar nodes for patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT). Fifty consecutive patients with NSCLC, treated using an SBRT technique, were identified. Of these patients, 38 had a prescription dose of 60 Gy in 20-Gy fractions and were eligible for analysis. For each patient, ipsilateral upper (level 2) and lower (level 4) paratracheal, and hilar (level 10) nodal regions were contoured on the planning computed tomography (CT) images. Using the clinical treatment plan, dose and volume calculations were performed retrospectivelymore » for each nodal region. SBRT to upper lobe tumors resulted in an average total ipsilateral mean dose of between 5.2 and 7.8 Gy for the most proximal paratracheal nodal stations (2R and 4R for right upper lobe lesions, 2L and 4L for left upper lobe lesions). SBRT to lower lobe tumors resulted in an average total ipsilateral mean dose of between 15.6 and 21.5 Gy for the most proximal hilar nodal stations (10R for right lower lobe lesions, 10 l for left lower lobe lesions). Doses to more distal nodes were substantially lower than 5 Gy. The often substantial incidental irradiation, delivered during SBRT for peripheral NSCLC of the lower lobes to the most proximal hilar lymph nodes may be therapeutic for low-volume, subclinical nodal disease. Treatment of peripheral upper lobe lung tumors delivers less incidental irradiation to the paratracheal lymph nodes with lower likelihood of therapeutic benefit.« less

Development of an automated size-based filtration system for isolation of circulating tumor cells in lung cancer patients.

PubMed

Yagi, Satomi; Koh, Yasuhiro; Akamatsu, Hiroaki; Kanai, Kuninobu; Hayata, Atsushi; Tokudome, Nahomi; Akamatsu, Keiichiro; Endo, Katsuya; Nakamura, Seita; Higuchi, Masayuki; Kanbara, Hisashige; Nakanishi, Masanori; Ueda, Hiroki; Yamamoto, Nobuyuki

2017-01-01

Circulating tumor cells (CTCs), defined as tumor cells circulating in the peripheral blood of patients with solid tumors, are relatively rare. Diagnosis using CTCs is expected to help in the decision-making for precision cancer medicine. We have developed an automated microcavity array (MCA) system to detect CTCs based on the differences in size and deformability between tumor cells and normal blood cells. Herein, we evaluated the system using blood samples from non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) patients. To evaluate the recovery of CTCs, preclinical experiments were performed by spiking NSCLC cell lines (NCI-H820, A549, NCI-H23 and NCI-H441) into peripheral whole blood samples from healthy volunteers. The recovery rates were 70% or more in all cell lines. For clinical evaluation, 6 mL of peripheral blood was collected from 50 patients with advanced lung cancer and from 10 healthy donors. Cells recovered on the filter were stained. We defined CTCs as DAPI-positive, cytokeratin-positive, and CD45-negative cells under the fluorescence microscope. The 50 lung cancer patients had a median age of 72 years (range, 48-85 years); 76% had NSCLC and 20% had SCLC, and 14% were at stage III disease whereas 86% were at stage IV. One or more CTCs were detected in 80% of the lung cancer patients (median 2.5). A comparison of the CellSearch system with our MCA system, using the samples from NSCLC patients, confirmed the superiority of our system (median CTC count, 0 versus 11 for CellSearch versus MCA; p = 0.0001, n = 17). The study results suggest that our MCA system has good clinical potential for diagnosing CTCs in lung cancer.

