Detecting cavitation in vivo from shock-wave therapy devices

NASA Astrophysics Data System (ADS)

Matula, Thomas J.; Yu, Jinfei; Bailey, Michael R.

2005-04-01

Extracorporeal shock-wave therapy (ESWT) has been used as a treatment for plantar faciitis, lateral epicondylitis, shoulder tendonitis, non-unions, and other indications where conservative treatments have been unsuccessful. However, in many areas, the efficacy of SW treatment has not been well established, and the mechanism of action, particularly the role of cavitation, is not well understood. Research indicates cavitation plays an important role in other ultrasound therapies, such as lithotripsy and focused ultrasound surgery, and in some instances, cavitation has been used as a means to monitor or detect a biological effect. Although ESWT can generate cavitation easily in vitro, it is unknown whether or not cavitation is a significant factor in vivo. The purpose of this investigation is to use diagnostic ultrasound to detect and monitor cavitation generated by ESWT devices in vivo. Diagnostic images are collected at various times during and after treatment. The images are then post-processed with image-processing algorithms to enhance the contrast between bubbles and surrounding tissue. The ultimate goal of this research is to utilize cavitation as a means for optimizing shock wave parameters such as amplitude and pulse repetition frequency. [Work supported by APL internal funds and NIH DK43881 and DK55674.

Automatic Detection of Seizures with Applications

NASA Technical Reports Server (NTRS)

Olsen, Dale E.; Harris, John C.; Cutchis, Protagoras N.; Cristion, John A.; Lesser, Ronald P.; Webber, W. Robert S.

1993-01-01

There are an estimated two million people with epilepsy in the United States. Many of these people do not respond to anti-epileptic drug therapy. Two devices can be developed to assist in the treatment of epilepsy. The first is a microcomputer-based system designed to process massive amounts of electroencephalogram (EEG) data collected during long-term monitoring of patients for the purpose of diagnosing seizures, assessing the effectiveness of medical therapy, or selecting patients for epilepsy surgery. Such a device would select and display important EEG events. Currently many such events are missed. A second device could be implanted and would detect seizures and initiate therapy. Both of these devices require a reliable seizure detection algorithm. A new algorithm is described. It is believed to represent an improvement over existing seizure detection algorithms because better signal features were selected and better standardization methods were used.

Molecular Medicine: Synthesis and In Vivo Detection of Agents for use in Boron Neutron Capture Therapy. Final Report

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

Kabalka, G. W.

2005-06-28

The primary objective of the project was the development of in vivo methods for the detection and evaluation of tumors in humans. The project was focused on utilizing positron emission tomography (PET) to monitor the distribution and pharamacokinetics of a current boron neutron capture therapy (BNCT) agent, p-boronophenylalanine (BPA) by labeling it with a fluorine-18, a positron emitting isotope. The PET data was then used to develop enhanced treatment planning protocols. The study also involved the synthesis of new tumor selective BNCTagents that could be labeled with radioactive nuclides for the in vivo detection of boron.

Clinical Applications of Circulating Tumor Cells and Circulating Tumor DNA as Liquid Biopsy.

PubMed

Alix-Panabières, Catherine; Pantel, Klaus

2016-05-01

"Liquid biopsy" focusing on the analysis of circulating tumor cells (CTC) and circulating cell-free tumor DNA (ctDNA) in the blood of patients with cancer has received enormous attention because of its obvious clinical implications for personalized medicine. Analyses of CTCs and ctDNA have paved new diagnostic avenues and are, to date, the cornerstones of liquid biopsy diagnostics. The present review focuses on key areas of clinical applications of CTCs and ctDNA, including detection of cancer, prediction of prognosis in patients with curable disease, monitoring systemic therapies, and stratification of patients based on the detection of therapeutic targets or resistance mechanisms. The application of CTCs and ctDNA for the early detection of cancer is of high public interest, but it faces serious challenges regarding specificity and sensitivity of the current assays. Prediction of prognosis in patients with curable disease can already be achieved in several tumor entities, particularly in breast cancer. Monitoring the success or failure of systemic therapies (i.e., chemotherapy, hormonal therapy, or other targeted therapies) by sequential measurements of CTCs or ctDNA is also feasible. Interventional studies on treatment stratification based on the analysis of CTCs and ctDNA are needed to implement liquid biopsy into personalized medicine. Cancer Discov; 6(5); 479-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Enhancing acute myeloid leukemia therapy - monitoring response using residual disease testing as a guide to therapeutic decision-making.

PubMed

Tomlinson, Benjamin; Lazarus, Hillard M

2017-06-01

Current standards for monitoring the response of acute myeloid leukemia (AML) are based on morphologic assessments of the bone marrow and recovery of peripheral blood counts. A growing experience is being developed to enhance the detection of small amounts of AML, or minimal residual disease (MRD). Areas covered: Available techniques include multi-color flow cytometry (MFC) of leukemia associated immunophenotypes (LAIP), quantitative reverse transcriptase polymerase chain reaction (QRT-PCR) for detecting fusion and mutated genes (RUNX1-RUNX1T1, CBFB-MYH11, and NPM1), overexpression of genes such as WT1, and next generation sequencing (NGS) for MRD. Expert commentary: While MRD monitoring is standard of care in some leukemia subsets such as acute promyelocytic leukemia, this approach for the broader AML population does not universally predict outcomes as some patients may experience relapse in the setting of undetectable leukemia while others show no obvious disease progression despite MRD positivity. However, there are instances where MRD can identify patients at increased risk for relapse that may change recommended therapy. Currently, prospective investigations to define clinically relevant MRD thresholds are ongoing. Risk-adapted trials are needed to best define the use of MRD in the follow up of AML patients after initial induction therapy.

Monitoring virologic responses to antiretroviral therapy in HIV-infected adults in Kenya: evaluation of a low-cost viral load assay.

PubMed

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S; Valentine, Fred

2009-08-28

A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure.

Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

PubMed Central

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S.; Valentine, Fred

2009-01-01

Background A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. Methodology/Principal Findings We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log10 copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of ≥400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. Conclusion The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure. PMID:19714253

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

PubMed Central

Vidal, J; Muinelo, L; Dalmases, A; Jones, F; Edelstein, D; Iglesias, M; Orrillo, M; Abalo, A; Rodríguez, C; Brozos, E; Vidal, Y; Candamio, S; Vázquez, F; Ruiz, J; Guix, M; Visa, L; Sikri, V; Albanell, J; Bellosillo, B; López, R; Montagut, C

2017-01-01

Abstract Background RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments. PMID:28419195

Management of delayed cerebral ischemia after subarachnoid hemorrhage.

PubMed

Francoeur, Charles L; Mayer, Stephan A

2016-10-14

For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.

High-sensitivity detection and monitoring of microcirculation using cutaneous and catheter probes for Doppler optical coherence tomography

NASA Astrophysics Data System (ADS)

Yang, Victor X.; Gordon, M. L.; Qi, B.; Yue, E. Seng; Tang, S.; Bisland, Stuart K.; Pekar, J.; Lo, S.; Marcon, Norman E.; Wilson, B.; Vitkin, Alex

2003-07-01

Background: Currently clinical Doppler ultrasound cannot detect microvascular blood flow and it is difficult to provide depth discrimination using laser Doppler flowmetry. Doppler optical coherence tomography (DOCT) is a novel technique for noninvasive subsurface imaging of microcirculation and tissue structure. Aims: To design handheld and catheter-based DOCT probes for clinical cutaneous and endoscopic imaging. To develop signal processing techniques for real-time detection and quantification of microvascular blood flow. Methods: A DOCT system, with interchangeable cutaneous and catheter probes, was developed. The axial spatial resolution was 10 μm, and the velocity resolution was 20 μm/s, using a 1300 nm broadband infrared light. The system achieved real-time imaging with frame rates up to 32 Hz at 512 x 256 pixels per frame. We used the system to detect microcirculation in human skin and rat esophagus, and to monitor microvascular responses to photodynamic therapy (PDT) in a rat tumor model. Results: We present experimental results from in vivo DOCT imaging of microcirculation in human skin arterio-venous malformations (AVM), normal rat esophagus, and a rat gliosarcoma PDT model. In the PDT model, we followed microvascular responses to PDT and observed differences in the microcirculation during and after therapy, which can have important implications for PDT dosimetry and treatment optimization. Conclusions: To our knowledge, this is the first demonstration of endoscopic catheter-based DOCT detection of microcirculation in vivo. In addition, AVM can be detected using handheld cutaneous DOCT probes under clinical settings. DOCT may serve as a real-time monitoring tool for PDT dosimetry, especially for vascular targeting photosensitizers.

Randomized trial of the ForeseeHome monitoring device for early detection of neovascular age-related macular degeneration. The HOme Monitoring of the Eye (HOME) study design - HOME Study report number 1.

PubMed

Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard A

2014-03-01

To evaluate the effects of a home-monitoring device with tele-monitoring compared with standard care in detection of progression to choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD), the leading cause of blindness in the US. Participants, aged 55 to 90 years, at high risk of developing CNV associated with AMD were recruited to the HOme Monitoring of Eye (HOME) Study, an unmasked, multi-center, randomized trial of the ForeseeHome (FH) device plus standard care vs. standard care alone. The FH device utilizes preferential hyperacuity perimetry and tele-monitoring to detect changes in vision function associated with development of CNV, potentially prior to symptom and visual acuity loss. After establishing baseline measurements, subsequent changes on follow-up are detected by the device, causing the monitoring center to alert the clinical center to recall participants for an exam. Standard care consists of instructions for self-monitoring visual changes with subsequent self-report to the clinical center. The primary objective of this study is to determine whether home monitoring plus standard care in comparison with standard care alone, results in earlier detection of incident CNV with better present visual acuity. The primary outcome is the decline in visual acuity at CNV diagnosis from baseline. Detection of CNV prior to substantial vision loss is critical as vision outcome following anti-angiogenic therapy is dependent on the visual acuity at initiation of treatment. HOME Study is the first large scale study to test the use of home tele-monitoring system in the management of AMD patients. Published by Elsevier Inc.

Using In-vivo Fluorescence Imaging in Personalized Cancer Diagnostics and Therapy, an Image and Treat Paradigm

PubMed Central

Ardeshirpour, Yasaman; Chernomordik, Victor; Capala, Jacek; Hassan, Moinuddin; Zielinsky, Rafal; Griffiths, Gary; Achilefu, Samuel; Smith, Paul; Gandjbakhckhe, Amir

2013-01-01

The major goal in developing drugs targeting specific tumor receptors, such as Monoclonal AntiBodies (MAB), is to make a drug compound that targets selectively the cancer-causing biomarkers, inhibits their functionality, and/or delivers the toxin specifically to the malignant cells. Recent advances in MABs show that their efficacy depends strongly on characterization of tumor biomarkers. Therefore, one of the main tasks in cancer diagnostics and treatment is to develop non-invasive in-vivo imaging techniques for detection of cancer biomarkers and monitoring their down regulation during the treatment. Such methods can potentially result in a new imaging and treatment paradigm for cancer therapy. In this article we have reviewed fluorescence imaging approaches, including those developed in our group, to detect and monitor Human Epidermal Growth Factor 2 (HER2) receptors before and during therapy. Transition of these techniques from the bench to bedside is the ultimate goal of our project. Similar approaches can be used potentially for characterization of other cancer related cell biomarkers. PMID:22066595

Cavity-Enhanced Absorption Spectroscopy and Photoacoustic Spectroscopy for Human Breath Analysis

NASA Astrophysics Data System (ADS)

Wojtas, J.; Tittel, F. K.; Stacewicz, T.; Bielecki, Z.; Lewicki, R.; Mikolajczyk, J.; Nowakowski, M.; Szabra, D.; Stefanski, P.; Tarka, J.

2014-12-01

This paper describes two different optoelectronic detection techniques: cavity-enhanced absorption spectroscopy and photoacoustic spectroscopy. These techniques are designed to perform a sensitive analysis of trace gas species in exhaled human breath for medical applications. With such systems, the detection of pathogenic changes at the molecular level can be achieved. The presence of certain gases (biomarkers), at increased concentration levels, indicates numerous human diseases. Diagnosis of a disease in its early stage would significantly increase chances for effective therapy. Non-invasive, real-time measurements, and high sensitivity and selectivity, capable of minimum discomfort for patients, are the main advantages of human breath analysis. At present, monitoring of volatile biomarkers in breath is commonly useful for diagnostic screening, treatment for specific conditions, therapy monitoring, control of exogenous gases (such as bacterial and poisonous emissions), as well as for analysis of metabolic gases.

Design optimisation of a TOF-based collimated camera prototype for online hadrontherapy monitoring

NASA Astrophysics Data System (ADS)

Pinto, M.; Dauvergne, D.; Freud, N.; Krimmer, J.; Letang, J. M.; Ray, C.; Roellinghoff, F.; Testa, E.

2014-12-01

Hadrontherapy is an innovative radiation therapy modality for which one of the main key advantages is the target conformality allowed by the physical properties of ion species. However, in order to maximise the exploitation of its potentialities, online monitoring is required in order to assert the treatment quality, namely monitoring devices relying on the detection of secondary radiations. Herein is presented a method based on Monte Carlo simulations to optimise a multi-slit collimated camera employing time-of-flight selection of prompt-gamma rays to be used in a clinical scenario. In addition, an analytical tool is developed based on the Monte Carlo data to predict the expected precision for a given geometrical configuration. Such a method follows the clinical workflow requirements to simultaneously have a solution that is relatively accurate and fast. Two different camera designs are proposed, considering different endpoints based on the trade-off between camera detection efficiency and spatial resolution to be used in a proton therapy treatment with active dose delivery and assuming a homogeneous target.

Wearable sensor platform and mobile application for use in cognitive behavioral therapy for drug addiction and PTSD.

PubMed

Fletcher, Richard Ribón; Tam, Sharon; Omojola, Olufemi; Redemske, Richard; Kwan, Joyce

2011-01-01

We present a wearable sensor platform designed for monitoring and studying autonomic nervous system (ANS) activity for the purpose of mental health treatment and interventions. The mobile sensor system consists of a sensor band worn on the ankle that continuously monitors electrodermal activity (EDA), 3-axis acceleration, and temperature. A custom-designed ECG heart monitor worn on the chest is also used as an optional part of the system. The EDA signal from the ankle bands provides a measure sympathetic nervous system activity and used to detect arousal events. The optional ECG data can be used to improve the sensor classification algorithm and provide a measure of emotional "valence." Both types of sensor bands contain a Bluetooth radio that enables communication with the patient's mobile phone. When a specific arousal event is detected, the phone automatically presents therapeutic and empathetic messages to the patient in the tradition of Cognitive Behavioral Therapy (CBT). As an example of clinical use, we describe how the system is currently being used in an ongoing study for patients with drug-addiction and post-traumatic stress disorder (PTSD).

Simultaneous determination of triple therapy for Helicobacter pylori in human plasma by reversed phase chromatography with online wavelength switching

NASA Astrophysics Data System (ADS)

Ahmed, Sameh; Atia, Noha N.

2015-02-01

The infection of gastric mucosa by Helicobacter pylori (HP) is an essential cofactor in the aetiology of gastroduodenal ulcer and gastric carcinoma. Because of the bacterial resistance, combination therapy containing omeprazole (OME), tinidazole (TNZ) and clarithromycin (CLA) is commonly used for eradication of HP. However, the simultaneous determination of the triple therapy in human plasma was not reported. A simple, reproducible, and selective HPLC method was developed for the simultaneous determination of the triple therapy mixture used for management of HP infections in human plasma. An HPLC procedure based on a liquid-liquid extraction, enrichment of the analytes and subsequent reversed-phase chromatography with UV detection was used. To enable sensitive and selective detection, the method involved the use of online wavelength switching detection, with two different detection wavelengths; 280 nm for detection of OME and TNZ and 210 nm for detection of CLA. Separations were performed on C18 analytical column with acetonitrile-10 mM phosphate buffer of pH = 3.0 at flow rate of 1.0 mL min-1. The linear ranges in human plasma were 0.05-10 μg mL-1 with correlation coefficients >0.9990. The detection limits in human plasma were 0.02-0.07 μg mL-1. Validation parameters were assessed in compliance with US-FDA guidelines. The method proved to be valuable for the therapeutic drug monitoring after oral administration of triple therapy tablets.

Early detection of tumor relapse/regrowth by consecutive minimal residual disease monitoring in high-risk neuroblastoma patients

PubMed Central

Hirase, Satoshi; Saitoh, Atsuro; Hartomo, Tri Budi; Kozaki, Aiko; Yanai, Tomoko; Hasegawa, Daiichiro; Kawasaki, Keiichiro; Kosaka, Yoshiyuki; Matsuo, Masafumi; Yamamoto, Nobuyuki; Mori, Takeshi; Hayakawa, Akira; Iijima, Kazumoto; Nishio, Hisahide; Nishimura, Noriyuki

2016-01-01

Neuroblastoma is an aggressive pediatric tumor accounting for ~15% of cancer-associated mortalities in children. Despite the current intensive therapy, >50% of high-risk patients experience tumor relapse or regrowth caused by the activation of minimal residual disease (MRD). Although several MRD detection protocols using various reverse transcription-quantitative polymerase chain reaction (RT-qPCR) markers have been reported to evaluate the therapeutic response and disease status of neuroblastoma patients, their clinical significance remains elusive. The present study reports two high-risk neuroblastoma patients, whose MRD was consecutively monitored using 11 RT-qPCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) during their course of treatment. The two patients initially responded to the induction therapy and reached MRD-negative status. The patients' MRD subsequently became positive with no elevation of their urinary homovanillic acid, urinary vanillylmandelic acid and serum neuron-specific enolase levels at 13 or 19 weeks prior to the clinical diagnosis of tumor relapse or regrowth. The present cases highlight the possibility of consecutive MRD monitoring using 11 markers to enable an early detection of tumor relapse or regrowth in high-risk neuroblastoma patients. PMID:27446404

Customized Interactive Robotic Treatment for Stroke: EMG-Triggered Therapy

PubMed Central

Dipietro, Laura; Ferraro, Mark; Palazzolo, Jerome Joseph; Krebs, Hermano Igo; Volpe, Bruce T.; Hogan, Neville

2009-01-01

A system for electromyographic (EMG) triggering of robot-assisted therapy (dubbed the EMG game) for stroke patients is presented. The onset of a patient’s attempt to move is detected by monitoring EMG in selected muscles, whereupon the robot assists her or him to perform point-to-point movements in a horizontal plane. Besides delivering customized robot-assisted therapy, the system can record signals that may be useful to better understand the process of recovery from stroke. Preliminary experiments aimed at testing the proposed system and gaining insight into the potential of EMG-triggered, robot-assisted therapy are reported. PMID:16200756

A low molecular weight zinc2+-dipicolylamine-based probe detects apoptosis during tumour treatment better than an annexin V-based probe.

PubMed

Palmowski, Karin; Rix, Anne; Lederle, Wiltrud; Behrendt, Florian F; Mottaghy, Felix M; Gray, Brian D; Pak, Koon Y; Palmowski, Moritz; Kiessling, Fabian

2014-02-01

Molecular imaging of apoptosis is frequently discussed for monitoring cancer therapies. Here, we compare the low molecular weight phosphatidylserine-targeting ligand zinc2+-dipicolylamine (Zn2+-DPA) with the established but reasonably larger protein annexin V. Molecular apoptosis imaging with the fluorescently labelled probes annexin V (750 nm, 36 kDa) and Zn2+-DPA (794 nm, 1.84 kDa) was performed in tumour-bearing mice (A431). Three animal groups were investigated: untreated controls and treated tumours after 1 or 4 days of anti-angiogenic therapy (SU11248). Additionally, μPET with 18 F-FDG was performed. Imaging data were displayed as tumour-to-muscle ratio (TMR) and validated by quantitative immunohistochemistry. Compared with untreated control tumours, TUNEL staining indicated significant apoptosis after 1 day (P < 0.05) and 4 days (P < 0.01) of treatment. Concordantly, Zn2+-DPA uptake increased significantly after 1 day (P < 0.05) and 4 days (P < 0.01). Surprisingly, annexin V failed to detect significant differences between control and treated animals. Contrary to the increasing uptake of Zn2+-DPA, 18 F-FDG tumour uptake decreased significantly at days 1 (P < 0.05) and 4 (P < 0.01). Increase in apoptosis during anti-angiogenic therapy was detected significantly better with the low molecular weight probe Zn2+-DPA than with the annexin V-based probe. Additionally, significant treatment effects were detectable as early using Zn2+-DPA as with measurements of the glucose metabolism using 18 F-FDG. • The detection of apoptosis by non-invasive imaging is important in oncology. • A new low molecular weight probe Zn2+-DPA shows promise in depicting anti-angiogenic effects. • The small Zn2+-DPA ligand appears well suited for monitoring therapy. • Treatment effects are detectable just as early with Zn2+-DPA as with 18F-FDG.

Three-dimensional power doppler ultrasound is useful to monitor the response to treatment in a patient with primary papillary serous carcinoma of the peritoneum.

PubMed

Su, Jen-Min; Huang, Yu-Fang; Chen, Helen H W; Cheng, Ya-Min; Chou, Cheng-Yang

2006-05-01

To date, this is the first report to monitor changes of intratumor vascularization and the response to radiation and Cyberknife therapy in a patient with recurrent primary papillary serous carcinoma of the peritoneum by three dimensional (3D) power Doppler ultrasonography (PDUS). Transvaginal 3D PDUS detected a recurrent presacral tumor with abundant intratumor vascularity. Serial examinations of the tumor volume and serum CA-125 level were studied before, during, and 6 mo after therapy. Meanwhile, the intratumor blood flow was measured and expressed as vascularity indices. All of the tumor volume, intratumor vascularity indices and serum CA-125 level decreased progressively following therapy. A remaining lesion with nearly absent intratumor power Doppler signals suggested a scarring lesion posttreatment. Indeed, CT-guided tissue biopsy confirmed fibrotic change. 3D PDUS is useful to monitor the response to treatments and to differentiate residual tumors from lesions of scarring change posttreatment. It provides more accurate posttreatment information than pelvic computed tomography.

Immunologic monitoring of cancer vaccine therapy: results of a workshop sponsored by the Society for Biological Therapy.

PubMed

Keilholz, Ulrich; Weber, Jeffrey; Finke, James H; Gabrilovich, Dmitry I; Kast, W Martin; Disis, Mary L; Kirkwood, John M; Scheibenbogen, Carmen; Schlom, Jeff; Maino, Vernon C; Lyerly, H Kim; Lee, Peter P; Storkus, Walter; Marincola, Franceso; Worobec, Alexandra; Atkins, Michael B

2002-01-01

The Society for Biological Therapy held a Workshop last fall devoted to immune monitoring for cancer immunotherapy trials. Participants included members of the academic and pharmaceutical communities as well as the National Cancer Institute and the Food and Drug Administration. Discussion focused on the relative merits and appropriate use of various immune monitoring tools. Six breakout groups dealt with assays of T-cell function, serologic and proliferation assays to assess B cell and T helper cell activity, and enzyme-linked immunospot assay, tetramer, cytokine flow cytometry, and reverse transcription polymerase chain reaction assays of T-cell immunity. General conclusions included: (1) future vaccine studies should be designed to determine whether T-cell dysfunction (tumor-specific and nonspecific) correlated with clinical outcome; (2) tetramer-based assays yield quantitative but not functional data (3) enzyme-linked immunospot assays have the lowest limit of detection (4) cytokine flow cytometry have a higher limit of detection than enzyme-linked immunospot assay, but offer the advantages of speed and the ability to identify subsets of reactive cells; (5) antibody tests are simple and accurate and should be incorporated to a greater extent in monitoring plans; (6) proliferation assays are imprecise and should not be emphasized in future studies; (7) the reverse transcription polymerase chain reaction assay is a promising research approach that is not ready for widespread application; and (8)there is a critical need to validate these assays as surrogates for vaccine potency and clinical effect. Current data and opinion support the use of a functional assay like the enzyme-linked immunospot assay or cytokine flow cytometry in combination with a quantitative assay like tetramers for immune monitoring. At present, assays appear to be most useful as measures of vaccine potency. Careful immune monitoring in association with larger scale clinical trials ultimately may enable the correlation of monitoring results with clinical benefit.

The nursing perspective on monitoring hemodynamics and oxygen transport.

PubMed

Tucker, Dawn; Hazinski, Mary Fran

2011-07-01

Maintenance of adequate systemic oxygen delivery requires careful clinical assessment integrated with hemodynamic measurements and calculations to detect and treat conditions that may compromise oxygen delivery and lead to life-threatening shock, respiratory failure, or cardiac arrest. The bedside nurse constantly performs such assessments and measurements to detect subtle changes and trends in patient condition. The purpose of this editorial is to highlight nursing perspectives about the hemodynamic and oxygen transport monitoring systems summarized in the Pediatric Cardiac Intensive Care Society Evidence- Based Review and Consensus Statement on Monitoring of Hemodynamics and Oxygen Transport Balance. There is no substitute for the observations of a knowledgeable and experienced clinician who understands the patient's condition and potential causes of deterioration and is able to evaluate response to therapy.

Machine learning-based patient specific prompt-gamma dose monitoring in proton therapy

NASA Astrophysics Data System (ADS)

Gueth, P.; Dauvergne, D.; Freud, N.; Létang, J. M.; Ray, C.; Testa, E.; Sarrut, D.

2013-07-01

Online dose monitoring in proton therapy is currently being investigated with prompt-gamma (PG) devices. PG emission was shown to be correlated with dose deposition. This relationship is mostly unknown under real conditions. We propose a machine learning approach based on simulations to create optimized treatment-specific classifiers that detect discrepancies between planned and delivered dose. Simulations were performed with the Monte-Carlo platform Gate/Geant4 for a spot-scanning proton therapy treatment and a PG camera prototype currently under investigation. The method first builds a learning set of perturbed situations corresponding to a range of patient translation. This set is then used to train a combined classifier using distal falloff and registered correlation measures. Classifier performances were evaluated using receiver operating characteristic curves and maximum associated specificity and sensitivity. A leave-one-out study showed that it is possible to detect discrepancies of 5 mm with specificity and sensitivity of 85% whereas using only distal falloff decreases the sensitivity down to 77% on the same data set. The proposed method could help to evaluate performance and to optimize the design of PG monitoring devices. It is generic: other learning sets of deviations, other measures and other types of classifiers could be studied to potentially reach better performance. At the moment, the main limitation lies in the computation time needed to perform the simulations.

Local ablation therapy with contrast-enhanced ultrasonography for hepatocellular carcinoma: a practical review

PubMed Central

Kim, Tae Kyoung; Khalili, Korosh; Jang, Hyun-Jung

2015-01-01

A successful program for local ablation therapy for hepatocellular carcinoma (HCC) requires extensive imaging support for diagnosis and localization of HCC, imaging guidance for the ablation procedures, and post-treatment monitoring. Contrast-enhanced ultrasonography (CEUS) has several advantages over computed tomography/magnetic resonance imaging (CT/MRI), including real-time imaging capability, sensitive detection of arterial-phase hypervascularity and washout, no renal excretion, no ionizing radiation, repeatability, excellent patient compliance, and relatively low cost. CEUS is useful for image guidance for isoechoic lesions. While contrast-enhanced CT/MRI is the standard method for the diagnosis of HCC and post-ablation monitoring, CEUS is useful when CT/MRI findings are indeterminate or CT/MRI is contraindicated. This article provides a practical review of the role of CEUS in imaging algorithms for pre- and post-ablation therapy for HCC. PMID:26169081

[Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis].

PubMed

Su, Fei; Zheng, Ke; Fu, Yiyun; Wu, Qian; Tang, Yuan; Wang, Weiya; Jiang, Lili

2018-05-20

Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Real-Time Monitoring of Singlet Oxygen and Oxygen Partial Pressure During the Deep Photodynamic Therapy In Vitro.

PubMed

Li, Weitao; Huang, Dong; Zhang, Yan; Liu, Yangyang; Gu, Yueqing; Qian, Zhiyu

2016-09-01

Photodynamic therapy (PDT) is an effective noninvasive method for the tumor treatment. The major challenge in current PDT research is how to quantitatively evaluate therapy effects. To our best knowledge, this is the first time to combine multi-parameter detection methods in PDT. More specifically, we have developed a set of system, including the high-sensitivity measurement of singlet oxygen, oxygen partial pressure and fluorescence image. In this paper, the detection ability of the system was validated by the different concentrations of carbon quantum dots. Moreover, the correlation between singlet oxygen and oxygen partial pressure with laser irradiation was observed. Then, the system could detect the signal up to 0.5 cm tissue depth with 660 nm irradiation and 1 cm tissue depth with 980 nm irradiation by using up-conversion nanoparticles during PDT in vitro. Furthermore, we obtained the relationship among concentration of singlet oxygen, oxygen partial pressure and tumor cell viability under certain conditions. The results indicate that the multi-parameter detection system is a promising asset to evaluate the deep tumor therapy during PDT. Moreover, the system might be potentially used for the further study in biology and molecular imaging.

A scintillator-based approach to monitor secondary neutron production during proton therapy.

PubMed

Clarke, S D; Pryser, E; Wieger, B M; Pozzi, S A; Haelg, R A; Bashkirov, V A; Schulte, R W

2016-11-01

The primary objective of this work is to measure the secondary neutron field produced by an uncollimated proton pencil beam impinging on different tissue-equivalent phantom materials using organic scintillation detectors. Additionally, the Monte Carlo code mcnpx-PoliMi was used to simulate the detector response for comparison to the measured data. Comparison of the measured and simulated data will validate this approach for monitoring secondary neutron dose during proton therapy. Proton beams of 155- and 200-MeV were used to irradiate a variety of phantom materials and secondary particles were detected using organic liquid scintillators. These detectors are sensitive to fast neutrons and gamma rays: pulse shape discrimination was used to classify each detected pulse as either a neutron or a gamma ray. The mcnpx-PoliMi code was used to simulate the secondary neutron field produced during proton irradiation of the same tissue-equivalent phantom materials. An experiment was performed at the Loma Linda University Medical Center proton therapy research beam line and corresponding models were created using the mcnpx-PoliMi code. The authors' analysis showed agreement between the simulations and the measurements. The simulated detector response can be used to validate the simulations of neutron and gamma doses on a particular beam line with or without a phantom. The authors have demonstrated a method of monitoring the neutron component of the secondary radiation field produced by therapeutic protons. The method relies on direct detection of secondary neutrons and gamma rays using organic scintillation detectors. These detectors are sensitive over the full range of biologically relevant neutron energies above 0.5 MeV and allow effective discrimination between neutron and photon dose. Because the detector system is portable, the described system could be used in the future to evaluate secondary neutron and gamma doses on various clinical beam lines for commissioning and prospective data collection in pediatric patients treated with proton therapy.

SU-F-J-202: Secondary Radiation Measurements for Charged Particle Therapy Monitoring: Fragmentation of Therapeutic He, C and O Ion Beams Impinging On a PMMA Target

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

Rucinski, A; Mancini-Terracciano, C; Paramatti, R

Purpose: In Charged Particle Therapy (CPT), besides protons, there has been recently a growing interest in 4He, 12C and 16O beams. The secondary radiation produced in the interaction of those beams with a patient could be potentially used for on-line monitoring of range uncertainties in order to fully exploit the advantages of those light ions resulting from increased Radio Biological Effectiveness, reduced multiple scattering and Oxygen Enhancement Ratio. The study and precise characterization of secondary radiation (beta+, prompt gamma, charged fragments) is the cornerstone of any R&D activity aiming for online monitoring development and purpose of the analysis presented here.more » Methods: We present the measurements of the secondary radiation generated by He, C and O beams impinging on a beam stopping PMMA target. The data has been collected at the Heidelberg Ionbeam Therapy center (HIT), where several millions of collisions were recorded at different energies, relevant for therapeutical applications. Results: The experimental setup, as well as the analysis strategies will be reviewed. The detected particle fluxes as a function of the primary beam energy and the emission angle with respect to the beam direction will be presented and compared to the results of other available measurements. In addition, the energy spectra and emission shapes of charged secondary particles will be shown and discussed in the context of the primary beam range monitoring technique that is being developed by the ARPG collaboration, within the INSIDE project funded by the Italian research ministry. The implications for dose monitoring applications will be discussed, in the context of the current (or planned) state-of- the-art detector solutions. Conclusion: The characterization of the radiation produced by 12C, 4He and 16O beams fully supports the feasibility of on-line range monitoring in the clinical practice of CPT by means of secondary particles detection.« less

Comparison between three quantitative assays in patients with chronic hepatitis C and their relevance in the prediction of response to therapy.

PubMed

Pradat, P; Chossegros, P; Bailly, F; Pontisso, P; Saracco, G; Sauleda, S; Thursz, M; Tillmann, H; Vlassopoulou, H; Alberti, A; Braconier, J H; Esteban, J I; Hadziyannis, S; Manns, M; Rizzetto, M; Thomas, H C; Trépo, C

2000-05-01

To compare three quantitative assays measuring viral load in patients with chronic hepatitis C and to determine their value in predicting response to interferon (IFN) therapy, we analysed serum from 896 patients from eight European Centres using QUANTIPLEXtrade mark bDNA, MONITOR AMPLICORtrade mark and SUPERQUANTtrade mark assays. Analyses were performed on the same sample. Viral genotype was assessed using INNO-LiPA HCV II kits. Intercentre variations were observed that were related to the handling of specimens not processed and stored within 6 h of blood sampling. Among sera with optimal handling, a stronger correlation was observed between bDNA and SUPERQUANT (0.806) than between bDNA and MONITOR (0.677) and between MONITOR and SUPERQUANT (0.632). These discrepancies were greatest with genotype 2 (bDNA/SUPERQUANT= 0.772; bDNA/MONITOR=0. 456; SUPERQUANT/MONITOR= 0.299). This correlation was influenced by viraemia level and was better at lower viral loads. The proportion of sera with undetectable viral load was 15% with bDNA, 9.7% with MONITOR and 7.7% with SUPERQUANT. For the three measurements, the best cut-offs of sustained response to IFN treatment were located at their detection threshold. Among patients with viral load below the detection level, a sustained response was observed in 35% tested with bDNA, 38% with MONITOR and 80% with SUPERQUANT. Hence a stronger correlation was observed between bDNA and SUPERQUANT than between either of these assays and MONITOR. SUPERQUANT was the most sensitive assay and this greater sensitivity was associated with a better predictive value of treatment response.

Cardio-oncology: a multidisciplinary approach for detection, prevention and management of cardiac dysfunction in cancer patients.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2017-08-01

Cardiac dysfunction that develops during or after completion of cancer therapy is a growing health concern that should be addressed in a multidisciplinary setting. Cardio-oncology is a new discipline that focuses on screening, monitoring and treating cardiovascular disease during and after cancer treatment. A baseline cardiovascular risk assessment is essential. For high-risk patients, a tailored and detailed plan for cardiovascular management throughout treatment and beyond should also be established. Anthracycline and/or trastuzumab-containing chemotherapy and chest-directed radiation therapy are well known cardiotoxic cancer therapies. Monitoring for the development of subclinical cardiotoxicity is crucial for the prevention of clinical heart failure. Detecting a decreased left ventricular ejection fraction after cancer therapy might be a late finding; therefore, earlier markers of cardiac injury are being actively explored. Abnormal myocardial strain and increased serum cardiac biomarkers (e.g. troponins and natriuretic peptides) are possible candidates for this purpose. An important method for preventing heart failure is the avoidance or minimization of the use of cardiotoxic therapies. Decisions must balance the anti-tumor efficacy of the treatment with its potential cardiotoxicity. If patients develop cardiac dysfunction or heart failure, they should be treated in accordance with established guidelines for heart failure. Cancer survivors who have been exposed to cardiotoxic cancer therapies are at high risk of developing heart failure. The management of cardiovascular risk factors and periodic screening with cardiac imaging and biomarkers should be considered in high-risk survivors. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Developing strategies for detection of gene doping.

PubMed

Baoutina, Anna; Alexander, Ian E; Rasko, John E J; Emslie, Kerry R

2008-01-01

It is feared that the use of gene transfer technology to enhance athletic performance, the practice that has received the term 'gene doping', may soon become a real threat to the world of sport. As recognised by the anti-doping community, gene doping, like doping in any form, undermines principles of fair play in sport and most importantly, involves major health risks to athletes who partake in gene doping. One attraction of gene doping for such athletes and their entourage lies in the apparent difficulty of detecting its use. Since the realisation of the threat of gene doping to sport in 2001, the anti-doping community and scientists from different disciplines concerned with potential misuse of gene therapy technologies for performance enhancement have focused extensive efforts on developing robust methods for gene doping detection which could be used by the World Anti-Doping Agency to monitor athletes and would meet the requirements of a legally defensible test. Here we review the approaches and technologies which are being evaluated for the detection of gene doping, as well as for monitoring the efficacy of legitimate gene therapy, in relation to the detection target, the type of sample required for analysis and detection methods. We examine the accumulated knowledge on responses of the body, at both cellular and systemic levels, to gene transfer and evaluate strategies for gene doping detection based on current knowledge of gene technology, immunology, transcriptomics, proteomics, biochemistry and physiology. (c) 2008 John Wiley & Sons, Ltd.

Disease management: remote monitoring in heart failure patients with implantable defibrillators, resynchronization devices, and haemodynamic monitors.

PubMed

Abraham, William T

2013-06-01

Heart failure represents a major public health concern, associated with high rates of morbidity and mortality. A particular focus of contemporary heart failure management is reduction of hospital admission and readmission rates. While optimal medical therapy favourably impacts the natural history of the disease, devices such as cardiac resynchronization therapy devices and implantable cardioverter defibrillators have added incremental value in improving heart failure outcomes. These devices also enable remote patient monitoring via device-based diagnostics. Device-based measurement of physiological parameters, such as intrathoracic impedance and heart rate variability, provide a means to assess risk of worsening heart failure and the possibility of future hospitalization. Beyond this capability, implantable haemodynamic monitors have the potential to direct day-to-day management of heart failure patients to significantly reduce hospitalization rates. The use of a pulmonary artery pressure measurement system has been shown to significantly reduce the risk of heart failure hospitalization in a large randomized controlled study, the CardioMEMS Heart Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients (CHAMPION) trial. Observations from a pilot study also support the potential use of a left atrial pressure monitoring system and physician-directed patient self-management paradigm; these observations are under further investigation in the ongoing LAPTOP-HF trial. All these devices depend upon high-intensity remote monitoring for successful detection of parameter deviations and for directing and following therapy.

Growth of melanoma brain tumors monitored by photoacoustic microscopy

NASA Astrophysics Data System (ADS)

Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

Improving atrial fibrillation detection in patients with implantable cardiac devices by means of a remote monitoring and management application.

PubMed

Zoppo, Franco; Facchin, Domenico; Molon, Giulio; Zanotto, Gabriele; Catanzariti, Domenico; Rossillo, Antonio; Baccillieri, Maria Stella; Menard, Cecile; Comisso, Jennifer; Gentili, Alessandra; Grammatico, Andrea; Bertaglia, Emanuele; Proclemer, Alessandro

2014-12-01

Atrial fibrillation (AF) is common in patients with cardiac implantable electronic devices (CIED) and has been associated with an increased stroke risk. The aim of our project was to assess the clinical value of a web-based application, Discovery Link AFinder, in improving AF detection in CIED patients. Seven Italian hospitals performed an observational study consisting of four phases. During phase 1, expert nurses and cardiologists prospectively followed-up CIED patients via in-hospital examinations and remote monitoring, and classified clinically relevant events, particularly AF occurrence. During phase 2, Discovery Link AFinder was exploited to identify patients who had suffered AF in the previous 12 months through the systematic scanning of device data remote transmissions. Phases 3 and 4 were repetitions of phases 1 and 2, respectively, and were implemented 6 months after the previous phases. A total of 472 consecutive patients were included in phase 1; AF occurred in 170 patients, 61 of whom were identified as new AF patients. Evidence of AF during this phase prompted prescription of oral anticoagulation (OAC) therapy in 30 patients. In phase 2, AFinder uncovered new AF, unidentified in phase 1, in 54 patients and prompted implementation of OAC therapy in 11 patients. During phase 3, 30 new AF patients were identified by means of remote monitoring, while during phase 4, a further three AF patients were identified by AFinder only. The AFinder web-based software, applied on top of standard in-hospital and remote monitoring, improved AF detection and enabled OAC treatment to be undertaken. ©2014 Wiley Periodicals, Inc.

Monitoring Daily Dynamics of Early Tumor Response to Targeted Therapy by Detecting Circulating Tumor DNA in Urine

PubMed Central

Husain, Hatim; Melnikova, Vladislava O.; Kosco, Karena; Woodward, Brian; More, Soham; Pingle, Sandeep C.; Weihe, Elizabeth; Park, Ben Ho; Tewari, Muneesh; Erlander, Mark G.; Cohen, Ezra; Lippman, Scott M.; Kurzrock, Razelle

2017-01-01

Purpose Non-invasive drug biomarkers for the early assessment of tumor response can enable adaptive therapeutic decision-making and proof-of-concept studies for investigational drugs. Circulating tumor DNA (ctDNA) is released into the circulation by tumor cell turnover and has been shown to be detectable in urine. Experimental Design We tested the hypothesis that dynamic changes in epidermal growth factor receptor (EGFR) activating (exon 19del and L858R) and resistance (T790M) mutation levels detected in urine could inform tumor response within days of therapy for advanced non-small cell lung cancer (NSCLC) patients receiving osimertinib, a second line third generation anti-EGFR tyrosine kinase inhibitor. Results Eight of nine evaluable NSCLC patients had detectable T790M-mutant DNA fragments in pre-treatment baseline samples. Daily monitoring of mutations in urine indicated a pattern of intermittent spikes throughout week 1 suggesting apoptosis with an overall decrease in fragment numbers between baselines to day 7 preceding radiographic response assessed at 6-12 weeks. Conclusions These findings suggest drug-induced tumor apoptosis within days of initial dosing. Daily sampling of ctDNA may enable early assessment of patient response and proof-of-concept studies for drug development. PMID:28420725

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

In-treatment tests for the monitoring of proton and carbon-ion therapy with a large area PET system at CNAO

NASA Astrophysics Data System (ADS)

Rosso, V.; Battistoni, G.; Belcari, N.; Camarlinghi, N.; Ciocca, M.; Collini, F.; Ferretti, S.; Kraan, A. C.; Lucenò, S.; Molinelli, S.; Pullia, M.; Sportelli, G.; Zaccaro, E.; Del Guerra, A.

2016-07-01

One of the most promising new radiotherapy techniques makes use of charged particles like protons and carbon ions, rather than photons. At present, there are more than 50 particle therapy centers operating worldwide, and many new centers are being constructed. Positron Emission Tomography (PET) is considered a well-established non-invasive technique to monitor range and delivered dose in patients treated with particle therapy. Nuclear interactions of the charged hadrons with the patient tissue lead to the production of β+ emitting isotopes (mainly 15O and 11C), that decay with a short lifetime producing a positron. The two 511 keV annihilation photons can be detected with a PET detector. In-beam PET is particularly interesting because it could allow monitoring the ions range also during dose delivery. A large area dual head PET prototype was built and tested. The system is based on an upgraded version of the previously developed DoPET prototype. Each head covers now 15×15 cm2 and is composed by 9 (3×3) independent modules. Each module consists of a 23×23 LYSO crystal matrix (2 mm pitch) coupled to H8500 PMT and is readout by custom front-end and a FPGA based data acquisition electronics. Data taken at the CNAO treatment facility in Pavia with proton and carbon beams impinging on heterogeneous phantoms demonstrate the DoPET capability to detect the presence of a small air cavity in the phantom.

Nano-sized Contrast Agents to Non-Invasively Detect Renal Inflammation by Magnetic Resonance Imaging

PubMed Central

Thurman, Joshua M.; Serkova, Natalie J.

2013-01-01

Several molecular imaging methods have been developed that employ nano-sized contrast agents to detect markers of inflammation within tissues. Renal inflammation contributes to disease progression in a wide range of autoimmune and inflammatory diseases, and a biopsy is currently the only method of definitively diagnosing active renal inflammation. However, the development of new molecular imaging methods that employ contrast agents capable of detecting particular immune cells or protein biomarkers will allow clinicians to evaluate inflammation throughout the kidneys, and to assess a patient's response to immunomodulatory drugs. These imaging tools will improve our ability to validate new therapies and to optimize the treatment of individual patients with existing therapies. This review describes the clinical need for new methods of monitoring renal inflammation, and recent advances in the development of nano-sized contrast agents for detection of inflammatory markers of renal disease. PMID:24206601

Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers

PubMed Central

Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A; Kassem, Moustapha; Zaher, Waleed; Alfayez, Musaad; Aldahmash, Abdullah; Alajez, Nehad M

2017-01-01

Effective management of breast cancer depends on early diagnosis and proper monitoring of patients’ response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising biomarker, given the ease with which miRNAs can be isolated and their structural stability under different conditions of sample processing and isolation. In this review, we provide current state-of-the-art of miRNA biogenesis, function and discuss the advantages, limitations, as well as pitfalls of using circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management. PMID:28880270

Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers.

PubMed

Hamam, Rimi; Hamam, Dana; Alsaleh, Khalid A; Kassem, Moustapha; Zaher, Waleed; Alfayez, Musaad; Aldahmash, Abdullah; Alajez, Nehad M

2017-09-07

Effective management of breast cancer depends on early diagnosis and proper monitoring of patients' response to therapy. However, these goals are difficult to achieve because of the lack of sensitive and specific biomarkers for early detection and for disease monitoring. Accumulating evidence in the past several years has highlighted the potential use of peripheral blood circulating nucleic acids such as DNA, mRNA and micro (mi)RNA in breast cancer diagnosis, prognosis and for monitoring response to anticancer therapy. Among these, circulating miRNA is increasingly recognized as a promising biomarker, given the ease with which miRNAs can be isolated and their structural stability under different conditions of sample processing and isolation. In this review, we provide current state-of-the-art of miRNA biogenesis, function and discuss the advantages, limitations, as well as pitfalls of using circulating miRNAs as diagnostic, prognostic or predictive biomarkers in breast cancer management.

Management of the baseline shift using a new and simple method for respiratory-gated radiation therapy: Detectability and effectiveness of a flexible monitoring system

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

Tachibana, Hidenobu; Kitamura, Nozomi; Ito, Yasushi

2011-07-15

Purpose: In respiratory-gated radiation therapy, a baseline shift decreases the accuracy of target coverage and organs at risk (OAR) sparing. The effectiveness of audio-feedback and audio-visual feedback in correcting the baseline shift in the breathing pattern of the patient has been demonstrated previously. However, the baseline shift derived from the intrafraction motion of the patient's body cannot be corrected by these methods. In the present study, the authors designed and developed a simple and flexible system. Methods: The system consisted of a web camera and a computer running our in-house software. The in-house software was adapted to template matching andmore » also to no preimage processing. The system was capable of monitoring the baseline shift in the intrafraction motion of the patient's body. Another marker box was used to monitor the baseline shift due to the flexible setups required of a marker box for gated signals. The system accuracy was evaluated by employing a respiratory motion phantom and was found to be within AAPM Task Group 142 tolerance (positional accuracy <2 mm and temporal accuracy <100 ms) for respiratory-gated radiation therapy. Additionally, the effectiveness of this flexible and independent system in gated treatment was investigated in healthy volunteers, in terms of the results from the differences in the baseline shift detectable between the marker positions, which the authors evaluated statistically. Results: The movement of the marker on the sternum [1.599 {+-} 0.622 mm (1 SD)] was substantially decreased as compared with the abdomen [6.547 {+-} 0.962 mm (1 SD)]. Additionally, in all of the volunteers, the baseline shifts for the sternum [-0.136 {+-} 0.868 (2 SD)] were in better agreement with the nominal baseline shifts than was the case for the abdomen [-0.722 {+-} 1.56 mm (2 SD)]. The baseline shifts could be accurately measured and detected using the monitoring system, which could acquire the movement of the marker on the sternum. The baseline shift-monitoring system with the displacement-based methods for highly accurate respiratory-gated treatments should be used to make most of the displacement-based gating methods. Conclusions: The advent of intensity modulated radiation therapy and volumetric modulated radiation therapy facilitates margin reduction for the planning target volumes and the OARs, but highly accurate irradiation is needed to achieve target coverage and OAR sparing with a small margin. The baseline shifts can affect treatment not only with the respiratory gating system but also without the system. Our system can manage the baseline shift and also enables treatment irradiation to be undertaken with high accuracy.« less

Organ transplant tissue rejection: detection and staging by fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

MacAulay, Calum E.; Whitehead, Peter D.; McManus, Bruce; Zeng, Haishan; Wilson-McManus, Janet; MacKinnon, Nick; Morgan, David C.; Dong, Chunming; Gerla, Paul; Kenyon, Jennifer

1998-07-01

Patients receiving heart or other organ transplants usually require some level of anti-rejection drug therapy, most commonly cyclosporine. The rejection status of the organ must be monitored to determine the optimal anti-rejection drug therapy. The current method for monitoring post-transplant rejection status of heart transplant patients consists of taking biopsies from the right ventricle. In this work we have developed a system employing optical and signal-processing techniques that will allow a cardiologist to measure spectral changes associated with tissue rejection using an optical catheter probe. The system employs time gated illumination and detection systems to deal with the dynamic signal acquisition problems associated with in vivo measurements of a beating heart. Spectral data processing software evaluates and processes the data to produce a simple numerical score. Results of measurements made on 100 excised transplanted isograft and allograft rat hearts have demonstrated the ability of the system to detect the presence of rejection and to accurately correlate the spectroscopic results with the ISHLT (International Society for Heart and Lung Transplantation) stage of rejection determined by histopathology. In vivo measurements using a pig transplant model are now in process.

A sensitive and accurate quantification method for the detection of hepatitis B virus covalently closed circular DNA by the application of a droplet digital polymerase chain reaction amplification system.

PubMed

Mu, Di; Yan, Liang; Tang, Hui; Liao, Yong

2015-10-01

To develop a sensitive and accurate assay system for the quantification of covalently closed circular HBV DNA (cccDNA) for future clinical monitoring of cccDNA fluctuation during antiviral therapy in the liver of infected patients. A droplet digital PCR (ddPCR)-based assay system detected template DNA input at the single copy level (or ~10(-5) pg of plasmid HBV DNA) by using serially diluted plasmid HBV DNA samples. Compared with the conventional quantitative PCR assay in the detection of cccDNA, which required at least 50 ng of template DNA input, a parallel experiment applying a ddPCR system demonstrates that the lowest detection limit of cccDNA from HepG2.215 cellular DNA samples is around 1 ng, which is equivalent to 0.54 ± 0.94 copies of cccDNA. In addition, we demonstrated that the addition of cccDNA-safe exonuclease and utilization of cccDNA-specific primers in the ddPCR assay system significantly improved the detection accuracy of HBV cccDNA from HepG2.215 cellular DNA samples. The ddPCR-based cccDNA detection system is a sensitive and accurate assay for the quantification of cccDNA in HBV-transfected HepG2.215 cellular DNA samples and may represent an important method for future application in monitoring cccDNA fluctuation during antiviral therapy.

Achilles tendon reflex measuring system

NASA Astrophysics Data System (ADS)

Szebeszczyk, Janina; Straszecka, Joanna

1995-06-01

The examination of Achilles tendon reflex is widely used as a simple, noninvasive clinical test in diagnosis and pharmacological therapy monitoring in such diseases as: hypothyroidism, hyperthyroidism, diabetic neuropathy, the lower limbs obstructive angiopathies and intermittent claudication. Presented Achilles tendon reflect measuring system is based on the piezoresistive sensor connected with the cylinder-piston system. To determinate the moment of Achilles tendon stimulation a detecting circuit was used. The outputs of the measuring system are connected to the PC-based data acquisition board. Experimental results showed that the measurement accuracy and repeatability is good enough for diagnostics and therapy monitoring purposes. A user friendly, easy-to-operate measurement system fulfills all the requirements related to recording, presentation and storing of the patients' reflexograms.

A computer vision-based system for monitoring Vojta therapy.

PubMed

Khan, Muhammad Hassan; Helsper, Julien; Farid, Muhammad Shahid; Grzegorzek, Marcin

2018-05-01

A neurological illness is t he disorder in human nervous system that can result in various diseases including the motor disabilities. Neurological disorders may affect the motor neurons, which are associated with skeletal muscles and control the body movement. Consequently, they introduce some diseases in the human e.g. cerebral palsy, spinal scoliosis, peripheral paralysis of arms/legs, hip joint dysplasia and various myopathies. Vojta therapy is considered a useful technique to treat the motor disabilities. In Vojta therapy, a specific stimulation is given to the patient's body to perform certain reflexive pattern movements which the patient is unable to perform in a normal manner. The repetition of stimulation ultimately brings forth the previously blocked connections between the spinal cord and the brain. After few therapy sessions, the patient can perform these movements without external stimulation. In this paper, we propose a computer vision-based system to monitor the correct movements of the patient during the therapy treatment using the RGBD data. The proposed framework works in three steps. In the first step, patient's body is automatically detected and segmented and two novel techniques are proposed for this purpose. In the second step, a multi-dimensional feature vector is computed to define various movements of patient's body during the therapy. In the final step, a multi-class support vector machine is used to classify these movements. The experimental evaluation carried out on the large captured dataset shows that the proposed system is highly useful in monitoring the patient's body movements during Vojta therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Temperature and pressure fiber-optic sensors applied to minimally invasive diagnostics and therapies

NASA Astrophysics Data System (ADS)

Hamel, Caroline; Pinet, Éric

2006-02-01

We present how fiber-optic temperature or pressure sensors could be applied to minimally invasive diagnostics and therapies. For instance a miniature pressure sensor based on micro-optical mechanical systems (MOMS) could solve most of the problems associated with fluidic pressure transduction presently used for triggering purposes. These include intra-aortic balloon pumping (IABP) therapy and other applications requiring detection of fast and/or subtle fluid pressure variations such as for intracranial pressure monitoring or for urology diagnostics. As well, miniature temperature sensors permit minimally invasive direct temperature measurement in diagnostics or therapies requiring energy transfer to living tissues. The extremely small size of fiber-optic sensors that we have developed allows quick and precise in situ measurements exactly where the physical parameters need to be known. Furthermore, their intrinsic immunity to electromagnetic interference (EMI) allows for the safe use of EMI-generating therapeutic or diagnostic equipments without compromising the signal quality. With the trend of ambulatory health care and the increasing EMI noise found in modern hospitals, the use of multi-parameter fiber-optic sensors will improve constant patient monitoring without any concern about the effects of EMI disturbances. The advantages of miniature fiberoptic sensors will offer clinicians new monitoring tools that open the way for improved diagnostic accuracy and new therapeutic technologies.

Advanced Tracers in PET Imaging of Cardiovascular Disease

PubMed Central

Zhang, Wei; Wu, Hua; Liu, Gang

2014-01-01

Cardiovascular disease is the leading cause of death worldwide. Molecular imaging with targeted tracers by positron emission tomography (PET) allows for the noninvasive detection and characterization of biological changes at the molecular level, leading to earlier disease detection, objective monitoring of therapies, and better prognostication of cardiovascular diseases progression. Here we review, the current role of PET in cardiovascular disease, with emphasize on tracers developed for PET imaging of cardiovascular diseases. PMID:25389529

Validation of an enzyme-linked immunosorbent assay that detects Histoplasma capsulatum antigenuria in Colombian patients with AIDS for diagnosis and follow-up during therapy.

PubMed

Caceres, Diego H; Scheel, Christina M; Tobón, Angela M; Ahlquist Cleveland, Angela; Restrepo, Angela; Brandt, Mary E; Chiller, Tom; Gómez, Beatriz L

2014-09-01

We validated an antigen capture enzyme-linked immunosorbent assay (ELISA) in Colombian persons with AIDS and proven histoplasmosis and evaluated the correlation between antigenuria and clinical improvement during follow-up. The sensitivity of the Histoplasma capsulatum ELISA was 86%, and the overall specificity was 94%. The antigen test successfully monitored the response to therapy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Detection of correct and incorrect measurements in real-time continuous glucose monitoring systems by applying a postprocessing support vector machine.

PubMed

Leal, Yenny; Gonzalez-Abril, Luis; Lorencio, Carol; Bondia, Jorge; Vehi, Josep

2013-07-01

Support vector machines (SVMs) are an attractive option for detecting correct and incorrect measurements in real-time continuous glucose monitoring systems (RTCGMSs), because their learning mechanism can introduce a postprocessing strategy for imbalanced datasets. The proposed SVM considers the geometric mean to obtain a more balanced performance between sensitivity and specificity. To test this approach, 23 critically ill patients receiving insulin therapy were monitored over 72 h using an RTCGMS, and a dataset of 537 samples, classified according to International Standards Organization (ISO) criteria (372 correct and 165 incorrect measurements), was obtained. The results obtained were promising for patients with septic shock or with sepsis, for which the proposed system can be considered as reliable. However, this approach cannot be considered suitable for patients without sepsis.

Urine colorimetry to detect Low rifampin exposure during tuberculosis therapy: a proof-of-concept study.

PubMed

Zentner, Isaac; Schlecht, Hans P; Khensouvann, Lorna; Tamuhla, Neo; Kutzler, Michele; Ivaturi, Vijay; Pasipanodya, Jotam G; Gumbo, Tawanda; Peloquin, Charles A; Bisson, Gregory P; Vinnard, Christopher

2016-06-01

The cost and complexity of current approaches to therapeutic drug monitoring during tuberculosis (TB) therapy limits widespread use in areas of greatest need. We sought to determine whether urine colorimetry could have a novel application as a form of therapeutic drug monitoring during anti-TB therapy. Among healthy volunteers, we evaluated 3 dose sizes of rifampin (150 mg, 300 mg, and 600 mg), performed intensive pharmacokinetic sampling, and collected a timed urine void at 4 h post-dosing. The absorbance peak at 475 nm was measured after rifamycin extraction. The optimal cutoff was evaluated in a study of 39 HIV/TB patients undergoing TB treatment in Botswana. In the derivation study, a urine colorimetric assay value of 4.0 × 10(-2) Abs, using a timed void 4 h after dosing, demonstrated a sensitivity of 92 % and specificity of 60 % to detect a peak rifampin concentration (Cmax) under 8 mg/L, with an area under the ROC curve of 0.92. In the validation study, this cutoff was specific (100 %) but insensitive (28 %). We observed similar test characteristics for a target Cmax target of 6.6 mg/L, and a target area under the drug concentration-versus-time curve (AUC0-8) target of 24.1 mg•hour/L. The urine colorimetric assay was specific but insensitive to detect low rifampin serum concentrations among HIV/TB patients. In future work we will attempt to optimize sampling times and assay performance, with the goal of delivering a method that can translate into a point-of-care assessment of rifampin exposure during anti-TB therapy.

[Latest Treatment of Viral Hepatitis--Overcoming Hepatitis C and Reactivation of Hepatitis B].

PubMed

Tanaka, Yasuhito

2016-02-01

Hepatitis B virus (HBV) and hepatitis C virus (HCV), discovered as causative viruses of post-transfusion hepatitis, become persistent infections, leading to chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). For HCV, recent IFN-free direct-acting antiviral (DAA) therapies have increased sustained virological response (SVR) rates and reduced adverse events. IFN-based therapies, still the standard of care in Asian countries, are influenced by IL28B genetic variants and the liver fibrosis stage, but the DAA combinations obscure the influence of these factors. These new therapies can eradicate HCV and prevent HCC development. On the other hand, it is difficult to eradicate HBV completely. Although HBV infection can be prevented by vaccination, reactivation of HBV following anti-cancer chemotherapy and immunosuppressive therapy is a well-known complication. HBV reactivation has been reported to be associated with anti-CD20 monoclonal antibody rituximab-containing chemotherapy and TNF-α inhibitor-containing immunosuppressive therapy in HBV-resolved patients. Our prospective observational study revealed that monthly monitoring of HBV DNA was useful for preventing HBV reactivation-related hepatitis among B-cell non-Hodgkin lymphoma patients with resolved HBV infection following rituximab-steroid-chemo, suggesting that preemptive therapy guided by serial HBV DNA monitoring should be recommended. Recently, highly sensitive HBsAg detection by Lumipulse HBsAg-HQ may be useful for several clinical applications. The sensitivity of this assay (5 mIU/mL) was approximately 10-fold higher than Abbott ARCHITECT, but still lower than HBV-DNA assays. The convenient HBsAg-HQ may be useful for detecting occult HBV infection and HBV reactivation in relatively low-risk groups except for those receiving rituximab-steroid-chemo. [

Characterization of scintillator crystals for usage as prompt gamma monitors in particle therapy

NASA Astrophysics Data System (ADS)

Roemer, K.; Pausch, G.; Bemmerer, D.; Berthel, M.; Dreyer, A.; Golnik, C.; Hueso-González, F.; Kormoll, T.; Petzoldt, J.; Rohling, H.; Thirolf, P.; Wagner, A.; Wagner, L.; Weinberger, D.; Fiedler, F.

2015-10-01

Particle therapy in oncology is advantageous compared to classical radiotherapy due to its well-defined penetration depth. In the so-called Bragg peak, the highest dose is deposited; the tissue behind the cancerous area is not exposed. Different factors influence the range of the particle and thus the target area, e.g. organ motion, mispositioning of the patient or anatomical changes. In order to avoid over-exposure of healthy tissue and under-dosage of cancerous regions, the penetration depth of the particle has to be monitored, preferably already during the ongoing therapy session. The verification of the ion range can be performed using prompt gamma emissions, which are produced by interactions between projectile and tissue, and originate from the same location and time of the nuclear reaction. The prompt gamma emission profile and the clinically relevant penetration depth are correlated. Various imaging concepts based on the detection of prompt gamma rays are currently discussed: collimated systems with counting detectors, Compton cameras with (at least) two detector planes, or the prompt gamma timing method, utilizing the particle time-of-flight within the body. For each concept, the detection system must meet special requirements regarding energy, time, and spatial resolution. Nonetheless, the prerequisites remain the same: the gamma energy region (2 to 10 MeV), high counting rates and the stability in strong background radiation fields. The aim of this work is the comparison of different scintillation crystals regarding energy and time resolution for optimized prompt gamma detection.

[Clinical benefit of HCV core antigen assay in patients receiving interferon and ribavirin combination therapy].

PubMed

Higashimoto, Makiko; Takahashi, Masahiko; Jokyu, Ritsuko; Saito, Hidetsugu

2006-02-01

A highly sensitive second generation HCV core antigen assay has recently been developed. We compared viral disappearance and kinetics data between commercially available core antigen assays, Lumipulse Ortho HCV Ag, and a quantitative HCV RNA PCR assay, Cobas Amplicor HCV Monitor Test, Version 2 to estimate the predictive benefit of sustained viral response (SVR) and non-SVR in 59 patients treated with interferon and ribavirin combination therapy. We found a good correlation between HCV core Ag and HCV RNA level regardless of genotype. Although the sensitivity of the core antigen assay was lower than PCR, the dynamic range was broader than that of the PCR assay, so that we did not need to dilute the samples in 59 patients. We detected serial decline of core Ag levels in 24 hrs, 7 days and 14 days after interferon combination therapy. The decline of core antigen levels was significant in SVR patients compared to non-SVR as well as in genotype 2a, 2b patients compared to 1b. Core antigen-negative on day 1 could predict all 10 SVR patients (PPV = 100%), whereas RNA-negative could predict 22 SVR out of 25 on day 14 (PPV = 88.0%). None of the patients who had detectable serum core antigen on day 14 became SVR(NPV = 100%), although NPV was 91.2% on RNA negativity. An easy, simple, low cost new HCV core antigen detecting system seems to be useful for assessing and monitoring IFN treatment for HCV.

Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry

PubMed Central

Soh, Kah Teong; Tario, Joseph D.; Wallace, Paul K.

2018-01-01

Synopsis Plasma cell dyscrasia (PCD) is a heterogeneous disease which has seen a tremendous change in outcomes due to improved therapies. Over the last few decades, multiparametric flow cytometry has played an important role in the detection and monitoring of PCDs. Flow cytometry is a high sensitivity assay for early detection of minimal residual disease (MRD) that correlates well with progression-free survival and overall survival. Before flow cytometry can be effectively implemented in the clinical setting sample preparation, panel configuration, analysis, and gating strategies must be optimized to ensure accurate results. Current consensus methods and reporting guidelines for MRD testing are discussed. PMID:29128071

Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial

PubMed Central

2018-01-01

ABSTRACT The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture (P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.) PMID:29367293

Efficacy of T2 Magnetic Resonance Assay in Monitoring Candidemia after Initiation of Antifungal Therapy: the Serial Therapeutic and Antifungal Monitoring Protocol (STAMP) Trial.

PubMed

Mylonakis, Eleftherios; Zacharioudakis, Ioannis M; Clancy, Cornelius J; Nguyen, M Hong; Pappas, Peter G

2018-04-01

The performance of blood culture for monitoring candidemia clearance is hampered by its low sensitivity, especially during antifungal therapy. The T2 magnetic resonance (T2MR) assay combines magnetic resonance with nanotechnology to identify whole Candida species cells. A multicenter clinical trial studied the performance of T2MR in monitoring candidemia clearance compared to blood culture. Adults with a blood culture positive for yeast were enrolled and had blood cultures and T2MR testing performed on prespecified days. Thirty-one patients completed the trial. Thirteen of the 31 patients (41.9%) had at least one positive surveillance T2MR and/or blood culture result. All positive blood cultures (7/7 [100%]) had an accompanying positive T2MR result with concordance in the identified Candida sp., while only 7/23 (30.4%) T2MR results had an accompanying positive blood culture. There was one case of discordance in species identification between T2MR and the preenrollment blood culture with evidence to support deep-seated infection by the Candida spp. detected by the T2MR assay. Based on the log rank test, there was a statistically significant improvement in posttreatment surveillance using the T2MR assay compared to blood culture ( P = 0.004). Limitations of the study include the small sample size and lack of outcome data. In conclusion, the T2MR assay significantly outperformed blood cultures for monitoring the clearance of candidemia in patients receiving antifungal therapy and may be useful in determining adequate source control, timing for deescalation, and optimal duration of treatment. However, further studies are needed to determine the viability of Candida species cells detected by the T2MR assay and correlate the results with patient outcomes. (This study is registered at ClinicalTrials.gov under registration number NCT02163889.). Copyright © 2018 Mylonakis et al.

Clinical utility of eco-color-power Doppler ultrasonography and contrast enhanced magnetic resonance imaging for interpretation and quantification of joint synovitis: a review.

PubMed

Carotti, Marina; Galeazzi, Vittoria; Catucci, Francesca; Zappia, Marcello; Arrigoni, Francesco; Barile, Antonio; Giovagnoni, Andrea

2018-01-19

With the introduction of new biologics such as anti-TNF-alpha antibodies and other therapies in the treatment of inflammatory arthritis, capable of halting joint destruction and functional disability, there are new pressures on diagnostic and prognostic imaging. Early demonstration of pre-erosive inflammatory features and monitoring of the long-term effects of treatment are becoming increasingly important. Early detection of synovitis offers advantages in terms of allowing early instigation of therapy and may allow the identification of those patients displaying more aggressive disease who might benefit from early intervention with expensive DMARD therapy. Advanced imaging techniques such as ultrasound (US) and magnetic resonance imaging (MRI) have focussed on the demonstration and quantification of synovitis and allow early diagnosis of inflammatory arthropathies such as rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Synovitis represents a potential surrogate measure of disease activity that can be monitored using either MRI or US; the techniques have, generally, focused on monitoring synovial volume or quality as assessed by its vascularity. However to achieve these goals, standardisation and validation of US and MRI are required to ensure accurate diagnosis, reproducibility and reliability. Each modality has different strengths and weaknesses and levels of validation. This article aims to increase the awareness of radiologists and rheumatologists about this field and to encourage them to participate and contribute to the ongoing development of these modalities. Without this collaboration, it is unlikely that these modalities will reach their full potential in the field of rheumatological imaging. This review is in two parts. The first part addresses the role of US and colour or power Doppler sonography (PDUS) in the detection and monitoring of synovitis in inflammatory arthropathies. The second part will look at advanced MR imaging and Dynamic contrast-enhanced MRI techniques and in particular how they are applied to the monitoring of the disease process.

Optoacoustic detection of thermal lesions

NASA Astrophysics Data System (ADS)

Arsenault, Michel G.; Kolios, Michael C.; Whelan, William M.

2009-02-01

Minimally invasive thermal therapy is being investigated as an alternative cancer treatment. It involves heating tissues to greater than 55°C over a period of a few minutes, which results in tissue coagulation. Optoacoustic (OA) imaging is a new imaging technique that involves exposing tissues to pulsed light and detecting the acoustic waves that are generated. In this study, adult bovine liver tissue samples were heated using continuous wave laser energy for various times, then scanned using an optoacoustic imaging system. Large optoacoustic signal variability was observed in the native tissue prior to heating. OA signal amplitude increased with maximum tissue temperature achieved, characterized by a correlation coefficient of 0.63. In this study we show that there are detectable changes in optoacoustic signal strength that arise from tissue coagulation, which demonstrates the potential of optoacoustic technology for the monitoring of thermal therapy delivery.

Using the ATL HDI 1000 to collect demodulated RF data for monitoring HIFU lesion formation

NASA Astrophysics Data System (ADS)

Anand, Ajay; Kaczkowski, Peter J.; Daigle, Ron E.; Huang, Lingyun; Paun, Marla; Beach, Kirk W.; Crum, Lawrence A.

2003-05-01

The ability to accurately track and monitor the progress of lesion formation during HIFU (High Intensity Focused Ultrasound) therapy is important for the success of HIFU-based treatment protocols. To aid in the development of algorithms for accurately targeting and monitoring formation of HIFU induced lesions, we have developed a software system to perform RF data acquisition during HIFU therapy using a commercially available clinical ultrasound scanner (ATL HDI 1000, Philips Medical Systems, Bothell, WA). The HDI 1000 scanner functions on a software dominant architecture, permitting straightforward external control of its operation and relatively easy access to quadrature demodulated RF data. A PC running a custom developed program sends control signals to the HIFU module via GPIB and to the HDI 1000 via Telnet, alternately interleaving HIFU exposures and RF frame acquisitions. The system was tested during experiments in which HIFU lesions were created in excised animal tissue. No crosstalk between the HIFU beam and the ultrasound imager was detected, thus demonstrating synchronization. Newly developed acquisition modes allow greater user control in setting the image geometry and scanline density, and enables high frame rate acquisition. This system facilitates rapid development of signal-processing based HIFU therapy monitoring algorithms and their implementation in image-guided thermal therapy systems. In addition, the HDI 1000 system can be easily customized for use with other emerging imaging modalities that require access to the RF data such as elastographic methods and new Doppler-based imaging and tissue characterization techniques.

Pharmacovigilance in oncology: evaluation of current practice and future perspectives.

PubMed

Baldo, Paolo; De Paoli, Paolo

2014-10-01

Pharmacovigilance (PV), or drug safety monitoring, aims to improve patient safety through the detection and management of drug-related adverse reactions. It is implemented both by spontaneous reporting of adverse drug reactions (ADRs) and by careful detection of signals suggestive of drug toxicity. PV is an important clinical topic in clinical practice and pharmacotherapy, assuring the maintenance of a safe risk/benefit ratio throughout the commercial life cycle of a drug. We conducted a structured literature search on PubMed, Scopus, Cinahl and the Cochrane Library. We also performed manual searches in international databases of ADR individual reports to outline a structured profile on the topic. Our goal was to review key elements that affect safety monitoring of cancer drugs and their appropriate use, highlighting the strengths and weaknesses of PV in oncology. This paper provides an understanding of the methodologies used by PV in current clinical practice and particularly in cancer drug therapy; a focus upon reporting of ADRs by health professionals and patients; and a focus upon methods used by PV to detect new signals of risk/harm related to medicines utilization. To our knowledge, few articles focus upon the importance of PV and post-marketing surveillance of cancer drug therapies. Structured management of spontaneous reports of ADRs and data collection is essential to monitoring the safe use of drugs in this field in which pharmacotherapy is affected by high incidence of drug-related complications and by a narrow benefit/risk ratio. © 2014 John Wiley & Sons, Ltd.

Value of molecular monitoring during the treatment of chronic myeloid leukemia: a Cancer and Leukemia Group B study.

PubMed

Stock, W; Westbrook, C A; Peterson, B; Arthur, D C; Szatrowski, T P; Silver, R T; Sher, D A; Wu, D; Le Beau, M M; Schiffer, C A; Bloomfield, C D

1997-01-01

Disappearance of the Philadelphia chromosome during treatment for chronic myeloid leukemia (CML) has become an important therapeutic end point. To determine the additional value of molecular monitoring during treatment for CML, we performed a prospective, sequential analysis using quantitative Southern blot monitoring of BCR gene rearrangements of blood and marrow samples from Cancer and Leukemia Group B (CALGB) study 8761. Sixty-four previously untreated adults with chronic-phase CML who were enrolled onto CALGB 8761, a molecular-monitoring companion study to a treatment study for adults with chronic-phase CML (CALGB 9013). Treatment consisted of repetitive cycles of interferon alfa and low-dose subcutaneous cytarabine. Blood and marrow Southern blot quantitation of BCR gene rearrangements was compared with marrow cytogenetic analysis before the initiation of treatment and of specified points during therapy. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis was performed to detect residual disease in patients who achieved a complete response by Southern blot or cytogenetic analysis. Quantitative molecular monitoring by Southern blot analysis of blood samples was found to be equivalent to marrow monitoring at all time points. Twelve of 62 (19%) follow-up samples studied by Southern blot analysis had a complete loss of BCR gene rearrangement in matched marrow and blood specimens. Southern blot monitoring of blood samples was also found to be highly correlated to marrow cytogenetic evaluation at all points, although there were four discordant cases in which Southern blot analysis of blood showed no BCR gene rearrangement, yet demonstrated from 12% to 20% Philadelphia chromosome-positive metaphase cells in the marrow. RT-PCR analysis detected residual disease in five of six patients in whom no malignant cells were detected using Southern blot or cytogenetic analyses. Quantitative Southern blot analysis of blood samples may be substituted for bone marrow to monitor the response to therapy in CML and results in the need for fewer bone marrow examinations. To avoid overestimating the degree of response, marrow cytogenetic analysis should be performed when patients achieve a complete response by Southern blot monitoring. This approach provides a rational, cost-effective strategy to monitor the effect of treatment of individual patients, as well as to analyze large clinical trials in CML.

Noninvasive Imaging of Immune Checkpoint Ligand PD-L1 in Tumors and Metastases for Guiding Immunotherapy

PubMed Central

Chatterjee, Samit; Lesniak, Wojciech G.

2017-01-01

Immunotherapy holds great promise in cancer treatment. The challenges in advancing immunotherapies lie in patient stratification and monitoring therapy. Noninvasive detection of immune checkpoint ligand PD-L1 can serve as an important biomarker for guidance and monitoring of immunotherapy. Here in, we provide an overview of our efforts to develop clinically translatable PD-L1-specific imaging agents for quantitative and real-time assessment of PD-L1 expression in tumor microenvironment. PMID:28707500

A new system for continuous and remote monitoring of patients receiving home mechanical ventilation

NASA Astrophysics Data System (ADS)

Battista, L.

2016-09-01

Home mechanical ventilation is the treatment of patients with respiratory failure or insufficiency by means of a mechanical ventilator at a patient's home. In order to allow remote patient monitoring, several tele-monitoring systems have been introduced in the last few years. However, most of them usually do not allow real-time services, as they have their own proprietary communication protocol implemented and some ventilation parameters are not always measured. Moreover, they monitor only some breaths during the whole day, despite the fact that a patient's respiratory state may change continuously during the day. In order to reduce the above drawbacks, this work reports the development of a novel remote monitoring system for long-term, home-based ventilation therapy; the proposed system allows for continuous monitoring of the main physical quantities involved during home-care ventilation (e.g., differential pressure, volume, and air flow rate) and is developed in order to allow observations of different remote therapy units located in different places of a city, region, or country. The developed remote patient monitoring system is able to detect various clinical events (e.g., events of tube disconnection and sleep apnea events) and has been successfully tested by means of experimental tests carried out with pulmonary ventilators typically used to support sick patients.

A new system for continuous and remote monitoring of patients receiving home mechanical ventilation.

PubMed

Battista, L

2016-09-01

Home mechanical ventilation is the treatment of patients with respiratory failure or insufficiency by means of a mechanical ventilator at a patient's home. In order to allow remote patient monitoring, several tele-monitoring systems have been introduced in the last few years. However, most of them usually do not allow real-time services, as they have their own proprietary communication protocol implemented and some ventilation parameters are not always measured. Moreover, they monitor only some breaths during the whole day, despite the fact that a patient's respiratory state may change continuously during the day. In order to reduce the above drawbacks, this work reports the development of a novel remote monitoring system for long-term, home-based ventilation therapy; the proposed system allows for continuous monitoring of the main physical quantities involved during home-care ventilation (e.g., differential pressure, volume, and air flow rate) and is developed in order to allow observations of different remote therapy units located in different places of a city, region, or country. The developed remote patient monitoring system is able to detect various clinical events (e.g., events of tube disconnection and sleep apnea events) and has been successfully tested by means of experimental tests carried out with pulmonary ventilators typically used to support sick patients.

Monitoring on the Move

NASA Technical Reports Server (NTRS)

2000-01-01

The MyoMonitor EMG system was developed by Delsys, Inc. under SBIR funding from Johnson Space Center. It is a wearable four-channel device that can monitor muscle performance. Presently, its application include rehabilitative therapy, injury prevention, sports medicine, exercise training, and various other muscle monitoring activities. The MyoMonitor uses a two-bar single differential electrode. Due to the electrode-skin interface in traditional EMG equipment, during rigorous muscular activity, the movement of the skin causes the electrode detection surfaces to become compromised. The MyoMonitor eliminates this problem, enabling a wide array of applications and experiments during intense muscular activity. The ability to make such recordings, for example, enables novel experiments aboard the International Space Station for investigating the effect of microgravity on muscle performance. Product still commercially available as of March 2002.

Comparison of warfarin therapy clinical outcomes following implementation of an automated mobile phone-based critical laboratory value text alert system.

