Widespread Environmental Contamination with Mycobacterium tuberculosis Complex Revealed by a Molecular Detection Protocol

PubMed Central

Santos, Nuno; Santos, Catarina; Valente, Teresa; Gortázar, Christian; Almeida, Virgílio; Correia-Neves, Margarida

2015-01-01

Environmental contamination with Mycobacterium tuberculosis complex (MTC) has been considered crucial for bovine tuberculosis persistence in multi-host-pathogen systems. However, MTC contamination has been difficult to detect due to methodological issues. In an attempt to overcome this limitation we developed an improved protocol for the detection of MTC DNA. MTC DNA concentration was estimated by the Most Probable Number (MPN) method. Making use of this protocol we showed that MTC contamination is widespread in different types of environmental samples from the Iberian Peninsula, which supports indirect transmission as a contributing mechanism for the maintenance of bovine tuberculosis in this multi-host-pathogen system. The proportion of MTC DNA positive samples was higher in the bovine tuberculosis-infected than in presumed negative area (0.32 and 0.18, respectively). Detection varied with the type of environmental sample and was more frequent in sediment from dams and less frequent in water also from dams (0.22 and 0.05, respectively). The proportion of MTC-positive samples was significantly higher in spring (p<0.001), but MTC DNA concentration per sample was higher in autumn and lower in summer. The average MTC DNA concentration in positive samples was 0.82 MPN/g (CI95 0.70–0.98 MPN/g). We were further able to amplify a DNA sequence specific of Mycobacterium bovis/caprae in 4 environmental samples from the bTB-infected area. PMID:26561038

A Prestressed Cable Network Model of the Adherent Cell Cytoskeleton

PubMed Central

Coughlin, Mark F.; Stamenović, Dimitrije

2003-01-01

A prestressed cable network is used to model the deformability of the adherent cell actin cytoskeleton. The overall and microstructural model geometries and cable mechanical properties were assigned values based on observations from living cells and mechanical measurements on isolated actin filaments, respectively. The models were deformed to mimic cell poking (CP), magnetic twisting cytometry (MTC) and magnetic bead microrheometry (MBM) measurements on living adherent cells. The models qualitatively and quantitatively captured the fibroblast cell response to the deformation imposed by CP while exhibiting only some qualitative features of the cell response to MTC and MBM. The model for CP revealed that the tensed peripheral actin filaments provide the key resistance to indentation. The actin filament tension that provides mechanical integrity to the network was estimated at ∼158 pN, and the nonlinear mechanical response during CP originates from filament kinematics. The MTC and MBM simulations revealed that the model is incomplete, however, these simulations show cable tension as a key determinant of the model response. PMID:12547813

A prestressed cable network model of the adherent cell cytoskeleton.

PubMed

Coughlin, Mark F; Stamenović, Dimitrije

2003-02-01

A prestressed cable network is used to model the deformability of the adherent cell actin cytoskeleton. The overall and microstructural model geometries and cable mechanical properties were assigned values based on observations from living cells and mechanical measurements on isolated actin filaments, respectively. The models were deformed to mimic cell poking (CP), magnetic twisting cytometry (MTC) and magnetic bead microrheometry (MBM) measurements on living adherent cells. The models qualitatively and quantitatively captured the fibroblast cell response to the deformation imposed by CP while exhibiting only some qualitative features of the cell response to MTC and MBM. The model for CP revealed that the tensed peripheral actin filaments provide the key resistance to indentation. The actin filament tension that provides mechanical integrity to the network was estimated at approximately 158 pN, and the nonlinear mechanical response during CP originates from filament kinematics. The MTC and MBM simulations revealed that the model is incomplete, however, these simulations show cable tension as a key determinant of the model response.

Modelling heterogeneity variances in multiple treatment comparison meta-analysis--are informative priors the better solution?

PubMed

Thorlund, Kristian; Thabane, Lehana; Mills, Edward J

2013-01-11

Multiple treatment comparison (MTC) meta-analyses are commonly modeled in a Bayesian framework, and weakly informative priors are typically preferred to mirror familiar data driven frequentist approaches. Random-effects MTCs have commonly modeled heterogeneity under the assumption that the between-trial variance for all involved treatment comparisons are equal (i.e., the 'common variance' assumption). This approach 'borrows strength' for heterogeneity estimation across treatment comparisons, and thus, ads valuable precision when data is sparse. The homogeneous variance assumption, however, is unrealistic and can severely bias variance estimates. Consequently 95% credible intervals may not retain nominal coverage, and treatment rank probabilities may become distorted. Relaxing the homogeneous variance assumption may be equally problematic due to reduced precision. To regain good precision, moderately informative variance priors or additional mathematical assumptions may be necessary. In this paper we describe four novel approaches to modeling heterogeneity variance - two novel model structures, and two approaches for use of moderately informative variance priors. We examine the relative performance of all approaches in two illustrative MTC data sets. We particularly compare between-study heterogeneity estimates and model fits, treatment effect estimates and 95% credible intervals, and treatment rank probabilities. In both data sets, use of moderately informative variance priors constructed from the pair wise meta-analysis data yielded the best model fit and narrower credible intervals. Imposing consistency equations on variance estimates, assuming variances to be exchangeable, or using empirically informed variance priors also yielded good model fits and narrow credible intervals. The homogeneous variance model yielded high precision at all times, but overall inadequate estimates of between-trial variances. Lastly, treatment rankings were similar among the novel approaches, but considerably different when compared with the homogenous variance approach. MTC models using a homogenous variance structure appear to perform sub-optimally when between-trial variances vary between comparisons. Using informative variance priors, assuming exchangeability or imposing consistency between heterogeneity variances can all ensure sufficiently reliable and realistic heterogeneity estimation, and thus more reliable MTC inferences. All four approaches should be viable candidates for replacing or supplementing the conventional homogeneous variance MTC model, which is currently the most widely used in practice.

Modelling heterogeneity variances in multiple treatment comparison meta-analysis – Are informative priors the better solution?

PubMed Central

2013-01-01

Background Multiple treatment comparison (MTC) meta-analyses are commonly modeled in a Bayesian framework, and weakly informative priors are typically preferred to mirror familiar data driven frequentist approaches. Random-effects MTCs have commonly modeled heterogeneity under the assumption that the between-trial variance for all involved treatment comparisons are equal (i.e., the ‘common variance’ assumption). This approach ‘borrows strength’ for heterogeneity estimation across treatment comparisons, and thus, ads valuable precision when data is sparse. The homogeneous variance assumption, however, is unrealistic and can severely bias variance estimates. Consequently 95% credible intervals may not retain nominal coverage, and treatment rank probabilities may become distorted. Relaxing the homogeneous variance assumption may be equally problematic due to reduced precision. To regain good precision, moderately informative variance priors or additional mathematical assumptions may be necessary. Methods In this paper we describe four novel approaches to modeling heterogeneity variance - two novel model structures, and two approaches for use of moderately informative variance priors. We examine the relative performance of all approaches in two illustrative MTC data sets. We particularly compare between-study heterogeneity estimates and model fits, treatment effect estimates and 95% credible intervals, and treatment rank probabilities. Results In both data sets, use of moderately informative variance priors constructed from the pair wise meta-analysis data yielded the best model fit and narrower credible intervals. Imposing consistency equations on variance estimates, assuming variances to be exchangeable, or using empirically informed variance priors also yielded good model fits and narrow credible intervals. The homogeneous variance model yielded high precision at all times, but overall inadequate estimates of between-trial variances. Lastly, treatment rankings were similar among the novel approaches, but considerably different when compared with the homogenous variance approach. Conclusions MTC models using a homogenous variance structure appear to perform sub-optimally when between-trial variances vary between comparisons. Using informative variance priors, assuming exchangeability or imposing consistency between heterogeneity variances can all ensure sufficiently reliable and realistic heterogeneity estimation, and thus more reliable MTC inferences. All four approaches should be viable candidates for replacing or supplementing the conventional homogeneous variance MTC model, which is currently the most widely used in practice. PMID:23311298

Wavelet-based multiscale analysis of minimum toe clearance variability in the young and elderly during walking.

PubMed

Khandoker, Ahsan H; Karmakar, Chandan K; Begg, Rezaul K; Palaniswami, Marimuthu

2007-01-01

As humans age or are influenced by pathology of the neuromuscular system, gait patterns are known to adjust, accommodating for reduced function in the balance control system. The aim of this study was to investigate the effectiveness of a wavelet based multiscale analysis of a gait variable [minimum toe clearance (MTC)] in deriving indexes for understanding age-related declines in gait performance and screening of balance impairments in the elderly. MTC during walking on a treadmill for 30 healthy young, 27 healthy elderly and 10 falls risk elderly subjects with a history of tripping falls were analyzed. The MTC signal from each subject was decomposed to eight detailed signals at different wavelet scales by using the discrete wavelet transform. The variances of detailed signals at scales 8 to 1 were calculated. The multiscale exponent (beta) was then estimated from the slope of the variance progression at successive scales. The variance at scale 5 was significantly (p<0.01) different between young and healthy elderly group. Results also suggest that the Beta between scales 1 to 2 are effective for recognizing falls risk gait patterns. Results have implication for quantifying gait dynamics in normal, ageing and pathological conditions. Early detection of gait pattern changes due to ageing and balance impairments using wavelet-based multiscale analysis might provide the opportunity to initiate preemptive measures to be undertaken to avoid injurious falls.

Assessing the growth of preterm infants using detailed anthropometry.

PubMed

Ashton, James J; Johnson, Mark J; Pond, Jenny; Crowley, Philippa; Dimitrov, Borislav D; Pearson, Freya; Beattie, R Mark

2017-06-01

Preterm infants display altered body composition compared to term infants, and weight gain is a crude indicator body composition. Childhood mid-upper arm circumference (MUAC) is a measure of nutritional status. This study investigates MUAC and mid-thigh circumference (MTC) to monitor growth in preterm infants. Preterm infants (<30-week gestation) were recruited. MUAC, MTC, weight, length and head circumference (HC) were measured at recruitment and weekly intervals until discharge. Descriptive, correlation and regression analyses were used. Ninety-three infants were recruited. Median measurement duration was eight weeks (1-19). Median gestational age was 27 weeks (23-29). Analysis by curve estimation displayed a mean increase of 2.58 mm/week (left MUAC) (p ≤ 0.0001), 2.56 mm/week (right MUAC) (p ≤ 0.0001), 4.16 mm/week (left MTC) (p ≤ 0.0001), 4.20 mm/week (right MTC) (p ≤ 0.0001). Coefficients of determination (R 2 ) were calculated using a growth regression model for MUAC and MTC (0.866-0.917); measures were comparable to growth modelling of weight (0.913), length (0.945) and HC (0.928). High concordance between left and right MUAC and MTC generated a Pearson's correlation coefficient of 0.999 (MUAC) (p ≤ 0.001) and 0.994 (MTC) (p ≤ 0.001). Data demonstrate the potential utility of MUAC and MTC as additional measures of growth in preterm infants that are reproducible over time. There is potential to gain insights to improve lean-mass accretion in preterm infants. ©2017 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

Multiple Transportable Carbohydrates During Exercise: Current Limitations and Directions for Future Research.

PubMed

Wilson, Patrick B

2015-07-01

The concept of multiple transportable carbohydrates (MTC) refers to a combination of saccharides that rely on distinct transporters for intestinal absorption. Ingestion of MTC during prolonged exercise has been purported to increase carbohydrate absorption efficiency, increase exogenous carbohydrate oxidation, reduce gastrointestinal (GI) distress, and improve athletic performance when carbohydrate intake is high (>50-60 g·h⁻¹). Although reviews of MTC research have been published previously, a comprehensive literature evaluation underscoring methodological limitations has not been conducted to guide future work. Accordingly, this review outlined the plausible mechanisms of MTC and subsequently evaluated MTC research based on several factors, including participant characteristics, exercise modality, exercise task, treatment formulation, treatment blinding, and pre-exercise nutrition status. A total of 27 articles examining MTC during exercise were identified and reviewed. Overall, ingestion of MTC led to increased exogenous carbohydrate oxidation, reduced GI distress, and improved performance during cycling lasting ≥2.5 hours, particularly when carbohydrate was ingested at ≥1.2 g·min⁻¹. Despite the apparent benefits, several limitations in the literature were apparent, including that only 3 studies used running, only 2 studies were conducted in the field, most participants were fasted, and women and adolescents were underrepresented. In addition, the majority of the studies fed carbohydrate at ≥1.2 g·min⁻¹, which may have inflated levels of GI distress and exaggerated performance decrements with single-saccharide feedings. Based on these limitations, future MTC investigations should consider focusing on running, examining team-based sports, including women and adolescents, conducting experiments under field conditions, examining the modifying effects of pre-exercise nutrition, and using modest feeding protocols (1.0-1.2 g·min⁻¹).

Benchmark experiment for the cross section of the 100Mo(p,2n)99mTc and 100Mo(p,pn)99Mo reactions

NASA Astrophysics Data System (ADS)

Takács, S.; Ditrói, F.; Aikawa, M.; Haba, H.; Otuka, N.