Computed Tomography–Guided Interstitial High-Dose-Rate Brachytherapy in Combination With Regional Positive Lymph Node Intensity-Modulated Radiation Therapy in Locally Advanced Peripheral Non–Small Cell Lung Cancer: A Phase 1 Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xiang, Li; Zhang, Jian-wen; Lin, Sheng

2015-08-01

Purpose: To assess the technical safety, adverse events, and efficacy of computed tomography (CT)-guided interstitial high-dose-rate (HDR) brachytherapy in combination with regional positive lymph node intensity modulated radiation therapy in patients with locally advanced peripheral non–small cell lung cancer (NSCLC). Methods and Materials: Twenty-six patients with histologically confirmed NSCLC were enrolled in a prospective, officially approved phase 1 trial. Primary tumors were treated with HDR brachytherapy. A single 30-Gy dose was delivered to the 90% isodose line of the gross lung tumor volume. A total dose of at least 70 Gy was administered to the 95% isodose line of the planningmore » target volume of malignant lymph nodes using 6-MV X-rays. The patients received concurrent or sequential chemotherapy. We assessed treatment efficacy, adverse events, and radiation toxicity. Results: The median follow-up time was 28 months (range, 7-44 months). There were 3 cases of mild pneumothorax but no cases of hemothorax, dyspnea, or pyothorax after the procedure. Grade 3 or 4 acute hematologic toxicity was observed in 5 patients. During follow-up, mild fibrosis around the puncture point was observed on the CT scans of 2 patients, but both patients were asymptomatic. The overall response rates (complete and partial) for the primary mass and positive lymph nodes were 100% and 92.3%, respectively. The 1-year and 2-year overall survival (OS) rates were 90.9% and 67%, respectively, with a median OS of 22.5 months. Conclusion: Our findings suggest that HDR brachytherapy is safe and feasible for peripheral locally advanced NSCLC, justifying a phase 2 clinical trial.« less

The safe zone for hip arthroscopy: a cadaveric assessment of central, peripheral, and lateral compartment portal placement.

PubMed

Robertson, William J; Kelly, Bryan T

2008-09-01

This study evaluated 11 arthroscopic portals (4 central, 4 peripheral, and 3 peritrochanteric) with regard to their proximity to neurovascular structures and the extra-articular path taken before entering their intended compartments. We established 11 standard portals in 10 cadaveric hips, under arthroscopic and fluoroscopic visualization, using 3/16-inch Steinmann pins. Each hip was dissected, and the relation of the pins to the pertinent anatomy was recorded to the nearest 1 mm. Only 2 of the 11 portals, the anterior and midanterior portals, came within 2 cm of a neurovascular structure before entering their respective compartments. The anterior portal placed the lateral femoral cutaneous nerve at risk, lying at a mean of 15.4 mm (range, 1 to 28 mm) away. The midanterior portal lies a mean of 19.2 mm (range, 5 to 42 mm) from the ascending branch of the lateral circumflex femoral artery. In addition, a small terminal branch of this artery courses a mean of 14.7 mm (range, 2 to 33 mm) and 10.1 mm (range, 1 to 23 mm) from the anterior portal and midanterior portal, respectively. This study showed that 11 arthroscopic portals can be safely inserted into the central, peripheral, and peritrochanteric compartments of the hip. The midanterior and anterior portals pass in close proximity to a small terminal branch of the ascending lateral circumflex femoral artery. The greatest risk still comes from the proximity of the anterior portal to the lateral femoral cutaneous nerve. However, a slightly more lateral location seems to provide substantial benefits. This study investigated 11 arthroscopic hip portals inserted in a standardized fashion. This knowledge should help surgeons place the necessary portals both safely and accurately.

Noninvasive computed tomography-guided marking technique for peripheral pulmonary nodules

PubMed Central

Matsuura, Yosuke; Nakao, Masayuki; Ichinose, Junji; Nakagawa, Ken; Okumura, Sakae