PubMed

Lin, Shu-Wen; Kang, Wen-Yi; Lin, Dong-Tsamn; Lee, James; Wu, Fe-Lin; Chen, Chuen-Liang; Tseng, Yufeng J

2014-01-01

Computerized alert and reminder systems have been widely accepted and applied to various patient care settings, with increasing numbers of clinical laboratories communicating critical laboratory test values to professionals via either manual notification or automated alerting systems/computerized reminders. Warfarin, an oral anticoagulant, exhibits narrow therapeutic range between treatment response and adverse events. It requires close monitoring of prothrombin time (PT)/international normalized ratio (INR) to ensure patient safety. This study was aimed to evaluate clinical outcomes of patients on warfarin therapy following implementation of a Personal Handy-phone System-based (PHS) alert system capable of generating and delivering text messages to communicate critical PT/INR laboratory results to practitioners' mobile phones in a large tertiary teaching hospital. A retrospective analysis was performed comparing patient clinical outcomes and physician prescribing behavior following conversion from a manual laboratory result alert system to an automated system. Clinical outcomes and practitioner responses to both alert systems were compared. Complications to warfarin therapy, warfarin utilization, and PT/INR results were evaluated for both systems, as well as clinician time to read alert messages, time to warfarin therapy modification, and monitoring frequency. No significant differences were detected in major hemorrhage and thromboembolism, warfarin prescribing patterns, PT/INR results, warfarin therapy modification, or monitoring frequency following implementation of the PHS text alert system. In both study periods, approximately 80% of critical results led to warfarin discontinuation or dose reduction. Senior physicians' follow-up response time to critical results was significantly decreased in the PHS alert study period (46.3% responded within 1 day) compared to the manual notification study period (24.7%; P = 0.015). No difference in follow-up response time was detected for junior physicians. Implementation of an automated PHS-based text alert system did not adversely impact clinical or safety outcomes of patients on warfarin therapy. Approximately 80% immediate recognition of text alerts was achieved. The potential benefits of an automated PHS alert for senior physicians were demonstrated.

Magnetic responsive cell based strategies for diagnostic and therapeutics.

PubMed

Gonçalves, Ana I; Miranda, Margarida S; Rodrigues, Márcia T; Reis, Rui Luis; Gomes, Manuela

2018-05-24

The potential of magnetically assisted strategies within the remit of cell-based therapies is increasing and creates new opportunities in biomedical platforms and in the field of tissue engineering and regenerative medicine (TERM). Among the magnetic elements approached to build magnetically responsive strategies, superparamagnetic iron oxide nanoparticles (SPIONs) represent tunable and precise tools whose properties can be modelled for detection, diagnosis, targeting and therapy purposes. The most investigated clinical role of SPIONs is as contrast imaging agents for tracking and monitoring cells and tissues. Nevertheless, magnetic detection also includes biomarker mapping, cell labelling and cell/drug targeting to monitor cell events and anticipate the disruption of homeostatic conditions and progression of disease. Additionally, isolation and screening techniques of cell subsets in heterogeneous populations or of proteins of interest have been explored in a magnetic sorting context. More recently, SPIONs-based technologies have been applied to stimulate cell differentiation and mechanotransduction processes and to transport genetic or drug cargo to study biological mechanisms and contribute for improved therapies. Magnetically based strategies significantly contribute for magnetic tissue engineering (magTE), in which magnetically responsive actuators built from magnetic labelled cells or magnetic functionalized systems can be remotely controlled and spatially manipulated upon the actuation of an external magnetic field for delivery or target of TE solutions. SPIONs functionalities combined with the magnetic responsiveness in multifactorial magnetically assisted platforms can revolutionize diagnosis and therapeutics providing new diagnosis and theranostic tools, encouraging regenerative medicine approaches and holding potential for more effective therapies. This review will address the contribution of SPIONs based technologies as multifunctional tools in boosting magnetically assisted cell based strategies to explore diagnostics and tracking solutions on the detection and analysis of pathologies and to generate improved treatments and therapies, envisioning precise and customized answers for the management of numerous diseases. . © 2018 IOP Publishing Ltd.

Clinical Application of Liquid Biopsy in Targeted Therapy of Metastatic Colorectal Cancer

PubMed Central

Trojan, Jörg; Klein-Scory, Susanne; Koch, Christine; Schmiegel, Wolff

2017-01-01

Background. Colorectal cancers (CRC) shed DNA into blood circulation. There is growing evidence that the analysis of circulating tumor DNA can be effectively used for monitoring of disease, to track tumor heterogeneity and to evaluate response to treatment. Case Presentation. Here, we describe two cases of patients with advanced CRC. The first case is about a patient with no available tissue for analysis of RAS mutation status. Liquid biopsy revealed RAS-wild-type and the therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibody cetuximab could be initiated. In the second case, the mutational profile of a patient with initial wild-type RAS-status was continually tracked during the course of treatment. An acquired KRAS exon 3 mutation was detected. The number of KRAS mutated fragments decreased continuously after the discontinuation of the therapy with EGFR-specific antibodies. Conclusion. Liquid biopsy provides a rapid genotype result, which accurately reproduces the current mutation status of tumor tissue. Furthermore, liquid biopsy enables close monitoring of the onset of secondary resistance to anti-EGFR therapy. PMID:28232873

Clinical Application of Liquid Biopsy in Targeted Therapy of Metastatic Colorectal Cancer.

PubMed

Trojan, Jörg; Klein-Scory, Susanne; Koch, Christine; Schmiegel, Wolff; Baraniskin, Alexander

2017-01-01

Background. Colorectal cancers (CRC) shed DNA into blood circulation. There is growing evidence that the analysis of circulating tumor DNA can be effectively used for monitoring of disease, to track tumor heterogeneity and to evaluate response to treatment. Case Presentation. Here, we describe two cases of patients with advanced CRC. The first case is about a patient with no available tissue for analysis of RAS mutation status. Liquid biopsy revealed RAS-wild-type and the therapy with anti-EGFR (epidermal growth factor receptor) monoclonal antibody cetuximab could be initiated. In the second case, the mutational profile of a patient with initial wild-type RAS-status was continually tracked during the course of treatment. An acquired KRAS exon 3 mutation was detected. The number of KRAS mutated fragments decreased continuously after the discontinuation of the therapy with EGFR-specific antibodies. Conclusion . Liquid biopsy provides a rapid genotype result, which accurately reproduces the current mutation status of tumor tissue. Furthermore, liquid biopsy enables close monitoring of the onset of secondary resistance to anti-EGFR therapy.

Secondary Stroke Prevention: Improving Diagnosis and Management with Newer Technologies.

PubMed

Imam, Yahia Z; D'Souza, Atlantic; Malik, Rayaz A; Shuaib, Ashfaq

2016-12-01

Treatment of hypertension, diabetes, high cholesterol, smoking cessation, and healthy lifestyle have all contributed to the decline in the incidence of vascular disease over the last several decades. Patients who suffer an acute stroke are at a high risk for recurrence. Introduction of newer technologies and their wider use allows for better identification of patients in whom the risk of recurrence following an acute stroke may be very high. Traditionally, the major focus for diagnosis and management has focused on patient history, examination, imaging for carotid stenosis/occlusion, and detection of AF and paroxysmal AF (PAF) with 24-48 h cardiac monitoring. This review focuses on the usefulness of three newer investigative tools that are becoming widely available and lead to better prevention. Continuous ambulatory blood pressure measurements for 24 h or longer and 3D Doppler measures of the carotid arteries provide key useful information on the state of vascular health and enhance our ability to monitor the response to preventive therapies. Furthermore, the detection of PAF can be significantly improved with prolonged cardiac monitoring for 3 weeks or longer, enabling the initiation of appropriate prevention therapy. This review will focus on the potential impact and importance of these emerging technologies on the prevention of recurrent stroke in high-risk patients.

Monitoring of Hadrontherapy Treatments by Means of Charged Particle Detection.

PubMed

Muraro, Silvia; Battistoni, Giuseppe; Collamati, Francesco; De Lucia, Erika; Faccini, Riccardo; Ferroni, Fernando; Fiore, Salvatore; Frallicciardi, Paola; Marafini, Michela; Mattei, Ilaria; Morganti, Silvio; Paramatti, Riccardo; Piersanti, Luca; Pinci, Davide; Rucinski, Antoni; Russomando, Andrea; Sarti, Alessio; Sciubba, Adalberto; Solfaroli-Camillocci, Elena; Toppi, Marco; Traini, Giacomo; Voena, Cecilia; Patera, Vincenzo

2016-01-01

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages.

Monitoring of Hadrontherapy Treatments by Means of Charged Particle Detection

PubMed Central

Muraro, Silvia; Battistoni, Giuseppe; Collamati, Francesco; De Lucia, Erika; Faccini, Riccardo; Ferroni, Fernando; Fiore, Salvatore; Frallicciardi, Paola; Marafini, Michela; Mattei, Ilaria; Morganti, Silvio; Paramatti, Riccardo; Piersanti, Luca; Pinci, Davide; Rucinski, Antoni; Russomando, Andrea; Sarti, Alessio; Sciubba, Adalberto; Solfaroli-Camillocci, Elena; Toppi, Marco; Traini, Giacomo; Voena, Cecilia; Patera, Vincenzo

2016-01-01

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages. PMID:27536555

A cost-effective monitoring technique in particle therapy via uncollimated prompt gamma peak integration

NASA Astrophysics Data System (ADS)

Krimmer, J.; Angellier, G.; Balleyguier, L.; Dauvergne, D.; Freud, N.; Hérault, J.; Létang, J. M.; Mathez, H.; Pinto, M.; Testa, E.; Zoccarato, Y.

2017-04-01

For the purpose of detecting deviations from the prescribed treatment during particle therapy, the integrals of uncollimated prompt gamma-ray timing distributions are investigated. The intention is to provide information, with a simple and cost-effective setup, independent from monitoring devices of the beamline. Measurements have been performed with 65 MeV protons at a clinical cyclotron. Prompt gamma-rays emitted from the target are identified by means of time-of-flight. The proton range inside the PMMA target has been varied via a modulator wheel. The measured variation of the prompt gamma peak integrals as a function of the modulator position is consistent with simulations. With detectors covering a solid angle of 25 msr (corresponding to a diameter of 3-4 in. at a distance of 50 cm from the beam axis) and 108 incident protons, deviations of a few per cent in the prompt gamma-ray count rate can be detected. For the present configuration, this change in the count rate corresponds to a 3 mm change in the proton range in a PMMA target. Furthermore, simulation studies show that a combination of the signals from multiple detectors may be used to detect a misplacement of the target. A different combination of these signals results in a precise number of the detected prompt gamma rays, which is independent on the actual target position.

The exploitation of inflammation in photodynamic therapy of pleural cancer (Conference Presentation)

NASA Astrophysics Data System (ADS)

Davis, Richard W.; Miller, Joann; Houser, Cassandra L.; Klampatsa, Astero; Jenkins, Tim; Cengel, Keith A.; Albelda, Steven M.; Busch, Theresa M.

2017-02-01

The onset of inflammation is a well-known physiology in tumors treated with photodynamic therapy (PDT). After PDT, the release of danger signals causes an influx of neutrophils, activation of dendritic cells, and an eventual initiation of the adaptive immune response. However, inflammation also lies at a crucial fulcrum for treatment outcome, as it can stimulate the expression of resistance factors. Therefore, effective treatment with PDT requires an understanding of the holistic contribution of inflammation. Within, we outline two means of studying tumor inflammation in the setting of PDT. Experiments are conducted in murine models of mesothelioma, including those that incorporate surgery prior to PDT or pleural propagation of the disease. First, we use a chemiluminescent agent, luminol, to detect the influx of neutrophils by in vivo molecular imaging. This longitudinal approach allows for the repeated non-invasive monitoring of PDT-induced neutrophil influx. Data clearly identify protocol-specific differences in tumor-associated neutrophil activity. Second, we describe the application of cone-beam CT to detect the fibrosis associated with murine orthotropic mesothelioma models. This approach incorporates novel methods in image segmentation to accurately identify diffuse disease in the thoracic cavity. These studies lay the foundation for future research to correlate long-term response with local PDT-induced inflammation. Such methods in monitoring of inflammation or tumor burden will enable characterization of the consequences of combinatorial therapy (e.g., intraoperative PDT). Resulting data will guide the selection of pharmacological agents or molecular imaging techniques that respectively exploit inflammation for therapeutic or monitoring purposes.

SU-D-BRB-02: Investigations of Secondary Ion Distributions in Carbon Ion Therapy Using the Timepix Detector.

PubMed

Gwosch, K; Hartmann, B; Jakubek, J; Granja, C; Soukup, P; Jaekel, O; Martisikova, M

2012-06-01

Due to the high conformity of carbon ion therapy, unpredictable changes in the patient's geometry or deviations from the planned beam properties can result in changes of the dose distribution. PET has been used successfully to monitor the actual dose distribution in the patient. However, it suffers from biological washout processes and low detection efficiency. The purpose of this contribution is to investigate the potential of beam monitoring by detection of prompt secondary ions emerging from a homogeneous phantom, simulating a patient's head. Measurements were performed at the Heidelberg Ion-Beam Therapy Center (Germany) using a carbon ion pencil beam irradiated on a cylindrical PMMA phantom (16cm diameter). For registration of the secondary ions, the Timepix detector was used. This pixelated silicon detector allows position-resolved measurements of individual ions (256×256 pixels, 55μm pitch). To track the secondary ions we used several parallel detectors (3D voxel detector). For monitoring of the beam in the phantom, we analyzed the directional distribution of the registered ions. This distribution shows a clear dependence on the initial beam energy, width and position. Detectable were range differences of 1.7mm, as well as vertical and horizontal shifts of the beam position by 1mm. To estimate the clinical potential of this method, we measured the yield of secondary ions emerging from the phantom for a beam energy of 226MeV/u. The differential distribution of secondary ions as a function of the angle from the beam axis for angles between 0 and 90° will be presented. In this setup the total yield in the forward hemisphere was found to be in the order of 10 -1 secondary ions per primary carbon ion. The presented measurements show that tracking of secondary ions provides a promising method for non-invasive monitoring of ion beam parameters for clinical relevant carbon ion fluences. Research with the pixel detectors was carried out in frame of the Medipix Collaboration. © 2012 American Association of Physicists in Medicine.

Polymedication Electronic Monitoring System (POEMS) - a new technology for measuring adherence.

PubMed

Arnet, Isabelle; Walter, Philipp N; Hersberger, Kurt E

2013-01-01

Reliable and precise measurement of patient adherence to medications is feasible by incorporating a microcircuitry into pharmaceutical packages of various designs, such that the maneuvers needed to remove a dose of drug are detected, time-stamped, and stored. The principle is called "electronic medication event monitoring" but is currently limited to the monitoring of a single drug therapy. Our aims were introducing a new technology; a clear, self-adhesive polymer film, with printed loops of conductive wires that can be affixed to multidrug punch cards for the electronic adherence monitoring of multiple medication regimens (Polymedication Electronic Monitoring System, POEMS), and illustrating potential benefits for patient care. We present a preliminary report with one patient experience. Our illustrative case was supplied with a pre-filled 7-day multiple medication punch card with unit-of-use doses for specific times of the day (six pills in the morning cavity, two pills in the evening cavity, and one pill in case of insomnia in the bedtime cavity), with the new electronic film affixed on it. The intake times over 1 week were extremely skewed (median intake hours at 2:00 pm for the morning doses and at 6:40 pm for the evening doses). After an intervention aimed at optimizing the timing adherence, the morning and evening intake hours became more balanced, with 42.3% of correct dosing intervals (±3 h) for drugs with twice daily intake (vs. 0% before the intervention). The electronic monitoring of the entire therapy revealed an intake pattern that would have remained undiscovered with any other device and allowed a personalized intervention to correct an inadequate medication intake behavior. POEMS may guide health professionals when they need to optimize a pharmacotherapy because of suspected insufficient adherence. Further, knowing the intake pattern of the entire pharmacotherapy can elucidate unreached clinical outcome, drug-drug interactions, and drug resistance. In the near future, one could imagine that medication adherence data over the entire therapy plan would be available as soon as the electronic wires are activated, so that a failure to take medication could be detected immediately and intervention could be taken if appropriate.

Developing laser-based therapy monitoring of early caries in pediatric dental settings

NASA Astrophysics Data System (ADS)

Zhou, Yaxuan; Jiang, Yang; Kim, Amy S.; Xu, Zheng; Berg, Joel H.; Seibel, Eric J.

2017-02-01

Optical imaging modalities and therapy monitoring protocols are required for the emergence of non-surgical interventions for treating infections in teeth to remineralize the enamel. Current standard of visual inspection, tactile probing and radiograph for caries detection is not highly sensitive, quantitative, and safe. Furthermore, the latter two are not viable options for interproximal caries. We present preliminary results of multimodal laser-based imaging and uorescence spectroscopy in a blinded clinical study comparing two topical therapies of early interproximal caries in children. With a spacer placed interproximally both at baseline and followup examinations, the 405-nm excited red porphyrin uorescence imaging with green auto uorescence is measured and compared to a 12-month follow-up. 405-nm laser-induced uorescence spectroscopy is also measured from the center of selected multimodal video imaging frames. These results of three subjects are analyzed both qualitatively by comparing spectra and quantitatively based on uorescence region segmentation, and then are compared to the standard of care(visual examination and radiograph interpretation). Furthermore, this study points out challenges associated with optically monitoring non-surgical dental interventions over long periods of time in clinical practice and also indicates future direction for improvement on the protocol.

Cell Phone-Based and Adherence Device Technologies for HIV Care and Treatment in Resource-Limited Settings: Recent Advances.

PubMed

Campbell, Jeffrey I; Haberer, Jessica E

2015-12-01

Numerous cell phone-based and adherence monitoring technologies have been developed to address barriers to effective HIV prevention, testing, and treatment. Because most people living with HIV and AIDS reside in resource-limited settings (RLS), it is important to understand the development and use of these technologies in RLS. Recent research on cell phone-based technologies has focused on HIV education, linkage to and retention in care, disease tracking, and antiretroviral therapy adherence reminders. Advances in adherence devices have focused on real-time adherence monitors, which have been used for both antiretroviral therapy and pre-exposure prophylaxis. Real-time monitoring has recently been combined with cell phone-based technologies to create real-time adherence interventions using short message service (SMS). New developments in adherence technologies are exploring ingestion monitoring and metabolite detection to confirm adherence. This article provides an overview of recent advances in these two families of technologies and includes research on their acceptability and cost-effectiveness when available. It additionally outlines key challenges and needed research as use of these technologies continues to expand and evolve.

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

..., plasma, urine, or other body fluids. This device is intended as an aid in monitoring patients for disease progress or response to therapy or for the detection of recurrent or residual disease. (b) Classification.... 866.6010 Section 866.6010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy.

PubMed

Lupini, Laura; Moretti, Anna; Bassi, Cristian; Schirone, Alessio; Pedriali, Massimo; Querzoli, Patrizia; Roncarati, Roberta; Frassoldati, Antonio; Negrini, Massimo

2018-03-12

Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0.01% of the total ESR1 allelic fraction. After COLD-PCR enrichment, methods based on next-generation sequencing or droplet-digital PCR were employed to detect and quantify ESR1 mutations. We applied the method to detect ESR1 mutations in circulating free DNA from the plasma of 56 patients with metastatic ER-positive BC. Fifteen of these patients were found to have ESR1 mutations at codons 536-538. This study demonstrates the utility of the enhanced-ice-COLD-PCR approach for simplifying and improving the detection of ESR1 tumor mutations in liquid biopsies. Because of its high sensitivity, the approach may potentially be applicable to patients with non-metastatic disease.

Detection and monitoring of cardiotoxicity-what does modern cardiology offer?

PubMed

Jurcut, Ruxandra; Wildiers, Hans; Ganame, Javier; D'hooge, Jan; Paridaens, Robert; Voigt, Jens-Uwe

2008-05-01

With new anticancer therapies, many patients can have a long life expectancy. Treatment-related comorbidities become an issue for cancer survivors. Cardiac toxicity remains an important side effect of anticancer therapies. Myocardial dysfunction can become apparent early or long after end of therapy and may be irreversible. Detection of cardiac injury is crucial since it may facilitate early therapeutic measures. Traditionally, chemotherapy-induced cardiotoxicity has been detected by measuring changes in left ventricular ejection fraction. This parameter is, however, insensitive to subtle changes in myocardial function as they occur in early cardiotoxicity. This review will discuss conventional and modern cardiologic approaches of assessing myocardial function. It will focus on Doppler myocardial imaging, a method which allows to sensitively measure myocardial function parameters like myocardial velocity, deformation (strain), or deformation rate (strain rate) and which has been shown to reliably detect early abnormalities in both regional and global myocardial function in an early stage. Other newer echocardiographic function estimators are based on automated border detection algorithms and ultrasonic integrated backscatter analysis. A further technique to be discussed is dobutamine stress echocardiography. The use of new biomarkers like B-type natriuretic peptide and troponin and less often used imaging techniques like magnetic resonance imaging and computed tomography will also be mentioned.

Future technologies for monitoring HIV drug resistance and cure.

PubMed

Parikh, Urvi M; McCormick, Kevin; van Zyl, Gert; Mellors, John W

2017-03-01

Sensitive, scalable and affordable assays are critically needed for monitoring the success of interventions for preventing, treating and attempting to cure HIV infection. This review evaluates current and emerging technologies that are applicable for both surveillance of HIV drug resistance (HIVDR) and characterization of HIV reservoirs that persist despite antiretroviral therapy and are obstacles to curing HIV infection. Next-generation sequencing (NGS) has the potential to be adapted into high-throughput, cost-efficient approaches for HIVDR surveillance and monitoring during continued scale-up of antiretroviral therapy and rollout of preexposure prophylaxis. Similarly, improvements in PCR and NGS are resulting in higher throughput single genome sequencing to detect intact proviruses and to characterize HIV integration sites and clonal expansions of infected cells. Current population genotyping methods for resistance monitoring are high cost and low throughput. NGS, combined with simpler sample collection and storage matrices (e.g. dried blood spots), has considerable potential to broaden global surveillance and patient monitoring for HIVDR. Recent adaptions of NGS to identify integration sites of HIV in the human genome and to characterize the integrated HIV proviruses are likely to facilitate investigations of the impact of experimental 'curative' interventions on HIV reservoirs.

Hemodynamic monitoring in the critically ill.

PubMed

Voga, G

1995-06-01

Monitoring of vital functions is one of the most important and essential tools in the management of critically ill patients in the ICU. Today it is possible to detect and analyze a great variety of physiological signals by various noninvasive and invasive techniques. An intensivist should be able to select and perform the most appropriate monitoring method for the individual patient considering risk-benefit ratio of the particular monitoring technique and the need for immediate therapy, specific diagnosis, continuous monitoring and evaluation of morphology should be included. Despite rapid development of noninvasive monitoring techniques, invasive hemodynamic monitoring in still one of the most basic ICU procedures. It enables monitoring of pressures, flow and saturation, pressures in the systemic and pulmonary circulation, estimation of cardiac performance and judgment of the adequacy of the cardiocirculatory system. Carefully and correctly obtained information are basis for proper hemodynamic assessment which usually effects the therapeutic decisions.

Therapeutic drug monitoring of tamoxifen using LC-MS/MS.

PubMed

Tchu, Simone M; Lynch, Kara L; Wu, Alan H B

2012-01-01

Tamoxifen is a selective estrogen receptor modulator (SERM) that is used widely in the treatment of estrogen receptor positive breast cancer (ER+). Therapeutic monitoring of tamoxifen, and its metabolites N-desmethyltamoxifen (NDTam) and 4-hydroxy-N-desmethyltamoxifen (endoxifen), may be clinically useful for guiding treatment decisions. Two significant barriers to tamoxifen efficacy are: (1) variability in conversion of tamoxifen into the potent antiestrogenic metabolite, endoxifen, and (2) poor compliance and adherence to tamoxifen therapy. Therapeutic monitoring can be used to address both of these issues. Low levels of endoxifen indicate either poor compliance or poor metabolism of tamoxifen. Low tamoxifen levels would suggest poor compliance while a low ratio of endoxifen to NDTam would be indicative of poor metabolism. Solid phase extraction of patient serum followed by liquid chromatography tandem mass spectrometry (LC-MS/MS) detection enables rapid, accurate, detection of tamoxifen, N-desmethyltamoxifen, and endoxifen.

Monitoring tissue metabolism via time-resolved laser fluorescence

NASA Astrophysics Data System (ADS)

Maerz, Holger K.; Buchholz, Rainer; Emmrich, Frank; Fink, Frank; Geddes, Clive L.; Pfeifer, Lutz; Raabe, Ferdinand; Marx, Uwe

1999-05-01

Most assays for drug screening are monitoring the metabolism of cells by detecting the NADH content, which symbolize its metabolic activity, indirectly. Nowadays, the performance of a LASER enables us to monitor the metabolic state of mammalian cells directly and on-line by using time-resolved autofluorescence detection. Therefore, we developed in combination with tissue engineering, an assay for monitoring minor toxic effects of volatile organic compounds (VOC), which are accused of inducing Sick Building Syndrome (SBS). Furthermore, we used the Laserfluoroscope (LF) for pharmacological studies on human bone marrow in vitro with special interest in chemotherapy simulation. In cancer research and therapy, the effect of chemostatica in vitro in the so-called oncobiogram is being tested; up to now without great success. However, it showed among other things that tissue structure plays a vital role. Consequently, we succeeded in simulating a chemotherapy in vitro on human bone marrow. Furthermore, after tumor ektomy we were able to distinguish between tumoric and its surrounding healthy tissue by using the LF. With its sensitive detection of metabolic changes in tissues the LF enables a wide range of applications in biotechnology, e.g. for quality control in artificial organ engineering or biocompatability testing.

Blood leakage detection during dialysis therapy based on fog computing with array photocell sensors and heteroassociative memory model

PubMed Central

Wu, Jian-Xing; Huang, Ping-Tzan; Li, Chien-Ming

2018-01-01

Blood leakage and blood loss are serious life-threatening complications occurring during dialysis therapy. These events have been of concerns to both healthcare givers and patients. More than 40% of adult blood volume can be lost in just a few minutes, resulting in morbidities and mortality. The authors intend to propose the design of a warning tool for the detection of blood leakage/blood loss during dialysis therapy based on fog computing with an array of photocell sensors and heteroassociative memory (HAM) model. Photocell sensors are arranged in an array on a flexible substrate to detect blood leakage via the resistance changes with illumination in the visible spectrum of 500–700 nm. The HAM model is implemented to design a virtual alarm unit using electricity changes in an embedded system. The proposed warning tool can indicate the risk level in both end-sensing units and remote monitor devices via a wireless network and fog/cloud computing. The animal experimental results (pig blood) will demonstrate the feasibility. PMID:29515815

Blood leakage detection during dialysis therapy based on fog computing with array photocell sensors and heteroassociative memory model.

PubMed

Wu, Jian-Xing; Huang, Ping-Tzan; Lin, Chia-Hung; Li, Chien-Ming

2018-02-01

Blood leakage and blood loss are serious life-threatening complications occurring during dialysis therapy. These events have been of concerns to both healthcare givers and patients. More than 40% of adult blood volume can be lost in just a few minutes, resulting in morbidities and mortality. The authors intend to propose the design of a warning tool for the detection of blood leakage/blood loss during dialysis therapy based on fog computing with an array of photocell sensors and heteroassociative memory (HAM) model. Photocell sensors are arranged in an array on a flexible substrate to detect blood leakage via the resistance changes with illumination in the visible spectrum of 500-700 nm. The HAM model is implemented to design a virtual alarm unit using electricity changes in an embedded system. The proposed warning tool can indicate the risk level in both end-sensing units and remote monitor devices via a wireless network and fog/cloud computing. The animal experimental results (pig blood) will demonstrate the feasibility.

Speed of sound estimation for thermal monitoring using an active ultrasound element during liver ablation therapy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kim, Younsu; Audigier, Chloé; Dillow, Austin; Cheng, Alexis; Boctor, Emad M.

2017-03-01

Thermal monitoring for ablation therapy has high demands for preserving healthy tissues while removing malignant ones completely. Various methods have been investigated. However, exposure to radiation, cost-effectiveness, and inconvenience hinder the use of X-ray or MRI methods. Due to the non-invasiveness and real-time capabilities of ultrasound, it is widely used in intraoperative procedures. Ultrasound thermal monitoring methods have been developed for affordable monitoring in real-time. We propose a new method for thermal monitoring using an ultrasound element. By inserting a Lead-zirconate-titanate (PZT) element to generate the ultrasound signal in the liver tissues, the single travel time of flight is recorded from the PZT element to the ultrasound transducer. We detect the speed of sound change caused by the increase in temperature during ablation therapy. We performed an ex vivo experiment with liver tissues to verify the feasibility of our speed of sound estimation technique. The time of flight information is used in an optimization method to recover the speed of sound maps during the ablation, which are then converted into temperature maps. The result shows that the trend of temperature changes matches with the temperature measured at a single point. The estimation error can be decreased by using a proper curve linking the speed of sound to the temperature. The average error over time was less than 3 degrees Celsius for a bovine liver. The speed of sound estimation using a single PZT element can be used for thermal monitoring.

[MRI/TRUS fusion-guided prostate biopsy : Value in the context of focal therapy].

PubMed

Franz, T; von Hardenberg, J; Blana, A; Cash, H; Baumunk, D; Salomon, G; Hadaschik, B; Henkel, T; Herrmann, J; Kahmann, F; Köhrmann, K-U; Köllermann, J; Kruck, S; Liehr, U-B; Machtens, S; Peters, I; Radtke, J P; Roosen, A; Schlemmer, H-P; Sentker, L; Wendler, J J; Witzsch, U; Stolzenburg, J-U; Schostak, M; Ganzer, R

2017-02-01

Several systems for MRI/TRUS fusion-guided biopsy of the prostate are commercially available. Many studies have shown superiority of fusion systems for tumor detection and diagnostic quality compared to random biopsy. The benefit of fusion systems in focal therapy of prostate cancer (PC) is less clear. Critical considerations of fusion systems for planning and monitoring of focal therapy of PC were investigated. A systematic literature review of available fusion systems for the period 2013-5/2016 was performed. A checklist of technical details, suitability for special anatomic situations and suitability for focal therapy was established by the German working group for focal therapy (Arbeitskreis fokale und Mikrotherapie). Eight fusion systems were considered (Artemis™, BioJet, BiopSee®, iSR´obot™ Mona Lisa, Hitachi HI-RVS, UroNav and Urostation®). Differences were found for biopsy mode (transrectal, perineal, both), fusion mode (elastic or rigid), navigation (image-based, electromagnetic sensor-based or mechanical sensor-based) and space requirements. Several consensus groups recommend fusion systems for focal therapy. Useful features are "needle tracking" and compatibility between fusion system and treatment device (available for Artemis™, BiopSee® and Urostation® with Focal One®; BiopSee®, Hitachi HI-RVS with NanoKnife®; BioJet, BiopSee® with cryoablation, brachytherapy). There are a few studies for treatment planning. However, studies on treatment monitoring after focal therapy are missing.

Impact and Programmatic Implications of Routine Viral Load Monitoring in Swaziland

PubMed Central

Parker, Lucy Anne; Azih, Charles; Okello, Velephi; Maphalala, Gugu; Jouquet, Guillaume; Kerschberger, Bernhard; Mekeidje, Calorine; Cyr, Joanne; Mafikudze, Arnold; Han, Win; Lujan, Johnny; Teck, Roger; Antierens, Annick; van Griensven, Johan; Reid, Tony

2014-01-01

Objective: To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. Design: Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). Results: Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization–defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The “fully loaded” cost of VL monitoring was $35 per patient-year. Conclusions: Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization–defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy. PMID:24872139

Liquid biopsy for detection of actionable oncogenic mutations in human cancers and electric field induced release and measurement liquid biopsy (eLB).

PubMed

Tu, Michael; Chia, David; Wei, Fang; Wong, David

2016-01-21

Oncogenic activations by mutations in key cancer genes such as EGFR and KRAS are frequently associated with human cancers. Molecular targeting of specific oncogenic mutations in human cancer is a major therapeutic inroad for anti-cancer drug therapy. In addition, progressive developments of oncogene mutations lead to drug resistance. Therefore, the ability to detect and continuously monitor key actionable oncogenic mutations is important to guide the use of targeted molecular therapies to improve long-term clinical outcomes in cancer patients. Current oncogenic mutation detection is based on direct sampling of cancer tissue by surgical resection or biopsy. Oncogenic mutations were recently shown to be detectable in circulating bodily fluids of cancer patients. This field of investigation, termed liquid biopsy, permits a less invasive means of assessing the oncogenic mutation profile of a patient. This paper will review the analytical strategies used to assess oncogenic mutations from biofluid samples. Clinical applications will also be discussed.

Liquid Biopsy for Detection of Actionable Oncogenic Mutations in Human Cancers and Electric Field Induced Release and Measurement Liquid Biopsy (eLB)

PubMed Central

Tu, Michael; Chia, David; Wei, Fang; Wong, David

2015-01-01

Oncogenic activations by mutations in key cancer genes such as EGFR and KRAS are frequently associated with human cancers. Molecular targeting of specific oncogenic mutations in human cancer is a major therapeutic inroad for anti-cancer drug therapy. In addition, progressive developments of oncogene mutations lead to drug resistance. Therefore, the ability to detect and continuously monitor key actionable oncogenic mutations is important to guide the use of targeted molecular therapies to improve long-term clinical outcomes in cancer patients. Current oncogenic mutation detection is based on direct sampling of cancer tissue by surgical resection or biopsy. Oncogenic mutations were recently shown to be detectable in circulating bodily fluids of cancer patients. This field of investigation, termed liquid biopsy, permits a less invasive means of assessing the oncogenic mutation profile of a patient. This paper will review the analytical strategies used to assess oncogenic mutations from biofluid samples. Clinical applications will also be discussed. PMID:26645892

Workshop on cancer biometrics: identifying biomarkers and surrogates of cancer in patients: a meeting held at the Masur Auditorium, National Institutes of Health.

PubMed

Lotze, Michael T; Wang, Ena; Marincola, Francesco M; Hanna, Nabil; Bugelski, Peter J; Burns, Christine A; Coukos, George; Damle, Nitin; Godfrey, Tony E; Howell, W Martin; Panelli, Monica C; Perricone, Michael A; Petricoin, Emanuel F; Sauter, Guido; Scheibenbogen, Carmen; Shivers, Steven C; Taylor, D Lansing; Weinstein, John N; Whiteside, Theresa L

2005-01-01

The current excitement about molecular targeted therapies has driven much of the recent dialog in cancer diagnosis and treatment. Particularly in the biologic therapy of cancer, identifiable antigenic T-cell targets restricted by MHC molecules and the related novel stress molecules such as MICA/B and Letal allow a degree of precision previously unknown in cancer therapy. We have previously held workshops on immunologic monitoring and angiogenesis monitoring. This workshop was designed to discuss the state of the art in identification of biomarkers and surrogates of tumor in patients with cancer, with particular emphasis on assays within the blood and tumor. We distinguish this from immunologic monitoring in the sense that it is primarily a measure of the tumor burden as opposed to the immune response to it. Recommendations for intensive investigation and targeted funding to enable such strategies were developed in seven areas: genomic analysis; detection of molecular markers in peripheral blood and lymph node by tumor capture and RT-PCR; serum, plasma, and tumor proteomics; immune polymorphisms; high content screening using flow and imaging cytometry; immunohistochemistry and tissue microarrays; and assessment of immune infiltrate and necrosis in tumors. Concrete recommendations for current application and enabling further development in cancer biometrics are summarized. This will allow a more informed, rapid, and accurate assessment of novel cancer therapies.

Stroke of Known Cause and Underlying Atrial Fibrillation (STROKE-AF) randomized trial: Design and rationale.

PubMed

Bernstein, Richard A; Kamel, Hooman; Granger, Christopher B; Kowal, Robert C; Ziegler, Paul D; Schwamm, Lee H

2017-08-01

Approximately 20% of ischemic strokes are associated with clinically apparent atrial fibrillation (AF). Regardless of stroke etiology, detection of AF in patients with ischemic strokes often changes antithrombotic treatment from anti-platelet to oral anticoagulation therapy. The role and the optimum duration of cardiac monitoring to detect AF in patients with strokes presumed due to large vessel atherosclerosis or small vessel disease is unknown. This manuscript describes the design and rationale of the STROKE-AF trial. STROKE-AF is a randomized, controlled, open-label, post-market clinical trial. Detection of AF will be evaluated using continuous arrhythmia monitoring with an insertable cardiac monitor (ICM) compared with standard of care follow-up in patients with stroke (within the prior 10 days) that is presumed due to large vessel cervical or intracranial atherosclerosis, or to small vessel disease. Approximately 500 patients will be enrolled at approximately 40 centers in the United States. Patients will be randomized 1:1 to arrhythmia monitoring with an ICM (continuous monitoring arm) or standard of care follow-up (control arm). Subjects will be followed for ≥12 months and up to 3 years. The primary objective is to compare the incidence rate of detected AF through 12 months of follow-up between the two arms. This trial will provide information on the value of ICMs to detect subclinical AF in patients with stroke presumed due to large vessel atherosclerosis or small vessel disease, which will have implications for guiding treatment with oral anticoagulation for secondary stroke prevention. Copyright © 2017 Elsevier Inc. All rights reserved.

Reliability and accuracy of sleep apnea scans in novel cardiac resynchronization therapy devices: an independent report of two cases.

PubMed

Fox, Henrik; Nölker, Georg; Gutleben, Klaus-Jürgen; Bitter, Thomas; Horstkotte, Dieter; Oldenburg, Olaf

2014-03-01

Pacemaker apnea scan algorithms are able to screen for sleep apnea. We investigated whether these systems were able to accurately detect sleep-disordered breathing (SDB) in two patients from an outpatient clinic. The first patient suffered from ischemic heart failure and severe central sleep apnea (CSA) and underwent adaptive servoventilation therapy (ASV). The second patient suffered from dilated cardiomyopathy and moderate obstructive sleep apnea (OSA). Pacemaker read-outs did not match polysomnography (PSG) recordings well and overestimated the apnea-hypopnea index. However, ASV therapy-induced SDB improvements were adequately recognized by the apnea scan of the Boston Scientific INVIVE® cardiac resynchronization therapy pacemaker. Detection of obstructive respiratory events using impedance-based technology may underestimate the number of events, as frustrane breathing efforts induce impedance changes without significant airflow. By contrast, in the second case, apnea scan overestimated the number of total events and of obstructive events, perhaps owing to a very sensitive but less specific hypopnea definition and detection within the diagnostic algorithm of the device. These two cases show that a pacemaker apnea scan is able to reflect SDB, but PSG precision is not met by far. The device scan revealed the decline of SDB through ASV therapy for CSA in one patient, but not for OSA in the second case. To achieve reliable monitoring of SDB, further technical developments and clinical studies are necessary.

Effectiveness of highly active antiretroviral therapy in HIV-positive children: evaluation at 12 months in a routine program in Cambodia.

PubMed

Janssens, Bart; Raleigh, Brian; Soeung, Seithaboth; Akao, Kazumi; Te, Vantha; Gupta, Jitendra; Vun, Mean Chhy; Ford, Nathan; Nouhin, Janin; Nerrienet, Eric

2007-11-01

Increasing access to highly active antiretroviral therapy to reach all those in need in developing countries (scale up) is slowly expanding to HIV-positive children, but documented experience remains limited. We aimed to describe the clinical, immunologic, and virologic outcomes of pediatric patients with >12 months of highly active antiretroviral therapy in 2 routine programs in Cambodia. Between June 2003 and March 2005, 212 children who were younger than 13 years started highly active antiretroviral therapy. Most patients started a standard first-line regimen of lamivudine, stavudine, and nevirapine, using split adult fixed-dosage combinations. CD4 percentage and body weight were monitored routinely. A cross-sectional virologic analysis was conducted in January 2006; genotype resistance testing was performed for patients with a detectable viral load. Mean age of the subjects was 6 years. Median CD4 percentage at baseline was 6. Survival was 92% at 12 months and 91% at 24 months; 13 patients died, and 4 were lost to follow-up. A total of 81% of all patients had an undetectable viral load. Among the patients with a detectable viral load, most mutations were associated with resistance to lamivudine and non-nucleoside reverse-transcriptase inhibitor drugs. Five patients had developed extensive antiretroviral resistance. Being an orphan was found to be a predictor of virologic failure. This study provides additional evidence of the effectiveness of integrating HIV/AIDS care with highly active antiretroviral therapy for children in a routine setting, with good virologic suppression and immunologic recovery achieved by using split adult fixed-dosage combinations. Viral load monitoring and HIV genotyping are valuable tools for the clinical follow-up of the patients. Orphans should receive careful follow-up and extra support.

Simultaneous Detection of Static and Dynamic Signals by a Flexible Sensor Based on 3D Graphene.

PubMed

Xu, Rongqing; Wang, Di; Zhang, Hongchao; Xie, Na; Lu, Shan; Qu, Ke

2017-05-08

A flexible acoustic pressure sensor was developed based on the change in electrical resistance of three-dimensional (3D) graphene change under the acoustic waves action. The sensor was constructed by 3D graphene foam (GF) wrapped in flexible polydimethylsiloxane (PDMS). Tuning forks and human physiological tests indicated that the acoustic pressure sensor can sensitively detect the deformation and the acoustic pressure in real time. The results are of significance to the development of graphene-based applications in the field of health monitoring, in vitro diagnostics, advanced therapies, and transient pressure detection.

Monitoring therapy responses at the leukemic subclone level by ultra-deep amplicon resequencing in acute myeloid leukemia.

PubMed

Ojamies, P N; Kontro, M; Edgren, H; Ellonen, P; Lagström, S; Almusa, H; Miettinen, T; Eldfors, S; Tamborero, D; Wennerberg, K; Heckman, C; Porkka, K; Wolf, M; Kallioniemi, O

2017-05-01

In our individualized systems medicine program, personalized treatment options are identified and administered to chemorefractory acute myeloid leukemia (AML) patients based on exome sequencing and ex vivo drug sensitivity and resistance testing data. Here, we analyzed how clonal heterogeneity affects the responses of 13 AML patients to chemotherapy or targeted treatments using ultra-deep (average 68 000 × coverage) amplicon resequencing. Using amplicon resequencing, we identified 16 variants from 4 patients (frequency 0.54-2%) that were not detected previously by exome sequencing. A correlation-based method was developed to detect mutation-specific responses in serial samples across multiple time points. Significant subclone-specific responses were observed for both chemotherapy and targeted therapy. We detected subclonal responses in patients where clinical European LeukemiaNet (ELN) criteria showed no response. Subclonal responses also helped to identify putative mechanisms underlying drug sensitivities, such as sensitivity to azacitidine in DNMT3A mutated cell clones and resistance to cytarabine in a subclone with loss of NF1 gene. In summary, ultra-deep amplicon resequencing method enables sensitive quantification of subclonal variants and their responses to therapies. This approach provides new opportunities for designing combinatorial therapies blocking multiple subclones as well as for real-time assessment of such treatments.

Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells

PubMed Central

Whang, Katherine A.; LeGall, Camille; Cragnolini, Juan J.; Bierie, Brian; Gostissa, Monica; Grotenbreg, Gijsbert M.; Bhan, Atul; Weinberg, Robert A.

2017-01-01

Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non–small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno–positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used 89Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8+ T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade. A 89Zr-labeled PEGylated anti-CD8 VHH detected thymus and secondary lymphoid structures as well as intratumoral CD8 T cells. Animals that responded to CTLA-4 therapy showed a homogeneous distribution of the anti-CD8 PET signal throughout the tumor, whereas more heterogeneous infiltration of CD8 T cells correlated with faster tumor growth and worse responses. To support the validity of these observations, we used two different transplantable breast cancer models, yielding results that conformed with predictions based on the antimelanoma response. It may thus be possible to use immuno-PET and monitor antitumor immune responses as a prognostic tool to predict patient responses to checkpoint therapies. PMID:28666979

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 1-Mechanisms, Efficacy, and Safety.

PubMed

McNamara, C; Sugrue, G; Murray, B; MacMahon, P J

2017-09-01

Imaging for the diagnosis and follow-up of patients with suspected or confirmed multiple sclerosis is a common scenario for many general radiologists and subspecialty neuroradiologists. The field of MS therapeutics has rapidly evolved with multiple new agents now being used in routine clinical practice. To provide an informed opinion in discussions concerning newer MS agents, radiologists must have a working understanding of the strengths and limitations of the various novel therapies. The role of imaging in MS has advanced beyond monitoring and surveillance of disease activity to include treatment complications. An understanding of the new generation of MS drugs in conjunction with the key role that MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse events is of vital importance to the radiologist and clinical physician alike. Radiologists are in a unique position to detect many of the described complications well in advance of clinical symptoms. Part 1 of this review outlines recent developments in the treatment of MS and discusses the published clinical data on the efficacy and safety of the currently approved and emerging therapies in this condition as they apply to the radiologist. Part 2 will cover pharmacovigilance and the role the neuroradiologist plays in monitoring patients for signs of opportunistic infection and/or disease progression. © 2017 by American Journal of Neuroradiology.

Monitoring early response to taxane therapy in advanced breast cancer with circulating tumor cells and [(18)F] 3´-deoxy-3´-fluorothymidine PET: a pilot study.

PubMed

Contractor, Kaiyumars; Aboagye, Eric O; Jacob, Jimmy; Challapalli, Amarnath; Coombes, R Charles; Stebbing, Justin

2012-04-01

Early markers of response to chemotherapy, measured by blood markers and imaging, may ultimately lead to tailored therapies that avoid cumulative toxicity. We performed a small pilot study to compare early changes in levels of circulatory tumor cells (CTCs) with changes in tumor proliferation, using metabolic imaging with [(18)F] 3´-deoxy-3´-fluorothymidine PET (FLT-PET) in women with advanced breast cancer, before and during docetaxel therapy. In those individuals in whom we could detect CTCs, a decrease in CTC count correlated with a decrease in FLT-PET signal, within 2 weeks. Combined, these two technologies are likely to provide a powerful, albeit expensive, tool to assess immediate responses to therapy.

[Clinical importance of semi-quantitative monitoring of lymphomas using the comparative polymerase chain reaction].

PubMed

Slavícková, A; Ivánek, R; Cerný, J; Sálková, J; Trnĕný, M

2002-11-22

PCR techniques detecting interchromosomal translocation and clonal immunoglobulin gene rearrangement (IgH) as disease markers in non-Hodgkin's lymphomas (NHL) has been utilised past ten years. However, qualitative PCR detection of persisted minimal residual disease cannot provide clinically useful prognostic information and presently, quantitative approaches are required to predict patient outcome and assess response to the treatment. In some cases, "end-point" quantifying techniques, such as comparative PCR, are applicable and the relative estimation of differences in target quantity may serve in disease monitoring rather than absolute number of target copies. Our method of comparative PCR employs co-amplification of sequences of interest (clonal CDR3, bcl2/Jh) and the segment of Hras 1 gene(ras) as an internal standard. Serial dilutions of stored diagnostic DNAs from blood and bone marrow are examined in the same PCR and, after gel densitometry, the amount of initial target is assessed by comparing exponential products of co-amplification. The comparative PCR assay was utilized in monitoring of NHL patients cured either with conventional therapy, or with high-dose regimens and transplantation with stem cells, or with chimaeric anti-CD20 monoclonal antibody (Rituximab). Results from 50 monitored intervals obtained during several months up to several years were supplemented with clinical statements retrospectively. Some of patients became PCR-negative, reappearance of PCR-positivity was observed as well. The decrease or increase of disease marker corresponded to clinical observations. Results obtained from bone marrow were in agreement with those obtained from blood. End-point quantifying PCR comparative assay may provide an information on the increased risk of relapse and impact of the therapy. The predictive value of these methods depends on the frequency of sample taking and on the sensitivity of the method, which should be monitored in negative cases.

HPV circulating tumor DNA to monitor the efficacy of anti-PD-1 therapy in metastatic squamous cell carcinoma of the anal canal: A case report.

PubMed

Cabel, Luc; Bidard, François-Clément; Servois, Vincent; Cacheux, Wulfran; Mariani, Pascale; Romano, Emanuela; Minsat, Mathieu; Bieche, Ivan; Farkhondeh, Fereshteh; Jeannot, Emmanuelle; Buecher, Bruno

2017-10-15

Squamous cell carcinoma of the anal canal (SCCA) is a rare HPV-associated cancer with limited sensitivity to standard chemotherapy. In a phase 2 study, nivolumab, an anti PD-1 immune checkpoint inhibitor, demonstrated significant efficacy as single-agent therapy in metastatic SCCA patients. Nevertheless, imaging assessment by standard RECIST criteria of the efficacy of immune therapy can be difficult in some patients due to tumor immune cell infiltration, and biomarkers of treatment efficacy are needed. We have previously developed a quantitative droplet digital PCR (ddPCR) technique to detect HPV circulating tumor DNA (HPV ctDNA), with excellent sensitivity and specificity. Here, we report, for the first time, the kinetics of HPV ctDNA during therapy in a patient with metastatic SCCA, who obtained sustained partial response to single-agent nivolumab. We observed an early and very significant decrease of HPV ctDNA during therapy from the baseline level of 3713 copies/ml plasma to 564 copies/ml plasma at 4 weeks, and 156 copies/ml at 6 weeks, followed by a plateau. This observation provides proof-of-concept that HPV ctDNA can be used as a noninvasive early dynamic biomarker to monitor the efficacy of new immunotherapy agents. © 2017 UICC.

Onset time of hyperkalaemia after angiotensin receptor blocker initiation: when should we start serum potassium monitoring?

PubMed

Park, I-W; Sheen, S S; Yoon, D; Lee, S-H; Shin, G-T; Kim, H; Park, R W

2014-02-01

Angiotensin receptor blockers (ARBs) frequently induce hyperkalaemia in high-risk patients. Early detection of hyperkalaemia can reduce the subsequent harmful effects. This study was performed to examine the onset time of hyperkalaemia after ARB therapy. We carried out a retrospective analysis to determine the onset time of hyperkalaemia (serum potassium >5·5 mm) among hospitalized patients newly starting ARB therapy between 2004 and 2012, in a tertiary teaching hospital. Predefined possible risk factors and concomitant medications were evaluated. During the 97-month study period, a total of 4267 hospitalized patients started ARBs as new drugs and 225 patients showed hyperkalaemia. A significantly increased risk of hyperkalaemia was detected among patients with a high baseline potassium [odds ratio (OR) 6·0] and those who took non-potassium-sparing diuretics (OR 2·2) or potassium supplements (OR 1·6). A high glomerular filtration rate (GFR) was associated with a lower risk of hyperkalaemia (OR 0·992). Fifty-two percentage of hyperkalaemic events occurred within the first week after initiation of ARB therapy. The highest frequency of hyperkalaemia occurred on the first day after initiation of ARBs. Hyperkalaemia occurred earlier in patients with a high baseline serum potassium level, reduced GFR, diabetes and in those without heart failure. Hyperkalaemia occurs most frequently at the beginning of ARB therapy in hospitalized patients. Monitoring of serum potassium and estimated GFR after initiation of ARBs should be started within a few days or not later than 1 week, especially in patients with risk factors. © 2013 John Wiley & Sons Ltd.

Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson's disease.

PubMed

Sulzer, David; Cassidy, Clifford; Horga, Guillermo; Kang, Un Jung; Fahn, Stanley; Casella, Luigi; Pezzoli, Gianni; Langley, Jason; Hu, Xiaoping P; Zucca, Fabio A; Isaias, Ioannis U; Zecca, Luigi

2018-01-01

The diagnosis of Parkinson's disease (PD) occurs after pathogenesis is advanced and many substantia nigra (SN) dopamine neurons have already died. Now that therapies to block this neuronal loss are under development, it is imperative that the disease be diagnosed at earlier stages and that the response to therapies is monitored. Recent studies suggest this can be accomplished by magnetic resonance imaging (MRI) detection of neuromelanin (NM), the characteristic pigment of SN dopaminergic, and locus coeruleus (LC) noradrenergic neurons. NM is an autophagic product synthesized via oxidation of catecholamines and subsequent reactions, and in the SN and LC it increases linearly during normal aging. In PD, however, the pigment is lost when SN and LC neurons die. As shown nearly 25 years ago by Zecca and colleagues, NM's avid binding of iron provides a paramagnetic source to enable electron and nuclear magnetic resonance detection, and thus a means for safe and noninvasive measure in living human brain. Recent technical improvements now provide a means for MRI to differentiate between PD patients and age-matched healthy controls, and should be able to identify changes in SN NM with age in individuals. We discuss how MRI detects NM and how this approach might be improved. We suggest that MRI of NM can be used to confirm PD diagnosis and monitor disease progression. We recommend that for subjects at risk for PD, and perhaps generally for older people, that MRI sequences performed at regular intervals can provide a pre-clinical means to detect presymptomatic PD.

Tumour marker measurements in the diagnosis and monitoring of breast cancer.

PubMed

Cheung, K L; Graves, C R; Robertson, J F

2000-04-01

Elevation of established blood tumour markers correlates with the stage of breast cancer. The major role of current blood markers is therefore in the diagnosis and monitoring of metastatic disease. A combination of markers is better than a single marker with the most widely adopted combination being CEA and one MUC1 mucin, commonly detected as either CA15.3 or CA27.29. Tumour marker measurement is now used as a complementary test in the diagnosis of symptomatic metastases. In the monitoring of therapeutic response to both endocrine and cytotoxic therapies in advanced disease, biochemical assessment using blood markers not only correlates with conventional UICC criteria but has a lot of advantages which make it a potentially superior way of assessment. In this regard, CA15.3, CEA and ESR are the best validated combination. Studies are ongoing to evaluate the use of sequential blood tumour marker measurements in the follow-up of patients after treatment for their primary breast cancer, in terms of both early detection and early therapeutic intervention. Further randomized studies are also required to ascertain that marker-directed therapy is superior to the current practice for metastatic disease. In line with clinical studies, intensive laboratory work is being carried out to optimize the use of blood markers in advanced disease as well as to exploit their use in screening and diagnosis of early primary breast cancer.

Development and testing of an optoacoustic imaging system for monitoring and guiding prostate cancer therapies

NASA Astrophysics Data System (ADS)

Spirou, Gloria M.; Vitkin, I. Alex; Wilson, B. C.; Whelan, William M.; Henrichs, Paul M.; Mehta, Ketan; Miller, Tom; Yee, Andrew; Meador, James; Oraevsky, Alexander A.

2004-07-01

Laser Optoacoustic Imaging System (LOIS) combines high tissue contrast based on the optical properties of tissue and high spatial resolution based on ultrawide-band ultrasonic detection. Patients undergoing thermal or photodynamic therapy of prostate cancer may benefit from capability of LOIS to detect and monitor treatment-induced changes in tissue optical properties and blood flow. The performance of a prototype LOIS was evaluated via 2D optoacoustic images of dye-colored objects of various shapes, small tubes with blood simulating veins and arteries, and thermally coagulated portions of chicken breasts imbedded tissue-mimicking gelatin phantoms. The optoacoustic image contrast was proportional to the ratio of the absorption coefficient between the embedded objects and the surrounding gel. The contrast of the venous blood relative to the background exceeded 250%, and the contrast of the thermally coagulated portions of flesh relative to the untreated tissue ranged between -100% to +200%, dependent on the optical wavelength. We used a 32-element optoacoustic transducer array and a novel design of low-noise preamplifiers and wide-band amplifiers to perform these studies. The system was optimized for imaging at a depth of ~50 mm. The system spatial resolution was better than 1-mm. The advantages and limitations of various signal-processing methods were investigated. LOIS demonstrates clinical potential for non- or minimally-invasive monitoring of treatment-induced tissue changes.

Nanotechnology applications in thoracic surgery

PubMed Central

Hofferberth, Sophie C.; Grinstaff, Mark W.; Colson, Yolonda L.

2016-01-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of ‘theranostic’ multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. PMID:26843431

Label-free glucose detection using cantilever sensor technology based on gravimetric detection principles.

PubMed

Hsieh, Shuchen; Hsieh, Shu-Ling; Hsieh, Chiung-Wen; Lin, Po-Chiao; Wu, Chun-Hsin

2013-01-01

Efficient maintenance of glucose homeostasis is a major challenge in diabetes therapy, where accurate and reliable glucose level detection is required. Though several methods are currently used, these suffer from impaired response and often unpredictable drift, making them unsuitable for long-term therapeutic practice. In this study, we demonstrate a method that uses a functionalized atomic force microscope (AFM) cantilever as the sensor for reliable glucose detection with sufficient sensitivity and selectivity for clinical use. We first modified the AFM tip with aminopropylsilatrane (APS) and then adsorbed glucose-specific lectin concanavalin A (Con A) onto the surface. The Con A/APS-modified probes were then used to detect glucose by monitoring shifts in the cantilever resonance frequency. To confirm the molecule-specific interaction, AFM topographical images were acquired of identically treated silicon substrates which indicated a specific attachment for glucose-Con A and not for galactose-Con A. These results demonstrate that by monitoring the frequency shift of the AFM cantilever, this sensing system can detect the interaction between Con A and glucose, one of the biomolecule recognition processes, and may assist in the detection and mass quantification of glucose for clinical applications with very high sensitivity.

Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor

NASA Astrophysics Data System (ADS)

Su, Li-Chen; Tian, Ya-Chung; Chang, Ying-Feng; Chou, Chien; Lai, Chao-Sung

2014-01-01

In renal transplant patients, immunosuppressive therapy may result in the reactivation of polyomavirus BK (BKV), leading to polyomavirus-associated nephropathy (PVAN), which inevitably causes allograft failure. Since the treatment outcomes of PVAN remain unsatisfactory, early identification and continuous monitoring of BKV reactivation and reduction of immunosuppressants are essential to prevent PVAN development. The present study demonstrated that the developed dual-channel heterodyne-based surface plasmon resonance (SPR) biosensor is applicable for the rapid detection of urinary BKV. The use of a symmetrical reference channel integrated with the poly(ethylene glycol)-based low-fouling self-assembled monolayer to reduce the environmental variations and the nonspecific noise was proven to enhance the sensitivity in urinary BKV detection. Experimentally, the detection limit of the biosensor for BKV detection was estimated to be around 8500 copies/mL. In addition, urine samples from five renal transplant patients were tested to rapidly distinguish PVAN-positive and PVAN-negative renal transplant patients. By virtue of its simplicity, rapidity, and applicability, the SPR biosensor is a remarkable potential to be used for continuous clinical monitoring of BKV reactivation.

Noninvasive and real-time monitoring of molecular targeting therapy for lymph node and peritoneal metastasis in nude mice bearing xenografts of human colorectal cancer cells tagged with GFP and DsRed

NASA Astrophysics Data System (ADS)

Nakanishi, Hayao; Hara, Masayasu; Ikehara, Yuzuru; Tatematsu, Masae

2007-02-01

We have developed an in vivo imaging system consisting of GFP- and DsRed-tagged human colonic cancer cell line, which has peritoneal and lymph node metastatic potential and show high sensitivity to EGFR targeting drugs, and convenient detection devices for GFP and DsRed. The latter includes a small handy fluorescence detection device for external monitoring of the therapeutic effect of the drug and a convenient stereo fluorescent microscope for internal visualization of micrometastases. We applied this imaging system to investigate anti-metastatic effects of EGFR targeting drugs such as gefitinib (Iressa). This system allowed sensitive detection of the development of peritoneal and lymph node metastases from the micrometastasis stage at the cellular level and also permited noninvasive, non-anesthetic monitoring of anti-metastatic effect of the drug in an animal facility without any pretreatment. Significant decreases in the intraabdominal metastatic tumor growth and prevention of inguinal lymph node metastasis by gefitinib treatment could be clearly monitored. These results suggest that convenient, low-cost, true real-time monitoring of therapeutic effect using such a fluorescence-mediated whole body imaging system seems to enhance the speed of preclinical study for novel anti-cancer agents and will allow us to understand the action mechanism of molecular targeting drugs.

Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study.

PubMed

Wen, Aiping; Li, Zhe; Yu, Junxian; Li, Ren; Cheng, Sheng; Duan, Meili; Bai, Jing

2016-01-01

The primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy. A prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated. Eighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test. Spent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients.

Cerebral Embolic Activity in a Patient during Acute Crisis of Takayasu's Arteritis

PubMed Central

Nogueira, Ricardo de Carvalho; Bor-Seng-Shu, Edson; Marchiori, Paulo Eurípedes; Teixeira, Manoel Jacobsen

2012-01-01

Takayasu's arteritis is a disease that affects large vessels and may cause neurological symptoms either by stenoses/occlusions or embolisms from vessels with an inflammatory process. Transcranial Doppler (TCD) ultrasound can provide useful information for diagnosis and monitoring during the active phase of the disease. Cerebral embolic signals can be detected by TCD and have been considered a risk factor for vascular events. We report a patient in whom TCD ultrasound was used to monitor cerebral embolic signals during the active phase of the disease. This case report suggests that embolic activity in Takayasu's arteritis may represent disease activity, and its monitoring may be useful for evaluating the response to therapy. PMID:22379479

Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab

PubMed Central

Vega, Estela; Garralda, Elena; Alvarez, Rafael; de la Varga, Lisardo U.; Pascual, Jesús R.; Sánchez, Gema; Sarno, Francesca; Prieto, Susana H.; Perea, Sofía; Lopéz-Casas, Pedro P.; López-Ríos, Fernando; Hidalgo, Manuel

2017-01-01

Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients. PMID:27852040

Clinical validation of prospective liquid biopsy monitoring in patients with wild-type RAS metastatic colorectal cancer treated with FOLFIRI-cetuximab.

PubMed

Toledo, Rodrigo A; Cubillo, Antonio; Vega, Estela; Garralda, Elena; Alvarez, Rafael; de la Varga, Lisardo U; Pascual, Jesús R; Sánchez, Gema; Sarno, Francesca; Prieto, Susana H; Perea, Sofía; Lopéz-Casas, Pedro P; López-Ríos, Fernando; Hidalgo, Manuel

2017-05-23

Cancer genomics and translational medicine rely on the molecular profiling of patient's tumor obtained during surgery or biopsy. Alternatively, blood is a less invasive source of tumor DNA shed, amongst other ways, as cell-free DNA (cfDNA). Highly-sensitive assays capable to detect cancer genetic events from patient's blood plasma became popularly known as liquid biopsy (LqB). Importantly, retrospective studies including small number of selected patients with metastatic colorectal cancer (mCRC) patients treated with anti-EGFR therapy have shown LqB capable to detect the acquired clonal mutations in RAS genes leading to therapy resistance. However, the usefulness of LqB in the real-life clinical monitoring of these patients still lack additional validation on controlled studies. In this context, we designed a prospective LqB clinical trial to monitor newly diagnosed KRAS wild-type (wt) mCRC patients who received a standard FOLFIRI-cetuximab regimen. We used BEAMing technique for evaluate cfDNA mutations in KRAS, NRAS, BRAF, and PIK3CA in twenty-five patients during a 2-y period. A total of 2,178 cfDNA mutation analyses were performed and we observed that: a) continued wt circulating status was correlated with a prolonged response; b) smoldering increases in mutant cfDNA were correlated with acquired resistance; while c) mutation upsurge/explosion anticipated a remarkable clinical deterioration. The current study provides evidences, obtained for the first time in an unbiased and prospective manner, that reinforces the utility of LqB for monitoring mCRC patients.

The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer

PubMed Central

Wei, Fang; Wong, David T.; Su, Wu-Chou

2015-01-01

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer. PMID:26448936

Taking a Closer Look--Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients with Type 2 Diabetes Mellitus Under Basal-Bolus Insulin Therapy.

PubMed

Schaupp, Lukas; Donsa, Klaus; Neubauer, Katharina M; Mader, Julia K; Aberer, Felix; Höll, Bernhard; Spat, Stephan; Augustin, Thomas; Beck, Peter; Pieber, Thomas R; Plank, Johannes

2015-09-01

Inpatient glucose management is based on four daily capillary blood glucose (BG) measurements. The aim was to test the capability of continuous glucose monitoring (CGM) for assessing the clinical impact and safety of basal-bolus insulin therapy in non-critically ill hospitalized patients with type 2 diabetes mellitus (T2DM). Eighty-four patients with T2DM (age, 68±10 years; glycosylated hemoglobin, 72±28 mmol/mol; body mass index, 31±7 kg/m(2)) were treated with basal-bolus insulin. CGM was performed with the iPro(®)2 system (Medtronic MiniMed, Northridge, CA) and calibrated retrospectively. A remarkable consistency between CGM and BG measurements and therapy improvement was shown over the study period of 501 patient-days. The number of CGM and BG measurements (CGM/BG) in the range from 3.9-10 mmol/L increased from 67.7%/67.2% (on Day 1) to 77.5%/78.6% (on the last day) (P<0.04). The number of low glycemic episodes (3.3 to <3.9 mmol/L) during nighttime detected by CGM was 15-fold higher, and the number of episodes >13.9 mmol/L detected by CGM during night was 12.5-fold higher than the values from the BG measurements. Ninety-nine percent of data points were in the clinically accurate or acceptable Clarke Error Grid Zones A+B, and the relative numbers of correctly identified episodes of <3.9 and >13.9 mmol/L detected by CGM (sensitivity) were 47.3% and 81.5%, respectively. Our data exhibit a good agreement between overall CGM and BG measurements, but there were a high number of missed hypo- and hyperglycemic episodes with BG measurements, particularly during nighttime. Overall assessment of glycemic control using CGM is feasible, whereas the use of CGM for individualized therapy decisions needs further improvement.

Radiation dosimetry with fiber Bragg gratings

NASA Astrophysics Data System (ADS)

Avino, S.; D'Avino, V.; Giorgini, A.; Pacelli, R.; Liuzzi, R.; Cella, L.; Gagliardi, G.; De Natale, P.

2014-05-01

The measurement and monitoring of radiation dose delivered in patient tissues is a critical aspect in radiation therapy. Various dosimeters have proven effective in measuring radiations at low doses. However, there is a growing demand for new dosimeters based on small, non-invasive and high resolution devices. Here we report on a miniature dosimeter based on an optical fiber cavity. We demonstrate an ultimate detection limit of 160 mGy with an effective interaction region of 6 x 10-4 mm3. Due to its reliability, compactness and biomedical dose level sensitivity, our system shows itself suitable for applications in radiation therapy dosimetry.

On the effectiveness of ion range determination from in-beam PET data

NASA Astrophysics Data System (ADS)

Fiedler, Fine; Shakirin, Georgy; Skowron, Judith; Braess, Henning; Crespo, Paulo; Kunath, Daniela; Pawelke, Jörg; Pönisch, Falk; Enghardt, Wolfgang

2010-04-01

At present, in-beam positron emission tomography (PET) is the only method for in vivo and in situ range verification in ion therapy. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH (GSI) Darmstadt, Germany, a unique in-beam PET installation has been operated from 1997 until the shut down of the carbon ion therapy facility in 2008. Therapeutic irradiation by means of 12C ion beams of more than 400 patients have been monitored. In this paper a first quantitative study on the accuracy of the in-beam PET method to detect range deviations between planned and applied treatment in clinically relevant situations using simulations based on clinical data is presented. Patient treatment plans were used for performing simulations of positron emitter distributions. For each patient a range difference of ± 6 mm in water was applied and compared to simulations without any changes. The comparisons were performed manually by six experienced evaluators for data of 81 patients. The number of patients required for the study was calculated using the outcome of a pilot study. The results indicate a sensitivity of (91 ± 3)% and a specificity of (96 ± 2)% for detecting an overrange, a reduced range is recognized with a sensitivity of (92 ± 3)% and a specificity of (96 ± 2)%. The positive and the negative predictive value of this method are 94% and 87%, respectively. The interobserver coefficient of variation is between 3 and 8%. The in-beam PET method demonstrated a high sensitivity and specificity for the detection of range deviations. As the range is a most indicative factor of deviations in the dose delivery, the promising results shown in this paper confirm the in-beam PET method as an appropriate tool for monitoring ion therapy.

Thermal Video Systems

NASA Technical Reports Server (NTRS)

1988-01-01

Hughes Aircraft Corporation's Probeye Model 3300 Thermal Video System consists of tripod mounted infrared scanner that detects the degree of heat emitted by an object and a TV monitor on which results are displayed. Latest addition to Hughes line of infrared medical applications can detect temperature variations as fine as one-tenth of a degree centigrade. Thermography, proving to be a valuable screening tool in diagnosis, can produce information to preclude necessity of performing more invasive tests that may be painful and hazardous. Also useful in verifying a patient's progress through therapy and rehabilitation.

Tracking Silent Hypersensitivity Reactions to Asparaginase during Leukemia Therapy Using Single-Chip Indirect Plasmonic and Fluorescence Immunosensing.

PubMed

Charbonneau, David M; Breault-Turcot, Julien; Sinnett, Daniel; Krajinovic, Maja; Leclerc, Jean-Marie; Masson, Jean-François; Pelletier, Joelle N

2017-12-22

Microbial asparaginase is an essential component of chemotherapy for the treatment of childhood acute lymphoblastic leukemia (cALL). Silent hypersensitivity reactions to this microbial enzyme need to be monitored accurately during treatment to avoid adverse effects of the drug and its silent inactivation. Here, we present a dual-response anti-asparaginase sensor that combines indirect SPR and fluorescence on a single chip to perform ELISA-type immunosensing, and correlate measurements with classical ELISA. Analysis of serum samples from children undergoing cALL therapy revealed a clear correlation between single-chip indirect SPR/fluorescence immunosensing and ELISA used in clinical settings (R 2 > 0.9). We also report that the portable SPR/fluorescence system had a better sensitivity than classical ELISA to detect antibodies in clinical samples with low antigenicity. This work demonstrates the reliability of dual sensing for monitoring clinically relevant antibody titers in clinical serum samples.

Cardio-oncology: cardiovascular complications of cancer therapy.

PubMed

Henning, Robert J; Harbison, Raymond D

2017-07-01

This paper focuses on three classes of commonly used anticancer drugs, which can cause cardiotoxicity: anthracyclines, monoclonal antibodies exemplified by trastuzumab and tyrosine kinase inhibitors. Anthracyclines can induce cardiomyocyte necrosis and fibrosis. Trastuzumab can cause cardiac stunning. The tyrosine kinase inhibitors can increase systemic arterial pressure and impair myocyte contractility. In addition, radiation therapy to the mediastinum or left chest can exacerbate the cardiotoxicity of these anticancer drugs and can also cause accelerated atherosclerosis, myocardial infarction, heart failure and arrhythmias. Left ventricular ejection fraction measurements are most commonly used to assess cardiac function in patients who receive chemo- or radiation-therapy. However, echocardiographic determinations of global longitudinal strain are more sensitive for detection of early left ventricular systolic dysfunction. Information on patient-risk stratification and monitoring is presented and guidelines for the medical treatment of cardiac dysfunction due to cancer therapies are summarized.

Prevention and management of hepatitis B virus reactivation in patients with hematological malignancies treated with anticancer therapy

PubMed Central

Law, Man Fai; Ho, Rita; Cheung, Carmen K M; Tam, Lydia H P; Ma, Karen; So, Kent C Y; Ip, Bonaventure; So, Jacqueline; Lai, Jennifer; Ng, Joyce; Tam, Tommy H C

2016-01-01

Hepatitis due to hepatitis B virus (HBV) reactivation can be severe and potentially fatal, but is preventable. HBV reactivation is most commonly reported in patients receiving cancer chemotherapy, especially rituximab-containing therapy for hematological malignancies and those receiving stem cell transplantation. All patients with hematological malignancies receiving anticancer therapy should be screened for active or resolved HBV infection by blood tests for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc). Patients found to be positive for HBsAg should be given prophylactic antiviral therapy to prevent HBV reactivation. For patients with resolved HBV infection, no standard strategy has yet been established to prevent HBV reactivation. There are usually two options. One is pre-emptive therapy guided by serial HBV DNA monitoring, whereby antiviral therapy is given as soon as HBV DNA becomes detectable. However, there is little evidence regarding the optimal interval and period of monitoring. An alternative approach is prophylactic antiviral therapy, especially for patients receiving high-risk therapy such as rituximab, newer generation of anti-CD20 monoclonal antibody, obinutuzumab or hematopoietic stem cell transplantation. This strategy may effectively prevent HBV reactivation and avoid the inconvenience of repeated HBV DNA monitoring. Entecavir or tenofovir are preferred over lamivudine as prophylactic therapy. Although there is no well-defined guideline on the optimal duration of prophylactic therapy, there is growing evidence to recommend continuing prophylactic antiviral therapy for at least 12 mo after cessation of chemotherapy, and even longer for those who receive rituximab or who had high serum HBV DNA levels before the start of immunosuppressive therapy. Many novel agents have recently become available for the treatment of hematological malignancies, and these agents may be associated with HBV reactivation. Although there is currently limited evidence to guide the optimal preventive measures, we recommend antiviral prophylaxis in HBsAg-positive patients receiving novel treatments, especially the Bruton tyrosine kinase inhibitors and the phosphatidylinositol 3-kinase inhibitors, which are B-cell receptor signaling modulators and reduce proliferation of malignant B-cells. Further studies are needed to clarify the risk of HBV reactivation with these agents and the best prophylactic strategy in the era of targeted therapy for hematological malignancies. PMID:27605883

Long-term monitoring shows hepatitis B virus resistance to entecavir in nucleoside-naïve patients is rare through 5 years of therapy.

PubMed

Tenney, Daniel J; Rose, Ronald E; Baldick, Carl J; Pokornowski, Kevin A; Eggers, Betsy J; Fang, Jie; Wichroski, Michael J; Xu, Dong; Yang, Joanna; Wilber, Richard B; Colonno, Richard J

2009-05-01

Patients with chronic hepatitis B virus (HBV) infection who develop antiviral resistance lose benefits of therapy and may be predisposed to further resistance. Entecavir (ETV) resistance (ETVr) results from HBV reverse transcriptase substitutions at positions T184, S202, or M250, which emerge in the presence of lamivudine (LVD) resistance substitutions M204I/V +/- L180M. Here, we summarize results from comprehensive resistance monitoring of patients with HBV who were continuously treated with ETV for up to 5 years. Monitoring included genotypic analysis of isolates from all patients at baseline and when HBV DNA was detectable by polymerase chain reaction (> or = 300 copies/mL) from Years 1 through 5. In addition, genotyping was performed on isolates from patients experiencing virologic breakthrough (> or = 1 log(10) rise in HBV DNA). In vitro phenotypic ETV susceptibility was determined for virologic breakthrough isolates, and for HBV containing novel substitutions emerging during treatment. The results over 5 years of therapy showed that in nucleoside-naïve patients, the cumulative probability of genotypic ETVr and genotypic ETVr associated with virologic breakthrough was 1.2% and 0.8%, respectively. In contrast, a reduced barrier to resistance was observed in LVD-refractory patients, as the LVD resistance substitutions, a partial requirement for ETVr, preexist, resulting in a 5-year cumulative probability of genotypic ETVr and genotypic ETVr associated with breakthrough of 51% and 43%, respectively. Importantly, only four patients who achieved < 300 copies/mL HBV DNA subsequently developed ETVr. Long-term monitoring showed low rates of resistance in nucleoside-naïve patients during 5 years of ETV therapy, corresponding with potent viral suppression and a high genetic barrier to resistance. These findings support ETV as a primary therapy that enables prolonged treatment with potent viral suppression and minimal resistance.

[Clinical relevance of ESR1 circulating mutations detection in hormone receptor positive metastatic breast cancer].

PubMed

Clatot, Florian; Perdrix, Anne; Sefrioui, David; Sarafan-Vasseur, Nasrin; Di Fiore, Frédéric

2018-01-01

If hormone therapy is a key treatment for hormone receptor positive advanced breast cancers, secondary resistance occurs as a rule. Recently, acquired alterations of the ESR1 gene have been identified as a mechanism of resistance on aromatase inhibitor (AI) treatment. The selective pressure by AI exposure during the metastatic setting triggers the emergence of ESR1 activating mutations. In that context, the "liquid biopsy" concept has been used to detect this molecular resistance before progression. Thus, the ESR1 circulating mutation detection will soon be used in daily practice to help monitoring patients on AI treatment and provide an early change for specific therapies that still have to be determined in prospective clinical trials. This review will present the acquired ESR1 mutations, as well as the methods used for their detection in blood and the potential clinical impact of this approach for hormone receptor positive breast cancer management. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

PubMed

Riegler, Johannes; Ebert, Antje; Qin, Xulei; Shen, Qi; Wang, Mouer; Ameen, Mohamed; Kodo, Kazuki; Ong, Sang-Ging; Lee, Won Hee; Lee, Grace; Neofytou, Evgenios; Gold, Joseph D; Connolly, Andrew J; Wu, Joseph C

2016-02-09

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Surface electromyography in orthodontics – a literature review

PubMed Central

WoŸniak, Krzysztof; Piątkowska, Dagmara; Lipski, Mariusz; Mehr, Katarzyna

2013-01-01

Electromyography is the most objective and reliable technique for evaluating muscle function and efficiency by detecting their electrical potentials. It makes it possible to assess the extent and duration of muscle activity. The main aim of surface electromyography is to detect signals from many muscle fibers in the area of the detecting surface electrodes. These signals consist of a weighted summation of the spatial and temporal activity of many motor units. Hence, the analysis of the recordings is restricted to an assessment of general muscle activity, the cooperation of different muscles, and the variability of their activity over time. This study presents the main assumptions in the assessment of electrical muscle activity through the use of surface electromyography, along with its limitations and possibilities for further use in many areas of orthodontics. The main clinical uses of sEMG include the diagnostics and therapy of temporomandibular joint disorders, an assessment of the extent of stomatognathic system dysfunctions in subjects with malocclusion, and the monitoring of orthodontic therapies. PMID:23722255

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

PubMed

Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer

PubMed Central

Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors. PMID:25414829

Feasibility of spatial frequency-domain imaging for monitoring palpable breast lesions

NASA Astrophysics Data System (ADS)

Robbins, Constance M.; Raghavan, Guruprasad; Antaki, James F.; Kainerstorfer, Jana M.

2017-12-01

In breast cancer diagnosis and therapy monitoring, there is a need for frequent, noninvasive disease progression evaluation. Breast tumors differ from healthy tissue in mechanical stiffness as well as optical properties, which allows optical methods to detect and monitor breast lesions noninvasively. Spatial frequency-domain imaging (SFDI) is a reflectance-based diffuse optical method that can yield two-dimensional images of absolute optical properties of tissue with an inexpensive and portable system, although depth penetration is limited. Since the absorption coefficient of breast tissue is relatively low and the tissue is quite flexible, there is an opportunity for compression of tissue to bring stiff, palpable breast lesions within the detection range of SFDI. Sixteen breast tissue-mimicking phantoms were fabricated containing stiffer, more highly absorbing tumor-mimicking inclusions of varying absorption contrast and depth. These phantoms were imaged with an SFDI system at five levels of compression. An increase in absorption contrast was observed with compression, and reliable detection of each inclusion was achieved when compression was sufficient to bring the inclusion center within ˜12 mm of the phantom surface. At highest compression level, contrasts achieved with this system were comparable to those measured with single source-detector near-infrared spectroscopy.