2016-05-01

As nuclear medicine community has shown an increasing interest in accelerator produced 99mTc radionuclide, the possible alternative direct production routes for producing 99mTc were investigated intensively. One of these accelerator production routes is based on the 100Mo(p,2n)99mTc reaction. The cross section of this nuclear reaction was studied by several laboratories earlier but the available data-sets are not in good agreement. For large scale accelerator production of 99mTc based on the 100Mo(p,2n)99mTc reaction, a well-defined excitation function is required to optimise the production process effectively. One of our recent publications pointed out that most of the available experimental excitation functions for the 100Mo(p,2n)99mTc reaction have the same general shape while their amplitudes are different. To confirm the proper amplitude of the excitation function, results of three independent experiments were presented (Takács et al., 2015). In this work we present results of a thick target count rate measurement of the Eγ = 140.5 keV gamma-line from molybdenum irradiated by Ep = 17.9 MeV proton beam, as an integral benchmark experiment, to prove the cross section data reported for the 100Mo(p,2n)99mTc and 100Mo(p,pn)99Mo reactions in Takács et al. (2015).

Radioisotopic Purity of Sodium Pertechnetate 99mTc Produced with a Medium-Energy Cyclotron: Implications for Internal Radiation Dose, Image Quality, and Release Specifications.

PubMed

Selivanova, Svetlana V; Lavallée, Éric; Senta, Helena; Caouette, Lyne; Sader, Jayden A; van Lier, Erik J; Zyuzin, Alexander; van Lier, Johan E; Guérin, Brigitte; Turcotte, Éric; Lecomte, Roger

2015-10-01

Cyclotron production of 99mTc is a promising route to supply 99mTc radiopharmaceuticals. Higher 99mTc yields can be obtained with medium-energy cyclotrons in comparison to those dedicated to PET isotope production. To take advantage of this capability, evaluation of the radioisotopic purity of 99mTc produced at medium energy (20-24 MeV) and its impact on image quality and dosimetry was required. Thick 100Mo (99.03% and 99.815%) targets were irradiated with incident energies of 20, 22, and 24 MeV for 2 or 6 h. The targets were processed to recover an effective thickness corresponding to approximately 5-MeV energy loss, and the resulting sodium pertechnetate 99mTc was assayed for chemical, radiochemical, and radionuclidic purity. Radioisotopic content in final formulation was quantified using γ-ray spectrometry. The internal radiation dose for 99mTc-pertechnetate was calculated on the basis of experimentally measured values and biokinetic data in humans. Planar and SPECT imaging were performed using thin capillary and water-filled Jaszczak phantoms. Extracted sodium pertechnetate 99mTc met all provisional quality standards. The formulated solution for injection had a pH of 5.0-5.5, contained greater than 98% of radioactivity in the form of pertechnetate ion, and was stable for at least 24 h after formulation. Radioisotopic purity of 99mTc produced with 99.03% enriched 100Mo was greater than 99.0% decay corrected to the end of bombardment (EOB). The radioisotopic purity of 99mTc produced with 99.815% enriched 100Mo was 99.98% or greater (decay corrected to the EOB). The estimated dose increase relative to 99mTc without any radionuclidic impurities was below 10% for sodium pertechnetate 99mTc produced from 99.03% 100Mo if injected up to 6 h after the EOB. For 99.815% 100Mo, the increase in effective dose was less than 2% at 6 h after the EOB and less than 4% at 15 h after the EOB when the target was irradiated at an incident energy of 24 MeV. Image spatial resolution and contrast with cyclotron-produced 99mTc were equivalent to those obtained with 99mTc eluted from a conventional generator. Clinical-grade sodium pertechnetate 99mTc was produced with a cyclotron at medium energies. Quality control procedures and release specifications were drafted as part of a clinical trial application that received approval from Health Canada. The results of this work are intended to contribute to establishing a regulatory framework for using cyclotron-produced 99mTc in routine clinical practice. © 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Development of medicine-intended isotope production technologies at Yerevan Physics Institute

NASA Astrophysics Data System (ADS)

Avetisyan, Albert; Avagyan, Robert; Kerobyan, Ivetta; Dallakyan, Ruben; Harutyunyan, Gevorg; Melkonyan, Aleksandr

2015-05-01

Accelerator-based 99mTc and 123I isotopes production technologies were created and developed at A.Alikhanyan National Science Laboratory (former Yerevan Physics Institute - YerPhI). The method involves the irradiation of natural molybdenum (for 99mTc production) and natural xenon (for 123I production) using high-intensity bremsstrahlung photons from the electron beam of the LUE50 linear electron accelerator located at the YerPhI. We have developed and tested the extraction of 99mTc and 123I from the irradiated natural MoO3 and natural Xe, respectively. The production method has been developed and shown to be successful. The current activity is devoted to creation and development of the technology of direct production 99mTc on the 100Mo as target materials using the proton beam from an IBA C18/18 cyclotron. The proton cyclotron C18/18 (producer - IBA, Belgium) was purchased and will be installed nearby AANL (YerPhI) till end 2014. The 18 MeV protons will be used to investigate accelerator-based schemes for the direct production of 99mTc. Main topics of studies will include experimental measurement of 99mTc production yield for different energies of protons, irradiation times, intensities, development of new methods of 99mTc extraction from irradiated materials, development of target preparation technology, development of target material recovery methods for multiple use and others.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced (99m)Tc yields.

PubMed

Tanguay, J; Hou, X; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2015-05-21

Cyclotron production of (99m)Tc through the (100)Mo(p,2n) (99m)Tc reaction channel is actively being investigated as an alternative to reactor-based (99)Mo generation by nuclear fission of (235)U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional (99m)Tc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity (99m)Tc. However, variations in proton beam currents and the thickness and isotopic composition of enriched (100)Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute (99m)Tc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including (100)Mo target thicknesses and proton beam currents, and reproducibility of absolute (99m)Tc yields (defined as the end of bombardment (EOB) (99m)Tc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB (99m)Tc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in (99m)Tc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of (99m)Tc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced (99m)Tc.

Quantitative analysis of relationships between irradiation parameters and the reproducibility of cyclotron-produced 99mTc yields

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-05-01

Cyclotron production of 99mTc through the 100Mo(p,2n) 99mTc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. An exciting aspect of this approach is that it can be implemented using currently-existing cyclotron infrastructure to supplement, or potentially replace, conventional 99mTc production methods that are based on aging and increasingly unreliable nuclear reactors. Successful implementation will require consistent production of large quantities of high-radionuclidic-purity 99mTc. However, variations in proton beam currents and the thickness and isotopic composition of enriched 100Mo targets, in addition to other irradiation parameters, may degrade reproducibility of both radionuclidic purity and absolute 99mTc yields. The purpose of this article is to present a method for quantifying relationships between random variations in production parameters, including 100Mo target thicknesses and proton beam currents, and reproducibility of absolute 99mTc yields (defined as the end of bombardment (EOB) 99mTc activity). Using the concepts of linear error propagation and the theory of stochastic point processes, we derive a mathematical expression that quantifies the influence of variations in various irradiation parameters on yield reproducibility, quantified in terms of the coefficient of variation of the EOB 99mTc activity. The utility of the developed formalism is demonstrated with an example. We show that achieving less than 20% variability in 99mTc yields will require highly-reproducible target thicknesses and proton currents. These results are related to the service rate which is defined as the percentage of 99mTc production runs that meet the minimum daily requirement of one (or many) nuclear medicine departments. For example, we show that achieving service rates of 84.0%, 97.5% and 99.9% with 20% variations in target thicknesses requires producing on average 1.2, 1.5 and 1.9 times the minimum daily activity requirement. The irradiation parameters that would be required to achieve these service rates are described. We believe the developed formalism will aid in the development of quality-control criteria required to ensure consistent supply of large quantities of high-radionuclidic-purity cyclotron-produced 99mTc.

Hereditary medullary thyroid carcinoma: the management dilemma.

PubMed

Zhou, Ping; Liu, Jian; Cheng, Shao-Wen; Wang, Bing; Yang, Rong; Peng, Ling

2012-06-01

Hereditary medullary thyroid carcinoma (hereditary MTC) is a rare malignancy, accounting for 25-30% of all MTC. It occurs as part of multiple endocrine neoplasia type 2 (MEN 2). Autosomal dominant gain-of-function mutations in the RET proto-oncogene is the cause of the disease, in which the common mutations are codons 609, 611, 618, 620, 630, 634 and 918. In recent years, the spectrum of RET gene mutations has changed. The classical mutations reduced, whereas the less aggressive mutations increased. Hereditary MTC is a time-dependent disease. Stages of the disorder at diagnosis can significantly influence survival rates. Based on the genotype-phenotype, RET mutations have been classified into four risk levels by American Thyroid Association (ATA) at 2009. The classification system guides the hereditary MTC management, including risk assessment, biochemical screenings and surgical intervention. Though the application of genetic testing and codon-specific phenotypes in hereditary MTC diagnosis is effective with high accuracy, there are some difficulties in implementing RET gene testing as a routine for MTC diagnosis. And most of carriers with RET mutations did not undergo thyroidectomy at the age recommended by the ATA guidelines. The aim of the study is to review the hereditary MTC and discuss the management dilemma.

Development and study of 99mTc-1-Thio-D-glucose for visualization of malignant tumors

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Skuridin, V.

2017-09-01

The preclinical studies of 99mTc-1-Thio-D-glucose, a new tumor-seeking agent based on technetium-99m-labeled glucose derivative, were conducted, and the feasibility of using this radiopharmaceutical for tumor visualization was studied. The preclinical studies were carried out strictly in accordance with the local legislation and were regulated by the generally accepted research standards. 99mTc-1-Thio-D-glucose was found to have optimal pharmacokinetic and physico-chemical properties for diagnostic imaging and was proved to belong to the low-toxic substances. The potential utility of 99mTc-1-thio-D-glucose for tumor imaging was studied in vitro and in vivo models. The present study demonstrated that 99mTc-1-Thio-D-glucose is a prospective radiopharmaceutical for cancer visualization.

Improvements in quality of care resulting from a formal multidisciplinary tumour clinic in the management of high-grade glioma.

PubMed

Back, Michael F; Ang, Emily L L; Ng, Wai-Hoe; See, Siew-Ju; Lim, C C Tchoyoson; Tay, Lee-Lee; Yeo, Tseng-Tsai

2007-05-01

There is increasing belief that a formal protocol-based multidisciplinary care model should be adopted as an optimal care model in oncology. However, there is minimal outcome evidence to demonstrate an improvement in patient care. The aim of this study was to compare clinical quality outcomes between patients with high-grade glioma managed at one hospital using a formal neuro-oncology multidisciplinary tumour clinic (MTC) and a second hospital with a traditional on-call referral pattern (non-MTC). Patients with high-grade glioma managed radically with radiation therapy at 2 Singapore hospitals from May 2002 to May 2006 were entered into a prospective database. Patients were grouped into management via MTC or non-MTC. Four clinical quality indicators were chosen retrospectively to assess the variation in practice: a) Use of computed tomography (CT) or magnetic resonance (MR) imaging post-resection (POI) for assessment of residual disease; b) Commencement of radiation therapy (RT) within 28 days of surgery; c) Adjuvant chemotherapy use for glioblastoma multiforme (CTGBM) and d) Median survival. Sixty-seven patients were managed radically, with 47 by MTC and by 20 by non-MTC. MTC patients were more likely to have POI (P = 0.042), and CTGBM (P = 0.025). Although the RT start time was similar for the whole cohort (60% versus 45%: P = 0.296); for GBM patients, the RT start was earlier (63% vs 33% P = 0.024). The median survival for the MTC group was 18.7 months versus 11.9 months for the non-MTC group (P = 0.11). Clinical quality outcomes were significantly improved in patients with high-grade glioma managed in this neuro-oncology MTC.

Evaluation of a Simple in-House Test to Presumptively Differentiate Mycobacterium tuberculosis Complex from Nontuberculous Mycobacteria by Detection of p-Nitrobenzoic Acid Metabolites

PubMed Central

Wang, Guirong; Yu, Xia; Liang, Qian; Chen, Suting; Wilson, Stuart; Huang, Hairong

2013-01-01

The timely differentiation of Mycobacterium tuberculosis complex (MTC) and non-tubercular mycobacterium (NTM) species is urgently needed in patient care since the routine laboratory method is time consuming and cumbersome. An easy and cheap method which can successfully distinguish MTC from NTM was established and evaluated. 38 mycobacterial type and reference strains and 65 clinical isolates representing 10 species of mycobacterium were included in this study. Metabolites of p-nitrobenzoic acid (PNB) reduction were identified using liquid chromatography and tandem mass spectrometry (LC/MS/MS). A spectrophotometric method was developed to detect these metabolites, which was evaluated on a number of MTC and NTM species. All of the tested NTM species and strains reduced PNB to p-aminobenzoic acid (PABA), while none of the MTC strains showed a similar activity. Spectrophotometric detection of PABA had 100% sensitivity and specificity for MTC and NTM differentiation among the type strains and the clinical isolates tested. PABA was identified as one of the metabolites of PNB reduction. All the tested NTM species metabolized PNB to PABA whereas the MTC members lacked this activity. A simple, specific and cost-effective method based on PABA production was established in order to discriminate MTC from NTM from cultured organisms. PMID:24260497

Non-MTC gait cycles: An adaptive toe trajectory control strategy in older adults.