2016-01-01

Background Identification of the exact location of small peripheral pulmonary nodules during thoracoscopic wedge resection (TWR) is crucial. We describe a new method of computed tomography (CT)-guided marking without puncturing the visceral pleura (VP) for minimally palpable pulmonary nodules. Methods Preoperative CT scans were performed 1 day before TWR with the patient in the lateral decubitus position. Under CT guidance, we marked the skin over the pulmonary nodule. During TS, an indwelling catheter was inserted perpendicular to the marked skin surface and put a mark with gentian violet (Pyoktanin blue®, Wako Pure Chemical Industries, Osaka, Japan) onto the VP. We palpated the nodules near the mark(s) and performed TWR. Results Between October 2012 and April 2016, we performed CT-guided marking in 54 patients (24 males and 30 females, median age 65 years). Cases included 39 primary lung cancers, 10 metastatic lung tumors, and 5 benign tumors. The mean diameter of the nodules was 10 mm (range, 3–26 mm), and the mean distance of the nodule from the VP was 4 mm (range, 0–17 mm). The mean time of intraoperative marking was 3.5 min (range, 1–4.5 min). The mean distance from the nodule to the marking point was 7.0 mm (range, 0–30 mm). We were able to identify the location of the nodule using this procedure in 53 patients (98%). Hematoma of the chest wall after marking was observed in one patient. There were no other complications. Conclusions This marking technique is a simple, economic, and effective procedure to locate small peripheral pulmonary nodules during TWR. PMID:28066668

The influence of artificial scotomas on eye movements during visual search.

PubMed

Cornelissen, Frans W; Bruin, Klaas J; Kooijman, Aart C

2005-01-01

Fixation durations are normally adapted to the difficulty of the foveal analysis task. We examine to what extent artificial central and peripheral visual field defects interfere with this adaptation process. Subjects performed a visual search task while their eye movements were registered. The latter were used to drive a real-time gaze-dependent display that was used to create artificial central and peripheral visual field defects. Recorded eye movements were used to determine saccadic amplitude, number of fixations, fixation durations, return saccades, and changes in saccade direction. For central defects, although fixation duration increased with the size of the absolute central scotoma, this increase was too small to keep recognition performance optimal, evident from an associated increase in the rate of return saccades. Providing a relatively small amount of visual information in the central scotoma did substantially reduce subjects' search times but not their fixation durations. Surprisingly, reducing the size of the tunnel also prolonged fixation duration for peripheral defects. This manipulation also decreased the rate of return saccades, suggesting that the fixations were prolonged beyond the duration required by the foveal task. Although we find that adaptation of fixation duration to task difficulty clearly occurs in the presence of artificial scotomas, we also find that such field defects may render the adaptation suboptimal for the task at hand. Thus, visual field defects may not only hinder vision by limiting what the subject sees of the environment but also by limiting the visual system's ability to program efficient eye movements. We speculate this is because of how visual field defects bias the balance between saccade generation and fixation stabilization.

Developmental visual perception deficits with no indications of prosopagnosia in a child with abnormal eye movements.

PubMed

Gilaie-Dotan, Sharon; Doron, Ravid

2017-06-01

Visual categories are associated with eccentricity biases in high-order visual cortex: Faces and reading with foveally-biased regions, while common objects and space with mid- and peripherally-biased regions. As face perception and reading are among the most challenging human visual skills, and are often regarded as the peak achievements of a distributed neural network supporting common objects perception, it is unclear why objects, which also rely on foveal vision to be processed, are associated with mid-peripheral rather than with a foveal bias. Here, we studied BN, a 9 y.o. boy who has normal basic-level vision, abnormal (limited) oculomotor pursuit and saccades, and shows developmental object and contour integration deficits but with no indication of prosopagnosia. Although we cannot infer causation from the data presented here, we suggest that normal pursuit and saccades could be critical for the development of contour integration and object perception. While faces and perhaps reading, when fixated upon, take up a small portion of central visual field and require only small eye movements to be properly processed, common objects typically prevail in mid-peripheral visual field and rely on longer-distance voluntary eye movements as saccades to be brought to fixation. While retinal information feeds into early visual cortex in an eccentricity orderly manner, we hypothesize that propagation of non-foveal information to mid and high-order visual cortex critically relies on circuitry involving eye movements. Limited or atypical eye movements, as in the case of BN, may hinder normal information flow to mid-eccentricity biased high-order visual cortex, adversely affecting its development and consequently inducing visual perceptual deficits predominantly for categories associated with these regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Gynecomastia due to hormone therapy for advanced prostate cancer: a report of ten surgically treated cases and a review of treatment options.