Overview of the role of nanotechnological innovations in the detection and treatment of solid tumors

PubMed Central

Frank, Derusha; Tyagi, Charu; Tomar, Lomas; Choonara, Yahya E; du Toit, Lisa C; Kumar, Pradeep; Penny, Clement; Pillay, Viness

2014-01-01

Nanotechnology, although still in its infantile stages, has the potential to revolutionize the diagnosis, treatment, and monitoring of disease progression and success of therapy for numerous diseases and conditions, not least of which is cancer. As it is a leading cause of mortality worldwide, early cancer detection, as well as safe and efficacious therapeutic intervention, will be indispensable in improving the prognosis related to cancers and overall survival rate, as well as health-related quality of life of patients diagnosed with cancer. The development of a relatively new field of nanomedicine, which combines various domains and technologies including nanotechnology, medicine, biology, pharmacology, mathematics, physics, and chemistry, has yielded different approaches to addressing these challenges. Of particular relevance in cancer, nanosystems have shown appreciable success in the realm of diagnosis and treatment. Characteristics attributable to these systems on account of the nanoscale size range allow for individualization of therapy, passive targeting, the attachment of targeting moieties for more specific targeting, minimally invasive procedures, and real-time imaging and monitoring of in vivo processes. Furthermore, incorporation into nanosystems may have the potential to reintroduce into clinical practice drugs that are no longer used because of various shortfalls, as well as aid in the registration of new, potent drugs with suboptimal pharmacokinetic profiles. Research into the development of nanosystems for cancer diagnosis and therapy is thus a rapidly emerging and viable field of study. PMID:24489467

[Performance evaluation of Abbott RealTime HBV Quantification Kit for HBV viral load by real-time PCR].

PubMed

Kim, Myeong Hee; Cha, Choong Hwan; An, Dongheui; Choi, Sung Eun; Oh, Heung Bum

2008-04-01

Hepatitis B virus (HBV) DNA quantification is necessary for starting and monitoring of antiviral therapy in patients with chronic hepatitis B. This study was intended to assess the clinical performance of Abbott RealTime HBV Quantification kit (Abbott Laboratories, USA). The performance was evaluated in terms of precision, linearity, detection sensitivity, cross-reactivity, and carry-over. A correlation with the Real-Q HBV Quantification kit (BioSewoom Inc., Korea) was also examined using serum samples from 64 patients diagnosed with chronic hepatitis B and underwent lamivudine therapy in Asan Medical Center. We verified the trueness of the system by comparing the outputs with the assigned values of the BBI panel (BBI Diagnostics, USA). Within-run and between-run coefficients of variation (CV) were 3.56-4.71% and 3.03-4.98%, respectively. Linearity was manifested ranging from 53 to 10(9)copies/mL and the detection sensitivity was verified to be 51 copies/mL. None of hepatitis C virus showed cross-reactivity. No cross-contamination occurred when negative and positive samples were alternatively placed in a row. It showed a good correlation with the Real-Q HBV (r(2)=0.9609) and the test results for the BBI panel were also well agreed to the assigned values (r(2)=0.9933). The performance of Abbott RealTime HBV Quantification kit was excellent; thus, it should be widely used in starting and monitoring of antiviral therapy in Korean patients with chronic hepatitis B.

Natural history of Mycobacterium fortuitum pulmonary infection presenting with migratory infiltrates: a case report with microbiological analysis.

PubMed

Okamori, Satoshi; Asakura, Takanori; Nishimura, Tomoyasu; Tamizu, Eiko; Ishii, Makoto; Yoshida, Mitsunori; Fukano, Hanako; Hayashi, Yuichiro; Fujita, Masaki; Hoshino, Yoshihiko; Betsuyaku, Tomoko; Hasegawa, Naoki

2018-01-02

Presence of Mycobacterium fortuitum in respiratory tracts usually indicates mere colonization or transient infection, whereas true pulmonary infection occurs in patients with gastroesophageal disease. However, little is known about the diagnostic indications for true M. fortuitum pulmonary infection and the natural history of the disease. A 59-year-old man was referred to our hospital for treatment against M. fortuitum pulmonary infection. Fifteen years before the referral, he underwent total gastrectomy, after which he experienced esophageal reflux symptoms. After the referral, the patient was closely monitored without antimicrobial therapy because of mild symptoms and no pathological evidence of M. fortuitum pulmonary infection. During the observation, chest imaging showed migratory infiltrates. Two years after the referral, his lung biopsy specimen revealed foamy macrophages and multinucleated giant cells, indicating lipoid pneumonia. However, he was continually monitored without any treatment because there was no evidence of nontuberculous mycobacterial infection. Four years after the referral, he developed refractory pneumonia despite receiving adequate antibiotic therapy. After confirmation of granulomatous lesions, multiple antimicrobial therapy for M. fortuitum resulted in a remarkable improvement with no exacerbation for over 5 years. Random amplified polymorphic DNA polymerase chain reaction analysis revealed identical M. fortuitum strains in seven isolates from six sputum and one intestinal fluid specimens obtained during the course of the disease. We have described a patient with M. fortuitum pulmonary infection who presented with migratory infiltrates. The pathological evidence and microbiological analysis suggested that M. fortuitum pulmonary infection was associated with lipoid pneumonia and chronic exposure to gastrointestinal fluid. Therefore, physicians should carefully monitor patients with M. fortuitum detected from lower respiratory tract specimens and consider antimicrobial therapy for M. fortuitum infection when the patient does not respond to adequate antibiotic therapy against common pneumonia pathogens.

High-b-value diffusion-weighted MR imaging for pretreatment prediction and early monitoring of tumor response to therapy in mice.

PubMed

Roth, Yiftach; Tichler, Thomas; Kostenich, Genady; Ruiz-Cabello, Jesus; Maier, Stephan E; Cohen, Jack S; Orenstein, Arie; Mardor, Yael

2004-09-01

To evaluate the use of diffusion-weighted magnetic resonance (MR) imaging with standard and high b values for pretreatment prediction and early detection of tumor response to various antineoplastic therapies in an animal model. Mice bearing C26 colon carcinoma tumors were treated with doxorubicin (n = 25) and with aminolevulinic acid-based photodynamic therapy (n = 23). Fourteen mice served as controls. Conventional T2-weighted fast spin-echo and diffusion-weighted MR images were acquired once before therapy and at 6, 24, and 48 hours after treatment. Pretreatment and early (1-2 days) posttreatment water diffusion parameters were calculated and compared with later changes in tumor volumes measured on conventional MR images by using the Pearson correlation test. In chemotherapy-treated tumors, a significant correlation (P <.002, r = 0.6) was observed between diffusion parameters that reflected tumor viability, measured prior to treatment, and changes in tumor volumes after therapy. This correlation implies that tumors with high pretreatment viability will respond better to chemotherapy than more necrotic tumors. In tumors treated with photodynamic therapy, no such correlation was found. Changes observed in water diffusion 1-2 days after treatment significantly correlated with later tumor growth rate for both therapies (P <.002, r = 0.54 for photodynamic therapy; P <.0003, r = 0.61 for chemotherapy). High-b-value diffusion-weighted MR imaging has potential use for the early detection of response to therapy and for predicting treatment outcome prior to initiation of chemotherapy. Copyright RSNA, 2004

Detection of Activating Estrogen Receptor Gene (ESR1) Mutations in Single Circulating Tumor Cells.

PubMed

Paolillo, Carmela; Mu, Zhaomei; Rossi, Giovanna; Schiewer, Matthew J; Nguyen, Thomas; Austin, Laura; Capoluongo, Ettore; Knudsen, Karen; Cristofanilli, Massimo; Fortina, Paolo

2017-10-15

Purpose: Early detection is essential for treatment plans before onset of metastatic disease. Our purpose was to demonstrate feasibility to detect and monitor estrogen receptor 1 ( ESR1 ) gene mutations at the single circulating tumor cell (CTC) level in metastatic breast cancer (MBC). Experimental Design: We used a CTC molecular characterization approach to investigate heterogeneity of 14 hotspot mutations in ESR1 and their correlation with endocrine resistance. Combining the CellSearch and DEPArray technologies allowed recovery of 71 single CTCs and 12 WBC from 3 ER-positive MBC patients. Forty CTCs and 12 WBC were subjected to whole genome amplification by MALBAC and Sanger sequencing. Results: Among 3 selected patients, 2 had an ESR1 mutation (Y537). One showed two different ESR1 variants in a single CTC and another showed loss of heterozygosity. All mutations were detected in matched cell-free DNA (cfDNA). Furthermore, one had 2 serial blood samples analyzed and showed changes in both cfDNA and CTCs with emergence of mutations in ESR1 (Y537S and T570I), which has not been reported previously. Conclusions: CTCs are easily accessible biomarkers to monitor and better personalize management of patients with previously demonstrated ER-MBC who are progressing on endocrine therapy. We showed that single CTC analysis can yield important information on clonal heterogeneity and can be a source of discovery of novel and potential driver mutations. Finally, we also validate a workflow for liquid biopsy that will facilitate early detection of ESR1 mutations, the emergence of endocrine resistance and the choice of further target therapy. Clin Cancer Res; 23(20); 6086-93. ©2017 AACR . ©2017 American Association for Cancer Research.

[Liquid biopsies, a revolution in oncology?].

PubMed

Jordan, Bertrand

2015-01-01

The detection and analysis of circulating tumour DNA and/or circulating tumour cells in the blood of cancer patients open new possibilities for cancer characterisation and management. The approach has generated much commercial interest, but still requires more proof of clinical utility; it is however likely to play an important role in monitoring the evolution of cancer cells during therapy. © 2015 médecine/sciences – Inserm.

Early detection of aging cartilage and osteoarthritis in mice and patient samples using atomic force microscopy

NASA Astrophysics Data System (ADS)

Stolz, Martin; Gottardi, Riccardo; Raiteri, Roberto; Miot, Sylvie; Martin, Ivan; Imer, Raphaël; Staufer, Urs; Raducanu, Aurelia; Düggelin, Marcel; Baschong, Werner; Daniels, A. U.; Friederich, Niklaus F.; Aszodi, Attila; Aebi, Ueli

2009-03-01

The pathological changes in osteoarthritis-a degenerative joint disease prevalent among older people-start at the molecular scale and spread to the higher levels of the architecture of articular cartilage to cause progressive and irreversible structural and functional damage. At present, there are no treatments to cure or attenuate the degradation of cartilage. Early detection and the ability to monitor the progression of osteoarthritis are therefore important for developing effective therapies. Here, we show that indentation-type atomic force microscopy can monitor age-related morphological and biomechanical changes in the hips of normal and osteoarthritic mice. Early damage in the cartilage of osteoarthritic patients undergoing hip or knee replacements could similarly be detected using this method. Changes due to aging and osteoarthritis are clearly depicted at the nanometre scale well before morphological changes can be observed using current diagnostic methods. Indentation-type atomic force microscopy may potentially be developed into a minimally invasive arthroscopic tool to diagnose the early onset of osteoarthritis in situ.

Digital PCR analysis of circulating nucleic acids.

PubMed

Hudecova, Irena

2015-10-01

Detection of plasma circulating nucleic acids (CNAs) requires the use of extremely sensitive and precise methods. The commonly used quantitative real-time polymerase chain reaction (PCR) poses certain technical limitations in relation to the precise measurement of CNAs whereas the costs of massively parallel sequencing are still relatively high. Digital PCR (dPCR) now represents an affordable and powerful single molecule counting strategy to detect minute amounts of genetic material with performance surpassing many quantitative methods. Microfluidic (chip) and emulsion (droplet)-based technologies have already been integrated into platforms offering hundreds to millions of nanoliter- or even picoliter-scale reaction partitions. The compelling observations reported in the field of cancer research, prenatal testing, transplantation medicine and virology support translation of this technology into routine use. Extremely sensitive plasma detection of rare mutations originating from tumor or placental cells among a large background of homologous sequences facilitates unraveling of the early stages of cancer or the detection of fetal mutations. Digital measurement of quantitative changes in plasma CNAs associated with cancer or graft rejection provides valuable information on the monitoring of disease burden or the recipient's immune response and subsequent therapy treatment. Furthermore, careful quantitative assessment of the viral load offers great value for effective monitoring of antiviral therapy for immunosuppressed or transplant patients. The present review describes the inherent features of dPCR that make it exceptionally robust in precise and sensitive quantification of CNAs. Moreover, I provide an insight into the types of potential clinical applications that have been developed by researchers to date. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Quantitative Detection of Nucleoside Analogues by Multi-enzyme Biosensors using Time-Resolved Kinetic Measurements.

PubMed

Muthu, Pravin; Lutz, Stefan

2016-04-05

Fast, simple and cost-effective methods for detecting and quantifying pharmaceutical agents in patients are highly sought after to replace equipment and labor-intensive analytical procedures. The development of new diagnostic technology including portable detection devices also enables point-of-care by non-specialists in resource-limited environments. We have focused on the detection and dose monitoring of nucleoside analogues used in viral and cancer therapies. Using deoxyribonucleoside kinases (dNKs) as biosensors, our chemometric model compares observed time-resolved kinetics of unknown analytes to known substrate interactions across multiple enzymes. The resulting dataset can simultaneously identify and quantify multiple nucleosides and nucleoside analogues in complex sample mixtures. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cherenkov Video Imaging Allows for the First Visualization of Radiation Therapy in Real Time

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

Jarvis, Lesley A., E-mail: Lesley.a.jarvis@hitchcock.org; Norris Cotton Cancer Center at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire; Zhang, Rongxiao

Purpose: To determine whether Cherenkov light imaging can visualize radiation therapy in real time during breast radiation therapy. Methods and Materials: An intensified charge-coupled device (CCD) camera was synchronized to the 3.25-μs radiation pulses of the clinical linear accelerator with the intensifier set × 100. Cherenkov images were acquired continuously (2.8 frames/s) during fractionated whole breast irradiation with each frame an accumulation of 100 radiation pulses (approximately 5 monitor units). Results: The first patient images ever created are used to illustrate that Cherenkov emission can be visualized as a video during conditions typical for breast radiation therapy, even with complex treatment plans,more » mixed energies, and modulated treatment fields. Images were generated correlating to the superficial dose received by the patient and potentially the location of the resulting skin reactions. Major blood vessels are visible in the image, providing the potential to use these as biological landmarks for improved geometric accuracy. The potential for this system to detect radiation therapy misadministrations, which can result from hardware malfunction or patient positioning setup errors during individual fractions, is shown. Conclusions: Cherenkoscopy is a unique method for visualizing surface dose resulting in real-time quality control. We propose that this system could detect radiation therapy errors in everyday clinical practice at a time when these errors can be corrected to result in improved safety and quality of radiation therapy.« less

Nanotechnology applications in thoracic surgery.

PubMed

Hofferberth, Sophie C; Grinstaff, Mark W; Colson, Yolonda L

2016-07-01

Nanotechnology is an emerging, rapidly evolving field with the potential to significantly impact care across the full spectrum of cancer therapy. Of note, several recent nanotechnological advances show particular promise to improve outcomes for thoracic surgical patients. A variety of nanotechnologies are described that offer possible solutions to existing challenges encountered in the detection, diagnosis and treatment of lung cancer. Nanotechnology-based imaging platforms have the ability to improve the surgical care of patients with thoracic malignancies through technological advances in intraoperative tumour localization, lymph node mapping and accuracy of tumour resection. Moreover, nanotechnology is poised to revolutionize adjuvant lung cancer therapy. Common chemotherapeutic drugs, such as paclitaxel, docetaxel and doxorubicin, are being formulated using various nanotechnologies to improve drug delivery, whereas nanoparticle (NP)-based imaging technologies can monitor the tumour microenvironment and facilitate molecularly targeted lung cancer therapy. Although early nanotechnology-based delivery systems show promise, the next frontier in lung cancer therapy is the development of 'theranostic' multifunctional NPs capable of integrating diagnosis, drug monitoring, tumour targeting and controlled drug release into various unifying platforms. This article provides an overview of key existing and emerging nanotechnology platforms that may find clinical application in thoracic surgery in the near future. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Serum galactomannan versus a combination of galactomannan and polymerase chain reaction-based Aspergillus DNA detection for early therapy of invasive aspergillosis in high-risk hematological patients: a randomized controlled trial.

PubMed

Aguado, José María; Vázquez, Lourdes; Fernández-Ruiz, Mario; Villaescusa, Teresa; Ruiz-Camps, Isabel; Barba, Pere; Silva, Jose T; Batlle, Montserrat; Solano, Carlos; Gallardo, David; Heras, Inmaculada; Polo, Marta; Varela, Rosario; Vallejo, Carlos; Olave, Teresa; López-Jiménez, Javier; Rovira, Montserrat; Parody, Rocío; Cuenca-Estrella, Manuel

2015-02-01

The benefit of the combination of serum galactomannan (GM) assay and polymerase chain reaction (PCR)-based detection of serum Aspergillus DNA for the early diagnosis and therapy of invasive aspergillosis (IA) in high-risk hematological patients remains unclear. We performed an open-label, controlled, parallel-group randomized trial in 13 Spanish centers. Adult patients with acute myeloid leukemia and myelodysplastic syndrome on induction therapy or allogeneic hematopoietic stem cell transplant recipients were randomized (1:1 ratio) to 1 of 2 arms: "GM-PCR group" (the results of serial serum GM and PCR assays were provided to treating physicians) and "GM group" (only the results of serum GM were informed). Positivity in either assay prompted thoracic computed tomography scan and initiation of antifungal therapy. No antimold prophylaxis was permitted. Overall, 219 patients underwent randomization (105 in the GM-PCR group and 114 in the GM group). The cumulative incidence of "proven" or "probable" IA (primary study outcome) was lower in the GM-PCR group (4.2% vs 13.1%; odds ratio, 0.29 [95% confidence interval, .09-.91]). The median interval from the start of monitoring to the diagnosis of IA was lower in the GM-PCR group (13 vs 20 days; P = .022), as well as the use of empirical antifungal therapy (16.7% vs 29.0%; P = .038). Patients in the GM-PCR group had higher proven or probable IA-free survival (P = .027). A combined monitoring strategy based on serum GM and Aspergillus DNA was associated with an earlier diagnosis and a lower incidence of IA in high-risk hematological patients. Clinical Trials Registration. NCT01742026. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Statistical process control and verifying positional accuracy of a cobra motion couch using step-wedge quality assurance tool.

PubMed

Binny, Diana; Lancaster, Craig M; Trapp, Jamie V; Crowe, Scott B

2017-09-01

This study utilizes process control techniques to identify action limits for TomoTherapy couch positioning quality assurance tests. A test was introduced to monitor accuracy of the applied couch offset detection in the TomoTherapy Hi-Art treatment system using the TQA "Step-Wedge Helical" module and MVCT detector. Individual X-charts, process capability (cp), probability (P), and acceptability (cpk) indices were used to monitor a 4-year couch IEC offset data to detect systematic and random errors in the couch positional accuracy for different action levels. Process capability tests were also performed on the retrospective data to define tolerances based on user-specified levels. A second study was carried out whereby physical couch offsets were applied using the TQA module and the MVCT detector was used to detect the observed variations. Random and systematic variations were observed for the SPC-based upper and lower control limits, and investigations were carried out to maintain the ongoing stability of the process for a 4-year and a three-monthly period. Local trend analysis showed mean variations up to ±0.5 mm in the three-monthly analysis period for all IEC offset measurements. Variations were also observed in the detected versus applied offsets using the MVCT detector in the second study largely in the vertical direction, and actions were taken to remediate this error. Based on the results, it was recommended that imaging shifts in each coordinate direction be only applied after assessing the machine for applied versus detected test results using the step helical module. User-specified tolerance levels of at least ±2 mm were recommended for a test frequency of once every 3 months to improve couch positional accuracy. SPC enables detection of systematic variations prior to reaching machine tolerance levels. Couch encoding system recalibrations reduced variations to user-specified levels and a monitoring period of 3 months using SPC facilitated in detecting systematic and random variations. SPC analysis for couch positional accuracy enabled greater control in the identification of errors, thereby increasing confidence levels in daily treatment setups. © 2017 Royal Brisbane and Women's Hospital, Metro North Hospital and Health Service. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Evaluation of Transabdominal Ultrasound with Oral Cellulose-Based Contrast Agent in the Detection and Surveillance of Gastric Ulcer.

PubMed

Liu, Zhijun; Guo, Jintao; Wang, Shupeng; Zhao, Ying; Liu, Zhining; Li, Jing; Ren, Weidong; Tang, Shaoshan; Xie, Limei; Huang, Ying; Sun, Siyu; Huang, Liping

2017-07-01

The aim of this study was to assess the role of transabdominal ultrasound with cellulose-based oral contrast agent (TUS-OCCA) in the detection and surveillance of gastric ulcer. The study was approved by the institutional review board at Shengjing Hospital of China Medical University. A total of 124 consecutive patients with benign gastric ulcer diagnosed by gastroscopy and biopsy were enrolled. Serial TUS-OCCA (approximately 1 exam every 2 wk) was performed to monitor the effects of treatment, and additional interventions were planned according to the results. TUS-OCCA detected gastric ulcer in 76% of patients (94 of 124). The detection rates for lesions of ≤5 mm, lesions of 5-10 mm, lesions of 10-15 mm and lesions >15 mm were 32% (10 of 31), 77% (27 of 35), 96% (25 of 26) and 100% (32 of 32), respectively. The detection rates for lesions located in the antrum, angle and body were 70%, 84% and 85%, respectively. Among 30 undetected lesions, which ranged 2-13 mm in size, 11 were at the antrum, 9 at the angle, 3 in the body, 6 at the cardia and 1 at the fundus. During the follow-up period, patients underwent a mean of 3.8 TUS-OCCA examinations (range 2-7), and ulcers were healed after 8 wk (range 2-12 wk) of standard therapy in 76 patients. Eighteen patients who did not show improvement after standard therapy underwent repeat gastroscopy with biopsy. Repeat biopsy was positive for gastric cancer in 4 of these: 2 of the remaining 14 were diagnosed with gastric cancer at gastrectomy, and 12 were diagnosed with chronic benign ulcer. These results indicate that serial TUS-OCCA can be used for close monitoring during routine treatment of gastric ulcers that are detectable by TUS-OCCA and that monitoring by TUS-OCCA can guide additional interventions. A non-invasive follow-up program based on TUS-OCCA can also help to detect gastric cancers that have been misdiagnosed as benign ulcers at the initial endoscopic biopsy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Advantage of impulse oscillometry over spirometry to diagnose chronic obstructive pulmonary disease and monitor pulmonary responses to bronchodilators: An observational study.

PubMed

Saadeh, Constantine; Saadeh, Charles; Cross, Blake; Gaylor, Michael; Griffith, Melissa

2015-01-01

This retrospective study was a comparative analysis of sensitivity of impulse oscillometry and spirometry techniques for use in a mixed chronic obstructive pulmonary disease group for assessing disease severity and inhalation therapy. A total of 30 patients with mild-to-moderate chronic obstructive pulmonary disease were monitored by impulse oscillometry, followed by spirometry. Lung function was measured at baseline after bronchodilation and at follow-up (3-18 months). The impulse oscillometry parameters were resistance in the small and large airways at 5 Hz (R5), resistance in the large airways at 15 Hz (R15), and lung reactance (area under the curve X; AX). After the bronchodilator therapy, forced expiratory volume in 1 second (FEV1) readings evaluated by spirometry were unaffected at baseline and at follow-up, while impulse oscillometry detected an immediate improvement in lung function, in terms of AX (p = 0.043). All impulse oscillometry parameters significantly improved at follow-up, with a decrease in AX by 37% (p = 0.0008), R5 by 20% (p = 0.0011), and R15 by 12% (p = 0.0097). Impulse oscillometry parameters demonstrated greater sensitivity compared with spirometry for monitoring reversibility of airway obstruction and the effect of maintenance therapy. Impulse oscillometry may facilitate early treatment dose optimization and personalized medicine for chronic obstructive pulmonary disease patients.

Clinical Validation of Therapeutic Drug Monitoring of Imipenem in Spent Effluent in Critically Ill Patients Receiving Continuous Renal Replacement Therapy: A Pilot Study

PubMed Central

Wen, Aiping; Li, Zhe; Yu, Junxian; Li, Ren; Cheng, Sheng; Duan, Meili; Bai, Jing

2016-01-01

Objectives The primary objective of this pilot study was to investigate whether the therapeutic drug monitoring of imipenem could be performed with spent effluent instead of blood sampling collected from critically ill patients under continuous renal replacement therapy. Methods A prospective open-label study was conducted in a real clinical setting. Both blood and effluent samples were collected pairwise before imipenem administration and 0.5, 1, 1.5, 2, 3, 4, 6, and 8 h after imipenem administration. Plasma and effluent imipenem concentrations were determined by reversed-phase high-performance liquid chromatography with ultraviolet detection. Pharmacokinetic and pharmacodynamic parameters of blood and effluent samples were calculated. Results Eighty-three paired plasma and effluent samples were obtained from 10 patients. The Pearson correlation coefficient of the imipenem concentrations in plasma and effluent was 0.950 (P<0.0001). The average plasma-to-effluent imipenem concentration ratio was 1.044 (95% confidence interval, 0.975 to 1.114) with Bland-Altman analysis. No statistically significant difference was found in the pharmacokinetic and pharmacodynamic parameters tested in paired plasma and effluent samples with Wilcoxon test. Conclusion Spent effluent of continuous renal replacement therapy could be used for therapeutic drug monitoring of imipenem instead of blood sampling in critically ill patients. PMID:27093294

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed Central

Ried, Karin; Eng, Peter; Sali, Avni

2017-01-01

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 out-of 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. PMID:28843267

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed

Ried, Karin; Eng, Peter; Sali, Avni

2017-08-27

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 outof 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. Creative Commons Attribution License

Measurement of secondary particle production induced by particle therapy ion beams impinging on a PMMA target

NASA Astrophysics Data System (ADS)

Toppi, M.; Battistoni, G.; Bellini, F.; Collamati, F.; De Lucia, E.; Durante, M.; Faccini, R.; Frallicciardi, P. M.; Marafini, M.; Mattei, I.; Morganti, S.; Muraro, S.; Paramatti, R.; Patera, V.; Pinci, D.; Piersanti, L.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Senzacqua, M.; Solfaroli Camillocci, E.; Traini, G.; Voena, C.

2016-05-01

Particle therapy is a technique that uses accelerated charged ions for cancer treatment and combines a high irradiation precision with a high biological effectiveness in killing tumor cells [1]. Informations about the secondary particles emitted in the interaction of an ion beam with the patient during a treatment can be of great interest in order to monitor the dose deposition. For this purpose an experiment at the HIT (Heidelberg Ion-Beam Therapy Center) beam facility has been performed in order to measure fluxes and emission profiles of secondary particles produced in the interaction of therapeutic beams with a PMMA target. In this contribution some preliminary results about the emission profiles and the energy spectra of the detected secondaries will be presented.

Immune monitoring of clinical trials with biotherapies.

PubMed

Whiteside, Theresa L

2008-01-01

Immune monitoring of biotherapy clinical trials has undergone a considerable change in recent years. Technical advances together with new insights into molecular immunology have ushered a new genre of assays into immune monitoring. Single-cell assays, multiplex profiling, and signaling molecule detection have replaced formerly used bulk assays, such as proliferation or cytotoxicity. The emphasis on immune cell functions and quantitation of antigen-specific T cells has been playing a major role in attempts to establish correlations between therapy-induced alterations in immune responses and clinical endpoints. However, this has been an elusive goal to achieve, and there is a special need for improving the quality of serial monitoring to ensure that it adequately and reliably measures changes induced by administered biotherapy. In this respect, monitoring performed in specialized reference laboratories operating as good laboratory practice (GLP) facilities and strengthening of interactions between the clinical investigator, the clinical immunologist, and the biostatistician are crucial for successful use of immune monitoring in clinical studies.

Detecting ionizing radiation with optical fibers down to biomedical doses

NASA Astrophysics Data System (ADS)

Avino, S.; D'Avino, V.; Giorgini, A.; Pacelli, R.; Liuzzi, R.; Cella, L.; De Natale, P.; Gagliardi, G.

2013-10-01

We report on a passive ionizing radiation sensor based on a fiber-optic resonant cavity interrogated by a high resolution interferometric technique. After irradiation in clinical linear accelerators, we observe significant variations of the fiber thermo-optic coefficient. Exploiting this effect, we demonstrate an ultimate detection limit of 160 mGy with an interaction volume of only 6 × 10-4 mm3. Thanks to its reliability, compactness, and sensitivity at biomedical dose levels, our system lends itself to real applications in radiation therapy procedures as well as in radiation monitoring and protection in medicine, aerospace, and nuclear power plants.

Flow Cytometric Immunobead Assay for Detection of BCR-ABL1 Fusion Proteins in Chronic Myleoid Leukemia: Comparison with FISH and PCR Techniques

PubMed Central

Recchia, Anna Grazia; Caruso, Nadia; Bossio, Sabrina; Pellicanò, Mariavaleria; De Stefano, Laura; Franzese, Stefania; Palummo, Angela; Abbadessa, Vincenzo; Lucia, Eugenio; Gentile, Massimo; Vigna, Ernesto; Caracciolo, Clementina; Agostino, Antolino; Galimberti, Sara; Levato, Luciano; Stagno, Fabio; Molica, Stefano; Martino, Bruno; Vigneri, Paolo; Di Raimondo, Francesco; Morabito, Fortunato

2015-01-01

Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR) defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometry based assays could be of clinical utility in evaluating residual disease in CML patients. Here we describe a flow-cytometry assay that detects the presence of BCR-ABL1 fusion proteins in CML lysates to determine the applicability, reliability, and specificity of this method for both diagnosis and monitoring of CML patients for initial response to therapy. We show that: i) CML can be properly diagnosed at onset, (ii) follow-up assessments show detectable fusion protein (i.e. relative mean fluorescent intensity, rMFI%>1) when BCR-ABL1IS transcripts are between 1–10%, and (iii) rMFI% levels predict CCyR as defined by FISH analysis. Overall, the FCBA assay is a rapid technique, fully translatable to the routine management of CML patients. PMID:26111048

On- and off-line monitoring of ion beam treatment

NASA Astrophysics Data System (ADS)

Parodi, Katia

2016-02-01

Ion beam therapy is an emerging modality for high precision radiation treatment of cancer. In comparison to conventional radiation sources (photons, electrons), ion beams feature major dosimetric advantages due to their finite range with a localized dose deposition maximum, the Bragg peak, which can be selectively adjusted in depth. However, due to several sources of treatment uncertainties, full exploitation of these dosimetric advantages in clinical practice would require the possibility to visualize the stopping position of the ions in vivo, ideally in real-time. To this aim, different imaging methods have been proposed and investigated, either pre-clinically or even clinically, based on the detection of prompt or delayed radiation following nuclear interaction of the beam with the irradiated tissue. However, the chosen or ad-hoc developed instrumentation has often relied on technologies originally conceived for different applications, thus compromising on the achievable performances for the sake of cost-effectiveness. This contribution will review major examples of used instrumentation and related performances, identifying the most promising detector developments for next generation devices especially dedicated to on-line monitoring of ion beam treatment. Moreover, it will propose an original combination of different techniques in a hybrid detection scheme, aiming to make the most of complementary imaging methods and open new perspectives of image guidance for improved precision of ion beam therapy.

A Wireless Monitoring System Using a Tunneling Sensor Array in a Smart Oral Appliance for Sleep Apnea Treatment

PubMed Central

Yeh, Kun-Ying; Yeh, Chao-Chi; Tang, Kuan; Wu, Jyun-Yi; Chen, Yun-Ting; Xu, Ming-Xin; Chen, Yunn-Jy; Yang, Yao-Joe; Lu, Shey-Shi

2017-01-01

Sleep apnea is a serious sleep disorder, and the most common type is obstructive sleep apnea (OSA). Untreated OSA will cause lots of potential health problems. Oral appliance therapy is an effective and popular approach for OSA treatment, but making a perfect fit for each patient is time-consuming and decreases its efficiency considerably. This paper proposes a System-on-a-Chip (SoC) enabled sleep monitoring system in a smart oral appliance, which is capable of intelligently collecting the physiological data about tongue movement through the whole therapy. A tunneling sensor array with an ultra-high sensitivity is incorporated to accurately detect the subtle pressure from the tongue. When the device is placed on the wireless platform, the temporary stored data will be retrieved and wirelessly transmitted to personal computers and cloud storages. The battery will be recharged by harvesting external RF power from the platform. A compact prototype module, whose size is 4.5 × 2.5 × 0.9 cm3, is implemented and embedded inside the oral appliance to demonstrate the tongue movement detection in continuous time frames. The functions of this design are verified by the presented measurement results. This design aims to increase efficiency and make it a total solution for OSA treatment. PMID:29035296

A detector for monitoring the onset of cavitation during therapy-level measurements of ultrasonic power

NASA Astrophysics Data System (ADS)

Hodnett, M.; Zeqiri, B.

2004-01-01

Acoustic cavitation occurring in the water path between a transducer and the target of a radiation force balance can provide a significant source of error during measurements of ultrasonic power. These problems can be particularly acute at physiotherapy levels (>1 W), and low frequencies (leq 1 MHz). The cavitating bubbles can absorb and scatter incident ultrasound, leading to an underestimate in the measured power. For these reasons, International Specification standards demand the use of degassed water. This imposes requirements that may actually be difficult to meet, for example, in the case of hospitals. Also, initially degassed water will rapidly re-gas, increasing the likelihood of cavitation occurring. For these reasons, NPL has developed a device that monitors acoustic emissions generated by bubble activity, for detecting the onset of cavitation during power measurements. A commercially available needle hydrophone is used to detect these emissions. The acoustic signals are then monitored using a Cavitation Detector (CD) unit, comprising an analogue electrical filter that may be tuned to detect frequency components generated by cavitating bubbles, and which provides an indication of when the measured level exceeds a pre-defined threshold. This paper describes studies to establish a suitable detection scheme, the principles of operation of the CD unit, and the performance tests carried out with a range of propagation media.

Algorithms for the detection of chewing behavior in dietary monitoring applications

NASA Astrophysics Data System (ADS)

Schmalz, Mark S.; Helal, Abdelsalam; Mendez-Vasquez, Andres

2009-08-01

The detection of food consumption is key to the implementation of successful behavior modification in support of dietary monitoring and therapy, for example, during the course of controlling obesity, diabetes, or cardiovascular disease. Since the vast majority of humans consume food via mastication (chewing), we have designed an algorithm that automatically detects chewing behaviors in surveillance video of a person eating. Our algorithm first detects the mouth region, then computes the spatiotemporal frequency spectrum of a small perioral region (including the mouth). Spectral data are analyzed to determine the presence of periodic motion that characterizes chewing. A classifier is then applied to discriminate different types of chewing behaviors. Our algorithm was tested on seven volunteers, whose behaviors included chewing with mouth open, chewing with mouth closed, talking, static face presentation (control case), and moving face presentation. Early test results show that the chewing behaviors induce a temporal frequency peak at 0.5Hz to 2.5Hz, which is readily detected using a distance-based classifier. Computational cost is analyzed for implementation on embedded processing nodes, for example, in a healthcare sensor network. Complexity analysis emphasizes the relationship between the work and space estimates of the algorithm, and its estimated error. It is shown that chewing detection is possible within a computationally efficient, accurate, and subject-independent framework.

Monitoring of breathing motion in image-guided PBS proton therapy: comparative analysis of optical and electromagnetic technologies.

PubMed

Fattori, Giovanni; Safai, Sairos; Carmona, Pablo Fernández; Peroni, Marta; Perrin, Rosalind; Weber, Damien Charles; Lomax, Antony John

2017-03-31

Motion monitoring is essential when treating non-static tumours with pencil beam scanned protons. 4D medical imaging typically relies on the detected body surface displacement, considered as a surrogate of the patient's anatomical changes, a concept similarly applied by most motion mitigation techniques. In this study, we investigate benefits and pitfalls of optical and electromagnetic tracking, key technologies for non-invasive surface motion monitoring, in the specific environment of image-guided, gantry-based proton therapy. Polaris SPECTRA optical tracking system and the Aurora V3 electromagnetic tracking system from Northern Digital Inc. (NDI, Waterloo, CA) have been compared both technically, by measuring tracking errors and system latencies under laboratory conditions, and clinically, by assessing their practicalities and sensitivities when used with imaging devices and PBS treatment gantries. Additionally, we investigated the impact of using different surrogate signals, from different systems, on the reconstructed 4D CT images. Even though in controlled laboratory conditions both technologies allow for the localization of static fiducials with sub-millimetre jitter and low latency (31.6 ± 1 msec worst case), significant dynamic and environmental distortions limit the potential of the electromagnetic approach in a clinical setting. The measurement error in case of close proximity to a CT scanner is up to 10.5 mm and precludes its use for the monitoring of respiratory motion during 4DCT acquisitions. Similarly, the motion of the treatment gantry distorts up to 22 mm the tracking result. Despite the line of sight requirement, the optical solution offers the best potential, being the most robust against environmental factors and providing the highest spatial accuracy. The significant difference in the temporal location of the reconstructed phase points is used to speculate on the need to apply the same monitoring system for imaging and treatment to ensure the consistency of detected phases.

Fractional exhaled nitric oxide-measuring devices: technology update

PubMed Central

Maniscalco, Mauro; Vitale, Carolina; Vatrella, Alessandro; Molino, Antonio; Bianco, Andrea; Mazzarella, Gennaro

2016-01-01

The measurement of exhaled nitric oxide (NO) has been employed in the diagnosis of specific types of airway inflammation, guiding treatment monitoring by predicting and assessing response to anti-inflammatory therapy and monitoring for compliance and detecting relapse. Various techniques are currently used to analyze exhaled NO concentrations under a range of conditions for both health and disease. These include chemiluminescence and electrochemical sensor devices. The cost effectiveness and ability to achieve adequate flexibility in sensitivity and selectivity of NO measurement for these methods are evaluated alongside the potential for use of laser-based technology. This review explores the technologies involved in the measurement of exhaled NO. PMID:27382340

Circulating tumor cells in clinical research and monitoring patients with colorectal cancer

PubMed Central

Burz, Claudia; Pop, Vlad-Vasile; Buiga, Rares; Daniel, Sur; Samasca, Gabriel; Aldea, Cornel; Lupan, Iulia

2018-01-01

Colorectal cancer remains a frequent disease to which screening and target therapy exist, but despite this is still marked by a high mortality rate. Even though radical surgery may be performed in many cases, patients relapse with metastatic disease. Circulating tumor cells were incriminated for tumor recurrence, that's why vigorous research started on their field. Owning prognostic and predictive value, it was revealed their usefulness in disease monitoring. Moreover, they may serve as liquid biopsies for genetic tests in cases where tissue biopsy is contraindicated or cannot be performed. In spite of these advantages, they were not included in clinical guidelines, despite CellSearch and many other detection methods were developed to ease the identification of circulating tumor cells. This review highlights the implication of circulating tumor cells in metastasis cascade, intrinsic tumor cells mechanisms and correlations with clinical parameters along with their utility for medical practice and detection techniques. PMID:29849961

Comparison of the Abbott m2000 HIV-1 Real-Time and Roche AMPLICOR Monitor v1.5 HIV-1 assays on plasma specimens from Rakai, Uganda.

PubMed

Ssebugenyi, I; Kizza, A; Mpoza, B; Aluma, G; Boaz, I; Newell, K; Laeyendecker, O; Shott, J P; Serwadda, D; Reynolds, S J

2011-07-01

The need for viral load (VL) monitoring of HIV patients receiving antiretroviral therapy (ART) in resource-limited settings (RLS) has become apparent with studies showing the limitations of immunological monitoring. We compared the Abbott m2000 Real-Time (Abbott) HIV-1 assay with the Roche AMPLICOR Monitor v1.5 (Roche) HIV-1 assay over a range of VL concentrations. Three hundred and eleven plasma samples were tested, including 164 samples from patients on ART ≥ six months and 147 from ART-naïve patients. The Roche assay detected ≥400 copies/mL in 158 (50.8%) samples. Of these, Abbott produced 145 (91.8%) detectable results ≥400 copies/mL; 13 (8.2%) samples produced discrepant results. Concordance between the assays for detecting HIV-1 RNA ≥400 copies/mL was 95.8% (298/311). The sensitivity, specificity, positive predictive value and negative predictive value of Abbott to detect HIV-1 RNA ≥400 copies/mL were 91.8%, 100%, 100% and 92.2%, respectively. For the 151 samples with HIV-1 RNA ≥400 copies/mL for both assays, a good linear correlation was found (r = 0.81, P < 0.0001; mean difference, 0.05). The limits of agreement were -0.97 and 1.07 log(10) copies/mL (mean ± 2 SD). The Abbott assay performed well in our setting, offering an alternative methodology for HIV-1 VL for laboratories with realtime polymerase chain reaction (PCR) capacity.

Venous leg ulcer healing with electric stimulation therapy: a pilot randomised controlled trial.

PubMed

Miller, C; McGuiness, W; Wilson, S; Cooper, K; Swanson, T; Rooney, D; Piller, N; Woodward, M

2017-03-02

Compression therapy is a gold standard treatment to promote venous leg ulcer (VLU) healing. Concordance with compression therapy is, however, often sub-optimal. The aim of this study was to evaluate the effectiveness of electric stimulation therapy (EST) to facilitate healing of VLUs among people who do not use moderate-to-high levels of compression (>25 mmHg). A pilot multicentre, single-blinded randomised controlled trial was conducted. Participants were randomised (2:1) to the intervention group or a control group where EST or a sham device was used 4 times daily for 20 minutes per session. Participants were monitored fortnightly for eight weeks. The primary outcome measure was percentage of area (wound size) change. In the 23 patients recruited, an average redution in wound size of 23.15% (standard deviation [SD]: 61.23) was observed for the control group compared with 32.67 % (SD: 42.54) for the intervention. A moderate effect size favouring the intervention group was detected from univariate [F(1,18)=1.588, p=0.224, partial eta squared=0.081] and multivariate repeated measures [F(1,18)=2.053, p=0.169, partial eta squared=0.102] analyses. The pilot study was not powered to detect statistical significance, however, the difference in healing outcomes are encouraging. EST may be an effective adjunct treatment among patients who have experienced difficulty adhering to moderate-to-high levels of compression therapy.

Proton therapy treatment monitoring with the DoPET system: activity range, positron emitters evaluation and comparison with Monte Carlo predictions

NASA Astrophysics Data System (ADS)

Muraro, S.; Battistoni, G.; Belcari, N.; Bisogni, M. G.; Camarlinghi, N.; Cristoforetti, L.; Del Guerra, A.; Ferrari, A.; Fracchiolla, F.; Morrocchi, M.; Righetto, R.; Sala, P.; Schwarz, M.; Sportelli, G.; Topi, A.; Rosso, V.

2017-12-01

Ion beam irradiations can deliver conformal dose distributions minimizing damage to healthy tissues thanks to their characteristic dose profiles. Nevertheless, the location of the Bragg peak can be affected by different sources of range uncertainties: a critical issue is the treatment verification. During the treatment delivery, nuclear interactions between the ions and the irradiated tissues generate β+ emitters: the detection of this activity signal can be used to perform the treatment monitoring if an expected activity distribution is available for comparison. Monte Carlo (MC) codes are widely used in the particle therapy community to evaluate the radiation transport and interaction with matter. In this work, FLUKA MC code was used to simulate the experimental conditions of irradiations performed at the Proton Therapy Center in Trento (IT). Several mono-energetic pencil beams were delivered on phantoms mimicking human tissues. The activity signals were acquired with a PET system (DoPET) based on two planar heads, and designed to be installed along the beam line to acquire data also during the irradiation. Different acquisitions are analyzed and compared with the MC predictions, with a special focus on validating the PET detectors response for activity range verification.

Clinical advances of nanocarrier-based cancer therapy and diagnostics.

PubMed

Luque-Michel, Edurne; Imbuluzqueta, Edurne; Sebastián, Víctor; Blanco-Prieto, María J

2017-01-01

Cancer is a leading cause of death worldwide and efficient new strategies are urgently needed to combat its high mortality and morbidity statistics. Fortunately, over the years, nanotechnology has evolved as a frontrunner in the areas of imaging, diagnostics and therapy, giving the possibility of monitoring, evaluating and individualizing cancer treatments in real-time. Areas covered: Polymer-based nanocarriers have been extensively studied to maximize cancer treatment efficacy and minimize the adverse effects of standard therapeutics. Regarding diagnosis, nanomaterials like quantum dots, iron oxide nanoparticles or gold nanoparticles have been developed to provide rapid, sensitive detection of cancer and, therefore, facilitate early treatment and monitoring of the disease. Therefore, multifunctional nanosystems with both imaging and therapy functionalities bring us a step closer to delivering precision/personalized medicine in the cancer setting. Expert opinion: There are multiple barriers for these new nanosystems to enter the clinic, but it is expected that in the near future, nanocarriers, together with new 'targeted drugs', could replace our current treatments and cancer could become a nonfatal disease with good recovery rates. Joint efforts between scientists, clinicians, the pharmaceutical industry and legislative bodies are needed to bring to fruition the application of nanosystems in the clinical management of cancer.

The vital signs of chronic disease management.

PubMed

Harries, Anthony D; Zachariah, Rony; Kapur, Anil; Jahn, Andreas; Enarson, Donald A

2009-06-01

The vital signs of pulse rate, blood pressure, temperature and respiratory rate are the 'nub' of individual patient management. At the programmatic level, vital signs could also be used to monitor the burden and treatment outcome of chronic disease. Case detection and treatment outcome constitute the vital signs of tuberculosis control within the WHO's 'DOTS' framework, and similar vital signs could be adapted and used for management of chronic diseases. The numbers of new patients started on therapy in each month or quarter (new incident cases) are sensitive indicators for programme performance and access to services. Using similar reporting cycles, treatment outcomes for all patients can be assessed, the vital signs being: alive and retained on therapy at the respective facility; died; stopped therapy; lost to follow-up; and transferred out to another facility. Retention on treatment constitutes the prevalent number of cases, the burden of disease, and this provides important strategic information for rational drug forecasting and logistic planning. If case numbers and outcomes of chronic diseases were measured reliably and consistently as part of an integrated programmatic approach, this would strengthen the ability of resource-poor countries to monitor and assess their response to these growing epidemics.

ASHP national survey of pharmacy practice in hospital settings: monitoring and patient education--2003.

PubMed

Pedersen, Craig A; Schneider, Philip J; Scheckelhoff, Douglas J

2004-03-01

Results of the 2003 ASHP national survey of pharmacy practice in hospital settings that pertain to monitoring and patient education are presented. A stratified random sample of pharmacy directors at 1173 general and children's medical-surgical hospitals in the United States was surveyed by mail. SMG Marketing Group, Inc., supplied data on hospital characteristics; the survey sample was drawn from SMG's hospital database. The response rate was 47.1%. Virtually all hospitals (95.3%) had pharmacists regularly monitoring medication therapy in some capacity. Patient monitoring has improved since 2000; fewer respondents reported monitoring less than 25% of patients in the hospital, and most hospitals reported an increase in the amount of time pharmacists devoted to monitoring activities. Pharmacists were provided computer access to laboratory information in 78% of hospitals to facilitate this function. Detection and reporting of adverse drug events (ADEs) have substantially increased since 1999, with an increase of 42% in events reported internally. Strategies to improve ADE reporting were in place in 84% of hospitals, indicating that pharmacists are adopting the widely recommended philosophy of learning from errors. Errors were less widely reported externally, limiting the value of aggregated data for improving the medication-use process. Most hospitals (85.5%) had an interprofessional infrastructure in place to discuss and learn from voluntary reports of ADEs. Medication counseling continued to be relatively infrequent, with nearly three fourths of hospitals reporting fewer than 26% of inpatients received medication education. Pharmacist staffing in hospitals has risen significantly, from an average of 8.6 full-time equivalents (FTEs) in 2002 to 9.4 FTEs per hospital. Vacancy rates for pharmacists decreased from 7.3% in 2002 to 43%. It is now estimated that there are 1846 vacancies in hospital pharmacies. Notable improvements in hospital pharmacy practice have been made. The percentage of patients whose medication therapy is monitored by pharmacists has increased, and most hospitals reported that the amount of time pharmacists spent monitoring patients' medication therapy had increased. Internal and external reporting of ADEs has increased, and pharmacist vacancies have decreased from 2002. Staffing has also improved, suggesting an abatement of the critical shortage of pharmacists in the hospital setting.

Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.

PubMed

Cabel, L; Riva, F; Servois, V; Livartowski, A; Daniel, C; Rampanou, A; Lantz, O; Romano, E; Milder, M; Buecher, B; Piperno-Neumann, S; Bernard, V; Baulande, S; Bieche, I; Pierga, J Y; Proudhon, C; Bidard, F-C

2017-08-01

Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB. This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria. ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004). This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Diagnosis and Anti-Reflux Therapy for GERD with Respiratory Symptoms: A Study Using Multichannel Intraluminal Impedance-pH Monitoring

PubMed Central

Zhang, Chao; Wu, Jimin; Hu, Zhiwei; Yan, Chao; Gao, Xiang; Liang, Weitao; Liu, Diangang; Li, Fei; Wang, Zhonggao

2016-01-01

Background/Aims Respiratory symptoms are often associated with gastroesophageal reflux disease (GERD). Although the role of multichannel intraluminal impedance–pH (MII-pH) monitoring in GERD is clear, little is known regarding the characteristics of patients with respiratory symptoms based on MII-pH monitoring and anti-reflux therapy. We evaluated a cohort of GERD patients to identify the MII-pH parameters of GERD-related respiratory symptoms and to assess the anti-reflux therapy outcomes. Methods We undertook a prospective study of patients who were referred for GERD evaluation from January 2011 to January 2012. One hundred ninety-five patients underwent MII-pH monitoring and esophageal manometry, and one hundred sixty-five patients underwent invasive anti-reflux therapy that included laparoscopic Toupet fundoplication (LTF) and the Stretta procedure. The patient characteristics and MII-pH parameters were analyzed, and the symptom scores were assessed at baseline and at 1- and 3-year follow-up evaluations. Results Of the 195 patients, 96 (49.2%) exhibited respiratory symptoms and significantly more reflux episodes (70.7±29.3) than patients without respiratory symptoms (64.7±24.4, p = 0.044) based on the MII-pH monitoring results. Moreover, the group of patients with respiratory symptoms exhibited more proximal reflux episodes (35.2±21.3) than the non-respiratory symptomatic group (28.3±17.9, p = 0.013). One hundred twenty-five patients following the Stretta procedure (n = 60, 31 with respiratory symptoms) or LTF (n = 65, 35 with respiratory symptoms) completed the designated 3-year follow-up period and were included in the final analysis. The symptom scores after anti-reflux therapy all decreased relative to the corresponding baseline values (p<0.05), and there were no significant differences in the control of respiration between the Stretta procedure and LTF (p>0.05). However, LTF significantly reduced the recurrence (re-operation) rate compared with the Stretta procedure (0 vs. 19.4%, p = 0.006). Conclusions MII-pH monitoring effectively detected respiratory-related predictive parameters, including total/proximal reflux episodes and symptom correlations. We found that GERD patients with respiratory symptoms exhibited more proximal and total reflux episodes but not more acid-related episodes, as determined by MII-pH monitoring. Thus, such monitoring could be useful for diagnosing atypical GERD patients with respiratory symptoms. Furthermore, LTF exhibited a more significant effect on controlling typical symptoms in all GERD patients and reducing the recurrence rate than the Stretta procedure in patients with respiratory symptoms. PMID:27532103

Advancements in nano-enabled therapeutics for neuroHIV management.

PubMed

Kaushik, Ajeet; Jayant, Rahul Dev; Nair, Madhavan

This viewpoint is a global call to promote fundamental and applied research aiming toward designing smart nanocarriers of desired properties, novel noninvasive strategies to open the blood-brain barrier (BBB), delivery/release of single/multiple therapeutic agents across the BBB to eradicate neurohuman immunodeficiency virus (HIV), strategies for on-demand site-specific release of antiretroviral therapy, developing novel nanoformulations capable to recognize and eradicate latently infected HIV reservoirs, and developing novel smart analytical diagnostic tools to detect and monitor HIV infection. Thus, investigation of novel nanoformulations, methodologies for site-specific delivery/release, analytical methods, and diagnostic tools would be of high significance to eradicate and monitor neuroacquired immunodeficiency syndrome. Overall, these developments will certainly help to develop personalized nanomedicines to cure HIV and to develop smart HIV-monitoring analytical systems for disease management.

Effectiveness of remote monitoring of CIEDs in detection and treatment of clinical and device-related cardiovascular events in daily practice: the HomeGuide Registry

PubMed Central

Ricci, Renato Pietro; Morichelli, Loredana; D'Onofrio, Antonio; Calò, Leonardo; Vaccari, Diego; Zanotto, Gabriele; Curnis, Antonio; Buja, Gianfranco; Rovai, Nicola; Gargaro, Alessio

2013-01-01

Aims The HomeGuide Registry was a prospective study (NCT01459874), implementing a model for remote monitoring of cardiac implantable electronic devices (CIEDs) in daily clinical practice, to estimate effectiveness in major cardiovascular event detection and management. Methods and results The workflow for remote monitoring [Biotronik Home Monitoring (HM)] was based on primary nursing: each patient was assigned to an expert nurse for management and to a responsible physician for medical decisions. In-person visits were scheduled once a year. Seventy-five Italian sites enrolled 1650 patients [27% pacemakers, 27% single-chamber implantable cardioverter defibrillators (ICDs), 22% dual-chamber ICDs, 24% ICDs with cardiac resynchronization therapy]. Population resembled the expected characteristics of CIED patients. During a 20 ± 13 month follow-up, 2471 independently adjudicated events were collected in 838 patients (51%): 2033 (82%) were detected during HM sessions; 438 (18%) during in-person visits. Sixty were classified as false-positive, with generalized estimating equation-adjusted sensitivity and positive predictive value of 84.3% [confidence interval (CI), 82.5–86.0%] and 97.4% (CI, 96.5–98.2%), respectively. Overall, 95% of asymptomatic and 73% of actionable events were detected during HM sessions. Median reaction time was 3 days [interquartile range (IQR), 1–14 days]. Generalized estimating equation-adjusted incremental utility, calculated according to four properties of major clinical interest, was in favour of the HM sessions: +0.56 (CI, 0.53–0.58%), P < 0.0001. Resource consumption: 3364 HM sessions performed (76% by nurses), median committed monthly manpower of 55.5 (IQR, 22.0–107.0) min × health personnel/100 patients. Conclusion Home Monitoring was highly effective in detecting and managing clinical events in CIED patients in daily practice with remarkably low manpower and resource consumption. PMID:23362021

Nanolock-Nanopore Facilitated Digital Diagnostics of Cancer Driver Mutation in Tumor Tissue.

PubMed

Wang, Yong; Tian, Kai; Shi, Ruicheng; Gu, Amy; Pennella, Michael; Alberts, Lindsey; Gates, Kent S; Li, Guangfu; Fan, Hongxin; Wang, Michael X; Gu, Li-Qun

2017-07-28

Cancer driver mutations are clinically significant biomarkers. In precision medicine, accurate detection of these oncogenic changes in patients would enable early diagnostics of cancer, individually tailored targeted therapy, and precise monitoring of treatment response. Here we investigated a novel nanolock-nanopore method for single-molecule detection of a serine/threonine protein kinase gene BRAF V600E mutation in tumor tissues of thyroid cancer patients. The method lies in a noncovalent, mutation sequence-specific nanolock. We found that the nanolock formed on the mutant allele/probe duplex can separate the duplex dehybridization procedure into two sequential steps in the nanopore. Remarkably, this stepwise unzipping kinetics can produce a unique nanopore electric marker, with which a single DNA molecule of the cancer mutant allele can be unmistakably identified in various backgrounds of the normal wild-type allele. The single-molecule sensitivity for mutant allele enables both binary diagnostics and quantitative analysis of mutation occurrence. In the current configuration, the method can detect the BRAF V600E mutant DNA lower than 1% in the tumor tissues. The nanolock-nanopore method can be adapted to detect a broad spectrum of both transversion and transition DNA mutations, with applications from diagnostics to targeted therapy.

Change detection technique for muscle tone during static stretching by continuous muscle viscoelasticity monitoring using wearable indentation tester.

PubMed

Okamura, Naomi; Kobayashi, Yo; Sugano, Shigeki; Fujie, Masakatsu G

2017-07-01

Static stretching is widely performed to decrease muscle tone as a part of rehabilitation protocols. Finding out the optimal duration of static stretching is important to minimize the time required for rehabilitation therapy and it would be helpful for maintaining the patient's motivation towards daily rehabilitation tasks. Several studies have been conducted for the evaluation of static stretching; however, the recommended duration of static stretching varies widely between 15-30 s in general, because the traditional methods for the assessment of muscle tone do not monitor the continuous change in the target muscle's state. We have developed a method to monitor the viscoelasticity of one muscle continuously during static stretching, using a wearable indentation tester. In this study, we investigated a suitable signal processing method to detect the time required to change the muscle tone, utilizing the data collected using a wearable indentation tester. By calculating a viscoelastic index with a certain time window, we confirmed that the stretching duration required to bring about a decrease in muscle tone could be obtained with an accuracy in the order of 1 s.

Wearable carbon nanotube-based fabric sensors for monitoring human physiological performance

NASA Astrophysics Data System (ADS)

Wang, Long; Loh, Kenneth J.

2017-05-01

A target application of wearable sensors is to detect human motion and to monitor physical activity for improving athletic performance and for delivering better physical therapy. In addition, measuring human vital signals (e.g., respiration rate and body temperature) provides rich information that can be used to assess a subject’s physiological or psychological condition. This study aims to design a multifunctional, wearable, fabric-based sensing system. First, carbon nanotube (CNT)-based thin films were fabricated by spraying. Second, the thin films were integrated with stretchable fabrics to form the fabric sensors. Third, the strain and temperature sensing properties of sensors fabricated using different CNT concentrations were characterized. Furthermore, the sensors were demonstrated to detect human finger bending motions, so as to validate their practical strain sensing performance. Finally, to monitor human respiration, the fabric sensors were integrated with a chest band, which was directly worn by a human subject. Quantification of respiration rates were successfully achieved. Overall, the fabric sensors were characterized by advantages such as flexibility, ease of fabrication, lightweight, low-cost, noninvasiveness, and user comfort.

Dual-Functionalization Device for Therapy through Dopamine Release and Monitoring.

PubMed

Fabregat, Georgina; Giménez, Alessia; Díaz, Angélica; Puiggalí, Jordi; Alemán, Carlos

2018-05-01

A dual-functional device is fabricated to release progressively dopamine (DA) from a biohydrogel under real-time monitoring via electrochemical detection. For this purpose, a poly-γ-glutamic acid biohydrogel is assembled with a poly(3,4-ethylenedioxythiophene) (PEDOT) layer, previously deposited onto a screen printed electrode. The biohydrogel is formulated to achieve dimensional stability and maximum DA-loading capacity. Conditions for DA-loading are influenced by the oxidation of the neurotransmitter in acid environments and the poor resistance of PEDOT to the lyophilization. The performance of the device is proved in a medium with the physiological pH of blood and the cerebrospinal fluid. The progressive release of DA is successfully monitored by the device, the limit of detection and sensitivity of the integrated sensor being 450 × 10 -9 m and 8 × 10 -5 mA µm -1 , respectively. The effect of electrochemical stimulation in the kinetics of the DA release is also investigated applying potential ramps in cyclic phase to alter the biohydrogel morphology. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Particle therapy of moving targets—the strategies for tumour motion monitoring and moving targets irradiation

PubMed Central

2016-01-01

Particle therapy of moving targets is still a great challenge. The motion of organs situated in the thorax and abdomen strongly affects the precision of proton and carbon ion radiotherapy. The motion is responsible for not only the dislocation of the tumour but also the alterations in the internal density along the beam path, which influence the range of particle beams. Furthermore, in case of pencil beam scanning, there is an interference between the target movement and dynamic beam delivery. This review presents the strategies for tumour motion monitoring and moving target irradiation in the context of hadron therapy. Methods enabling the direct determination of tumour position (fluoroscopic imaging of implanted radio-opaque fiducial markers, electromagnetic detection of inserted transponders and ultrasonic tumour localization systems) are presented. Attention is also drawn to the techniques which use external surrogate motion for an indirect estimation of target displacement during irradiation. The role of respiratory-correlated CT [four-dimensional CT (4DCT)] in the determination of motion pattern prior to the particle treatment is also considered. An essential part of the article is the review of the main approaches to moving target irradiation in hadron therapy: gating, rescanning (repainting), gated rescanning and tumour tracking. The advantages, drawbacks and development trends of these methods are discussed. The new accelerators, called “cyclinacs”, are presented, because their application to particle therapy will allow making a breakthrough in the 4D spot scanning treatment of moving organs. PMID:27376637

Optoacoustic theranostics

NASA Astrophysics Data System (ADS)

Petrov, Irene Y.; Micci, Maria-Adelaide; Prough, Donald S.; Petrov, Yuriy; Guptarak, Jutatip; Grant, Auston C.; Parsley, Margaret A.; Bolding, Ian J.; Esenaliev, Rinat O.

2018-03-01

Optoacoustic diagnostics is based on detection and analysis of optoacoustic waves induced in tissues. It may find a number of important clinical applications in large populations of patients such as diagnostics of cerebral hypoxia, circulatory shock, etc. Recently, we proposed Nano-Pulse Laser Therapy (NPLT) which utilizes short optical pulses (typically, shorter than hundreds of nanoseconds) to generate optoacoustic waves in tissues upon stress-confined irradiation. It is well known that continuous wave low-level near-infrared light can be used for therapy/photobiomodulation to stimulate, repair, regenerate, and protect injured tissue. In the past few years, new works emerged on therapeutic effects of low-intensity ultrasound waves. The NPLT consists of irradiating tissue by both lowlevel light and optoacoustic waves/ultrasound that combines merits of low-level light and ultrasound therapies. In this work we propose optoacoustic theranostics that can be used for diagnostics, optoacoustic therapy/NPLT, and monitoring of therapeutic response during and after therapy. We developed and built pulsed, tunable, near infrared (680-1064 nm), fiber-coupled systems for optoacoustic theranostics and tested them in rats with traumatic brain injury (TBI). Low energy pulses were used for optoacoustic monitoring of cerebral blood oxygenation, while higher energy pulses were used for the NPLT. Our studies show that TBI results in cerebral hypoxia, while a 5-minute transcranial application of NPLT significantly reduces negative effects of TBI as assessed by vestibulomotor, cognitive, and immunofluorescence tests. The obtained results suggest that the optoacoustic theranostics may be used for diagnostics and management of TBI and other disorders.

Combined multichannel intraluminal impedance and pH monitoring is helpful in managing children with suspected gastro-oesophageal reflux disease.

PubMed

Rossi, Paolo; Isoldi, Sara; Mallardo, Saverio; Papoff, Paola; Rossetti, Danilo; Dilillo, Anna; Oliva, Salvatore

2018-04-05

Gastro-oesophageal reflux is very common in the paediatric age group. There is no single and reliable test to distinguish between physiologic and pathological gastro-oesophageal reflux, and this lack of clear distinction between disease and normal can have a negative impact on the management of children. To evaluate the usefulness of 24-h oesophageal pH-impedance study in infants and children with suspected gastro-oesophageal reflux disease. Patients were classified by age groups (A-C) and reflux-related symptoms (typical and atypical). All underwent pH-impedance study. If the latter suggested an abnormal reflux, patients received therapy in accordance with NASPGHAN/ESPGHAN recommendations, while those with normal study had an additional diagnostic work-up. The efficacy of therapy was evaluated with a specific standardized questionnaire for different ages. The study was abnormal in 203/428 patients (47%) while normal in 225/428 (53%). Of those with abnormal study, 109 exhibited typical symptoms (54%), and 94 atypical (46%). The great majority of the patients with abnormal study were responsive to medical anti-reflux therapy. We confirm the utility of prolonged oesophageal pH-impedance study in detecting gastro-oesophageal reflux disease in children and in guiding therapy. Performing oesophageal pH-impedance monitoring in children with suspected gastro-oesophageal reflux disease is helpful to establish the diagnosis and avoid unnecessary therapy. Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

The evolution of invasive cerebral vasospasm treatment in patients with spontaneous subarachnoid hemorrhage and delayed cerebral ischemia-continuous selective intracarotid nimodipine therapy in awake patients without sedation.

PubMed

Paľa, Andrej; Schneider, Max; Brand, Christine; Pedro, Maria Teresa; Özpeynirci, Yigit; Schmitz, Bernd; Wirtz, Christian Rainer; Kapapa, Thomas; König, Ralph; Braun, Michael

2018-05-26

Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are major factors that limit good outcome in patients with spontaneous subarachnoid hemorrhage (SAH). Continuous therapy with intra-arterial calcium channel blockers has been introduced as a new step in the invasive treatment cascade of CV and DCI. Sedation is routinely necessary for this procedure. We report about the feasibility to apply this therapy in awake compliant patients without intubation and sedation. Out of 67 patients with invasive endovascular treatment of cerebral vasospasm due to spontaneous SAH, 5 patients underwent continuous superselective intracarotid nimodipine therapy without intubation and sedation. Complications, neurological improvement, and outcome at discharge were summarized. Very good outcome was achieved in all 5 patients. The Barthel scale was 100 and the modified Rankin scale 0-1 in all cases at discharge. We found no severe complications and excellent neurological monitoring was possible in all cases due to patients' alert status. Symptoms of DCI resolved within 24 h in all 5 cases. We could demonstrate the feasibility and safety of selective intracarotid arterial nimodipine treatment in awake, compliant patients with spontaneous SAH and symptomatic CV and DCI. Using this method, an excellent monitoring of neurological function as well as early detection of other complications is possible. It might be an important step in the risk reduction of invasive CV therapy to improve the outcome with CV and DCI after SAH in selected patients.

Monitoring the distribution of prompt gamma rays in boron neutron capture therapy using a multiple-scattering Compton camera: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Lee, Taewoong; Lee, Hyounggun; Lee, Wonho

2015-10-01

This study evaluated the use of Compton imaging technology to monitor prompt gamma rays emitted by 10B in boron neutron capture therapy (BNCT) applied to a computerized human phantom. The Monte Carlo method, including particle-tracking techniques, was used for simulation. The distribution of prompt gamma rays emitted by the phantom during irradiation with neutron beams is closely associated with the distribution of the boron in the phantom. Maximum likelihood expectation maximization (MLEM) method was applied to the information obtained from the detected prompt gamma rays to reconstruct the distribution of the tumor including the boron uptake regions (BURs). The reconstructed Compton images of the prompt gamma rays were combined with the cross-sectional images of the human phantom. Quantitative analysis of the intensity curves showed that all combined images matched the predetermined conditions of the simulation. The tumors including the BURs were distinguishable if they were more than 2 cm apart.

Noninvasive optical monitoring multiple physiological parameters response to cytokine storm

NASA Astrophysics Data System (ADS)

Li, Zebin; Li, Ting

2018-02-01

Cancer and other disease originated by immune or genetic problems have become a main cause of death. Gene/cell therapy is a highlighted potential method for the treatment of these diseases. However, during the treatment, it always causes cytokine storm, which probably trigger acute respiratory distress syndrome and multiple organ failure. Here we developed a point-of-care device for noninvasive monitoring cytokine storm induced multiple physiological parameters simultaneously. Oxy-hemoglobin, deoxy-hemoglobin, water concentration and deep-tissue/tumor temperature variations were simultaneously measured by extended near infrared spectroscopy. Detection algorithms of symptoms such as shock, edema, deep-tissue fever and tissue fibrosis were developed and included. Based on these measurements, modeling of patient tolerance and cytokine storm intensity were carried out. This custom device was tested on patients experiencing cytokine storm in intensive care unit. The preliminary data indicated the potential of our device in popular and milestone gene/cell therapy, especially, chimeric antigen receptor T-cell immunotherapy (CAR-T).

[Diagnostics and antimicrobial therapy of severe community-acquired pneumonia].

PubMed

Sinopalnikov, A I; Zaitsev, A A

2015-04-01

In the current paper authors presented the latest information concerning etiology of severe community-acquired pneumonia. Most cases are caused by a relatively small number ofpathogenic bacterial and viral natures. The frequency of detection of various pathogens of severe community-acquired pneumonia may vary greatly depending on the region, season and clinical profile of patients, availability of relevant risk factors. Authors presented clinical characteristics of severe community-acquired pneumonia and comparative evaluation of a number of scales to assess the risk of adverse outcome of the disease. Diagnosis of severe community-acquired pneumonia includes the following: collecting of epidemiological history, identification of pneumonia, detection of sepsis and identification of multiple organ dysfunction syndrome, detection of acute respiratory failure, assessment of comorbidity. Authors gave recommendations concerning evaluation of the clinical manifestations of the disease, the use of instrumental and laboratory methods for diagnosis of severe community-acquired pneumonia. To select the mode of antimicrobial therapy is most important local monitoring antimicrobial resistance of pathogens. The main criteria for the effectiveness of treatment are to reduce body temperature, severe intoxication, respiratory and organ failure.

Electrochemical Detection of Anti-Breast-Cancer Agents in Human Serum by Cytochrome P450-Coated Carbon Nanotubes

PubMed Central

Baj-Rossi, Camilla; De Micheli, Giovanni; Carrara, Sandro

2012-01-01

We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8–925 nA/μM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4). A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS) as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side-effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug-monitoring in personalized therapy. PMID:22778656

Thrombolytic therapeutic effect monitoring based on functional near-infrared spectroscopy

NASA Astrophysics Data System (ADS)

Pan, Boan; Wang, Pengbo; Li, Yaoxian; Gao, Yuan; Li, Ting

2017-02-01

Deep vein thrombosis (DVT) is of serious mortality and morbidity, which often happens in inpatients and especially with the postoperative population [1]. The golden standard to diagnose DVT is venography, which relies on complicated imaging modalities requiring to be injected in a vein below the clot invasively and ionizing procedures that employing xray imaging to show where and how the DVT blocks. The near-infrared spectroscopy (NIRS) is recently found to be an intriguing and potential method detecting DVT in clinics. It has been reported recently that employing NIRS to diagnose DVT. Arteriosclerosis obliterans (ASO), local extremities manifestations of systemic atherosclerosis, usually cause thrombosis and the reduction of distal blood flow. Thrombolytic therapy is to use exogenous activator to activate the dissolution system, which can dissolve intracoronary thrombus. Here we attempt to monitor the DVT and ASO patients during the whole procedure of thrombolytic treatment, then compare the data with those DVT and ASO patients did not take treatments and normal population. 8 DVT and 9 ASO patients and 12 normal subjects were recruited to take the measurements of concentration variation of oxy- and deoxy-hemoglobins (Δ[HbO2] and Δ[Hb]) by NIRS-based thrombosis monitor. Thereinto, 5 DVT and 6 ASO patients has taken the thrombolytic treatment, and the data for the periods before treatment, during treatment, and after treatment were extracted for analysis. We found that Δ[HbO2] fluctuates and even decreases in DVT and ASO patients. After the thrombolytic therapy, Δ[HbO2] increases about 45% and converge to the curves of normal subjects. And the Δ[Hb] emerges the similar trends, except for the rising trend in the beginning and the downtrend after thrombolytic therapy. The findings indicated NIRS has big potential in clinical monitoring of DVT and ASO patients and offering reliable and quantitative evaluation of thrombolytic therapy outcomes.

Use of viscoelastic haemostatic assay in emergency and elective surgery.

PubMed

Yeung, Maximus C F; Tong, Steven Y T; Tong, Paul Y W; Cheung, Billy H H; Ng, Joanne Y W; Leung, Gilberto K K

2015-02-01

To review the current evidence for the use of viscoelastic haemostatic assays in different surgical settings including trauma, cardiac surgery, liver transplantation, as well as the monitoring of antiplatelet agents and anticoagulants prior to surgery. PubMed database. Key words for the literature search were "thromboelastography" or "ROTEM" in combination with "trauma", "antiplatelet", "cardiac surgery", "liver transplantation" or "anticoagulants". Original and major review articles related to the use of viscoelastic haemostatic assays. Haemostatic function is a critical factor determining patient outcomes in emergency or elective surgery. The increasing use of antiplatelet agents and anticoagulants has potentially increased the risks of haemorrhages and the need for transfusion. Conventional coagulation tests have limitations in detecting haemostatic dysfunctions in subgroups of patients and are largely ineffective in diagnosing hyperfibrinolysis. The viscoelastic haemostatic assays are potentially useful point-of-care tools that provide information on clot formation, clot strength, and fibrinolysis, as well as to guide goal-directed transfusion and antifibrinolytic therapy. They may also be used to monitor antiplatelet and anticoagulant therapy. However, standardisation of techniques and reference ranges is required before these tests can be widely used in different clinical settings. Viscoelastic haemostatic assays, as compared with conventional coagulation tests, are better for detecting coagulopathy and are the only tests that can provide rapid diagnosis of hyperfibrinolysis. Goal-directed administration of blood products based on the results of viscoelastic haemostatic assays was associated with reduction in allogeneic blood product transfusions in trauma, cardiac surgery, and liver transplantation cases. However, there is currently no evidence to support the routine use of viscoelastic haemostatic assays for monitoring platelet function prior to surgery.

Systems identification and application systems development for monitoring the physiological and health status of crewmen in space

NASA Technical Reports Server (NTRS)

Leonard, J. I.; Furukawa, S.; Vannordstrand, P. C.

1975-01-01

The use of automated, analytical techniques to aid medical support teams is suggested. Recommendations are presented for characterizing crew health in terms of: (1) wholebody function including physiological, psychological and performance factors; (2) a combination of critical performance indexes which consist of multiple factors of measurable parameters; (3) specific responses to low noise level stress tests; and (4) probabilities of future performance based on present and periodic examination of past performance. A concept is proposed for a computerized real time biomedical monitoring and health care system that would have the capability to integrate monitored data, detect off-nominal conditions based on current knowledge of spaceflight responses, predict future health status, and assist in diagnosis and alternative therapies. Mathematical models could play an important role in this approach, especially when operating in a real time mode. Recommendations are presented to update the present health monitoring systems in terms of recent advances in computer technology and biomedical monitoring systems.

Molecular Thermometry

PubMed Central

McCabe, Kevin M.; Hernandez, Mark

2010-01-01

Conventional temperature measurements rely on material responses to heat, which can be detected visually. When Galileo developed an air expansion based device to detect temperature changes, Santorio, a contemporary physician, added a scale to create the first thermometer. With this instrument, patients’ temperatures could be measured, recorded and related to changing health conditions. Today, advances in materials science and bioengineering provide new ways to report temperature at the molecular level in real time. In this review the scientific foundations and history of thermometry underpin a discussion of the discoveries emerging from the field of molecular thermometry. Intracellular nanogels and heat sensing biomolecules have been shown to accurately report temperature changes at the nano-scale. Various systems will soon provide the ability to accurately measure temperature changes at the tissue, cellular, and even sub-cellular level, allowing for detection and monitoring of very small changes in local temperature. In the clinic this will lead to enhanced detection of tumors and localized infection, and accurate and precise monitoring of hyperthermia based therapies. Some nanomaterial systems have even demonstrated a theranostic capacity for heat-sensitive, local delivery of chemotherapeutics. Just as early thermometry moved into the clinic, so too will these molecular thermometers. PMID:20139796

Overview of the improvement of the ring-stage survival assay-a novel phenotypic assay for the detection of artemisinin-resistant Plasmodium falciparum.

PubMed

Zhang, Jie; Feng, Guo-Hua; Zou, Chun-Yan; Su, Pin-Can; Liu, Huai-E; Yang, Zhao-Qing

2017-11-18

Artemisinin resistance in Plasmodium falciparum threatens the remarkable efficacy of artemisinin-based combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications.

Waterproof stretchable optoelectronics

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

Rogers, John A.; Kim, Rak-Hwan; Kim, Dae-Hyeong

Described herein are flexible and stretchable LED arrays and methods utilizing flexible and stretchable LED arrays. Assembly of flexible LED arrays alongside flexible plasmonic crystals is useful for construction of fluid monitors, permitting sensitive detection of fluid refractive index and composition. Co-integration of flexible LED arrays with flexible photodetector arrays is useful for construction of flexible proximity sensors. Application of stretchable LED arrays onto flexible threads as light emitting sutures provides novel means for performing radiation therapy on wounds.

Scintigraphic detection of occult hemorrhage using RBCs labeled in vitro with technetium Tc 99m sodium pertechnetate

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

Bunker, S.R.; Kolina, J.S.; Kaplan, K.A.

1983-05-01

Scintigraphy with RBCs labeled with technetium Tc 99m sodium pertechnetate effectively located the source of hemorrhage in a patient receiving long-term anticoagulant therapy. (The patient was initially seen with a large hematoma on the flank.) More important, the procedure was used to monitor activity in this otherwise-occult bleeding site. Scintigraphic studies may be useful in the management of these difficult clinical problems.

DOE Center of Excellence in Medical Laser Applications. Final report

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

Jacques, S.L.

1998-01-01

An engineering network of collaborating medical laser laboratories are developing laser and optical technologies for medical diagnosis and therapy and are translating the engineering into medical centers in Portland, OR, Houston, TX, and Galveston, TX. The Center includes the University of Texas M.D. Anderson Cancer Center, the University of Texas-Austin, Texas A and M University, Rice University, the University Texas Medical Branch-Galveston, Oregon Medical Laser Center (Providence St. Vincent Medical Center, Oregon Health Sciences University, and Oregon Graduate Institute, Portland, OR), and the University of Oregon. Diagnostics include reflectance, fluorescence, Raman IR, laser photoacoustics, optical coherence tomography, and several newmore » video techniques for spectroscopy and imaging. Therapies include photocoagulation therapy, laser welding, pulsed laser ablation, and light-activated chemotherapy of cancer (photodynamic therapy, or PDT). Medical applications reaching the clinic include optical monitoring of hyperbilirubinemia in newborns, fluorescence detection of cervical dysplasia, laser thrombolysis of blood clots in heart attack and brain stroke, photothermal coagulation of benign prostate hyperplasia, and PDT for both veterinary and human cancer. New technologies include laser optoacoustic imaging of breast tumors and hemorrhage in head trauma and brain stroke, quality control monitoring of dosimetry during PDT for esophageal and lung cancer, polarization video reflectometry of skin cancer, laser welding of artificial tissue replacements, and feedback control of laser welding.« less

DOE Center of Excellence in Medical Laser Applications. Final report, December 1, 1994--November 30, 1997

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

Jacques, S.L.