PubMed

Santhiranayagam, Braveena K; Sparrow, W A; Lai, Daniel T H; Begg, Rezaul K

2017-03-01

Minimum-toe-clearance (MTC) above the walking surface is a critical representation of toe-trajectory control due to its association with tripping risk. Not all gait cycles exhibit a clearly defined MTC within the swing phase but there have been few previous accounts of the biomechanical characteristics of non-MTC gait cycles. The present report investigated the within-subject non-MTC gait cycle characteristics of 15 older adults (mean 73.1 years) and 15 young controls (mean 26.1 years). Participants performed the following tasks on a motorized treadmill: preferred speed walking, dual task walking (carrying a glass of water) and a dual-task speed-matched control. Toe position-time coordinates were acquired using a 3 dimensional motion capture system. When MTC was present, toe height at MTC (MTC height ) was extracted. The proportion of non-MTC gait cycles was computed for the age groups and individuals. For non-MTC gait cycles an 'indicative' toe height at the individual's average swing phase time (MTC time ) for observed MTC cycles was averaged across multiple non-MTC gait cycles. In preferred-speed walking Young demonstrated 2.9% non-MTC gait cycles and Older 18.7%. In constrained walking conditions both groups increased non-MTC gait cycles and some older adults revealed over 90%, confirming non-MTC gait cycles as an ageing-related phenomenon in lower limb trajectory control. For all participants median indicative toe-height on non-MTC gait cycles was greater than median MTC height . This result suggests that eliminating the biomechanically hazardous MTC event by adopting more of the higher-clearance non-MTC gait cycles, is adaptive in reducing the likelihood of toe-ground contact. Copyright © 2017 Elsevier B.V. All rights reserved.

Anatomical-based partial volume correction for low-dose dedicated cardiac SPECT/CT

NASA Astrophysics Data System (ADS)

Liu, Hui; Chan, Chung; Grobshtein, Yariv; Ma, Tianyu; Liu, Yaqiang; Wang, Shi; Stacy, Mitchel R.; Sinusas, Albert J.; Liu, Chi

2015-09-01

Due to the limited spatial resolution, partial volume effect has been a major degrading factor on quantitative accuracy in emission tomography systems. This study aims to investigate the performance of several anatomical-based partial volume correction (PVC) methods for a dedicated cardiac SPECT/CT system (GE Discovery NM/CT 570c) with focused field-of-view over a clinically relevant range of high and low count levels for two different radiotracer distributions. These PVC methods include perturbation geometry transfer matrix (pGTM), pGTM followed by multi-target correction (MTC), pGTM with known concentration in blood pool, the former followed by MTC and our newly proposed methods, which perform the MTC method iteratively, where the mean values in all regions are estimated and updated by the MTC-corrected images each time in the iterative process. The NCAT phantom was simulated for cardiovascular imaging with 99mTc-tetrofosmin, a myocardial perfusion agent, and 99mTc-red blood cell (RBC), a pure intravascular imaging agent. Images were acquired at six different count levels to investigate the performance of PVC methods in both high and low count levels for low-dose applications. We performed two large animal in vivo cardiac imaging experiments following injection of 99mTc-RBC for evaluation of intramyocardial blood volume (IMBV). The simulation results showed our proposed iterative methods provide superior performance than other existing PVC methods in terms of image quality, quantitative accuracy, and reproducibility (standard deviation), particularly for low-count data. The iterative approaches are robust for both 99mTc-tetrofosmin perfusion imaging and 99mTc-RBC imaging of IMBV and blood pool activity even at low count levels. The animal study results indicated the effectiveness of PVC to correct the overestimation of IMBV due to blood pool contamination. In conclusion, the iterative PVC methods can achieve more accurate quantification, particularly for low count cardiac SPECT studies, typically obtained from low-dose protocols, gated studies, and dynamic applications.

Simple-random-sampling-based multiclass text classification algorithm.

PubMed

Liu, Wuying; Wang, Lin; Yi, Mianzhu

2014-01-01

Multiclass text classification (MTC) is a challenging issue and the corresponding MTC algorithms can be used in many applications. The space-time overhead of the algorithms must be concerned about the era of big data. Through the investigation of the token frequency distribution in a Chinese web document collection, this paper reexamines the power law and proposes a simple-random-sampling-based MTC (SRSMTC) algorithm. Supported by a token level memory to store labeled documents, the SRSMTC algorithm uses a text retrieval approach to solve text classification problems. The experimental results on the TanCorp data set show that SRSMTC algorithm can achieve the state-of-the-art performance at greatly reduced space-time requirements.

Theoretical modeling of yields for proton-induced reactions on natural and enriched molybdenum targets.

PubMed

Celler, A; Hou, X; Bénard, F; Ruth, T

2011-09-07

Recent acute shortage of medical radioisotopes prompted investigations into alternative methods of production and the use of a cyclotron and ¹⁰⁰Mo(p,2n)(99m)Tc reaction has been considered. In this context, the production yields of (99m)Tc and various other radioactive and stable isotopes which will be created in the process have to be investigated, as these may affect the diagnostic outcome and radiation dosimetry in human studies. Reaction conditions (beam and target characteristics, and irradiation and cooling times) need to be optimized in order to maximize the amount of (99m)Tc and minimize impurities. Although ultimately careful experimental verification of these conditions must be performed, theoretical calculations can provide the initial guidance allowing for extensive investigations at little cost. We report the results of theoretically determined reaction yields for (99m)Tc and other radioactive isotopes created when natural and enriched molybdenum targets are irradiated by protons. The cross-section calculations were performed using a computer program EMPIRE for the proton energy range 6-30 MeV. A computer graphical user interface for automatic calculation of production yields taking into account various reaction channels leading to the same final product has been created. The proposed approach allows us to theoretically estimate the amount of (99m)Tc and its ratio relative to (99g)Tc and other radioisotopes which must be considered reaction contaminants, potentially contributing to additional patient dose in diagnostic studies.

Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks

PubMed Central

Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

2016-01-01

Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network. PMID:27936011

Overload Control for Signaling Congestion of Machine Type Communications in 3GPP Networks.

PubMed

Lu, Zhaoming; Pan, Qi; Wang, Luhan; Wen, Xiangming

2016-01-01

Because of the limited resources on radio access channels of third generation partnership projection (3GPP) network, one of the most challenging tasks posted by 3GPP cellular-based machine type communications (MTC) is congestion due to massive requests for connection to radio access network (RAN). In this paper, an overload control algorithm in 3GPP RAN is proposed, which proactively disperses the simultaneous access attempts in evenly distributed time window. Through periodic reservation strategy, massive access requests of MTC devices are dispersed in time, which reduces the probability of confliction of signaling. By the compensation and prediction mechanism, each device can communicate with MTC server with dynamic load of air interface. Numerical results prove that proposed method makes MTC applications friendly to 3GPP cellular network.

Minimum toe clearance events in divided attention treadmill walking in older and young adults: a cross-sectional study.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Sparrow, W A; Begg, Rezaul K

2015-07-12

Falls in older adults during walking frequently occur while performing a concurrent task; that is, dividing attention to respond to other demands in the environment. A particularly hazardous fall-related event is tripping due to toe-ground contact during the swing phase of the gait cycle. The aim of this experiment was to determine the effects of divided attention on tripping risk by investigating the gait cycle event Minimum Toe Clearance (MTC). Fifteen older adults (mean 73.1 years) and 15 young controls (mean 26.1 years) performed three walking tasks on motorized treadmill: (i) at preferred walking speed (preferred walking), (ii) while carrying a glass of water at a comfortable walking speed (dual task walking), and (iii) speed-matched control walking without the glass of water (control walking). Position-time coordinates of the toe were acquired using a 3 dimensional motion capture system (Optotrak NDI, Canada). When MTC was present, toe height at MTC (MTC_Height) and MTC timing (MTC_Time) were calculated. The proportion of non-MTC gait cycles was computed and for non-MTC gait cycles, toe-height was extracted at the mean MTC_Time. Both groups maintained mean MTC_Height across all three conditions. Despite greater MTC_Height SD in preferred gait, the older group reduced their variability to match the young group in dual task walking. Compared to preferred speed walking, both groups attained MTC earlier in dual task and control conditions. The older group's MTC_Time SD was greater across all conditions; in dual task walking, however, they approximated the young group's SD. Non-MTC gait cycles were more frequent in the older group across walking conditions (for example, in preferred walking: young - 2.9 %; older - 18.7 %). In response to increased attention demands older adults preserve MTC_Height but exercise greater control of the critical MTC event by reducing variability in both MTC_Height and MTC_Time. A further adaptive locomotor control strategy to reduce the likelihood of toe-ground contacts is to attain higher mid-swing clearance by eliminating the MTC event, i.e. demonstrating non-MTC gaits cycles.

Calendar Year 2007 Program Benefits for U.S. EPA Energy Star Labeled Products: Expanded Methodology

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

Sanchez, Marla; Homan, Gregory; Lai, Judy

2009-09-24

This report provides a top-level summary of national savings achieved by the Energy Star voluntary product labeling program. To best quantify and analyze savings for all products, we developed a bottom-up product-based model. Each Energy Star product type is characterized by product-specific inputs that result in a product savings estimate. Our results show that through 2007, U.S. EPA Energy Star labeled products saved 5.5 Quads of primary energy and avoided 100 MtC of emissions. Although Energy Star-labeled products encompass over forty product types, only five of those product types accounted for 65percent of all Energy Star carbon reductions achieved tomore » date, including (listed in order of savings magnitude)monitors, printers, residential light fixtures, televisions, and furnaces. The forecast shows that U.S. EPA?s program is expected to save 12.2 Quads of primary energy and avoid 215 MtC of emissions over the period of 2008?2015.« less

Feasibility studies towards future self-sufficient supply of the 99Mo-99mTc isotopes with Japanese accelerators

PubMed Central

NAKAI, Kozi; TAKAHASHI, Naruto; HATAZAWA, Jun; SHINOHARA, Atsushi; HAYASHI, Yoshihiko; IKEDA, Hayato; KANAI, Yasukazu; WATABE, Tadashi; FUKUDA, Mitsuhiro; HATANAKA, Kichiji

2014-01-01

In order to establish a self-sufficient supply of 99mTc, we studied feasibilities to produce its parent nucleus, 99Mo, using Japanese accelerators. The daughter nucleus, 99mTc, is indispensable for medical diagnosis. 99Mo has so far been imported from abroad, which is separated from fission products generated in nuclear reactors using enriched 235U fuel. We investigated 99mTc production possibilities based on the following three scenarios: (1) 99Mo production by the (n, 2n) reaction by spallation neutrons at the J-PARC injector, LINAC; (2) 99Mo production by the (p, pn) reaction at Ep = 50–80 MeV proton at the RCNP cyclotron; (3) 99mTc direct production with a 20 MeV proton beam from the PET cyclotron. Among these three scenarios, scenario (1) is for a scheme on a global scale, scenario (2) works in a local area, and both cases take a long time for negotiations. Scenario (3) is attractive because we can use nearly 50 PET cyclotrons in Japan for 99mTc production. We here consider both the advantages and disadvantages among the three scenarios by taking account of the Japanese accelerator situation. PMID:25504230

Contraction dynamics and function of the muscle-tendon complex depend on the muscle fibre-tendon length ratio: a simulation study.

PubMed

Mörl, Falk; Siebert, Tobias; Häufle, Daniel

2016-02-01

Experimental studies show different muscle-tendon complex (MTC) functions (e.g. motor or spring) depending on the muscle fibre-tendon length ratio. Comparing different MTC of different animals examined experimentally, the extracted MTC functions are biased by, for example, MTC-specific pennation angle and fibre-type distribution or divergent experimental protocols (e.g. influence of temperature or stimulation on MTC force). Thus, a thorough understanding of variation of these inner muscle fibre-tendon length ratios on MTC function is difficult. In this study, we used a hill-type muscle model to simulate MTC. The model consists of a contractile element (CE) simulating muscle fibres, a serial element (SE) as a model for tendon, and a parallel elastic element (PEE) modelling tissue in parallel to the muscle fibres. The simulation examines the impact of length variations of these components on contraction dynamics and MTC function. Ensuring a constant overall length of the MTC by L(MTC) = L(SE) + L(CE), the SE rest length was varied over a broad physiological range from 0.1 to 0.9 MTC length. Five different MTC functions were investigated by simulating typical physiological experiments: the stabilising function with isometric contractions, the motor function with contractions against a weight, the capability of acceleration with contractions against a small inertial mass, the braking function by decelerating a mass, and the spring function with stretch-shortening cycles. The ratio of SE and CE mainly determines the MTC function. MTC with comparably short tendon generates high force and maximal shortening velocity and is able to produce maximal work and power. MTC with long tendon is suitable to store and release a maximum amount of energy. Variation of muscle fibre-tendon ratio yielded two peaks for MTC's force response for short and long SE lengths. Further, maximum work storage capacity of the SE is at long relL(SE,0). Impact of fibre-tendon length ratio on MTC functions will be discussed. Considering a constant set of MTC parameters, quantitative changes in MTC performance (work, stiffness, force, energy storage, dissipation) depending on varying muscle fibre-tendon length ratio were provided, which enables classification and grading of different MTC designs.