PubMed

Prezioso, Domenico; Piccirillo, Giuseppe; Galasso, Raffaele; Altieri, Vincenzo; Mirone, Vincenzo; Lotti, Tullio

2004-01-01

Gynecomastia is an abnormal increase in the volume of the male breast that is generally considered to be due to an increased estrogen/androgen ratio. Pathological causes of gynecomastia include organic diseases and therapy, such as the administration of estrogens and antiandrogens, which alter the ratio of circulating hormones. Hormone therapy for prostate cancer is generally well tolerated but often accompanied by the occurrence of gynecomastia and breast pain or tenderness. The increased use of antiandrogens as monotherapy is leading to an increase in the number of patients affected by gynecomastia. Treatments are available to alleviate or prevent the development of gynecomastia, including medical treatment with antiestrogens and aromatase inhibitors. Alternatively, mastectomy with excision of the gland, liposuction or an association of the two techniques have proved to be effective. Radiation therapy may provide effective relief from the breast pain associated with gynecomastia. In this paper we show the good results of mastectomy performed with a lower semicircular periareolar incision in men suffering from gynecomastia due to antiandrogen therapy for inoperable prostate cancer. In addition, we present a review of the various techniques used for the treatment of gynecomastia. During the period from September 1998 to May 2001, 10 patients receiving hormone treatment for metastatic or inoperable prostatic cancer were selected for the study if they had breast pain and bilateral gynecomastia. Five of these patients had been offered prophylactic radiotherapy before treatment but refused, while the remaining five patients had refused radiotherapy after hormone treatment. These patients were therefore given the option of surgical treatment. Before surgery all patients underwent clinical and ultrasound examination of the breast. All surgical samples were examined histopathologically. During follow-up clinical examinations were carried out one week, one month, six months, one year and two years after surgery. The results were satisfactory in all patients especially from an aesthetic point of view. Moreover, breast pain disappeared about one week after surgery. After a follow-up of 6-36 months (average, 22.8 months) no recurrences were observed. Only a few immediate postoperative complications were recorded (hematoma in one case and seroma in another). Histological examination of the excised glands showed fibrosclerotic tissue and a small amount of fat. Surgical liposuction can be considered an effective treatment for gynecomastia, in particular in the very early stages because the breast becomes irreversibly fibrous as the disease progresses. This surgical technique is simple and effective and is therefore to be considered favorable, especially because of the very short hospitalization and the absence of complications.

Tube introducer and modified Celestin tube for use in palliative intubation of oesophagogastric neoplasms at fibreoptic endoscopy.

PubMed Central

Atkinson, M; Ferguson, R; Parker, G C

1978-01-01

A new method for palliative intubation of inoperable neoplasms at or near the cardia is described. A guidewire is passed through the stricture, which is dilated using Eder Puestow metal olive dilators. The tube to be inserted is mounted on an introducer, which grips its distal end from inside, and is slid into position along the wire under radiological control. Twenty-five patients have been intubated with one death directly resulting from the procedure. The method provides a simple and relatively safe means of relieving dysphagia and improving nutrition. Images Fig. 2 PMID:79517