1998-01-01

An engineering network of collaborating medical laser laboratories are developing laser and optical technologies for medical diagnosis and therapy and are translating the engineering into medical centers in Portland OR, Houston TX, and Galveston TX. The Center includes the University of Texas M.D. Anderson Cancer Center, the University of Texas-Austin, Texas A and M University, Rice University, the University Texas Medical Branch-Galveston, Oregon Medical Laser Center (Providence St. Vincent Medical Center, Oregon Health Sciences University, and Oregon Graduate Institute, Portland, OR), and the University of Oregon. Diagnostics include reflectance, fluorescence, Raman IR, laser photoacoustics, optical coherence tomography, and several newmore » video techniques for spectroscopy and imaging. Therapies include photocoagulation therapy, laser welding, pulsed laser ablation, and light-activated chemotherapy of cancer (photodynamic therapy, or PDT). Medical applications reaching the clinic include optical monitoring of hyperbilirubinemia in newborns, fluorescence detection of cervical dysplasia, laser thrombolysis of blood clots in heart attack and brain stroke, photothermal coagulant of benign prostate hyperplasia, and PDT for both veterinary and human cancer. New technologies include laser optoacoustic imaging of breast tumors and hemorrhage in head trauma and brain stroke, quality control monitoring of dosimetry during PDT for esophageal and lung cancer, polarization video reflectometry of skin cancer, laser welding of artificial tissue replacements, and feedback control of laser welding.« less

Noninvasive optoacoustic monitoring of cerebral venous blood oxygenation in newborns

NASA Astrophysics Data System (ADS)

Petrov, Irene Y.; Wynne, Karon E.; Petrov, Yuriy; Esenaliev, Rinat O.; Richardson, C. Joan; Prough, Donald S.

2012-02-01

Cerebral ischemia after birth and during labor is a major cause of death and severe complications such as cerebral palsy. In the USA alone, cerebral palsy results in permanent disability of 10,000 newborns per year and approximately 500,000 of the total population. Currently, no technology is capable of direct monitoring of cerebral oxygenation in newborns. This study proposes the use of an optoacoustic technique for noninvasive cerebral ischemia monitoring by probing the superior sagittal sinus (SSS), a large central cerebral vein. We developed and built a multi-wavelength, near-infrared optoacoustic system suitable for noninvasive monitoring of cerebral ischemia in newborns with normal weight (NBW), low birth-weight (LBW, 1500 - 2499 g) and very low birth-weight (VLBW, < 1500 g). The system was capable of detecting SSS signals through the open anterior and posterior fontanelles as well as through the skull. We tested the system in NBW, LBW, and VLBW newborns (weight range: from 675 g to 3,000 g) admitted to the neonatal intensive care unit. We performed single and continuous measurements of the SSS blood oxygenation. The data acquisition, processing and analysis software developed by our group provided real-time, absolute SSS blood oxygenation measurements. The SSS blood oxygenation ranged from 60% to 80%. Optoacoustic monitoring of the SSS blood oxygenation provides valuable information because adequate cerebral oxygenation would suggest that no therapy was necessary; conversely, evidence of cerebral ischemia would prompt therapy to increase cerebral blood flow.

Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis

PubMed Central

Gerona, Roy; Wen, Anita; Chin, Aaron T.; Koss, Catherine A.; Bacchetti, Peter; Metcalfe, John; Gandhi, Monica

2016-01-01

Background Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. Methods A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay’s suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. Results Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10–25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05–50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. Conclusions An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV. PMID:27191185

Optoacoustic imaging of an animal model of prostate cancer

NASA Astrophysics Data System (ADS)

Patterson, Michelle P.; Arsenault, Michel; Riley, Chris; Kolios, Michael; Whelan, William M.

2010-02-01

Prostate cancer is currently the most common cancer among Canadian men. Due to an increase in public awareness and screening, prostate cancer is being detected at earlier stages and in much younger men. This is raising the need for better treatment monitoring approaches. Optoacoustic imaging is a new technique that involves exposing tissues to pulsed light and detecting the acoustic waves generated by the tissue. Optoacoustic images of a tumour bearing mouse and an agematched control were acquired for a 775 nm illumination using a reverse-mode imaging system. A murine model of prostate cancer, TRAMP (transgenetic adenocarcinoma of mouse prostate), was investigated. The results show an increase in optoacoustic signal generated by the tumour compared to that generated by the surrounding tissues with a contrast ratio of 3.5. The dimensions of the tumour in the optoacoustic image agreed with the true tumour dimensions to within 0.5 mm. In this study we show that there are detectable changes in optoacoustic signal strength that arise from the presence of a tumour in the prostate, which demonstrates the potential of optoacoustic imaging for the monitoring of prostate cancer therapy.

An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin.

PubMed

Favaloro, Emmanuel J; Bonar, Roslyn; Sioufi, John; Wheeler, Michael; Low, Joyce; Aboud, Margaret; Lloyd, John; Street, Alison; Marsden, Katherine

2005-06-01

We conducted a survey of laboratory practice for assessment of heparin anticoagulant therapy by participants of the Royal College of Pathologists of Australasia Quality Assurance Program (RCPA QAP). A questionnaire was sent to 646 laboratories enrolled in the Haematology component of the QAP, requesting details of tests used for monitoring heparin therapy. Seventy laboratories (10.8%) returned results that indicated that they performed laboratory monitoring of heparin therapy. Most laboratories (69/70 = 98.6%) use the activated partial thromboplastin time (APTT) to monitor unfractionated heparin, with eight (11.4%) also using the APTT for monitoring low molecular weight (LMW) heparin. Five (7.1%) laboratories use the thrombin time (TT) test to help monitor heparin therapy and 37 (52.9%) laboratories use an anti-Xa assay to monitor heparin (either LMW or unfractionated). Normal reference ranges (NRR) for APTT differed considerably between laboratories, even those using the same reagent. Therapeutic ranges (TR) also differed considerably between laboratories, for both APTT and the anti-Xa assay. Laboratory differences in NRR and TR using the same reagents could only be partly explained by the use of different instrumentation. There is a large variation in current laboratory practice relating to monitoring of heparin anticoagulant therapy. This finding is similar to that of a similar survey conducted by the RCPA QAP almost a decade ago. This study suggests that better standardisation is still required for laboratory monitoring of heparin therapy.

[Continuous glucose monitoring with type 1 diabetes mellitus].

PubMed

López-Siguero, J P; García Arias, M J; del Pino de la Fuente, A; Moreno Molina, J A

2003-03-01

Appropriate metabolic control of children with type 1 diabetes mellitus (DM) is based on frequent measurements of capillary glycemia. However, this method offers only partial information on fluctuations in glycemia during the day, while episodes of postprandial hyperglycemia and hypoglycemia, mainly nocturnal, go unnoticed. To analyze pre- and postprandial blood glucose levels, as well as the presence and duration of hypoglycemic episodes in diabetic children aged more than 8 years old with more than one year of disease duration. Seventeen patients of both sexes (mean age: 12 years old) with type 1 DM were monitored with the continuous glucose monitoring system (CGMS) during working days. Maximum values of pre- and postprandial glucose (1-3 hours after breakfast, lunch and dinner) were registered. Data were downloaded with a Com-station. The mean duration of sensor-wearing was 2.97 days. Pre- and postprandial values were high: mean preprandial values were between 144.9 and 160.5 mg % and mean postprandial values were between 230.4 and 248.8 mg %. The mean number of hypoglycemic episodes detected with the sensor was 4.9 compared with 1.8 detected with the glucometer (p < 0.05). Episodes of mainly nocturnal asymptomatic hypoglycemia were detected with a mean duration of 145 minutes during the night and 75 minutes during the day. The use of continuous subcutaneous glucose monitoring demonstrates that glycemic objectives are not achieved by conventional insulin therapy. It also shows that there are a high number of hypoglycemic episodes, most of which are asymptomatic.

Improved murine glioma detection following modified diet and photobleaching of skin PpIX fluorescence

NASA Astrophysics Data System (ADS)

Gibbs, Summer L.; O'Hara, Julia A.; Hoopes, P. Jack; Pogue, Brian W.

2007-02-01

The Aminolevulinic Acid (ALA) - Protoporphyrin IX (PpIX) system is unique in the world of photosensitizers in that the prodrug ALA is enzymatically transformed via the tissue of interest into fluorescently detectable levels of PpIX. This system can be used to monitor cellular metabolism of tumor tissue for applications such as therapy monitoring. Detecting PpIX fluorescence noninvasively has proven difficult due to the high levels of PpIX produced in the skin compared to other tissue both with and without ALA administration. In the current study, methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration have been examined. Use of a purified diet is found to decrease both skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration, while addition of a broad spectrum antibiotic to the water shows little effect. Following ALA administration, improved brain tumor detection is seen when skin PpIX fluorescence is photobleached via blue light prior to transmission spectroscopic measurements of tumor bearing and control animals. Both of these methods to decrease skin PpIX autofluorescence and skin PpIX fluorescence following ALA administration are shown to have a large effect on the ability to detect tumor tissue PpIX fluorescence noninvasively in vivo.

Non-invasive, multi-modal sensing of skin stretch and bioimpedance for detecting infiltration during intravenous therapy.

PubMed

Jambulingam, Jambu A; McCrory, Russell; West, Leanne; Inan, Omer T

2016-08-01

Intravenous infiltration is a condition wherein an infused solution leaks inadvertently into soft tissue surrounding a hypodermic needle site. This occurrence affects approximately 6.5% of patients in hospitals worldwide, and can lead to severe tissue damage if not treated immediately. The methods currently used by medical staff to detect an infiltration are subjective and can potentially be prone to error. Infiltration is an even larger concern in pediatric patients, who have smaller veins than adults and have more difficulty in communicating pain or other discomfort associated with the infiltration with medical staff. For these reasons, automatic IV infiltration detection could potentially reduce the risk associated with this damaging condition. This paper proposes a novel proof-of-concept system that uses non-invasive sensing in conjunction with a low-power embedded computing platform to deliver continuous infiltration monitoring around the IV catheter site. This kind of system could be able to detect an infiltration by non-invasively monitoring for known symptoms: swelling of soft tissue and increased skin firmness; these symptoms can be sensed by measuring skin stretch and local bioimpedance. Moreover, the low-power design and wireless capabilities can potentially enable continuous wear. The proposed automatic IV infiltration detection system could significantly improve the number of infiltrations identified and treated on time.

Near-infrared autofluorescence induced by intraplaque hemorrhage and heme degradation as marker for high-risk atherosclerotic plaques.

PubMed

Htun, Nay Min; Chen, Yung Chih; Lim, Bock; Schiller, Tara; Maghzal, Ghassan J; Huang, Alex L; Elgass, Kirstin D; Rivera, Jennifer; Schneider, Hans G; Wood, Bayden R; Stocker, Roland; Peter, Karlheinz

2017-07-13

Atherosclerosis is a major cause of mortality and morbidity, which is mainly driven by complications such as myocardial infarction and stroke. These complications are caused by thrombotic arterial occlusion localized at the site of high-risk atherosclerotic plaques, of which early detection and therapeutic stabilization are urgently needed. Here we show that near-infrared autofluorescence is associated with the presence of intraplaque hemorrhage and heme degradation products, particularly bilirubin by using our recently created mouse model, which uniquely reflects plaque instability as seen in humans, and human carotid endarterectomy samples. Fluorescence emission computed tomography detecting near-infrared autofluorescence allows in vivo monitoring of intraplaque hemorrhage, establishing a preclinical technology to assess and monitor plaque instability and thereby test potential plaque-stabilizing drugs. We suggest that near-infrared autofluorescence imaging is a novel technology that allows identification of atherosclerotic plaques with intraplaque hemorrhage and ultimately holds promise for detection of high-risk plaques in patients.Atherosclerosis diagnosis relies primarily on imaging and early detection of high-risk atherosclerotic plaques is important for risk stratification of patients and stabilization therapies. Here Htun et al. demonstrate that vulnerable atherosclerotic plaques generate near-infrared autofluorescence that can be detected via emission computed tomography.

Cherenkov imaging and biochemical sensing in vivo during radiation therapy

NASA Astrophysics Data System (ADS)

Zhang, Rongxiao

While Cherenkov emission was discovered more than eighty years ago, the potential applications of imaging this during radiation therapy have just recently been explored. With approximately half of all cancer patients being treated by radiation at some point during their cancer management, there is a constant challenge to ensure optimal treatment efficiency is achieved with maximal tumor to normal tissue therapeutic ratio. To achieve this, the treatment process as well as biological information affecting the treatment should ideally be effective and directly derived from the delivery of radiation to the patient. The value of Cherenkov emission imaging was examined here, primarily for visualization of treatment monitoring and then secondarily for Cherenkov-excited luminescence for tissue biochemical sensing within tissue. Through synchronized gating to the short radiation pulses of a linear accelerator (200Hz & 3 micros pulses), and applying a gated intensified camera for imaging, the Cherenkov radiation can be captured near video frame rates (30 frame per sec) with dim ambient room lighting. This procedure, sometimes termed Cherenkoscopy, is readily visualized without affecting the normal process of external beam radiation therapy. With simulation, phantoms and clinical trial data, each application of Cherenkoscopy was examined: i) for treatment monitoring, ii) for patient position monitoring and motion tracking, and iii) for superficial dose imaging. The temporal dynamics of delivered radiation fields can easily be directly imaged on the patient's surface. Image registration and edge detection of Cherenkov images were used to verify patient positioning during treatment. Inter-fraction setup accuracy and intra-fraction patient motion was detectable to better than 1 mm accuracy. Cherenkov emission in tissue opens up a new field of biochemical sensing within the tissue environment, using luminescent agents which can be activated by this light. In the first study of its kind with external beam irradiation, a dendritic platinum-based phosphor (PtG4) was used at micro-molar concentrations (~5 microM) to generate Cherenkov-induced luminescent signals, which are sensitive to the partial pressure of oxygen. Both tomographic reconstruction methods and linear scanned imaging were investigated here to examine the limits of detection. Recovery of optical molecular distributions was shown in tissue phantoms and small animals, with high accuracy (~1 microM), high spatial resolution (~0.2 mm) and deep-tissue detectability (~2 cm for Cherenkov luminescence scanned imaging (CELSI)), indicating potentials for in vivo and clinical use. In summary, many of the physical and technological details of Cherenkov imaging and Cherenkov-excited emission imaging were specified in this study.

The role of general nuclear medicine in breast cancer

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

Greene, Lacey R, E-mail: lgreene@csu.edu.au; Wilkinson, Deborah; Faculty of Science, Charles Sturt University, Wagga Wagga, New South Wales

The rising incidence of breast cancer worldwide has prompted many improvements to current care. Routine nuclear medicine is a major contributor to a full gamut of clinical studies such as early lesion detection and stratification; guiding, monitoring, and predicting response to therapy; and monitoring progression, recurrence or metastases. Developments in instrumentation such as the high-resolution dedicated breast device coupled with the diagnostic versatility of conventional cameras have reinserted nuclear medicine as a valuable tool in the broader clinical setting. This review outlines the role of general nuclear medicine, concluding that targeted radiopharmaceuticals and versatile instrumentation position nuclear medicine as amore » powerful modality for patients with breast cancer.« less

Whole organic electronic synapses for dopamine detection

NASA Astrophysics Data System (ADS)

Giordani, Martina; Di Lauro, Michele; Berto, Marcello; Bortolotti, Carlo A.; Vuillaume, Dominique; Gomes, Henrique L.; Zoli, Michele; Biscarini, Fabio

2016-09-01

A whole organic artificial synapse has been fabricated by patterning PEDOT:PSS electrodes on PDMS that are biased in frequency to yield a STP response. The timescale of the STP response is shown to be sensitive to the concentration of dopamine, DA, a neurotransmitter relevant for monitoring the development of Parkinson's disease and potential locoregional therapies. The sensitivity of the sensor towards DA has been validated comparing signal variation in the presence of DA and its principal interfering agent, ascorbic acid, AA. The whole organic synapse is biocompatible, soft and flexible, and is attractive for implantable devices aimed to real-time monitoring of DA concentration in bodily fluids. This may open applications in chronic neurodegenerative diseases such as Parkinson's disease.

[THE COMPARISON OF RESULTS OF DETECTION OF MINIMAL RESIDUAL DISEASE IN PERIPHERAL BLOOD AND MARROW IN CHILDREN OF THE FIRST YEAR OF LIFE WITH ACUTE LYMPHOBLASTIC LEUCOSIS].

PubMed

Tsaur, G A; Riger, T O; Popov, A M; Nasedkina, T V; Kustanovich, A M; Solodovnikov, A G; Streneva, O V; Shorikov, E V; Tsvirenko, S V; Saveliev, L I; Fechina, L G

2015-04-01

The occurrence of minimal residual disease is an important prognostic factor under acute lymphoblastic leucosis in children and adults. In overwhelming majority of research studies bone marrow is used to detect minimal residual disease. The comparative characteristic of detection of minimal residual disease in peripheral blood and bone marrow was carried out. The prognostic role of occurrence of minimal residual disease in peripheral blood and bone marrow under therapy according protocol MLL-Baby was evaluated. The analysis embraced 142 pair samples from 53 patients with acute lymphoblastic leucosis and various displacements of gene MLL younger than 365 days. The minimal residual disease was detected by force of identification of chimeric transcripts using polymerase chain reaction in real-time mode in 7 sequential points of observation established by protocol of therapy. The comparability of results of qualitative detection of minimal residual disease in bone marrow and peripheral blood amounted to 84.5%. At that, in all 22 (15.5%) discordant samples minimal residual disease was detected only in bone marrow. Despite of high level of comparability of results of detection of minimal residual disease in peripheral blood and bone marrow the occurrence of minimal residual disease in peripheral blood at various stages of therapy demonstrated no independent prognostic significance. The established differences had no relationship with sensitivity of method determined by value of absolute expression of gene ABL. Most likely, these differences reflected real distribution of tumor cells. The results of study demonstrated that application of peripheral blood instead of bone marrow for monitoring of minimal residual disease under acute lymphoblastic leucosis in children of first year of life is inappropriate. At the same time, retention of minimal residual disease in TH4 in bone marrow was an independent and prognostic unfavorable factor under therapy of acute lymphoblastic leucosis of children of first year of life according protocol MLL-Baby (OO=7.326, confidence interval 2.378-22.565).

Toward the design of a wearable system for contact thermography in telemedicine.

PubMed

Giansanti, Daniele; Maccioni, Giovanni; Bernhardt, Paola

2009-04-01

Thermal imaging of the skin has been used for several decades for monitoring of temperature distribution of human skin for the detection of thermal abnormalities indicating pathologies (malignancies, inflammation, infection, and vascular, dermatological, and rheumatic disorders). Literature has shown that to detect and monitor the thermal abnormalities related to pathologic conditions, there is a need to extend acquisition over 8, 12, 16, or 24 hours. A wearable device is strongly needed in contact thermography to reach the objective of long-term monitoring of contact thermography, especially in telemedicine applications. A wearable system has been designed and constructed that allows the continuous thermographic monitoring of a skin region at the point of affixation. Measurement allowed by this system is direct and not hampered by the influence of the environment--as with IR thermography--nor by the geometry of skin surface (curvatures, roughness) thanks to the flexible adaptation of the sensing head to the surface. The validation of the system embedded in a pilot preliminary telemedicine application was successful. The next step will be the wide focusing and adaptation to telemedicine clinical applications to assess the response to the chemotherapy and tune the therapy at home of the breast cancer or the response to the inflammation care.

In Situ Sensor Advancements for Osteoporosis Prevention, Diagnosis, and Treatment.

PubMed

Liu, Luting; Webster, Thomas J

2016-12-01

Osteoporosis is still a serious issue in healthcare, and will continue to increase due to the aging and growth of the population. Early diagnosis is the key to successfully treating many diseases. The earlier the osteoporosis is diagnosed, the more quickly people can take action to stop bone deterioration. Motivated by this, researchers and companies have begun developing smart in situ bone sensors in order to dramatically help people to monitor their bone mass density (BMD), bone strain or bone turnover markers (BTMs); promptly track early signs of osteoporosis; and even monitor the healing process following surgery or antiresorptive therapy. This paper focuses on the latest advancements in the field of bone biosensing materials and sensor technologies and how they can help now and in the future to detect disease and monitor bone health.

Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model

NASA Astrophysics Data System (ADS)

Seifert, Eric; Roh, Young-Jung; Fritz, Andreas; Park, Young Gun; Kang, Seungbum; Theisen-Kunde, Dirk; Brinkmann, Ralf

2013-06-01

Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.

Crystal digital droplet PCR for detection and quantification of circulating EGFR sensitizing and resistance mutations in advanced non-small cell lung cancer

PubMed Central

Madic, Jordan; Remon, Jordi; Honoré, Aurélie; Girard, Romain; Rouleau, Etienne; André, Barbara; Besse, Benjamin; Droniou, Magali; Lacroix, Ludovic

2017-01-01

Over the past years, targeted therapies using tyrosine kinase inhibitors (TKI) have led to an increase in progression-free survival and response rate for a subgroup of non-small cell lung cancer (NSCLC) patients harbouring specific gene abnormalities compared with chemotherapy. However long-lasting tumor regression is rarely achieved, due to the development of resistant tumoral subclones, which requires alternative therapeutic approaches. Molecular profile at progressive disease is a challenge for making adaptive treatment decisions. The aim of this study was to monitor EGFR-mutant tumors over time based on the quantity of mutant DNA circulating in plasma (ctDNA), comparing two different methods, Crystal™ Digital™ PCR and Massive Parallel Sequencing (MPS). In plasma circulating cell free DNA (cfDNA) of 61 advanced NSCLC patients we found an overall correlation of 78% between mutated allelic fraction measured by Crystal Digital PCR and MPS. 7 additional samples with sensitizing mutations and 4 additional samples with the resistance mutation were detected with Crystal Digital PCR, but not with MPS. Monitoring levels of both mutation types over time showed a correlation between levels and trends of mutated ctDNA detected and clinical assessment of disease for the 6 patients tested. In conclusion, Crystal Digital PCR exhibited good performance for monitoring mutational status in plasma cfDNA, and also appeared as better suited to the detection of known mutations than MPS in terms of features such as time to results. PMID:28829811

Monitoring early tumor response to drug therapy with diffuse optical tomography

NASA Astrophysics Data System (ADS)

Flexman, Molly L.; Vlachos, Fotios; Kim, Hyun Keol; Sirsi, Shashank R.; Huang, Jianzhong; Hernandez, Sonia L.; Johung, Tessa B.; Gander, Jeffrey W.; Reichstein, Ari R.; Lampl, Brooke S.; Wang, Antai; Borden, Mark A.; Yamashiro, Darrell J.; Kandel, Jessica J.; Hielscher, Andreas H.

2012-01-01

Although anti-angiogenic agents have shown promise as cancer therapeutics, their efficacy varies between tumor types and individual patients. Providing patient-specific metrics through rapid noninvasive imaging can help tailor drug treatment by optimizing dosages, timing of drug cycles, and duration of therapy--thereby reducing toxicity and cost and improving patient outcome. Diffuse optical tomography (DOT) is a noninvasive three-dimensional imaging modality that has been shown to capture physiologic changes in tumors through visualization of oxygenated, deoxygenated, and total hemoglobin concentrations, using non-ionizing radiation with near-infrared light. We employed a small animal model to ascertain if tumor response to bevacizumab (BV), an anti-angiogenic agent that targets vascular endothelial growth factor (VEGF), could be detected at early time points using DOT. We detected a significant decrease in total hemoglobin levels as soon as one day after BV treatment in responder xenograft tumors (SK-NEP-1), but not in SK-NEP-1 control tumors or in non-responder control or BV-treated NGP tumors. These results are confirmed by magnetic resonance imaging T2 relaxometry and lectin perfusion studies. Noninvasive DOT imaging may allow for earlier and more effective control of anti-angiogenic therapy.

Screening for residual disease in pediatric burkitt lymphoma using consensus primer pools.

PubMed

Agsalda, Melissa; Kusao, Ian; Troelstrup, David; Shiramizu, Bruce

2009-01-01

Assessing molecular persistent or minimal residual disease (PD/MRD) in childhood Burkitt lymphoma (BL) is challenging because access to original tumor is usually needed to design patient-specific primers (PSPs). Because BL is characterized by rearranged immunoglobulin heavy chain (IgV(H)) genes, IgV(H) primer pools from IgV(H1)-IgV(H7) regions were tested to detect PD/MRD, thus eliminating the need for original tumor. The focus of the current study was to assess the feasibility of using IgV(H) primer pools to detect disease in clinical specimens. Fourteen children diagnosed with B-NHL had follow-up repository specimens available to assess PD/MRD. Of the 14 patients, 12 were PD/MRD negative after 2 months of therapy and remained in remission at the end of therapy; 2/14 patients were PD/MRD positive at 2-3 months and later relapsed. PSP-based assays from these 14 patients showed 100% concordance with the current assay. This feasibility study warrants further investigation to assess PD/MRD using IgV(H) primer pools, which could have clinical significance as a real-time assessment tool to monitor pediatric BL and possibly other B-cell non-Hodgkin lymphoma therapy.

The use of personalized biomarkers and liquid biopsies to monitor treatment response and disease recurrence in locally advanced rectal cancer after neoadjuvant chemoradiation.

PubMed

Carpinetti, Paola; Donnard, Elisa; Bettoni, Fabiana; Asprino, Paula; Koyama, Fernanda; Rozanski, Andrei; Sabbaga, Jorge; Habr-Gama, Angelita; Parmigiani, Raphael B; Galante, Pedro A F; Perez, Rodrigo O; Camargo, Anamaria A

2015-11-10

Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the mainstay treatment for locally advanced rectal cancer. Variable degrees of tumor regression are observed after nCRT and alternative treatment strategies, including close surveillance without immediate surgery, have been investigated to spare patients with complete tumor regression from potentially adverse outcomes of radical surgery. However, clinical and radiological assessment of response does not allow accurate identification of patients with complete response. In addition, surveillance for recurrence is similarly important for these patients, as early detection of recurrence allows salvage resections and adjuvant interventions. We report the use of liquid biopsies and personalized biomarkers for monitoring treatment response to nCRT and detecting residual disease and recurrence in patients with rectal cancer. We sequenced the whole-genome of four rectal tumors to identify patient-specific chromosomal rearrangements that were used to monitor circulating tumor DNA (ctDNA) in liquid biopsies collected at diagnosis and during nCRT and follow-up. We compared ctDNA levels to clinical, radiological and pathological response to nCRT. Our results indicate that personalized biomarkers and liquid biopsies may not be sensitive for the detection of microscopic residual disease. However, it can be efficiently used to monitor treatment response to nCRT and detect disease recurrence, preceding increases in CEA levels and radiological diagnosis. Similar good results were observed when assessing tumor response to systemic therapy and disease progression. Our study supports the use of personalized biomarkers and liquid biopsies to tailor the management of rectal cancer patients, however, replication in a larger cohort is necessary to introduce this strategy into clinical practice.

Antiretroviral therapy for human immunodeficiency virus infection in 1997.

PubMed Central

Katzenstein, D A

1997-01-01

It has become clear that the acquired immunodeficiency syndrome follows continuous replication of the human immunodeficiency virus (HIV) and a decrease in immune capability, most obviously a decline in the number of CD4 lymphocytes. An understanding of key elements in the infectious life cycle of HIV has led to the development of potent antiretroviral drugs selectively targeting unique reverse transcriptase and protease enzymes of the virus. Completed clinical trials have shown that antiretroviral therapy for HIV infection, begun early, reduces viral replication and reverses the decline in CD4 lymphocyte numbers. Recent studies of combination therapies have shown that decreases in plasma HIV viremia to low levels and sustained increases in CD4 cell numbers are associated with longer survival. Potent combination regimens including protease inhibitors and non-nucleoside reverse transcriptase inhibitors suppress detectable viral replication and have demonstrated clinical benefits in patients with advanced disease. Progress in antiretroviral therapy and methods to monitor responses to treatment are providing new hope in the treatment of HIV infection. PMID:9217434

Vascular leakage in dengue--clinical spectrum and influence of parenteral fluid therapy.

PubMed

Rosenberger, Kerstin D; Lum, Lucy; Alexander, Neal; Junghanss, Thomas; Wills, Bridget; Jaenisch, Thomas

2016-03-01

Clinical management of dengue relies on careful monitoring of fluid balance combined with judicious intravenous (IV) fluid therapy. However, in patients with significant vascular leakage, IV fluids may aggravate serosal fluid accumulation and result in respiratory distress. Trained physicians followed suspected dengue cases prospectively at seven hospitals across Asia and Latin America, using a comprehensive case report form that included daily clinical assessment and detailed documentation of parenteral fluid therapy. Applying Cox regression, we evaluated risk factors for the development of shock or respiratory distress with fluid accumulation. Most confirmed dengue patients (1524/1734, 88%) never experienced dengue shock syndrome (DSS). Among those with DSS, 176/210 (84%) had fluid accumulation, and in the majority (83%), this was detectable clinically. Among all cases with clinically detectable fluid accumulation, 179/447 (40%) were diagnosed with shock or respiratory distress. The risk for respiratory distress with fluid accumulation increased significantly as the infused volume over the preceding 24 h increased (hazard ratio 1.18 per 10 ml/kg increase; P < 0.001). Longer duration of IV therapy, use of a fluid bolus in the preceding 24 h, female gender and poor nutrition also constituted independent risk factors. Shock and respiratory distress are relatively rare manifestations of dengue, but some evidence of fluid accumulation is seen in around 50% of cases. IV fluids play a crucial role in management, but they must be administered with caution. Clinically and/or radiologically detectable fluid accumulations have potential as intermediate severity endpoints for therapeutic intervention trials and/or pathogenesis studies. © 2016 John Wiley & Sons Ltd.

Short Diffusion Time Diffusion-Weighted Imaging With Oscillating Gradient Preparation as an Early Magnetic Resonance Imaging Biomarker for Radiation Therapy Response Monitoring in Glioblastoma: A Preclinical Feasibility Study.

PubMed

Bongers, Andre; Hau, Eric; Shen, Han

2018-01-04

To investigate a novel alternative diffusion-weighted imaging (DWI) approach using oscillating gradients preparation (OGSE) to obtain much shorter effective diffusion times (Δ eff ) for tumor response monitoring by apparent diffusion coefficient (ADC) mapping in a glioblastoma mouse model. Twenty-four BALB/c nude mice inoculated with U87 glioblastoma cells were randomized into a control group and an irradiation group, which underwent a 15-day fractioned radiation therapy (RT) course with 2 Gy/d. Therapy response was assessed by mapping of ADCs at 6 time points using an in-house implementation of a cos-OGSE DWI sequence with Δ eff  = 1.25 ms and compared with a standard pulsed gradient DWI protocol (PGSE) with typical clinical diffusion time Δ eff  = 18 ms. Longitudinal ADC changes in tumor and contralateral white matter (WM) were statistically assessed using repeated-measures analysis of variance and post hoc (Sidak) testing. On short Δ eff OGSE maps tumor ADC was generally 30%-50% higher than in surrounding WM. Areas correlated well with histology. Tumor identification was generally more difficult on PGSE maps owing to nonsignificant WM/tumor contrast. During RT, OGSE maps also showed significant tumor ADC increase (approximately 15%) in response to radiation, consistently seen after 14-Gy RT dose. The clinical reference (PGSE) showed lower sensitivity to radiation changes, and no significant response across the radiation group and time course could be detected. Our short Δ eff DWI method using OGSE better reflected histologically defined tumor areas and enabled more consistent and earlier detection of microstructural radiation changes than conventional methods. Oscillating gradients preparation offers significant potential as a robust microstructural RT response biomarker, potentially helping to shift important therapy decisions to earlier stages in the RT time course. Copyright © 2018 Elsevier Inc. All rights reserved.

Diffuse Optical Monitoring of the Neoadjuvant Breast Cancer Therapy

PubMed Central

Choe, Regine; Durduran, Turgut

2012-01-01

Recent advances in the use of diffuse optical techniques for monitoring the hemodynamic, metabolic and physiological signatures of the neoadjuvant breast cancer therapy effectiveness is critically reviewed. An extensive discussion of the state-of-theart diffuse optical mammography is presented alongside a discussion of the current approaches to breast cancer therapies. Overall, the diffuse optics field is growing rapidly with a great deal of promise to fill an important niche in the current approaches to monitor, predict and personalize neoadjuvant breast cancer therapies. PMID:23243386

Biomarkers of alcohol consumption in body fluids - possibilities and limitations of application in toxicological analysis.

PubMed

Woźniak, Mateusz K; Wiergowski, Marek; Namieśnik, Jacek; Biziuk, Marek

2017-10-05

Ethyl alcohol is the most popular legal drug, but its excessive consumption causes social problems. Despite many public campaigns against alcohol use, car accidents, instances of aggressive behaviour, sexual assaults and deterioration in labor productivity caused by inebriated people is still commonplace. Fast and easy diagnosis of alcohol consumption is required in order to introduce proper and effective therapy, and is crucial in forensic toxicology analysis. The easiest method to prove alcohol intake is determination of ethanol in body fluids or in breath. However, since ethanol is rapidly metabolized in the human organism, only recent consumption can be detected using this method. Because of that, the determination of alcohol biomarkers was introduced for monitoring alcohol consumption over a wider range of time. The markers described in this article are ethanol, its non-oxidative metabolites (ethyl glucuronide, ethyl sulfate, phosphatidylethanol, ethyl phosphate, fatty acid ethyl esters) and oxidative metabolites (acetaldehyde and acetaldehyde adducts). The objective of this study is to review published studies focusing on the sample preparation methods and chromatographic or biochemical techniques for the determination of alcohol biomarkers in whole blood, plasma, serum and urine. Authors also described issues concerning the detection window of these biomarkers, and possibilities and limitations of their use in routine analytical toxicology for monitoring alcohol consumption or sobriety during alcohol therapy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cardiac or Other Implantable Electronic Devices and Sleep-disordered Breathing – Implications for Diagnosis and Therapy

PubMed Central

Bitter, Thomas; Gutleben, Klaus-Jürgen; Horstkotte, Dieter; Oldenburg, Olaf

2014-01-01

Sleep-disordered breathing (SDB) is of growing interest in cardiology because SDB is a highly prevalent comorbidity in patients with a variety of cardiovascular diseases. The prevalence of SDB is particularly high in patients with cardiac dysrhythmias and/or heart failure. In this setting, many patients now have implantable cardiac devices, such as pacemakers, implantable cardioverter-defibrillators or implanted cardiac resynchronisation therapy devices (CRT). Treatment of SDB using implantable cardiac devices has been studied previously, with atrial pacing and CRT being shown not to bring about satisfactory results in SDB care. The latest generations of these devices have the capacity to determine transthoracic impedance, to detect and quantify breathing efforts and to identify SDB. The capability of implantable cardiac devices to detect SDB is of potential importance for patients with cardiovascular disease, allowing screening for SDB, monitoring of the course of SDB in relation to cardiac status, and documenting of the effects of treatment. PMID:26835077

Cardiac or Other Implantable Electronic Devices and Sleep-disordered Breathing - Implications for Diagnosis and Therapy.

PubMed

Fox, Henrik; Bitter, Thomas; Gutleben, Klaus-Jürgen; Horstkotte, Dieter; Oldenburg, Olaf

2014-08-01

Sleep-disordered breathing (SDB) is of growing interest in cardiology because SDB is a highly prevalent comorbidity in patients with a variety of cardiovascular diseases. The prevalence of SDB is particularly high in patients with cardiac dysrhythmias and/or heart failure. In this setting, many patients now have implantable cardiac devices, such as pacemakers, implantable cardioverter-defibrillators or implanted cardiac resynchronisation therapy devices (CRT). Treatment of SDB using implantable cardiac devices has been studied previously, with atrial pacing and CRT being shown not to bring about satisfactory results in SDB care. The latest generations of these devices have the capacity to determine transthoracic impedance, to detect and quantify breathing efforts and to identify SDB. The capability of implantable cardiac devices to detect SDB is of potential importance for patients with cardiovascular disease, allowing screening for SDB, monitoring of the course of SDB in relation to cardiac status, and documenting of the effects of treatment.

Monitoring circulating prostate tumor cells after tumor resection by in vivo flow cytometry

NASA Astrophysics Data System (ADS)

Ding, Nan; Zhu, Xi; Xie, Chengying; Wei, Dan; Yang, Zhangru; Suo, Yuanzhen; Wei, Xunbin

2018-02-01

Prostate cancer has already become the biggest threat among all cancer types for male people and many people died because of its bone metastases. Circulating tumor cells (CTCs) can be used as early metastasis marker so that the detection of CTCs in blood is meaningful for early diagnosis and treatment. However, the relationship between these therapies and metastasis has not been fully clarified yet. Hence, we built PC3 subcutaneous tumor model and developed in vivo flow cytometer (IVFC) platform to record the dynamics of CTC before and after tumor resection. We found out that tumor resection can reduce CTC quantities instantaneously while having a good control of metastasis. CTC re-occurred 7 days after surgery, which might be correlated with early disseminated and deposited tumors. In conclusion, in vivo flow cytometry (IVFC) is capable of detecting CTC dynamics in prostate subcutaneous tumor model and this method could facilitate further research about relationship between other cancer therapies and circulating tumor cells.

Randomized trial of a home monitoring system for early detection of choroidal neovascularization home monitoring of the Eye (HOME) study.

PubMed

Chew, Emily Y; Clemons, Traci E; Bressler, Susan B; Elman, Michael J; Danis, Ronald P; Domalpally, Amitha; Heier, Jeffrey S; Kim, Judy E; Garfinkel, Richard

2014-02-01

To determine whether home monitoring with the ForeseeHome device (Notal Vision Ltd, Tel Aviv, Israel), using macular visual field testing with hyperacuity techniques and telemonitoring, results in earlier detection of age-related macular degeneration-associated choroidal neovascularization (CNV), reflected in better visual acuity, when compared with standard care. The main predictor of treatment outcome from anti-vascular endothelial growth factor (VEGF) agents is the visual acuity at the time of CNV treatment. Unmasked, controlled, randomized clinical trial. One thousand nine hundred and seventy participants 53 to 90 years of age at high risk of CNV developing were screened. Of these, 1520 participants with a mean age of 72.5 years were enrolled in the Home Monitoring of the Eye study at 44 Age-Related Eye Disease Study 2 clinical centers. In the standard care and device arms arm, investigator-specific instructions were provided for self-monitoring vision at home followed by report of new symptoms to the clinic. In the device arm, the device was provided with recommendations for daily testing. The device monitoring center received test results and reported changes to the clinical centers, which contacted participants for examination. The main outcome measure was the difference in best-corrected visual acuity scores between baseline and detection of CNV. The event was determined by investigators based on clinical examination, color fundus photography, fluorescein angiography, and optical coherence tomography findings. Masked graders at a central reading center evaluated the images using standardized protocols. Seven hundred sixty-three participants were randomized to device monitoring and 757 participants were randomized to standard care and were followed up for a mean of 1.4 years between July 2010 and April 2013. At the prespecified interim analysis, 82 participants progressed to CNV, 51 in the device arm and 31 in the standard care arm. The primary analysis achieved statistical significance, with the participants in the device arm demonstrating a smaller decline in visual acuity with fewer letters lost from baseline to CNV detection (median, -4 letters; interquartile range [IQR], -11.0 to -1.0 letters) compared with standard care (median, -9 letters; IQR, -14.0 to -4.0 letters; P = 0.021), resulting in better visual acuity at CNV detection in the device arm. The Data and Safety Monitoring Committee recommended early study termination for efficacy. Persons at high risk for CNV developing benefit from the home monitoring strategy for earlier detection of CNV development, which increases the likelihood of better visual acuity results after intravitreal anti-VEGF therapy. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Home blood pressure-guided antihypertensive therapy in chronic kidney disease: more data are needed.

PubMed

Georgianos, Panagiotis I; Champidou, Eleni; Liakopoulos, Vassilios; Balaskas, Elias V; Zebekakis, Pantelis E

2018-04-01

In the era of newly introduced hypertension guidelines recommending lower blood pressure (BP) targets for drug-treated hypertensives, the necessity for optimized management of hypertension becomes even more urgent. The concept of home BP-guided antihypertensive therapy is for long suggested as a simple and feasible approach to improve BP control rates and optimize the management of hypertension. Home BP-guided antihypertensive therapy is particularly applicable to hypertensives with chronic kidney disease (CKD) for several reasons including the following: (1) difficult-to-control BP and high BP variability in the CKD setting; (2) poor accuracy of office BP in determining hypertension control status and detecting "white-coat" and "masked" hypertension; (3) poor value of routine office BP recordings in predicting the longitudinal progression of target-organ damage; and (4) superiority of home BP over office BP recordings in prognosticating the risk of incident end-stage renal disease or death. The concept of home BP-guided antihypertensive therapy is even more relevant for those on hemodialysis, given the high intradialytic and interdialytic BP variability and poor value of conventional peridialytic BP recordings in estimating the actual BP load recorded outside of dialysis with the use of home or ambulatory BP monitoring. Randomized trials comparing home BP-guided antihypertensive therapy versus usual care are warranted to prove the feasibility and effectiveness of this therapeutic approach and convince clinicians for using home BP monitoring as the standard of care when managing hypertension, particularly in people with CKD or end-stage renal disease. Copyright © 2018 American Heart Association. Published by Elsevier Inc. All rights reserved.

Commissioning of an integrated platform for time-resolved treatment delivery in scanned ion beam therapy by means of optical motion monitoring.

PubMed

Fattori, G; Saito, N; Seregni, M; Kaderka, R; Pella, A; Constantinescu, A; Riboldi, M; Steidl, P; Cerveri, P; Bert, C; Durante, M; Baroni, G

2014-12-01

The integrated use of optical technologies for patient monitoring is addressed in the framework of time-resolved treatment delivery for scanned ion beam therapy. A software application has been designed to provide the therapy control system (TCS) with a continuous geometrical feedback by processing the external surrogates tridimensional data, detected in real-time via optical tracking. Conventional procedures for phase-based respiratory phase detection were implemented, as well as the interface to patient specific correlation models, in order to estimate internal tumor motion from surface markers. In this paper, particular attention is dedicated to the quantification of time delays resulting from system integration and its compensation by means of polynomial interpolation in the time domain. Dedicated tests to assess the separate delay contributions due to optical signal processing, digital data transfer to the TCS and passive beam energy modulation actuation have been performed. We report the system technological commissioning activities reporting dose distribution errors in a phantom study, where the treatment of a lung lesion was simulated, with both lateral and range beam position compensation. The zero-delay systems integration with a specific active scanning delivery machine was achieved by tuning the amount of time prediction applied to lateral (14.61 ± 0.98 ms) and depth (34.1 ± 6.29 ms) beam position correction signals, featuring sub-millimeter accuracy in forward estimation. Direct optical target observation and motion phase (MPh) based tumor motion discretization strategies were tested, resulting in 20.3(2.3)% and 21.2(9.3)% median (IQR) percentual relative dose difference with respect to static irradiation, respectively. Results confirm the technical feasibility of the implemented strategy towards 4D treatment delivery, with negligible percentual dose deviations with respect to static irradiation.

Experimental photodynamic laser therapy for rheumatoid arthritis with a second generation photosensitizer.

PubMed

Hendrich, C; Hüttmann, G; Vispo-Seara, J L; Houserek, S; Siebert, W E

2000-01-01

Photodynamic laser therapy has been shown to be a new method for the treatment of synovitis in various animal models. Its principle is the accumulation of a photosensitizing drug in the inflamed synovium which is destroyed by photoactivation of the drug. In the present animal study we demonstrate the effect of a second-generation photosensitizer and suggest a concept for light dosimetry within the joint. We used 38 inbred rabbits for the IgG-induced arthritis model; 2 mg/kg of the benzoporphyrin derivative monoacid ring-A (BPD-MA) Verteporfin were administered 3 h before irradiation, which was performed using a 690-nm diode laser coupled to quartz glass fiber with a cylinder diffusor tip at a total light energy of either 180 or 470 J. During irradiation specific fluorescence of BPD-MA was monitored using a spectroscopy unit. The effect of the photodynamic laser therapy was documented grossly and histologically after 1 week. Within the 470 J-group a complete necrosis of the inflamed synovium was observed. The bradytrophic structures of the joint, however, remained unchanged. Throughout the 180 J-group the extent of necrosis was minor. During irradiation the tissue fluorescence of BPD-MA showed a dose-dependent decrease. Using BPD-MA as a photosensitizer a highly selective and minimal invasive synoviorthesis can be performed. At a dose of 2 mg/kg the histological effect depends on the light dose. For optimum efficacy a total energy of 470 J seems favorable. Online fluorescence detection can be used to monitor the effect of light administration. For dosimetry therefore an online tissue fluorescence detection may represent a technical solution.

Versatile graphene biosensors for enhancing human cell therapy.

PubMed

Vlăsceanu, George M; Amărandi, Roxana-Maria; Ioniță, Mariana; Tite, Teddy; Iovu, Horia; Pilan, Luisa; Burns, Jorge S

2018-05-01

Technological advances in engineering and cell biology stimulate novel approaches for medical treatment, in particular cell-based therapy. The first cell-based gene therapy against cancer was recently approved by the US Food and Drug Administration. Progress in cancer diagnosis includes a blood test detecting five cancer types. Numerous stem cell phase I/II clinical trials showing safety and efficacy will soon pursue qualifying criteria for advanced therapy medicinal products (ATMP), aspiring to join the first stem-cell therapy approved by the European Medicines Agency. Cell based therapy requires extensive preclinical characterisation of biomarkers indicating mechanisms of action crucial to the desired therapeutic effect. Quantitative analyses monitoring critical functions for the manufacture of optimal cell and tissue-based clinical products include successful potency assays for implementation. The challenge to achieve high quality measurement is increasingly met by progress in biosensor design. We adopt a cell therapy perspective to highlight recent examples of graphene-enhanced biointerfaces for measurement of biomarkers relevant to cancer treatment, diagnosis and tissue regeneration. Graphene based biosensor design problems can thwart their use for health care transformative point of care testing and real-time applications. We discuss concerns to be addressed and emerging solutions for establishing clinical grade biosensors to accelerate human cell therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

[Telemonitoring of swallowing function: technologies in speech therapy practice.

PubMed

Tedesco, Angela; Lavermicocca, Valentina; Notarnicola, Marilina; De Francesco, Luca; Dellomonaco, Anna Rita

2018-02-01

The process of medical-healthcare technological revolution represents an advantage for the patient and for the care provider, in terms of costs and distances reduction. The telehomecare approach could be useful for monitoring the swallowing disorder in neurodegenerative diseases, preventing complications. In this study the applicability of telemedicine techniques for the monitoring of swallowing function, in patients affected by Huntington's disease (HD), was evaluated through the acquisition and analysis of the sound of swallowing. Two patients with HD were outpatient screened for dysphagia through the Bedside Swallowing Assessment Scale (BSAS) sensitized with pulse oximetry and cervical auscultation. Subsequently, the swallowing functionality was telemonitored for three months with Skype. The swallowing sounds were acquired with a detection microphone attached to the lateral edge of the trachea during fluid intake. The sounds were instantly processed and graphically represented through the Praat software. The analysis of the acoustic signal acquired remotely has made it possible to identify the situations that required immediate speech therapy intervention, suggesting to the patients further modifications of food consistencies, and saving frequent moving to the hospital even in the absence of critical situations. Remote assistance applied to speech therapy could represent a benefit for patients and their carers and a more efficient use of medical and health resources.

Photodynamic diagnosis and related optical techniques for the management of malignant glioma

NASA Astrophysics Data System (ADS)

Sroka, R.; Stepp, H.; Beyer, W.; Markwardt, N.; Rühm, A.

2017-04-01

Malignant gliomas are a devastating brain tumor disease with very poor prognosis. Stereotactic biopsy sampling is routinely used in larger neurosurgical centers to confirm the diagnosis of a suspected brain tumor. This procedure is associated with risk of blood vessel rupture as well as false-negative results. Recent investigations suggest a potential of light-based techniques to improve both therapy and diagnosis of GBM. Optical guidance can be utilized to improve the biopsy sampling procedure in terms of safety, reliability, and efficacy. Recording of optical signals (transmission, remission, fluorescence) can be potentially integrated into a biopsy needle for providing optical detection of tumor tissue and blood vessel recognition during the biopsy sampling. Optical signals can also be used for monitoring purposes during photodynamic therapy. Here, fluorescence signals recorded before the treatment indicate the presence and accumulation level of photosensitizer, while photobleaching of the photosensitizer fluorescence during the treatment can be used as a measure of the effectiveness of the therapy. Finally, transmitted light can reveal problematic tissue-optical conditions as well as changes of the optical properties of the treated tissue, which may be relevant with regard to treatment prognosis and strategy. Different optical concepts for interstitial PDT monitoring and optical tissue property assessment are presented.

What evidence do we have to replace in-hospital implantable cardioverter defibrillator follow-up?

PubMed

Brugada, P

2006-01-01

Due to the increasing number of patients with an implantable cardioverter defibrillator (ICD), new options for ICD patient follow-up management are required. Patients with ICD indication according to the guidelines received an ICD with Home Monitoring technology. The devices enabled the transmission of the relevant episode, therapy, and system integrity data. Patients were followed for 12 months with routine controls every 3 months. The physician analyzed the Home Monitoring data before the routine follow-up visit (FU) and gave a forecast on the necessity of the pending FU, which was compared with the evaluation after the FU. Based on the derived forecast reliability, a patient management scheme was developed and its impact on patient safety was assessed retrospectively. A total of 271 patients were enrolled (40 f, mean age 62+/-12 years, mean LVEF 39+/-15%, 65% ischemic heart disease, 20% cardiomyopathy) and followed for 339+/-109 days. Of 908 pairs of Home Monitoring data and FU data evaluation, 129 there were false negative results for 92 patients. Safety concerns from false negative forecasts can be minimized with a patient management scheme containing the following elements: 1) never skip the first routine FU; 2) never skip a routine FU for a patient having already shown pacing threshold problems; 3) perform FU following hospitalizations; 4) perform FU following episode detection by the ICD; and 5) perform a routine FU if the patient reports symptoms. The retrospective analysis showed, that if the patients had been managed using this scheme, 503 of 1079 routine FU could have been skipped with only one safety concern, a three month delay in the detection of silent paroxysmal atrial fibrillation in one patient. Home Monitoring in ICD therapy over 12 months is feasible. The data transmitted relevantly contribute to a remarkable reduction of follow-up burden and enable the individualization of routine follow-up.

Optimization of circulating cell-free DNA recovery for KRAS mutation and HPV detection in plasma.

PubMed

Mazurek, Agnieszka M; Fiszer-Kierzkowska, A; Rutkowski, T; Składowski, K; Pierzyna, M; Scieglińska, D; Woźniak, G; Głowacki, G; Kawczyński, R; Małusecka, E

2013-01-01

The precise analysis of tumour markers in blood such as circulating cell-free DNA (cfDNA) could have a significant impact in facilitating monitoring of patients after initial therapy. Although high levels of total cfDNA in plasma of cancer patients are consistently demonstrated, a low sensitivity of DNA alterations is reported. The major question regards the recovery of tumour-specific cfDNA such as KRAS mutated DNA and cancer-associated type 16 of human papillomavirus (HPV16). TaqMan technology was used for detection of KRAS mutation, HPV16 and to quantify cfDNA in blood plasma. Comparison of four different column-based commercial kits shows that the cfDNA purification carried out by the Genomic Mini AX Body Fluids kit and the QIAamp Circulating Nucleic Acid kit gave us the possibility to improve the sensitivity of detection of KRAS mutation and HPV16. The optimized method was used to follow the reduction in cancer-specific cfDNA after therapy. We found that large volume extractions with low volume of DNA eluate enabled trace amounts of tumour-specific cfDNA from cancer patients to be effectively identified. Data presented in this study facilitate detection of tumour-specific cfDNA and improve standards needed for the implementation of cfDNA technology into routine clinical practice.

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

NASA Astrophysics Data System (ADS)

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapy was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.

Circulating Cell Free Tumor DNA Detection as a Routine Tool for Lung Cancer Patient Management

PubMed Central

Vendrell, Julie A.; Mau-Them, Frédéric Tran; Béganton, Benoît; Godreuil, Sylvain; Coopman, Peter; Solassol, Jérôme

2017-01-01

Circulating tumoral DNA (ctDNA), commonly named “liquid biopsy”, has emerged as a new promising noninvasive tool to detect biomarker in several cancers including lung cancer. Applications involving molecular analysis of ctDNA in lung cancer have increased and encompass diagnosis, response to treatment, acquired resistance and prognosis prediction, while bypassing the problem of tumor heterogeneity. ctDNA may then help perform dynamic genetic surveillance in the era of precision medicine through indirect tumoral genomic information determination. The aims of this review were to examine the recent technical developments that allowed the detection of genetic alterations of ctDNA in lung cancer. Furthermore, we explored clinical applications in patients with lung cancer including treatment efficiency monitoring, acquired therapy resistance mechanisms and prognosis value. PMID:28146051

Concise review: Nanoparticles and cellular carriers-allies in cancer imaging and cellular gene therapy?

PubMed Central

Tang, Catherine; Russell, Pamela J; Martiniello-Wilks, Rosetta; J Rasko, John E; Khatri, Aparajita

2010-01-01

Ineffective treatment and poor patient management continue to plague the arena of clinical oncology. The crucial issues include inadequate treatment efficacy due to ineffective targeting of cancer deposits, systemic toxicities, suboptimal cancer detection and disease monitoring. This has led to the quest for clinically relevant, innovative multifaceted solutions such as development of targeted and traceable therapies. Mesenchymal stem cells (MSCs) have the intrinsic ability to “home” to growing tumors and are hypoimmunogenic. Therefore, these can be used as (a) “Trojan Horses” to deliver gene therapy directly into the tumors and (b) carriers of nanoparticles to allow cell tracking and simultaneous cancer detection. The camouflage of MSC carriers can potentially tackle the issues of safety, vector, and/or transgene immunogenicity as well as nanoparticle clearance and toxicity. The versatility of the nanotechnology platform could allow cellular tracking using single or multimodal imaging modalities. Toward that end, noninvasive magnetic resonance imaging (MRI) is fast becoming a clinical favorite, though there is scope for improvement in its accuracy and sensitivity. In that, use of superparamagnetic iron-oxide nanoparticles (SPION) as MRI contrast enhancers may be the best option for tracking therapeutic MSC. The prospects and consequences of synergistic approaches using MSC carriers, gene therapy, and SPION in developing cancer diagnostics and therapeutics are discussed. STEM CELLS 2010; 28:1686–1702. PMID:20629172

Biomarkers and Imaging Findings of Anderson–Fabry Disease—What We Know Now

PubMed Central

Beirão, Idalina; Cabrita, Ana; Torres, Márcia; Silva, Fernando; Aguiar, Patrício; Laranjeira, Francisco; Gomes, Ana Marta

2017-01-01

Anderson–Fabry disease (AFD) is an X-linked lysosomal storage disorder, caused by deficiency or absence of the alpha-galactosidase A activity, with a consequent glycosphingolipid accumulation. Biomarkers and imaging findings may be useful for diagnosis, identification of an organ involvement, therapy monitoring and prognosis. The aim of this article is to review the current available literature on biomarkers and imaging findings of AFD patients. An extensive bibliographic review from PubMed, Medline and Clinical Key databases was performed by a group of experts from nephrology, neurology, genetics, cardiology and internal medicine, aiming for consensus. Lyso-GB3 is a valuable biomarker to establish the diagnosis. Proteinuria and creatinine are the most valuable to detect renal damage. Troponin I and high-sensitivity assays for cardiac troponin T can identify patients with cardiac lesions, but new techniques of cardiac imaging are essential to detect incipient damage. Specific cerebrovascular imaging findings are present in AFD patients. Techniques as metabolomics and proteomics have been developed in order to find an AFD fingerprint. Lyso-GB3 is important for evaluating the pathogenic mutations and monitoring the response to treatment. Many biomarkers can detect renal, cardiac and cerebrovascular involvement, but none of these have proved to be important to monitoring the response to treatment. Imaging features are preferred in order to find cardiac and cerebrovascular compromise in AFD patients. PMID:28933368

Optical monitoring of thermal effects in RPE during heating

NASA Astrophysics Data System (ADS)

Schuele, G.; Huie, Ph.; Yellachich, D.; Molnar, F. E.; O'Conell-Rodwell, C.; Vitkin, E.; Perelman, L. T.; Palanker, D.

2005-04-01

Fast and non-invasive detection of cellular stress is useful for fundamental research and practical applications in medicine and biology. Using Light Scattering Spectroscopy we extract information about changes in refractive index and size of the cellular organelles. Particle sizes down to 50nm in diameter can be detected using light within the spectral range of 450-850 nm. We monitor the heat-induced sub-cellular structural changes in human RPE cells and, for comparison, in transfected NIH-3T3 cells which express luciferase linked to the heat shock protein (HSP). Using inverse light scattering fitting algorithm, we reconstruct the size distribution of the sub-micron organelles from the light scattering spectrum. The most significant (up to 70%) and rapid (20sec) temperature-related changes can be linked to an increase of refractive index of the 160nm sized mitochondria. The start of this effect coincides with the onset of HSP expression. This technique provides an insight into metabolic processes within organelles larger than 50nm without exogenous staining and opens doors for non-invasive real-time assessment of cellular stress, which can be used for monitoring of retinal laser treatments like transpupillary thermo therapy or PDT.

A focus group on cognition-enhancing medications in Alzheimer disease: disparities between professionals and consumers.

PubMed

Post, S G; Stuckey, J C; Whitehouse, P J; Ollerton, S; Durkin, C; Robbins, D; Fallcreek, S J

2001-01-01

The emergence of cognition-enhancing drugs in the treatment of Alzheimer disease raises questions about quality of lives for those with dementia and for their caregivers, and about the perceptions of health care professionals. This pilot study analyzes a limited data from a series of three focus groups on the experience of treatment. These groups engaged both Alzheimer disease-affected persons, their caregivers, and a multidisciplinary professional core. We conclude that therapeutic goals need to be better addressed with patients and families, as well as better monitored, with the possibility of withdrawing therapy as appropriate. We also detected, as hypothesized, considerable disparity between the perspectives of professionals and consumers regarding the benefits of therapy.

Successful Immunosuppressive Therapy for Severe Infectious Mononucleosis in a Patient with Clonal Proliferation of EBV-infected CD8-positive Cells.

PubMed

Hosoi, Hiroki; Sonoki, Takashi; Murata, Shogo; Mushino, Toshiki; Kuriyama, Kodai; Nishikawa, Akinori; Hanaoka, Nobuyoshi; Ohshima, Koichi; Imadome, Ken-Ichi; Nakakuma, Hideki

2015-01-01

A 30-year-old woman was diagnosed with severe infectious mononucleosis (IM). The Epstein-Barr virus (EBV) had infected both CD19- and CD8-positive cells, and clonal proliferation of EBV-infected cells and T-cells was detected. Although we suspected malignant lymphoma, her condition improved following immunosuppressive therapy. A similar case was recently reported; therefore, this case is the second case of IM with EBV-infected CD8-positive cells and clonal proliferation of EBV-infected cells. Our results demonstrate that the clonal proliferation of EBV-infected cells is not always an indication for chemotherapy in the primary infection phase and that monitoring the EBV viral load is useful for therapeutic decision-making.

[Noninvasive alternatives to CPAP in therapy of obstructive sleep apnea syndrome].

PubMed

Fritsch, K; Bloch, K E

2000-07-01

Non-surgical treatment of the sleep apnea syndrome comprises behavioral modification such as sleep hygiene, weight reduction, and positional training as an adjunct to standard therapy with continuous positive airway pressure (CPAP) applied via a nasal mask. For patients who cannot tolerate or are not willing to use CPAP for psychological or other reasons, removable intraoral appliances that advance the mandible during sleep are a valuable treatment alternative. Randomised controlled trials have confirmed effectiveness of intraoral appliances in relieving symptoms and measured sleep and respiratory disturbances. Side effects including hypersalivation, mucosal dryness, tooth and temporo-mandibular joint discomfort are common but usually mild. To timely detect effects of oral appliances on occlusion and on the temporo-mandibular joint longterm orthodontic monitoring is advisable.

Effective data validation of high-frequency data: time-point-, time-interval-, and trend-based methods.

PubMed

Horn, W; Miksch, S; Egghart, G; Popow, C; Paky, F

1997-09-01

Real-time systems for monitoring and therapy planning, which receive their data from on-line monitoring equipment and computer-based patient records, require reliable data. Data validation has to utilize and combine a set of fast methods to detect, eliminate, and repair faulty data, which may lead to life-threatening conclusions. The strength of data validation results from the combination of numerical and knowledge-based methods applied to both continuously-assessed high-frequency data and discontinuously-assessed data. Dealing with high-frequency data, examining single measurements is not sufficient. It is essential to take into account the behavior of parameters over time. We present time-point-, time-interval-, and trend-based methods for validation and repair. These are complemented by time-independent methods for determining an overall reliability of measurements. The data validation benefits from the temporal data-abstraction process, which provides automatically derived qualitative values and patterns. The temporal abstraction is oriented on a context-sensitive and expectation-guided principle. Additional knowledge derived from domain experts forms an essential part for all of these methods. The methods are applied in the field of artificial ventilation of newborn infants. Examples from the real-time monitoring and therapy-planning system VIE-VENT illustrate the usefulness and effectiveness of the methods.

A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood.

PubMed

Cartwright, Mark; Rottman, Martin; Shapiro, Nathan I; Seiler, Benjamin; Lombardo, Patrick; Gamini, Nazita; Tomolonis, Julie; Watters, Alexander L; Waterhouse, Anna; Leslie, Dan; Bolgen, Dana; Graveline, Amanda; Kang, Joo H; Didar, Tohid; Dimitrakakis, Nikolaos; Cartwright, David; Super, Michael; Ingber, Donald E

2016-07-01

Blood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis. An Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries. The FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (<1h) detected the presence of active infection in animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein. The FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Passive microlesion detection and mapping for treatment of hypertrophic cardiomyopathy

NASA Astrophysics Data System (ADS)

Zhu, Yiying I.; Miller, Douglas L.; Dou, Chunyan; Kripfgans, Oliver D.

2017-03-01

Intermittent high intensity ultrasound pulses with circulating contrast agent microbubbles can induce scattered microlesions of potential value for myocardial reduction therapy. This paper presents an in vitro setup imitating the treatment for monitoring development. A preclinical imaging system with a single element transducer, synchronization and receive-only imaging transducer array has been implemented on a research platform. Contrast agent microbubbles pumped in a dialysis tubing setup were exposed to high intensity focused ultrasound at 1.0/3.5 MHz center frequencies. Polystyrene spheres were employed as linear scatterers compared to contrast agents for system transfer function equalization. A cavitation mapping technique was employed to spatially locate and depict microbubble activity during treatment. For high acoustic pressure amplitudes a 5 dB difference between contrast agent and solid spheres was observed and spatially mapped. The in-plane resolution was 4.5 mm for axial and 1.5 mm laterally. In the future, this cavitation detection scheme will be applied to monitor in vivo microlesioning in real-time.

In vivo quantitative bioluminescence tomography using heterogeneous and homogeneous mouse models.

PubMed

Liu, Junting; Wang, Yabin; Qu, Xiaochao; Li, Xiangsi; Ma, Xiaopeng; Han, Runqiang; Hu, Zhenhua; Chen, Xueli; Sun, Dongdong; Zhang, Rongqing; Chen, Duofang; Chen, Dan; Chen, Xiaoyuan; Liang, Jimin; Cao, Feng; Tian, Jie

2010-06-07

Bioluminescence tomography (BLT) is a new optical molecular imaging modality, which can monitor both physiological and pathological processes by using bioluminescent light-emitting probes in small living animal. Especially, this technology possesses great potential in drug development, early detection, and therapy monitoring in preclinical settings. In the present study, we developed a dual modality BLT prototype system with Micro-computed tomography (MicroCT) registration approach, and improved the quantitative reconstruction algorithm based on adaptive hp finite element method (hp-FEM). Detailed comparisons of source reconstruction between the heterogeneous and homogeneous mouse models were performed. The models include mice with implanted luminescence source and tumor-bearing mice with firefly luciferase report gene. Our data suggest that the reconstruction based on heterogeneous mouse model is more accurate in localization and quantification than the homogeneous mouse model with appropriate optical parameters and that BLT allows super-early tumor detection in vivo based on tomographic reconstruction of heterogeneous mouse model signal.

Dosimetry control and monitoring of selective retina therapy using optical coherence tomography

NASA Astrophysics Data System (ADS)

Kaufmann, Daniel; Burri, Christian; Arnold, Patrik; Koch, Volker M.; Meier, Christoph; Považay, Boris; Justiz, Joern

2017-07-01

Selective retina therapy and optical coherence tomography have been combined to monitor laser-tissue interaction in real-time. An ex-vivo study of porcine eyes unveils mechanisms that enable automated and accurate dose-control during laser-therapy.

Analysis of arrhythmic events is useful to detect lead failure earlier in patients followed by remote monitoring.

PubMed

Nishii, Nobuhiro; Miyoshi, Akihito; Kubo, Motoki; Miyamoto, Masakazu; Morimoto, Yoshimasa; Kawada, Satoshi; Nakagawa, Koji; Watanabe, Atsuyuki; Nakamura, Kazufumi; Morita, Hiroshi; Ito, Hiroshi

2018-03-01

Remote monitoring (RM) has been advocated as the new standard of care for patients with cardiovascular implantable electronic devices (CIEDs). RM has allowed the early detection of adverse clinical events, such as arrhythmia, lead failure, and battery depletion. However, lead failure was often identified only by arrhythmic events, but not impedance abnormalities. To compare the usefulness of arrhythmic events with conventional impedance abnormalities for identifying lead failure in CIED patients followed by RM. CIED patients in 12 hospitals have been followed by the RM center in Okayama University Hospital. All transmitted data have been analyzed and summarized. From April 2009 to March 2016, 1,873 patients have been followed by the RM center. During the mean follow-up period of 775 days, 42 lead failure events (atrial lead 22, right ventricular pacemaker lead 5, implantable cardioverter defibrillator [ICD] lead 15) were detected. The proportion of lead failures detected only by arrhythmic events, which were not detected by conventional impedance abnormalities, was significantly higher than that detected by impedance abnormalities (arrhythmic event 76.2%, 95% CI: 60.5-87.9%; impedance abnormalities 23.8%, 95% CI: 12.1-39.5%). Twenty-seven events (64.7%) were detected without any alert. Of 15 patients with ICD lead failure, none has experienced inappropriate therapy. RM can detect lead failure earlier, before clinical adverse events. However, CIEDs often diagnose lead failure as just arrhythmic events without any warning. Thus, to detect lead failure earlier, careful human analysis of arrhythmic events is useful. © 2017 Wiley Periodicals, Inc.

Range assessment in particle therapy based on prompt γ-ray timing measurements

NASA Astrophysics Data System (ADS)

Golnik, Christian; Hueso-González, Fernando; Müller, Andreas; Dendooven, Peter; Enghardt, Wolfgang; Fiedler, Fine; Kormoll, Thomas; Roemer, Katja; Petzoldt, Johannes; Wagner, Andreas; Pausch, Guntram

2014-09-01

Proton and ion beams open up new vistas for the curative treatment of tumors, but adequate technologies for monitoring the compliance of dose delivery with treatment plans in real time are still missing. Range assessment, meaning the monitoring of therapy-particle ranges in tissue during dose delivery (treatment), is a continuous challenge considered a key for tapping the full potential of particle therapies. In this context the paper introduces an unconventional concept of range assessment by prompt-gamma timing (PGT), which is based on an elementary physical effect not considered so far: therapy particles penetrating tissue move very fast, but still need a finite transit time—about 1-2 ns in case of protons with a 5-20 cm range—from entering the patient’s body until stopping in the target volume. The transit time increases with the particle range. This causes measurable effects in PGT spectra, usable for range verification. The concept was verified by proton irradiation experiments at the AGOR cyclotron, KVI-CART, University of Groningen. Based on the presented kinematical relations, we describe model calculations that very precisely reproduce the experimental results. As the clinical treatment conditions entail measurement constraints (e.g. limited treatment time), we propose a setup, based on clinical irradiation conditions, capable of determining proton range deviations within a few seconds of irradiation, thus allowing for a fast safety survey. Range variations of 2 mm are expected to be clearly detectable.

The role of multiparametric flow cytometry in the detection of minimal residual disease in acute leukaemia.

PubMed

Lee, Denise; Grigoriadis, George; Westerman, David

2015-12-01

Flow cytometry is the most accessible method for minimal residual disease (MRD) detection due to its availability in most haematological centres. Using a precise combination of different antibodies, immunophenotypic detection of MRD in acute leukaemia can be performed by identifying abnormal combinations or expressions of antigens on malignant cells at diagnosis, during and post treatment. These abnormal phenotypes, referred to as leukaemia-associated immunophenotypes (LAIPs) are either absent or expressed at low frequency in normal bone marrow (BM) cells and are used to monitor the behaviour and quantitate the amount of residual disease following treatment. In paediatric acute lymphoblastic leukaemia (ALL), the level of MRD by multiparametric flow cytometry (MPFC) during therapy is recognised as an important predictor of outcome. Although less extensively studied, adult ALL and adult and paediatric acute myeloid leukaemia (AML) have also demonstrated similar findings. The challenge now is incorporating this information for risk-stratification so that therapy can be tailored individually and ultimately improve outcome while also limiting treatment-related toxicity. In this review we will elaborate on the current and future role of MPFC in MRD in acute leukaemia while also addressing its limitations.

Multimodal brain monitoring in fulminant hepatic failure

PubMed Central

Paschoal Jr, Fernando Mendes; Nogueira, Ricardo Carvalho; Ronconi, Karla De Almeida Lins; de Lima Oliveira, Marcelo; Teixeira, Manoel Jacobsen; Bor-Seng-Shu, Edson

2016-01-01

Acute liver failure, also known as fulminant hepatic failure (FHF), embraces a spectrum of clinical entities characterized by acute liver injury, severe hepatocellular dysfunction, and hepatic encephalopathy. Cerebral edema and intracranial hypertension are common causes of mortality in patients with FHF. The management of patients who present acute liver failure starts with determining the cause and an initial evaluation of prognosis. Regardless of whether or not patients are listed for liver transplantation, they should still be monitored for recovery, death, or transplantation. In the past, neuromonitoring was restricted to serial clinical neurologic examination and, in some cases, intracranial pressure monitoring. Over the years, this monitoring has proven insufficient, as brain abnormalities were detected at late and irreversible stages. The need for real-time monitoring of brain functions to favor prompt treatment and avert irreversible brain injuries led to the concepts of multimodal monitoring and neurophysiological decision support. New monitoring techniques, such as brain tissue oxygen tension, continuous electroencephalogram, transcranial Doppler, and cerebral microdialysis, have been developed. These techniques enable early diagnosis of brain hemodynamic, electrical, and biochemical changes, allow brain anatomical and physiological monitoring-guided therapy, and have improved patient survival rates. The purpose of this review is to discuss the multimodality methods available for monitoring patients with FHF in the neurocritical care setting. PMID:27574545

Assessment of Fluid Balance and the Approach to Fluid Therapy in the Perioperative Patient.

PubMed

Boller, Elise; Boller, Manuel

2015-09-01

Perioperative patients can be highly dynamic and have various metabolic, physiologic, and organ system derangements that necessitate smart monitoring strategies and careful fluid therapy. The interplay between changing patient status, therapeutic interventions, and patient response makes effective monitoring crucial to successful treatment. Monitoring the perioperative patient and an approach to fluid therapy are discussed in this text. Copyright © 2015 Elsevier Inc. All rights reserved.

Validation of Heat Shock Protein 70 as a Tumor-Specific Biomarker for Monitoring the Outcome of Radiation Therapy in Tumor Mouse Models

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

Bayer, Christine; Liebhardt, Michael E.; Schmid, Thomas E.

2014-03-01

Purpose: Tumor cells, in contrast to normal cells, frequently overexpress heat shock protein 70 (Hsp70) in the cytosol, present it on their cell surface, and actively release it. Therefore, soluble Hsp70 (sHsp70) was investigated as a potential tumor biomarker for monitoring the outcome of radiation therapy. Methods and Materials: Plasma from mice bearing membrane Hsp70 (mHsp70)-positive FaDu human squamous cell carcinoma of the head and neck and spontaneous pancreatic ductal adenocarcinoma (PDAC) was investigated. A cohort of mice with FaDu tumors (0.32 cm{sup 3}) was irradiated with 30 Gy, and plasma was collected 24 hours after irradiation, after the tumors had shrunk tomore » 50% of their starting volume and after complete remission. sHsp70 levels in the plasma were quantified by enzyme-linked immunosorbent assay. Results: sHsp70 levels were significantly higher in the blood of tumor-bearing mice than that of control animals. A correlation between increasing sHsp70 plasma levels and tumor volume in the range of 0.01 cm{sup 3} to 0.66 cm{sup 3} was observed. Radiation-induced regression of the tumors was associated with significantly decreased sHsp70 levels, which returned to the level of control animals after complete remission. Conclusion: We propose sHsp70 as an innovative biomarker for detecting tumors and for monitoring the clinical outcome of radiation therapy in cancer patients.« less

Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer

NASA Astrophysics Data System (ADS)

Kopelman, Raoul; Lee Koo, Yong-Eun; Philbert, Martin; Moffat, Bradford A.; Ramachandra Reddy, G.; McConville, Patrick; Hall, Daniel E.; Chenevert, Thomas L.; Bhojani, Mahaveer Swaroop; Buck, Sarah M.; Rehemtulla, Alnawaz; Ross, Brian D.

2005-05-01

A paradigm for brain cancer detection, treatment, and monitoring is established. Multifunctional biomedical nanoparticles (30-60 nm) containing photosensitizer externally deliver reactive oxygen species (ROS) to cancer cells while simultaneously enhancing magnetic resonance imaging (MRI) contrast providing real-time tumor kill measurement. Plasma residence time control and specific cell targeting are achieved. A 5 min treatment in rats halted and even reversed in vivo tumor growth after 3-4 days post-treatment.

Comparison of two strategies for detection of reactive oxygen species

NASA Astrophysics Data System (ADS)

Gao, Weidong; Zhou, Yuanshu; Gu, Yueqing

2014-09-01

Photodynamic therapy (PDT) is a clinically approved treatment that was applied to oncology , dermatology, and ophthalmology. Reactive oxygen species (ROS) play a important role in the efficacy of PDT. Online monitoring of reactive oxygen species is the key to understand effect of PDT treatment. We used Fluorescence probes DPBF and luminescent probe luminal to measure the ROS in cells. And we revaluate the relationship between the amount of light and cell survival. There is strongly correlated between the amount of light and cell kill.

Solid State Radiation Dosimeters for Space and Medical Applications

NASA Technical Reports Server (NTRS)

Buehler, Martin G. (Editor)

1996-01-01

This report describes the development of two radiation monitors (RADMON's) for use in detecting total radiation dose and high-energy particles. These radiation detectors are chip-size devices fabricated in 1.2 micrometer CMOS and have flown in space on both experimental and commercial spacecraft. They have been used to characterize protons and electrons in the Earth's radiation belts, particles from the Sun, and protons used for medical therapy. Having proven useful in a variety of applications, the detector is now being readied for commercialization.

PIK3CA and KRAS mutations in cell free circulating DNA are useful markers for monitoring ovarian clear cell carcinoma

PubMed Central

Morikawa, Asuka; Hayashi, Tomoatsu; Shimizu, Naomi; Kobayashi, Mana; Taniue, Kenzui; Takahashi, Akiko; Tachibana, Kota; Saito, Misato; Kawabata, Ayako; Iida, Yasushi; Ueda, Kazu; Saito, Motoaki; Yanaihara, Nozomu; Tanabe, Hiroshi; Yamada, Kyosuke; Takano, Hirokuni; Nureki, Osamu; Okamoto, Aikou; Akiyama, Tetsu

2018-01-01

Ovarian clear cell carcinoma (OCCC) exhibits distinct phenotypes, such as resistance to chemotherapy, poor prognosis and an association with endometriosis. Biomarkers and imaging techniques currently in use are not sufficient for reliable diagnosis of this tumor or prediction of therapeutic response. It has recently been reported that analysis of somatic mutations in cell-free circulating DNA (cfDNA) released from tumor tissues can be useful for tumor diagnosis. In the present study, we attempted to detect mutations in PIK3CA and KRAS in cfDNA from OCCC patients using droplet digital PCR (ddPCR). Here we show that we were able to specifically detect PIK3CA-H1047R and KRAS-G12D in cfDNA from OCCC patients and monitor their response to therapy. Furthermore, we found that by cleaving wild-type PIK3CA using the CRISPR/Cas9 system, we were able to improve the sensitivity of the ddPCR method and detect cfDNA harboring PIK3CA-H1047R. Our results suggest that detection of mutations in cfDNA by ddPCR would be useful for the diagnosis of OCCC, and for predicting its recurrence. PMID:29632642

pH-sensitive pHluorins as a molecular sensor for in situ monitoring of enzyme-catalyzed prodrug activation.

PubMed

Liu, Hui; Cao, Xiaodan; Wang, Ping; Ma, Xingyuan

2017-07-01

This work examines the feasibility of using a pH-sensitive fluorescent protein as a molecular reporter for enzyme-catalyzed prodrug activation reaction. Specifically, a ratiometric pHluorins was examined for detection of the activity of horseradish peroxidase (HRP) for the activation of indole-3-acetic acid. The pHluorins and HRP were conjugated chemically, forming a biocatalyst with a self-reporting function. Results showed that the characteristic fluorescence intensity ratio of the conjugate shifted from 1.47 to 1.40 corresponding to the progress of the prodrug activation reaction. The effectiveness of applying the conjugate for inhibition of the growth of Bcap-37 cells was also demonstrated simultaneously with reaction monitoring. The results reveal a very promising approach to realizing in situ monitoring of enzyme activities based on pH shifting for enzyme-based prodrug therapy applications. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Ultrasound Imaging of DNA-Damage Effects in Live Cultured Cells and in Brain Tissue.