When did a Mediterranean-type climate originate in southwestern Australia?

NASA Astrophysics Data System (ADS)

Lamont, Byron B.; He, Tianhua

2017-09-01

Knowing the environments under which biota have evolved is essential for understanding the functional traits that they possess. Here, we ask when a Mediterranean-type climate (MTC) originated in Western Australia that might help to explain some of its special plant adaptations to summer drought and heat, mild wet winters and intense summer fires. Periodic drought and fire can be traced back to the Cretaceous in southwestern Australia (SWA) but its seasonality is unknown. Previous estimates of the origin of the MTC in SWA have varied from 30 to 3 million years ago (Ma). An early proposal was that it originated in northwestern Australia 30 Ma and migrated south to its present location for which we find independent support. We collated 47 cases of what is currently known about the time of origin of adaptive responses to summer drought and heat, wet winters and periodic intense fire among flowering plants in SWA. About 15% arose in the 40-30-million-year (My) period, 32% in the 30-20-My period and 47% in the 20-10-My period, suggesting that a MTC may have been widespread in SWA by the mid-Miocene, but there may have been local appearances (proto-MTC) up to 20 My earlier. Uncertainties remain about the location of lineages at various times, the fitness benefits of apparent adaptive traits and their confinement to a MTC, and the significance of the origin versus the onset of diversification of traits. The current dearth of C4 grasses in SWA is consistent with other indications of the absence of a prior history of a summer-dominant rainfall, suggesting that the current MTC arose from a uniform-rainfall climate. Other lines of evidence that might refine these findings include the chemical composition of, and application of geochronometers to, laterites, carbonates and corals that have been used with success elsewhere. We conclude by noting that there may have been a mixture of climates for much of the time, indicated by the persistence of a few rainforest species up to 3 Ma, while there have been strong climatic oscillations about a MTC 'mean' over the last 5 My.

Measurement and Estimation of the 99Mo Production Yield by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Minato, Futoshi; Tsukada, Kazuaki; Sato, Nozomi; Watanabe, Satoshi; Saeki, Hideya; Kawabata, Masako; Hashimoto, Shintaro; Nagai, Yasuki

2017-11-01

We, for the first time, measured the yield of 99Mo, the mother nuclide of 99mTc used in nuclear medicine diagnostic procedures, produced by the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The neutrons with a continuous energy spectrum from the thermal energy up to about 40 MeV were provided by the C(d,n) reaction with 40 MeV deuteron beams. It was proved that the 99Mo yield agrees with that estimated by using the latest data on neutrons from the C(d,n) reaction and the evaluated cross section of the 100Mo(n,2n)99Mo reaction given in the Japanese Evaluated Nuclear Data Library. On the basis of the agreement, a systematic calculation was carried out to search for an optimum condition that enables us to produce as much 99Mo as possible with a good 99Mo/100Mo value from an economical point of view. The calculated 99Mo yield from a 150 g 100MoO3 sample indicated that about 30% of the demand for 99Mo in Japan can be met with a single accelerator capable of 40 MeV, 2 mA deuteron beams. Here, by referring to an existing 18F-fluorodeoxyglucose (FDG) distribution system we assumed that 99mTc radiopharmaceuticals formed after separating 99mTc from 99Mo can be delivered to hospitals from a radiopharmaceutical company within 6 h. The elution of 99mTc from 99Mo twice a day would meet about 50% of the demand for 99Mo.

Atmospheric variability of methane over Pakistan, Afghanistan and adjoining areas using retrievals from SCIAMACHY/ENVISAT

NASA Astrophysics Data System (ADS)

ul-Haq, Zia; Tariq, Salman; Ali, Muhammad

2015-12-01

In the present work we have studied spatial and temporal variability of methane total column (MTC) over Pakistan and neighboring regions of Afghanistan, India and Iran by using observations of SCanning Imaging Absorption SpectroMeter for Atmospheric CHartographY (SCIAMACHY) aboard EOS ENVISAT. Satellite measurements show large spatio-temporal variations in MTC over the study domain at different time scales. We find an average MTC of 1787±22 ppb (annual average±standard deviation) with 3.7% (slope 7.14±1.28, y-intercept 1751±7.19, r=0.91) increase during the period of January 2003 to April 2012. An enhanced MTC is observed mostly over the Indo-Gangetic Plain and areas with high anthropogenic activities. MTC exhibits a seasonal peak of 1804±28 ppb in summer followed by autumn (1800±25 ppb) and winter (1777±24 ppb). We have also discussed anthropogenic emission estimates in the study area obtained from EDGAR database. Substantial increments of 77% and 61% are observed in anthropogenic CH4 emissions for Pakistan and Afghanistan, respectively, during 1990-2008. Anthropogenic CH4 emissions from enteric fermentation and livestock sectors are found to be the highest. EDGAR data have also identified megacity Lahore, Sukkur, megacity Karachi, Dera Ghazi Khan, megacity Delhi and Ahmedabad as large point sources of CH4 emissions in the region. The emissions from Karachi show the highest increase of 107%, while Lahore is found with the highest annual average emissions of 8.8×10-10 kg m-2 s-1.

High prevalence of exon 8 G533C mutation in apparently sporadic medullary thyroid carcinoma in Greece.

PubMed

Sarika, H L; Papathoma, A; Garofalaki, M; Vasileiou, V; Vlassopoulou, B; Anastasiou, E; Alevizaki, M

2012-12-01

Genetic screening for ret mutation has become routine practice in the evaluation of medullary thyroid carcinoma (MTC). Approximately 25% of these tumours are familial, and they occur as components of the multiple endocrine neoplasia type 2 syndromes (MEN 2A and 2B) or familial MTC. In familial cases, the majority of mutations are found in exons 10, 11, 13, 14 or 15 of the ret gene. A rare mutation involving exon 8 (G533C) has recently been reported in familial cases of MTC in Brazil and Greece; some of these cases were originally thought to be sporadic. The aim of this study was to re-evaluate a series of sporadic cases of MTC, with negative family history, and screen them for germline mutations in exon 8. Genomic DNA was extracted from peripheral lymphocytes in 129 unrelated individuals who had previously been characterized as 'sporadic' based on the negative family history and negative screening for ret gene mutations. Samples were analysed in Applied Biosystems 7500 real-time PCR and confirmed by sequencing. The G533C exon 8 mutation was identified in 10 of 129 patients with sporadic MTC. Asymptomatic gene carriers were subsequently identified in other family members. In our study, we found that 7·75% patients with apparently sporadic MTC do carry G533C mutation involving exon 8 of ret. We feel that there is now a need to include exon 8 mutation screening in all patients diagnosed as sporadic MTC, in Greece. © 2012 Blackwell Publishing Ltd.

Mycobacterium tuberculosis complex genetic diversity: mining the fourth international spoligotyping database (SpolDB4) for classification, population genetics and epidemiology

PubMed Central

Brudey, Karine; Driscoll, Jeffrey R; Rigouts, Leen; Prodinger, Wolfgang M; Gori, Andrea; Al-Hajoj, Sahal A; Allix, Caroline; Aristimuño, Liselotte; Arora, Jyoti; Baumanis, Viesturs; Binder, Lothar; Cafrune, Patricia; Cataldi, Angel; Cheong, Soonfatt; Diel, Roland; Ellermeier, Christopher; Evans, Jason T; Fauville-Dufaux, Maryse; Ferdinand, Séverine; de Viedma, Dario Garcia; Garzelli, Carlo; Gazzola, Lidia; Gomes, Harrison M; Guttierez, M Cristina; Hawkey, Peter M; van Helden, Paul D; Kadival, Gurujaj V; Kreiswirth, Barry N; Kremer, Kristin; Kubin, Milan; Kulkarni, Savita P; Liens, Benjamin; Lillebaek, Troels; Ly, Ho Minh; Martin, Carlos; Martin, Christian; Mokrousov, Igor; Narvskaïa, Olga; Ngeow, Yun Fong; Naumann, Ludmilla; Niemann, Stefan; Parwati, Ida; Rahim, Zeaur; Rasolofo-Razanamparany, Voahangy; Rasolonavalona, Tiana; Rossetti, M Lucia; Rüsch-Gerdes, Sabine; Sajduda, Anna; Samper, Sofia; Shemyakin, Igor G; Singh, Urvashi B; Somoskovi, Akos; Skuce, Robin A; van Soolingen, Dick; Streicher, Elisabeth M; Suffys, Philip N; Tortoli, Enrico; Tracevska, Tatjana; Vincent, Véronique; Victor, Tommie C; Warren, Robin M; Yap, Sook Fan; Zaman, Khadiza; Portaels, Françoise; Rastogi, Nalin; Sola, Christophe

2006-01-01

Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database. Results The fourth international spoligotyping database, SpolDB4, describes 1939 shared-types (STs) representative of a total of 39,295 strains from 122 countries, which are tentatively classified into 62 clades/lineages using a mixed expert-based and bioinformatical approach. The SpolDB4 update adds 26 new potentially phylogeographically-specific MTC genotype families. It provides a clearer picture of the current MTC genomes diversity as well as on the relationships between the genetic attributes investigated (spoligotypes) and the infra-species classification and evolutionary history of the species. Indeed, an independent Naïve-Bayes mixture-model analysis has validated main of the previous supervised SpolDB3 classification results, confirming the usefulness of both supervised and unsupervised models as an approach to understand MTC population structure. Updated results on the epidemiological status of spoligotypes, as well as genetic prevalence maps on six main lineages are also shown. Our results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network. Conclusion Our results broaden the knowledge of the global phylogeography of the MTC complex. SpolDB4 should be a very useful tool to better define the identity of a given MTC clinical isolate, and to better analyze the links between its current spreading and previous evolutionary history. The building and mining of extended MTC polymorphic genetic databases is in progress. PMID:16519816

Influence of muscle-tendon complex geometrical parameters on modeling passive stretch behavior with the Discrete Element Method.

PubMed

Roux, A; Laporte, S; Lecompte, J; Gras, L-L; Iordanoff, I

2016-01-25

The muscle-tendon complex (MTC) is a multi-scale, anisotropic, non-homogeneous structure. It is composed of fascicles, gathered together in a conjunctive aponeurosis. Fibers are oriented into the MTC with a pennation angle. Many MTC models use the Finite Element Method (FEM) to simulate the behavior of the MTC as a hyper-viscoelastic material. The Discrete Element Method (DEM) could be adapted to model fibrous materials, such as the MTC. DEM could capture the complex behavior of a material with a simple discretization scheme and help in understanding the influence of the orientation of fibers on the MTC׳s behavior. The aims of this study were to model the MTC in DEM at the macroscopic scale and to obtain the force/displacement curve during a non-destructive passive tensile test. Another aim was to highlight the influence of the geometrical parameters of the MTC on the global mechanical behavior. A geometrical construction of the MTC was done using discrete element linked by springs. Young׳s modulus values of the MTC׳s components were retrieved from the literature to model the microscopic stiffness of each spring. Alignment and re-orientation of all of the muscle׳s fibers with the tensile axis were observed numerically. The hyper-elastic behavior of the MTC was pointed out. The structure׳s effects, added to the geometrical parameters, highlight the MTC׳s mechanical behavior. It is also highlighted by the heterogeneity of the strain of the MTC׳s components. DEM seems to be a promising method to model the hyper-elastic macroscopic behavior of the MTC with simple elastic microscopic elements. Copyright © 2015 Elsevier Ltd. All rights reserved.

TheatreLink: Wired to Make Plays Together at a Distance

ERIC Educational Resources Information Center

Shookhoff, David

2004-01-01

Now entering its eighth year, TheatreLink, Manhattan Theater Club's Internet-based distance-learning project remains the most exciting and most challenging initiative. MTC's Education Program had existed for seven years (since 1989 to be exact) before it started TheatreLink. During that early period MTC created an array of programs, all of them…

Isothiocyanate-functionalized bifunctional chelates and fac-[MI(CO)3]+ (M = Re, 99mTc) complexes for targeting uPAR in prostate cancer

USDA-ARS?s Scientific Manuscript database

Developing strategies to rapidly incorporate the fac-[MI(CO)3]+ (M = Re, 99mTc) core into biological targeting vectors is a growing realm in radiopharmaceutical development. This work presents the preparation of a novel isothiocyanate-functionalized bifunctional chelate based on 2,2´-dipicolylamine ...

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

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

Zeltchan, R., E-mail: r.zelchan@yandex.ru; Medvedeva, A.; Sinilkin, I.