Maintenance Task Data Base for Buildings: Architectural Systems

DTIC Science & Technology

1991-05-01

EXTERIOR DOOR Task Descriptin REPLACE METAL WIRE MESH PAINTD EEIO DOOR Unit of Measure: CWNT~ Fr enc of ccrence: H: i.~UU A: 15U.UU L: 160.00 Persons...5R.ULA5S:REPL.3RD FL.WD.FR.PAIN.)DL.EX .WIND0WS Unit of Measure: COURT- Freq.. enc OfOcr ee : 0.Yu A: 1.UU L: 1AiI Persons per Team: 1 Task DuRation: 0...System: EXTERIOR WINDOWS Susystem: INOPERABLE WIND)OWS Tak ecrpRtVLACE 2ND FLOOR STEEL FRAME(PAIT ETWINDOWS Unit of Measure: - JN I Frequjeng orOc ence : N

KSC-05PD-0364

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. Preparing for Return to Flight, workers at KSC walk the grounds around Launch Pad 39B looking for Foreign Object Debris, or FOD. The pad was recently refurbished and any possible debris left behind must be removed from the area prior to launch. Foreign objects that are alien to flight systems may cause material damage or may make the system or equipment inoperable, unsafe or less efficient. The Return to Flight mission STS-114 aboard Space Shuttle Discovery will carry supplies and equipment to the International Space Station. Discovery is scheduled for launch in a window from May 15 to June 3.

KSC-05PD-0366

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. Preparing for Return to Flight, workers at KSC walk the grounds around Launch Pad 39B looking for Foreign Object Debris, or FOD. The pad was recently refurbished and any possible debris left behind must be removed from the area prior to launch. Foreign objects that are alien to flight systems may cause material damage or may make the system or equipment inoperable, unsafe or less efficient. The Return to Flight mission STS-114 aboard Space Shuttle Discovery will carry supplies and equipment to the International Space Station. Discovery is scheduled for launch in a window from May 15 to June 3.

KSC-05PD-0363

NASA Technical Reports Server (NTRS)

2005-01-01

KENNEDY SPACE CENTER, FLA. Preparing for Return to Flight, workers at KSC walk the grounds around Launch Pad 39B looking for Foreign Object Debris, or FOD. The pad was recently refurbished and any possible debris left behind must be removed from the area prior to launch. Foreign objects that are alien to flight systems may cause material damage or may make the system or equipment inoperable, unsafe or less efficient. The Return to Flight mission STS-114 aboard Space Shuttle Discovery will carry supplies and equipment to the International Space Station. Discovery is scheduled for launch in a window from May 15 to June 3.

Core power and decay time limits for a disabled LOFT ECCS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Atkinson, S.A.

1978-01-09

An analysis was done to determine at what LOFT total core power (nuclear plus decay power) the ECCS could be inoperable. The criteria used for the analysis was that the maximum fuel clad temperature should not exceed 1650/sup 0/F given a loss of coolant. Calculations for natural convection cooling of the fuel by air with an inlet temperature of 580/sup 0/F determined that the limiting core power is 25 kW (discounted by 15 percent to 20 percent for potential uncertainties). Shutdown times are listed for when the LOFT ECCS can be safely bypassed or disabled.

Heat exchanger with auxiliary cooling system

DOEpatents

Coleman, John H.

1980-01-01

A heat exchanger with an auxiliary cooling system capable of cooling a nuclear reactor should the normal cooling mechanism become inoperable. A cooling coil is disposed around vertical heat transfer tubes that carry secondary coolant therethrough and is located in a downward flow of primary coolant that passes in heat transfer relationship with both the cooling coil and the vertical heat transfer tubes. A third coolant is pumped through the cooling coil which absorbs heat from the primary coolant which increases the downward flow of the primary coolant thereby increasing the natural circulation of the primary coolant through the nuclear reactor.

National Program for Inspection of Non-Federal Dams. Upper Eddy Pond Dam (VT 00231), Richelieu River Basin, Rutland, Vermont. Phase I Inspection Report.