PubMed

Tadayyon, Hadi; Gangeh, Mehrdad J; Vlad, Roxana; Kolios, Michael C; Czarnota, Gregory J

2017-01-01

High-frequency ultrasound (>20 MHz) spectroscopy can be used to detect noninvasively DNA damage in cell samples in vitro, and in live tissue both ex vivo and in vivo. This chapter focuses on the former two aspects. Experimental evidence suggests that morphological changes that occur in cells undergoing apoptosis result in changes in frequency-dependent ultrasound backscatter. With advances in research, ultrasound spectroscopy is advancing the boundaries of fast, label-free, noninvasive DNA damage detection technology with potential use in personalized medicine and early therapy response monitoring. Depending on the desired resolution, parametric ultrasound images can be computed and displayed within minutes to hours after ultrasound examination for cell death.

Autoimmune encephalitis in children: clinical phenomenology, therapeutics, and emerging challenges.

PubMed

Dale, Russell C; Gorman, Mark P; Lim, Ming

2017-06-01

Auto-antibodies that bind to conformational extracellular epitopes of neuronal receptors or synaptic proteins have provided clinicians with essential biomarkers in acute neurology. This review summarizes the current status and challenges in the field. In children, anti-N-methyl-D-aspartate receptor encephalitis remains the most identifiable autoimmune encephalitis, although many patients have a clinical syndrome of brain inflammation in which no antibodies are identified. Anti-myelin oligodendrocyte glycoprotein antibody associated demyelination is now recognized as a major cause of monophasic and relapsing demyelination, often presenting with encephalopathy. We discuss the importance of auto-antibody detection methodology and the possible influence of intrathecal antibody synthesis on the speed of recovery and response to immune therapy. The current, often pragmatic rather than evidence-based therapeutic pathway will be discussed, highlighting key challenges such as the timing of second-line therapy, monitoring of disease activity, and identifying the patient who is responding poorly to treatment. Although there have been significant developments, future priorities include the need for paediatric-specific consensus definitions for seronegative suspected autoimmune encephalitis, novel tools for monitoring patients with autoimmune encephalitis, consensus treatment recommendations, and neuroprotective strategies.

A novel high resolution, high sensitivity SPECT detector for molecular imaging of cardiovascular diseases

NASA Astrophysics Data System (ADS)

Cusanno, F.; Argentieri, A.; Baiocchi, M.; Colilli, S.; Cisbani, E.; De Vincentis, G.; Fratoni, R.; Garibaldi, F.; Giuliani, F.; Gricia, M.; Lucentini, M.; Magliozzi, M. L.; Majewski, S.; Marano, G.; Musico, P.; Musumeci, M.; Santavenere, F.; Torrioli, S.; Tsui, B. M. W.; Vitelli, L.; Wang, Y.

2010-05-01

Cardiovascular diseases are the most common cause of death in western countries. Understanding the rupture of vulnerable atherosclerotic plaques and monitoring the effect of innovative therapies of heart failure is of fundamental importance. A flexible, high resolution, high sensitivity detector system for molecular imaging with radionuclides on small animal models has been designed for this aim. A prototype has been built using tungsten pinhole and LaBr3(Ce) scintillator coupled to Hamamatsu Flat Panel PMTs. Compact individual-channel readout has been designed, built and tested. Measurements with phantoms as well as pilot studies on mice have been performed, the results show that the myocardial perfusion in mice can be determined with sufficient precision. The detector will be improved replacing the Hamamatsu Flat Panel with Silicon Photomultipliers (SiPMs) to allow integration of the system with MRI scanners. Application of LaBr3(Ce) scintillator coupled to photosensor with high photon detection efficiency and excellent energy resolution will allow dual-label imaging to monitor simultaneously the cardiac perfusion and the molecular targets under investigation during the heart therapy.

Real-time monitoring of disintegration activity of catalytic core domain of HIV-1 integrase using molecular beacon.

PubMed

Zhang, Da-wei; Zhao, Ming-ming; He, Hong-qiu; Guo, Shun-xing

2013-09-15

HIV-1 integrase, an essential enzyme for retroviral replication, is a validated target for anti-HIV therapy development. The catalytic core domain of integrase (IN-CCD) is capable of catalyzing disintegration reaction. In this work, a hairpin-shaped disintegration substrate was designed and validated by enzyme-linked immunosorbent assay; a molecular beacon-based assay was developed for disintegration reaction of IN-CCD. Results showed that the disintegration substrate could be recognized and catalyzed by IN-CCD, and the disintegration reaction can be monitored according to the increase of fluorescent signal. The assay can be applied to real-time detection of disintegration with advantages of simplicity, high sensitivity, and excellent specificity. Copyright © 2013 Elsevier Inc. All rights reserved.

Detection of microparticles from human red blood cells by multiparametric flow cytometry

PubMed Central

Grisendi, Giulia; Finetti, Elena; Manganaro, Daniele; Cordova, Nicoletta; Montagnani, Giuliano; Spano, Carlotta; Prapa, Malvina; Guarneri, Valentina; Otsuru, Satoru; Horwitz, Edwin M.; Mari, Giorgio; Dominici, Massimo

2015-01-01

Background During storage, red blood cells (RBC) undergo chemical and biochemical changes referred to as “storage lesions”. These events determine the loss of RBC integrity, resulting in lysis and release of microparticles. There is growing evidence of the clinical importance of microparticles and their role in blood transfusion-related side effects and pathogen transmission. Flow cytometry is currently one of the most common techniques used to quantify and characterise microparticles. Here we propose multiparametric staining to monitor and quantify the dynamic release of microparticles by stored human RBC. Material and methods RBC units (n=10) were stored under blood bank conditions for up to 42 days. Samples were tested at different time points to detect microparticles and determine the haemolysis rate (HR%). Microparticles were identified by flow cytometry combining carboxyfluorescein diacetate succinimidyl ester (CFSE) dye, annexin V and anti-glycophorin A antibody. Results We demonstrated that CFSE can be successfully used to label closed vesicles with an intact membrane. The combination of CFSE and glycophorin A antibody was effective for monitoring and quantifying the dynamic release of microparticles from RBC during storage. Double staining with CFSE/glycophorin A was a more precise approach, increasing vesicle detection up to 4.7-fold vs the use of glycophorin A/annexin V alone. Moreover, at all the time points tested, we found a robust correlation (R=0.625; p=0.0001) between HR% and number of microparticles detected. Discussion Multiparametric staining, based on a combination of CFSE, glycophorin A antibody and annexin V, was able to detect, characterise and monitor the release of microparticles from RBC units during storage, providing a sensitive approach to labelling and identifying microparticles for transfusion medicine and, more broadly, for cell-based therapies. PMID:25369588

Early Detection of Physical Activity for People With Type 1 Diabetes Mellitus.

PubMed

Dasanayake, Isuru S; Bevier, Wendy C; Castorino, Kristin; Pinsker, Jordan E; Seborg, Dale E; Doyle, Francis J; Dassau, Eyal

2015-06-30

Early detection of exercise in individuals with type 1 diabetes mellitus (T1DM) may allow changes in therapy to prevent hypoglycemia. Currently there is limited experience with automated methods that detect the onset and end of exercise in this population. We sought to develop a novel method to quickly and reliably detect the onset and end of exercise in these individuals before significant changes in blood glucose (BG) occur. Sixteen adults with T1DM were studied as outpatients using a diary, accelerometer, heart rate monitor, and continuous glucose monitor for 2 days. These data were used to develop a principal component analysis based exercise detection method. Subjects also performed 60 and 30 minute exercise sessions at 30% and 50% predicted heart rate reserve (HRR), respectively. The detection method was applied to the exercise sessions to determine how quickly the detection of start and end of exercise occurred relative to change in BG. Mild 30% HRR and moderate 50% HRR exercise onset was identified in 6 ± 3 and 5 ± 2 (mean ± SD) minutes, while completion was detected in 3 ± 8 and 6 ± 5 minutes, respectively. BG change from start of exercise to detection time was 1 ± 6 and -1 ± 3 mg/dL, and, from the end of exercise to detection time was 6 ± 4 and -17 ± 13 mg/dL, respectively, for the 2 exercise sessions. False positive and negative ratios were 4 ± 2% and 21 ± 22%. The novel method for exercise detection identified the onset and end of exercise in approximately 5 minutes, with an average BG change of only -6 mg/dL. © 2015 Diabetes Technology Society.

T cell Bim levels reflect responses to anti–PD-1 cancer therapy

PubMed Central

Dronca, Roxana S.; Liu, Xin; Harrington, Susan M.; Chen, Lingling; Cao, Siyu; Kottschade, Lisa A.; McWilliams, Robert R.; Block, Matthew S.; Nevala, Wendy K.; Thompson, Michael A.; Mansfield, Aaron S.; Park, Sean S.; Markovic, Svetomir N.

2016-01-01

Immune checkpoint therapy with PD-1 blockade has emerged as an effective therapy for many advanced cancers; however, only a small fraction of patients achieve durable responses. To date, there is no validated blood-based means of predicting the response to PD-1 blockade. We report that Bim is a downstream signaling molecule of the PD-1 pathway, and its detection in T cells is significantly associated with expression of PD-1 and effector T cell markers. High levels of Bim in circulating tumor-reactive (PD-1+CD11ahiCD8+) T cells were prognostic of poor survival in patients with metastatic melanoma who did not receive anti–PD-1 therapy and were also predictive of clinical benefit in patients with metastatic melanoma who were treated with anti–PD-1 therapy. Moreover, this circulating tumor-reactive T cell population significantly decreased after successful anti–PD-1 therapy. Our study supports a crucial role of Bim in both T cell activation and apoptosis as regulated by PD-1 and PD-L1 interactions in effector CD8+ T cells. Measurement of Bim levels in circulating T cells of patients with cancer may provide a less invasive strategy to predict and monitor responses to anti–PD-1 therapy, although future prospective analyses are needed to validate its utility. PMID:27182556

Immunomodulatory therapies for acute pancreatitis

PubMed Central

Li, Jing; Yang, Wen-Juan; Huang, Lu-Ming; Tang, Cheng-Wei

2014-01-01

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (< 24 h), and appropriate immunostimulatory therapies should be administered during the period from the 3rd d to the 14th d in the course of AP. A combination therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. PMID:25493006

Complementary and Alternative Medicine Use for HIV Management in the State of Florida: Medical Monitoring Project

PubMed Central

Okafor, Chukwuemeka N.; Harman, Jeffrey S.; Canidate, Shantrel S.; Cook, Christa L.; Cook, Robert L.

2016-01-01

Abstract Objective: The aims of this study were to describe complementary and alternative medicine (CAM) use and to assess the relationships between CAM use and antiretroviral therapy (ART) adherence and human immunodeficiency virus (HIV) RNA viral load suppression among a sample of persons living with HIV (PLWH) engaged in care in the state of Florida. Design: The Florida Medical Monitoring Project (n = 803) collected repeated cross-sectional data for surveillance of clinical outcomes among PLWH from 2009 to 2010. Past-year CAM use specifically for the management of HIV was measured via self-report. Logistic regression models were conducted to assess the effect of CAM use on ART adherence and viral load suppression, controlling for demographic and clinical factors using backwards stepwise deletion of factors with a p-value of >0.25. Results: CAM use was reported in 53.3% (n = 428). In bivariate analysis, CAM use was the highest among those 40–49 years of age (61%; p < 0.05), males (56%; p < 0.01), whites (61%; p = 0.001), and those educated beyond high school (59%; p < 0.05). Among those using CAM, 63% and 37% reported one and two or more CAM modalities, respectively. CAM modalities included biologically based therapies (89%), mind–body medicine/manipulative body-based therapies (30%), spiritual healing (23%), energy therapies (6%), and whole medical systems (6%). In multivariable analyses, any CAM use and number of CAM methods used were not associated with ART adherence. Any CAM use was not associated with detectable viral load (adjusted odds ratio [aOR] 0.81; 95% confidence interval [CI] 0.58–1.12; p = 0.20). Those using two or more methods had significantly decreased risk for detectable viral load (aOR 0.60; 95% CI 0.39–0.92; p < 0.02). Conclusions: CAM use was not associated with negative effects on ART adherence. CAM users were less likely to have detectable viral load compared with non-users. Future research should focus on CAM use among PLWH not engaged in HIV care and the longitudinal patterns of CAM use and possible effects of long-term health outcomes. PMID:27631385

MONDO: a neutron tracker for particle therapy secondary emission characterisation

NASA Astrophysics Data System (ADS)

Marafini, M.; Gasparini, L.; Mirabelli, R.; Pinci, D.; Patera, V.; Sciubba, A.; Spiriti, E.; Stoppa, D.; Traini, G.; Sarti, A.

2017-04-01

Tumour control is performed in particle therapy using particles and ions, whose high irradiation precision enhances the effectiveness of the treatment, while sparing the healthy tissue surrounding the target volume. Dose range monitoring devices using photons and charged particles produced by the beam interacting with the patient’s body have already been proposed, but no attempt has been made yet to exploit the detection of the abundant neutron component. Since neutrons can release a significant dose far away from the tumour region, precise measurements of their flux, production energy and angle distributions are eagerly sought in order to improve the treatment planning system (TPS) software. It will thus be possible to predict not only the normal tissue toxicity in the target region, but also the risk of late complications in the whole body. The aforementioned issues underline the importance of an experimental effort devoted to the precise characterisation of neutron production, aimed at the measurement of their abundance, emission point and production energy. The technical challenges posed by a neutron detector aimed at high detection efficiency and good backtracking precision are addressed within the MONDO (monitor for neutron dose in hadrontherapy) project, whose main goal is to develop a tracking detector that can target fast and ultrafast neutrons. A full reconstruction of two consecutive elastic scattering interactions undergone by the neutrons inside the detector material will be used to measure their energy and direction. The preliminary results of an MC simulation performed using the FLUKA software are presented here, together with the DSiPM (digital SiPM) readout implementation. New detector readout implementations specifically tailored to the MONDO tracker are also discussed, and the neutron detection efficiency attainable with the proposed neutron tracking strategy are reported.

Neural activity based biofeedback therapy for Autism spectrum disorder through wearable wireless textile EEG monitoring system

NASA Astrophysics Data System (ADS)

Sahi, Ahna; Rai, Pratyush; Oh, Sechang; Ramasamy, Mouli; Harbaugh, Robert E.; Varadan, Vijay K.

2014-04-01

Mu waves, also known as mu rhythms, comb or wicket rhythms are synchronized patterns of electrical activity involving large numbers of neurons, in the part of the brain that controls voluntary functions. Controlling, manipulating, or gaining greater awareness of these functions can be done through the process of Biofeedback. Biofeedback is a process that enables an individual to learn how to change voluntary movements for purposes of improving health and performance through the means of instruments such as EEG which rapidly and accurately 'feedback' information to the user. Biofeedback is used for therapeutic purpose for Autism Spectrum Disorder (ASD) by focusing on Mu waves for detecting anomalies in brain wave patterns of mirror neurons. Conventional EEG measurement systems use gel based gold cup electrodes, attached to the scalp with adhesive. It is obtrusive and wires sticking out of the electrodes to signal acquisition system make them impractical for use in sensitive subjects like infants and children with ASD. To remedy this, sensors can be incorporated with skull cap and baseball cap that are commonly used for infants and children. Feasibility of Textile based Sensor system has been investigated here. Textile based multi-electrode EEG, EOG and EMG monitoring system with embedded electronics for data acquisition and wireless transmission has been seamlessly integrated into fabric of these items for continuous detection of Mu waves. Textile electrodes were placed on positions C3, CZ, C4 according to 10-20 international system and their capability to detect Mu waves was tested. The system is ergonomic and can potentially be used for early diagnosis in infants and planning therapy for ASD patients.

Design of a surface plasmon resonance immunoassay for therapeutic drug monitoring of amikacin.

PubMed

Losoya-Leal, Adrian; Estevez, M-Carmen; Martínez-Chapa, Sergio O; Lechuga, Laura M

2015-08-15

The therapeutic drug monitoring (TDM) of pharmaceutical drugs with narrow therapeutic ranges is of great importance in the clinical setting. It provides useful information towards the enhancement of drug therapies, aiding in dosage control and toxicity risk management. Amikacin is an aminoglycoside antibiotic commonly used in neonatal therapies that is indicated for TDM due to the toxicity risks inherent in its use. Current techniques for TDM such as high performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) are costly, time consuming, and cannot be performed at the site of action. Over the last decades, surface plasmon resonance (SPR) biosensors have become increasingly popular in clinical diagnostics due to their ability to detect biomolecular interactions in real-time. We present an SPR-based competitive immunoassay for the detection of the antibiotic amikacin, suitable for TDM in both adults and neonates. We have obtained high specificity and sensitivity levels with an IC50 value of 1.4ng/mL and a limit of detection of 0.13ng/mL, which comfortably comply with the drug's therapeutic range. Simple dilution of serum can therefore be sufficient to analyze low-volume real samples from neonates, increasing the potential of the methodology for TDM. Compared to current TDM conventional methods, this SPR-based immunoassay can provide advantages such as simplicity, potential portability, and label-free measurements with the possibility of high throughput. This work is the foundation towards the development of an integrated, simple use, highly sensitive, fast, and point-of-care sensing platform for the opportune TDM of antibiotics and other drugs in a clinical setting. Copyright © 2015 Elsevier B.V. All rights reserved.

MONDO: a neutron tracker for particle therapy secondary emission characterisation.

PubMed

Marafini, M; Gasparini, L; Mirabelli, R; Pinci, D; Patera, V; Sciubba, A; Spiriti, E; Stoppa, D; Traini, G; Sarti, A

2017-04-21

Tumour control is performed in particle therapy using particles and ions, whose high irradiation precision enhances the effectiveness of the treatment, while sparing the healthy tissue surrounding the target volume. Dose range monitoring devices using photons and charged particles produced by the beam interacting with the patient's body have already been proposed, but no attempt has been made yet to exploit the detection of the abundant neutron component. Since neutrons can release a significant dose far away from the tumour region, precise measurements of their flux, production energy and angle distributions are eagerly sought in order to improve the treatment planning system (TPS) software. It will thus be possible to predict not only the normal tissue toxicity in the target region, but also the risk of late complications in the whole body. The aforementioned issues underline the importance of an experimental effort devoted to the precise characterisation of neutron production, aimed at the measurement of their abundance, emission point and production energy. The technical challenges posed by a neutron detector aimed at high detection efficiency and good backtracking precision are addressed within the MONDO (monitor for neutron dose in hadrontherapy) project, whose main goal is to develop a tracking detector that can target fast and ultrafast neutrons. A full reconstruction of two consecutive elastic scattering interactions undergone by the neutrons inside the detector material will be used to measure their energy and direction. The preliminary results of an MC simulation performed using the FLUKA software are presented here, together with the DSiPM (digital SiPM) readout implementation. New detector readout implementations specifically tailored to the MONDO tracker are also discussed, and the neutron detection efficiency attainable with the proposed neutron tracking strategy are reported.

Drug detection in breath: non-invasive assessment of illicit or pharmaceutical drugs.

PubMed

Trefz, Phillip; Kamysek, Svend; Fuchs, Patricia; Sukul, Pritam; Schubert, Jochen K; Miekisch, Wolfram

2017-03-20

Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towards personalized medicine. This review gives an overview of the current state of drug detection in breath, including both volatile and non-volatile substances. The review is divided into two sections. The first section deals with qualitative detection of drugs (drugs of abuse), while the second is related to quantitative drug detection (medical drugs). Chances and limitations are discussed for both aspects. The detection of the intravenous anesthetic propofol is presented as a detailed example that demonstrates the potential, requirements, pitfalls and limitations of therapeutic drug monitoring by means of breath analysis.

Alarmin S100A8/S100A9 as a biomarker for molecular imaging of local inflammatory activity.

PubMed

Vogl, Thomas; Eisenblätter, Michel; Völler, Tom; Zenker, Stefanie; Hermann, Sven; van Lent, Peter; Faust, Andreas; Geyer, Christiane; Petersen, Beatrix; Roebrock, Kirsten; Schäfers, Michael; Bremer, Christoph; Roth, Johannes

2014-08-06

Inflammation has a key role in the pathogenesis of various human diseases. The early detection, localization and monitoring of inflammation are crucial for tailoring individual therapies. However, reliable biomarkers to detect local inflammatory activities and to predict disease outcome are still missing. Alarmins, which are locally released during cellular stress, are early amplifiers of inflammation. Here, using optical molecular imaging, we demonstrate that the alarmin S100A8/S100A9 serves as a sensitive local and systemic marker for the detection of even sub-clinical disease activity in inflammatory and immunological processes like irritative and allergic contact dermatitis. In a model of collagen-induced arthritis, we use S100A8/S100A9 imaging to predict the development of disease activity. Furthermore, S100A8/S100A9 can act as a very early and sensitive biomarker in experimental leishmaniasis for phagocyte activation linked to an effective Th1-response. In conclusion, the alarmin S100A8/S100A9 is a valuable and sensitive molecular target for novel imaging approaches to monitor clinically relevant inflammatory disorders on a molecular level.

Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam

PubMed Central

Greiner-Sosanko, Elizabeth; Giannoutsos, Spiros; Lower, Darla R.; Virji, Mohamed A.; Krasowski, Matthew D.

2008-01-01

A high-performance liquid chromatography (HPLC) assay using ultraviolet detection is described for the simultaneous measurement of the newer generation anti-epileptic medications lamotrigine, oxcarbazepine (parent drug and active metabolite 10-hydroxycarbazepine), and zonisamide. Detection of all four compounds can be done at 230 nm; however, there is a potential interference with zonisamide in patients on clonazepam therapy. Therefore, the method uses dual wavelength detection: 230 nm for oxcarbazepine and 10-hydroxycarbazepine and 270 nm for lamotrigine and zonisamide. In addition, a simple gas chromatography method using a nitrogen-phosphorus detector is described for measurement of levetiracetam, another of the recently approved anti-epileptic medications. For both methods, limits of quantitation, linearities, accuracies, and imprecisions cover the therapeutic range for drug monitoring of patients. A wide variety of clinical drugs, including other anti-epileptic drugs, do not interfere with these assays. These procedures would be of special interest to clinical laboratories, particularly due to the limited availability of immunoassays for newer generation anti-epileptic medications and that therapeutic uses of these drugs are expanding beyond epilepsy to other neurologic and psychiatric disorders. PMID:17988451

Activation of Phosphatidylcholine-Specific Phospholipase C in Breast and Ovarian Cancer: Impact on MRS-Detected Choline Metabolic Profile and Perspectives for Targeted Therapy

PubMed Central

Podo, Franca; Paris, Luisa; Cecchetti, Serena; Spadaro, Francesca; Abalsamo, Laura; Ramoni, Carlo; Ricci, Alessandro; Pisanu, Maria Elena; Sardanelli, Francesco; Canese, Rossella; Iorio, Egidio

2016-01-01

Elucidation of molecular mechanisms underlying the aberrant phosphatidylcholine cycle in cancer cells plays in favor of the use of metabolic imaging in oncology and opens the way for designing new targeted therapies. The anomalous choline metabolic profile detected in cancer by magnetic resonance spectroscopy and spectroscopic imaging provides molecular signatures of tumor progression and response to therapy. The increased level of intracellular phosphocholine (PCho) typically detected in cancer cells is mainly attributed to upregulation of choline kinase, responsible for choline phosphorylation in the biosynthetic Kennedy pathway, but can also be partly produced by activation of phosphatidylcholine-specific phospholipase C (PC-PLC). This hydrolytic enzyme, known for implications in bacterial infection and in plant survival to hostile environmental conditions, is reported to be activated in mitogen- and oncogene-induced phosphatidylcholine cycles in mammalian cells, with effects on cell signaling, cell cycle regulation, and cell proliferation. Recent investigations showed that PC-PLC activation could account for 20–50% of the intracellular PCho production in ovarian and breast cancer cells of different subtypes. Enzyme activation was associated with PC-PLC protein overexpression and subcellular redistribution in these cancer cells compared with non-tumoral counterparts. Moreover, PC-PLC coimmunoprecipitated with the human epidermal growth factor receptor-2 (HER2) and EGFR in HER2-overexpressing breast and ovarian cancer cells, while pharmacological PC-PLC inhibition resulted into long-lasting HER2 downregulation, retarded receptor re-expression on plasma membrane and antiproliferative effects. This body of evidence points to PC-PLC as a potential target for newly designed therapies, whose effects can be preclinically and clinically monitored by metabolic imaging methods. PMID:27532027

Follow-up segmentation of lung tumors in PET and CT data

NASA Astrophysics Data System (ADS)

Opfer, Roland; Kabus, Sven; Schneider, Torben; Carlsen, Ingwer C.; Renisch, Steffen; Sabczynski, Jörg

2009-02-01

Early response assessment of cancer therapy is a crucial component towards a more effective and patient individualized cancer therapy. Integrated PET/CT systems provide the opportunity to combine morphologic with functional information. We have developed algorithms which allow the user to track both tumor volume and standardized uptake value (SUV) measurements during the therapy from series of CT and PET images, respectively. To prepare for tumor volume estimation we have developed a new technique for a fast, flexible, and intuitive 3D definition of meshes. This initial surface is then automatically adapted by means of a model-based segmentation algorithm and propagated to each follow-up scan. If necessary, manual corrections can be added by the user. To determine SUV measurements a prioritized region growing algorithm is employed. For an improved workflow all algorithms are embedded in a PET/CT therapy monitoring software suite giving the clinician a unified and immediate access to all data sets. Whenever the user clicks on a tumor in a base-line scan, the courses of segmented tumor volumes and SUV measurements are automatically identified and displayed to the user as a graph plot. According to each course, the therapy progress can be classified as complete or partial response or as progressive or stable disease. We have tested our methods with series of PET/CT data from 9 lung cancer patients acquired at Princess Margaret Hospital in Toronto. Each patient underwent three PET/CT scans during a radiation therapy. Our results indicate that a combination of mean metabolic activity in the tumor with the PET-based tumor volume can lead to an earlier response detection than a purely volume based (CT diameter) or purely functional based (e.g. SUV max or SUV mean) response measures. The new software seems applicable for easy, faster, and reproducible quantification to routinely monitor tumor therapy.

HIV-1 Viral Escape in Cerebrospinal Fluid of Subjects on Suppressive Antiretroviral Treatment

PubMed Central

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W.; Gisslén, Magnus

2010-01-01

Background. Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Methods. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Results. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54–213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Conclusions. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice. PMID:21050119

HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment.

PubMed

Edén, Arvid; Fuchs, Dietmar; Hagberg, Lars; Nilsson, Staffan; Spudich, Serena; Svennerholm, Bo; Price, Richard W; Gisslén, Magnus

2010-12-15

Occasional cases of viral escape in cerebrospinal fluid (CSF) despite suppression of plasma human immunodeficiency virus type 1 (HIV-1) RNA have been reported. We investigated CSF viral escape in subjects treated with commonly used antiretroviral therapy regimens in relation to intrathecal immune activation and central nervous system penetration effectiveness (CPE) rank. Sixty-nine neurologically asymptomatic subjects treated with antiretroviral therapy >6 months and plasma HIV-1 RNA <50 copies/mL were cross-sectionally included in the analysis. Antiretroviral therapy regimens included efavirenz, lopinavir/ritonavir or atazanavir/ritonavir combined with tenofovir, abacavir, or zidovudine and emtricitabine or lamivudine. HIV-1 RNA was analyzed with real-time polymerase chain reaction assays. Neopterin was analyzed by enzyme-linked immunosorbent assay. Seven (10%) of the 69 subjects had detectable CSF HIV-1 RNA, in median 121 copies/mL (interquartile range, 54-213 copies/mL). Subjects with detectable CSF virus had significantly higher CSF neopterin and longer duration of treatment. Previous treatment interruptions were more common in subjects with CSF escape. Central nervous system penetration effectiveness rank was not a significant predictor of detectable CSF virus or CSF neopterin levels. Viral escape in CSF is more common than previously reported, suggesting that low-grade central nervous system infection may continue in treated patients. Although these findings need extension in longitudinal studies, they suggest the utility of monitoring CSF responses, as new treatment combinations and strategies modify clinical practice.

Wireless patient monitoring on shoe for the assessment of foot dysfunction: an overview

NASA Astrophysics Data System (ADS)

Abraham, Jose K.; Whitchurch, Ashwin K.; Varadan, Vijay K.; Sarukesi, Karunakaran

2003-04-01

This paper presents an overview of the wireless monitoring and quantitative assessment of joint dynamics of ankle which has suffered from soft tissue injury, immobilization or any dysfunction with special focus on the treatment and rehabilitation applications. The inadequacy of a reliable and easy method for continuous measurement and recording of ankle movement while doing physical therapy makes the monitoring of its progress difficult. Development of a wireless ankle motion monitoring system inside the shoe provides information on several aspects of activities associated with a dysfunctional foot. The system is based on continuous wireless monitoring of signals from accelerometers and gyroscopes fixed inside the shoe. From these signals, the duration, rate, and moment of occurrence of activities associated with mobility (e.g., lying, sitting, standing, walking up and down, running, cycling, wheelchair use and general movement) and transitions (changes in angle) can be detected. Information about the movement can be obtained by the acceleration sensors, which is related to the intensity of body-segment movement. Apart from monitoring accelerations, other signals due to turning and angular movements can be obtained using the miniature gyroscope attached to the shoe.

Practice-based learning and systems-based practice: detection and treatment monitoring of generalized anxiety and depression in primary care.

PubMed

Zupancic, Melanie; Yu, Siegfried; Kandukuri, Rajeev; Singh, Shilpa; Tumyan, Anna

2010-09-01

Quality assurance/quality improvement projects are an important part of professional development in graduate medical education. The purpose of our quality improvement study was to evaluate whether (1) the Generalized Anxiety Disorder (GAD-7) scale questionnaire increases detection of anxiety and (2) the Quick Inventory for Depressive Symptomatology Self Report (QIDS-SR) increases detection of depression in a primary care setting. We also aimed to determine whether monitoring patients with depression or generalized anxiety using the QIDS-SR and GAD-7 scales influences treatment changes in the primary care setting. Patients seen in a general internal medicine clinic between August 2008 and March 2009 were asked to fill out the QID-SR questionnaire and GAD-7 as part of a resident quality improvement project. We measured the prevalence of anxiety and depression during 6 months prior to the use of the GAD-7 and QIDS-SR instruments during the intervention period. We also compared the frequency of treatment changes initiated both 12 months prior to and during the intervention period. The aforementioned measures were performed with use of a retrospective chart review. The prevalence of anxiety was 15.2% in the pre-intervention period and 33.3% in the intervention period, and the prevalence of depression was 38.9% in the prescreening period and 54.8% during the screening period (P value for both was <0.001). The change in anxiety therapy was 21.6% in the prescreening period and 62.2% in the screening period (P  =  .028). The change in depression therapy was 23.2% in the pre-intervention period and 52.1% in the intervention period (P  =  .025). Routine screening for depression and anxiety may help clinicians detect previously undiagnosed anxiety and depression and also may facilitate identification of needed treatment changes. Further work is needed to determine whether routine screening improves patient outcomes.

Nanotechnology for the detection and therapy of stroke.

PubMed

Kyle, Stuart; Saha, Sikha

2014-11-01

Over the years, nanotechnology has greatly developed, moving from careful design strategies and synthesis of novel nanostructures to producing them for specific medical and biological applications. The use of nanotechnology in diagnostics, drug delivery, and tissue engineering holds great promise for the treatment of stroke in the future. Nanoparticles are employed to monitor grafted cells upon implantation, or to enhance the imagery of the tissue, which is coupled with a noninvasive imaging modality such as magnetic resonance imaging, computed axial tomography or positron emission tomography scan. Contrast imaging agents used can range from iron oxide, perfluorocarbon, cerium oxide or platinum nanoparticles to quantum dots. The use of nanomaterial scaffolds for neuroregeneration is another area of nanomedicine, which involves the creation of an extracellular matrix mimic that not only serves as a structural support but promotes neuronal growth, inhibits glial differentiation, and controls hemostasis. Promisingly, carbon nanotubes can act as scaffolds for stem cell therapy and functionalizing these scaffolds may enhance their therapeutic potential for treatment of stroke. This Progress Report highlights the recent developments in nanotechnology for the detection and therapy of stroke. Recent advances in the use of nanomaterials as tissue engineering scaffolds for neuroregeneration will also be discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

New Approaches to Sepsis: Molecular Diagnostics and Biomarkers

PubMed Central

Bauer, Michael; Riedemann, Niels C.; Hartog, Christiane S.

2012-01-01

Summary: Sepsis is among the most common causes of death in hospitals. It arises from the host response to infection. Currently, diagnosis relies on nonspecific physiological criteria and culture-based pathogen detection. This results in diagnostic uncertainty, therapeutic delays, the mis- and overuse of antibiotics, and the failure to identify patients who might benefit from immunomodulatory therapies. There is a need for new sepsis biomarkers that can aid in therapeutic decision making and add information about screening, diagnosis, risk stratification, and monitoring of the response to therapy. The host response involves hundreds of mediators and single molecules, many of which have been proposed as biomarkers. It is, however, unlikely that one single biomarker is able to satisfy all the needs and expectations for sepsis research and management. Among biomarkers that are measurable by assays approved for clinical use, procalcitonin (PCT) has shown some usefulness as an infection marker and for antibiotic stewardship. Other possible new approaches consist of molecular strategies to improve pathogen detection and molecular diagnostics and prognostics based on transcriptomic, proteomic, or metabolic profiling. Novel approaches to sepsis promise to transform sepsis from a physiologic syndrome into a group of distinct biochemical disorders and help in the development of better diagnostic tools and effective adjunctive sepsis therapies. PMID:23034322

Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?

PubMed

Baig, Abdul Mannan; Khan, Naveed Ahmed; Abbas, Farhat

2015-03-01

Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.

SU-D-304-07: Application of Proton Boron Fusion Reaction to Radiation Therapy

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

Jung, J; Yoon, D; Shin, H

Purpose: we present the introduction of a therapy method using the proton boron fusion reaction. The purpose of this study is to verify the theoretical validity of proton boron fusion therapy using Monte Carlo simulations. Methods: After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton’s maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here we show thatmore » the effectiveness of the proton boron fusion therapy (PBFT) was verified using Monte Carlo simulations. Results: We found that a dramatic increase by more than half of the proton’s maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton’s maximum dose point was located within the boron uptake region (BUR). In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. Conclusion: This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

Quantitative multi-target RNA profiling in Epstein-Barr virus infected tumor cells.

PubMed

Greijer, A E; Ramayanti, O; Verkuijlen, S A W M; Novalić, Z; Juwana, H; Middeldorp, J M

2017-03-01

Epstein-Barr virus (EBV) is etiologically linked to multiple acute, chronic and malignant diseases. Detection of EBV-RNA transcripts in tissues or biofluids besides EBV-DNA can help in diagnosing EBV related syndromes. Sensitive EBV transcription profiling yields new insights on its pathogenic role and may be useful for monitoring virus targeted therapy. Here we describe a multi-gene quantitative RT-PCR profiling method that simultaneously detects a broad spectrum (n=16) of crucial latent and lytic EBV transcripts. These transcripts include (but are not restricted to), EBNA1, EBNA2, LMP1, LMP2, BARTs, EBER1, BARF1 and ZEBRA, Rta, BGLF4 (PK), BXLF1 (TK) and BFRF3 (VCAp18) all of which have been implicated in EBV-driven oncogenesis and viral replication. With this method we determine the amount of RNA copies per infected (tumor) cell in bulk populations of various origin. While we confirm the expected RNA profiles within classic EBV latency programs, this sensitive quantitative approach revealed the presence of rare cells undergoing lytic replication. Inducing lytic replication in EBV tumor cells supports apoptosis and is considered as therapeutic approach to treat EBV-driven malignancies. This sensitive multi-primed quantitative RT-PCR approach can provide broader understanding of transcriptional activity in latent and lytic EBV infection and is suitable for monitoring virus-specific therapy responses in patients with EBV associated cancers. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Prostate tumor alignment and continuous, real-time adaptive radiation therapy using electromagnetic fiducials: clinical and cost-utility analyses.

PubMed

Quigley, Martin M; Mate, Timothy P; Sylvester, John E

2009-01-01

To evaluate the accuracy, utility, and cost effectiveness of a new electromagnetic patient positioning and continuous, real-time monitoring system, which uses permanently implanted resonant transponders in the target (Calypso 4D Localization System and Beacon transponders, Seattle, WA) to continuously monitor tumor location and movement during external beam radiation therapy of the prostate. This clinical trial studied 43 patients at 5 sites. All patients were implanted with 3 transponders each. In 41 patients, the system was used for initial alignment at each therapy session. Thirty-five patients had continuous monitoring during their radiation treatment. Over 1,000 alignment comparisons were made to a commercially available kV X-ray positioning system (BrainLAB ExacTrac, Munich, Germany). Using decision analysis and Markov processes, the outcomes of patients were simulated over a 5-year period and measured in terms of costs from a payer's perspective and quality-adjusted life years (QALYs). All patients had satisfactory transponder implantations for monitoring purposes. In over 75% of the treatment sessions, the correction to conventional positioning (laser and tattoos) directed by an electromagnetic patient positioning and monitoring system was greater than 5 mm. Ninety-seven percent (34/35) of the patients who underwent continuous monitoring had target motion that exceeded preset limits at some point during the course of their radiation therapy. Exceeding preset thresholds resulted in user intervention at least once during the therapy in 80% of the patients (28/35). Compared with localization using ultrasound, electronic portal imaging devices (EPID), or computed tomography (CT), localization with the electromagnetic patient positioning and monitoring system yielded superior gains in QALYs at comparable costs. Most patients positioned with conventional tattoos and lasers for prostate radiation therapy were found by use of the electromagnetic patient positioning and monitoring system to have alignment errors exceeding 5 mm. Almost all patients undergoing external beam radiation of the prostate have been shown to have target organ movement exceeding 3 mm during radiation therapy delivery. The ability of the electromagnetic technology to monitor tumor target location during the same time as radiation therapy is being delivered allows clinicians to provide real time adaptive radiation therapy for prostate cancer. This permits clinicians to intervene when the prostate moves outside the radiation isocenter, which should decrease adverse events and improve patient outcomes. Additionally, a cost-utility analysis has demonstrated that the electromagnetic patient positioning and monitoring system offers patient outcome benefits at a cost that falls well within the payer's customary willingness to pay (WTP) threshold of $50,000 per QALY.

Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction.

PubMed

Zhang, Li-Yong; Xing, Tao; Du, Li-Xin; Li, Qing-Min; Liu, Wei-Dong; Wang, Ji-Yue; Cai, Jing

2015-01-01

Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice.

Applications of Molecular Imaging

PubMed Central

Galbán, Craig; Galbán, Stefanie; Van Dort, Marcian; Luker, Gary D.; Bhojani, Mahaveer S.; Rehemtualla, Alnawaz; Ross, Brian D.

2015-01-01

Today molecular imaging technologies play a central role in clinical oncology. The use of imaging techniques in early cancer detection, treatment response and new therapy development is steadily growing and has already significantly impacted clinical management of cancer. In this chapter we will overview three different molecular imaging technologies used for the understanding of disease biomarkers, drug development, or monitoring therapeutic outcome. They are (1) optical imaging (bioluminescence and fluorescence imaging) (2) magnetic resonance imaging (MRI), and (3) nuclear imaging (e.g, single photon emission computed tomography (SPECT) and positron emission tomography (PET)). We will review the use of molecular reporters of biological processes (e.g. apoptosis and protein kinase activity) for high throughput drug screening and new cancer therapies, diffusion MRI as a biomarker for early treatment response and PET and SPECT radioligands in oncology. PMID:21075334

Reducing bone lead content by chelation treatment in chronic lead poisoning: an in vivo X-ray fluorescence and bone biopsy study

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

Batuman, V.; Wedeen, R.P.; Bogden, J.D.

1989-02-01

A stained-glass artist with longstanding exposure to lead presented with neuropsychiatric symptoms. He was evaluated before and after chelation treatment by the CaNa2 EDTA lead mobilization test, iliac crest bone lead measurement, and in vivo tibial X-ray fluorescence (XRF). The three methods showed a progressive fall in body lead stores during chelation therapy in association with improvement in symptoms and a fall in blood lead and zinc protoporphyrin levels. In vivo tibial XRF is a safe, rapid, and noninvasive technique for detecting excessive body lead burdens. XRF measurement of bone lead content is a practical method for monitoring the efficacymore » of therapy as well as for establishing the diagnosis.« less

Initial clinical evaluation of PET-based ion beam therapy monitoring under consideration of organ motion

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

Kurz, Christopher, E-mail: christopher.kurz@physik.uni-muenchen.de; Bauer, Julia; Unholtz, Daniel

2016-02-15

Purpose: Intrafractional organ motion imposes considerable challenges to scanned ion beam therapy and demands for a thorough verification of the applied treatment. At the Heidelberg Ion-Beam Therapy Center (HIT), the scanned ion beam delivery is verified by means of postirradiation positron-emission-tomography (PET) imaging. This work presents a first clinical evaluation of PET-based treatment monitoring in ion beam therapy under consideration of target motion. Methods: Three patients with mobile liver lesions underwent scanned carbon ion irradiation at HIT and postirradiation PET/CT (x-ray-computed-tomography) imaging with a commercial scanner. Respiratory motion was recorded during irradiation and subsequent image acquisition. This enabled a time-resolvedmore » (4D) calculation of the expected irradiation-induced activity pattern and, for one patient where an additional 4D CT was acquired at the PET/CT scanner after treatment, a motion-compensated PET image reconstruction. For the other patients, PET data were reconstructed statically. To verify the treatment, calculated prediction and reconstructed measurement were compared with a focus on the ion beam range. Results: Results in the current three patients suggest that for motion amplitudes in the order of 2 mm there is no benefit from incorporating respiratory motion information into PET-based treatment monitoring. For a target motion in the order of 10 mm, motion-related effects become more severe and a time-resolved modeling of the expected activity distribution can lead to an improved data interpretation if a sufficient number of true coincidences is detected. Benefits from motion-compensated PET image reconstruction could not be shown conclusively at the current stage. Conclusions: The feasibility of clinical PET-based treatment verification under consideration of organ motion has been shown for the first time. Improvements in noise-robust 4D PET image reconstruction are deemed necessary to enhance the clinical potential.« less

Spatial and Temporal Monitoring Resolutions for CO2 Leakage Detection at Carbon Storage Sites

NASA Astrophysics Data System (ADS)

Yang, Y. M.; Dilmore, R. M.; Daley, T. M.; Carroll, S.; Mansoor, K.; Gasperikova, E.; Harbert, W.; Wang, Z.; Bromhal, G. S.; Small, M.

2016-12-01

Different leakage monitoring techniques offer different strengths in detection sensitivity, coverage, feedback time, cost, and technology availability, such that they may complement each other when applied together. This research focuses on quantifying the spatial coverage and temporal resolution of detection response for several geophysical remote monitoring and direct groundwater monitoring techniques for an optimal monitoring plan for CO2 leakage detection. Various monitoring techniques with different monitoring depths are selected: 3D time-lapse seismic survey, wellbore pressure, groundwater chemistry and soil gas. The spatial resolution in terms of leakage detectability is quantified through the effective detection distance between two adjacent monitors, given the magnitude of leakage and specified detection probability. The effective detection distances are obtained either from leakage simulations with various monitoring densities or from information garnered from field test data. These spatial leakage detection resolutions are affected by physically feasible monitoring design and detection limits. Similarly, the temporal resolution, in terms of leakage detectability, is quantified through the effective time to positive detection of a given size of leak and a specified detection probability, again obtained either from representative leakage simulations with various monitoring densities or from field test data. The effective time to positive detection is also affected by operational feedback time (associated with sampling, sample analysis and data interpretation), with values obtained mainly through expert interviews and literature review. In additional to the spatial and temporal resolutions of these monitoring techniques, the impact of CO2 plume migration speed and leakage detection sensitivity of each monitoring technique are also discussed with consideration of how much monitoring is necessary for effective leakage detection and how these monitoring techniques can be better combined in a time-space framework. The results of the spatial and temporal leakage detection resolutions for several geophysical monitoring techniques and groundwater monitoring are summarized to inform future monitoring designs at carbon storage sites.

The cost-effectiveness of hepatic venous pressure gradient monitoring in the prevention of recurrent variceal hemorrhage.

PubMed

Targownik, Laura E; Spiegel, Brennan M R; Dulai, Gareth S; Karsan, Hetal A; Gralnek, Ian M

2004-07-01

Recurrent variceal hemorrhage is common following an initial bleed in patients with cirrhosis. The current standard of care for secondary prophylaxis is endoscopic band ligation (EBL). Combination of beta-blocker and nitrate therapy, guided by hepatic venous pressure gradient (HVPG) monitoring, is a novel alternative strategy. We sought to determine the cost-effectiveness of these competing strategies. Decision analysis with Markov modeling was used to calculate the cost-effectiveness of three competing strategies: (1) EBL; (2) beta-blocker and nitrate therapy without HVPG monitoring (HVPG-); and (3) beta-blocker and nitrate therapy with HVPG monitoring (HVPG+). Patients in the HVPG+ strategy who failed to achieve an HVPG decline from medical therapy were offered EBL. Cost estimates were from a third-party payer perspective. The main outcome measure was the cost per recurrent variceal hemorrhage prevented. Under base-case conditions, the HVPG+ strategy was the most effective yet most expensive approach, followed by EBL and HVPG-. Compared to the EBL strategy, the HVPG+ strategy cost an incremental 5,974 dollars per recurrent bleed prevented. In a population with 100% compliance with all therapies, the incremental cost of HVPG-versus EBL fell to 5,270 dollars per recurrent bleed prevented. The model results were sensitive to the cost of EBL, the cost of HVPG monitoring, and the probability of medical therapy producing an adequate HVPG decline. Compared to EBL for the secondary prophylaxis of variceal rebleeding, combination medical therapy guided by HVPG monitoring is more effective and only marginally more expensive.

Current and Emerging Therapies in Multiple Sclerosis: Implications for the Radiologist, Part 2-Surveillance for Treatment Complications and Disease Progression.

PubMed

McNamara, C; Sugrue, G; Murray, B; MacMahon, P J

2017-09-01

An understanding of the new generation of MS drugs in conjunction with the key role MR imaging plays in the detection of disease progression, opportunistic infections, and drug-related adverse effects is of vital importance to the neuroradiologist. Part 1 of this review outlined the current treatment options available for MS and examined the mechanisms of action of the various medications. It also covered specific complications associated with each form of therapy. Part 2, in turn deals with the subject of pharmacovigilance and the optimal frequency of MRI monitoring for each individual patient, depending on his or her unique risk profile. Special attention is given to the diagnosing of progressive multifocal leukoencephalopathy in patients treated with natalizumab as this is a key area in which neuroradiologists can contribute to improved patient outcomes. This article also outlines the aims of treatment and reviews the possibility of "no evidence of disease activity" becoming a treatment goal with the availability of more effective therapies. Potential future areas and technologies including image subtraction, brain volume measurement and advanced imaging techniques such as double inversion recovery are also reviewed. It is anticipated that such advancements in this rapidly developing field will improve the accuracy of monitoring an individual patient's response to treatment. © 2017 by American Journal of Neuroradiology.

Automatic lesion tracking for a PET/CT based computer aided cancer therapy monitoring system

NASA Astrophysics Data System (ADS)

Opfer, Roland; Brenner, Winfried; Carlsen, Ingwer; Renisch, Steffen; Sabczynski, Jörg; Wiemker, Rafael

2008-03-01

Response assessment of cancer therapy is a crucial component towards a more effective and patient individualized cancer therapy. Integrated PET/CT systems provide the opportunity to combine morphologic with functional information. However, dealing simultaneously with several PET/CT scans poses a serious workflow problem. It can be a difficult and tedious task to extract response criteria based upon an integrated analysis of PET and CT images and to track these criteria over time. In order to improve the workflow for serial analysis of PET/CT scans we introduce in this paper a fast lesion tracking algorithm. We combine a global multi-resolution rigid registration algorithm with a local block matching and a local region growing algorithm. Whenever the user clicks on a lesion in the base-line PET scan the course of standardized uptake values (SUV) is automatically identified and shown to the user as a graph plot. We have validated our method by a data collection from 7 patients. Each patient underwent two or three PET/CT scans during the course of a cancer therapy. An experienced nuclear medicine physician manually measured the courses of the maximum SUVs for altogether 18 lesions. As a result we obtained that the automatic detection of the corresponding lesions resulted in SUV measurements which are nearly identical to the manually measured SUVs. Between 38 measured maximum SUVs derived from manual and automatic detected lesions we observed a correlation of 0.9994 and a average error of 0.4 SUV units.

Time-resolved singlet oxygen luminescence detection under photodynamic therapy relevant conditions: comparison of ex vivo application of two photosensitizer formulations

NASA Astrophysics Data System (ADS)

Schlothauer, Jan C.; Hackbarth, Steffen; Jäger, Lutz; Drobniewski, Kai; Patel, Hemantbhai; Gorun, Sergiu M.; Röder, Beate

2012-11-01

Singlet oxygen plays a crucial role in photo-dermatology and photodynamic therapy (PDT) of cancer. Its direct observation by measuring the phosphorescence at 1270 nm, however, is still challenging due to the very low emission probability. It is especially challenging for the time-resolved detection of singlet oxygen kinetics in vivo which is of special interest for biomedical applications. Photosensitized generation of singlet oxygen, in pig ear skin as model for human skin, is investigated here. Two photosensitizers (PS) were topically applied to the pig ear skin and examined in a comparative study, which include the amphiphilic pheophorbide-a and the highly hydrophobic perfluoroalkylated zinc phthalocyanine (F64PcZn). Fluorescence microscopy indicates the exclusive accumulation of pheophorbide-a in the stratum corneum, while F64PcZn can also accumulate in deeper layers of the epidermis of the pig ear skin. The kinetics obtained with phosphorescence measurements show the singlet oxygen interaction with the PS microenvironment. Different generation sites of singlet oxygen correlate with the luminescence kinetics. The results show that singlet oxygen luminescence detection can be used as a diagnostic tool, not only for research, but also during treatment. The detection methodology is suitable for the monitoring of chemical quenchers' oxidation as well as O2 saturation at singlet oxygen concentration levels relevant to PDT treatment protocols.

Specific Detection of Naturally Occurring Hepatitis C Virus Mutants with Resistance to Telaprevir and Boceprevir (Protease Inhibitors) among Treatment-Naïve Infected Individuals

PubMed Central

Fonseca-Coronado, Salvador; Escobar-Gutiérrez, Alejandro; Ruiz-Tovar, Karina; Cruz-Rivera, Mayra Yolanda; Rivera-Osorio, Pilar; Vazquez-Pichardo, Mauricio; Carpio-Pedroza, Juan Carlos; Ruíz-Pacheco, Juan Alberto; Cazares, Fernando

2012-01-01

The use of telaprevir and boceprevir, both protease inhibitors (PI), as part of the specifically targeted antiviral therapy for hepatitis C (STAT-C) has significantly improved sustained virologic response (SVR) rates. However, different clinical studies have also identified several mutations associated with viral resistance to both PIs. In the absence of selective pressure, drug-resistant hepatitis C virus (HCV) mutants are generally present at low frequency, making mutation detection challenging. Here, we describe a mismatch amplification mutation assay (MAMA) PCR method for the specific detection of naturally occurring drug-resistant HCV mutants. MAMA PCR successfully identified the corresponding HCV variants, while conventional methods such as direct sequencing, endpoint limiting dilution (EPLD), and bacterial cloning were not sensitive enough to detect circulating drug-resistant mutants in clinical specimens. Ultradeep pyrosequencing was used to confirm the presence of the corresponding HCV mutants. In treatment-naïve patients, the frequency of all resistant variants was below 1%. Deep amplicon sequencing allowed a detailed analysis of the structure of the viral population among these patients, showing that the evolution of the NS3 is limited to a rather small sequence space. Monitoring of HCV drug resistance before and during treatment is likely to provide important information for management of patients undergoing anti-HCV therapy. PMID:22116161

Liquid chromatography-mass spectrometry for measuring deoxythioguanosine in DNA from thiopurine-treated patients.

PubMed

Coulthard, Sally A; Berry, Phil; McGarrity, Sarah; Ansari, Azhar; Redfern, Christopher P F

2016-08-15

Adverse reactions and non-response are common in patients treated with thiopurine drugs. Current monitoring of drug metabolite levels for guiding treatment are limited to analysis of thioguanine nucleotides (TGNs) in erythrocytes after chemical derivatisation. Erythrocytes are not the target tissue and TGN levels show poor correlations with clinical response. We have developed a sensitive assay to quantify deoxythioguanosine (dTG) without derivatisation in the DNA of nucleated blood cells. Using liquid chromatography and detection by tandem mass spectrometry, an intra- and inter-assay variability below 7.8% and 17.0% respectively were achieved. The assay had a detection limit of 0.0003125ng (1.1 femtomoles) dTG and was quantified in DNA samples relative to endogenous deoxyadenosine (dA) in a small group of 20 patients with inflammatory bowel disease, all of whom had been established on azathioprine (AZA) therapy for more than 25 weeks. These patients had dTG levels of 20-1360mol dTG/10(6)mol dA; three patients who had not started therapy had no detectable dTG. This method, comparable to previous methods in sensitivity, enables the direct detection of a cytotoxic thiopurine metabolite without derivatisation in an easily obtainable, stable sample and will facilitate a better understanding of the mechanisms of action of these inexpensive yet effective drugs. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Deconstructing autofluorescence: non-invasive detection and monitoring of biochemistry in cells and tissues (Conference Presentation)

NASA Astrophysics Data System (ADS)

Goldys, Ewa M.; Gosnell, Martin E.; Anwer, Ayad G.; Cassano, Juan C.; Sue, Carolyn M.; Mahbub, Saabah B.; Pernichery, Sandeep M.; Inglis, David W.; Adhikary, Partho P.; Jazayeri, Jalal A.; Cahill, Michael A.; Saad, Sonia; Pollock, Carol; Sutton-Mcdowall, Melanie L.; Thompson, Jeremy G.

2016-03-01

Automated and unbiased methods of non-invasive cell monitoring able to deal with complex biological heterogeneity are fundamentally important for biology and medicine. Label-free cell imaging provides information about endogenous fluorescent metabolites, enzymes and cofactors in cells. However extracting high content information from imaging of native fluorescence has been hitherto impossible. Here, we quantitatively characterise cell populations in different tissue types, live or fixed, by using novel image processing and a simple multispectral upgrade of a wide-field fluorescence microscope. Multispectral intrinsic fluorescence imaging was applied to patient olfactory neurosphere-derived cells, cell model of a human metabolic disease MELAS (mitochondrial myopathy, encephalomyopathy, lactic acidosis, stroke-like syndrome). By using an endogenous source of contrast, subtle metabolic variations have been detected between living cells in their full morphological context which made it possible to distinguish healthy from diseased cells before and after therapy. Cellular maps of native fluorophores, flavins, bound and free NADH and retinoids unveiled subtle metabolic signatures and helped uncover significant cell subpopulations, in particular a subpopulation with compromised mitochondrial function. The versatility of our method is further illustrated by detecting genetic mutations in cancer, non-invasive monitoring of CD90 expression, label-free tracking of stem cell differentiation, identifying stem cell subpopulations with varying functional characteristics, tissue diagnostics in diabetes, and assessing the condition of preimplantation embryos. Our optimal discrimination approach enables statistical hypothesis testing and intuitive visualisations where previously undetectable differences become clearly apparent.

Pediatric tuberculosis-human immunodeficiency virus co-infection in the United Kingdom highlights the need for better therapy monitoring tools: a case report.

PubMed

Evangelopoulos, Dimitrios; Whittaker, Elizabeth; Honeyborne, Isobella; McHugh, Timothy D; Klein, Nigel; Shingadia, Delane

2017-02-26

Tuberculosis is an infection that requires at least 6 months of chemotherapy in order to clear the bacteria from the patient's lungs. Usually, therapeutic monitoring is dependent on smear microscopy where a decline in acid-fast bacilli is observed. However, this might not be indicative of the actual decline of bacterial load and thus other tools such as culture and molecular assays are required for patient management. Here, we report the case of a 12-year-old Black African boy co-infected with tuberculosis and human immunodeficiency virus who remained smear culture positive and liquid culture negative for a prolonged period of time following chemotherapy. In order to determine whether there was any live bacteria present in his specimens, we applied the newly developed molecular bacterial load assay that detects the presence of 16S ribosomal ribonucleic acid derived from the bacteria. Using this methodology, we were able to quantify his bacterial load and inform the management of his treatment in order to reduce the disease burden. Following this intervention he went on to make a complete recovery. This case report highlights the value of improved biomarkers for monitoring the treatment of tuberculosis and the role of molecular assays such as the molecular bacterial load assay applied here. The molecular bacterial load assay detects bacterial ribonucleic acid which corresponds closely with the number of live bacilli as compared with polymerase chain reaction that detects deoxyribonucleic acid and may include dead bacteria.

Rational use and interpretation of urine drug testing in chronic opioid therapy.

PubMed

Reisfield, Gary M; Salazar, Elaine; Bertholf, Roger L

2007-01-01

Urine drug testing (UDT) has become an essential feature of pain management, as physicians seek to verify adherence to prescribed opioid regimens and to detect the use of illicit or unauthorized licit drugs. Results of urine drug tests have important consequences in regard to therapeutic decisions and the trust between physician and patient. However, reliance on UDT to confirm adherence can be problematic if the results are not interpreted correctly, and evidence suggests that many physicians lack an adequate understanding of the complexities of UDT and the factors that can affect test results. These factors include metabolic conversion between drugs, genetic variations in drug metabolism, the sensitivity and specificity of the analytical method for a particular drug or metabolite, and the effects of intentional and unintentional interferants. In this review, we focus on the technical features and limitations of analytical methods used for detecting drugs or their metabolites in urine, the statistical constructs that are pertinent to ordering UDT and interpreting test results, and the application of these concepts to the clinical monitoring of patients maintained on chronic opioid therapy.

A dual function fusion protein of Herpes simplex virus type 1 thymidine kinase and firefly luciferase for noninvasive in vivo imaging of gene therapy in malignant glioma.

PubMed

Söling, Ariane; Theiss, Christian; Jungmichel, Stephanie; Rainov, Nikolai G

2004-08-04

BACKGROUND: Suicide gene therapy employing the prodrug activating system Herpes simplex virus type 1 thymidine kinase (HSV-TK)/ ganciclovir (GCV) has proven to be effective in killing experimental brain tumors. In contrast, glioma patients treated with HSV-TK/ GCV did not show significant treatment benefit, most likely due to insufficient transgene delivery to tumor cells. Therefore, this study aimed at developing a strategy for real-time noninvasive in vivo monitoring of the activity of a therapeutic gene in brain tumor cells. METHODS: The HSV-TK gene was fused to the firefly luciferase (Luc) gene and the fusion construct HSV-TK-Luc was expressed in U87MG human malignant glioma cells. Nude mice with subcutaneous gliomas stably expressing HSV-TK-Luc were subjected to GCV treatment and tumor response to therapy was monitored in vivo by serial bioluminescence imaging. Bioluminescent signals over time were compared with tumor volumes determined by caliper. RESULTS: Transient and stable expression of the HSV-TK-Luc fusion protein in U87MG glioma cells demonstrated close correlation of both enzyme activities. Serial optical imaging of tumor bearing mice detected in all cases GCV induced death of tumor cells expressing the fusion protein and proved that bioluminescence can be reliably used for repetitive and noninvasive quantification of HSV-TK/ GCV mediated cell kill in vivo. CONCLUSION: This approach may represent a valuable tool for the in vivo evaluation of gene therapy strategies for treatment of malignant disease.

Detection of atrial fibrillation and flutter by a dual-chamber implantable cardioverter-defibrillator. For the Worldwide Jewel AF Investigators.

PubMed

Swerdlow, C D; Schsls, W; Dijkman, B; Jung, W; Sheth, N V; Olson, W H; Gunderson, B D

2000-02-29

To distinguish prolonged episodes of atrial fibrillation (AF) that require cardioversion from self-terminating episodes that do not, an atrial implantable cardioverter-defibrillator (ICD) must be able to detect AF continuously for extended periods. The ICD should discriminate between atrial tachycardia/flutter (AT), which may be terminated by antitachycardia pacing, and AF, which requires cardioversion. We studied 80 patients with AT/AF and ventricular arrhythmias who were treated with a new atrial/dual-chamber ICD. During a follow-up period lasting 6+/-2 months, we validated spontaneous, device-defined AT/AF episodes by stored electrograms in all patients. In 58 patients, we performed 80 Holter recordings with telemetered atrial electrograms, both to validate the continuous detection of AT/AF and to determine the sensitivity of the detection of AT/AF. Detection was appropriate in 98% of 132 AF episodes and 88% of 190 AT episodes (98% of 128 AT episodes with an atrial cycle length <300 ms). Intermittent sensing of far-field R waves during sinus tachycardia caused 27 inappropriate AT/AF detections; these detections lasted 2.6+/-2.0 minutes. AT/AF was detected continuously in 27 of 28 patients who had spontaneous episodes of AT/AF (96%). The device memory recorded 90 appropriate AT/AF episodes lasting >1 hour, for a total of 2697 hours of continuous detection of AT/AF. During Holter monitoring, the sensitivity of the detection of AT/AF (116 hours) was 100%; the specificity of the detection of non-AT/AF rhythms (1290 hours) was 99.99%. Of 166 appropriate episodes detected as AT, 45% were terminated by antitachycardia pacing. A new ICD detects AT/AF accurately and continuously. Therapy may be programmed for long-duration AT/AF, with a low risk of underdetection. Discrimination of AT from AF permits successful pacing therapy for a significant fraction of AT.

Dystrophin Immunity in Duchenne’s Muscular Dystrophy

PubMed Central

Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

2010-01-01

SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

A global look into human T cell subsets before and after cryopreservation using multiparametric flow cytometry and two-dimensional visualization analysis.

PubMed

Lemieux, Jennifer; Jobin, Christine; Simard, Carl; Néron, Sonia

2016-07-01

The cryopreservation of human lymphocytes is an essential step for the achievement of several cellular therapies. Besides, T cells are considered as promising actors in cancer therapy for their cytotoxic and regulatory properties. Consequently, the development of tools to monitor the impact of freezing and thawing processes on their fine distribution may be an asset to achieve quality control in cellular therapy. In this study, the phenotypes of freshly isolated human mononuclear cells were compared to those observed following one cycle of cryopreservation and rest periods 0h, 1h and 24h after thawing but before staining. T cells were scrutinized for their distribution according to naive, memory effector, regulatory and helper subsets. Flow cytometry analyses were done using eight-color antibody panels as proposed by the Human Immunophenotyping Consortium. Data were further analyzed by using conventional directed gating and clustering software, namely SPADE and viSNE. Overall, SPADE and viSNE tools were very efficient to monitor the outcome of PBMC populations and T cell subsets. T cells were more sensitive to cryopreservation than other cells. Our results indicated that submitting the thawed cells to a 1h rest period improved the detection of some cell markers when compared to fresh samples. In contrast, cells submitted to a 24h rest period, or to none, were less representative of fresh sample distribution. The heterogeneity of PBMC, as well as the effects of freeze-thaw cycle on their distribution, can be easily monitored by using SPADE and viSNE. Copyright © 2016 Elsevier B.V. All rights reserved.

A prototype scintillating fibre beam profile monitor for Ion Therapy beams

NASA Astrophysics Data System (ADS)

Leverington, B. D.; Dziewiecki, M.; Renner, L.; Runze, R.

2018-05-01

A prototype plastic scintillating fibre based beam profile monitor was tested at the Heidelberg Ion Therapy Centre/Heidelberg Ionenstrahl Therapiezentrum (HIT) in 2016 to determine its beam property reconstruction performance and the feasibility of further developing an expanded system. At HIT protons, helium, carbon, and oxygen ions are available for therapy and experiments. The beam can be scanned in two dimensions using fast deflection magnets. A tracking system is used to monitor beam position and to adjust scanning magnet currents online. A new detector system with a finer granularity and without the drift time delay of the current MWPC system with a similar amount of material along the beamline would prove valuable in patient treatment. The sensitive detector components in the tested prototype detector are double-clad Kuraray SCSF-78MJ scintillating fibres with a diameter of 0.250 mm wound as a thin multi-layer ribbon. The scintillation light is detected at the end of the ribbon with Hamamatsu S11865-64 photodiode arrays with a pitch of 0.8 mm. Commercial or readily available readout electronics have been used to evaluate the system feasibility. The results shown in this paper include the linearity with respect to beam intensity, the RMS of the beam intensity as measured by two planes, along with the RMS of the mean position, and the measured beam width RMS. The Signal-to-Noise ratio of the current system is also measured as an indicator of potential performance. Additionally, the non-linear light yield of the scintillating fibres as measured by the photodiode arrays is compared to two models which describe the light yield as a function of the ion stopping power and Lorentz β.

ISHNE/EHRA expert consensus on remote monitoring of cardiovascular implantable electronic devices (CIEDs).

PubMed

Dubner, Sergio; Auricchio, Angelo; Steinberg, Jonathan S; Vardas, Panos; Stone, Peter; Brugada, Josep; Piotrowicz, Ryszard; Hayes, David L; Kirchhof, Paulus; Breithardt, Günter; Zareba, Wojciech; Schuger, Claudio; Aktas, Mehmet K; Chudzik, Michal; Mittal, Suneet; Varma, Niraj

2012-02-01

We are in the midst of a rapidly evolving era of technology-assisted medicine. The field of telemedicine provides the opportunity for highly individualized medical management in a way that has never been possible before. Evolving medical technologies using cardiac implantable devices (CIEDs) with capabilities for remote monitoring permit evaluation of multiple parameters of cardiovascular physiology and risk, including cardiac rhythm, device function, blood pressure values, the presence of myocardial ischaemia, and the degree of compensation of congestive heart failure. Cardiac risk, device status, and response to therapies can now be assessed with these electronic systems of detection and reporting. This document reflects the extensive experience from investigators and innovators around the world who are shaping the evolution of this rapidly expanding field, focusing in particular on implantable pacemakers (IPGs), implantable cardioverter-defibrillators (ICDs), devices for cardiac resynchronization therapy (CRT) (both, with and without defibrillation properties), loop recorders, and haemodynamic monitoring devices. This document covers the basic methodologies, guidelines for their use, experience with existing applications, and the legal and reimbursement aspects associated with their use. To adequately cover this important emerging topic, the International Society for Holter and Noninvasive Electrocardiology (ISHNE) and the European Heart Rhythm Association (EHRA) combined their expertise in this field. We hope that the development of this field can contribute to improve care of our cardiovascular patients.

Neuropathogenesis of HIV-associated neurocognitive disorders: roles for immune activation, HIV blipping and viral tropism.

PubMed

Chen, Maria F; Gill, Alexander J; Kolson, Dennis L

2014-11-01

The purpose of this study is to discuss why HIV-associated neurocognitive disorders (HAND) persist despite apparently effective HIV suppression by highly active antiretroviral therapy (ART). As many as 50% of HIV-infected individuals suffer from HAND despite ART suppression of HIV replication to apparently undetectable levels in most treated individuals. Prior to ART, HIV-associated dementia (HAD), the severest form of HAND, affected nearly 20% of infected individuals; HAD now affects only nearly 2% of ART-treated persons, although less severe HAND forms persist. Recent studies link persistent immune activation, inflammation and viral escape/blipping in ART-treated individuals, as well as comorbid conditions, to HIV disease progression and increased HAND risk. Despite sustained HIV suppression in most ART-treated individuals, indicated by routine plasma monitoring and occasional cerebrospinal fluid (CSF) monitoring, 'blips' of HIV replication are often detected with more frequent monitoring, thus challenging the concept of viral suppression. Although the causes of HIV blipping are unclear, CSF HIV blipping associates with neuroinflammation and, possibly, central nervous system (CNS) injury. The current theory that macrophage-tropic HIV strains within the CNS predominate in driving HAND and these associated factors is now also challenged. Protection of the CNS by ART is incomplete, probably due to combined effects of incomplete HIV suppression, persistent immune activation and host comorbidity factors. Adjunctive therapies to ART are necessary for more effective protection.

Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring.

PubMed

Yajima, Takahiro; Yajima, Kumiko; Hayashi, Makoto; Takahashi, Hiroshi; Yasuda, Keigo

2016-12-01

Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy. Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration. The median total daily insulin dose significantly reduced from 18 (9-24)U to 6 (0-14)U (p<0.0001). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9±1.0mmol/L to 4.4±0.9mmol/L, p=0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p=0.049). Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke

PubMed Central

Delgado-Mederos, Raquel; Gregori-Pla, Clara; Zirak, Peyman; Blanco, Igor; Dinia, Lavinia; Marín, Rebeca; Durduran, Turgut; Martí-Fàbregas, Joan

2018-01-01

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time. PMID:29541519

Transcranial diffuse optical assessment of the microvascular reperfusion after thrombolysis for acute ischemic stroke.

PubMed

Delgado-Mederos, Raquel; Gregori-Pla, Clara; Zirak, Peyman; Blanco, Igor; Dinia, Lavinia; Marín, Rebeca; Durduran, Turgut; Martí-Fàbregas, Joan

2018-03-01

In this pilot study, we have evaluated bedside diffuse optical monitoring combining diffuse correlation spectroscopy and near-infrared diffuse optical spectroscopy to assess the effect of thrombolysis with an intravenous recombinant tissue plasminogen activator (rtPA) on cerebral hemodynamics in an acute ischemic stroke. Frontal lobes of five patients with an acute middle cerebral artery occlusion were measured bilaterally during rtPA treatment. Both ipsilesional and contralesional hemispheres showed significant increases in cerebral blood flow, total hemoglobin concentration and oxy-hemoglobin concentration during the first 2.5 hours after rtPA bolus. The increases were faster and higher in the ipsilesional hemisphere. The results show that bedside optical monitoring can detect the effect of reperfusion therapy for ischemic stroke in real-time.

Continuous pulse oximeter monitoring for inapparent hypoxemia after long bone fractures.

PubMed

Wong, Margaret Wan Nar; Tsui, Hon For; Yung, Shu Heng; Chan, Kai Ming; Cheng, Jack Chun Yiu

2004-02-01

Continuous pulse oximeter monitoring (CPOM) and daily intermittent arterial blood gas (ABG) were used to define the incidence, pattern, and severity of inapparent hypoxemia after long bone fractures. Twenty long bone fracture patients and 19 normal control patients were studied. CPOM, daily ABG, hypoxic symptoms, and features of fat embolism syndrome were monitored for 72 hours after fractures and after surgical interventions. CPOM trend curves showed that all fracture patients except one had recurrent desaturations below 90% Sao2 of varying duration and depth. The lowest Sao2 was down to 60% and the longest episode lasted for 1.47 hours. ABG analysis could not show the recurrent phenomena and never detected the corresponding desaturation episodes. Long bone fracture patients had more desaturation episodes, longer total desaturation duration, and larger total area under desaturation curves in both the postfracture and postoperative periods (p < 0.05). The mean Sao2 was significantly lower in the postfracture period. Although most patients remained asymptomatic and recovered spontaneously, two required transient oxygen therapy and one progressed to fat embolism syndrome. Inapparent hypoxia with profound desaturation is common after long bone fractures. CPOM of all patients admitted with long bone fractures is recommended for early detection. In patients who develop inapparent hypoxia, additional pulmonary insult should be avoided or undertaken with care and well timed.

Advanced detection and measurement of cells on membrane from peripheral blood by laser scanning cytometry (LSC) in early stage breast cancer patients.

PubMed

Sanislo, L; Kuliffay, P; Sedlak, J; Kausitz, J; Galbavy, S

2010-01-01

The aim of our study was the potential detection of circulating tumour cells (CTCs) in early stage breast cancer patients. Our approach was cell microfiltration through polycarbonate membrane as a concentration method suitable for CTC selection in peripheral blood. The isolated cells on membrane were further analysed by laser scanning cytometry. Sixteen patients were enrolled in the study, of which 13 had early stage breast carcinoma and 3 patients had metastatic breast carcinoma. The analyses were performed from 9 ml of peripheral blood, in one patient blood was drawn twice. Blood samples were taken after adjuvant chemotherapy but prior to adjuvant radiotherapy. The control group consisted of 12 clinically healthy subjects. In the control group 3 subjects out of 12 had 1 CTC, the mean CTC numbers being 0.25 +/- 0.45. In the early stage breast cancer patients 0-36 CTCs were detected (mean 13.9 +/- 12.9 CTCs. 10 patients out of 13 had more than 2 CTCs (62%). The detection and measurement of cells on membrane is a simple and reproducible method of detection of CTCs in peripheral blood. Sensitivity of the method is 88.5%. Detection of CTCs seems to be a promising method for the monitoring of adjuvant therapy in early stage breast cancer patients and for the identification of high risk patients in whom elevated numbers of CTCs are persisting following the termination of adjuvant therapy (Tab. 1, Fig. 4, Ref. 35). Full Text (Free, PDF) www.bmj.sk.

TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients.

PubMed

Yáñez, Yania; Hervás, David; Grau, Elena; Oltra, Silvestre; Pérez, Gema; Palanca, Sarai; Bermúdez, Mar; Márquez, Catalina; Cañete, Adela; Castel, Victoria

2016-03-01

In metastatic neuroblastoma (NB) patients, accurate risk stratification and disease monitoring would reduce relapse probabilities. This study aims to evaluate the independent prognostic significance of detecting tyrosine hydroxylase (TH) and doublecortin (DCX) mRNAs by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) in peripheral blood (PB) and bone marrow (BM) samples from metastatic NB patients. RT-qPCR was performed on PB and BM samples from metastatic NB patients at diagnosis, post-induction therapy and at the end of treatment for TH and DCX mRNAs detection. High levels of TH and DCX mRNAs when detected in PB and BM at diagnosis independently predicted worse outcome in a cohort of 162 metastatic NB. In the subgroup of high-risk metastatic NB, TH mRNA detected in PB remained as independent predictor of EFS and OS at diagnosis. After the induction therapy, high levels of TH mRNA in PB and DCX mRNA in BM independently predicted poor EFS and OS. Furthermore TH mRNA when detected in BM predicted worse EFS. TH mRNA in PB samples at the end of treatment is an independent predictor of worse outcome. TH and DCX mRNAs levels in PB and BM assessed by RT-qPCR should be considered in new pre-treatment risk stratification strategies to reliable estimate outcome differences in metastatic NB patients. In those high-risk metastatic NB, TH and DCX mRNA quantification could be used for the assessment of response to treatment and for early detection of progressive disease or relapses.

MONDO: A tracker for the characterization of secondary fast and ultrafast neutrons emitted in particle therapy

NASA Astrophysics Data System (ADS)

Mirabelli, R.; Battistoni, G.; Giacometti, V.; Patera, V.; Pinci, D.; Sarti, A.; Sciubba, A.; Traini, G.; Marafini, M.

2018-01-01

In Particle Therapy (PT) accelerated charged particles and light ions are used for treating tumors. One of the main limitation to the precision of PT is the emission of secondary particles due to the beam interaction with the patient: secondary emitted neutrons can release a significant dose far from the tumor. Therefore, a precise characterization of their flux, production energy and angle distribution is eagerly needed in order to improve the Treatment Planning Systems (TPS) codes. The principal aim of the MONDO (MOnitor for Neutron Dose in hadrOntherapy) project is the development of a tracking device optimized for the detection of fast and ultra-fast secondary neutrons emitted in PT. The detector consists of a matrix of scintillating square fibres coupled with a CMOS-based readout. Here, we present the characterization of the detector tracker prototype and CMOS-based digital SPAD (Single Photon Avalanche Diode) array sensor tested with protons at the Beam Test Facility (Frascati, Italy) and at the Proton Therapy Centre (Trento, Italy), respectively.

Advanced magnetic resonance imaging methods for planning and monitoring radiation therapy in patients with high-grade glioma.

PubMed

Lupo, Janine M; Nelson, Sarah J

2014-10-01

This review explores how the integration of advanced imaging methods with high-quality anatomical images significantly improves the characterization, target definition, assessment of response to therapy, and overall management of patients with high-grade glioma. Metrics derived from diffusion-, perfusion-, and susceptibility-weighted magnetic resonance imaging in conjunction with magnetic resonance spectroscopic imaging, allows us to characterize regions of edema, hypoxia, increased cellularity, and necrosis within heterogeneous tumor and surrounding brain tissue. Quantification of such measures may provide a more reliable initial representation of tumor delineation and response to therapy than changes in the contrast-enhancing or T2 lesion alone and have a significant effect on targeting resection, planning radiation, and assessing treatment effectiveness. In the long term, implementation of these imaging methodologies can also aid in the identification of recurrent tumor and its differentiation from treatment-related confounds and facilitate the detection of radiationinduced vascular injury in otherwise normal-appearing brain tissue.

Intracranial Pressure Monitoring in Infants and Young Children With Traumatic Brain Injury.

PubMed

Dixon, Rebecca R; Nocera, Maryalice; Zolotor, Adam J; Keenan, Heather T

2016-11-01

To examine the use of intracranial pressure monitors and treatment for elevated intracranial pressure in children 24 months old or younger with traumatic brain injury in North Carolina between April 2009 and March 2012 and compare this with a similar cohort recruited 2000-2001. Prospective, observational cohort study. Twelve PICUs in North Carolina. All children 24 months old or younger with traumatic brain injury, admitted to an included PICU. None. The use of intracranial pressure monitors and treatments for elevated intracranial pressure were evaluated in 238 children with traumatic brain injury. Intracranial pressure monitoring (risk ratio, 3.7; 95% CI, 1.5-9.3) and intracranial pressure therapies were more common in children with Glasgow Coma Scale less than or equal to 8 compared with Glasgow Coma Scale greater than 8. However, only 17% of children with Glasgow Coma Scale less than or equal to 8 received a monitoring device. Treatments for elevated intracranial pressure were more common in children with monitors; yet, some children without monitors received therapies traditionally used to lower intracranial pressure. Unadjusted predictors of monitoring were Glasgow Coma Scale less than or equal to 8, receipt of cardiopulmonary resuscitation, nonwhite race. Logistic regression showed no strong predictors of intracranial pressure monitor use. Compared with the 2000 cohort, children in the 2010 cohort with Glasgow Coma Scale less than or equal to 8 were less likely to receive monitoring (risk ratio, 0.5; 95% CI, 0.3-1.0), although the estimate was not precise, or intracranial pressure management therapies. Children in the 2010 cohort with a Glasgow Coma Scale less than or equal to 8 were less likely to receive an intracranial pressure monitor or hyperosmolar therapy than children in the 2000 cohort; however, about 10% of children without monitors received therapies to decrease intracranial pressure. This suggests treatment heterogeneity in children 24 months old or younger with traumatic brain injury and a need for better evidence to support treatment recommendations for this group of children.