Purpose: to study the potential utility of 1-thio-D-glucose labeled with {sup 99m}Tc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of {sup 99m}Tc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with {sup 99m}Tc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normalmore » and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of {sup 99m}Tc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with {sup 99m}Tc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of {sup 99m}Tc-1-thio-D-glucose at the tumor site. The accumulation of {sup 99m}Tc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that {sup 99m}Tc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of {sup 99m}Tc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.« less

Experimental study of radiopharmaceuticals based on technetium-99m labeled derivative of glucose for tumor diagnosis

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Bragina, O.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.; Dergilev, A.

2016-06-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 minutes at room temperature. After centrifugation of the vials with cells, the supernatant was removed. Radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B 1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 minutes. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D- glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3±0.15MBq and 1.07±0.6MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio- D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

Study of potential utility of new radiopharmaceuticals based on technetium-99m labeled derivative of glucose

NASA Astrophysics Data System (ADS)

Zeltchan, R.; Medvedeva, A.; Sinilkin, I.; Chernov, V.; Stasyuk, E.; Rogov, A.; Il'ina, E.; Larionova, L.; Skuridin, V.

2016-08-01

Purpose: to study the potential utility of 1-thio-D-glucose labeled with 99mTc for cancer imaging in laboratory animals. Materials and method: the study was carried out in cell cultures of normal CHO (Chinese hamster ovary cells CHO) and malignant tissues MCF-7 (human breast adenocarcinoma MCF-7). To evaluate the uptake of 99mTc-1-thio-D-glucose in normal and tumor tissue cells, 25 MBq of 1-thio-D-glucose labeled with 99mTc was added to the vials with 3 million cells and incubated for 30 min at room temperature. After centrifugation of the vials with cells, the supernatant was removed. The radioactivity in vials with normal and tumor cells was then measured. In addition, the study included 40 mice of C57B1/6j lines with tumor lesion of the right femur. For neoplastic lesions, Lewis lung carcinoma model was used. Following anesthesia, mice were injected intravenously with 25 MBq of 99mTc-1-thio-D-glucose. Planar scintigraphy was performed 15 minutes later in a matrix of 512x512 pixels for 5 min. Results: when measuring the radioactivity of normal and malignant cells after incubation with 99mTc-1-thio-D-glucose, it was found that the radioactivity of malignant cells was higher than that of normal cells. The mean values of radioactivity levels in normal and malignant cells were 0.3 ± 0.15 MBq and 1.07 ± 0.6 MBq, respectively. All examined animals had increased accumulation of 99mTc-1-thio-D-glucose at the tumor site. The accumulation of 99mTc-1-thio-D-glucose in the tumor was on average twice as high as compared to the symmetric region. Conclusion: The present study demonstrated that 99mTc-1-thio-D-glucose is a prospective radiopharmaceutical for cancer visualization. In addition, high accumulation of 99mTc-1-thio-D-glucose in the culture of cancer cells and in tumor tissue of animals demonstrates tumor tropism of the radiopharmaceutical.

Detection of tripping gait patterns in the elderly using autoregressive features and support vector machines.

PubMed

Lai, Daniel T H; Begg, Rezaul K; Taylor, Simon; Palaniswami, Marimuthu

2008-01-01

Elderly tripping falls cost billions annually in medical funds and result in high mortality rates often perpetrated by pulmonary embolism (internal bleeding) and infected fractures that do not heal well. In this paper, we propose an intelligent gait detection system (AR-SVM) for screening elderly individuals at risk of suffering tripping falls. The motivation of this system is to provide early detection of elderly gait reminiscent of tripping characteristics so that preventive measures could be administered. Our system is composed of two stages, a predictor model estimated by an autoregressive (AR) process and a support vector machine (SVM) classifier. The system input is a digital signal constructed from consecutive measurements of minimum toe clearance (MTC) representative of steady-state walking. The AR-SVM system was tested on 23 individuals (13 healthy and 10 having suffered at least one tripping fall in the past year) who each completed a minimum of 10 min of walking on a treadmill at a self-selected pace. In the first stage, a fourth order AR model required at least 64 MTC values to correctly detect all fallers and non-fallers. Detection was further improved to less than 1 min of walking when the model coefficients were used as input features to the SVM classifier. The system achieved a detection accuracy of 95.65% with the leave one out method using only 16 MTC samples, but was reduced to 69.57% when eight MTC samples were used. These results demonstrate a fast and efficient system requiring a small number of strides and only MTC measurements for accurate detection of tripping gait characteristics.

Immunohistochemistry of medullary thyroid carcinoma and C-cell hyperplasia by an affinity-purified anti-human calcitonin antiserum.

PubMed

Hayashida, C Y; Alves, V A; Kanamura, C T; Ezabella, M C; Abelin, N M; Nicolau, W; Bisi, H; Toledo, S P

1993-08-15

The diagnosis of medullary thyroid carcinoma (MTC) depends on the calcitonin immunohistochemistry. Familial MTC is associated with C-cell hyperplasia (CCH), whereas sporadic MTC is not. A specific and sensitive calcitonin immunohistochemistry is necessary for the diagnosis of MTC and CCH. An affinity-purified anti-calcitonin antiserum (APxCT) was used for immunohistochemistry of the thyroids of 15 patients with MTC. The thyroids of five patients with familial MTC were studied in detail, with each gland sectioned in 48 areas. Between three and ten independent MTC were found in each thyroid, and CCH was found in all five patients (24.2%, varying from 8.4-56.3% of the 48 areas from each thyroid). MTC and CCH were localized mainly in the middle third and in the central axis of the thyroid lobes. They often were found together in the same area (in a total of 21 areas for the five thyroids sectioned in 48 areas) but ten areas with MTC did not have CCH, and 37 areas with CCH did not have MTC. In ten thyroids partially studied, CCH was indicated in three patients thought to have sporadic MTC. In two thyroids, with follicular and papillary carcinoma, a higher density of C-cells was found around the tumors, but disease was not characterized as CCH. APxCT antiserum increased the immunohistochemical specificity and sensitivity. The distinction of the familial from the sporadic MTC requires a careful and extensive search of CCH. C-cells in high density may be found around follicular cell carcinomas, being a potential source of diagnostic error.

MCNPX CALCULATIONS OF SPECIFIC ABSORBED FRACTIONS IN SOME ORGANS OF THE HUMAN BODY DUE TO APPLICATION OF 133Xe, 99mTc and 81mKr RADIONUCLIDES.

PubMed

Jovanovic, Z; Krstic, D; Nikezic, D; Ros, J M Gomez; Ferrari, P

2018-03-01

Monte Carlo simulations were performed to evaluate treatment doses with wide spread used radionuclides 133Xe, 99mTc and 81mKr. These different radionuclides are used in perfusion or ventilation examinations in nuclear medicine and as indicators for cardiovascular and pulmonary diseases. The objective of this work was to estimate the specific absorbed fractions in surrounding organs and tissues, when these radionuclides are incorporated in the lungs. For this purpose a voxel thorax model has been developed and compared with the ORNL phantom. All calculations and simulations were performed by means of the MCNP5/X code.

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis

PubMed Central

Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-01

Objectives: To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Methods: Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Results: Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Conclusions: Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management. PMID:27992368

Early detection of rheumatoid arthritis in rats and humans with 99mTc-3PRGD2 scintigraphy: imaging synovial neoangiogenesis.

PubMed

Wu, Yu; Zhang, Guojian; Wang, Xiangcheng; Zhao, Zhenfang; Wang, Tao; Wang, Xuemei; Li, Xiao-Feng

2017-01-24

To validate 99mTc-labeled arginylglycylaspartic acid (99mTc-3PRGD2) scintigraphy as a means to image synovial neoangiogenesis in joints afflicted by rheumatoid arthritis and to investigate its potential in the early detection and management of rheumatoid arthritis. Rheumatoid arthritis and osteoarthritis were generated in Sprague Dawley rats by type II collagen immunization and papain injection, respectively. Rats were imaged with 99mTc-3PRGD2 and 99mTc- methyl diphosphonate (99mTc MDP). X-ray images were also obtained and assessed by a radiologist. Immunohistochemistry of αvβ3 and CD31confirmed the onset of synovial neoangiogenesis. The effect of bevacizumab on rheumatoid arthritis was followed with 99mTc-3PRGD2 scintigraphy. A patient with rheumatoid arthritis and a healthy volunteer were scanned with 99mTc-3PRGD2. Two weeks after immunization, a significant increase in 99mTc-3PRGD2 was observed in the joints of the rheumatoid arthritis model though uptake in osteoarthritis model and untreated controls was low. 99mTc-MDP whole body scans failed to distinguish early rheumatoid arthritis joints from healthy controls. The expression of αvβ3 and CD31was significantly higher in the joints of rheumatoid arthritis rats compared to normal controls. In serial 99mTc-3PRGD2 scintigraphy studies, 99mTc-3PRGD2 uptake increased in parallel with disease progression. Bevacizumab anti-angiogenetic therapy both improved the symptoms of the rheumatoid arthritis rats and significantly decreased 99mTc-3PRGD2 uptake. Significantly higher 99mTc-3PRGD2 accumulation was also observed in rheumatoid arthritis joints in the patient. Our findings indicate that 99mTc-3PRGD2 scintigraphy could detect early rheumatoid arthritis by imaging the associated synovial neoangiogenesis, and may be useful in disease management.

Hydroxyapatite Based 99Mo - 99Tc and 188W - 188Re Generator Systems

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

Knapp Jr, Russ F; Monroy-Guzman, F.; Badillo, V. E.

2006-01-01

This paper describes studies evaluating the use of hydroxyapatite as the adsorbent material for both {sup 99}Mo-{sup 99m}Tc and {sup 188}W-{sup 188}Re generator systems. Hydroxyapatite is an insoluble solid with anion exchange properties. A study of the sorption behaviour of {sup 99}Mo, {sup 99m}Tc, {sup 188}W and {sup 188}Re on hydroxyapatite in NaCl medium was evaluated by batch experiments. The results demonstrated that while {sup 99}Mo, {sup 99m}Tc and {sup 188}Re are not adsorbed by the hydroxyapatite in NaCl solutions (Kd <5), {sup 188}W is strongly adsorbed (Kd >500). On the basis of these measurements, hydroxyapatite {sup 188}W-{sup 188}Re generatormore » systems were then constructed and eluted in NaCl solutions. The hydroxyapatite based {sup 188}W-{sup 188}Re generator performances are presented.« less

Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma.

PubMed

Wells, Samuel A; Asa, Sylvia L; Dralle, Henning; Elisei, Rossella; Evans, Douglas B; Gagel, Robert F; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G

2015-06-01

The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice.

Revised American Thyroid Association Guidelines for the Management of Medullary Thyroid Carcinoma

PubMed Central

Asa, Sylvia L.; Dralle, Henning; Elisei, Rossella; Evans, Douglas B.; Gagel, Robert F.; Lee, Nancy; Machens, Andreas; Moley, Jeffrey F.; Pacini, Furio; Raue, Friedhelm; Frank-Raue, Karin; Robinson, Bruce; Rosenthal, M. Sara; Santoro, Massimo; Schlumberger, Martin; Shah, Manisha; Waguespack, Steven G.

2015-01-01

Introduction: The American Thyroid Association appointed a Task Force of experts to revise the original Medullary Thyroid Carcinoma: Management Guidelines of the American Thyroid Association. Methods: The Task Force identified relevant articles using a systematic PubMed search, supplemented with additional published materials, and then created evidence-based recommendations, which were set in categories using criteria adapted from the United States Preventive Services Task Force Agency for Healthcare Research and Quality. The original guidelines provided abundant source material and an excellent organizational structure that served as the basis for the current revised document. Results: The revised guidelines are focused primarily on the diagnosis and treatment of patients with sporadic medullary thyroid carcinoma (MTC) and hereditary MTC. Conclusions: The Task Force developed 67 evidence-based recommendations to assist clinicians in the care of patients with MTC. The Task Force considers the recommendations to represent current, rational, and optimal medical practice. PMID:25810047

Comparison of Biological Properties of 99mTc-Labeled Cyclic RGD Peptide Trimer and Dimer Useful as SPECT Radiotracers for Tumor Imaging

PubMed Central

Zhao, Zuo-Quan; Yang, Yong; Fang, Wei; Liu, Shuang

2016-01-01

Introduction This study sought to evaluate a 99mTc-labeled trimeric cyclic RGD peptide (99mTc-4P-RGD3) as the new radiotracer for tumor imaging. The objective was to compare its biological properties with those of 99mTc-3P-RGD2 in the same animal model. Methods HYNIC-4P-RGD3 was prepared by reacting 4P-RGD3 with excess HYNIC-OSu in the presence of diisopropylethylamine. 99mTc-4P-RGD3 was prepared using a kit formulation, and evaluated for its tumor-targeting capability and biodistribution properties in the BALB/c nude mice with U87MG human glioma xenografts. Planar and SPECT imaging studies were performed in athymic nude mice with U87MG glioma xenografts. For comparison purpose, 99mTc-3P-RGD2 (a αvβ3-targeted radiotracer currently under clinical evaluation for tumor imaging in cancer patients) was also evaluated in the same animal models. Blocking experiments were used to demonstrate the αvβ3 specificity of 99mTc-4P-RGD3. Results 99mTc-4P-RGD3 was prepared with >95% RCP and high specific activity (~200 GBq/µmol). 99mTc-4P-RGD3 and 99mTc-3P-RGD2 shared almost identical tumor uptake and similar biodistribution properties. 99mTc-4P-RGD3 had higher uptake than 99mTc-3P-RGD2 in the intestines and kidneys; but it showed better metabolic stability. The U87MG tumors were clearly visualized by SPECT with excellent contrast with 99mTc-4P-RGD3 and 99mTc-3P-RGD2. Conclusion Increasing peptide multiplicity from 3P-RGD2 to 4P-RGD3 offers no advantages with respect to the tumor-targeting capability. 99mTc-4P-RGD3 is as good a SPECT radiotracer as 99mTc-3P-RGD2 for imaging αvβ3-positive tumors. PMID:27556955

Impact of intracellular metallothionein on metal biouptake and partitioning dynamics at bacterial interfaces.