DTIC Science & Technology

1981-04-01

crest. There Is a pond drain about 18 inches in dimeter which is reported to be Inoperable. The top of dam stor-5 age is estimated to be 51 acre-fot...related to lateral movements and/or settlement of the rubbish fill. The dumped material should be removed and the embankment regraded. The seep- age area...drain- age area. 6 5.2 DESIGN DATA No hydraulic or hydrologic design data or criteria were available. 5.3 EXPERIENCE DATA There is no evidence of recent

Emergency Flight Control Using Computer-Controlled Thrust

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Fullerton, C. Gordon; Stewart, James F.; Gilyard, Glenn B.; Conley, Joseph A.

1995-01-01

Propulsion Controlled Aircraft (PCA) systems are digital electronic control systems undergoing development to provide limited maneuvering ability through variations of individual engine thrusts in multiple-engine airplanes. Provide landing capability when control surfaces inoperable. Incorporated on existing and future airplanes that include digital engine controls, digital flight controls, and digital data buses, adding no weight for additional hardware to airplane. Possible to handle total failure of hydraulic system, depending on how surfaces respond to loss of hydraulic pressure, and broken control cables or linkages. Future airplanes incorporate data from Global Positioning System for guidance to any suitable emergency runway in world.

Successful two-stage correction of ventricular septal defect and patent ductus arteriosus in a patient with fixed pulmonary hypertension.

PubMed

Pac, Aysenur; Polat, Tugcin Bora; Vural, Kerem; Pac, Mustafa

2010-01-01

We report a case of a 6-year-old boy with fixed severe pulmonary artery hypertension secondary to a ventricular septal defect (VSD) together with a patent ductus arteriosus (PDA). As a preliminary step, PDA embolization was performed following therapy with inhaled prostacyclin over a period of 6 months. Further, the patient underwent successful surgical VSD closure. We postulate that a staged procedure with long-term prostaglandin therapy might be capable of reducing pulmonary artery resistance and permitting total correction in a patient once considered to have inoperable pulmonary arteriopathy.

Life in the cloud and freedom of speech.

PubMed

Harris, John

2013-05-01

This paper is primarily about the personal and public responsibilities of ethics and of ethicists in speaking, writing and commenting publicly about issues of ethical, political and social significance. The paper argues that any such interventions are 'willy-nilly', actually or potentially, in the public domain in ways that make any self-conscious decision about intended publics or audiences problematic. In it is argued that a famous, and hitherto useful, distinction relating to the ethical limitations on freedom of speech which we owe to John Stuart Mill may, because of the emergence of 'the cloud' have become redundant or inoperable.

The effect of omalizumab on small airway inflammation as measured by exhaled nitric oxide in moderate-to-severe asthmatic patients.

PubMed

Pasha, M Asghar; Jourd'heuil, David; Jourd'heuil, Francis; Mahon, Lori; Romero, Francisco; Feustel, Paul J; Evans, Mary; Smith, Thomas; Mitchell, Jesse; Gendapodi, Pradeep; Demeyere-Coursey, Kelly C; Townley, Robert G

2014-01-01

Measurement of fractional nitric oxide concentration in exhaled breath (FENO) is a simple, noninvasive method to evaluate eosinophilic airway inflammation. Nitric oxide (NO) arising from peripheral small airways/alveoli (alveolar NO concentration [CalvNO]) can be estimated using multiple flow rates and a two-compartment model of the airways and alveoli. Omalizumab, a monoclonal anti-IgE antibody, is approved for the treatment of allergic asthma and also has been shown to decrease FENO levels. This study investigates the effects of omalizumab, when added to an inhaled corticosteroid (ICS) ± long-acting beta-adrenergic agonist (LABA) treatment, on peripheral small airway/alveolar inflammation reflected by FENO measurements at higher flow rates. We hypothesized that compared with placebo, omalizumab would decrease CalvNO levels in asthmatic patients on ICS ± LABA. Forty-two patients with moderate-to-severe asthma were randomly assigned 2:1 to either omalizumab (n = 29) or placebo treatment (n = 13) for 16 weeks. Selection criteria included moderate-to-severe asthmatic patients on an ICS ± LABA, positive skin test to one or more perennial allergen, screening FENO of >13 ppb, and a baseline IgE of 30-700 IU/mL. FENO measured at multiple flow rates was used to calculate CalvNO over the course of 16 weeks. FENO levels decrease with increasing flow rates (p < 0.05 repeated measures ANOVA) but no differences between the placebo and treatment groups in overall CalvNO levels or in the changes of CalvNO with time were found. Omalizumab did not lower the CalvNO, which could have been caused by the initial low CalvNO in this asthmatic population. The model used may not be completely sufficient and/or sensitive enough to detect small changes in CalvNO.