Validation of amino-acids measurement in dried blood spot by FIA-MS/MS for PKU management.

PubMed

Bruno, C; Dufour-Rainfray, D; Patin, F; Vourc'h, P; Guilloteau, D; Maillot, F; Labarthe, F; Tardieu, M; Andres, C R; Emond, P; Blasco, H

2016-09-01

Phenylketonuria (PKU) is a metabolic disorder leading to high concentrations of phenylalanine (Phe) and low concentrations of tyrosine (Tyr) in blood and brain that may be neurotoxic. This disease requires a regular monitoring of plasma Phe and Tyr as well as branched-chain amino-acids concentrations to adapt the Phe-restricted diet and other therapy that may be prescribed in PKU. We validated a Flow Injection Analysis tandem Mass Spectrometry (FIA-MS/MS) to replace the enzymatic method routinely used for neonatal screening in order to monitor in parallel to Phe, Tyr and branched-chain amino-acids not detected by the enzymatic method. We ascertained the performances of the method: linearity, detection and quantification limits, contamination index, accuracy. We cross validated the FIA-MS/MS and enzymatic methods and we evaluated our own reference ranges to monitor Phe, Tyr, Leu, Val on 59 dried blood spots of normal controls. We also evaluated Tyr, Leu and Val concentrations in PKU patients to detect some potential abnormalities, not evaluated by the enzymatic method. We developed a rapid method with excellent performances including precision and accuracy <15%. We noted an excellent correlation of Phe concentrations between FIA-MS/MS and enzymatic methods (p<0.0001) based on our database which are similar to references ranges published. We observed that 50% of PKU patients had lower concentrations of Tyr, Leu and/or Val that could not be detected by the enzymatic method. Based on laboratory accreditation recommendations, we validated a robust, rapid and reliable FIA-MS/MS method to monitor plasma Phe concentrations but also Tyr, Leu and Val concentrations, suitable for PKU management. We evaluated our own reference ranges of concentration for a routine application of this method. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

SU-D-17A-07: Development and Evaluation of a Prototype Ultrasonography Respiratory Monitoring System for 4DCT Reconstruction

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

Yan, P; Cheng, S; Chao, C

Purpose: Respiratory motion artifacts are commonly seen in the abdominal and thoracic CT images. A Real-time Position Management (RPM) system is integrated with CT simulator using abdominal surface as a surrogate for tracking the patient respiratory motion. The respiratory-correlated four-dimensional computed tomography (4DCT) is then reconstructed by GE advantage software. However, there are still artifacts due to inaccurate respiratory motion detecting and sorting methods. We developed an Ultrasonography Respiration Monitoring (URM) system which can directly monitor diaphragm motion to detect respiratory cycles. We also developed a new 4DCT sorting and motion estimation method to reduce the respiratory motion artifacts. Themore » new 4DCT system was compared with RPM and the GE 4DCT system. Methods: Imaging from a GE CT scanner was simultaneously correlated with both the RPM and URM to detect respiratory motion. A radiation detector, Blackcat GM-10, recorded the X-ray on/off and synchronized with URM. The diaphragm images were acquired with Ultrasonix RP system. The respiratory wave was derived from diaphragm images and synchronized with CT scanner. A more precise peaks and valleys detection tool was developed and compared with RPM. The motion is estimated for the slices which are not in the predefined respiratory phases by using block matching and optical flow method. The CT slices were then sorted into different phases and reconstructed, compared with the images reconstructed from GE Advantage software using respiratory wave produced from RPM system. Results: The 4DCT images were reconstructed for eight patients. The discontinuity at the diaphragm level due to an inaccurate identification of phases by the RPM was significantly improved by URM system. Conclusion: Our URM 4DCT system was evaluated and compared with RPM and GE 4DCT system. The new system is user friendly and able to reduce motion artifacts. It also has the potential to monitor organ motion during therapy.« less

Follow-up of differentiated thyroid carcinoma.

PubMed

Pagano, L; Klain, M; Pulcrano, M; Angellotti, G; Pasano, F; Salvatore, M; Lombardi, G; Biondi, B

2004-12-01

Thyroid cancer is the most common endocrine malignancy. More than 90% of primary thyroid cancers are differentiated papillary or follicular types. The treatment of differentiated thyroid carcinoma (DTC) consists of total thyroidectomy and radioactive iodine ablation therapy, followed by L-thyroxine therapy. The extent of initial surgery, the indication for radioiodine ablation therapy and the degree of TSH-suppression are all issues that are still being debated cancers are in relation to the risk of recurrence. Total thyroidectomy reduces the risk of recurrence and facilitates (131)I ablation of thyroid remnants. The aim of radioiodine ablation is to destroy any normal or neoplastic residuals of thyroid tissue. These procedures also improve the sensitivity of thyroglobulin (Tg) as a marker of disease, and increase the sensitivity of (131)I total body scan (TBS) for the detection of persistent or recurrent disease. The aim of TSH-suppressive therapy is to restore euthyroidism and to decrease serum TSH levels, in order to reduce the growth and progression of thyroid cancer. After initial treatment, the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound (US) and serum Tg and (131)I TBS after TSH stimulation. The follow-up protocol should be adapted to the risk of recurrence. Recent advances in the follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and the ultrasensitive methods for Tg measurement. Undetectable serum Tg during TSH suppressive therapy with L-T4 does not exclude persistent disease, therefore serum Tg should be measured after TSH stimulation. The results of rhTSH administration and L-thyroxine therapy withdrawal are equivalent in detecting recurrent thyroid cancer, but the use of rhTSH helps to avoid the onset of hypothyroid symptoms and the negative effects of acute hypothyroidism on cardiovascular, hepatic, renal and neurological function. In low-risk DTC patients serum Tg after TSH stimulation, together with ultrasound of the neck, should be used to monitor persistent disease, avoiding diagnostic TBS which has a poor sensitivity. These recommendations do not apply when Tg antibodies are present in the serum, in patients with persistent or recurrent disease or limited thyroid surgery. Low-risk patients may be considered to be in remission when undetectable Tg after TSH stimulation and negative US evaluation of the neck are present. On the contrary, detectable Tg after TSH stimulation is an indicator in selecting patients who are candidates for further diagnostic procedures.

Monitoring the autonomic nervous activity as the objective evaluation of music therapy for severely and multiply disabled children.

PubMed

Orita, Makiko; Hayashida, Naomi; Shinkawa, Tetsuko; Kudo, Takashi; Koga, Mikitoshi; Togo, Michita; Katayama, Sotetsu; Hiramatsu, Kozaburo; Mori, Shunsuke; Takamura, Noboru

2012-07-01

Severely and multiply disabled children (SMDC) are frequently affected in more than one area of development, resulting in multiple disabilities. The aim of the study was to evaluate the efficacy of music therapy in SMDC using monitoring changes in the autonomic nervous system, by the frequency domain analysis of heart rate variability. We studied six patients with SMDC (3 patients with cerebral palsy, 1 patient with posttraumatic syndrome after head injury, 1 patient with herpes encephalitis sequelae, and 1 patient with Lennox-Gastaut syndrome characterized by frequent seizures, developmental delay and psychological and behavioral problems), aged 18-26 (mean 22.5 ± 3.5). By frequency domain method using electrocardiography, we measured the high frequency (HF; with a frequency ranging from 0.15 to 0.4 Hz), which represents parasympathetic activity, the low frequency/high frequency ratio, which represents sympathetic activity between the sympathetic and parasympathetic activities, and heart rate. A music therapist performed therapy to all patients through the piano playing for 50 min. We monitored each study participant for 150 min before therapy, 50 min during therapy, and 10 min after therapy. Interestingly, four of 6 patients showed significantly lower HF components during music therapy than before therapy, suggesting that these four patients might react to music therapy through the suppression of parasympathetic nervous activities. Thus, music therapy can suppress parasympathetic nervous activities in some patients with SMDC. The monitoring changes in the autonomic nervous activities could be a powerful tool for the objective evaluation of music therapy in patients with SMDC.

Detection of viral infections using colloidal quantum dots

NASA Astrophysics Data System (ADS)

Bentzen, Elizabeth L.; House, Frances S.; Utley, Thomas J.; Crowe, James E., Jr.; Wright, David W.

2006-02-01

Fluorescence is a tool widely employed in biological assays. Fluorescent semiconducting nanocrystals, quantum dots (QDs), are beginning to find their way into the tool box of many biologist, chemist and biochemist. These quantum dots are an attractive alternative to the traditional organic dyes due to their broad excitation spectra, narrow emission spectra and photostability. Quantum dots were used to detect and monitor the progession of viral glycoproteins, F (fusion) and G (attachment), from Respiratory Syncytial Virus (RSV) in HEp-2 cells. Additionally, oligo-Qdot RNA probes have been developed for identification and detection of mRNA of the N(nucleocapsid) protein for RSV. The use of quantum dot-FISH probes provides another confirmatory route to diagnostics as well as a new class of probes for monitoring the flux and fate of viral RNA RSV is the most common cause of lower respiratory tract infection in children worldwide and the most common cause of hospitalization of infants in the US. Antiviral therapy is available for treatment of RSV but is only effective if given within the first 48 hours of infection. Existing test methods require a virus level of at least 1000-fold of the amount needed for infection of most children and require several days to weeks to obtain results. The use of quantum dots may provide an early, rapid method for detection and provide insight into the trafficking of viral proteins during the course of infection.

Mutation-based detection and monitoring of cell-free tumor DNA in peripheral blood of cancer patients.

PubMed

Benesova, L; Belsanova, B; Suchanek, S; Kopeckova, M; Minarikova, P; Lipska, L; Levy, M; Visokai, V; Zavoral, M; Minarik, M

2013-02-15

Prognosis of solid cancers is generally more favorable if the disease is treated early and efficiently. A key to long cancer survival is in radical surgical therapy directed at the primary tumor followed by early detection of possible progression, with swift application of subsequent therapeutic intervention reducing the risk of disease generalization. The conventional follow-up care is based on regular observation of tumor markers in combination with computed tomography/endoscopic ultrasound/magnetic resonance/positron emission tomography imaging to monitor potential tumor progression. A recent development in methodologies allowing screening for a presence of cell-free DNA (cfDNA) brings a new viable tool in early detection and management of major cancers. It is believed that cfDNA is released from tumors primarily due to necrotization, whereas the origin of nontumorous cfDNA is mostly apoptotic. The process of cfDNA detection starts with proper collection and treatment of blood and isolation and storage of blood plasma. The next important steps include cfDNA extraction from plasma and its detection and/or quantification. To distinguish tumor cfDNA from nontumorous cfDNA, specific somatic DNA mutations, previously localized in the primary tumor tissue, are identified in the extracted cfDNA. Apart from conventional mutation detection approaches, several dedicated techniques have been presented to detect low levels of cfDNA in an excess of nontumorous (nonmutated) DNA, including real-time polymerase chain reaction (PCR), "BEAMing" (beads, emulsion, amplification, and magnetics), and denaturing capillary electrophoresis. Techniques to facilitate the mutant detection, such as mutant-enriched PCR and COLD-PCR (coamplification at lower denaturation temperature PCR), are also applicable. Finally, a number of newly developed miniaturized approaches, such as single-molecule sequencing, are promising for the future. Copyright © 2012 Elsevier Inc. All rights reserved.

High WT1 expression is an early predictor for relapse in patients with acute promyelocytic leukemia in first remission with negative PML-RARa after anthracycline-based chemotherapy: a single-center cohort study.

PubMed

Yoon, Jae-Ho; Kim, Hee-Je; Kwak, Dae-Hun; Park, Sung-Soo; Jeon, Young-Woo; Lee, Sung-Eun; Cho, Byung-Sik; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong Wook; Min, Woo-Sung

2017-01-23

Wilms' tumor gene 1 (WT1) expression is a well-known predictor for relapse in acute myeloid leukemia. We monitored WT1 decrement along the treatment course to identify its significant role as a marker for residual disease in acute promyelocytic leukemia (APL) and tried to suggest its significance for relapse prediction. In this single center retrospective study, we serially measured PML-RARa and WT1 expression from 117 APL patients at diagnosis, at post-induction and post-consolidation chemotherapies, and at every 3 months after starting maintenance therapy. All 117 patients were in molecular remission after treatment of at least 2 consolidation chemotherapies. We used WT1 ProfileQuant™ kit (Ipsogen) for WT1 monitoring. High WT1 expression (>120 copies/10 4 ABL1) after consolidation and at early period (3 months) after maintenance therapy significantly predicted subsequent relapse. All paired PML-RARa RQ-PCR were not detected except for one sample with early relapse. Patients with high WT1 expression at 3 months after maintenance therapy (n = 40) showed a significantly higher relapse rate (30.5 vs. 6.9%, P < 0.001) and inferior disease free survival (62.8 vs. 91.4%, P < 0.001). Multivariate analysis revealed that high peak leukocyte counts at diagnosis (HR = 6.4, P < 0.001) and high WT1 expression at 3 months after maintenance therapy (HR = 7.1, P < 0.001) were significant factors for prediction of relapse. Our data showed high post-remission WT1 expression was a reliable marker for prediction of subsequent molecular relapse in APL. In this high-risk group, early intervention with ATRA ± ATO, anti-CD33 antibody therapy, and WT1-specific therapy may be used for relapse prevention. Clinical Research Information Service (CRIS), KCT0002079.

Update on the core and developing cerebrospinal fluid biomarkers for Alzheimer disease

PubMed Central

Babić, Mirjana; Švob Štrac, Dubravka; Mück-Šeler, Dorotea; Pivac, Nela; Stanić, Gabrijela; Hof, Patrick R.; Šimić, Goran

2014-01-01

Alzheimer disease (AD) is a complex neurodegenerative disorder, whose prevalence will dramatically rise by 2050. Despite numerous clinical trials investigating this disease, there is still no effective treatment. Many trials showed negative or inconclusive results, possibly because they recruited only patients with severe disease, who had not undergone disease-modifying therapies in preclinical stages of AD before severe degeneration occurred. Detection of AD in asymptomatic at risk individuals (and a few presymptomatic individuals who carry an autosomal dominant monogenic AD mutation) remains impractical in many of clinical situations and is possible only with reliable biomarkers. In addition to early diagnosis of AD, biomarkers should serve for monitoring disease progression and response to therapy. To date, the most promising biomarkers are cerebrospinal fluid (CSF) and neuroimaging biomarkers. Core CSF biomarkers (amyloid β1-42, total tau, and phosphorylated tau) showed a high diagnostic accuracy but were still unreliable for preclinical detection of AD. Hence, there is an urgent need for detection and validation of novel CSF biomarkers that would enable early diagnosis of AD in asymptomatic individuals. This article reviews recent research advances on biomarkers for AD, focusing mainly on the CSF biomarkers. In addition to core CSF biomarkers, the potential usefulness of novel CSF biomarkers is discussed. PMID:25165049

Real-time in vivo Cherenkoscopy imaging during external beam radiation therapy.

PubMed

Zhang, Rongxiao; Gladstone, David J; Jarvis, Lesley A; Strawbridge, Rendall R; Jack Hoopes, P; Friedman, Oscar D; Glaser, Adam K; Pogue, Brian W

2013-11-01

Cherenkov radiation is induced when charged particles travel through dielectric media (such as biological tissue) faster than the speed of light through that medium. Detection of this radiation or excited luminescence during megavoltage external beam radiotherapy (EBRT) can allow emergence of a new approach to superficial dose estimation, functional imaging, and quality assurance for radiation therapy dosimetry. In this letter, the first in vivo Cherenkov images of a real-time Cherenkoscopy during EBRT are presented. The imaging system consisted of a time-gated intensified charge coupled device (ICCD) coupled with a commercial lens. The ICCD was synchronized to the linear accelerator to detect Cherenkov photons only during the 3.25-μs radiation bursts. Images of a tissue phantom under irradiation show that the intensity of Cherenkov emission is directly proportional to radiation dose, and images can be acquired at 4.7 frames/s with SNR>30. Cherenkoscopy was obtained from the superficial regions of a canine oral tumor during planned, Institutional Animal Care and Use Committee approved, conventional (therapeutically appropriate) EBRT irradiation. Coregistration between photography and Cherenkoscopy validated that Cherenkov photons were detected from the planned treatment region. Real-time images correctly monitored the beam field changes corresponding to the planned dynamic wedge movement, with accurate extent of overall beam field, and expected cold and hot regions.

Continuous remote monitoring of COPD patients-justification and explanation of the requirements and a survey of the available technologies.

PubMed

Tomasic, Ivan; Tomasic, Nikica; Trobec, Roman; Krpan, Miroslav; Kelava, Tomislav

2018-04-01

Remote patient monitoring should reduce mortality rates, improve care, and reduce costs. We present an overview of the available technologies for the remote monitoring of chronic obstructive pulmonary disease (COPD) patients, together with the most important medical information regarding COPD in a language that is adapted for engineers. Our aim is to bridge the gap between the technical and medical worlds and to facilitate and motivate future research in the field. We also present a justification, motivation, and explanation of how to monitor the most important parameters for COPD patients, together with pointers for the challenges that remain. Additionally, we propose and justify the importance of electrocardiograms (ECGs) and the arterial carbon dioxide partial pressure (PaCO 2 ) as two crucial physiological parameters that have not been used so far to any great extent in the monitoring of COPD patients. We cover four possibilities for the remote monitoring of COPD patients: continuous monitoring during normal daily activities for the prediction and early detection of exacerbations and life-threatening events, monitoring during the home treatment of mild exacerbations, monitoring oxygen therapy applications, and monitoring exercise. We also present and discuss the current approaches to decision support at remote locations and list the normal and pathological values/ranges for all the relevant physiological parameters. The paper concludes with our insights into the future developments and remaining challenges for improvements to continuous remote monitoring systems. Graphical abstract ᅟ.

Real-time detection and monitoring of the drug resistance of single myeloid leukemia cells by diffused total internal reflection.

PubMed

Liang, L; Jin, Y X; Zhu, X Q; Zhou, F L; Yang, Y

2018-05-15

Real-time detection and monitoring of the drug resistance of single cells have important significance in clinical diagnosis and therapy. Traditional methods operate a number of times for each individual concentration, and innovation is required for the design of more simple and efficient manipulation platforms with necessary higher sensitivity. Here, we have developed a novel diffused total internal reflection (TIR) method to perform drug metabolism and cytotoxicity analysis of trapped myeloid leukemia cells. Molm-13 cells, a type of acute myeloid leukemia cell, were chosen and injected into the device and fittingly captured by cell traps. Differing from previous studies, a series of different concentrations of azelaic acid (AZA) drug could be used from 0 mM to 50 mM through convection and diffusion processes in a single chip, with each concentration region featuring 50 cells, with a total of 549 cell trapping units. Thanks to the high sensitivity of the TIR method, only cells with the same drug concentration could be illuminated in the detection process. By adjusting the incident angle, we could exactly detect and monitor the drug resistance of the cells using different drug concentrations and the experimental resolution of the drug concentration was as small as 5 mM. Images of the membrane integrity and morphology of the cells in the bright field were measured and we also monitored the cell viabilities in the dark field over 2 hours. The effects of AZA on the Molm-13 cells were explored in different concentrations at the single cell level. Compared with the results of the traditional MTT assay method, the experimental results are more simple and accurate. A cell death of 5% at an AZA concentration of 5 mM was observed after 30 minutes, while a concentration of 40 mM corresponded to a 98% cell death. The designed method in this study provides a novel toolkit to control and monitor drug resistance at the single cell level more easily with higher sensitivity and we believe it has significant potential application in single cell quality assessment and medicine analysis in clinical practice.

SU-G-JeP4-03: Anomaly Detection of Respiratory Motion by Use of Singular Spectrum Analysis

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

Kotoku, J; Kumagai, S; Nakabayashi, S

Purpose: The implementation and realization of automatic anomaly detection of respiratory motion is a very important technique to prevent accidental damage during radiation therapy. Here, we propose an automatic anomaly detection method using singular value decomposition analysis. Methods: The anomaly detection procedure consists of four parts:1) measurement of normal respiratory motion data of a patient2) calculation of a trajectory matrix representing normal time-series feature3) real-time monitoring and calculation of a trajectory matrix of real-time data.4) calculation of an anomaly score from the similarity of the two feature matrices. Patient motion was observed by a marker-less tracking system using a depthmore » camera. Results: Two types of motion e.g. cough and sudden stop of breathing were successfully detected in our real-time application. Conclusion: Automatic anomaly detection of respiratory motion using singular spectrum analysis was successful in the cough and sudden stop of breathing. The clinical use of this algorithm will be very hopeful. This work was supported by JSPS KAKENHI Grant Number 15K08703.« less

Hair analysis for long-term monitoring of buprenorphine intake in opiate withdrawal.

PubMed

Pirro, Valentina; Fusari, Ivana; Di Corcia, Daniele; Gerace, Enrico; De Vivo, Enrico; Salomone, Alberto; Vincenti, Marco

2014-12-01

Buprenorphine (BUP) is a psychoactive pharmaceutical drug largely used to treat opiate addiction. Short-term therapeutic monitoring is supported by toxicological analysis of blood and urine samples, whereas long-term monitoring by means of hair analysis is rarely used. Aim of this work was to develop and validate a highly sensitive ultrahigh-performance liquid chromatography tandem mass spectrometry method to detect BUP and norbuprenorphine (NBUP) in head hair. Interindividual correlation between oral dosage of BUP and head hair concentration was investigated. Furthermore, an intra-individual study by means of segmental analysis was performed on subjects with variable maintenance dosage. Hair samples from a population of 79 patients in treatment for opiate addiction were analyzed. The validated ultrahigh-performance liquid chromatography tandem mass spectrometry protocol allowed to obtain limits of detection and quantification at 0.6 and 2.2 pg/mg for BUP and 5.0 and 17 pg/mg for NBUP, respectively. Validation criteria were satisfied, assuring selective analyte identification, high detection capability, and precise and accurate quantification. Significant positive correlation was found between constant oral BUP dosage (1-32 mg/d) and the summed up head hair concentrations of BUP and NBUP. Nevertheless, substantial interindividual variability limits the chance to predict the oral dosage taken by each subject from the measured concentrations in head hair. In contrast, strong correlation was observed in the results of intra-individual segmental analysis, which proved reliable to detect oral dosage variations during therapy. Remarkably, all hair samples yielded BUP concentrations higher than 10 pg/mg, even when the lowest dosage was administered. Thus, these results support the selection of 10 pg/mg as a cutoff value.

TH-AB-202-07: Radar Tracking of Respiratory Motion in Real Time

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

Fung, A; Li, C; Torres, C

Purpose: To propose a method of real time tracking of respiratory motion in patients undergoing radiation therapy. Radar technology can be employed to detection the movement of diaphragm and thoracic anatomy. Methods: A radar transceiver was specially designed. During experiment, the radar device was securely attached to a fixed frame. Respiratory motion was simulated with: 1) Varian RPM phantom, 2) Standard Imaging Respiratory Gating Platform. Signals recorded with radar equipment were compared with those measured with Varian RPM system as a reference. Results: Motion generated by Varian RPM phantom was recorded by the radar device, and compared to the signalsmore » recorded by RPM camera. The results showed exact agreement between the two monitoring equipments. Motion was also generated by Standard Imaging Respiratory Motion Platform. The results showed the radar device was capable of measuring motion of various amplitudes and periods. Conclusion: The proposed radar device is able to measure movements such as respiratory motion. Compared to state-of-the-art respiratory detection instrument, the radar device is shown to be equally precise and effective for monitoring respiration in radiation oncology patients.« less

Appetite-Focused Cognitive-Behavioral Therapy in the Treatment of Binge Eating with Purging

ERIC Educational Resources Information Center

Dicker, Stacy L.; Craighead, Linda Wilcoxon

2004-01-01

The first-line treatment for bulimia nervosa (BN), cognitive-behavioral therapy (CBT), uses food-based self-monitoring. Six young women presenting with BN or significant purging behavior were treated with a modification, Appetite-Focused CBT (CBT-AF), in which self-monitoring is based on appetite cues and food monitoring is proscribed. This change…

System theory in industrial patient monitoring: an overview.

PubMed

Baura, G D

2004-01-01

Patient monitoring refers to the continuous observation of repeating events of physiologic function to guide therapy or to monitor the effectiveness of interventions, and is used primarily in the intensive care unit and operating room. Commonly processed signals are the electrocardiogram, intraarterial blood pressure, arterial saturation of oxygen, and cardiac output. To this day, the majority of physiologic waveform processing in patient monitors is conducted using heuristic curve fitting. However in the early 1990s, a few enterprising engineers and physicians began using system theory to improve their core processing. Applications included improvement of signal-to-noise ratio, either due to low signal levels or motion artifact, and improvement in feature detection. The goal of this mini-symposium is to review the early work in this emerging field, which has led to technologic breakthroughs. In this overview talk, the process of system theory algorithm research and development is discussed. Research for industrial monitors involves substantial data collection, with some data used for algorithm training and the remainder used for validation. Once the algorithms are validated, they are translated into detailed specifications. Development then translates these specifications into DSP code. The DSP code is verified and validated per the Good Manufacturing Practices mandated by FDA.

A cancer cell-specific fluorescent probe for imaging Cu2 + in living cancer cells

NASA Astrophysics Data System (ADS)

Wang, Chao; Dong, Baoli; Kong, Xiuqi; Song, Xuezhen; Zhang, Nan; Lin, Weiying

2017-07-01

Monitoring copper level in cancer cells is important for the further understanding of its roles in the cell proliferation, and also could afford novel copper-based strategy for the cancer therapy. Herein, we have developed a novel cancer cell-specific fluorescent probe for the detecting Cu2 + in living cancer cells. The probe employed biotin as the cancer cell-specific group. Before the treatment of Cu2 +, the probe showed nearly no fluorescence. However, the probe can display strong fluorescence at 581 nm in response to Cu2 +. The probe exhibited excellent sensitivity and high selectivity for Cu2 + over the other relative species. Under the guidance of biotin group, could be successfully used for detecting Cu2 + in living cancer cells. We expect that this design strategy could be further applied for detection of the other important biomolecules in living cancer cells.

[Electroencephalography (EEG) recording techniques and artifact detection in early premature babies].

PubMed

Wallois, F; Vecchierini, M-F; Héberlé, C; Walls-Esquivel, E

2007-01-01

EEG recording techniques in early premature babies are not very different from those used for full-term neonates. Here, we emphasise the most important points: asepsis precautions, full knowledge of the clinical data and drug therapies, the fundamental role of a well-trained technician in supervising the EEG recording and monitoring the baby. The best electrode positions, the most informative montages and their standardisation between neurophysiological laboratories, are suggested. Artifact detection constitutes an important aspect of EEG signal analysis in preterm babies of less than 30 weeks. It is obviously necessary to discriminate between meaningful information and artefacts. The complexity of the signal in neonates makes artifact detection difficult. We present some characteristic features and describe some methods for eliminating them. We underline the positive aspect of some artifacts and their clinical use. We emphasise the crucial role of the technicians.

M13 phage-functionalized single-walled carbon nanotubes as nanoprobes for second near-infrared window fluorescence imaging of targeted tumors.

PubMed

Yi, Hyunjung; Ghosh, Debadyuti; Ham, Moon-Ho; Qi, Jifa; Barone, Paul W; Strano, Michael S; Belcher, Angela M

2012-03-14

Second near-infrared (NIR) window light (950-1400 nm) is attractive for in vivo fluorescence imaging due to its deep penetration depth in tissues and low tissue autofluorescence. Here we show genetically engineered multifunctional M13 phage can assemble fluorescent single-walled carbon nanotubes (SWNTs) and ligands for targeted fluorescence imaging of tumors. M13-SWNT probe is detectable in deep tissues even at a low dosage of 2 μg/mL and up to 2.5 cm in tissue-like phantoms. Moreover, targeted probes show specific and up to 4-fold improved uptake in prostate specific membrane antigen positive prostate tumors compared to control nontargeted probes. This M13 phage-based second NIR window fluorescence imaging probe has great potential for specific detection and therapy monitoring of hard-to-detect areas. © 2012 American Chemical Society

M13 phage-functionalized single-walled carbon nanotubes as nanoprobes for second near-infrared window fluorescence imaging of targeted tumors

PubMed Central

HAM, MOON-HO; QI, JIFA; BARONE, PAUL W.; STRANO, MICHAEL S.; BELCHER, ANGELA M.

2014-01-01

Second near-infrared (NIR) window light (950-1,400 nm) is attractive for in vivo fluorescence imaging due to its deep penetration depth in tissues and low tissue autofluorescence. Here we show genetically engineered multifunctional M13 phage can assemble fluorescent single-walled carbon nanotubes (SWNTs) and ligands for targeted fluorescence imaging of tumors. M13-SWNT probe is detectable in deep tissues even at a low dosage of 2 μg/mL and up to 2.5 cm in tissue-like phantoms. Moreover, targeted probes show specific and up to four-fold improved uptake in prostate specific membrane antigen positive prostate tumors compared to control non-targeted probes. This M13 phage-based second NIR window fluorescence imaging probe has great potential for specific detection and therapy monitoring of hard-to-detect areas. PMID:22268625

Prompt gamma and neutron detection in BNCT utilizing a CdTe detector.

PubMed

Winkler, Alexander; Koivunoro, Hanna; Reijonen, Vappu; Auterinen, Iiro; Savolainen, Sauli

2015-12-01

In this work, a novel sensor technology based on CdTe detectors was tested for prompt gamma and neutron detection using boronated targets in (epi)thermal neutron beam at FiR1 research reactor in Espoo, Finland. Dedicated neutron filter structures were omitted to enable simultaneous measurement of both gamma and neutron radiation at low reactor power (2.5 kW). Spectra were collected and analyzed in four different setups in order to study the feasibility of the detector to measure 478 keV prompt gamma photons released from the neutron capture reaction of boron-10. The detector proved to have the required sensitivity to detect and separate the signals from both boron neutron and cadmium neutron capture reactions, which makes it a promising candidate for monitoring the spatial and temporal development of in vivo boron distribution in boron neutron capture therapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple Hotspot Mutations Scanning by Single Droplet Digital PCR.

PubMed

Decraene, Charles; Silveira, Amanda B; Bidard, François-Clément; Vallée, Audrey; Michel, Marc; Melaabi, Samia; Vincent-Salomon, Anne; Saliou, Adrien; Houy, Alexandre; Milder, Maud; Lantz, Olivier; Ychou, Marc; Denis, Marc G; Pierga, Jean-Yves; Stern, Marc-Henri; Proudhon, Charlotte

2018-02-01

Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan ® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. The KRAS and EGFR assays were highly specific and both reached a limit of detection of <0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy. © 2017 American Association for Clinical Chemistry.

A comparison of two prompt gamma imaging techniques with collimator-based cameras for range verification in proton therapy

NASA Astrophysics Data System (ADS)

Lin, Hsin-Hon; Chang, Hao-Ting; Chao, Tsi-Chian; Chuang, Keh-Shih

2017-08-01

In vivo range verification plays an important role in proton therapy to fully utilize the benefits of the Bragg peak (BP) for delivering high radiation dose to tumor, while sparing the normal tissue. For accurately locating the position of BP, camera equipped with collimators (multi-slit and knife-edge collimator) to image prompt gamma (PG) emitted along the proton tracks in the patient have been proposed for range verification. The aim of the work is to compare the performance of multi-slit collimator and knife-edge collimator for non-invasive proton beam range verification. PG imaging was simulated by a validated GATE/GEANT4 Monte Carlo code to model the spot-scanning proton therapy and cylindrical PMMA phantom in detail. For each spot, 108 protons were simulated. To investigate the correlation between the acquired PG profile and the proton range, the falloff regions of PG profiles were fitted with a 3-line-segment curve function as the range estimate. Factors including the energy window setting, proton energy, phantom size, and phantom shift that may influence the accuracy of detecting range were studied. Results indicated that both collimator systems achieve reasonable accuracy and good response to the phantom shift. The accuracy of range predicted by multi-slit collimator system is less affected by the proton energy, while knife-edge collimator system can achieve higher detection efficiency that lead to a smaller deviation in predicting range. We conclude that both collimator systems have potentials for accurately range monitoring in proton therapy. It is noted that neutron contamination has a marked impact on range prediction of the two systems, especially in multi-slit system. Therefore, a neutron reduction technique for improving the accuracy of range verification of proton therapy is needed.

Monitoring evolution of HIFU-induced lesions with backscattered ultrasound

NASA Astrophysics Data System (ADS)

Anand, Ajay; Kaczkowski, Peter J.

2003-04-01

Backscattered radio frequency (rf) data from a modified commercial ultrasound scanner were collected in a series of in vitro experiments in which high intensity focused ultrasound (HIFU) was used to create lesions in freshly excised bovine liver tissue. Two signal processing approaches were used to visualize the temporal evolution of lesion formation. First, apparent tissue motion due to temperature rise was detected using cross-correlation techniques. Results indicate that differential processing of travel time can provide temperature change information throughout the therapy delivery phase and after HIFU has been turned off, over a relatively large spatial region. Second, changes in the frequency spectrum of rf echoes due to changes in the scattering properties of the heated region were observed well before the appearance of hyper-echogenic spots in the focal zone. Furthermore, the increase in attenuation in the lesion zone changes the measured backscatter spectrum from regions distal to it along the imaging beam. Both effects were visualized using spectral processing and display techniques that provide a color spatial map of these features for the clinician. Our results demonstrate potential for these ultrasound-based techniques in targeting and monitoring of HIFU therapy, and perhaps post-treatment visualization of HIFU-induced lesions.

Implementation and reimbursement of remote monitoring for cardiac implantable electronic devices in Europe: a survey from the health economics committee of the European Heart Rhythm Association.

PubMed

Mairesse, Georges H; Braunschweig, Frieder; Klersy, Katherine; Cowie, Martin R; Leyva, Francisco

2015-05-01

Remote monitoring (RM) of cardiac implantable electronic devices (CIEDs) permits early detection of arrhythmias, device, and lead failure and may also be useful in risk-predicting patient-related outcomes. Financial benefits for patients and healthcare organizations have also been shown. We sought to assess the implementation and funding of RM of CIEDs, including conventional pacemakers (PMs), implantable cardioverter defibrillators (ICDs), and cardiac resynchronization therapy (CRT) devices in Europe. Electronic survey from 43 centres in 15 European countries. In the study sample, RM was available in 22% of PM patients, 74% of ICD patients, and 69% of CRT patients. The most significant perceived benefits were the early detection of atrial arrhythmias in pacemaker patients, lead failure in ICD patients, and worsening heart failure in CRT patients. Remote monitoring was reported to lead a reduction of in-office follow-ups for all devices. The most important reported barrier to the implementation of RM for all CIEDs was lack of reimbursement (80% of centres). Physicians regard RM of CIEDs as a clinically useful technology that affords significant benefits for patients and healthcare organizations. Remote monitoring, however, is perceived as increasing workload. Reimbursement for RM is generally perceived as a major barrier to implementation. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Biosensors for Non-Invasive Detection of Celiac Disease Biomarkers in Body Fluids.

PubMed

Pasinszki, Tibor; Krebsz, Melinda

2018-06-16

Celiac disease is a chronic gluten-initiated autoimmune disorder that predominantly damages the mucosa of the small intestine in genetically-susceptible individuals. It affects a large and increasing number of the world’s population. The diagnosis of this disease and monitoring the response of patients to the therapy, which is currently a life-long gluten-free diet, require the application of reliable, rapid, sensitive, selective, simple, and cost-effective analytical tools. Celiac disease biomarker detection in full blood, serum, or plasma offers a non-invasive way to do this and is well-suited to being the first step of diagnosis. Biosensors provide a novel and alternative way to perform conventional techniques in biomarker sensing, in which electrode material and architecture play important roles in achieving sensitive, selective, and stable detection. There are many opportunities to build and modify biosensor platforms using various materials and detection methods, and the aim of the present review is to summarize developments in this field.

Detection of Life Threatening Ventricular Arrhythmia Using Digital Taylor Fourier Transform.

PubMed

Tripathy, Rajesh K; Zamora-Mendez, Alejandro; de la O Serna, José A; Paternina, Mario R Arrieta; Arrieta, Juan G; Naik, Ganesh R

2018-01-01

Accurate detection and classification of life-threatening ventricular arrhythmia episodes such as ventricular fibrillation (VF) and rapid ventricular tachycardia (VT) from electrocardiogram (ECG) is a challenging problem for patient monitoring and defibrillation therapy. This paper introduces a novel method for detection and classification of life-threatening ventricular arrhythmia episodes. The ECG signal is decomposed into various oscillatory modes using digital Taylor-Fourier transform (DTFT). The magnitude feature and a novel phase feature namely the phase difference (PD) are evaluated from the mode Taylor-Fourier coefficients of ECG signal. The least square support vector machine (LS-SVM) classifier with linear and radial basis function (RBF) kernels is employed for detection and classification of VT vs. VF, non-shock vs. shock and VF vs. non-VF arrhythmia episodes. The accuracy, sensitivity, and specificity values obtained using the proposed method are 89.81, 86.38, and 93.97%, respectively for the classification of Non-VF and VF episodes. Comparison with the performance of the state-of-the-art features demonstrate the advantages of the proposition.

Detection of Life Threatening Ventricular Arrhythmia Using Digital Taylor Fourier Transform

PubMed Central

Tripathy, Rajesh K.; Zamora-Mendez, Alejandro; de la O Serna, José A.; Paternina, Mario R. Arrieta; Arrieta, Juan G.; Naik, Ganesh R.

2018-01-01

Accurate detection and classification of life-threatening ventricular arrhythmia episodes such as ventricular fibrillation (VF) and rapid ventricular tachycardia (VT) from electrocardiogram (ECG) is a challenging problem for patient monitoring and defibrillation therapy. This paper introduces a novel method for detection and classification of life-threatening ventricular arrhythmia episodes. The ECG signal is decomposed into various oscillatory modes using digital Taylor-Fourier transform (DTFT). The magnitude feature and a novel phase feature namely the phase difference (PD) are evaluated from the mode Taylor-Fourier coefficients of ECG signal. The least square support vector machine (LS-SVM) classifier with linear and radial basis function (RBF) kernels is employed for detection and classification of VT vs. VF, non-shock vs. shock and VF vs. non-VF arrhythmia episodes. The accuracy, sensitivity, and specificity values obtained using the proposed method are 89.81, 86.38, and 93.97%, respectively for the classification of Non-VF and VF episodes. Comparison with the performance of the state-of-the-art features demonstrate the advantages of the proposition.

Novel fluorescence molecular imaging of chemotherapy-induced intestinal apoptosis

NASA Astrophysics Data System (ADS)

Levin, Galit; Shirvan, Anat; Grimberg, Hagit; Reshef, Ayelet; Yogev-Falach, Merav; Cohen, Avi; Ziv, Ilan

2009-09-01

Chemotherapy-induced enteropathy (CIE) is one of the most serious complications of anticancer therapy, and tools for its early detection and monitoring are highly needed. We report on a novel fluorescence method for detection of CIE, based on molecular imaging of the related apoptotic process. The method comprises systemic intravenous administration of the ApoSense fluorescent biomarker (N,N'-didansyl-L-cystine DDC) in vivo and subsequent fluorescence imaging of the intestinal mucosa. In the reported proof-of-concept studies, mice were treated with either taxol+cyclophosphamide or doxil. DDC was administered in vivo at various time points after drug administration, and tracer uptake by ileum tissue was subsequently evaluated by ex vivo fluorescent microscopy. Chemotherapy caused marked and selective uptake of DDC in ileal epithelial cells, in correlation with other hallmarks of apoptosis (i.e., DNA fragmentation and Annexin-V binding). Induction of DDC uptake occurred early after chemotherapy, and its temporal profile was parallel to that of the apoptotic process, as assessed histologically. DDC may therefore serve as a useful tool for detection of CIE. Future potential integration of this method with fluorescent endoscopic techniques, or development of radio-labeled derivatives of DDC for emission tomography, may advance early diagnosis and monitoring of this severe adverse effect of chemotherapy.

Quantitative evaluation of alternatively spliced mRNA isoforms by label-free real-time plasmonic sensing.

PubMed

Huertas, César S; Carrascosa, L G; Bonnal, S; Valcárcel, J; Lechuga, L M

2016-04-15

Alternative splicing of mRNA precursors enables cells to generate different protein outputs from the same gene depending on their developmental or homeostatic status. Its deregulation is strongly linked to disease onset and progression. Current methodologies for monitoring alternative splicing demand elaborate procedures and often present difficulties in discerning between closely related isoforms, e.g. due to cross-hybridization during their detection. Herein, we report a general methodology using a Surface Plasmon Resonance (SPR) biosensor for label-free monitoring of alternative splicing events in real-time, without any cDNA synthesis or PCR amplification requirements. We applied this methodology to RNA isolated from HeLa cells for the quantification of alternatively spliced isoforms of the Fas gene, involved in cancer progression through regulation of programmed cell death. We demonstrate that our methodology is isoform-specific, with virtually no cross-hybridization, achieving limits of detection (LODs) in the picoMolar (pM) range. Similar results were obtained for the detection of the BCL-X gene mRNA isoforms. The results were independently validated by RT-qPCR, with excellent concordance in the determination of isoform ratios. The simplicity and robustness of this biosensor technology can greatly facilitate the exploration of alternative splicing biomarkers in disease diagnosis and therapy. Copyright © 2015 Elsevier B.V. All rights reserved.

HSV2 acute retinal necrosis: diagnosis and monitoring with quantitative polymerase chain reaction.

PubMed

Cottet, L; Kaiser, L; Hirsch, H H; Baglivo, E

2009-06-01

To describe a case of HSV2 acute retinal necrosis (ARN) diagnosed and monitored with quantitative polymerase chain reaction (PCR) in ocular fluids. Case report. Quantitative PCR was performed in the aqueous humor (AH) and vitreous using primers specific for herpes virus. A positive PCR was found for HSV2 in the AH (>100,000,000 viral copies - 8.00 log/ml). After therapy, another anterior chamber tap showed a reduction of the viral load at 4.28 log/ml (19205 copies), confirming the efficacy of the treatment. After six months, PCR on the vitreous still showed the presence of HSV2 viral particles in the eye (3.14 log DNA copies/ml, 1379 copies) although the lesion was healed. This case demonstrates that PCR is useful to detect viral DNA in AH and vitreous and to monitor viral activity and therapeutic response. Viral DNA persists in ocular fluids for months in the presence of a healed infection.

Annual literature review of donor-specific HLA antibodies after organ transplantation.

PubMed

Kaneku, Hugo

2011-01-01

The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

Safety of air travel following acute myocardial infarction.

PubMed

Roby, Howard; Lee, Anna; Hopkins, Andrew

2002-02-01

A randomized, single-blind, controlled trial was carried out to: 1) examine the safety of patients flying on commercial airlines 2 wk after a myocardial infarction; 2) determine whether or not the use of supplemental oxygen was associated with a reduced risk of in-flight adverse events; and 3) determine the need for a medical escort. There were 38 patients who were prospectively and randomly assigned supplemental continuous oxygen therapy (2 L x min(-1) via nasal prongs; n = 19) or no oxygen (n = 19) during the flight. Prior to flying, an escorting doctor completed a medical questionnaire for each patient. Both groups underwent Holter monitoring throughout the flight. The major end-point was the development of inflight myocardial ischemia, as detected by Holter monitoring. Minor end-points included patients complaining of chest pain or dyspnea; the detection of bigeminy or trigeminy by Holter monitoring; or oxygen desaturation to less than 90%, as measured by pulse oximetry. Of the 38 patients enrolled, there was only 1 major end-point. This patient had a brief, self-limiting, asymptomatic episode of myocardial ischemia diagnosed by Holter monitoring. Minor end-points occurred in 13 (34%) patients. One patient had asymptomatic evidence of S-T depression on a transport monitor, but not on the Holter. Five patients had transient low (<90%) oxygen saturations, two complained of chest pain, and five had complex ventricular ectopic beats or periods of transient ventricular tachycardia. None of the minor end-points were associated with Holter evidence of myocardial ischemia. Of the 30 patients with completed questionnaires and Holter results, there was no difference in the incidence of minor end-points between the oxygen (5/13) and no oxygen groups (6/15) (p = 0.93). Intervention by the medical escort consisted of commencing oxygen therapy on those patients with low oxygen saturations and those with chest pain. Use of an already dispensed glyceryl trinitrate spray was initiated in one patient with chest pain that turned out to be non-ischemic when the Holter traces were later analyzed. This study suggests that, provided that care is taken during the immediate preflight and postflight phases not to overexert the patients, neither supplemental oxygen nor medical escorts are needed in the transportation of patients who fly 2 wk after acute myocardial infarction.

Understanding the positive benefit:risk profile of alemtuzumab in relapsing multiple sclerosis: perspectives from the Alemtuzumab Clinical Development Program.

PubMed

Havrdova, Eva; Cohen, Jeffrey A; Horakova, Dana; Kovarova, Ivana; Meluzinova, Eva

2017-01-01

The introduction of high-efficacy therapies for relapsing-remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss. In two of the studies, alemtuzumab-treated patients had a significantly reduced risk of 6-month confirmed disease worsening, compared with subcutaneous interferon beta-1a. Benefits were maintained throughout 5 years, with a majority of patients receiving no alemtuzumab retreatment or other disease-modifying therapy. Trial results support alemtuzumab's manageable, consistent safety profile in relapsing-remitting multiple sclerosis. Infusion-associated reactions, the most frequent adverse events (AEs), can be minimized by corticosteroid pretreatment, monitoring, and symptomatic management. Other AEs include infections and autoimmune events. Oral anti-herpes prophylaxis should be initiated on the first day of each alemtuzumab treatment course and continued according to local guidelines. Overall cancer risk was lower in the alemtuzumab clinical trials than in a reference population; however, continuing surveillance will determine if alemtuzumab may be associated with certain malignancies such as thyroid papillary carcinoma and melanoma, which are currently identified as potential risks. The post-approval risk management strategy includes a safety monitoring program. Autoimmune AEs (thyroid events, immune thrombocytopenia, nephropathies) can be detected in a timely manner with the monitoring program, which includes physician and patient education about the signs and symptoms, monthly renal and hematologic monitoring, and quarterly thyroid function monitoring for 48 months after the last alemtuzumab course. Education, vigilance by physicians and patients, and monthly laboratory monitoring are recommended to maintain alemtuzumab's positive benefit:risk profile.

Neural underpinnings for model-oriented therapy of aphasic word production.

PubMed

Abel, Stefanie; Weiller, Cornelius; Huber, Walter; Willmes, Klaus

2014-05-01

Model-oriented therapies of aphasic word production have been shown to be effective, with item-specific therapy effects being larger than generalisation effects for untrained items. However, it remains unclear whether semantic versus phonological therapy lead to differential effects, depending on type of lexical impairment. Functional imaging studies revealed that mainly left-hemisphere, perisylvian brain areas were involved in successful therapy-induced recovery of aphasic word production. However, the neural underpinnings for model-oriented therapy effects have not received much attention yet. We aimed at identifying brain areas indicating (1) general therapy effects using a naming task measured by functional magnetic resonance imaging (fMRI) in 14 patients before and after a 4-week naming therapy, which comprised increasing semantic and phonological cueing-hierarchies. We also intended to reveal differential effects (2) of training versus generalisation, (3) of therapy methods, and (4) of type of impairment as assessed by the connectionist Dell model. Training effects were stronger than generalisation effects, even though both were significant. Furthermore, significant impairment-specific therapy effects were observed for patients with phonological disorders (P-patients). (1) Left inferior frontal gyrus, pars opercularis (IFGoper), was a positive predictor of therapy gains while the right caudate was a negative predictor. Moreover, less activation decrease due to therapy in left-hemisphere temporo-parietal language areas was positively correlated with therapy gains. (2) Naming of trained compared to untrained words yielded less activation decrease in left superior temporal gyrus (STG) and precuneus, bilateral thalamus, and right caudate due to therapy. (3) Differential therapy effects could be detected in the right superior parietal lobule for the semantic method, and in regions involving bilateral anterior and mid cingulate, right precuneus, and left middle/superior frontal gyrus for the phonological method. (4) Impairment-specific changes of activation were found for P-patients in left IFGoper. Patients with semantic disorders (S-patients) relied on right frontal areas involving IFG, pars triangularis. After therapy, they revealed less activation decrease in areas involving left STG, caudate, paracentral lobule, and right rolandic operculum. Regarding naming performance, the present study corroborates previous findings on training and generalisation effects and reveals differential therapy effects for P-patients. Moreover, brain imaging results confirm a predominance of (1) general effects in the left brain hemisphere. (2) Brain regions related to visual strategy, monitoring/feedback, and articulatory patterns were characteristic for the familiar trained items. (3) Distinct regions associated with strategies, monitoring capacities, and linguistic information indicate the specific therapeutic influence on word retrieval. (4) While P-patients relied more on preserved phonological functions in the left hemisphere, S-patients revealed right-sided compensation of semantic processing as well as increased strategic efforts in both hemispheres. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Use of case-based reasoning to enhance intensive management of patients on insulin pump therapy.

PubMed

Schwartz, Frank L; Shubrook, Jay H; Marling, Cynthia R

2008-07-01

This study was conducted to develop case-based decision support software to improve glucose control in patients with type 1 diabetes mellitus (T1DM) on insulin pump therapy. While the benefits of good glucose control are well known, achieving and maintaining good glucose control remains a difficult task. Case-based decision support software may assist by recalling past problems in glucose control and their associated therapeutic adjustments. Twenty patients with T1DM on insulin pumps were enrolled in a 6-week study. Subjects performed self-glucose monitoring and provided daily logs via the Internet, tracking insulin dosages, work, sleep, exercise, meals, stress, illness, menstrual cycles, infusion set changes, pump problems, hypoglycemic episodes, and other events. Subjects wore a continuous glucose monitoring system at weeks 1, 3, and 6. Clinical data were interpreted by physicians, who explained the relationship between life events and observed glucose patterns as well as treatment rationales to knowledge engineers. Knowledge engineers built a prototypical system that contained cases of problems in glucose control together with their associated solutions. Twelve patients completed the study. Fifty cases of clinical problems and solutions were developed and stored in a case base. The prototypical system detected 12 distinct types of clinical problems. It displayed the stored problems that are most similar to the problems detected, and offered learned solutions as decision support to the physician. This software can screen large volumes of clinical data and glucose levels from patients with T1DM, identify clinical problems, and offer solutions. It has potential application in managing all forms of diabetes.

Clinical feasibility test on a minimally invasive laser therapy system in microsurgery of nerves.

PubMed

Mack, K F; Leinung, M; Stieve, M; Lenarz, T; Schwab, B

2008-01-01

The clinical feasibility test described here evaluates the basis for a laser therapy system that enables tumour tissue to be separated from nerves in a minimally invasive manner. It was first investigated whether, using an Er:YAG laser, laser-induced nerve (specifically, facial nerve) responses in the rabbit in vivo can be reliably detected with the hitherto standard monitoring techniques. Peripherally recordable neuromuscular signals (i.e. compound action potentials, CAPs) were used to monitor nerve function and to establish a feedback loop. The first occurrence of laser-evoked CAPs was taken as the criterion for deciding when to switch off the laser. When drawing up criteria governing the control and termination of the laser application, the priority was the maintenance of nerve function. Five needle-electrode arrays specially developed for this purpose, each with a miniature preamplifier, were then placed into the facial musculature instead of single-needle electrodes. The system was tested in vivo under realistic surgical conditions (i.e. facial-nerve surgery in the rabbit). This modified multi-channel electromyography (EMG) system enabled laser-evoked CAPs to be detected that have amplitudes 10 times smaller than those picked up by commercially available systems. This optimization, and the connection of the neuromuscular unit with the Er:YAG laser via the electrode array to create a feedback loop, were designed to make it possible to maintain online control of the laser ablation process in the vicinity of neuronal tissue, thus ensuring that tissue excision is both reliable and does not affect function. Our results open up new possibilities in minimally invasive surgery near neural structures.

Clinical significance of minimal residual disease at day 15 and at the end of therapy in childhood acute lymphoblastic leukaemia.

PubMed

Sutton, Rosemary; Venn, Nicola C; Tolisano, Jonathan; Bahar, Anita Y; Giles, Jodie E; Ashton, Lesley J; Teague, Lochie; Rigutto, Gemma; Waters, Keith; Marshall, Glenn M; Haber, Michelle; Norris, Murray D

2009-08-01

Detection of minimal residual disease (MRD) after induction and consolidation therapy is highly predictive of outcome for childhood acute lymphoblastic leukaemia (ALL) and is used to identify patients at high risk of relapse in several current clinical trials. To evaluate the prognostic significance of MRD at other treatment phases, MRD was measured by real-time quantitative polymerase chain reaction on a selected group of 108 patients enrolled on the Australian and New Zealand Children's Cancer Study Group Study VII including 36 patients with a bone marrow or central nervous system relapse and 72 matched patients in first remission. MRD was prognostic of outcome at all five treatment phases tested: at day 15 (MRD > or = 5 x 10(-2), log rank P < 0.0001), day 35 (> or =1 x 10(-2), P = 0.0001), 4 months (> or =5 x 10(-4), P < 0.0001), 12 months (MRD > or = 1 x 10(-4), P = 0.006) and 24 months (MRD > or = 1 x 10(-4), P < 0.0001). Day 15 was the best early MRD time-point to differentiate between patients with high, intermediate and low risk of relapse. MRD testing at 12 and particularly at 24 months, detected molecular relapses in some patients up to 6 months before clinical relapse. This raised the question of whether a strategy of late monitoring and salvage therapy will improve outcome.

Visual detection of glial cell line-derived neurotrophic factor based on a molecular translator and isothermal strand-displacement polymerization reaction

PubMed Central

Zhang, Li-Yong; Xing, Tao; Du, Li-Xin; Li, Qing-Min; Liu, Wei-Dong; Wang, Ji-Yue; Cai, Jing

2015-01-01

Background Glial cell line-derived neurotrophic factor (GDNF) is a small protein that potently promotes the survival of many types of neurons. Detection of GDNF is vital to monitoring the survival of sympathetic and sensory neurons. However, the specific method for GDNF detection is also un-discovered. The purpose of this study is to explore the method for protein detection of GDNF. Methods A novel visual detection method based on a molecular translator and isothermal strand-displacement polymerization reaction (ISDPR) has been proposed for the detection of GDNF. In this study, a molecular translator was employed to convert the input protein to output deoxyribonucleic acid signal, which was further amplified by ISDPR. The product of ISDPR was detected by a lateral flow biosensor within 30 minutes. Results This novel visual detection method based on a molecular translator and ISDPR has very high sensitivity and selectivity, with a dynamic response ranging from 1 pg/mL to 10 ng/mL, and the detection limit was 1 pg/mL of GDNF. Conclusion This novel visual detection method exhibits high sensitivity and selectivity, which is very simple and universal for GDNF detection to help disease therapy in clinical practice. PMID:25848224

Application of proton boron fusion reaction to radiation therapy: A Monte Carlo simulation study

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

Yoon, Do-Kun; Jung, Joo-Young; Suh, Tae Suk, E-mail: suhsanta@catholic.ac.kr

2014-12-01

Three alpha particles are emitted from the point of reaction between a proton and boron. The alpha particles are effective in inducing the death of a tumor cell. After boron is accumulated in the tumor region, the emitted from outside the body proton can react with the boron in the tumor region. An increase of the proton's maximum dose level is caused by the boron and only the tumor cell is damaged more critically. In addition, a prompt gamma ray is emitted from the proton boron reaction point. Here, we show that the effectiveness of the proton boron fusion therapymore » was verified using Monte Carlo simulations. We found that a dramatic increase by more than half of the proton's maximum dose level was induced by the boron in the tumor region. This increase occurred only when the proton's maximum dose point was located within the boron uptake region. In addition, the 719 keV prompt gamma ray peak produced by the proton boron fusion reaction was positively detected. This therapy method features the advantages such as the application of Bragg-peak to the therapy, the accurate targeting of tumor, improved therapy effects, and the monitoring of the therapy region during treatment.« less

Sudden blast phase in chronic myeloid leukemia developed during nilotinib therapy after major molecular response was achieved.

PubMed

Okada, Yosuke; Sato, Ken; Kobayashi, Shinichi; Nagao, Shigeki; Takano, Kosuke; Teramoto, Masahiro; Tachi, Noriaki; Kawamura, Toshikuni; Horiuchi, Toshikatsu; Kato, Shoichiro; Saga, Reina; Maekawa, Takaaki; Yamamura, Takeshi; Watanabe, Junichi; Kobayashi, Ayako; Kimura, Fumihiko

2018-04-01

Sudden blast phase (SBP) is a rare event in which patients with chronic myeloid leukemia (CML) in complete cytogenetic response (CCyR) rapidly progress to the blast phase. Few patients on second-generation tyrosine kinase inhibitors (2nd TKIs) have been reported to develop SBP. Here, we report a 45-year-old man diagnosed with CML in the chronic phase in April 2008 and immediately started on imatinib therapy. He achieved CCyR 12 months after starting imatinib therapy. Imatinib was followed by treatment with the 2nd TKIs nilotinib and dasatinib from January 2011 to yield a better response. He achieved major molecular response (MMR) during dasatinib therapy in February 2012, but did not tolerate dasatinib well; hence, he was switched to nilotinib in July 2012. In December 2015, he presented at our hospital with fever and lumbago. A complete blood count revealed a white blood cell count of 30,500/µL with 60% blasts, leading to diagnosis of SBP. After dasatinib therapy and conventional chemotherapy, he again achieved MMR. This case demonstrates that SBP may occur after achieving MMR on treatment with 2nd TKIs. Continuous careful monitoring is required for the early detection of SBP, even in patients who have achieved MMR.

A systematic review of goal directed fluid therapy: rating of evidence for goals and monitoring methods.

PubMed

Wilms, Heath; Mittal, Anubhav; Haydock, Matthew D; van den Heever, Marc; Devaud, Marcello; Windsor, John A

2014-04-01

To review the literature on goal directed fluid therapy and evaluate the quality of evidence for each combination of goal and monitoring method. A search of major digital databases and hand search of references was conducted. All studies assessing the clinical utility of a specific fluid therapy goal or set of goals using any monitoring method were included. Data was extracted using a pre-determined pro forma and papers were evaluated using GRADE principles to assess evidence quality. Eighty-one papers met the inclusion criteria, investigating 31 goals and 22 methods for monitoring fluid therapy in 13052 patients. In total there were 118 different goal/method combinations. Goals with high evidence quality were central venous lactate and stroke volume index. Goals with moderate quality evidence were sublingual microcirculation flow, the oxygen extraction ratio, cardiac index, cardiac output, and SVC collapsibility index. This review has highlighted the plethora of goals and methods for monitoring fluid therapy. Strikingly, there is scant high quality evidence, in particular for non-invasive G/M combinations in non-operative and non-intensive care settings. There is an urgent need to address this research gap, which will be helped by methodologies to compare utility of G/M combinations. Copyright © 2014 Elsevier Inc. All rights reserved.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target.

PubMed

Mattei, I; Bini, F; Collamati, F; De Lucia, E; Frallicciardi, P M; Iarocci, E; Mancini-Terracciano, C; Marafini, M; Muraro, S; Paramatti, R; Patera, V; Piersanti, L; Pinci, D; Rucinski, A; Russomando, A; Sarti, A; Sciubba, A; Solfaroli Camillocci, E; Toppi, M; Traini, G; Voena, C; Battistoni, G

2017-02-21

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at [Formula: see text] and [Formula: see text] with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

Secondary radiation measurements for particle therapy applications: prompt photons produced by 4He, 12C and 16O ion beams in a PMMA target

NASA Astrophysics Data System (ADS)

Mattei, I.; Bini, F.; Collamati, F.; De Lucia, E.; Frallicciardi, P. M.; Iarocci, E.; Mancini-Terracciano, C.; Marafini, M.; Muraro, S.; Paramatti, R.; Patera, V.; Piersanti, L.; Pinci, D.; Rucinski, A.; Russomando, A.; Sarti, A.; Sciubba, A.; Solfaroli Camillocci, E.; Toppi, M.; Traini, G.; Voena, C.; Battistoni, G.

2017-02-01

Charged particle beams are used in particle therapy (PT) to treat oncological patients due to their selective dose deposition in tissues with respect to the photons and electrons used in conventional radiotherapy. Heavy (Z  >  1) PT beams can additionally be exploited for their high biological effectiveness in killing cancer cells. Nowadays, protons and carbon ions are used in PT clinical routines. Recently, interest in the potential application of helium and oxygen beams has been growing. With respect to protons, such beams are characterized by their reduced multiple scattering inside the body, increased linear energy transfer, relative biological effectiveness and oxygen enhancement ratio. The precision of PT demands online dose monitoring techniques, crucial to improving the quality assurance of any treatment: possible patient mis-positioning and biological tissue changes with respect to the planning CT scan could negatively affect the outcome of the therapy. The beam range confined in the irradiated target can be monitored thanks to the neutral or charged secondary radiation emitted by the interactions of hadron beams with matter. Among these secondary products, prompt photons are produced by nuclear de-excitation processes, and at present, different dose monitoring and beam range verification techniques based on prompt-γ detection are being proposed. It is hence of importance to perform γ yield measurement in therapeutic-like conditions. In this paper we report on the yields of prompt photons produced by the interaction of helium, carbon and oxygen ion beams with a poly-methyl methacrylate (PMMA) beam stopping target. The measurements were performed at the Heidelberg Ion-Beam Therapy Center (HIT) with beams of different energies. An LYSO scintillator, placed at {{60}\\circ} and {{90}\\circ} with respect to the beam direction, was used as the photon detector. The obtained γ yields for the carbon ion beams are compared with results from the literature, while no other results from helium and oxygen beams have been published yet. A discussion on the expected resolution of a slit camera detector is presented, demonstrating the feasibility of a prompt-γ-based monitoring technique for PT treatments using helium, carbon and oxygen ion beams.

GC-MS/MS detects potential pregabalin abuse in susceptible subjects' hair.

PubMed

Ianni, Federica; Aroni, Kyriaki; Gili, Alessio; Sardella, Roccaldo; Bacci, Mauro; Lancia, Massimo; Natalini, Benedetto; Gambelunghe, Cristiana

2018-06-01

Pregabalin, a GABA analogue, binds to the alpha 2 delta subunit of voltage-dependent calcium channels. It is recognised as efficacious in pathologies such as epilepsy, neuropathic pain, and anxiety disorders. Since pregabalin prescriptions have increased worldwide, reports of its abuse have been accumulating, mainly in patients with opioid abuse disorders. The present study investigated potential pregabalin abuse by means of hair analysis, a matrix that provides valuable retrospective information. Half of the pool of 280 susceptible patients had been occasional drug users and were being monitored for driving licence renewals. The other 140 patients had a history of opiate dependency and were monitored to assess compliance with methadone therapy. In view of determining pregabalin in hair samples, it was extracted in methanol, successfully derivatised to give the ethyl chloroformate derivative, and finally pregabalin was analysed by gas chromatography-tandem mass spectrometry. Selectivity, linearity, limit of detection, limit of quantification, recovery, intra- and inter-day precision, and accuracy of the quantification procedure were appraised. Pregabalin limits of detection and quantification were 30 pg/mg and 50 pg/mg, respectively. We found 10.7% of hair samples from methadone patients and 4.29% from occasional drug users were positive to pregabalin without medical prescription. The mean pregabalin concentration in hair was higher than in consumers with medical indications (1.45 ng/mg vs 0.74 ng/mg). These results suggest that pregabalin possesses a significant abuse potential particularly among individuals attending opiate dependence services and that pregabalin abuse is a serious emerging issue, which should be carefully monitored. Copyright © 2017 John Wiley & Sons, Ltd.

Diagnostic value of prehospital ECG in acute stroke patients.

PubMed

Bobinger, Tobias; Kallmünzer, Bernd; Kopp, Markus; Kurka, Natalia; Arnold, Martin; Heider, Stefan; Schwab, Stefan; Köhrmann, Martin

2017-05-16

To investigate the diagnostic yield of prehospital ECG monitoring provided by emergency medical services in the case of suspected stroke. Consecutive patients with acute stroke admitted to our tertiary stroke center via emergency medical services and with available prehospital ECG were prospectively included during a 12-month study period. We assessed prehospital ECG recordings and compared the results to regular 12-lead ECG on admission and after continuous ECG monitoring at the stroke unit. Overall, 259 patients with prehospital ECG recording were included in the study (90.3% ischemic stroke, 9.7% intracerebral hemorrhage). Atrial fibrillation (AF) was detected in 25.1% of patients, second-degree or greater atrioventricular block in 5.4%, significant ST-segment elevation in 5.0%, and ventricular ectopy in 9.7%. In 18 patients, a diagnosis of new-onset AF with direct clinical consequences for the evaluation and secondary prevention of stroke was established by the prehospital recordings. In 2 patients, the AF episodes were limited to the prehospital period and were not detected by ECG on admission or during subsequent monitoring at the stroke unit. Of 126 patients (48.6%) with relevant abnormalities in the prehospital ECG, 16.7% received medical antiarrhythmic therapy during transport to the hospital, and 6.4% were transferred to a cardiology unit within the first 24 hours in the hospital. In a selected cohort of patients with stroke, the in-field recordings of the ECG detected a relevant rate of cardiac arrhythmia. The results can add to the in-hospital evaluation and should be considered in prehospital care of acute stroke. © 2017 American Academy of Neurology.

A protocol for a prospective observational study using chest and thumb ECG: transient ECG assessment in stroke evaluation (TEASE) in Sweden.

PubMed

Magnusson, Peter; Koyi, Hirsh; Mattsson, Gustav

2018-04-03

Atrial fibrillation (AF) causes ischaemic stroke and based on risk factor evaluation warrants anticoagulation therapy. In stroke survivors, AF is typically detected with short-term ECG monitoring in the stroke unit. Prolonged continuous ECG monitoring requires substantial resources while insertable cardiac monitors are invasive and costly. Chest and thumb ECG could provide an alternative for AF detection poststroke.The primary objective of our study is to assess the incidence of newly diagnosed AF during 28 days of chest and thumb ECG monitoring in cryptogenic stroke. Secondary objectives are to assess health-related quality of life (HRQoL) using short-form health survey (SF-36) and the feasibility of the Coala Heart Monitor in patients who had a stroke. Stroke survivors in Region Gävleborg, Sweden, will be eligible for the study from October 2017. Patients with a history of ischaemic stroke without documented AF before or during ECG evaluation in the stroke unit will be evaluated by the chest and thumb ECG system Coala Heart Monitor. The monitoring system is connected to a smartphone application which allows for remote monitoring and prompt advice on clinical management. Over a period of 28 days, patients will be monitored two times a day and may activate the ECG recording at symptoms. On completion, the system is returned by mail. This system offers a possibility to evaluate the presence of AF poststroke, but the feasibility of this system in patients who recently suffered from a stroke is unknown. In addition, HRQoL using SF-36 in comparison to Swedish population norms will be assessed. The feasibility of the Coala Heart Monitor will be assessed by a self-developed questionnaire. The study was approved by The Regional Ethical Committee in Uppsala (2017/321). The database will be closed after the last follow-up, followed by statistical analyses, interpretation of results and dissemination to a scientific journal. NCT03301662; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Gold Nanoparticle Based Platforms for Circulating Cancer Marker Detection

PubMed Central

Huang, Xiaohua; O'Connor, Ryan; Kwizera, Elyahb Allie

2017-01-01

Detection of cancer-related circulating biomarkers in body fluids has become a cutting-edge technology that has the potential to noninvasively screen cancer, diagnose cancer at early stage, monitor tumor progression, and evaluate therapy responses. Traditional molecular and cellular detection methods are either insensitive for early cancer intervention or technically costly and complicated making them impractical for typical clinical settings. Due to their exceptional structural and functional properties that are not available from bulk materials or discrete molecules, nanotechnology is opening new horizons for low cost, rapid, highly sensitive, and highly specific detection of circulating cancer markers. Gold nanoparticles have emerged as a unique nanoplatform for circulating biomarker detection owning to their advantages of easy synthesis, facile surface chemistry, excellent biocompatibility, and remarkable structure and environment sensitive optical properties. In this review, we introduce current gold nanoparticle-based technology platforms for the detection of four major classes of circulating cancer markers - circulating tumor cells, vesicles, nucleic acids, and proteins. The techniques will be summarized in terms of signal detection strategies. Distinctive examples are provided to highlight the state-of-the-art technologies that significantly advance basic and clinical cancer research. PMID:28217434

[Diabetes and pregnancy].

PubMed

Somville, T

1990-01-01

In recent years, new findings in the pathophysiology and treatment of diabetes mellitus during pregnancy and the development of improved fetal monitoring methods have considerably reduced the risk for mother and child. Given good metabolism the fertility of diabetics is comparable to that of nondiabetics. Perinatal mortality in centers is below 2%, and in 40% of the cases it is caused by congenital malformations. The incidence of malformations is 4-8%. Regulation of metabolism to near-normal values is vital for further improvement of mortality and morbidity rates, and should be aimed for prior to conception. In many cases insufficient attention is given to gestational diabetes. The risks accompanying untreated gestational diabetes are underestimated. In approx. 15% of such patients insulin therapy during pregnancy is necessary in addition to dietary measures. The goal of near normal metabolism (60-120 mg/dl, with mean daily values around 85-90 mg/dl) can usually be achieved during training, either prior to conception or at the latest during early pregnancy, by improved substitutional insulin therapy or insulin pump therapy. Short-term combined internalistic-obstetric follow-up at 14-day intervals ensures early prevention and detection of complications. The pregnancy can be continued to term in over 80% of cases, and spontaneous birth aimed for as the primary goal in the majority. With careful monitoring of metabolism, diabetics with no vascular complications may take low-dosage ovulation inhibitors to prevent conception. In isolated cases termination may be indicated in patients with severe vascular complications (proliferative retinopathy, severe nephropathy).

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay.

PubMed

Naik, Rishi D; Vaezi, Michael F

2015-07-01

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.

Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

PubMed

Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

2016-11-01

Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., <500 copies/mL plasma) using generalized linear mixed-effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

Molecular imaging of photodynamic therapy

NASA Astrophysics Data System (ADS)

Chang, Sung K.; Errabelli, Divya; Rizvi, Imran; Solban, Nicolas; O'Riordan, Katherine; Hasan, Tayyaba

2006-02-01

Recent advances in light sources, detectors and other optical imaging technologies coupled with the development of novel optical contrast agents have enabled real-time, high resolution, in vivo monitoring of molecular targets. Noninvasive monitoring of molecular targets is particularly relevant to photodynamic therapy (PDT), including the delivery of photosensitizer in the treatment site and monitoring of molecular and physiological changes following treatment. Our lab has developed optical imaging technologies to investigate these various aspects of photodynamic therapy (PDT). We used a laser scanning confocal microscope to monitor the pharmacokinetics of various photosensitizers in in vitro as well as ex vivo samples, and developed an intravital fluorescence microscope to monitor photosensitizer delivery in vivo in small animals. A molecular specific contrast agent that targets the vascular endothelial growth factor (VEGF) was developed to monitor the changes in the protein expression following PDT. We were then able to study the physiological changes due to post-treatment VEGF upregulation by quantifying vascular permeability with in vivo imaging.

Monitoring and Management of Toxicities of Novel B Cell Signaling Agents.

PubMed

Rhodes, Joanna; Mato, Anthony; Sharman, Jeff P

2018-04-11

B cell signaling agents, including ibrutinib, idelalisib, and the BCL-2 inhibitor venetoclax have become an integral part of therapy for patients with non-Hodgkin's lymphomas. The toxicity profiles of these medications is distinct from chemoimmunotherapy. Here, we will review the mechanism of action of these drugs, their efficacy, and toxicity management. Ibrutinib use is associated with increased risk of atrial fibrillation and bleeding which can be managed using dose interruptions and modifications. Patients on idelalisib require close clinical and frequent laboratory monitoring, particularly of liver function tests to ensure there are no serious adverse events. Monitoring for infections is important in patients on both idelalisib and ibrutinib. Venetoclax requires close clinical and laboratory monitoring to prevent significant tumor lysis. Targeted B cell receptor therapies each have unique side effect profiles which require careful clinical monitoring. As we continue to use these therapies, optimal management strategies will continue to be elucidated.

Supervision, monitoring and evaluation of nationwide scale-up of antiretroviral therapy in Malawi.

PubMed Central

Libamba, Edwin; Makombe, Simon; Mhango, Eustice; de Ascurra Teck, Olga; Limbambala, Eddie; Schouten, Erik J.; Harries, Anthony D.

2006-01-01

OBJECTIVE: To describe the supervision, monitoring and evaluation strategies used to assess the delivery of antiretroviral therapy during nationwide scale-up of treatment in Malawi. METHODS: In the first quarter of 2005, the HIV Unit of the Ministry of Health and its partners (the Lighthouse Clinic; Médecins Sans Frontières-Belgium, Thyolo district; and WHO's Country Office) undertook structured supervision and monitoring of all public sector health facilities in Malawi delivering antiretroviral therapy. FINDINGS: Data monitoring showed that by the end of 2004, there were 13,183 patients (5274 (40%) male, 12 527 (95%) adults) who had ever started antiretroviral therapy. Of patients who had ever started, 82% (10 761/13,183) were alive and taking antiretrovirals; 8% (1026/13,183) were dead; 8% (1039/13,183) had been lost to follow up; <1% (106/13,183) had stopped treatment; and 2% (251/13,183) had transferred to another facility. Of those alive and on antiretrovirals, 98% (7098/7258) were ambulatory; 85% (6174/7258) were fit to work; 10% (456/4687) had significant side effects; and, based on pill counts, 96% (6824/7114) had taken their treatment correctly. Mistakes in the registration and monitoring of patients were identified and corrected. Drug stocks were checked, and one potential drug stock-out was averted. As a result of the supervisory visits, by the end of March 2005 recruitment of patients to facilities scheduled to start delivering antiretroviral therapy had increased. CONCLUSION: This report demonstrates the importance of early supervision for sites that are starting to deliver antiretroviral therapy, and it shows the value of combining data collection with supervision. Making regular supervisory and monitoring visits to delivery sites are essential for tracking the national scale-up of delivery of antiretrovirals. PMID:16628306

Analysis of different device-based intrathoracic impedance vectors for detection of heart failure events (from the Detect Fluid Early from Intrathoracic Impedance Monitoring study).

PubMed

Heist, E Kevin; Herre, John M; Binkley, Philip F; Van Bakel, Adrian B; Porterfield, James G; Porterfield, Linda M; Qu, Fujian; Turkel, Melanie; Pavri, Behzad B

2014-10-15

Detect Fluid Early from Intrathoracic Impedance Monitoring (DEFEAT-PE) is a prospective, multicenter study of multiple intrathoracic impedance vectors to detect pulmonary congestion (PC) events. Changes in intrathoracic impedance between the right ventricular (RV) coil and device can (RVcoil→Can) of implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy ICDs (CRT-Ds) are used clinically for the detection of PC events, but other impedance vectors and algorithms have not been studied prospectively. An initial 75-patient study was used to derive optimal impedance vectors to detect PC events, with 2 vector combinations selected for prospective analysis in DEFEAT-PE (ICD vectors: RVring→Can + RVcoil→Can, detection threshold 13 days; CRT-D vectors: left ventricular ring→Can + RVcoil→Can, detection threshold 14 days). Impedance changes were considered true positive if detected <30 days before an adjudicated PC event. One hundred sixty-two patients were enrolled (80 with ICDs and 82 with CRT-Ds), all with ≥1 previous PC event. One hundred forty-four patients provided study data, with 214 patient-years of follow-up and 139 PC events. Sensitivity for PC events of the prespecified algorithms was as follows: ICD: sensitivity 32.3%, false-positive rate 1.28 per patient-year; CRT-D: sensitivity 32.4%, false-positive rate 1.66 per patient-year. An alternative algorithm, ultimately approved by the US Food and Drug Administration (RVring→Can + RVcoil→Can, detection threshold 14 days), resulted in (for all patients) sensitivity of 21.6% and a false-positive rate of 0.9 per patient-year. The CRT-D thoracic impedance vector algorithm selected in the derivation study was not superior to the ICD algorithm RVring→Can + RVcoil→Can when studied prospectively. In conclusion, to achieve an acceptably low false-positive rate, the intrathoracic impedance algorithms studied in DEFEAT-PE resulted in low sensitivity for the prediction of heart failure events. Copyright © 2014 Elsevier Inc. All rights reserved.

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

PubMed

Kress, B C; Mizrahi, I A; Armour, K W; Marcus, R; Emkey, R D; Santora, A C

1999-07-01

Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. Bone ALP decreased significantly from baseline at 3 months (P

Towards eradication of inappropriate therapies for ICD lead failure by combining comprehensive remote monitoring and lead noise alerts.

PubMed

Ploux, Sylvain; Swerdlow, Charles D; Strik, Marc; Welte, Nicolas; Klotz, Nicolas; Ritter, Philippe; Haïssaguerre, Michel; Bordachar, Pierre

2018-06-02

Recognition of implantable cardioverter defibrillator (ICD) lead malfunction before occurrence of life threatening complications is crucial. We aimed to assess the effectiveness of remote monitoring associated or not with a lead noise alert for early detection of ICD lead failure. From October 2013 to April 2017, a median of 1,224 (578-1,958) ICD patients were remotely monitored with comprehensive analysis of all transmitted materials. ICD lead failure and subsequent device interventions were prospectively collected in patients with (RMLN) and without (RM) a lead noise alert (Abbott Secure Sense™ or Medtronic Lead Integrity Alert™) in their remote monitoring system. During a follow-up of 4,457 patient years, 64 lead failures were diagnosed. Sixty-one (95%) of the diagnoses were made before any clinical complication occurred. Inappropriate shocks were delivered in only one patient of each group (3%), with an annual rate of 0.04%. All high voltage conductor failures were identified remotely by a dedicated impedance alert in 10 patients. Pace-sense component failures were correctly identified by a dedicated alert in 77% (17 of 22) of the RMLN group versus 25% (8 of 32) of the RM group (P = 0.002). The absence of a lead noise alert was associated with a 16-fold increase in the likelihood of initiating either a shock or ATP (OR: 16.0, 95% CI 1.8-143.3; P = 0.01). ICD remote monitoring with systematic review of all transmitted data is associated with a very low rate of inappropriate shocks related to lead failure. Dedicated noise alerts further reduce inappropriate detection of ventricular arrhythmias. © 2018 Wiley Periodicals, Inc.