PubMed

Présent, Romain M; Rotureau, Elise; Billard, Patrick; Pagnout, Christophe; Sohm, Bénédicte; Flayac, Justine; Gley, Renaud; Pinheiro, José P; Duval, Jérôme F L

2017-11-08

Genetically engineered microorganisms are alternatives to physicochemical methods for remediation of metal-contaminated aquifers due to their remarkable bioaccumulation capacities. The design of such biosystems would benefit from the elaboration of a sound quantitative connection between performance in terms of metal removal from aqueous solution and dynamics of the multiscale processes leading to metal biouptake. In this work, this elaboration is reported for Escherichia coli cells modified to overexpress intracellular metallothionein (MTc), a strong proteinaceous metal chelator. Depletion kinetics of Cd(ii) from bulk solution following biouptake and intracellular accumulation is addressed as a function of cell volume fraction using electroanalytical probes and ligand exchange-based analyses. It is shown that metal biouptake in the absence and presence of MTc is successfully interpreted on the basis of a formalism recently developed for metal partitioning dynamics at biointerfaces with integration of intracellular metal speciation. The analysis demonstrates how fast sequestration of metals by intracellular MTc bypasses metal excretion (efflux) and enhances the rate of metal depletion to an extent such that complete removal is achieved at sufficiently large cell volume fractions. The magnitude of the stability constant of nanoparticulate metal-MTc complexes, as derived from refined analysis of macroscopic bulk metal depletion data, is further confirmed by independent electrochemical measurement of metal binding by purified MTc extracts.

Estimation of end point foot clearance points from inertial sensor data.

PubMed

Santhiranayagam, Braveena K; Lai, Daniel T H; Begg, Rezaul K; Palaniswami, Marimuthu

2011-01-01

Foot clearance parameters provide useful insight into tripping risks during walking. This paper proposes a technique for the estimate of key foot clearance parameters using inertial sensor (accelerometers and gyroscopes) data. Fifteen features were extracted from raw inertial sensor measurements, and a regression model was used to estimate two key foot clearance parameters: First maximum vertical clearance (m x 1) after toe-off and the Minimum Toe Clearance (MTC) of the swing foot. Comparisons are made against measurements obtained using an optoelectronic motion capture system (Optotrak), at 4 different walking speeds. General Regression Neural Networks (GRNN) were used to estimate the desired parameters from the sensor features. Eight subjects foot clearance data were examined and a Leave-one-subject-out (LOSO) method was used to select the best model. The best average Root Mean Square Errors (RMSE) across all subjects obtained using all sensor features at the maximum speed for m x 1 was 5.32 mm and for MTC was 4.04 mm. Further application of a hill-climbing feature selection technique resulted in 0.54-21.93% improvement in RMSE and required fewer input features. The results demonstrated that using raw inertial sensor data with regression models and feature selection could accurately estimate key foot clearance parameters.

Assessment of the direct cyclotron production of (99m)Tc: An approach to crisis management of (99m)Tc shortage.

PubMed

Rovais, Mohammad Reza Aboudzadeh; Aardaneh, Khosro; Aslani, Gholamreza; Rahiminejad, Ali; Yousefi, Kamran; Boulouri, Fatemeh

2016-06-01

Nowadays, the cyclotron production of technetium-99m ((99m)Tc) has been increased, due to the worldwide (99m)Tc generator shortage. In the present work, an improved strategy for the production of (99m)Tc, using the proton irradiation of the enriched (100)Mo was developed. The performance of this method in terms of the production yield, chemical purity, radiochemical purity, as well as radionuclide purity was evaluated. The average production yield was measured to be 356MBqμA(-1)h(-1). A good agreement was found between the calculated production yield and the experimental one. The radiochemical separation and total recovery yields of (99m)Tc were 92% and 69%, respectively. The radiochemical and the radionuclide purities of the (99m)Tc were 99% and >99.99% at the end of purification, respectively. The results of quality control tests (QC) support the concept that cyclotron-produced (99m)Tc is suitable for preparation of USP-compliant. Copyright © 2016 Elsevier Ltd. All rights reserved.

Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer.

PubMed

Borrego, Salud; Fernández, Raquel M; Dziema, Heather; Japón, Miguel A; Marcos, Irene; Eng, Charis; Antiñolo, Guillermo

2002-11-01

The etiology of sporadic medullary thyroid carcinoma (sMTC) remains elusive. While germline gain-of-function mutations in the RET proto-oncogene cause hereditary MTC, somatic RET mutations have been described in a variable number of sMTC. So far, S836S of RET, is the only variant whose association with sMTC has been found in several European cohorts. Because RET variants seem to be associated with MTC, it is plausible that variants in genes encoding for RET coreceptors may play a role in the pathogenesis of sMTC. Recently, we described two possible low penetrance susceptibility alleles in the gene encoding RET coreceptor GFRalpha1, -193C > G and 537T > C, in a German series of sMTC. In this study, we have genotyped nine polymorphisms within GFRA1-3 genes for 51 Spanish sMTC, and 100 normal controls. Our results show that no statistical signification was found when Spanish sMTC patients were compared to controls. Taken together with the observations in the German sMTC series, the present findings suggest that GFRA1-193C > G and 537T > C could be in linkage disequilibrium with other loci responsible for the disease with a founder effect in Germany. Alternatively, the combined observations might also suggest that, if indeed the polymorphisms are functional, the effect is small.

Controlled delivery of metoclopramide using an injectable semi-solid poly(ortho ester) for veterinary application.

PubMed

Schwach-Abdellaoui, Khadija; Moreau, Marinette; Schneider, Marc; Boisramć, Bernard; Gurny, Robert

2002-11-06

In animal health care, current therapeutic regimens for gastrointestinal disorders require repeated oral or parenteral dosage forms of anti-emetic agents. However, fluctuations of plasma concentrations produce severe side effects. The aim of this work is to develop a subcutaneous and biodegradable controlled release system containing metoclopramide (MTC). Semi-solid poly(ortho ester)s (POE) prepared by a transesterification reaction between trimethyl orthoacetate and 1,2,6,-hexanetriol were investigated as injectable bioerodible polymers for the controlled release of MTC. MTC is present in the polymeric matrix as a solubilised form and it is released rapidly from the POE by erosion and diffusion because of its acidic character and its high hydrosolubility. If a manual injection is desired, only low molecular weight can be used. However, low molecular weight POEs release the drug rapidly. In order to extend polymer lifetime and decrease drug release rate, a sparingly water-soluble base Mg(OH)(2) was incorporated to the formulation. It was possible to produce low molecular weight POE that can be manually injected and releasing MTC over a period of several days.

The study of interaction of modified fatty acid with {sup 99m}Tc in alcoholic media

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

Skuridin, V. S.; Stasyuk, E. S.; Varlamova, N. V.

2016-08-02

The paper presents the results of laboratory research aimed at the development of methods of synthesis of new radiodiagnostic agents based on modified fatty acid labelled with technetium-99m intended for scintigraphic evaluation of myocardial metabolism. In particular, the interaction of substance with {sup 99m}Tc in alcoholic media and the use of ethanol as solvent in the synthesis of the radiopharmaceutical were studied.

Methylthioninium chloride reverses cognitive deficits induced by scopolamine: comparison with rivastigmine.

PubMed

Deiana, Serena; Harrington, Charles R; Wischik, Claude M; Riedel, Gernot

2009-01-01

The cholinergic system is involved in cognition as well as in age-related cognitive decline and Alzheimer disease (AD). Cholinergic enhancers ameliorate AD symptoms and represent the main current therapy for AD. MTC (Methylthioninium chloride), an antioxidant with metabolism-enhancing properties may be a novel candidate with pro-cognitive capacities. This study was performed: (1) to assess the pro-cognitive efficacy of MTC and establish its dose-response; (2) to compare the efficacy of MTC with rivastigmine and (3) to determine the potential for combination therapy by co-administration of MTC and rivastigmine. Spatial cognition of female NMRI mice was tested in a reference memory water maze task. Subjects received intra-peritoneal injections of scopolamine (0.5 mg/kg) followed by vehicle, and/or MTC and/or rivastigmine (0.15-4 mg/kg MTC; 0.1-0.5 mg/kg rivastigmine) in mono or combination treatment. Scopolamine treatment prevented spatial learning in NMRI female mice and the deficit was reversed by both rivastigmine and MTC in a dose-dependent manner. Mono-therapy with high doses of rivastigmine (>0.5 mg/kg) caused severe side effects but MTC was safe up to 4 mg/kg. Co-administration of sub-effective doses of both drugs acted synergistically in reversing learning deficits and scopolamine-induced memory impairments. In our model, MTC reversed the spatial learning impairment. When combined with the ChEI rivastigmine, the effect of MTC appeared to be amplified indicating that combination therapy could potentially improve not only symptoms but also contribute beneficially to neuronal metabolism by minimising side effects at lower doses.

{sup 99m}Tc generators for clinical use based on zirconium molybdate gel and (n, gamma) produced {sup 99}Mo: Indian experience in the development and deployment of indigenous technology and processing facilities

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

Saraswathy, P.; Dey, A.C.; Sarkar, S.K.

The Indian pursuit of gel generator technology for {sup 99m}Tc was driven mainly by three considerations, namely, (i) well-established and ease of reliable production of (n, gamma)-based {sup 99}Mo in several tens of GBq quantities in the research reactors in Trombay/Mumbai, India, (ii) need for relatively low-cost alternate technology to replace the solvent (MEK) extraction generator system in use in India since 1970s and (iii) minimize dependency on weekly import of fission-produced {sup 99}Mo raw material required for alumina column generator. Extensive investigations on process standardisation for zirconium molybdate gel (ZMG) led to a steady progress, achieved both in termsmore » of process technology and final performance of {sup 99m}Tc gel generators. The {sup 99m}Tc final product purity from the Indian gel system was comparable to that obtained from the gold-standard alumina column generators. Based on the feasibility established for reliable small-scale production, as well as satisfactory clinical experience with a number of gel generators used in collaborating hospital radiopharmacies, full-fledged mechanised processing facilities for handling up to 150 g of ZMG were set up. The indigenous design and development included setting up of shielded plant facilities with pneumatic-driven as well as manual controls and special gadgets such as, microwave heating of the zirconium molybdate cake, dispenser for gel granules, loading of gel columns into pre-assembled generator housing etc. Formal review of the safety features was carried out by the regulatory body and stage-wise clearance for processing low and medium level {sup 99}Mo activity was granted. Starting from around 70 GBq {sup 99}Mo handling, the processing facilities have since been successfully operated at a level of 740 GBq {sup 99}Mo, twice a month. In all 18 batches of gel have been processed and 156 generators produced. The individual generator capacity was 15 to 30 GBq with an elution yield of nearly 75%. 129 generators were supplied to 11 user hospitals and the estimated number of clinical studies done is well over 5000. The salient aspects of the Indian experience have been reported in many a forum and shared with the IAEA through the on-going CRP. The detailed process know-how is available for technology transfer from BRIT, India. (author)« less

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis.

PubMed

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC 50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

Multibus-based parallel processor for simulation

NASA Technical Reports Server (NTRS)

Ogrady, E. P.; Wang, C.-H.

1983-01-01

A Multibus-based parallel processor simulation system is described. The system is intended to serve as a vehicle for gaining hands-on experience, testing system and application software, and evaluating parallel processor performance during development of a larger system based on the horizontal/vertical-bus interprocessor communication mechanism. The prototype system consists of up to seven Intel iSBC 86/12A single-board computers which serve as processing elements, a multiple transmission controller (MTC) designed to support system operation, and an Intel Model 225 Microcomputer Development System which serves as the user interface and input/output processor. All components are interconnected by a Multibus/IEEE 796 bus. An important characteristic of the system is that it provides a mechanism for a processing element to broadcast data to other selected processing elements. This parallel transfer capability is provided through the design of the MTC and a minor modification to the iSBC 86/12A board. The operation of the MTC, the basic hardware-level operation of the system, and pertinent details about the iSBC 86/12A and the Multibus are described.