A balloon-expandable sheath facilitates transfemoral TAVR in patients with peripheral vascular disease and tortuosity.

PubMed

Goldsweig, Andrew M; Faheem, Osman; Cleman, Michael W; Forrest, John K

2015-06-01

We sought to perform transcatheter aortic valve replacement (TAVR) via the transfemoral approach in patients with peripheral arterial disease (PAD), small caliber ileofemoral vessels and vascular tortuosity. For patients with increased surgical risk, TAVR is associated with a higher 1-year survival rate than surgical aortic valve replacement (SAVR). Transfemoral vascular access for TAVR results in superior outcomes versus procedures performed via other routes in terms of mortality, morbidity and healthcare economics. In many patients, the ability to safely perform the procedure via the transfemoral approach is limited by narrow, diseased and tortuous ileofemoral vasculature. We employed the SoloPath Balloon Expandable TransFemoral Access System (Terumo Med. Corp., Tokyo, Japan) to perform transfemoral TAVR in five patients with PAD, small caliber ileofemoral vessels and vascular tortuosity. We report our experience using this balloon-expandable sheath during 5 cases of transfemoral TAVR in patients with inhospitable ileofemoral vasculature of mean diameter ⩽ 5.8 mm. The unexpanded sheath's malleable structure and hydrophilic coating permitted deployment despite severe stenoses and tortuosity. Subsequent inflation to 18 Fr facilitated successful TAVR. Postprocedural angiography demonstrated no significant vascular access complications. In one case, the entire procedure was performed percutaneously, without common femoral artery surgical cutdown. The SoloPath sheath system permits transfemoral TAVR in patients with PAD small caliber ileofemoral vessels and vascular tortuosity. The transfemoral balloon-expandable sheath allowed these patients to avoid the increased morbidity and mortality risks associated with direct aortic or transapical access. © The Author(s), 2015.

Analyzing Pulse-Code Modulation On A Small Computer

NASA Technical Reports Server (NTRS)

Massey, David E.

1988-01-01

System for analysis pulse-code modulation (PCM) comprises personal computer, computer program, and peripheral interface adapter on circuit board that plugs into expansion bus of computer. Functions essentially as "snapshot" PCM decommutator, which accepts and stores thousands of frames of PCM data, sifts through them repeatedly to process according to routines specified by operator. Enables faster testing and involves less equipment than older testing systems.

Micro-buffy coats of whole blood: a method for the electron microscopic study of mononuclear cells.

PubMed

Nunes, J F; Soares, J O; Alves de Matos, A P

1979-09-01

A method for the electron microscopic study of human peripheral lymphocytes by which very small buffy coats are obtained through centrifugation of heparinized whole blood in glass or plastic microhematocrit tubes is presented. This method is time saving and efficient, yielding well preserved material and a comparatively large number of mononuclear cells (mainly lymphocytes) in each thin section.

The use of alvimopan for postoperative ileus in small and large bowel resections.

PubMed

Brady, Justin T; Dosokey, Eslam M G; Crawshaw, Benjamin P; Steele, Scott R; Delaney, Conor P

2015-01-01

Transient ileus is a normal physiologic process after surgery. When prolonged, it is an important contributor to postoperative complications, increased length of stay and increased healthcare costs. Efforts have been made to prevent and manage postoperative ileus; alvimopan is an oral, peripheral μ-opioid receptor antagonist, and the only currently US FDA-approved medication to accelerate the return of gastrointestinal function postoperatively.