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring.

PubMed

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min -1 . Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean : R 2   =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Monitoring Astronaut Health at the Nanoscale Cellular Level Through the Eye

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Singh, Bhim S.; Rovati, Luigi; Docchio, Franco; Sebag, Jerry

2000-01-01

A user friendly goggles-like head-mounted device equipped with a suite of instruments for several non-invasive and quantitative medical evaluation of the eye, skin, and brain is desired for monitoring the health of astronauts during space travel and exploration of neighboring and distant planets. Real-time non-invasive evaluation of the different structures within the above organs can provide indices of the health of not just these organs, but the entire body. The techniques such as dynamic light scattering (for the early detection of uveitis, cholesterol levels, cataract, changes in the vitreous and possibly Alzheimer's disease), corneal autofluorescence (to assess extracellular matrix biology e.g., in diabetes), optical activity measurements (of anterior ocular fluid to evaluate blood-glucose levels), laser Doppler velocimetry (to assess retinal, optic nerve, and choroidal blood flow), reflectometry/oximetry (for assessing ocular and central nervous system oxygen metabolism), optical coherence tomography (to determine retinal tissue microstructure) and possibly scanning laser technology (for intraocular tissue imaging and scanning) will he integrated into this compact device. Skin sensors will also be mounted on the portion of the device in contact with the periocular region. This will enable monitoring of body temperature, EEG, and electrolyte status. This device will monitor astronaut health during long-duration space travel by detecting aberrations from pre-established "nonns", enabling prompt diagnosis and possibly the initiation of early preventative/curative therapy. The non-invasive nature of the device technologies permits frequent repetition of tests, enabling real-time complete crew health monitoring. This device may ultimately be useful in tele-medicine to bring modern healthcare to under-served areas on Earth as well as in so-called "advanced" care settings (e.g. diabetes in the USA).

Error detection capability of a novel transmission detector: a validation study for online VMAT monitoring

NASA Astrophysics Data System (ADS)

Pasler, Marlies; Michel, Kilian; Marrazzo, Livia; Obenland, Michael; Pallotta, Stefania; Björnsgard, Mari; Lutterbach, Johannes

2017-09-01

The purpose of this study was to characterize a new single large-area ionization chamber, the integral quality monitor system (iRT, Germany), for online and real-time beam monitoring. Signal stability, monitor unit (MU) linearity and dose rate dependence were investigated for static and arc deliveries and compared to independent ionization chamber measurements. The dose verification capability of the transmission detector system was evaluated by comparing calculated and measured detector signals for 15 volumetric modulated arc therapy plans. The error detection sensitivity was tested by introducing MLC position and linac output errors. Deviations in dose distributions between the original and error-induced plans were compared in terms of detector signal deviation, dose-volume histogram (DVH) metrics and 2D γ-evaluation (2%/2 mm and 3%/3 mm). The detector signal is linearly dependent on linac output and shows negligible (<0.4%) dose rate dependence up to 460 MU min-1. Signal stability is within 1% for cumulative detector output; substantial variations were observed for the segment-by-segment signal. Calculated versus measured cumulative signal deviations ranged from  -0.16%-2.25%. DVH, mean 2D γ-value and detector signal evaluations showed increasing deviations with regard to the respective reference with growing MLC and dose output errors; good correlation between DVH metrics and detector signal deviation was found (e.g. PTV D mean: R 2  =  0.97). Positional MLC errors of 1 mm and errors in linac output of 2% were identified with the transmission detector system. The extensive tests performed in this investigation show that the new transmission detector provides a stable and sensitive cumulative signal output and is suitable for beam monitoring during patient treatment.

Rapid and sensitive method for simultaneous determination of first-line anti-tuberculosis drugs in human plasma by HPLC-MS/MS: Application to therapeutic drug monitoring.

PubMed

Gao, Shouhong; Wang, Zhipeng; Xie, Xinfang; You, Chunhua; Yang, Yang; Xi, Yanhai; Chen, Wansheng

2018-03-01

First-line anti-tuberculosis drugs are playing vital roles for curbing rapid spread of tuberculosis. Multidrug therapies are commonly applied in clinical to achieve better treatment outcomes. However, drug resistance and adverse reactions come along with this therapies and therapeutic drug monitoring is a feasible way to precaution them. For this reasons, a simple and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) and single protein precipitation was developed and validated for simultaneously quantifying of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin in human plasma. Optimized chromatographic separation was achieved on a ZORBAX SB-C 18 column with heptafluorobutyric acid, an ion-pair reagent, in the mobile phase at a flow rate of 0.3 mL/min. The mass detection was achieved using electrospray ionization in the positive ion mode with a multiple reaction monitoring mode. The lower limit of quantification (LLOQ) and dynamic range of pyrazinamide, isoniazid, ethambutol, streptomycin and rifampicin were 200-4000 ng/mL, 80-2000 ng/mL, 0.2-1000 ng/mL, 2000-200000 ng/mL and 200-4000 ng/mL, respectively. The Inter-day and intra-day accuracy and precision were within ±15.0% and less than 15%. The method had been successfully applied to simultaneous determination of four first-line Anti-tuberculosis drugs in plasma from tuberculosis patients. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical evaluation of the COBAS Ampliprep/COBAS TaqMan for HCV RNA quantitation in comparison with the branched-DNA assay.

PubMed

Pittaluga, Fabrizia; Allice, Tiziano; Abate, Maria Lorena; Ciancio, Alessia; Cerutti, Francesco; Varetto, Silvia; Colucci, Giuseppe; Smedile, Antonina; Ghisetti, Valeria

2008-02-01

Diagnosis and monitoring of HCV infection relies on sensitive and accurate HCV RNA detection and quantitation. The performance of the COBAS AmpliPrep/COBAS TaqMan 48 (CAP/CTM) (Roche, Branchburg, NJ), a fully automated, real-time PCR HCV RNA quantitative test was assessed and compared with the branched-DNA (bDNA) assay. Clinical evaluation on 576 specimens obtained from patients with chronic hepatitis C showed a good correlation (r = 0.893) between the two test, but the CAP/CTM scored higher HCV RNA titers than the bDNA across all viral genotypes. The mean bDNA versus CAP/CTM log10 IU/ml differences were -0.49, -0.4, -0.54, -0.26 for genotype 1a, 1b, 2a/2c, 3a, and 4, respectively. These differences reached statistical significance for genotypes 1b, 2a/c, and 3a. The ability of the CAP/CTM to monitor patients undergoing antiviral therapy and correctly identify the weeks 4 and 12 rapid and early virological responses was confirmed. The broader dynamic range of the CAP/CTM compared with the bDNA allowed for a better definition of viral kinetics. In conclusion, the CAP/CTM appears as a reliable and user-friendly assay to monitor HCV viremia during treatment of patients with chronic hepatitis. Its high sensitivity and wide dynamic range may help a better definition of viral load changes during antiviral therapy. (Copyright) 2007 Wiley-Liss, Inc.

Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison

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

Hoecht, Stefan; Wachtlin, Joachim; Bechrakis, Nikolaos E.

2006-10-01

Purpose: The aim of this study was to compare, on a retrospective basis, the results of therapy in patients with uveal hemangioma treated with photon or proton irradiation at a single center. Methods and Materials: From 1993 to 2002 a total of 44 patients were treated. Until 1998 radiotherapy was given with 6 MV photons in standard fractionation of 2.0 Gy 5 times per week. In 1998 proton therapy became available and was used since then. A dose of 20 to 22.5 Cobalt Gray Equivalent (CGE) 68 MeV protons was given on 4 consecutive days. Progressive symptoms or deterioration ofmore » vision were the indications for therapy. Results: Of the 44 patients treated, 36 had circumscribed choroidal hemangiomas and 8 had diffuse choroidal hemangiomas (DCH) and Sturge-Weber syndrome. Of the patients, 19 were treated with photons with a total dose in the range of 16 to 30 Gy. A total of 25 patients were irradiated with protons. All patients with DCH but 1 were treated with photons. Stabilization of visual acuity was achieved in 93.2% of all patients. Tumor thickness decreased in 95.4% and retinal detachment resolved in 92.9%. Late effects, although generally mild or moderate, were frequently detected. In all, 40.9% showed radiation-induced optic neuropathy, maximum Grade I. Retinopathy was found in 29.5% of cases, but only 1 patient experienced more than Grade II severity. Retinopathy and radiation-induced optic neuropathy were reversible in some of the patients and in some resolved completely. No differences could be detected between patients with circumscribed choroidal hemangiomas treated with protons and photons. Treatment was less effective in DCH patients (75%). Conclusions: Radiotherapy is effective in treating choroidal hemangiomas with respect to visual acuity and tumor thickness but a benefit of proton therapy could not be detected. Side effects are moderate but careful monitoring for side effects should be part of the follow-up procedures.« less

Comparison of clinical application of the Abbott HBV PCR kit and the VERSANT HBV DNA 3.0 test to measure serum hepatitis B virus DNA in Taiwanese patients.

PubMed

Yang, Jeng-Fu; Lin, Ya-Yun; Huang, Jee-Fu; Liu, Shu-Fen; Chu, Pei-Yu; Hsieh, Ming-Yen; Lin, Zu-Yau; Chen, Shinn-Cherng; Wang, Liang-Yen; Dai, Chia-Yen; Chuang, Wan-Long; Yu, Ming-Lung

2009-08-01

With an estimated 350-400 million people worldwide chronically infected with hepatitis B virus (HBV), and the subsequent serious complications caused by liver damage including cirrhosis, liver failure, and hepatocellular carcinoma, HBV infection remains a global health issue, particularly in Taiwan, an HBV-hyperendemic area. Sensitive and accurate quantification of HBV DNA is necessary to monitor patients with chronic hepatitis B who are receiving antiviral therapy to determine treatment response and adapt therapy. We evaluated and compared the clinical performance of two HBV DNA assays based on different technologies: the RealArt HBV PCR Kit (Abbott HBV DNA PCR kit, real-time polymerase chain reaction assay, detection limit: 27 IU/mL) and the VERSANT bDNA 3.0 assay (Bayer, branched DNA signal amplification assay, detection limit: 357 IU/mL). Serum levels of HBV DNA in 173 chronic HBV carriers were determined using both the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 test. Of the 173 samples analyzed for baseline viral load detection, HBV DNA was quantifiable in 147 patients (82.1%) by the RealArt HBV PCR Kit, which was significantly higher than the 92 (53.2%) samples quantified by the VERSANT bDNA 3.0 assay. A total of 86 (49.7%) samples were quantifiable by both assays, whereas 25 (14.5%) were below the detection limit of both assays. The HBV DNA quantification values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were positively correlated (Spearman's rank correlation coefficient r = 0.932, p < 0.001). On average, the results derived from the RealArt HBV PCR Kit were 0.67 log lower than those of the VERSANT bDNA 3.0 assay. HBV DNA concentrations were significantly higher in 63 HBV e antigen (HBeAg)-seropositive patients than in 110 HBeAg-seronegative patients (5.42 +/- 2.34 logs vs. 3.21 +/- 2.27 logs, p < 0.001). The RealArt HBV PCR Kit is more sensitive and has a wider dynamic range than the VERSANT bDNA 3.0 assay in the clinical setting of chronic hepatitis B patients. The sensitivity and wide dynamic range of the PCR assay allow optimal monitoring and timely adaptation of antiviral therapy. Nevertheless, the HBV DNA values measured by the RealArt HBV PCR Kit and the VERSANT bDNA 3.0 assay were significantly correlated.

A polymerase chain reaction-based methodology to detect gene doping.

PubMed

Carter, Adam; Flueck, Martin

2012-04-01

The non-therapeutic use of genes to enhance athletic performance (gene doping) is a novel threat to the world of sports. Skeletal muscle is a prime target of gene therapy and we asked whether we can develop a test system to produce and detect gene doping. Towards this end, we introduced a plasmid (pCMV-FAK, 3.8 kb, 50 μg) for constitutive expression of the chicken homologue for the regulator of muscle growth, focal adhesion kinase (FAK), via gene electro transfer in the anti-gravitational muscle, m. soleus, or gastrocnemius medialis of rats. Activation of hypertrophy signalling was monitored by assessing the ribosomal kinase p70S6K and muscle fibre cross section. Detectability of the introduced plasmid was monitored with polymerase chain reaction in deoxyribonucleic acids (DNA) from transfected muscle and serum. Muscle transfection with pCMV-FAK elevated FAK expression 7- and 73-fold, respectively, and increased mean cross section by 52 and 16% in targeted muscle fibres of soleus and gastrocnemius muscle 7 days after gene electro transfer. Concomitantly p70S6K content was increased in transfected soleus muscle (+110%). Detection of the exogenous plasmid sequence was possible in DNA and cDNA of muscle until 7 days after transfection, but not in serum except close to the site of plasmid deposition, 1 h after injection and surgery. The findings suggest that the reliable detection of gene doping in the immoral athlete is not possible unless a change in the current practice of tissue sampling is applied involving the collection of muscle biopsy close to the site of gene injection.

Application of Protein Microarrays for Multiplexed Detection of Antibodies to Tumor Antigens in Breast Cancer

PubMed Central

Anderson, Karen S.; Ramachandran, Niroshan; Wong, Jessica; Raphael, Jacob V.; Hainsworth, Eugenie; Demirkan, Gokhan; Cramer, Daniel; Aronzon, Diana; Hodi, F. Stephen; Harris, Lyndsay; Logvinenko, Tanya; LaBaer, Joshua

2012-01-01

There is strong preclinical evidence that cancer, including breast cancer, undergoes immune surveillance. This continual monitoring, by both the innate and the adaptive immune systems, recognizes changes in protein expression, mutation, folding, glycosylation, and degradation. Local immune responses to tumor antigens are amplified in draining lymph nodes, and then enter the systemic circulation. The antibody response to tumor antigens, such as p53 protein, are robust, stable, and easily detected in serum, may exist in greater concentrations than their cognate antigens, and are potential highly specific biomarkers for cancer. However, antibodies have limited sensitivities as single analytes, and differences in protein purification and assay characteristics have limited their clinical application. For example, p53 autoantibodies in the sera are highly specific for cancer patients, but are only detected in the sera of 10-20% of patients with breast cancer. Detection of p53 autoantibodies is dependent on tumor burden, p53 mutation, rapidly decreases with effective therapy, but is relatively independent of breast cancer subtype. Although antibodies to hundreds of other tumor antigens have been identified in the sera of breast cancer patients, very little is known about the specificity and clinical impact of the antibody immune repertoire to breast cancer. Recent advances in proteomic technologies have the potential for rapid identification of immune response signatures for breast cancer diagnosis and monitoring. We have adapted programmable protein microarrays for the specific detection of autoantibodies in breast cancer. Here, we present the first demonstration of the application of programmable protein microarray ELISAs for the rapid identification of breast cancer autoantibodies. PMID:18311903

Calibration Experiments Conducted for Noninvasive Blood Glucose Sensing Through the Eye

NASA Technical Reports Server (NTRS)

Ansari, Rafat R.; Bockle, Stefan; Suh, Kwang I.; Rovati, Luigi L.

2004-01-01

There are more than 16 million diabetics in the United States and more than 100 million worldwide. Diabetes can lead to severe complications over time such as blindness, renal and cardiovascular diseases, and peripheral neuropathy in the limbs. Poor blood circulation in diabetics can lead to gangrene and the subsequent amputation of extremities. In addition, this pathology is the fourth leading cause of death in the United States. The most effective way to manage diabetes is frequent blood glucose monitoring performed by the patients themselves. However, because of pain, inconvenience, and the fear of developing infections from finger-prick blood tests or implants, many patients monitor their blood glucose levels less frequently than is recommended by their physicians. Therefore, a noninvasive, painless, and convenient method to monitor blood glucose would greatly benefit diabetics. Likewise, detecting, preventing, and treating the untoward effects of prolonged space travel (e.g., a human mission to Mars) in real-time requires the development of noninvasive diagnostic technologies that are compact and powerful. As a "window to the body," the eye offers the opportunity to use light in various forms to detect ocular and systemic abnormalities long before clinical symptoms appear and to help develop preventative and therapeutic countermeasures early. The noninvasive feature of these technologies permits frequent repetition of tests, enabling an evaluation of the response to therapy.

The biology of cancer: what do oncology nurses really need to know.

PubMed

Eggert, Julie

2011-02-01

To describe the impact of genetics and genomics on the biology of cancer and the implications for patient care. Pubmed; CINAHL. Cancer research in genetics/genomics has identified new mechanisms influencing personalized risk assessment/management, early detection, cancer treatment, and long-term screening/surveillance. Understanding the basics of genetics/genomics on the biology of cancer will facilitate patient education and care delivery, including the administration and monitoring of genetically targeted therapies whose toxicities may in part be mediated by the molecular pathways targeted by the specific agent. Copyright © 2011 Elsevier Inc. All rights reserved.

Detecting and Managing Adverse Effects of Antipsychotic Medications: Current State of Play.

PubMed

Ames, Donna; Carr-Lopez, Sian M; Gutierrez, Mary A; Pierre, Joseph M; Rosen, Jennifer A; Shakib, Susan; Yudofsky, Lynn M

2016-06-01

Antipsychotics are some of the most frequently prescribed medications not only for psychotic disorders and symptoms but also for a wide range of on-label and off-label indications. Because second-generation antipsychotics have largely replaced first-generation antipsychotics as first-line options due to their substantially decreased risk of extrapyramidal side effects, attention has shifted to other clinically concerning adverse events associated with antipsychotic therapy. The focus of this article is to update the nonextrapyramidal side effects associated with second-generation antipsychotics. Issues surrounding diagnosis and monitoring as well as clinical management are addressed. Published by Elsevier Inc.

[SPECIFIC CLINICAL FEATURES OF TYPE 1 AUTOIMMUNE POLYGLANDULAR SYNDROME].

PubMed

Mikhina, M S; Molashenko, N V; Troshina, E A; Orlova, E M; Sozaeva, L S; Eystein, S H; Breivik, S

2015-01-01

Autoimmune polyglandular syndrome is a primary autoimmune disorder affecting two or more peripheral endocrine glands and responsible for their incompetence. It is frequently combined with various organ-specific non-endocrine diseases. Patients with this pathology need life-long replacement therapy and dynamic observation by endocrinologists and other specialists to monitor the effectiveness of the treatment and detect new components of the disease. We report a variant of type 1 autoimmune polyglandular syndrome. Special emphasis is laid on the importance of succession of actions of endocrinologists and specialists in related medical disciplines dealing with children and adult patients.

Management of coronary artery disease

NASA Astrophysics Data System (ADS)

Safri, Z.

2018-03-01

Coronary Artery Disease (CAD) is associated with significant morbidity and mortality, therefore it’s important to early and accurate detection and appropriate management. Diagnosis of CAD include clinical examination, noninvasive techniques such as biochemical testing, a resting ECG, possibly ambulatory ECG monitoring, resting echocardiography, chest X-ray in selected patients; and catheterization. Managements of CAD patients include lifestyle modification, control of CAD risk factors, pharmacologic therapy, and patient education. Revascularization consists of percutaneous coronary angioplasty and coronary artery bypass grafting. Cardiac rehabilitation should be considered in all patients with CAD. This comprehensive review highlights strategies of management in patients with CAD.

Future and Advances in Endoscopy

PubMed Central

Elahi, Sakib F.; Wang, Thomas D.

2012-01-01

The future of endoscopy will be dictated by rapid technological advances in the development of light sources, optical fibers, and miniature scanners that will allow for images to be collected in multiple spectral regimes, with greater tissue penetration, and in three dimensions. These engineering breakthroughs will be integrated with novel molecular probes that are highly specific for unique proteins to target diseased tissues. Applications include early cancer detection by imaging molecular changes that occur before gross morphological abnormalities, personalized medicine by visualizing molecular targets specific to individual patients, and image guided therapy by localizing tumor margins and monitoring for recurrence. PMID:21751414

Nuclear Science Symposium, 19th, and Nuclear Power Systems Symposium, 4th, Miami, Fla., December 6-8, 1972, Proceedings.

NASA Technical Reports Server (NTRS)

1973-01-01

Major topics covered include radiation monitoring instrumentation, nuclear circuits and systems, biomedical applications of nuclear radiation in diagnosis and therapy, plasma research for fusion power, reactor control and instrumentation, nuclear power standards, and applications of digital computers in nuclear power plants. Systems and devices for space applications are described, including the Apollo alpha spectrometer, a position sensitive detection system for UV and X-ray photons, a 4500-volt electron multiplier bias supply for satellite use, spark chamber systems, proportional counters, and other devices. Individual items are announced in this issue.

Current Approaches and Challenges for Monitoring Treatment Response in Colon and Rectal Cancer

PubMed Central

McKeown, Elizabeth; Nelson, Daniel W.; Johnson, Eric K.; Maykel, Justin A.; Stojadinovic, Alexander; Nissan, Aviram; Avital, Itzhak; Brücher, Björn LDM; Steele, Scott R.

2014-01-01

Introduction: With the advent of multidisciplinary and multimodality approaches to the management of colorectal cancer patients, there is an increasing need to define how we monitor response to novel therapies in these patients. Several factors ranging from the type of therapy used to the intrinsic biology of the tumor play a role in tumor response. All of these can aid in determining the ideal course of treatment, and may fluctuate over time, pending down-staging or progression of disease. Therefore, monitoring how disease responds to therapy requires standardization in order to ultimately optimize patient outcomes. Unfortunately, how best to do this remains a topic of debate among oncologists, pathologists, and colorectal surgeons. There may not be one single best approach. The goal of the present article is to shed some light on current approaches and challenges to monitoring treatment response for colorectal cancer. Methods: A literature search was conducted utilizing PubMed and the OVID library. Key-word combinations included colorectal cancer metastases, neoadjuvant therapy, rectal cancer, imaging modalities, CEA, down-staging, tumor response, and biomarkers. Directed searches of the embedded references from the primary articles were also performed in selected circumstances. Results: Pathologic examination of the post-treatment surgical specimen is the gold standard for monitoring response to therapy. Endoscopy is useful for evaluating local recurrence, but not in assessing tumor response outside of the limited information gained by direct examination of intra-lumenal lesions. Imaging is used to monitor tumors throughout the body for response, with CT, PET, and MRI employed in different circumstances. Overall, each has been validated in the monitoring of patients with colorectal cancer and residual tumors. Conclusion: Although there is no imaging or serum test to precisely correlate with a tumor's response to chemo- or radiation therapy, these modalities, when used in combination, can aid in allowing clinicians to adjust medical therapy, pursue operative intervention, or (in select cases) identify complete responders. Improvements are needed, however, as advances across multiple modalities could allow appropriate selection of patients for a close surveillance regimen in the absence of operative intervention. PMID:24396496

Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT.

PubMed

Shi, Bowen; Lin, Huimin; Zhang, Miao; Lu, Wei; Qu, Ying; Zhang, Huan

2018-01-22

Gastric cancer remains fourth in cancer incidence worldwide with a five-year survival of only 20%-30%. Peritoneal metastasis is the most frequent type of metastasis that accompanies unresectable gastric cancer and is a definitive determinant of prognosis. Preventing and controlling the development of peritoneal metastasis could play a role in helping to prolong the survival of gastric cancer patients. A non-invasive and efficient imaging technique will help us to identify the invasion and metastasis process of peritoneal metastasis and to monitor the changes in tumor nodules in response to treatments. This will enable us to obtain an accurate description of the development process and molecular mechanisms of gastric cancer. We have recently described experiment using dual energy CT (DECT) and positron emission tomography/computed tomography (PET/CT) platforms for the detection and monitoring of gastric tumor metastasis in nude mice models. We have shown that weekly continuous monitoring with DECT and PET/CT can identify dynamic changes in peritoneal metastasis. The sFRP1-overexpression in gastric cancer mice models showed positive radiological performance, a higher FDG uptake and increasing enhancement, and the SUVmax (standardized uptake value) of nodules demonstrated an obvious alteration trend in response to targeted therapy of TGF-β1 inhibitor. In this article, we described the detailed non-invasive imaging procedures to conduct more complex research on gastric cancer peritoneal metastasis using animal models and provided representative imaging results. The use of non-invasive imaging techniques should enable us to better understand the mechanisms of tumorigenesis, monitor tumor growth, and evaluate the effect of therapeutic interventions for gastric cancer.

In-vivo luminescence model for the study of tumor regression and regrowth following combination regimens with differentiation-promoting agents and photodynamic therapy

NASA Astrophysics Data System (ADS)

Rollakanti, K.; Anand, S.; Maytin, E. V.

2013-03-01

Photodynamic therapy with aminolevulinic acid can be modified by pretreatment regimens with drugs such as 5- Fluorouracil (5-FU) or Vitamin D (calcitriol) that enhance accumulation of protoporphyrin IX (PpIX) within tumor tissue which presumably will enhance the therapeutic response to light. However, histological approaches for monitoring therapeutic responses are poorly suited for studying long term survival because large numbers of mice need to be sacrificed. To address this limitation, a non-invasive model to monitor tumor regression and regrowth has been established. Breast cancer cells, stably transfected with firefly luciferase (MDA-Luc cell line), are implanted orthotopically in nude mice (0.25 - 1 x 106 cells/site), and monitored 0-60 min after s.c. injection of luciferin, with Xenogen in-vivo imaging system. Luminescence is detectable at day 1 post-implantation. Tumors are suitable for experimentation on day 6, when daily injections of pretreatment agents (5-FU, 300 mg/kg; calcitriol, 1 μg/kg) begin. On day 9, ALA (75 mg/kg i.p.) is given for 4 hr, followed by illumination (633 nm, 100 J/cm2). Tumor luminescence post- PDT is monitored daily and compared with caliper measurements. Pretreatments (5-FU, calcitriol) by themselves do not inhibit luciferase expression, and all tumors grow at a similar rate during the pretreatment period. Results from in vivo survival experiments can be correlated to survival responses of MDA-Luc cells grown in monolayer cultures +/- PDT and +/- pretreatments, and additional mechanistic information (e.g. Ki67 and E-cadherin expression) obtained. In summary, this noninvasive model will permit testing of the therapeutic survival advantages of various pretreatments during cPDT.

Label-Free Isolation and mRNA Detection of Circulating Tumor Cells from Patients with Metastatic Lung Cancer for Disease Diagnosis and Monitoring Therapeutic Efficacy.

PubMed

Wang, Jidong; Lu, Wenjing; Tang, Chuanhao; Liu, Yi; Sun, Jiashu; Mu, Xuan; Zhang, Lin; Dai, Bo; Li, Xiaoyan; Zhuo, Hailong; Jiang, Xingyu

2015-12-01

We develop an inertial-based microfluidic cell sorter combined with an integrated membrane filter, allowing for size-based, label-free, and high-efficiency separation and enrichment of circulating tumor cells (CTCs) in whole blood. The cell sorter is composed of a double spiral microchannel that hydrodynamically focuses and separates large CTCs from small blood cells. The focused CTCs with the equilibrium position around the midline of microchannel are further captured and enriched by a membrane filter (pore size of 8 μm) attached at the middle outlet. This integrated microfluidic device can process 1 mL of whole blood containing spiked tumor cells (A549, human lung adenocarcinoma epithelial cell line) within 15 min, with the capture efficiency of 74.4% at the concentration as low as tens of A549 cells per mL of whole blood. This microfluidic cell sorter is further adopted for isolation of CTCs from peripheral blood samples of patients with metastatic lung cancer. The immunostaining and CK-19 mRNA detection are applied for identification of captured CTCs, showing that our method can detect 90% of metastatic lung cancer patients before therapy, whereas the commercially used system can only detect 40% of the same patients. We also use the expression of CK-19 mRNA from captured CTCs as an indicator for monitoring the therapeutic efficiency, which correlates well with X-ray computed tomography (CT) assessment of the disease.

Less or more hemodynamic monitoring in critically ill patients.

PubMed

Jozwiak, Mathieu; Monnet, Xavier; Teboul, Jean-Louis

2018-06-07

Hemodynamic investigations are required in patients with shock to identify the type of shock, to select the most appropriate treatments and to assess the patient's response to the selected therapy. We discuss how to select the most appropriate hemodynamic monitoring techniques in patients with shock as well as the future of hemodynamic monitoring. Over the last decades, the hemodynamic monitoring techniques have evolved from intermittent toward continuous and real-time measurements and from invasive toward less-invasive approaches. In patients with shock, current guidelines recommend the echocardiography as the preferred modality for the initial hemodynamic evaluation. In patients with shock nonresponsive to initial therapy and/or in the most complex patients, it is recommended to monitor the cardiac output and to use advanced hemodynamic monitoring techniques. They also provide other useful variables that are useful for managing the most complex cases. Uncalibrated and noninvasive cardiac output monitors are not reliable enough in the intensive care setting. The use of echocardiography should be initially encouraged in patients with shock to identify the type of shock and to select the most appropriate therapy. The use of more invasive hemodynamic monitoring techniques should be discussed on an individualized basis.

Efficacy of plasma vascular endothelial growth factor in monitoring first-line chemotherapy in patients with advanced non-small cell lung cancer

PubMed Central

2009-01-01

Background Along with the development of new cancer therapeutics, more effective tools for the estimation of response to therapy and prediction of disease progression are required for the better management of inoperable cancer patients. Methods We studied 134 newly diagnosed and primarily untreated advanced non-small cell lung cancer patients and 100 controls. Forty two patients received platinum-based chemotherapy. Plasma VEGF levels were quantified in all samples at baseline and also before second and third chemotherapy cycle in 42 patients and correlated with response to therapy as assessed by computed tomography after the third chemotherapy cycle. Results We observed that, patients who went into remission had significantly lower baseline VEGF levels before second and third cycles of chemotherapy when compared with patients with no change and progression. Plasma VEGF levels showed a greater decrease from cycle 1 to 2 and from cycle 1 to 3 in patients who showed remission in comparison to those with no change or progression. Plasma VEGF levels before the second cycle detected poor response to therapy with a sensitivity and specificity of 76.9% and 75.0%, respectively (area under the ROC curve = 0.724). Early prediction of disease progression was achieved with a sensitivity and specificity of 71.4% for plasma VEGF before cycle 2 (area under the ROC curve = 0.805). The kinetics of VEGF form cycle 1 to 2 and cycle 1 to 3 also gave significant information for predicting disease progression as well as insufficient therapy response. Conclusion Monitoring of plasma VEGF levels during the course of first-line chemotherapy could identify patients who are likely to have insufficient response to therapy and disease progression at an early stage. This may help in individualizing treatment and could lead to better management of the advanced stage lung cancer. PMID:19958548

Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer.

PubMed

Cheng, Feifei; Su, Li; Qian, Cheng

2016-07-26

Tissue biopsy is the standard diagnostic procedure for cancers and also provides a material for genotyping, which can assist in the targeted therapies of cancers. However, tissue biopsy-based cancer diagnostic procedures have limitations in their assessment of cancer development, prognosis and genotyping, due to tumor heterogeneity and evolution. Circulating tumor DNA (ctDNA) is single- or double-stranded DNA released by the tumor cells into the blood and it thus harbors the mutations of the original tumor. In recent years, liquid biopsy based on ctDNA analysis has shed a new light on the molecular diagnosis and monitoring of cancer. Studies found that the screening of genetic mutations using ctDNA is highly sensitive and specific, suggesting that ctDNA analysis may significantly improve current systems of tumor diagnosis, even facilitating early-stage detection. Moreover, ctDNA analysis is capable of accurately determining the tumor progression, prognosis and assisting in targeted therapy. Therefore, using ctDNA as a liquid biopsy may herald a revolution for tumor management. Herein, we review the biology of ctDNA, its detection methods and potential applications in tumor diagnosis, treatment and prognosis.

Circulating tumor DNA: a promising biomarker in the liquid biopsy of cancer

PubMed Central

Cheng, Feifei; Su, Li; Qian, Cheng

2016-01-01

Tissue biopsy is the standard diagnostic procedure for cancers and also provides a material for genotyping, which can assist in the targeted therapies of cancers. However, tissue biopsy-based cancer diagnostic procedures have limitations in their assessment of cancer development, prognosis and genotyping, due to tumor heterogeneity and evolution. Circulating tumor DNA (ctDNA) is single- or double-stranded DNA released by the tumor cells into the blood and it thus harbors the mutations of the original tumor. In recent years, liquid biopsy based on ctDNA analysis has shed a new light on the molecular diagnosis and monitoring of cancer. Studies found that the screening of genetic mutations using ctDNA is highly sensitive and specific, suggesting that ctDNA analysis may significantly improve current systems of tumor diagnosis, even facilitating early-stage detection. Moreover, ctDNA analysis is capable of accurately determining the tumor progression, prognosis and assisting in targeted therapy. Therefore, using ctDNA as a liquid biopsy may herald a revolution for tumor management. Herein, we review the biology of ctDNA, its detection methods and potential applications in tumor diagnosis, treatment and prognosis. PMID:27223063

Evaluating Chagas disease progression and cure through blood-derived biomarkers: a systematic review.

PubMed

Requena-Méndez, Ana; López, Manuel Carlos; Angheben, Andrea; Izquierdo, Luis; Ribeiro, Isabela; Pinazo, Maria-Jesús; Gascon, Joaquim; Muñoz, José

2013-09-01

This article reviews the usefulness of various types of blood-derived biomarkers that are currently being studied to predict the progression of Chagas disease in patients with the indeterminate form, to assess the efficacy of antiparasitic drugs and to identify early cardiac and gastrointestinal damage. The authors used a search strategy based on MEDLINE, Cochrane Library Register for systematic review, EmBase, Global Health and LILACS databases. Out of 1716 screened articles, only 166 articles were eligible for final inclusion. The authors classified the biomarkers according to their biochemical structure and primary biological activity in four groups: i) markers of inflammation and cellular injury, ii) metabolic biomakers, iii) prothrombotic biomarkers and iv) markers derived from specific antigens of the parasite. Several potential biomarkers might have clinical potential for the detection of early cardiopathy. Such capacity is imperative in order to detect high-risk patients who require intensive monitoring and earlier therapy. Prospective studies with longer follow-ups are needed for the appraisal of biomarkers assessing clinical or microbiological cure after therapy. At the same time, studies evaluating more than one biomarker are useful to compare the efficacy among them given the lack of a recognized gold standard.

Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

PubMed Central

Joshi, Bishnu P.; Wang, Thomas D.

2010-01-01

Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

BCR-ABL PCR testing in chronic myelogenous leukemia: molecular diagnosis for targeted cancer therapy and monitoring.

PubMed

Luu, Martin H; Press, Richard D

2013-09-01

The use of tyrosine kinase inhibitors (TKIs) to treat chronic myeloid leukemia (CML) represents the paradigm for modern targeted cancer therapy. Importantly, molecular monitoring using BCR-ABL real-time quantitative reverse transcription polymerase chain reaction (RQ-PCR) for assessing treatment efficacy and quantitating minimal residual disease is a major determinate of practical therapeutic decision-making in the long-term management of this now chronic disease. Herein, we present an overview of CML and the use of TKIs for targeted CML therapy, with an emphasis on the role, application and future aspects of PCR-based molecular monitoring.

Incidence and economic burden of suspected adverse events and adverse event monitoring during AF therapy.

PubMed

Kim, M H; Lin, J; Hussein, M; Battleman, D

2009-12-01

Rhythm- and rate-control therapies are an essential part of atrial fibrillation (AF) management; however, the use of existing agents is often limited by the occurrence of adverse events. The aim of this study was to evaluate suspected adverse events and adverse event monitoring, and associated medical costs, in patients receiving AF rhythm-control and/or rate-control therapy. This retrospective cohort study used claims data from the Integrated Healthcare Information Systems National Managed Care Benchmark Database from 2002-2006. Patients hospitalized for AF (primary diagnosis), and who had at least 365 days' enrollment before and after the initial (index) AF hospitalization, were included in the analysis. Suspected AF therapy-related adverse events and function tests for adverse event monitoring were identified according to pre-specified diagnosis codes/procedures, and examined over the 12 months following discharge from the index hospitalization. Events/function tests had to have occurred within 90 days of a claim for AF therapy to be considered a suspected adverse event/adverse event monitoring. Of 4174 AF patients meeting the study criteria, 3323 received AF drugs; 428 received rhythm-control only (12.9%), 2130 rate-control only (64.1%), and 765 combined rhythm/rate-control therapy (23.0%). Overall, 50.1% of treated patients had a suspected adverse event and/or function test for adverse event monitoring (45.5% with rate-control, 53.5% with rhythm-control, and 61.2% with combined rhythm/rate-control). Suspected cardiovascular adverse events were the most common events (occurring in 36.1% of patients), followed by pulmonary (6.1%), and endocrine events (5.9%). Overall, suspected adverse events/function tests were associated with mean annual per-patient costs of $3089 ($1750 with rhythm-control, $2041 with rate control, and $6755 with combined rhythm/rate-control). As a retrospective analysis, the study is subject to potential selection bias, while its reliance on diagnostic codes for identification of AF and suspected adverse events is a source of potential investigator error. A direct cause-effect relationship between suspected adverse events/function tests and AF therapy cannot be confirmed based on the claims data available. The incidence of suspected adverse events and adverse event monitoring during AF rhythm-control and/or rate-control therapy is high. Costs associated with adverse events and adverse event monitoring are likely to add considerably to the overall burden of AF management.

Integration of remote blood glucose meter upload technology into a clinical pharmacist medication therapy management service.

PubMed

Schenk, Robert J; Schenk, Jenna

2011-01-01

A pharmacist-delivered, outpatient-focused medication therapy management (MTM) program is using a remote blood glucose (BG) meter upload device to provide better care and to improve outcomes for its patients with diabetes. Sharing uploaded BG meter data, presented in easily comprehensible graphs and charts, enables patients, caregivers, and the medical team to better understand how the patients' diabetes care is progressing. Pharmacists are becoming increasingly more active in helping to manage patients' complex medication regimens in an effort to help detect and avoid medication-related problems. Working together with patients and their physicians as part of an interdisciplinary health care team, pharmacists are helping to improve medication outcomes. This article focuses on two case studies highlighting the Diabetes Monitoring Program, one component of the Meridian Pharmacology Institute MTM service, and discusses the clinical application of a unique BG meter upload device. © 2010 Diabetes Technology Society.

Quantitative evaluation of redox ratio and collagen characteristics during breast cancer chemotherapy using two-photon intrinsic imaging.

PubMed

Wu, Shulian; Huang, Yudian; Tang, Qinggong; Li, Zhifang; Horng, Hannah; Li, Jiatian; Wu, Zaihua; Chen, Yu; Li, Hui

2018-03-01

Preoperative neoadjuvant treatment in locally advanced breast cancer is recognized as an effective adjuvant therapy, as it improves treatment outcomes. However, the potential complications remain a threat, so there is an urgent clinical need to assess both the tumor response and changes in its microenvironment using non-invasive and precise identification techniques. Here, two-photon microscopy was employed to detect morphological alterations in breast cancer progression and recession throughout chemotherapy. The changes in structure were analyzed based on the autofluorescence and collagen of differing statuses. Parameters, including optical redox ratio, the ratio of second harmonic generation and auto-fluorescence signal, collagen density, and collagen shape orientation, were studied. Results indicate that these parameters are potential indicators for evaluating breast tumors and their microenvironment changes during progression and chemotherapy. Combined analyses of these parameters could provide a quantitative, novel method for monitoring tumor therapy.

Sticky-flares for in situ monitoring of human telomerase RNA in living cells.

PubMed

Wu, Qilong; Liu, Zhengjie; Su, Lei; Han, Guangmei; Liu, Renyong; Zhao, Jun; Zhao, Tingting; Jiang, Changlong; Zhang, Zhongping

2018-05-17

Human telomerase RNA (hTR), a template of telomerase for telomeric repeat synthesis, was used to reflect the telomerase activity and act as a potential target of antitumor therapy. Here, we report a novel DNA-conjugated AuNP probe termed sticky-flares for the in situ detection of intracellular human telomerase RNA. The sticky-flares probe is capable of entering living cells directly without any auxiliary and recognizing the binding domain of human telomerase RNA. On recognition, the fluorophore-modified recognition flares can specifically bind to the target, separate from the sticky-flares and act as a fluorescent reporter to quantify and dynamically profile human telomerase RNA in living cells. We envision that the sticky-flares probe would be a valuable platform to investigate the function and regulation of hTR in antitumor therapy and hTR-related drug invention.

Biosimilars: A new scenario in biologic therapies.

PubMed

Serra López-Matencio, José M; Morell Baladrón, Alberto; Castañeda, Santos

There is no doubt that biologic therapies provide added value for health systems. However, due to their special nature, they also raise some questions that make highly rigorous and demanding quality control and monitoring of their use indispensable. This circumstance is reinforced with the appearance on the scene of biosimilars, which, given their lower cost, are having an increasing impact on the international market. The purpose of this article is to review the major issues posed by their manufacture, distribution and control systems, as well as the most important aspects related to their safety in clinical practice. In this report, we assess the pharmacovigilance of these products, with special attention to traceability, as a key tool to enable earlier detection of adverse events. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

MR-guided prostate interventions.

PubMed

Tempany, Clare; Straus, Sarah; Hata, Nobuhiko; Haker, Steven

2008-02-01

In this article the current issues of diagnosis and detection of prostate cancer are reviewed. The limitations for current techniques are highlighted and some possible solutions with MR imaging and MR-guided biopsy approaches are reviewed. There are several different biopsy approaches under investigation. These include transperineal open magnet approaches to closed-bore 1.5T transrectal biopsies. The imaging, image processing, and tracking methods are also discussed. In the arena of therapy, MR guidance has been used in conjunction with radiation methods, either brachytherapy or external delivery. The principles of the radiation treatment, the toxicities, and use of images are outlined. The future role of imaging and image-guided interventions lie with providing a noninvasive surrogate for cancer surveillance or monitoring treatment response. The shift to minimally invasive focal therapies has already begun and will be very exciting when MR-guided focused ultrasound surgery reaches its full potential. (Copyright) 2008 Wiley-Liss, Inc.

MR-Guided Prostate Interventions

PubMed Central

Tempany, Clare; Straus, Sarah; Hata, Nobuhiko; Haker, Steven

2009-01-01

In this article the current issues of diagnosis and detection of prostate cancer are reviewed. The limitations for current techniques are highlighted and some possible solutions with MR imaging and MR-guided biopsy approaches are reviewed. There are several different biopsy approaches under investigation. These include transperineal open magnet approaches to closed-bore 1.5T transrectal biopsies. The imaging, image processing, and tracking methods are also discussed. In the arena of therapy, MR guidance has been used in conjunction with radiation methods, either brachytherapy or external delivery. The principles of the radiation treatment, the toxicities, and use of images are outlined. The future role of imaging and image-guided interventions lie with providing a noninvasive surrogate for cancer surveillance or monitoring treatment response. The shift to minimally invasive focal therapies has already begun and will be very exciting when MR-guided focused ultrasound surgery reaches its full potential. PMID:18219689

PSMA-Based Radioligand Therapy for Metastatic Castration-Resistant Prostate Cancer: The Bad Berka Experience Since 2013.

PubMed

Kulkarni, Harshad R; Singh, Aviral; Schuchardt, Christiane; Niepsch, Karin; Sayeg, Manal; Leshch, Yevgeniy; Wester, Hans-Juergen; Baum, Richard P

2016-10-01

A potential milestone in personalized nuclear medicine is theranostics of metastatic castration-resistant prostate cancer (mCRPC) based on molecular imaging using PET/CT with 68 Ga-labeled prostate-specific membrane antigen (PSMA) ligands and molecular radiotherapy using PSMA-targeted radioligand therapy (PRLT) with 177 Lu-PSMA ligands. 68 Ga-PSMA PET/CT enables accurate detection of mCRPC lesions with high diagnostic sensitivity and specificity and provides quantitative and reproducible data that can be used to select patients for PRLT and therapeutic monitoring. Our comprehensive experience over the last 3 years using different radioligands indicates that PRLT is highly effective for the treatment of mCRPC, even in advanced cases, and potentially lends a significant benefit to overall and progression-free survival. Additionally, significant improvement in clinical symptoms and excellent palliation of pain can be achieved. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

RGB imaging system for monitoring of skin vascular malformation's laser therapy

NASA Astrophysics Data System (ADS)

Jakovels, Dainis; Kuzmina, Ilona; Berzina, Anna; Spigulis, Janis

2012-06-01

A prototype RGB imaging system for mapping of skin chromophores consists of a commercial RGB CMOS sensor, RGB LEDs ring-light illuminator and orthogonally orientated polarizers for reducing specular reflectance. The system was used for monitoring of vascular malformations (hemagiomas and telangiectasias) therapy.

Specific, sensitive, and rapid assay for human immunodeficiency virus type 1 pol mutations associated with resistance to zidovudine and didanosine.

PubMed Central

Frenkel, L M; Wagner, L E; Atwood, S M; Cummins, T J; Dewhurst, S

1995-01-01

The effectiveness of antiretroviral therapy may be limited by the development of human immunodeficiency virus type 1 (HIV-1) resistance. Monitoring for resistance will perhaps allow changes in therapy prior to deterioration in the patient's clinical or immunologic status. Our objective was to develop a rapid, specific, and sensitive genotypic assay for HIV-1 resistance to zidovudine (ZDV) and didanosine (ddI) which is simple to perform. In our assay the DNA of HIV-1 pol was amplified by PCR using two sets of nested oligonucleotide primers. Mutations of reverse transcriptase (RT) encoding amino acids (aa) 74 and 41, 70, and 215 which have been associated with HIV-1 resistance to ddI and ZDV, respectively, were detected with a ligase detection reaction (LDR) and indicated colorimetrically. The RT genotypes of 35 patient specimens (140 codons) blindly assessed for these mutations were in agreement by PCR-LDR and by dideoxynucleotide sequencing. To evaluate the limits of the assay, other specimens with mutations close to the ligation site were evaluated by PCR-LDR. The assay was sensitive and specific for all specimens except when mutations occurred within 2 bases on either side of the ligation site. In summary, this PCR-LDR assay specifically, sensitively, and rapidly detected pol mutations (RT aa 74, 41, 70, and 215) associated with HIV-1 resistance to ddI and ZDV. PMID:7714190

Volumetric Contrast-Enhanced Ultrasound Imaging to Assess Early Response to Apoptosis-Inducing Anti–Death Receptor 5 Antibody Therapy in a Breast Cancer Animal Model

PubMed Central

Hoyt, Kenneth; Sorace, Anna; Saini, Reshu

2013-01-01

Objectives The objective of this study was to determine whether volumetric contrast-enhanced ultrasound (US) imaging could detect early tumor response to anti–death receptor 5 antibody (TRA-8) therapy alone or in combination with chemotherapy in a preclinical triple-negative breast cancer animal model. Methods Animal experiments had Institutional Animal Care and Use Committee approval. Thirty breast tumor–bearing mice were administered Abraxane (paclitaxel; Celgene Corporation, Summit, NJ), TRA-8, TRA-8 + Abraxane, or saline as a control on days 0, 3, 7, 10, 14, and 17. Volumetric contrast-enhanced US imaging was performed on days 0, 1, 3, and 7 before dosing. Changes in parametric maps of tumor perfusion were compared with the tumor volume and immunohistologic findings. Results Therapeutic efficacy was detected within 7 days after drug administration using parametric volumetric contrast-enhanced US imaging. Decreased tumor perfusion was observed in both the TRA-8-alone– and TRA-8 + Abraxane–dosed animals compared to control tumors (P = .17; P = .001, respectively). The reduction in perfusion observed in the TRA-8 + Abraxane group was matched with a corresponding regression in tumor size over the same period. Survival curves illustrate that the combination of TRA-8 + Abraxane improves drug efficacy compared to the same drugs administered alone. Immunohistologic analysis revealed increased levels of apoptotic activity in the TRA-8-dosed tumors, confirming enhanced antitumor effects. Conclusions Preliminary results are encouraging, and volumetric contrast-enhanced US-based tumor perfusion imaging may prove clinically feasible for detecting and monitoring the early antitumor effects in response to combination TRA-8 + Abraxane therapy. PMID:23091246

Results of ENHANCED Implantable Cardioverter Defibrillator Programming to Reduce Therapies and Improve Quality of Life (from the ENHANCED-ICD Study).

PubMed

Mastenbroek, Mirjam H; Pedersen, Susanne S; van der Tweel, Ingeborg; Doevendans, Pieter A; Meine, Mathias

2016-02-15

Novel implantable cardioverter defibrillator (ICD) discrimination algorithms and programming strategies have significantly reduced the incidence of inappropriate shocks, but there are still gains to be made with respect to reducing appropriate but unnecessary antitachycardia pacing (ATP) and shocks. We examined whether programming a number of intervals to detect (NID) of 60/80 for ventricular tachyarrhythmia (VT)/ventricular fibrillation (VF) detection was safe and the impact of this strategy on (1) adverse events related to ICD shocks and syncopal events; (2) ATPs/shocks; and (3) patient-reported outcomes. The "ENHANCED Implantable Cardioverter Defibrillator programming to reduce therapies and improve quality of life" study (ENHANCED-ICD study) was a prospective, safety-monitoring study enrolling 60 primary and secondary prevention patients at the University Medical Center Utrecht. Patients implanted with any type of ICD with SmartShock technology and aged 18 to 80 years were eligible to participate. In all patients, a prolonged NID 60/80 was programmed. The cycle length for VT/fast VT/VF was 360/330/240 ms, respectively. Programming a NID 60/80 proved safe for ICD patients. Because of the new programming strategy, unnecessary ICD therapy was prevented in 10% of ENHANCED-ICD patients during a median follow-up period of 1.3 years. With respect to patient-reported outcomes, levels of distress were highest and perceived health status lowest at the time of implantation, which both gradually improved during follow-up. In conclusion, the ENHANCED-ICD study demonstrates that programming a NID 60/80 for VT/VF detection is safe for ICD patients and does not negatively impact their quality of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Long-term wireless pH monitoring of the distal esophagus: prolonging the test beyond 48 hours is unnecessary and may be misleading.

PubMed

Capovilla, G; Salvador, R; Spadotto, L; Voltarel, G; Pesenti, E; Perazzolo, A; Nicoletti, L; Merigliano, S; Costantini, M

2017-10-01

Wireless pH monitoring of the esophagus has been widely used to detect GERD for more than a decade. It is generally well tolerated and accepted by patients, but it is still unclear whether prolonging a recording beyond the usual 48 hours can improve the test's diagnostic value. The aim of this study is to examine the diagnostic yield of 96-hour pH monitoring vis-à-vis 24- and 48-hour tests, and to ascertain whether any gain in diagnostic terms was of genuine clinical utility. Patients with suspected GERD underwent 4-day PPI-off wireless pH monitoring of the distal esophagus. The capsule was inserted under endoscopic control, 6 cm above the squamocolumnar junction. Average acid exposure time was calculated after 24, 48, and 96 hours of recording. Ninety-nine patients completed the 96 hour test, and formed the study sample. The wireless test method was used in 42 patients (42.4%) unable to tolerate the traditional pH-monitoring catheter, and in 57 (57.6%) with a previous negative pH study despite symptoms suggestive of GERD. On complete analysis, 47 patients (47.5%) had a pathological test result: 19 patients within the first 24 hours (19.2%, 24 hour group); another 16 after 48 hours (+16.2%, 48 hour group), and a further 12 (+12.1%, 96 hour group) only after 96 hours of monitoring. All 47 patients with an abnormal acid exposure were offered and accepted surgery (10 patients) or medical therapy (37 patients). Clinical follow-up was obtained in all patients with a positive Bravo test result after a median 67 months (IQR: 38-98) using a validated symptom questionnaire. A good outcome after fundoplication or medical therapy was achieved in 73.7% of patients in the 24 hour group, in 62.5% of those in the 48 hour group, and in only 25% of those in the 96 hour group, P = 0.02. Long-term wireless pH monitoring enables an increase in the diagnostic yield over traditional 24- and 48-hour pH studies, but prolonging the test may constitute an unwanted bias and prompt the recruitment of more complex patients, in whom the outcome of surgical or medical therapy may prove less than satisfactory. These findings should be taken into account when establishing the guidelines for assessing GERD with such long-term pH monitoring methods. © The Authors 2017. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Diagnosis and therapy of atrial tachyarrhythmias in the dual chamber implantable cardioverter defibrillator.

PubMed

Dijkman, B; Wellens, H J

2000-11-01

Devices capable of monitoring and treating atrial tachyarrhythmias provide information about the natural history of the arrhythmias and potentially can influence their natural course by electrical therapy early after onset. Types of atrial arrhythmias and efficacy of device therapies were evaluated in 30 patients implanted with the Medtronic model 7250 Jewel AF implantable cardioverter defibrillator (ICD). All patients had structural heart disease and documented sustained ventricular and atrial arrhythmias (27 with atrial fibrillation [AF]) before implant. Twenty patients were taking amiodarone, and three were taking sotalol. During 20+/-10 months of follow-up, 600 atrial arrhythmia recurrences were documented in 50% of patients. AF was diagnosed in 19%, fast polymorphic atrial tachycardia (AT) in 20%, fast monomorphic AT in 57%, and slow AT in 4% of episodes. The two adaptive pacing therapies, burst and ramp, together with the 50-Hz burst, were successful in 57% of detected atrial arrhythmias. Burst and ramp were responsible for 49% and 50-Hz burst for 51% of successfully treated arrhythmias; 33% of the episodes terminated spontaneously. No ventricular proarrhythmia was observed due to atrial pacing therapies. In 30% of episodes, dual chamber pacing was required due to post termination bradycardia. Atrial arrhythmia recurrences in patients with dilated cardiomyopathy were not amenable to pacing therapies. Several aspects of atrial arrhythmia diagnosis, therapy, and documentation that are specific for functioning of the Jewel AF are discussed. Atrial arrhythmias in ICD patients with diseased hearts who are taking Class III antiarrhythmics frequently had longer cycle lengths than AF. Half of these arrhythmias could be terminated with pacing therapies; one third terminated spontaneously.

FIRST experiment: Fragmentation of Ions Relevant for Space and Therapy

NASA Astrophysics Data System (ADS)

Agodi, C.; Abou-Haidar, Z.; Alvarez, M. A. G.; Aumann, T.; Balestra, F.; Battistoni, G.; Bocci, A.; Bohlen, T. T.; Bondì, M.; Boudard, A.; Brunetti, A.; Carpinelli, M.; Cappuzzello, F.; Cavallaro, M.; Carbone, D.; Cirrone, G. A. P.; Cortes-Giraldo, M. A.; Cuttone, G.; De Napoli, M.; Durante, M.; Fernandez-Garcia, J. P.; Finck, C.; Foti, A.; Gallardo, M. I.; Golosio, B.; Iarocci, E.; Iazzi, F.; Ickert, G.; Introzzi, R.; Juliani, D.; Krimmer, J.; Kurz, N.; Labalme, M.; Lavagno, A.; Leifels, Y.; Le Fevre, A.; Leray, S.; Marchetto, F.; Monaco, V.; Morone, M. C.; Nicolosi, D.; Oliva, P.; Paoloni, A.; Patera, V.; Piersanti, L.; Pleskac, R.; Quesada, J. M.; Randazzo, N.; Romano, F.; Rossi, D.; Rosso, V.; Rousseau, M.; Sacchi, R.; Sala, P.; Sarti, A.; Scheidenberger, C.; Schuy, C.; Sciubba, A.; Sfienti, C.; Simon, H.; Sipala, V.; Spiriti, E.; Stuttge, L.; Tropea, S.; Younis, H.

2013-03-01

Nuclear fragmentation processes are relevant in different fields of basic research and applied physics and are of particular interest for tumor therapy and for space radiation protection applications. The FIRST (Fragmentation of Ions Relevant for Space and Therapy) experiment at SIS accelerator of GSI laboratory in Darmstadt, has been designed for the measurement of different ions fragmentation cross sections at different energies between 100 and 1000 MeV/nucleon. The experiment is performed by an international collaboration made of institutions from Germany, France, Italy and Spain. The experimental apparatus is partly based on an already existing setup made of the ALADIN magnet, the MUSIC IV TPC, the LAND2 neutron detector and the TOFWALL scintillator TOF system, integrated with newly designed detectors in the interaction Region (IR) around the carbon removable target: a scintillator Start Counter, a Beam Monitor drift chamber, a silicon Vertex Detector and a Proton Tagger for detection of light fragments emitted at large angles (KENTROS). The scientific program of the FIRST experiment started on summer 2011 with the study of the 400 MeV/nucleon 12C beam fragmentation on thin (8mm) carbon target.

The role of biomarkers in the management of epithelial ovarian cancer.

PubMed

Yang, Wei-Lei; Lu, Zhen; Bast, Robert C

2017-06-01

Despite advances in surgery and chemotherapy for ovarian cancer, 70% of women still succumb to the disease. Biomarkers have contributed to the management of ovarian cancer by monitoring response to treatment, detecting recurrence, distinguishing benign from malignant pelvic masses and attempting to detect disease at an earlier stage. Areas covered: This review focuses on recent advances in biomarkers and imaging for management of ovarian cancer with particular emphasis on early detection. Relevant literature has been reviewed and analyzed. Expert commentary: Rising or persistent CA125 blood levels provide a highly specific biomarker for epithelial ovarian cancer, but not an optimally sensitive biomarker. Addition of HE4, CA 72.4, anti-TP53 autoantibodies and other biomarkers can increase sensitivity for detecting early stage or recurrent disease. Detecting disease recurrence will become more important as more effective therapy is developed. Early detection will require the development not only of biomarker panels, but also of more sensitive and specific imaging strategies. Effective biomarker strategies are already available for distinguishing benign from malignant pelvic masses, but their use in identifying and referring patients with probable ovarian cancer to gynecologic oncologists for cytoreductive operations must be encouraged.

Molecular Detection of Antimicrobial Resistance

PubMed Central

Fluit, Ad C.; Visser, Maarten R.; Schmitz, Franz-Josef

2001-01-01

The determination of antimicrobial susceptibility of a clinical isolate, especially with increasing resistance, is often crucial for the optimal antimicrobial therapy of infected patients. Nucleic acid-based assays for the detection of resistance may offer advantages over phenotypic assays. Examples are the detection of the methicillin resistance-encoding mecA gene in staphylococci, rifampin resistance in Mycobacterium tuberculosis, and the spread of resistance determinants across the globe. However, molecular assays for the detection of resistance have a number of limitations. New resistance mechanisms may be missed, and in some cases the number of different genes makes generating an assay too costly to compete with phenotypic assays. In addition, proper quality control for molecular assays poses a problem for many laboratories, and this results in questionable results at best. The development of new molecular techniques, e.g., PCR using molecular beacons and DNA chips, expands the possibilities for monitoring resistance. Although molecular techniques for the detection of antimicrobial resistance clearly are winning a place in routine diagnostics, phenotypic assays are still the method of choice for most resistance determinations. In this review, we describe the applications of molecular techniques for the detection of antimicrobial resistance and the current state of the art. PMID:11585788

Molecular Signature of Pseudomonas aeruginosa with Simultaneous Nanomolar Detection of Quorum Sensing Signaling Molecules at a Boron-Doped Diamond Electrode

NASA Astrophysics Data System (ADS)

Buzid, Alyah; Shang, Fengjun; Reen, F. Jerry; Muimhneacháin, Eoin Ó.; Clarke, Sarah L.; Zhou, Lin; Luong, John H. T.; O'Gara, Fergal; McGlacken, Gerard P.; Glennon, Jeremy D.

2016-07-01

Electroanalysis was performed using a boron-doped diamond (BDD) electrode for the simultaneous detection of 2-heptyl-3-hydroxy-4-quinolone (PQS), 2-heptyl-4-hydroxyquinoline (HHQ) and pyocyanin (PYO). PQS and its precursor HHQ are two important signal molecules produced by Pseudomonas aeruginosa, while PYO is a redox active toxin involved in virulence and pathogenesis. This Gram-negative and opportunistic human pathogen is associated with a hospital-acquired infection particularly in patients with compromised immunity and is the primary cause of morbidity and mortality in cystic fibrosis (CF) patients. Early detection is crucial in the clinical management of this pathogen, with established infections entering a biofilm lifestyle that is refractory to conventional antibiotic therapies. Herein, a detection procedure was optimized and proven for the simultaneous detection of PYO, HHQ and PQS in standard mixtures, biological samples, and P. aeruginosa spiked CF sputum samples with remarkable sensitivity, down to nanomolar levels. Differential pulse voltammetry (DPV) scans were also applicable for monitoring the production of PYO, HHQ and PQS in P. aeruginosa PA14 over 8 h of cultivation. The simultaneous detection of these three compounds represents a molecular signature specific to this pathogen.

Real-time beam monitoring in scanned proton therapy

NASA Astrophysics Data System (ADS)

Klimpki, G.; Eichin, M.; Bula, C.; Rechsteiner, U.; Psoroulas, S.; Weber, D. C.; Lomax, A.; Meer, D.

2018-05-01

When treating cancerous tissues with protons beams, many centers make use of a step-and-shoot irradiation technique, in which the beam is steered to discrete grid points in the tumor volume. For safety reasons, the irradiation is supervised by an independent monitoring system validating cyclically that the correct amount of protons has been delivered to the correct position in the patient. Whenever unacceptable inaccuracies are detected, the irradiation can be interrupted to reinforce a high degree of radiation protection. At the Paul Scherrer Institute, we plan to irradiate tumors continuously. By giving up the idea of discrete grid points, we aim to be faster and more flexible in the irradiation. But the increase in speed and dynamics necessitates a highly responsive monitoring system to guarantee the same level of patient safety as for conventional step-and-shoot irradiations. Hence, we developed and implemented real-time monitoring of the proton beam current and position. As such, we read out diagnostic devices with 100 kHz and compare their signals against safety tolerances in an FPGA. In this paper, we report on necessary software and firmware enhancements of our control system and test their functionality based on three exemplary error scenarios. We demonstrate successful implementation of real-time beam monitoring and, consequently, compliance with international patient safety regulations.

Monitoring of Intracranial Pressure in Patients with Traumatic Brain Injury

PubMed Central

Hawthorne, Christopher; Piper, Ian

2014-01-01

Since Monro published his observations on the nature of the contents of the intracranial space in 1783, there has been investigation of the unique relationship between the contents of the skull and the intracranial pressure (ICP). This is particularly true following traumatic brain injury (TBI), where it is clear that elevated ICP due to the underlying pathological processes is associated with a poorer clinical outcome. Consequently, there is considerable interest in monitoring and manipulating ICP in patients with TBI. The two techniques most commonly used in clinical practice to monitor ICP are via an intraventricular or intraparenchymal catheter with a microtransducer system. Both of these techniques are invasive and are thus associated with complications such as hemorrhage and infection. For this reason, significant research effort has been directed toward development of a non-invasive method to measure ICP. The principle aims of ICP monitoring in TBI are to allow early detection of secondary hemorrhage and to guide therapies that limit intracranial hypertension (ICH) and optimize cerebral perfusion. However, information from the ICP value and the ICP waveform can also be used to assess the intracranial volume–pressure relationship, estimate cerebrovascular pressure reactivity, and attempt to forecast future episodes of ICH. PMID:25076934

Lung Volume Reduction in Pulmonary Emphysema from the Radiologist's Perspective.

PubMed

Doellinger, F; Huebner, R H; Kuhnigk, J M; Poellinger, A

2015-08-01

Pulmonary emphysema causes decrease in lung function due to irreversible dilatation of intrapulmonary air spaces, which is linked to high morbidity and mortality. Lung volume reduction (LVR) is an invasive therapeutical option for pulmonary emphysema in order to improve ventilation mechanics. LVR can be carried out by lung resection surgery or different minimally invasive endoscopical procedures. All LVR-options require mandatory preinterventional evaluation to detect hyperinflated dysfunctional lung areas as target structures for treatment. Quantitative computed tomography can determine the volume percentage of emphysematous lung and its topographical distribution based on the lung's radiodensity. Modern techniques allow for lobebased quantification that facilitates treatment planning. Clinical tests still play the most important role in post-interventional therapy monitoring, but CT is crucial in the detection of postoperative complications and foreshadows the method's high potential in sophisticated experimental studies. Within the last ten years, LVR with endobronchial valves has become an extensively researched minimally-invasive treatment option. However, this therapy is considerably complicated by the frequent occurrence of functional interlobar shunts. The presence of "collateral ventilation" has to be ruled out prior to valve implantations, as the presence of these extraanatomical connections between different lobes may jeopardize the success of therapy. Recent experimental studies evaluated the automatic detection of incomplete lobar fissures from CT scans, because they are considered to be a predictor for the existence of shunts. To date, these methods are yet to show acceptable results. Today, surgical and various minimal invasive methods of lung volume reduction are in use. Radiological and nuclear medical examinations are helpful in the evaluation of an appropriate lung area. Imaging can detect periinterventional complications. Reduction of lung volume has not yet been conclusively proven to be effective and is a therapeutical option with little scientific evidence. © Georg Thieme Verlag KG Stuttgart · New York.

Detection of minimal residual disease following induction immunochemotherapy predicts progression free survival in mantle cell lymphoma: final results of CALGB 59909

PubMed Central

Liu, Hongtao; Johnson, Jeffrey L.; Koval, Greg; Malnassy, Greg; Sher, Dorie; Damon, Lloyd E.; Hsi, Eric D.; Bucci, Donna Marie; Linker, Charles A.; Cheson, Bruce D.; Stock, Wendy

2012-01-01

Background In the present study, the prognostic impact of minimal residual disease during treatment on time to progression and overall survival was analyzed prospectively in patients with mantle cell lymphoma treated on the Cancer and Leukemia Group B 59909 clinical trial. Design and Methods Peripheral blood and bone marrow samples were collected during different phases of the Cancer and Leukemia Group B 59909 study for minimal residual disease analysis. Minimal residual disease status was determined by quantitative polymerase chain reaction of IgH and/or BCL-1/JH gene rearrangement. Correlation of minimal residual disease status with time to progression and overall survival was determined. In multivariable analysis, minimal residual disease, and other risk factors were correlated with time to progression. Results Thirty-nine patients had evaluable, sequential peripheral blood and bone marrow samples for minimal residual disease analysis. Using peripheral blood monitoring, 18 of 39 (46%) achieved molecular remission following induction therapy. The molecular remission rate increased from 46 to 74% after one course of intensification therapy. Twelve of 21 minimal residual disease positive patients (57%) progressed within three years of follow up compared to 4 of 18 (22%) molecular remission patients (P=0.049). Detection of minimal residual disease following induction therapy predicted disease progression with a hazard ratio of 3.7 (P=0.016). The 3-year probability of time to progression among those who were in molecular remission after induction chemotherapy was 82% compared to 48% in patients with detectable minimal residual disease. The prediction of time to progression by post-induction minimal residual disease was independent of other prognostic factors in multivariable analysis. Conclusions Detection of minimal residual disease following induction immunochemotherapy was an independent predictor of time to progression following immunochemotherapy and autologous stem cell transplantation for mantle cell lymphoma. The clinical trial was registered at ClinicalTrials.gov: NCT00020943. PMID:22102709

Nanoplasmonic Quantification of Tumor-derived Extracellular Vesicles in Plasma Microsamples for Diagnosis and Treatment Monitoring

PubMed Central

Liang, Kai; Liu, Fei; Fan, Jia; Sun, Dali; Liu, Chang; Lyon, Christopher J.; Bernard, David W.; Li, Yan; Yokoi, Kenji; Katz, Matthew H.; Koay, Eugene J.; Zhao, Zhen; Hu, Ye

2017-01-01

Tumour-derived extracellular vesicles (EVs) are of increasing interest as a resource of diagnostic biomarkers. However, most EV assays require large samples, are time-consuming, low-throughput and costly, and thus impractical for clinical use. Here, we describe a rapid, ultrasensitive and inexpensive nanoplasmon-enhanced scattering (nPES) assay that directly quantifies tumor-derived EVs from as little as 1 μL of plasma. The assay uses the binding of antibody-conjugated gold nanospheres and nanorods to EVs captured by EV-specific antibodies on a sensor chip to produce a local plasmon effect that enhances tumour-derived EV detection sensitivity and specificity. We identified a pancreatic cancer EV biomarker, ephrin type-A receptor 2 (EphA2), and demonstrate that an nPES assay for EphA2-EVs distinguishes pancreatic cancer patients from pancreatitis patients and healthy subjects. EphA2-EVs were also informative in staging tumour progression and in detecting early responses to neoadjuvant therapy, with better performance than a conventional enzyme-linked immunosorbent assay. The nPES assay can be easily refined for clinical use, and readily adapted for diagnosis and monitoring of other conditions with disease-specific EV biomarkers. PMID:28791195

Correlation of immune activation with HIV-1 RNA levels assayed by real-time RT-PCR in HIV-1 Subtype C infected patients in Northern India

PubMed Central

Agarwal, Atima; Sankaran, Sumathi; Vajpayee, Madhu; Sreenivas, V; Seth, Pradeep; Dandekar, Satya

2014-01-01

Background Assays with specificity and cost effectiveness are needed for the measurement of HIV-1 burden to monitor disease progression or response to anti-retroviral therapy (ART) in HIV-1 subtype C infected patients. Objectives The objective of this study was to develop and validate an affordable; one step Real-Time RT-PCR assay with high specificity and sensitivity to measure plasma HIV-1 loads in HIV-1 subtype C infected patients. Results We developed an RT-PCR assay to detect and quantitate plasma HIV-1 levels in HIV-1 subtype C infected patients. An inverse correlation between plasma viral loads (PVL) and CD4+ T-cell numbers was detected at all CDC stages. Significant correlations were found between CD8+ T-cell activation and PVL, as well as with the clinical and immunological status of the patients. Conclusions The RT-PCR assay provides a sensitive method to measure PVL in HIV-1 subtype C infected patients. Viral loads correlated with immune activation and can be used to monitor HIV care in India. PMID:17962068

Ulcerative Colitis: Update on Medical Management.

PubMed

Iskandar, Heba N; Dhere, Tanvi; Farraye, Francis A

2015-11-01

Ulcerative colitis (UC) is a chronic inflammatory bowel disease whose pathogenesis is multifactorial and includes influences from genes, the environment, and the gut microbiome. Recent advances in diagnosis and treatment have led to significant improvement in managing the disease. Disease monitoring with the use of therapeutic drug monitoring, stool markers, and assessment of mucosal healing have garnered much attention. The recent approval of vedolizumab for treatment of moderate to severe UC has been a welcome addition. Newer biologics, including those targeting the Janus tyrosine kinase (JAK) pathway, are on the horizon to add to the current armamentarium of anti-TNF alpha and anti-integrin therapies. The recent publication of the SCENIC consensus statement on surveillance and management of dysplasia in UC patients supports the use of chromoendoscopy over random biopsies in detecting dysplasia. This review highlights these recent advances along with others that have been made with ulcerative colitis.

Real-time detection of fast and thermal neutrons in radiotherapy with CMOS sensors.

PubMed

Arbor, Nicolas; Higueret, Stephane; Elazhar, Halima; Combe, Rodolphe; Meyer, Philippe; Dehaynin, Nicolas; Taupin, Florence; Husson, Daniel

2017-03-07

The peripheral dose distribution is a growing concern for the improvement of new external radiation modalities. Secondary particles, especially photo-neutrons produced by the accelerator, irradiate the patient more than tens of centimeters away from the tumor volume. However the out-of-field dose is still not estimated accurately by the treatment planning softwares. This study demonstrates the possibility of using a specially designed CMOS sensor for fast and thermal neutron monitoring in radiotherapy. The 14 microns-thick sensitive layer and the integrated electronic chain of the CMOS are particularly suitable for real-time measurements in γ/n mixed fields. An experimental field size dependency of the fast neutron production rate, supported by Monte Carlo simulations and CR-39 data, has been observed. This dependency points out the potential benefits of a real-time monitoring of fast and thermal neutron during beam intensity modulated radiation therapies.

Esophageal Impedance Monitoring for Gastroesophageal Reflux

PubMed Central

Mousa, Hayat M.; Rosen, Rachel; Woodley, Frederick W.; Orsi, Marina; Armas, Daneila; Faure, Christophe; Fortunato, John; O'Connor, Judith; Skaggs, Beth; Nurko, Samuel

2014-01-01

Dual pH-multichannel intraluminal impedance (pH-MII) is a sensitive tool for evaluating overall gastroesophageal reflux disease, and particularly for permitting detection of nonacid reflux events. pH-MII technology is especially useful in the postprandial period or at other times when gastric contents are nonacidic. pH-MII was recently recognized by the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition as being superior to pH monitoring alone for evaluation of the temporal relation between symptoms and gastroesophageal reflux. In children, pHMII is useful to correlate symptoms with reflux (particularly nonacid reflux), to quantify reflux during tube feedings and the postprandial period, and to assess efficacy of antireflux therapy. This clinical review is simply an evidence-based overview addressing the indications, limitations, and recommended protocol for the clinical use of pH-MII in children. PMID:21240010

Human cervical carcinoma detection and glucose monitoring in blood micro vasculatures with swept source OCT

NASA Astrophysics Data System (ADS)

Ullah, H.; Ahmed, E.; Ikram, M.

2013-08-01

We report a pilot method, i.e., speckle variance (SV) and structured optical coherence tomography to visualize normal and malignant blood microvasculature in three and two dimensions and to monitor the glucose levels in blood by analyzing the Brownian motion of the red blood cells. The technique was applied on nude live mouse's skin and the obtained images depict the enhanced intravasculature network forum up to the depth of ˜2 mm with axial resolution of ˜8 μm. Microscopic images have also been obtained for both types of blood vessels to observe the tumor spatially. Our SV-OCT methodologies and results give satisfactory techniques in real time imaging and can potentially be applied during therapeutic techniques such as photodynamic therapy as well as to quantify the higher glucose levels injected intravenously to animal by determining the translation diffusion coefficient.

Clinical Impact of Accurate Point-of-Care Glucose Monitoring for Tight Glycemic Control in Severely Burned Children.

PubMed

Tran, Nam K; Godwin, Zachary R; Steele, Amanda N; Wolf, Steven E; Palmieri, Tina L

2016-09-01

The goal of this study was to retrospectively evaluate the clinical impact of an accurate autocorrecting blood glucose monitoring system in children with severe burns. Blood glucose monitoring system accuracy is essential for providing appropriate intensive insulin therapy and achieving tight glycemic control in critically ill patients. Unfortunately, few comparison studies have been performed to evaluate the clinical impact of accurate blood glucose monitoring system monitoring in the high-risk pediatric burn population. Retrospective analysis of an electronic health record system. Pediatric burn ICU at an academic medical center. Children (aged < 18 yr) with severe burns (≥ 20% total body surface area) receiving intensive insulin therapy guided by either a noncorrecting (blood glucose monitoring system-1) or an autocorrecting blood glucose monitoring system (blood glucose monitoring system-2). Patient demographics, insulin rates, and blood glucose monitoring system measurements were collected. The frequency of hypoglycemia and glycemic variability was compared between the two blood glucose monitoring system groups. A total of 122 patient charts from 2001 to 2014 were reviewed. Sixty-three patients received intensive insulin therapy using blood glucose monitoring system-1 and 59 via blood glucose monitoring system-2. Patient demographics were similar between the two groups. Mean insulin infusion rates (5.1 ± 3.8 U/hr; n = 535 paired measurements vs 2.4 ± 1.3 U/hr; n = 511 paired measurements; p < 0.001), glycemic variability, and frequency of hypoglycemic events (90 vs 12; p < 0.001) were significantly higher in blood glucose monitoring system-1-treated patients. Compared with laboratory measurements, blood glucose monitoring system-2 yielded the most accurate results (mean ± SD bias: -1.7 ± 6.9 mg/dL [-0.09 ± 0.4 mmol/L] vs 7.4 ± 13.5 mg/dL [0.4 ± 0.7 mmol/L]). Blood glucose monitoring system-2 patients achieve glycemic control more quickly (5.7 ± 4.3 vs 13.1 ± 6.9 hr; p< 0.001) and stayed within the target glycemic control range longer compared with blood glucose monitoring system-1 patients (85.2% ± 13.9% vs 57.9% ± 29.1%; p < 0.001). Accurate autocorrecting blood glucose monitoring system optimizes intensive insulin therapy, improves tight glycemic control, and reduces the risk of hypoglycemia and glycemic variability. The use of an autocorrecting blood glucose monitoring system for intensive insulin therapy may improve glycemic control in severely burned children.

Imaging transplanted stem cells in real time using an MRI dual-contrast method

PubMed Central

Ngen, Ethel J.; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-01-01

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies. PMID:26330231

Occupational Therapy Students' Perceptions of the Role of Robots in the Care for Older People Living in the Community.

PubMed

Tobis, Sławomir; Cylkowska-Nowak, Mirosława; Wieczorowska-Tobis, Katarzyna; Pawlaczyk, Mariola; Suwalska, Aleksandra

2017-01-01

The question arises how recent developments in robotics can contribute to the care for older people. The study is part of the EU-funded ENRICHME project. The aim of the study was to investigate opinions of occupational therapy students (OTS), as future professional caregivers, on the use of robots in care for older people. It included 26 OTS from Poznan University of Medical Sciences. To collect data, the Users' Needs, Requirements, and Abilities Questionnaire (UNRAQ) was developed. OTS perceived the robot as "a useful device" and "an assistant" rather than "a companion" ( p < 0.01). In their opinion, the most important functions of the robot were related to health aspects (emergency alarms, health parameters monitoring, physical activity and memory training, and reminders about medication, drinks, etc.), scored positively by 23-26 OTS. Functions such as mood detection, encouraging to contact with friends, and monitoring of food consumption were accepted by 16-17 OTS. Two statements concerning social functions (accompanying in everyday activities and decreasing the sense of loneliness) were rated positively by less the than half of the participants. A module concerning technology use, including robotics, should constitute an important part of the curricula of both academic and continuous education of OTS.

Imaging transplanted stem cells in real time using an MRI dual-contrast method.