Direct production of 99mTc using a small medical cyclotron

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

Lapi, Suzanne

This project describes an investigation towards the production of 99mTc with a small medical cyclotron. This endeavor addresses the current urgent problem of availability of 99mTc due to the ongoing production reactor failures and the upcoming Canadian reactor shut down. Currently, 99mTc is produced via nuclear fission using highly enriched uranium which is a concern due to nuclear proliferation risks. In addition to this, the United States is dependent solely on currently unreliable foreign sources of this important medical isotope. Clearly, a need exists to probe alternative production routes of 99mTc. In the first year, this project measured cross-sections andmore » production yields of potential pathways to 99mTc and associated radionuclidic impurities produced via these pathways using a small 15 MeV medical cyclotron. During the second and third years target systems for the production of 99mTc via the most promising reaction routes were developed and separation techniques for the isolation of 99mTc from the irradiated target material will be investigated. Systems for the recycling of the enriched target isotopes as well as automated target processing systems were examined in years four and five. This project has the potential to alleviate some of the current crisis in the medical community by developing a technique to produce 99mTc on location at a university hospital. This technology will be applicable at many other sites in the United States as many other similar, low energy (<20 MeV) cyclotrons (currently used for a few hours per day for the production of [ 18F]fluorodeoxyglucose) are available for production of 99mTc though this method, thus leading to job creation and preservation.« less

Reduction in clonogenic survival of sodium-iodide symporter (NIS)-positive cells following intracellular uptake of (99m)Tc versus (188)Re.

PubMed

Freudenberg, Robert; Wendisch, Maria; Runge, Roswitha; Wunderlich, Gerd; Kotzerke, Jörg

2012-12-01

Cellular radionuclide uptake increases the heterogeneity of absorbed dose to biological structures. Dose increase depends on uptake yield and emission characteristics of radioisotopes. We used an in vitro model to compare the impact of cellular uptake of (188)Re-perrhenate and (99m)Tc-pertechnetate on cellular survival. Rat thyroid PC Cl3 cells in culture were incubated with (188)Re or (99m)Tc in the presence or absence of perchlorate for 1 hour. Clonogenic cell survival was measured by colony formation. In addition, intracellular radionuclide uptake was quantified. Dose effect curves were established for (188)Re and (99m)Tc for various extra- and intracellular distributions of the radioactivity. In the presence of perchlorate, no uptake of radionuclides was detected and (188)Re reduced cell survival more efficiently than (99m)Tc. A(37), the activity that is necessary to yield 37% cell survival was 14 MBq/ml for (188)Re and 480 MBq/ml for (99m)Tc. In the absence of perchlorate, both radionuclides showed similar uptakes; however, A(37) was reduced by 30% for the beta-emitter and by 95% for (99m)Tc. The dose D(37) that yields 37% cell survival was between 2.3 and 2.8 Gy for both radionuclides. Uptake of (188)Re and (99m)Tc decreased cell survival. Intracellular (99m)Tc yielded a dose increase that was higher compared to (188)Re due to emitted Auger and internal conversion-electrons. Up to 5 Gy there was no difference in radiotoxicity of (188)Re and (99m)Tc. At doses higher than 5 Gy intracellular (99m)Tc became less radiotoxic than (188)Re, probably due to a non-uniform lognormal radionuclide uptake.

The impact of major trauma network triage systems on patients with major burns.

PubMed

Nizamoglu, Metin; O'Connor, Edmund Fitzgerald; Bache, Sarah; Theodorakopoulou, Evgenia; Sen, Sankhya; Sherren, Peter; Barnes, David; Dziewulski, Peter

2016-12-01

Trauma is a leading cause of death and disability worldwide. Patients presenting with severe trauma and burns benefit from specifically trained multidisciplinary teams. Regional trauma systems have shown improved outcomes for trauma patients. The aim of this study is to determine whether the development of major trauma systems have improved the management of patients with major burns. A retrospective study was performed over a four-year period reviewing all major burns in adults and children received at a regional burns centre in the UK before and after the implementation of the regional trauma systems and major trauma centres (MTC). Comparisons were drawn between three areas: (1) Patients presenting before the introduction of MTC and after the introduction of MTC. (2) Patients referred from MTC and non-MTC within the region, following the introduction of MTC. (3) Patients referred using the urban trauma protocol and the rural trauma protocol. Following the introduction of regional trauma systems and major trauma centres (MTC), isolated burn patients seen at our regional burns centre did not show any significant improvement in transfer times, admission resuscitation parameters, organ dysfunction or survival when referred from a MTC compared to a non-MTC emergency department. There was also no significant difference in survival when comparing referrals from all hospitals pre and post establishment of the major trauma network. No significant outcome benefit was demonstrated for burns patients referred via MTCs compared to non-MTCs. We suggest further research is needed to ascertain whether burns patients benefit from prolonged transfer times to a MTC compared to those seen at their local hospitals prior to transfer to a regional burns unit for further specialist care. Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.

Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

PubMed Central

Shahnaz, Gul; Edagwa, Benson J; McMillan, JoEllyn; Akhtar, Sohail; Raza, Abida; Qureshi, Naveeda A; Yasinzai, Masoom; Gendelman, Howard E

2017-01-01

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized. Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities. Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug. Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages. PMID:27879160

Dose calibrator linearity test: 99mTc versus 18F radioisotopes*

PubMed Central

Willegaignon, José; Sapienza, Marcelo Tatit; Coura-Filho, George Barberio; Garcez, Alexandre Teles; Alves, Carlos Eduardo Gonzalez Ribeiro; Cardona, Marissa Anabel Rivera; Gutterres, Ricardo Fraga; Buchpiguel, Carlos Alberto

2015-01-01

Objective The present study was aimed at evaluating the viability of replacing 18F with 99mTc in dose calibrator linearity testing. Materials and Methods The test was performed with sources of 99mTc (62 GBq) and 18F (12 GBq) whose activities were measured up to values lower than 1 MBq. Ratios and deviations between experimental and theoretical 99mTc and 18F sources activities were calculated and subsequently compared. Results Mean deviations between experimental and theoretical 99mTc and 18F sources activities were 0.56 (± 1.79)% and 0.92 (± 1.19)%, respectively. The mean ratio between activities indicated by the device for the 99mTc source as measured with the equipment pre-calibrated to measure 99mTc and 18F was 3.42 (± 0.06), and for the 18F source this ratio was 3.39 (± 0.05), values considered constant over the measurement time. Conclusion The results of the linearity test using 99mTc were compatible with those obtained with the 18F source, indicating the viability of utilizing both radioisotopes in dose calibrator linearity testing. Such information in association with the high potential of radiation exposure and costs involved in 18F acquisition suggest 99mTc as the element of choice to perform dose calibrator linearity tests in centers that use 18F, without any detriment to the procedure as well as to the quality of the nuclear medicine service. PMID:25798005

A comparison of rat SPECT images obtained using (99m)Tc derived from 99Mo produced by an electron accelerator with that from a reactor.

PubMed

Galea, R; Wells, R G; Ross, C K; Lockwood, J; Moore, K; Harvey, J T; Isensee, G H

2013-05-07

Recent shortages of molybdenum-99 ((99)Mo) have led to an examination of alternate production methods that could contribute to a more robust supply. An electron accelerator and the photoneutron reaction were used to produce (99)Mo from which technetium-99m ((99m)Tc) is extracted. SPECT images of rat anatomy obtained using the accelerator-produced (99m)Tc with those obtained using (99m)Tc from a commercial generator were compared. Disks of (100)Mo were irradiated with x-rays produced by a 35 MeV electron beam to generate about 1110 MBq (30 mCi) of (99)Mo per disk. After target dissolution, a NorthStar ARSII unit was used to separate the (99m)Tc, which was subsequently used to tag pharmaceuticals suitable for cardiac and bone imaging. SPECT images were acquired for three rats and compared to images for the same three rats obtained using (99m)Tc from a standard reactor (99)Mo generator. The efficiency of (99)Mo-(99m)Tc separation was typically greater than 90%. This study demonstrated the delivery of (99m)Tc from the end of beam to the end user of approximately 30 h. Images obtained using the heart and bone scanning agents using reactor and linac-produced (99m)Tc were comparable. High-power electron accelerators are an attractive option for producing (99)Mo on a national scale.

Testing Eurasian wild boar piglets for serum antibodies against Mycobacterium bovis.

PubMed

Che' Amat, A; González-Barrio, D; Ortiz, J A; Díez-Delgado, I; Boadella, M; Barasona, J A; Bezos, J; Romero, B; Armenteros, J A; Lyashchenko, K P; Venteo, A; Rueda, P; Gortázar, C

2015-09-01

Animal tuberculosis (TB) caused by infection with Mycobacterium bovis and closely related members of the M. tuberculosis complex (MTC), is often reported in the Eurasian wild boar (Sus scrofa). Tests detecting antibodies against MTC antigens are valuable tools for TB monitoring and control in suids. However, only limited knowledge exists on serology test performance in 2-6 month-old piglets. In this age-class, recent infections might cause lower antibody levels and lower test sensitivity. We examined 126 wild boar piglets from a TB-endemic site using 6 antibody detection tests in order to assess test performance. Bacterial culture (n=53) yielded a M. bovis infection prevalence of 33.9%, while serum antibody prevalence estimated by different tests ranged from 19% to 38%, reaching sensitivities between 15.4% and 46.2% for plate ELISAs and between 61.5% and 69.2% for rapid immunochromatographic tests based on dual path platform (DPP) technology. The Cohen kappa coefficient of agreement between DPP WTB (Wildlife TB) assay and culture results was moderate (0.45) and all other serological tests used had poor to fair agreements. This survey revealed the ability of several tests for detecting serum antibodies against the MTC antigens in 2-6 month-old naturally infected wild boar piglets. The best performance was demonstrated for DPP tests. The results confirmed our initial hypothesis of a lower sensitivity of serology for detecting M. bovis-infected piglets, as compared to older wild boar. Certain tests, notably the rapid animal-side tests, can contribute to TB control strategies by enabling the setup of test and cull schemes or improving pre-movement testing. However, sub-optimal test performance in piglets as compared to that in older wild boar should be taken into account. Copyright © 2015 Elsevier B.V. All rights reserved.

Midwest Transportation Consortium : 2004-2005 annual report.

DOT National Transportation Integrated Search

2005-01-01

Introduction: The Midwest Transportation Consortium (MTC) recently completed its sixth year of : operation. The MTC has become an established portion of the research and educational : programs at ISU and its partner universities. The MTC continues to...

Technetium-99m generator system

DOEpatents

Mirzadeh, S.; Knapp, F.F. Jr.; Collins, E.D.

1998-06-30

A {sup 99}Mo/{sup 99m}Tc generator system includes a sorbent column loaded with a composition containing {sup 99}Mo. The sorbent column has an effluent end in fluid communication with an anion-exchange column for concentrating {sup 99m}Tc eluted from the sorbent column. A method of preparing a concentrated solution of {sup 99m}Tc includes the general steps of: (a) providing a sorbent column loaded with a composition containing {sup 99}Mo, the sorbent column having an effluent end in fluid communication with an anion-exchange column; (b) eluting the sorbent column with a salt solution to elute {sup 99m}Tc from the sorbent and to trap and concentrate the eluted {sup 99m}Tc on the ion-exchange column; and (c) eluting the concentrated {sup 99m}Tc from the ion-exchange column with a solution comprising a reductive complexing agent. 1 fig.

Enhanced detection of tuberculous mycobacteria in animal tissues using a semi-nested probe-based real-time PCR.

PubMed

Costa, Pedro; Ferreira, Ana S; Amaro, Ana; Albuquerque, Teresa; Botelho, Ana; Couto, Isabel; Cunha, Mónica V; Viveiros, Miguel; Inácio, João

2013-01-01

Bovine tuberculosis has been tackled for decades by costly eradication programs in most developed countries, involving the laboratory testing of tissue samples from allegedly infected animals for detection of Mycobacterium tuberculosis complex (MTC) members, namely Mycobacterium bovis. Definitive diagnosis is usually achieved by bacteriological culture, which may take up to 6-12 weeks, during which the suspect animal carcass and herd are under sanitary arrest. In this work, a user-friendly DNA extraction protocol adapted for tissues was coupled with an IS6110-targeted semi-nested duplex real-time PCR assay to enhance the direct detection of MTC bacteria in animal specimens, reducing the time to achieve a diagnosis and, thus, potentially limiting the herd restriction period. The duplex use of a novel β-actin gene targeted probe, with complementary targets in most mammals, allowed the assessment of amplification inhibitors in the tissue samples. The assay was evaluated with a group of 128 fresh tissue specimens collected from bovines, wild boars, deer and foxes. Mycobacterium bovis was cultured from 57 of these samples. Overall, the full test performance corresponds to a diagnostic sensitivity and specificity of 98.2% (CIP95% 89.4-99.9%) and 88.7% (CIP95% 78.5-94.7%), respectively. An observed kappa coefficient was estimated in 0.859 (CI P95% 0.771-0.948) for the overall agreement between the semi-nested PCR assay and the bacteriological culture. Considering only bovine samples (n = 69), the diagnostic sensitivity and specificity were estimated in 100% (CIP95% 84.0-100%) and 97.7% (CIP95% 86.2-99.9%), respectively. Eight negative culture samples exhibiting TB-like lesions were detected by the semi-nested real-time PCR, thus emphasizing the increased potential of this molecular approach to detect MTC-infected animal tissues. This novel IS6110-targeted assay allows the fast detection of tuberculous mycobacteria in animal specimens with very high sensitivity and specificity, being amenable and cost effective for use in the routine veterinary diagnostic laboratory with further automation possibilities.