SU-F-T-307: Peripheral Dose Comparison Between Static and Dynamic Jaw Tracking On a High Definition MLC System

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perez-Andujar, A; Cheung, J; Chuang, C

Purpose: To investigate the effect of dynamic and static jaw tracking on patient peripheral doses. Materials and Methods: A patient plan with a large sacral metastasis (volume 800cm3, prescription 600cGyx5) was selected for this study. The plan was created using 2-field RapidArc with jaw tracking enabled (Eclipse, V11.0.31). These fields were then exported and edited in MATLAB with static jaw positions using the control point with the largest field size for each respective arc, but preserving the optimized leaf sequences for delivery. These fields were imported back into Eclipse for dose calculation and comparison and copied to a Rando phantommore » for delivery analysis. Points were chosen in the phantom at depth and on the phantom surface at locations outside the primary radiation field, at distances of 12cm, 20cm, and 30cm from the isocenter. Measurements were acquired with OSLDs placed at these positions in the phantom with both the dynamic and static jaw deliveries for comparison. Surface measurements included an additional 1cm bolus over the OSLDs to ensure electron equilibrium. Results: The static jaw deliveries resulted in cumulative jaw-defined field sizes of 17.3% and 17.4% greater area than the dynamic jaw deliveries for each arc. The static jaw plan resulted in very small differences in calculated dose in the treatment planning system ranging from 0–16cGy. The measured dose differences were larger than calculated, but the differences in absolute dose were small. The measured dose differences at depth (surface) between the two deliveries showed an increase for the static jaw delivery of 2.2%(11.4%), 15.6%(20.0%), and 12.7%(12.7%) for distances of 12cm, 20cm, and 30cm, respectively. Eclipse calculates a difference of 0–3.1% for all of these points. The largest absolute dose difference between all points was 6.2cGy. Conclusion: While we demonstrated larger than expected differences in peripheral dose, the absolute dose differences were small.« less

TH-C-12A-02: Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Stage I and II Peripheral Lung Tumors with Unflattened Beams

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, B; Lu, J; Chen, J

2014-06-15

Purpose: The full arcs strategy used in SBRT with RapidArc and unflattened (FFF) beams in large and heterogeneous peripheral non-smallcell lung cancer (NSCLC) appears to be suboptimal as it increases the disadvantageous dose to the contralateral lung, which potentially increases the toxicity to surrounding tissues. In this study, we investigated, for the first time, the dose delivery strategies using partial arcs (PA) and the fully rotational arcs with avoidance sectors (FAAS) for SBRT with FFF beams in peripheral NSCLC patients. Methods: Eighteen patients with NSCLC (stage I and II) were selected for this study. Nine patients with a GTV <=more » 10cc were designated as the small tumor group. The remaining nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OAR), total MU, out-of-field dose, and delivery time were analyzed. Delta4 and Portal dosimetry were employed to evaluate the delivery accuracy. Results: or the small tumor group, the FAAS plans significantly achieved a better conformity index, the lower total MU and out-of-field dose, a shorter treatment time, and the reduced doses to cord, heart, and lung (p < 0.05). But the target doses were slightly higher than that delivered by PA plans. For the large tumor group, the PA plans significantly attained a better conformity index and a shorter treatment time (p < 0.05). Furthermore, all plans achieved a high pass rate, with all the gamma indices greater than 97% at the Γ{sub 3mm,} {sub 3%} threshold. Conclusion: This study suggests that FAAS strategy is more beneficial for small tumor patients undergoing lung SBRT with FFF beams. However, for large tumor patients, PA strategy is recommended. NIH/NIGMS grant U54 GM104944, Lincy Endowed Assistant Professorship.« less