PubMed

Ngen, Ethel J; Wang, Lee; Kato, Yoshinori; Krishnamachary, Balaji; Zhu, Wenlian; Gandhi, Nishant; Smith, Barbara; Armour, Michael; Wong, John; Gabrielson, Kathleen; Artemov, Dmitri

2015-09-02

Stem cell therapies are currently being investigated for the repair of brain injuries. Although exogenous stem cell labelling with superparamagnetic iron oxide nanoparticles (SPIONs) prior to transplantation provides a means to noninvasively monitor stem cell transplantation by magnetic resonance imaging (MRI), monitoring cell death is still a challenge. Here, we investigate the feasibility of using an MRI dual-contrast technique to detect cell delivery, cell migration and cell death after stem cell transplantation. Human mesenchymal stem cells were dual labelled with SPIONs and gadolinium-based chelates (GdDTPA). The viability, proliferation rate, and differentiation potential of the labelled cells were then evaluated. The feasibility of this MRI technique to distinguish between live and dead cells was next evaluated using MRI phantoms, and in vivo using both immune-competent and immune-deficient mice, following the induction of brain injury in the mice. All results were validated with bioluminescence imaging. In live cells, a negative (T2/T2*) MRI contrast predominates, and is used to track cell delivery and cell migration. Upon cell death, a diffused positive (T1) MRI contrast is generated in the vicinity of the dead cells, and serves as an imaging marker for cell death. Ultimately, this technique could be used to manage stem cell therapies.

Consumer-Based Physical Activity Monitor as a Practical Way to Measure Walking Intensity During Inpatient Stroke Rehabilitation.

PubMed

Klassen, Tara D; Semrau, Jennifer A; Dukelow, Sean P; Bayley, Mark T; Hill, Michael D; Eng, Janice J

2017-09-01

Identifying practical ways to accurately measure exercise intensity and dose in clinical environments is essential to advancing stroke rehabilitation. This is especially relevant in monitoring walking activity during inpatient rehabilitation where recovery is greatest. This study evaluated the accuracy of a readily available consumer-based physical activity monitor during daily inpatient stroke rehabilitation physical therapy sessions. Twenty-one individuals admitted to inpatient rehabilitation were monitored for a total of 471 one-hour physical therapy sessions which consisted of walking and nonwalking therapeutic activities. Participants wore a consumer-based physical activity monitor (Fitbit One) and the gold standard for assessing step count (StepWatch Activity Monitor) during physical therapy sessions. Linear mixed modeling was used to assess the relationship of the step count of the Fitbit to the StepWatch Activity Monitor. Device accuracy is reported as the percent error of the Fitbit compared with the StepWatch Activity Monitor. A strong relationship (slope=0.99; 95% confidence interval, 0.97-1.01) was found between the number of steps captured by the Fitbit One and the StepWatch Activity Monitor. The Fitbit One had a mean error of 10.9% (5.3) for participants with walking velocities <0.4 m/s, 6.8% (3.0) for walking velocities between 0.4 and 0.8 m/s, and 4.4% (2.8) for walking velocities >0.8 m/s. This study provides preliminary evidence that the Fitbit One, when positioned on the nonparetic ankle, can accurately measure walking steps early after stroke during inpatient rehabilitation physical therapy sessions. URL: https://www.clinicaltrials.gov. Unique identifier: NCT01915368. © 2017 American Heart Association, Inc.

The development of skin immersion clearing method for increasing of laser exposure efficiency on subcutaneous objects

NASA Astrophysics Data System (ADS)

Kozina, Alexandra M.; Genina, Elina A.; Terentyuk, Georgy S.; Terentyuk, Artem G.; Bashkatov, Alexey N.; Tuchin, Valery V.; Khlebtsov, Boris N.

2012-06-01

In this paper we have studied effect of a hyperosmotic optical clearing agent (OCA), such as polyethylene glycol, on the fluorescence intensity from a target located in subcutaneous area in the model experiments. As a fluorescence agent the nanocomposite including gold nanorods with hematophorphyrin was used. The remitted fluorescent signal traveling to the tissue surface was monitored over time as the tissue was treated with the OCA. The detected fluorescent signal increased as the scattering in tissue samples was substantially reduced. The study has shown how OCA can be used to improve the detected signal at localization of subcutaneous target tissue at the photothermal or photodynamic therapy. Immersion clearing of skin can be also useful for improvement of laser exposure efficiency due to the increasing of light penetration depth.

Current wound healing procedures and potential care.

PubMed

Dreifke, Michael B; Jayasuriya, Amil A; Jayasuriya, Ambalangodage C

2015-03-01

In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting microRNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage microenvironment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection - all in the hopes of early detection of complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Current wound healing procedures and potential care

PubMed Central

Dreifke, Michael B.; Jayasuriya, Amil A.; Jayasuriya, Ambalangodage C.

2015-01-01

In this review, we describe current and future potential wound healing treatments for acute and chronic wounds. The current wound healing approaches are based on autografts, allografts, and cultured epithelial autografts, and wound dressings based on biocompatible and biodegradable polymers. The Food and Drug Administration approved wound healing dressings based on several polymers including collagen, silicon, chitosan, and hyaluronic acid. The new potential therapeutic intervention for wound healing includes sustained delivery of growth factors, and siRNA delivery, targeting micro RNA, and stem cell therapy. In addition, environment sensors can also potentially utilize to monitor and manage micro environment at wound site. Sensors use optical, odor, pH, and hydration sensors to detect such characteristics as uric acid level, pH, protease level, and infection – all in the hopes of early detection of complications. PMID:25579968

Imaging the delivery of brain-penetrating PLGA nanoparticles in the brain using magnetic resonance.

PubMed

Strohbehn, Garth; Coman, Daniel; Han, Liang; Ragheb, Ragy R T; Fahmy, Tarek M; Huttner, Anita J; Hyder, Fahmeed; Piepmeier, Joseph M; Saltzman, W Mark; Zhou, Jiangbing

2015-02-01

Current therapy for glioblastoma multiforme (GBM) is largely ineffective, with nearly universal tumor recurrence. The failure of current therapy is primarily due to the lack of approaches for the efficient delivery of therapeutics to diffuse tumors in the brain. In our prior study, we developed brain-penetrating nanoparticles that are capable of penetrating brain tissue and distribute over clinically relevant volumes when administered via convection-enhanced delivery (CED). We demonstrated that these particles are capable of efficient delivery of chemotherapeutics to diffuse tumors in the brain, indicating that they may serve as a groundbreaking approach for the treatment of GBM. In the original study, nanoparticles in the brain were imaged using positron emission tomography (PET). However, clinical translation of this delivery platform can be enabled by engineering a non-invasive detection modality using magnetic resonance imaging (MRI). For this purpose, we developed chemistry to incorporate superparamagnetic iron oxide (SPIO) into the brain-penetrating nanoparticles. We demonstrated that SPIO-loaded nanoparticles, which retain the same morphology as nanoparticles without SPIO, have an excellent transverse (T(2)) relaxivity. After CED, the distribution of nanoparticles in the brain (i.e., in the vicinity of injection site) can be detected using MRI and the long-lasting signal attenuation of SPIO-loaded brain-penetrating nanoparticles lasted over a one-month timecourse. Development of these nanoparticles is significant as, in future clinical applications, co-administration of SPIO-loaded nanoparticles will allow for intraoperative monitoring of particle distribution in the brain to ensure drug-loaded nanoparticles reach tumors as well as for monitoring the therapeutic benefit with time and to evaluate tumor relapse patterns.

Comparison of the Abbott RealTime HCV and Roche COBAS Ampliprep/COBAS TaqMan HCV assays for the monitoring of sofosbuvir-based therapy.

PubMed

Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Shimizu, Motohiro; Toyoda, Kazuhiro; Hotta, Taeko; Uchiumi, Takeshi; Hayashi, Jun

2017-01-01

On-treatment HCV kinetics play an invaluable role in evaluating the efficacy of interferon-based therapies. However, the importance of HCV RNA monitoring has not been well discussed concerning treatment with sofosbuvir (SOF)-based regimens, especially for the utility of the Abbott RealTime HCV (ART) assay. This study consisted of 151 patients infected with HCV genotype-1 or -2, including patients with prior treatment-experience or cirrhosis. HCV genotype-1 patients were treated with SOF/ledipasvir and genotype-2 patients with SOF/ribavirin, both for 12 weeks. Serial measurements of HCV RNA were performed with both the ART and COBAS AmpliPrep/COBAS TaqMan v2.0 (CAP/CTM) assays simultaneously at weeks 0, 1, 2, 4, 6, 8, 10 and 12 of treatment. The rates of HCV RNA target not detected (TND) by ART were significantly lower than those by CAP/CTM between weeks 2 and 12 (end of treatment [EOT]), irrespective of prior treatment-experience or cirrhosis. 11 (11.6%) genotype-1 and 8 (14.3%) genotype-2 patients did not achieve HCV RNA TND by ART at EOT, in contrast to all having HCV RNA TND by CAP/CTM; however, all achieved sustained virological response. The time at which HCV RNA became TND or unquantifiable was not associated with treatment outcome by either the ART or CAP/CTM assay. Over 10% of the patients continued to have detectable HCV RNA by ART at EOT, irrespective of HCV genotype, prior treatment-experience and/or cirrhosis. However, prolonged residual HCV RNA was not associated with treatment failure.

Review of the Methods to Obtain Paediatric Drug Safety Information: Spontaneous Reporting and Healthcare Databases, Active Surveillance Programmes, Systematic Reviews and Meta-analyses

PubMed

Gentili, Marta; Pozzi, Marco; Peeters, Gabrielle; Radice, Sonia; Carnovale, Carla

2018-02-06

Knowledge of drugs safety collected during the pre-marketing phase is inevitably limited because the randomized clinical trials (RCTs) are rarely designed to evaluate safety. The small and selective groups of enrolled individuals and the limited duration of trials may hamper the ability to characterize fully the safety profiles of drugs. Additionally, information about rare adverse drug reactions (ADRs) in special groups is often incomplete or not available for most of the drugs commonly used in the daily clinical practice. In the paediatric setting several highimpact safety issues have emerged. Hence, in recent years, there has been a call for improved post-marketing pharmacoepidemiological studies, in which cohorts of patients are monitored for sufficient time in order to determine the precise risk-benefit ratio. In this review, we discuss the current available strategies enhancing the post-marketing monitoring activities of the drugs in the paediatric setting and define criteria whereby they can provide valuable information to improve the management of therapy in daily clinical practice including both safety and efficacy aspects. The strategies we cover include the signal detection using international pharmacovigilance and/or healthcare databases, the promotion of active surveillance initiatives which can generate complete, informative data sets for the signal detection and systematic review/meta-analysis. Together, these methods provide a comprehensive picture of causality and risk improving the management of therapy in a paediatric setting and they should be considered as a unique tool to be integrated with post-marketing activities. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Using bone densitometry to monitor therapy in treating osteoporosis: pros and cons.

PubMed

Deal, C L

2001-06-01

Measurement of bone density is crucial for evaluating fracture risk. Low bone mass is a powerful predictor of fracture and is necessary to assess the need for treatment. Dual energy x-ray absorptiometry is accurate and precise. Use of bone density for monitoring therapy is an important tool for evaluating response to therapy, but an understanding of the limitations of the procedure are important for the practicing physician. Precision error of the technology and what change in density is clinically significant (least significant change) are important concepts to interpret results and make appropriate treatment decisions. This article reviews the use of bone densitometry as a tool for monitoring treatment in patients with low bone mass.

Comparison of Two Commercial Automated Nucleic Acid Extraction and Integrated Quantitation Real-Time PCR Platforms for the Detection of Cytomegalovirus in Plasma

PubMed Central

Tsai, Huey-Pin; Tsai, You-Yuan; Lin, I-Ting; Kuo, Pin-Hwa; Chen, Tsai-Yun; Chang, Kung-Chao; Wang, Jen-Ren

2016-01-01

Quantitation of cytomegalovirus (CMV) viral load in the transplant patients has become a standard practice for monitoring the response to antiviral therapy. The cut-off values of CMV viral load assays for preemptive therapy are different due to the various assay designs employed. To establish a sensitive and reliable diagnostic assay for preemptive therapy of CMV infection, two commercial automated platforms including m2000sp extraction system integrated the Abbott RealTime (m2000rt) and the Roche COBAS AmpliPrep for extraction integrated COBAS Taqman (CAP/CTM) were evaluated using WHO international CMV standards and 110 plasma specimens from transplant patients. The performance characteristics, correlation, and workflow of the two platforms were investigated. The Abbott RealTime assay correlated well with the Roche CAP/CTM assay (R2 = 0.9379, P<0.01). The Abbott RealTime assay exhibited higher sensitivity for the detection of CMV viral load, and viral load values measured with Abbott RealTime assay were on average 0.76 log10 IU/mL higher than those measured with the Roche CAP/CTM assay (P<0.0001). Workflow analysis on a small batch size at one time, using the Roche CAP/CTM platform had a shorter hands-on time than the Abbott RealTime platform. In conclusion, these two assays can provide reliable data for different purpose in a clinical virology laboratory setting. PMID:27494707

Application of radiofrequency energy in surgical and interventional procedures: are there interactions with ICDs?

PubMed

Fiek, Michael; Dorwarth, Uwe; Durchlaub, Ilka; Janko, Sabine; Von Bary, Christian; Steinbeck, Gerhard; Hoffmann, Ellen

2004-03-01

During surgical and interventional procedures, interference may occur between ICDs and electrical cautery or with the application of RF energy. This may lead to the false induction of ICD therapies or could even result in device malfunction, which represents a potential perioperative hazard for the patient. This study analyzed the intraoperative interactions in 45 consecutive ICD patients in reference to different surgical and interventional procedures. A total of 33 surgical operations (general surgery [n = 14], urologic [n = 5], abdominal [n = 10], gynecological [n = 2], thoracic [n = 1], neurosurgical [n = 1]) and 12 interventional therapies (RF catheter ablation [n = 10], endoscopic papillotomy [n = 2]) were performed. The ICD devices were all located in left pectoral position and consisted of 25 single and 20 dual chamber defibrillators. During the procedure, tachyarrhythmia detection (VF 296 +/- 20 ms, VT 376 +/- 49 ms) of the devices was maintained active (monitoring mode), only ICD therapies were inactivated. The indifferent electrode of the electrical cauter/RF generator was placed in standard positions (right/left mid-femoral position [n = 27/8], thoracic spine area [n = 10]). After the procedure, the ICD memory was checked for detections and for changes in the programming. There was no oversensing, reprogramming, or damage of any defibrillator caused by RF energy. Despite the lack of undesired interactions, ICDs should be inactivated preoperatively to assure maximum patient safety. However, should inactivation not be possible, or the achievement uncertain, electromagnetic interference is highly unlikely.

Evaluation of a GEM and CAT-based detector for radiation therapy beam monitoring

NASA Astrophysics Data System (ADS)

Brahme, A.; Danielsson, M.; Iacobaeus, C.; Ostling, J.; Peskov, V.; Wallmark, M.

2000-11-01

We are developing a radiation therapy beam monitor for the Karolinska Institute. This monitor will consist of two consecutive detectors confined in one gas chamber: a "keV-photon detector", which will allow diagnostic quality visualization of the patient, and a "MeV-photon detector", that will measure the absolute intensity of the therapy beam and its position with respect to the patient. Both detectors are based on highly radiation resistant gas and solid photon to electron converters, combined with GEMs and a CAT as amplification structures. We have performed systematic studies of the high-rate characteristics of the GEM and the CAT, as well as tested the electron transfer through these electron multipliers and various types of converters. The tests show that the GEM and the CAT satisfy all requirements for the beam monitoring system. As a result of these studies we successfully developed and tested a full section of the beam monitor equipped with a MeV-photon converter placed between the GEM and the CAT.

Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke

NASA Astrophysics Data System (ADS)

Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

2014-01-01

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

Transcranial diffuse optical monitoring of microvascular cerebral hemodynamics after thrombolysis in ischemic stroke.

PubMed

Zirak, Peyman; Delgado-Mederos, Raquel; Dinia, Lavinia; Carrera, David; Martí-Fàbregas, Joan; Durduran, Turgut

2014-01-01

The ultimate goal of therapeutic strategies for ischemic stroke is to reestablish the blood flow to the ischemic region of the brain. However, currently, the local cerebral hemodynamics (microvascular) is almost entirely inaccessible for stroke clinicians at the patient bed-side, and the recanalization of the major cerebral arteries (macrovascular) is the only available measure to evaluate the therapy, which does not always reflect the local conditions. Here we report the case of an ischemic stroke patient whose microvascular cerebral blood flow and oxygenation were monitored by a compact hybrid diffuse optical monitor during thrombolytic therapy. This monitor combined diffuse correlation spectroscopy and near-infrared spectroscopy. The reperfusion assessed by hybrid diffuse optics temporally correlated with the recanalization of the middle cerebral artery (assessed by transcranial-Doppler) and was in agreement with the patient outcome. This study suggests that upon further investigation, diffuse optics might have a potential for bed-side acute stroke monitoring and therapy guidance by providing hemodynamics information at the microvascular level.

Failure of imidocarb dipropionate to eliminate Hepatozoon canis in naturally infected dogs based on parasitological and molecular evaluation methods.

PubMed

Sasanelli, Mariateresa; Paradies, Paola; Greco, Beatrice; Eyal, Osnat; Zaza, Valeria; Baneth, Gad

2010-08-04

The efficacy of imidocarb dipropionate for the treatment of Hepatozoon canis infection was studied in three naturally infected asymptomatic dogs followed longitudinally over 8 months. Response to treatment was followed by monitoring blood counts, parasitemia levels in blood, parasite in concentrated buffy-coat smears and by PCR. The dogs were initially treated with a low dose of 3 mg/kg imidocarb dipropionate twice a month and when parasitemia persisted after five treatments, with the regular dose of 6 mg/kg. In one dog, H. canis gamonts were no longer detectable by blood and buffy-coat microscopy after 2 months of therapy with 6 mg/kg while in the two other dogs gamonts were intermittently found in blood but persistently detectable in buffy-coat smears during the whole study period. Furthermore, combined therapy with doxycycline monohydrate administered at 10 mg/kg/day PO for 4 weeks also failed to eliminate H. canis. PCR revealed that parasite DNA was present in the blood of all dogs at all sampling dates regardless of treatment refuting the effectiveness of treatment suggested by negative blood microscopy. Detection of H. canis in buffy coat was found to be twice as sensitive than by blood smear and detection by PCR was even more sensitive revealing infection in eight samples (16% of total samples) negative by blood and buffy-coat microscopy. In conclusion, imidocarb dipropionate was not effective in eliminating H. canis from dogs treated repeatedly over 8 months. Microscopical detection is not sufficient for the evaluation of treatment response in H. canis infection and follow up by molecular techniques is recommended. Copyright 2010 Elsevier B.V. All rights reserved.

The internal and external responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in patients with prostate cancer.

PubMed

Choi, Edmond P H; Wong, Carlos K H; Wan, Eric Y F; Tsu, James H L; Chin, W Y; Kung, Kenny; Yiu, M K

2016-09-01

To examine the responsiveness of Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Short Form-12 Health Survey version 2 (SF-12 v2) in prostate cancer patients because there is a lack of evidence to support their responsiveness in this patient population. One hundred sixty-eight subjects with prostate cancer were surveyed at baseline and at 6 months using the SF-12 v2 and FACT-P version 4. Internal responsiveness was assessed using paired t test and generalized estimating equation. External responsiveness was evaluated using receiver operating characteristic curve analysis. The internal responsiveness of the FACT-P and SF-12 v2 to detect positive change was satisfactory. The FACT-P and SF-12 v2 could not detect negative change. The FACT-P and the SF-12 v2 performed the best in distinguishing between improved general health and worsened general health. The FACT-P performed better in distinguishing between unchanged general health and worsened general health. The SF-12 v2 performed better in distinguishing between unchanged general health and improved general health. Positive change detected by these measures should be interpreted with caution as they might be too responsive to detect "noise," which is not clinically significant. The ability of the FACT-P and the SF-12 v2 to detect negative change was disappointing. The internal and external responsiveness of the social well-being of the FACT-P cannot be supported, suggesting that it is not suitable to longitudinally monitor the social component of HRQOL in prostate cancer patients. The study suggested that generic and disease-specific measures should be used together to complement each other.

Monitoring ASA and P2Y12-specific platelet inhibition--comparison of conventional (single) and multiple electrode aggregometry.

PubMed

Krüger, Jan-Christopher; Meves, Saskia H; Kara, Kaffer; Mügge, Andreas; Neubauer, Horst

2014-10-01

Several platelet function test systems exist for the evaluation of the platelet inhibitory effect in patients on P2Y12 inhibitors and/or acetylsalicylic acid (ASA, aspirin) therapy. Studies comparing different available assays found only a poor correlation. The objective of the present study was to evaluate the correlation and agreement between single electrode (SEA) and multiple electrode (MEA) aggregometry. In whole blood arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation was measured simultaneously using SEA (Chrono-Log) and MEA (Multiplate). We analyzed a total of 226 measurements taken from 58 patients on single ASA therapy or dual antiplatelet therapy with ASA and a thienopyridine. A cut-off value for clopidogrel/prasugrel high on-treatment platelet reactivity (HPR) of > 47 units (U) was chosen for MEA testing using hirudin and > 5 Ohm for SEA with citrate anticoagulated blood samples. The respective cut-off values for ASA HPR were > 30 U for the MEA assay and > 1 Ohm for SEA testing. There was a good correlation of the prevalence of thienopyridine-HPR in both whole blood assays (Spearman rank correlation coefficient r = 0.698) and a good inter-rate accordance (Cohen's Kappa statistic κ = 0.648). For AA-induced aggregation, the correlation of the results obtained was significant (r = 0.536; p < 0.001) and detecting ASA-HPR revealed a moderate (κ = 0.482) correlation between both impedance aggregometry assays. Platelet function testing using SEA and MEA provided both good accordance and correlation and therefore study results obtained by these two assays similarly enabled the detection of HPR of thienopyridine (and ASA) therapy.

Protection by Inhaled Hydrogen Therapy in a Rat Model of Acute Lung Injury can be Tracked in vivo Using Molecular Imaging.

PubMed

Audi, Said H; Jacobs, Elizabeth R; Zhang, Xiao; Camara, Amadou K S; Zhao, Ming; Medhora, Meetha M; Rizzo, Benjamin; Clough, Anne V

2017-10-01

Inhaled hydrogen gas (H2) provides protection in rat models of human acute lung injury (ALI). We previously reported that biomarker imaging can detect oxidative stress and endothelial cell death in vivo in a rat model of ALI. Our objective was to evaluate the ability of Tc-hexamethylpropyleneamineoxime (HMPAO) and Tc-duramycin to track the effectiveness of H2 therapy in vivo in the hyperoxia rat model of ALI. Rats were exposed to room air (normoxia), 98% O2 + 2% N2 (hyperoxia) or 98% O2 + 2% H2 (hyperoxia+H2) for up to 60 h. In vivo scintigraphy images were acquired following injection of Tc-HMPAO or Tc-duramycin. For hyperoxia rats, Tc-HMPAO and Tc-duramycin lung uptake increased in a time-dependent manner, reaching a maximum increase of 270% and 150% at 60 h, respectively. These increases were reduced to 120% and 70%, respectively, in hyperoxia+H2 rats. Hyperoxia exposure increased glutathione content in lung homogenate (36%) more than hyperoxia+H2 (21%), consistent with increases measured in Tc-HMPAO lung uptake. In 60-h hyperoxia rats, pleural effusion, which was undetectable in normoxia rats, averaged 9.3 gram/rat, and lung tissue 3-nitrotyrosine expression increased by 790%. Increases were reduced by 69% and 59%, respectively, in 60-h hyperoxia+H2 rats. This study detects and tracks the anti-oxidant and anti-apoptotic properties of H2 therapy in vivo after as early as 24 h of hyperoxia exposure. The results suggest the potential utility of these SPECT biomarkers for in vivo assessment of key cellular pathways in the pathogenesis of ALI and for monitoring responses to therapies.

Biomaterial-based technologies for brain anti-cancer therapeutics and imaging.

PubMed

Orive, G; Ali, O A; Anitua, E; Pedraz, J L; Emerich, D F

2010-08-01

Treating malignant brain tumors represents one of the most formidable challenges in oncology. Contemporary treatment of brain tumors has been hampered by limited drug delivery across the blood-brain barrier (BBB) to the tumor bed. Biomaterials are playing an increasingly important role in developing more effective brain tumor treatments. In particular, polymer (nano)particles can provide prolonged drug delivery directly to the tumor following direct intracerebral injection, by making them physiochemically able to cross the BBB to the tumor, or by functionalizing the material surface with peptides and ligands allowing the drug-loaded material to be systemically administered but still specifically target the tumor endothelium or tumor cells themselves. Biomaterials can also serve as targeted delivery devices for novel therapies including gene therapy, photodynamic therapy, anti-angiogenic and thermotherapy. Nanoparticles also have the potential to play key roles in the diagnosis and imaging of brain tumors by revolutionizing both preoperative and intraoperative brain tumor detection, allowing early detection of pre-cancerous cells, and providing real-time, longitudinal, non-invasive monitoring/imaging of the effects of treatment. Additional efforts are focused on developing biomaterial systems that are uniquely capable of delivering tumor-associated antigens, immunotherapeutic agents or programming immune cells in situ to identify and facilitate immune-mediated tumor cell killing. The continued translation of current research into clinical practice will rely on solving challenges relating to the pharmacology of nanoparticles but it is envisioned that novel biomaterials will ultimately allow clinicians to target tumors and introduce multiple, pharmaceutically relevant entities for simultaneous targeting, imaging, and therapy in a unique and unprecedented manner. Copyright 2010 Elsevier B.V. All rights reserved.

Experimental Study of Nasopharyngeal Carcinoma Radionuclide Imaging and Therapy Using Transferred Human Sodium/Iodide Symporter Gene

PubMed Central

Zhong, Xing; Shi, Changzheng; Gong, Jian; Guo, Bin; Li, Mingzhu; Xu, Hao

2015-01-01

Purpose The aim of this study was to design a method of radionuclide for imaging and therapy of nasopharyngeal carcinoma (NPC) using the transferred human sodium/iodide symporter (hNIS) gene. Methods A stable NPC cell line expressing hNIS was established (CNE-2-hNIS). After 131I treatment, we detected proliferation and apoptosis of NPC cells, both in vitro and vivo. In vivo, the radioactivity of different organs of nude mice was counted and 99mTc imaging using SPECT was performed. The apparent diffusion coefficient (ADC) value changes of tumor xenografts were observed by diffusion-weighted magnetic resonance imaging (DW-MRI) within 6–24 days of 131I treatment. The correlation of ADC changes with apoptosis and proliferation was investigated. Post-treatment expression levels of P53, Bax, Bcl-2, Caspase-3, and Survivin proteins were detected by western blotting. Results 131I uptake was higher in CNE-2-hNIS than in CNE-2 cells. The proliferation and apoptosis rate decreased and increased respectively both in vitro and vivo in the experimental group after 131I treatment. The experimental group tumors accumulated 99mTc in vivo, leading to a good visualization by SPECT. DW-MRI showed that ADC values increased in the experimental group 6 days after treatment, while ADC values were positively and negatively correlated with the apoptotic and Ki-67 proliferation indices, respectively. After treatment, CNE-2-hNIS cells up-regulated the expression of P53 and Survivin proteins and activated Caspase-3, and down-regulated the expression of Bcl-2 proteins. Conclusions The radionuclide imaging and therapy technique for NPC hNIS-transfected cell lines can provide a new therapy strategy for monitoring and treatment of NPC. PMID:25615643

The extracellular domain of Her2 in serum as a biomarker of breast cancer.

PubMed

Perrier, Alexandre; Gligorov, Joseph; Lefèvre, Guillaume; Boissan, Mathieu

2018-02-28

Breast cancer is a major health problem worldwide. In ~15% of breast cancers, the epidermal growth factor receptor HER2, a transmembrane protein, is overexpressed. This HER2 overexpression is associated with an aggressive form of the disease and a poor clinical prognosis. The extracellular domain (ECD) of HER2 is released into the blood by a proteolytic mechanism known as "ECD shedding". This proteolytic shedding leaves a constitutively active truncated receptor in the membrane that is 10-100-fold more oncogenic than the full-length receptor and promotes the growth and survival of cancer cells. Shedding of the HER2 ECD is increased during metastasis: whereas 15% of primary breast cancer patients have elevated levels of serum HER2 ECD (sHER2 ECD), the levels reach 45% in patients with metastatic disease. Thus, sHER2 ECD has been proposed as a promising biomarker for cancer recurrence and for monitoring the disease status of patients overexpressing HER2. Nevertheless, in 2016, the American Society of Clinical Oncology advises clinicians not to use soluble HER2 levels to guide their choice of adjuvant therapy for patients with HER2-positive breast cancer, because the evidence was considered not strong enough. Currently, biomarkers such as carcinoembryonic antigen and cancer antigen 15-3 are widely used to monitor metastatic breast cancer disease even if the level of evidence of clinical impact of this monitoring is poor. In this article, we review the evidence that sHER2 ECD might be used in some situations as a biomarker for breast cancer. Although this serum biomarker will not replace the direct measurement of tumor HER2 status for diagnosis of early-stage tumors; it might be especially useful in metastatic disease for prognosis, as an indicator of cancer progression and of therapy response, particularly to anti-HER2 therapies. Owing to these data, sHER2 ECD should be considered as a promising biomarker to detect cancer recurrence and metastasis.

Imaging of oxidation-specific epitopes with targeted nanoparticles to detect high-risk atherosclerotic lesions: Progress and future directions

PubMed Central

Briley-Saebo, Karen; Yeang, Calvin; Witztum, Joseph L.; Tsimikas, Sotirios

2014-01-01

Oxidation-specific epitopes (OSE) within developing atherosclerotic lesions are key antigens that drive innate and adaptive immune responses in atherosclerosis, leading to chronic inflammation. Oxidized phospholipids and malondialdehyde-lysine epitopes are well-characterized OSE present in human atherosclerotic lesions, particularly in pathologically defined vulnerable plaques. Using murine and human OSE-specific antibodies as targeting agents, we have developed radionuclide and magnetic resonance based nanoparticles, containing gadolinium, manganese or lipid-coated ultrasmall superparamagnetic iron oxide, to noninvasively image OSE within experimental atherosclerotic lesions. These methods quantitate plaque burden, allow detection of lesion progression and regression, plaque stabilization, and accumulation of OSE within macrophage-rich areas of the artery wall, suggesting they detect the most active lesions. Future studies will focus on using “natural” antibodies, lipopeptides and mimotopes for imaging applications. These approaches should enhance the clinical translation of this technique to image, monitor, evaluate efficacy of novel therapeutic agents and guide optimal therapy of high-risk atherosclerotic lesions. PMID:25297940

HE4 as a biomarker for ovarian and endometrial cancer management

PubMed Central

Li, Jinping; Dowdy, Sean; Tipton, Tracy; Podratz, Karl; Lu, Wei-Guo; Xie, Xing; Jiang, Shi-Wen

2012-01-01

Ovarian and endometrial cancer will be diagnosed in over 63,000 women in 2009, resulting in 22,000 deaths in the USA. Histologic screening, such as pap smears for detection of cervical cancer, is not feasible for these diseases given difficulty with access to the tissue. Thus, a serum-screening test using a biomarker or panel of biomarkers would be useful to aid in cancer diagnosis, detection of recurrence and as a means to monitor response to therapy. In this review, we focus on the human epididymis protein (HE)4 gene, which appears to have potential as a biomarker for both of these diseases. The structure and methods of detection of HE4 are discussed. Preliminary data show that HE4 may have more potential than cancer antigen 125 in discriminating benign from cancerous ovarian masses, and has the strongest correlation with endometrial cancer of all markers tested to date. Utilizing risk stratification, a panel of biomarkers including HE4 may ultimately be useful for detecting ovarian and endometrial cancer at an early stage in patients at high risk. PMID:19732003

Circulating Tumor DNA Measurement by Picoliter Droplet-Based Digital PCR and Vemurafenib Plasma Concentrations in Patients with Advanced BRAF-Mutated Melanoma.

PubMed

Garlan, Fanny; Blanchet, Benoit; Kramkimel, Nora; Puszkiel, Alicja; Golmard, Jean-Louis; Noe, Gaelle; Dupin, Nicolas; Laurent-Puig, Pierre; Vidal, Michel; Taly, Valerie; Thomas-Schoemann, Audrey

2017-06-01

Circulating tumor DNA (ctDNA) has been reported as a prognostic marker in melanoma. In BRAF V600-mutant melanoma, a plasma under-exposure to vemurafenib could favor emerging resistance but no biological data are available to support this hypothesis. We aimed to investigate the relationship between vemurafenib plasma concentrations and the ctDNA plasma concentration during follow-up of BRAF-mutated melanoma patients. Eleven patients treated with single-agent vemurafenib for advanced BRAF V600-mutant melanoma were analyzed in an exploratory monocentric study. The vemurafenib plasma concentration was measured by liquid chromatography. ctDNA was extracted from plasma samples and the ctDNA concentration was evaluated using picoliter droplet-based digital PCR with Taqman ® detection probes targeting the BRAF p.V600E/K mutation and wild-type BRAF sequences. At baseline, plasma ctDNA was detectable in 72% (n = 8/11) of patients and the ctDNA concentration decreased in 88% of these patients (n = 7/8) from day (D) 0 to D15 after vemurafenib initiation. During follow-up, an increased ctDNA concentration was detected in nine patients: in five patients, the first increase in ctDNA concentrations followed a decrease in vemurafenib concentrations. More interestingly, an inverse correlation between vemurafenib concentration and ctDNA concentrations was demonstrated (p = 0.026). The ctDNA concentration at baseline was associated with overall survival (hazard ratio = 2.61, 95% CI 1.04-6.56; p = 0.04). This study demonstrates the relevance of vemurafenib plasma monitoring during the follow-up of metastatic melanoma patients. Plasma drug monitoring and ctDNA concentrations could be combined to monitor tumor evolution in melanoma patients treated with anti-BRAF therapies.

Remote monitoring of patients with cardiac implantable electronic devices: a Southeast Asian, single-centre pilot study.

PubMed

Lim, Paul Chun Yih; Lee, Audry Shan Yin; Chua, Kelvin Chi Ming; Lim, Eric Tien Siang; Chong, Daniel Thuan Tee; Tan, Boon Yew; Ho, Kah Leng; Teo, Wee Siong; Ching, Chi Keong

2016-07-01

Remote monitoring of cardiac implantable electronic devices (CIED) has been shown to improve patient safety and reduce in-office visits. We report our experience with remote monitoring via the Medtronic CareLink(®) network. Patients were followed up for six months with scheduled monthly remote monitoring transmissions in addition to routine in-office checks. The efficacy of remote monitoring was evaluated by recording compliance to transmissions, number of device alerts requiring intervention and time from transmission to review. Questionnaires were administered to evaluate the experiences of patients, physicians and medical technicians. A total of 57 patients were enrolled; 16 (28.1%) had permanent pacemakers, 34 (59.6%) had implantable cardioverter defibrillators and 7 (12.3%) had cardiac resynchronisation therapy defibrillators. Overall, of 334 remote transmissions scheduled, 73.7% were on time, 14.5% were overdue and 11.8% were missed. 84.6% of wireless transmissions were on time, compared to 53.8% of non-wireless transmissions. Among all transmissions, 4.4% contained alerts for which physicians were informed and only 1.8% required intervention. 98.6% of remote transmissions were reviewed by the second working day. 73.2% of patients preferred remote monitoring. Physicians agreed that remote transmissions provided information equivalent to in-office checks 97.1% of the time. 77.8% of medical technicians felt that remote monitoring would help the hospital improve patient management. No adverse events were reported. Remote monitoring of CIED is safe and feasible. It has possible benefits to patient safety through earlier detection of arrhythmias or device malfunction, permitting earlier intervention. Wireless remote monitoring, in particular, may improve compliance to device monitoring. Patients may prefer remote monitoring due to possible improvements in quality of life. Copyright: © Singapore Medical Association.

Remote monitoring of patients with cardiac implantable electronic devices: a Southeast Asian, single-centre pilot study

PubMed Central

Lim, Paul Chun Yih; Lee, Audry Shan Yin; Chua, Kelvin Chi Ming; Lim, Eric Tien Siang; Chong, Daniel Thuan Tee; Tan, Boon Yew; Ho, Kah Leng; Teo, Wee Siong; Ching, Chi Keong

2016-01-01

INTRODUCTION Remote monitoring of cardiac implantable electronic devices (CIED) has been shown to improve patient safety and reduce in-office visits. We report our experience with remote monitoring via the Medtronic CareLink® network. METHODS Patients were followed up for six months with scheduled monthly remote monitoring transmissions in addition to routine in-office checks. The efficacy of remote monitoring was evaluated by recording compliance to transmissions, number of device alerts requiring intervention and time from transmission to review. Questionnaires were administered to evaluate the experiences of patients, physicians and medical technicians. RESULTS A total of 57 patients were enrolled; 16 (28.1%) had permanent pacemakers, 34 (59.6%) had implantable cardioverter defibrillators and 7 (12.3%) had cardiac resynchronisation therapy defibrillators. Overall, of 334 remote transmissions scheduled, 73.7% were on time, 14.5% were overdue and 11.8% were missed. 84.6% of wireless transmissions were on time, compared to 53.8% of non-wireless transmissions. Among all transmissions, 4.4% contained alerts for which physicians were informed and only 1.8% required intervention. 98.6% of remote transmissions were reviewed by the second working day. 73.2% of patients preferred remote monitoring. Physicians agreed that remote transmissions provided information equivalent to in-office checks 97.1% of the time. 77.8% of medical technicians felt that remote monitoring would help the hospital improve patient management. No adverse events were reported. CONCLUSION Remote monitoring of CIED is safe and feasible. It has possible benefits to patient safety through earlier detection of arrhythmias or device malfunction, permitting earlier intervention. Wireless remote monitoring, in particular, may improve compliance to device monitoring. Patients may prefer remote monitoring due to possible improvements in quality of life. PMID:27439396

Advances in Monitoring Cell-Based Therapies with Magnetic Resonance Imaging: Future Perspectives

PubMed Central

Ngen, Ethel J.; Artemov, Dmitri

2017-01-01

Cell-based therapies are currently being developed for applications in both regenerative medicine and in oncology. Preclinical, translational, and clinical research on cell-based therapies will benefit tremendously from novel imaging approaches that enable the effective monitoring of the delivery, survival, migration, biodistribution, and integration of transplanted cells. Magnetic resonance imaging (MRI) offers several advantages over other imaging modalities for elucidating the fate of transplanted cells both preclinically and clinically. These advantages include the ability to image transplanted cells longitudinally at high spatial resolution without exposure to ionizing radiation, and the possibility to co-register anatomical structures with molecular processes and functional changes. However, since cellular MRI is still in its infancy, it currently faces a number of challenges, which provide avenues for future research and development. In this review, we describe the basic principle of cell-tracking with MRI; explain the different approaches currently used to monitor cell-based therapies; describe currently available MRI contrast generation mechanisms and strategies for monitoring transplanted cells; discuss some of the challenges in tracking transplanted cells; and suggest future research directions. PMID:28106829

Hemodynamic changes in a rat parietal cortex after endothelin-1-induced middle cerebral artery occlusion monitored by optical coherence tomography

NASA Astrophysics Data System (ADS)

Liu, Jian; Ma, Yushu; Dou, Shidan; Wang, Yi; La, Dongsheng; Liu, Jianghong; Ma, Zhenhe

2016-07-01

A blockage of the middle cerebral artery (MCA) on the cortical branch will seriously affect the blood supply of the cerebral cortex. Real-time monitoring of MCA hemodynamic parameters is critical for therapy and rehabilitation. Optical coherence tomography (OCT) is a powerful imaging modality that can produce not only structural images but also functional information on the tissue. We use OCT to detect hemodynamic changes after MCA branch occlusion. We injected a selected dose of endothelin-1 (ET-1) at a depth of 1 mm near the MCA and let the blood vessels follow a process first of occlusion and then of slow reperfusion as realistically as possible to simulate local cerebral ischemia. During this period, we used optical microangiography and Doppler OCT to obtain multiple hemodynamic MCA parameters. The change trend of these parameters from before to after ET-1 injection clearly reflects the dynamic regularity of the MCA. These results show the mechanism of the cerebral ischemia-reperfusion process after a transient middle cerebral artery occlusion and confirm that OCT can be used to monitor hemodynamic parameters.

In Vivo Monitoring of Staphylococcus aureus Biofilm Infections and Antimicrobial Therapy by [18F]Fluoro-Deoxyglucose–MicroPET in a Mouse Model

PubMed Central

Garrido, Victoria; Collantes, María; Barberán, Montserrat; Peñuelas, Iván; Arbizu, Javier; Amorena, Beatriz

2014-01-01

A mouse model was developed for in vivo monitoring of infection and the effect of antimicrobial treatment against Staphylococcus aureus biofilms, using the [18F]fluoro-deoxyglucose–MicroPET ([18F]FDG-MicroPET) image technique. In the model, sealed Vialon catheters were briefly precolonized with S. aureus strains ATCC 15981 or V329, which differ in cytotoxic properties and biofilm matrix composition. After subcutaneous implantation of catheters in mice, the S. aureus strain differences found in bacterial counts and the inflammatory reaction triggered were detected by the regular bacteriological and histological procedures and also by [18F]FDG-MicroPET image signal intensity determinations in the infection area and regional lymph node. Moreover, [18F]FDG-MicroPET imaging allowed the monitoring of the rifampin treatment effect, identifying the periods of controlled infection and those of reactivated infection due to the appearance of bacteria naturally resistant to rifampin. Overall, the mouse model developed may be useful for noninvasive in vivo determinations in studies on S. aureus biofilm infections and assessment of new therapeutic approaches. PMID:25155589

Robot-assisted motor activation monitored by time-domain optical brain imaging

NASA Astrophysics Data System (ADS)

Steinkellner, O.; Wabnitz, H.; Schmid, S.; Steingräber, R.; Schmidt, H.; Krüger, J.; Macdonald, R.

2011-07-01

Robot-assisted motor rehabilitation proved to be an effective supplement to conventional hand-to-hand therapy in stroke patients. In order to analyze and understand motor learning and performance during rehabilitation it is desirable to develop a monitor to provide objective measures of the corresponding brain activity at the rehabilitation progress. We used a portable time-domain near-infrared reflectometer to monitor the hemodynamic brain response to distal upper extremity activities. Four healthy volunteers performed two different robot-assisted wrist/forearm movements, flexion-extension and pronation-supination in comparison with an unassisted squeeze ball exercise. A special headgear with four optical measurement positions to include parts of the pre- and postcentral gyrus provided a good overlap with the expected activation areas. Data analysis based on variance of time-of-flight distributions of photons through tissue was chosen to provide a suitable representation of intracerebral signals. In all subjects several of the four detection channels showed a response. In some cases indications were found of differences in localization of the activated areas for the various tasks.

Real-Time Event Detection for Monitoring Natural and Source ...

EPA Pesticide Factsheets

The use of event detection systems in finished drinking water systems is increasing in order to monitor water quality in both operational and security contexts. Recent incidents involving harmful algal blooms and chemical spills into watersheds have increased interest in monitoring source water quality prior to treatment. This work highlights the use of the CANARY event detection software in detecting suspected illicit events in an actively monitored watershed in South Carolina. CANARY is an open source event detection software that was developed by USEPA and Sandia National Laboratories. The software works with any type of sensor, utilizes multiple detection algorithms and approaches, and can incorporate operational information as needed. Monitoring has been underway for several years to detect events related to intentional or unintentional dumping of materials into the monitored watershed. This work evaluates the feasibility of using CANARY to enhance the detection of events in this watershed. This presentation will describe the real-time monitoring approach used in this watershed, the selection of CANARY configuration parameters that optimize detection for this watershed and monitoring application, and the performance of CANARY during the time frame analyzed. Further, this work will highlight how rainfall events impacted analysis, and the innovative application of CANARY taken in order to effectively detect the suspected illicit events. This presentation d

Surface-Enhanced Raman Scattering-Based Immunoassay Technologies for Detection of Disease Biomarkers

PubMed Central

Smolsky, Joseph; Kaur, Sukhwinder; Hayashi, Chihiro; Batra, Surinder K.; Krasnoslobodtsev, Alexey V.

2017-01-01

Detection of biomarkers is of vital importance in disease detection, management, and monitoring of therapeutic efficacy. Extensive efforts have been devoted to the development of novel diagnostic methods that detect and quantify biomarkers with higher sensitivity and reliability, contributing to better disease diagnosis and prognosis. When it comes to such devastating diseases as cancer, these novel powerful methods allow for disease staging as well as detection of cancer at very early stages. Over the past decade, there have been some advances in the development of platforms for biomarker detection of diseases. The main focus has recently shifted to the development of simple and reliable diagnostic tests that are inexpensive, accurate, and can follow a patient’s disease progression and therapy response. The individualized approach in biomarker detection has been also emphasized with detection of multiple biomarkers in body fluids such as blood and urine. This review article covers the developments in Surface-Enhanced Raman Scattering (SERS) and related technologies with the primary focus on immunoassays. Limitations and advantages of the SERS-based immunoassay platform are discussed. The article thoroughly describes all components of the SERS immunoassay and highlights the superior capabilities of SERS readout strategy such as high sensitivity and simultaneous detection of a multitude of biomarkers. Finally, it introduces recently developed strategies for in vivo biomarker detection using SERS. PMID:28085088

Correlation between positron emission tomography and Cerenkov luminescence imaging in vivo and ex vivo using 64Cu-labeled antibodies in a neuroblastoma mouse model.

PubMed

Maier, Florian C; Schmitt, Julia; Maurer, Andreas; Ehrlichmann, Walter; Reischl, Gerald; Nikolaou, Konstantin; Handgretinger, Rupert; Pichler, Bernd J; Thaiss, Wolfgang M

2016-10-11

Antibody-based therapies gain momentum in clinical therapy, thus the need for accurate imaging modalities with respect to target identification and therapy monitoring are of increasing relevance. Cerenkov luminescence imaging (CLI) are a novel method detecting charged particles emitted during radioactive decay with optical imaging. Here, we compare Position Emission Tomography (PET) with CLI in a multimodal imaging study aiming at the fast and efficient screening of monoclonal antibodies (mAb) designated for targeting of the neuroblastoma-characteristic epitope disialoganglioside GD2. Neuroblastoma-bearing SHO mice were injected with a 64Cu-labeled GD2-specific mAb. The tumor uptake was imaged 3 h, 24 h and 48 h after tracer injection with both, PET and CLI, and was compared to the accumulation in GD2-negative control tumors (human embryonic kidney, HEK-293). In addition to an in vivo PET/CLI-correlation over time, we also demonstrate linear correlations of CLI- and γ-counter-based biodistribution analysis. CLI with its comparably short acquisition time can thus be used as an attractive one-stop-shop modality for the longitudinal monitoring of antibody-based tumor targeting and ex vivo biodistribution.These findings suggest CLI as a reliable alternative for PET and biodistribution studies with respect to fast and high-throughput screenings in subcutaneous tumors traced with radiolabeled antibodies. However, in contrast to PET, CLI is not limited to positron-emitting isotopes and can therefore also be used for the visualization of mAb labeled with therapeutic isotopes like electron emitters.

Nurse management for hypertension. A systems approach.

PubMed

Rudd, Peter; Miller, Nancy Houston; Kaufman, Judy; Kraemer, Helena C; Bandura, Albert; Greenwald, George; Debusk, Robert F

2004-10-01

Standard office-based approaches to controlling hypertension show limited success. Such suboptimal hypertension control reflects in part the absence of both an infrastructure for patient education and frequent, regular blood pressure (BP) monitoring. We tested the efficacy of a physician-directed, nurse-managed, home-based system for hypertension management with standardized algorithms to modulate drug therapy, based on patients' reports of home BP. We randomized outpatients requiring drug therapy for hypertension according to the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI) criteria to receive usual medical care only (UC, n = 76) or usual care plus nurse care management intervention (INT, n = 74) over a 6-month period. Patients receiving INT achieved greater reductions in office BP values at 6 months than those receiving UC: 14.2 +/- 18.1 versus 5.7 +/- 18.7 mm Hg systolic (P < .01) and 6.5 +/- 10.0 versus 3.4 +/- 7.9 mm Hg diastolic, respectively (P < .05). At 6 months, we observed one or more changes in drug therapy in 97% of INT patients versus 43% of UC patients, and 70% of INT patients received two or more drugs versus 46% of UC. Average daily adherence to medication, measured by electronic drug event monitors, was superior among INT subjects (mean +/- SD, 80.5% +/- 23.0%) than among UC subjects (69.2 +/- 31.1%; t(113) = 2.199, P = .03). There were no significant adverse drug reactions in either group. Telephone-mediated nurse management can successfully address many of the systems-related and patient-related issues that limit pharmacotherapeutic effectiveness for hypertension.

Ultrasound monitoring of the treatment of clinically significant knee osteoarthritis.

PubMed

Vojtassak, J; Vojtassak, J

2014-01-01

The study presented an ultrasound (US) monitoring of treatment as a new imaging US method with the results of therapy of clinically significant knee osteoarthritis. X-ray is widely used for knee osteoarthritis classification, which does not involve the evaluation of the soft tissue. High frequency and high resolution US of joints (arthrosonography, echoarthrography) assess not only morphologic but also functional changes in the knee joint. In the prospective study, 110 patients with clinically significant knee osteoarthritis were treated non-operative. US examination and US monitoring of therapy was performed during 24 weeks therapy period. A remission of pathomorphologic (marginal osteofytes) and pathophysiologic (effusion in anterior knee and Baker´s cyst) attributes were evaluated according the US classification. Pathomorphologic attributes changes showed a static state, without remission or progression. Pathophysiologic attributes changes showed a remission during the study period. The highest remission was in the first three weeks, 60 % anterior knee effusion and 62 % Baker´s cyst. At the end of study, no changes from the initial US grade was observed in 16 % of effusion in anterior knee and 22 % of Baker´s cyst. Therapeutic resistant Baker´s cyst was present at the end of study in 36 %. We demonstrated a new method - US monitoring of therapy, which can objectivize the efficiency of treatment of clinically significant knee osteoarthritis. We would recommend US monitoring of therapy for the routine use in orthopedic clinical praxis (Tab. 6, Graph 3, Fig. 3, Ref. 15).

Minimally invasive ultrasound thermal therapy with MR thermal monitoring and guidance

NASA Astrophysics Data System (ADS)

Diederich, Chris J.; Stafford, R. Jason; Price, Roger E.; Nau, William H.; Tyreus, Per Daniel; Rivera, Belinda; Schomer, Donald; Olsson, Lars; Hazle, John D.

2001-06-01

In this study both transurethral and interstitial ultrasound thermal therapy were applied to thermally coagulate targeted portions of the canine prostate or brain and implanted TVT tumors while using MRI-based thermal mapping techniques to monitor the therapy. MRI was also used for target definition, positioning of the applicator, and evaluation of target viability post-therapy. The complex phase-difference mapping technique using an iGE-EPI sequence with lipid suppression was used for determining temperature elevations within the in vivo prostate or brain and surrounding structures. Calculated temperature distributions, thermal dose exposures, T2-wieghted & T1-contrast enhanced images, gross inspection, and histology of sectioned prostates and brains were in good agreement with each other in defining destroyed tissue zones. Interstitial and transurethral ultrasound applicators produce directed zones of thermal coagulation within targeted tissue and implanted tumor, which can be accurately monitored and evaluated by MRI.

Salivary uric acid as a noninvasive biomarker for monitoring the efficacy of urate-lowering therapy in a patient with chronic gouty arthropathy.

PubMed

Zhao, Jianxing; Huang, Ying

2015-10-23

Monitoring blood uric acid (UA) is important in all patients on urate-lowering therapy so that the selection of the effective drugs and dosage adjustments could be made until the target level is reached. The issue is that frequent needle jabs are unacceptable. Reported mean levels of salivary UA were 185-240 μmol/l in healthy adults. A linear correlation was demonstrated between UA concentrations in saliva and plasma. We monitored salivary UA instead of plasmatic UA in a patient with gout. Allopurinol and benzbromarone were used as the therapeutic drugs. Salivary UA; urinary UA and creatinine; and plasmatic UA, creatinine, kynurenine and tryptophan were measured by HPLC. Salivary UA indicated the efficacy of therapy accurately and conveniently. After eight weeks therapy, the weekly mean levels of salivary UA were reduced and maintained to <300 μmol/l, which was equivalent to <360 μmol/l of plasmatic UA according to the salivary UA/plasmatic UA ratio of this patient. Measurement of salivary UA is a noninvasive and useful way for monitoring the status of hyperuricemia and the therapeutic efficacy of urate-lowering therapy. It has value for the management of hyperuricemia and gout. Copyright © 2015 Elsevier B.V. All rights reserved.

αvß3-Integrin-Targeted Magnetic Resonance Imaging for the Assessment of Early Antiangiogenic Therapy Effects in Orthotopic Breast Cancer Xenografts.

PubMed

Kazmierczak, Philipp Maximilian; Schneider, Moritz; Habereder, Thomas; Hirner-Eppeneder, Heidrun; Eschbach, Ralf S; Moser, Matthias; Reiser, Maximilian F; Lauber, Kirsten; Nikolaou, Konstantin; Cyran, Clemens C

2016-11-01

The aim of this study was to investigate magnetic resonance imaging (MRI) with αvß3-integrin-targeted ultrasmall superparamagnetic iron oxide nanoparticles (RGD-USPIO) for the in vivo monitoring of early antiangiogenic therapy effects in experimental breast cancer. Orthotopic human breast cancer (MDA-MB-231) xenograft-bearing severe combined immunodeficiency mice were imaged before and after a 1-week therapy with the vascular endothelial growth factor receptor-antibody bevacizumab or placebo (n = 10 per group, daily intraperitoneal injections of bevacizumab or a volume-equivalent placebo solution, respectively) on a clinical 3 T scanner (Magnetom Skyra; Siemens Healthcare, Erlangen, Germany) before and 60 minutes after the intravenous injection of RGD-USPIO (P04000; Guerbet, Villepinte, France). R2 relaxometry employing a T2-weighted spin-echo sequence with 4 echo times (echo time, 20/40/60/80 milliseconds; repetition time, 3800 milliseconds; matrix, 128 × 128; field of view, 50 × 50; slice thickness, 1.2 mm; time to acquisition, 25 minutes) was used as semiquantitative measure to determine RGD-USPIO endothelial binding. In addition, the T2-weighted images were used to perform volumetric tumor response assessments. Imaging results were validated by ex vivo multiparametric immunohistochemistry with regard to αvß3-integrin expression, microvascular density (CD31), proliferation (Ki-67), and apoptosis (TUNEL). RGD-USPIO endothelial binding was significantly reduced after vascular endothelial growth factor inhibition, compared with the control group in which an increased endothelial binding was detected ([INCREMENT]R2Therapy = -0.80 ± 0.78 s; [INCREMENT]R2Control = +0.27 ± 0.59 s; P = 0.002). Correspondingly, immunohistochemistry revealed a significantly lower αvß3-integrin expression (91 ± 30 vs 357 ± 72; P < 0.001), microvascular density (CD31, 109 ± 46 vs 440 ± 208; P < 0.001), tumor cell proliferation (Ki-67, 4040 ± 1373 vs 6530 ± 1217; P < 0.001), as well as significantly higher apoptosis (TUNEL, 11186 ± 4387 vs 4017 ± 1191; P = 0.004) in the therapy compared with the control group. Contrary to the changes in αvß3-integrin expression detected by RGD-USPIO MRI, morphology-based tumor response assessments did not show a significant intergroup difference in tumor volume development over the course of the experiment (ΔVolTherapy +71 ± 40 μL vs ΔVolControl +125 ± 81 μL; P > 0.05). RGD-USPIO MRI allows for the noninvasive assessment of αvß3-integrin expression in the investigated breast cancer model. RGD-USPIO MRI may be applicable for the in vivo monitoring of early antiangiogenic therapy effects in experimental breast cancer, generating possible complementary molecular imaging biomarkers to morphology-based tumor response assessments.

Cerebral hemodynamics in patients with obstructive sleep apnea syndrome monitored with near-infrared spectroscopy (NIRS) during positive airways pressure (CPAP) therapy: a pilot study

NASA Astrophysics Data System (ADS)

Zhang, Zhongxing; Schneider, Maja; Laures, Marco; Fritschi, Ursula; Lehner, Isabella; Qi, Ming; Khatami, Ramin

2014-03-01

In obstructive sleep apnea syndrome (OSA) the periodic reduction or cessation of breathing due to narrowing or occlusion of the upper airway during sleep leads to daytime symptoms and increased cardiovascular risk, including stroke. The higher risk of stroke is related to the impairment in cerebral vascular autoregulation. Continuous positive airways pressure (CPAP) therapy at night is the most effective treatment for OSA. However, there is no suitable bedside monitoring method evaluating the treatment efficacy of CPAP therapy, especially to monitor the recovery of cerebral hemodynamics. NIRS is ideally suited for non-invasive monitoring the cerebral hemodynamics during sleep. In this study, we will for first time assess dynamic changes of cerebral hemodynamics during nocturnal CPAP therapy in 3 patients with OSA using NIRS. We found periodic oscillations in HbO2, HHb, tissue oxygenation index (TOI) and blood volume associated with periodic apnea events without CPAP in all OSA patients. These oscillations were gradually attenuated and finally eliminated with the stepwise increments of CPAP pressures. The oscillations were totally eliminated in blood volume earlier than in other hemodynamic parameters. These results suggested that 1) the cerebral hemodynamic oscillations induced by OSA events can effectively be attenuated by CPAP therapy, and 2) blood flow and blood volume recovered first during CPAP therapy, followed by the recovery of oxygen consumption. Our study suggested that NIRS is a useful tool to evaluate the efficacy of CPAP therapy in patients with OSA bedside and in real time.

A mobile cloud-based Parkinson's disease assessment system for home-based monitoring.

PubMed

Pan, Di; Dhall, Rohit; Lieberman, Abraham; Petitti, Diana B

2015-03-26

Parkinson's disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients' motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson's is subjective and mostly conducted by brief observations made during patient visits. Changes in patients' motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, "PD Dr", which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts' rating on standardized rating scales. The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management.

A Mobile Cloud-Based Parkinson’s Disease Assessment System for Home-Based Monitoring

PubMed Central

Petitti, Diana B

2015-01-01

Background Parkinson’s disease (PD) is the most prevalent movement disorder of the central nervous system, and affects more than 6.3 million people in the world. The characteristic motor features include tremor, bradykinesia, rigidity, and impaired postural stability. Current therapy based on augmentation or replacement of dopamine is designed to improve patients’ motor performance but often leads to levodopa-induced adverse effects, such as dyskinesia and motor fluctuation. Clinicians must regularly monitor patients in order to identify these effects and other declines in motor function as soon as possible. Current clinical assessment for Parkinson’s is subjective and mostly conducted by brief observations made during patient visits. Changes in patients’ motor function between visits are hard to track and clinicians are not able to make the most informed decisions about the course of therapy without frequent visits. Frequent clinic visits increase the physical and economic burden on patients and their families. Objective In this project, we sought to design, develop, and evaluate a prototype mobile cloud-based mHealth app, “PD Dr”, which collects quantitative and objective information about PD and would enable home-based assessment and monitoring of major PD symptoms. Methods We designed and developed a mobile app on the Android platform to collect PD-related motion data using the smartphone 3D accelerometer and to send the data to a cloud service for storage, data processing, and PD symptoms severity estimation. To evaluate this system, data from the system were collected from 40 patients with PD and compared with experts’ rating on standardized rating scales. Results The evaluation showed that PD Dr could effectively capture important motion features that differentiate PD severity and identify critical symptoms. For hand resting tremor detection, the sensitivity was .77 and accuracy was .82. For gait difficulty detection, the sensitivity was .89 and accuracy was .81. In PD severity estimation, the captured motion features also demonstrated strong correlation with PD severity stage, hand resting tremor severity, and gait difficulty. The system is simple to use, user friendly, and economically affordable. Conclusions The key contribution of this study was building a mobile PD assessment and monitoring system to extend current PD assessment based in the clinic setting to the home-based environment. The results of this study proved feasibility and a promising future for utilizing mobile technology in PD management. PMID:25830687

Implantable cardiac resynchronization therapy devices to monitor heart failure clinical status.

PubMed

Fung, Jeffrey Wing-Hong; Yu, Cheuk-Man

2007-03-01

Cardiac resynchronization therapy is a standard therapy for selected patients with heart failure. With advances in technology and storage capacity, the device acts as a convenient platform to provide valuable information about heart failure status in these high-risk patients. Unlike other modalities of investigation which may only allow one-off evaluation, heart failure status can be monitored by device diagnostics including heart rate variability, activity status, and intrathoracic impedance in a continuous basis. These parameters do not just provide long-term prognostic information but also may be useful to predict upcoming heart failure exacerbation. Prompt and early intervention may abort decompensation, prevent hospitalization, improve quality of life, and reduce health care cost. Moreover, this information may be applied to titrate the dosage of medication and monitor response to heart failure treatment. This review will focus on the prognostic and predictive values of heart failure status monitoring provided by these devices.

Daylight photodynamic therapy with methylene blue in plane warts: a randomized double-blind placebo-controlled study.

PubMed

Fathy, Ghada; Asaad, Marwa Kamal; Rasheed, Haval Mohamad

2017-07-01

Conventional photodynamic therapy is associated with inconveniently long clinic visits and discomfort during therapy. Daylight-photodynamic therapy (DL-PDT) is an effective treatment, nearly pain free and more convenient for both the clinics and patients. There are no published studies of methylene blue (MB) as a photosensitizer (PS) used in DL-PDT. Forty patients had multiple plane warts; 20 patients were subjected to DL-PDT with topical 10% methylene blue gel, and 20 patients were subjected to DL-PDT with hematoxylin (placebo). Improvement was evaluated by change of the number of warts and the dermoscope picture. A total of 20 (100%) patients in group II showed no response to placebo, 13 patients (65%) in group I showed complete clearance, 2 (10%) patients showed a good response, and 5 (25%) patients had poor response to treatment (P < 0.01). No serious side effects and patients tolerated the pain well. No relapse was detected during the follow-up period (12 months). Daylight exposure was not monitored with a dosimeter. Daylight-PDT using MB is safe, easy to carry out, economic, effective, acceptable cosmetic results with no recurrence, convenient especially for children and nearly painless treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Aptamers and their Applications in Nanomedicine

PubMed Central

Sun, Hongguang; Zu, Youli

2015-01-01

Aptamers are composed of short RNA or single-stranded DNA sequences that, when folded into their unique three-dimensional conformation, can specifically bind to their cognate targets with high specificity and affinity. Although functionally similar to protein antibodies, oligonucleotide aptamers offer several advantages over protein antibodies in biomedical and clinical applications. Additionally, through the enhanced permeability and retention (EPR) effect, nanomedicines can improve the therapeutic index of a treatment and reduce side effects by enhancing accumulation at the disease site. However, this EPR effect is “passive targeting” to tumors and thus, may not be an ideal approach for targeted cancer therapy. To construct ligand-directed “active targeting” nano-based delivery systems, aptamer technology has been widely studied. The aptamer-equipped nanomedicines have been tested for in vitro diagnosis, in vivo imaging, targeted cancer therapy, theranostic approaches, sub-cellular molecule detection, food safety, and environment monitoring. This review will focus on the development of aptamer-conjugated nanomedicines and their application for in vivo imaging, targeted therapy, and theranostics. In some applications, aptamers can also be used as drug carriers or ON/OFF switches. Herein, some outstanding therapeutic approaches are also discussed on a case-by-case basis, such as an “on-command” release system and a combinational therapy strategy. PMID:25677591

Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers.

PubMed

Miyauchi, Masaaki; Toyoda, Masao; Kaneyama, Noriko; Miyatake, Han; Tanaka, Eitaro; Kimura, Moritsugu; Umezono, Tomoya; Fukagawa, Masafumi

2016-01-01

We compared the efficacy of activity monitor (which displays exercise intensity and number of steps) versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group ( n = 92) and pedometer group ( n = 95). The primary goal was improvement in hemoglobin A1c (HbA1c). The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents). The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients.

An investigation of the concomitant use of angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs and diuretics.

PubMed

Bucsa, C; Moga, D C; Farcas, A; Mogosan, C; Dumitrascu, D L

2015-08-01

To determine in retrospective data the prevalence at hospital discharge of co-prescribing angiotensin-converting enzyme inhibitors (ACE-I) and non-steroidal anti-inflammatory drugs (NSAIDs) and ACE-I/NSAIDs and diuretics and to identify factors associated with the co-prescription. Secondary, we evaluated the extent of serum creatinine and potassium monitoring in patients treated with ACE-I and these associations and determined the prevalence of values above the upper normal limit (UNL) in monitored patients. Hospitalized patients with ACE-I in their therapy at discharge were included in 3 groups as follows: ACE-I, DT (double therapy with ACE-I and NSAIDs) and TT (triple therapy with ACE-I, NSAIDs and diuretics) groups. We evaluated differences on demographic characteristics, co-morbidities, medications, laboratory monitoring and quantified the patients with serum creatinine and potassium levels above the UNL using descriptive statistics. Logistic regression analysis with backward elimination was performed to identify significant predictors of combination therapy. Of 9960 admitted patients, 1214 were prescribed ACE-I, 40 were prescribed ACE-I/NSAIDs and 22 were prescribed ACE-I/NSAIDs/diuretics (3.13% and 1.72%, respectively, of the patients prescribed with ACE-I). Serum creatinine and potassium were monitored for the great majority of patients from all groups. The highest percentage of hyperkalemia was found in the DT group (10% of the patients) and of serum creatinine above UNL in the TT group (45.45%). The logistic regression final model showed that younger patients and monitoring for potassium were significantly associated with combination therapy. The prevalence of patients receiving DT/TT was relatively low and their monitoring during hospitalization was high. Factors associated with the combinations were younger patients and patients not tested for serum potassium.

Hepatitis B virus replication is upregulated in proliferated peripheral blood lymphocytes.

PubMed

Yan, Qin; Lan, Ying-Hua; Huang, Yan-Xin; Fan, Rong-Shan; Liu, Lan; Song, Shu-Peng; Li, Yong-Guo

2016-04-01

Increasing evidence indicates that the hepatitis B virus (HBV) replicates in peripheral blood mononuclear cells (PBMCs), but at a low level. The present study aimed to establish a reliable and sensitive method that effectively detects HBV viral products for monitoring antiviral therapy, organ transplantation screening, and diagnosing occult HBV infection. In the present study, PBMCs (obtained from six healthy volunteers) were inoculated with HBV, and cultured with phytohemagglutinin (PHA) and interleukin‑2 (IL‑2) to stimulate cell proliferation. PBMCs were harvested, and quantitative detection of HBV DNA in cell suspension and intracellular hepatitis B surface antigen (HBsAg) was conducted on days 0, 1, 6 and 12, respectively. In situ hybridization, immunohistochemistry and reverse transcription‑polymerase chain reaction (RT‑PCR) were performed to analyze the HBV infection. The results demonstrated that HBV DNA increased concurrently with proliferation of PBMCs isolated from three of six healthy volunteers, and the mean number of PBMCs on day 12 was 13.61 times higher than the initially seeded cell number (P<0.01). The mean copies of HBV DNA at day 12 were 2.98 times higher compared with initial levels (P<0.05). Furthermore, intracellular HBsAg levels increased concurrently with proliferation of PBMCs in one group of cultured PBMCs, which was accompanied by increased HBV DNA levels. In addition, HBV nucleic acids were detected in PBMCs using in situ hybridization. Intracellular HBsAg was observed in PBMCs and HBV RNA was also detected by RT‑PCR. The present study demonstrated that HBV replicates in proliferating PBMCs, which were induced by PHA and IL‑2. This method offers a novel investigative tool to detect HBV infection in PBMCs and to monitor the course of HBV infection.

Postinduction minimal residual disease monitoring by polymerase chain reaction in children with acute lymphoblastic leukemia.

PubMed

Paganin, Maddalena; Fabbri, Giulia; Conter, Valentino; Barisone, Elena; Polato, Katia; Cazzaniga, Giovanni; Giraldi, Eugenia; Fagioli, Franca; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe

2014-11-01

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Monitoring minimal residual disease (MRD) by using real-time quantitative polymerase chain reaction (RQ-PCR) provides information for patient stratification and individual risk-directed treatment. Cooperative studies have documented that measurement of blast clearance from the bone marrow during and after induction therapy identifies patient populations with different risk of relapse. We explored the possible contribution of measurements of MRD during the course of treatment. We used RQ-PCR to detect MRD in 110 unselected patients treated in Italy in the International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia (AIEOP-BFM ALL 2000). The trial took place in AIEOP centers during postinduction chemotherapy. Results were categorized as negative, low positive (below the quantitative range [< 5 × 10(-4)]), or high positive (≥ 5 × 10(-4)). Patients with at least one low-positive or high-positive result were assigned to the corresponding subgroup. Patients who tested high positive, low positive, or negative had significantly different cumulative incidences of leukemia relapse: 83.3%, 34.8%, and 8.6%, respectively (P < .001). Two thirds of positive cases were identified within 4 months after induction-consolidation therapy, suggesting that this time frame may be most suitable for cost-effective MRD monitoring, particularly in patients who did not clear their disease at the end of consolidation. These findings provide further insights into the dynamic of MRD and the ongoing effort to define molecular relapse in childhood ALL. © 2014 by American Society of Clinical Oncology.

Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

PubMed Central

Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

2015-01-01

Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy

PubMed Central

Chen, Der-Yuan; Chen, Hsin-Hua; Hsieh, Chia-Wei; Yeh, Yea-Wen; Lan, Joung-Liang

2016-01-01

QuantiFERON-TB-Gold (QFT-G) conversion is frequently observed in rheumatoid arthritis (RA) patients receiving biologic therapy. However, there have not been any known biomarkers available for detecting tuberculosis (TB) in QFT-G converters. We aimed to evaluate clinical utility of cytokines/chemokines for detecting TB in patients with QFT-G conversion. Among a total of 227 RA patients who underwent QFT-G assay, 187 QFT-G-negative patients received biologic therapy without isoniazid prophylaxis. QFT-G assay was repeated at week 52 of biologic therapy or at the time of TB diagnosis. Levels of cytokines/chemokines were determined by magnetic bead array or ELISA in QFT-G converters and 12 non-RA patients with TB (non-RA TB). QFT-G conversion was found in 54 (28.9%) of 187 baseline QFT-G-negative patients, of which 7 (13.0%) developed active TB during the one-year follow-up period. Among the examined cytokines/chemokines, non-stimulated and TB-antigen-stimulated neopterin levels were significantly higher in RA patients who developed TB (RA-TB) (median, 24.5pg/ml and 23053pg/ml, respectively) and non-RA TB patients (12.2pg/ml and 9633pg/ml, respectively) compared with QFT-G converters without TB (3.0pg/ml and 2720pg/ml, respectively, both p<0.001). Rising levels of neopterin relative to baseline (non-stimulated levels, 4.4pg/ml vs. 24.5pg/ml; TB-antigen-stimulated levels, 1801pg/ml vs. 23053pg/ml) were observed in QFT-G converters who developed TB. A high proportion (85.7%) of QFT-G converters with high plasma neopterin levels developed TB during the one-year follow-up period. In conclusion, RA patients with QFT-G conversion during the period of biologic therapy should be carefully monitored for elevation of neopterin levels, which is associated with TB risk in QFT-G converters, particularly in TB-endemic areas. PMID:27861525

Range Verification Methods in Particle Therapy: Underlying Physics and Monte Carlo Modeling

PubMed Central

Kraan, Aafke Christine

2015-01-01

Hadron therapy allows for highly conformal dose distributions and better sparing of organs-at-risk, thanks to the characteristic dose deposition as function of depth. However, the quality of hadron therapy treatments is closely connected with the ability to predict and achieve a given beam range in the patient. Currently, uncertainties in particle range lead to the employment of safety margins, at the expense of treatment quality. Much research in particle therapy is therefore aimed at developing methods to verify the particle range in patients. Non-invasive in vivo monitoring of the particle range can be performed by detecting secondary radiation, emitted from the patient as a result of nuclear interactions of charged hadrons with tissue, including β+ emitters, prompt photons, and charged fragments. The correctness of the dose delivery can be verified by comparing measured and pre-calculated distributions of the secondary particles. The reliability of Monte Carlo (MC) predictions is a key issue. Correctly modeling the production of secondaries is a non-trivial task, because it involves nuclear physics interactions at energies, where no rigorous theories exist to describe them. The goal of this review is to provide a comprehensive overview of various aspects in modeling the physics processes for range verification with secondary particles produced in proton, carbon, and heavier ion irradiation. We discuss electromagnetic and nuclear interactions of charged hadrons in matter, which is followed by a summary of some widely used MC codes in hadron therapy. Then, we describe selected examples of how these codes have been validated and used in three range verification techniques: PET, prompt gamma, and charged particle detection. We include research studies and clinically applied methods. For each of the techniques, we point out advantages and disadvantages, as well as clinical challenges still to be addressed, focusing on MC simulation aspects. PMID:26217586

Development of a chemiluminescence competitive PCR for the detection and quantification of parvovirus B19 DNA using a microplate luminometer.

PubMed

Fini, F; Gallinella, G; Girotti, S; Zerbini, M; Musiani, M

1999-09-01

Quantitative PCR of viral nucleic acids can be useful clinically in diagnosis, risk assessment, and monitoring of antiviral therapy. We wished to develop a chemiluminescence competitive PCR (cPCR) for parvovirus B19. Parvovirus DNA target sequences and competitor sequences were coamplified and directly labeled. Amplified products were then separately hybridized by specific biotin-labeled probes, captured onto streptavidin-coated ELISA microplates, and detected immunoenzymatically using chemiluminescent substrates of peroxidase. Chemiluminescent signals were quantitatively analyzed by a microplate luminometer and were correlated to the amounts of amplified products. Luminol-based systems displayed constant emission but had a higher detection limit (100-1000 genome copies) than the acridan-based system (20 genome copies). The detection limit of chemiluminescent substrates was lower (20 genome copies) than colorimetric substrates (50 genome copies). In chemiluminescence cPCR, the titration curves showed linear correlation above 100 target genome copies. Chemiluminescence cPCR was positive in six serum samples from patients with parvovirus infections and negative in six control sera. The chemiluminescence cPCR appears to be a sensitive and specific method for the quantitative detection of viral DNAs.

[Usefulness of continuous glucose monitoring system (CGMS) in monitoring glycaemic profile in small children with diabetes type 1].

PubMed

Głowińska-Olszewska, Barbara; Urban, Mirosława; Peczyńska, Jadwiga; Florys, Bozena; Kowalewski, Marek

2005-01-01

Improved methods of diabetes therapy result in a near normoglycaemic state in many patients. This leads however unfortunately to more frequent hypoglycaemic incidents. Particularly small children, whose nervous system is not fully mature, are at high risk of central nervous system damage in case of hypoglycaemia. A new method of detail monitoring of glycaemia provides CGMS system. The aim of the study was to compare the glycaemic profile, with high attention to hypoglycaemia in groups of young and older children with diabetes type 1, using CGMS and routine glucose meter. We studied 32 children with diabetes type 1. Children were divided into groups: group I--small children, n=17 (<7 yrs of age), mean age 5,8 years, with disease duration--2,46 years, with mean HbA1c level--7,22%, and group II--older children, n=15 (>10 years of age), mean age--12 years, with disease duration--3 years, with HbA1c level--7,21%. Continuous glucose monitoring system (CGMS), by MiniMed, was applied in outpatient or hospital conditions, after short training of patient and parents; together with routine glucose meter measurements, 4-8 times/24 hours. In 9 patients from small children group CGMS was repeated after 2 months. Hypoglycaemic incidents detected with CGMS were similar in both groups: 4,6 in I group vs. 4,2 in II group (ns). Hypoglycaemic incidents found with meter were lower in I group--1,6 vs. 2,3 in II group (ns). Mean hypoglycaemic time/24 hour was longer in small children group: 101 min vs. 74 min in group II (p<00,05). In I group we found higher number of hypoglycaemic incidents during the night compared to group II--1,7 vs. 0,8 (p<00,05) and longer duration of night hypoglycaemia: in I group--56 min vs. 32 min in group II (p<00,05). Repeated CGMS study in 9 children from I group revealed decreased mean time of hypoglycaemia/24 hours from 134 min/24 h to 90 min/24 h (p<00,05) and decreased time of night hypoglycaemia from 65 min to 40 min (p<00,05), with a comparable number of hypoglycaemic incidents. Hypoglycaemic incidents found with routine meter measurements in small children were 1,6 vs. 4,6 hypoglycaemia found with CGMS (p<00,05), in the older children group routine measurement found 2,3 hypoglycaemia vs. 4,2 detected with CGMS (ns). 1. CGMS can be particularly usefull in monitoring glucose profile and detecting hypoglycaemia incidents, mainly nocturnal in small children. 2. CGMS allows to verify meal dose of insulin and to decrease postprandial hyperglycaemia. 3. Modification of insulin therapy on the base of CGMS helps to decrease the time of hypoglycaemia and hyperglycemia, particularly during the night.

Monitoring acute phase proteins in retrovirus infected cats undergoing feline interferon-ω therapy.

PubMed

Leal, R O; Gil, S; Sepúlveda, N; McGahie, D; Duarte, A; Niza, M M R E; Tavares, L

2014-01-01

Recombinant feline interferon-ω therapy is an immunomodulator currently used in the treatment of different retroviral diseases including feline immune deficiency virus and feline leukaemia virus. Although its mechanism of action remains unclear, this drug appears to potentiate the innate response. Acute phase proteins are one of the key components of innate immunity and studies describing their use as a monitoring tool for the immune system in animals undergoing interferon-ω therapy are lacking. This study aimed to determine whether interferon-ω therapy influences acute phase protein concentrations namely serum amyloid-A, α-1-glycoprotein and C-reactive protein. A single-arm study was performed using 16 cats, living in an animal shelter, naturally infected with retroviruses and subjected to the interferon-ω therapy licensed protocol. Samples were collected before (D0), during (D10 and D30) and after therapy (D65). Serum amyloid-A and C-reactive protein were measured by specific enzyme-linked immunosorbent assay kits and α-1-glycoprotein by single radial immunodiffusion. All the acute phase proteins significantly increased in cats undergoing interferon-ω therapy (D0/D65: P<0·05) CLINICAL SIGNIFICANCE: Acute phase proteins appear to be reasonable predictors of innate-immune stimulation and may be useful in the individual monitoring of naturally retroviral infected cats undergoing interferon-ω therapy. © 2013 British Small Animal Veterinary Association.