Simultaneous 99mtc/111in spect reconstruction using accelerated convolution-based forced detection monte carlo

NASA Astrophysics Data System (ADS)

Karamat, Muhammad I.; Farncombe, Troy H.

2015-10-01

Simultaneous multi-isotope Single Photon Emission Computed Tomography (SPECT) imaging has a number of applications in cardiac, brain, and cancer imaging. The major concern however, is the significant crosstalk contamination due to photon scatter between the different isotopes. The current study focuses on a method of crosstalk compensation between two isotopes in simultaneous dual isotope SPECT acquisition applied to cancer imaging using 99mTc and 111In. We have developed an iterative image reconstruction technique that simulates the photon down-scatter from one isotope into the acquisition window of a second isotope. Our approach uses an accelerated Monte Carlo (MC) technique for the forward projection step in an iterative reconstruction algorithm. The MC estimated scatter contamination of a radionuclide contained in a given projection view is then used to compensate for the photon contamination in the acquisition window of other nuclide. We use a modified ordered subset-expectation maximization (OS-EM) algorithm named simultaneous ordered subset-expectation maximization (Sim-OSEM), to perform this step. We have undertaken a number of simulation tests and phantom studies to verify this approach. The proposed reconstruction technique was also evaluated by reconstruction of experimentally acquired phantom data. Reconstruction using Sim-OSEM showed very promising results in terms of contrast recovery and uniformity of object background compared to alternative reconstruction methods implementing alternative scatter correction schemes (i.e., triple energy window or separately acquired projection data). In this study the evaluation is based on the quality of reconstructed images and activity estimated using Sim-OSEM. In order to quantitate the possible improvement in spatial resolution and signal to noise ratio (SNR) observed in this study, further simulation and experimental studies are required.

Development of a patient-specific dosimetry estimation system in nuclear medicine examination

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

Lin, H. H.; Dong, S. L.; Yang, H. J.

2011-07-01

The purpose of this study is to develop a patient-specific dosimetry estimation system in nuclear medicine examination using a SimSET-based Monte Carlo code. We added a dose deposition routine to store the deposited energy of the photons during their flights in SimSET and developed a user-friendly interface for reading PET and CT images. Dose calculated on ORNL phantom was used to validate the accuracy of this system. The S values for {sup 99m}Tc, {sup 18}F and {sup 131}I obtained by the system were compared to those from the MCNP4C code and OLINDA. The ratios of S values computed by thismore » system to those obtained with OLINDA for various organs were ranged from 0.93 to 1.18, which are comparable to that obtained from MCNP4C code (0.94 to 1.20). The average ratios of S value were 0.99{+-}0.04, 1.03{+-}0.05, and 1.00{+-}0.07 for isotopes {sup 131}I, {sup 18}F, and {sup 99m}Tc, respectively. The simulation time of SimSET was two times faster than MCNP4C's for various isotopes. A 3D dose calculation was also performed on a patient data set with PET/CT examination using this system. Results from the patient data showed that the estimated S values using this system differed slightly from those of OLINDA for ORNL phantom. In conclusion, this system can generate patient-specific dose distribution and display the isodose curves on top of the anatomic structure through a friendly graphic user interface. It may also provide a useful tool to establish an appropriate dose-reduction strategy to patients in nuclear medicine environments. (authors)« less

Medullary thyroid cancer: the functions of raf-1 and human achaete-scute homologue-1.

PubMed

Chen, Herbert; Kunnimalaiyaan, Muthusamy; Van Gompel, Jamie J

2005-06-01

Medullary thyroid cancer (MTC) is a prototypic neuroendocrine tumor of the thyroid C cells. Other than surgery, there are no curative therapies for MTC. In this review, we detail recent studies that suggest that targeting specific signaling pathways may be a viable strategy to control MTC tumor progression. Specifically, we discuss the role of the raf-1 and achaete-scute homologue-1 pathways in the MTC tumor growth and differentiation.

Evaluation of technetium-99m decay on Escherichia coli inactivation: effects of physical or chemical agents.

PubMed Central

Silva, C. R.; Valsa, J. O.; Caniné, M. S.; Caldeira-de-Araújo, A.; Bernardo-Filho, M.

1998-01-01

Technetium-99m (99mTc) has been used in nuclear medicine and in biomedical research to label molecular and cellular structures employed as radiotracers. Here, we have evaluated, on a DNA repair proficient Escherichia coli strain, the 99mTc decay inactivation and the influence of the (i) pre-treatment with metal ion chelators or of the (ii) treatment with a free radical scavenger on the protection of the cells against the lethal effect of the 99mTc. As SnCl2 is frequently used as a reducing agent in the 99mTc-labeling process, we have also studied the capability of SnCl2 to alter the biological effects induced by the 99mTc decay. As we are exposed to either chemical or physical agents in the nature, we have decided to study a possible influence of the ultraviolet solar radiation in the biological phenomena induced by the 99mTc decay. Our data point out (i) a very important role of the Auger and/or conversion electrons in the cytotoxicity induced by the 99mTc decay; (ii) SnCl2, the metal ion chelators and the free radical scavenger protect the cells against the lethal effect of the 99mTc; and (iii) near-UV does not alter the lethal effect of the 99mTc decay. PMID:9713950

A new approach for manufacturing and processing targets to produce 99mTc with cyclotrons

NASA Astrophysics Data System (ADS)

Matei, L.; McRae, G.; Galea, R.; Niculae, D.; Craciun, L.; Leonte, R.; Surette, G.; Langille, S.; Louis, C. St.; Gelbart, W.; Abeysekera, B.; Johnson, R. R.

2017-06-01

The most important radioisotope for nuclear medicine is 99mTc. After the supply crisis of 99Mo starting in 2008, the availability of 99mTc became a worldwide concern. Alternative methods for producing the medical imaging isotope 99mTc are actively being developed around the world. The reaction 100Mo(p, 2n)99mTc provides a direct route that can be incorporated into routine production in nuclear medicine centers that possess medical cyclotrons for production of other isotopes, such as those used for Positron Emission Tomography. This paper describes a new approach for manufacturing targets for the (p, 2n) nuclear reaction on 100Mo and the foundation for the subsequent commercial separation and purification of the 99mTc produced. Two designs of targets are presented. The targets used to produce 99mTc are subject to a number of operational constraints.They must withstand the temperatures generated by the irradiation, accommodate temperature gradients from cooling system of the target, must be resilient and must be easily post-processed to separate the 99mTc. After irradiation, the separation of Tc from Mo was carried out using an innovative two-step approach. The process described in this paper can be automated with modules that easily fit in standard production hot cells found in nuclear medicine facilities.

Development of (99m)Tc-Labeled Pyridyl Benzofuran Derivatives To Detect Pancreatic Amylin in Islet Amyloid Model Mice.

PubMed

Yoshimura, Masashi; Ono, Masahiro; Watanabe, Hiroyuki; Kimura, Hiroyuki; Saji, Hideo

2016-06-15

While islet amyloid deposition comprising amylin is one of pathological hallmarks of type 2 diabetes mellitus (T2DM), no useful amylin-imaging probe has been reported. In this study, we evaluated two (99m)Tc-labeled pyridyl benzofuran derivatives as novel amylin-imaging probes using the newly established islet amyloid model mouse. Binding experiments in vitro demonstrated that [(99m)Tc]1 displayed a higher affinity for amylin aggregates than [(99m)Tc]2. Autoradiographic studies using human pancreas sections with T2DM revealed that [(99m)Tc]1 clearly labeled islet amyloid in T2DM pancreatic sections, while [(99m)Tc]2 did not. Although the initial uptake of [(99m)Tc]1 by the normal mouse pancreas was low (0.74%ID/g at 2 min post-injection), [(99m)Tc]1 showed higher retention in the model mouse pancreas than that of the normal mouse, and exhibited strong binding to amylin aggregates in the living pancreas of the model mice. These results suggest that [(99m)Tc]1 is a potential imaging probe targeting islet amyloids in the T2DM pancreas.

Histone Deacetylase Inhibitors: A Novel Therapeutic Weapon Against Medullary Thyroid Cancer?

PubMed

Damaskos, Christos; Garmpis, Nikolaos; Valsami, Serena; Spartalis, Eleftherios; Antoniou, Efstathios A; Tomos, Periklis; Karamaroudis, Stefanos; Zoumpou, Theofano; Pergialiotis, Vasilios; Stergios, Konstantinos; Michaelides, Constantinos; Kontzoglou, Konstantinos; Perrea, Despina; Nikiteas, Nikolaos; Dimitroulis, Dimitrios

2016-10-01

Medullary thyroid cancer (MTC) is highly malignant, metastatic and recurrent, remaining generally incurable, and responsible for approximately 14% of all thyroid carcinoma-related deaths. MTC can metastasize to lymph nodes, trachea and distant organs, such as brain, lungs, liver and bones. MTC cells are resistant to chemotherapy and traditional external therapies are not showing definite clinical benefits. Scientists are trying to understand the molecular background of carcinogenesis and histone deacetylase (HDAC) seems to play a potential role to gene transcription. On the other hand, HDAC inhibitors (HDACI) hamper the HDAC action giving promising results as new anticancer drugs. The purpose of this review was to evaluate the current status of research considering the role of HDACIs in MTC treatment and to present the latest trends in MTC treatment protocols. This literature review was accomplished using the MEDLINE database. The key words/phrases were; HDACI, medullary thyroid cancer, HDACI in the therapy of neuroendocrine tumors, HDACI in MTC. Forty-one articles were selected from the total number of the search's results. Only sixteen papers focus on the use of HDACIs in the treatment of MTC. In order to extract our conclusions, we took into account some studies whose main topic does not strictly refer to the MTC but they contain noteworthy and useful information. Only English articles published up to August 2016 were assessed and used for writing this review. Molecules, such as valproid acid (VPA), vorinostat, suberoyl bis-hydroxamic acid (SBHA), depsipeptide, belinostat, m-carboxycinnamic acid bis-hydroxamine (CBHA) and AB3 have shown promising antitumor effects against MTC. HDACIs represent a promising field for targeted therapy both for its anticancer properties, as well as for augmenting radiotherapeutic modalities. More trials are needed. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-12-01

Cyclotron-produced 99mTc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99mTc. However, the small amount of 92-98Mo in the irradiation of enriched 100Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

Improving core surgical training in a major trauma centre.

PubMed

Morris, Daniel L J; Bryson, David J; Ollivere, Ben J; Forward, Daren P

2016-06-01

English Major Trauma Centres (MTCs) were established in April 2012. Increased case volume and complexity has influenced trauma and orthopaedic (T&O) core surgical training in these centres. To determine if T&O core surgical training in MTCs meets Joint Committee on Surgical Training (JCST) quality indicators including performance of T&O operative procedures and consultant supervised session attendance. An audit cycle assessing the impact of a weekly departmental core surgical trainee rota. The rota included allocated timetabled sessions that optimised clinical and surgical learning opportunities. Intercollegiate Surgical Curriculum Programme (ISCP) records for T&O core surgical trainees at a single MTC were analysed for 8 months pre and post rota introduction. Outcome measures were electronic surgical logbook evidence of leading T&O operative procedures and consultant validated work-based assessments (WBAs). Nine core surgical trainees completed a 4 month MTC placement pre and post introduction of the core surgical trainee rota. Introduction of core surgical trainee rota significantly increased the mean number of T&O operative procedures led by a core surgical trainee during a 4 month MTC placement from 20.2 to 34.0 (p<0.05). The mean number of hip hemiarthroplasty procedures led by a core surgical trainee during a 4 month MTC placement was significantly increased (0.3 vs 2.4 [p=0.04]). Those of dynamic hip screw fixation (2.3 vs 3.6) and ankle fracture fixation (0.7 vs 1.6) were not. Introduction of a core surgical trainee rota significantly increased the mean number of consultant validated WBAs completed by a core surgical trainee during a 4 month MTC placement from 1.7 to 6.6 (p<0.0001). Introduction of a departmental core surgical trainee rota utilising a 'problem-based' model can significantly improve T&O core surgical training in MTCs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight

PubMed Central

Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels. PMID:28817602

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

PubMed

Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

Evaluation of the Speed-oligo Direct Mycobacterium tuberculosis Assay for Molecular Detection of Mycobacteria in Clinical Respiratory Specimens

PubMed Central

Lara-Oya, Ana; Mendoza-Lopez, Pablo; Rodriguez-Granger, Javier; Fernández-Sánchez, Ana María; Bermúdez-Ruiz, María Pilar; Toro-Peinado, Inmaculada; Palop-Borrás, Begoña; Navarro-Marí, Jose María

2013-01-01

We present the first evaluation of a novel molecular assay, the Speed-oligo Direct Mycobacterium tuberculosis (SO-DMT) assay, which is based on PCR combined with a dipstick for the detection of mycobacteria and the specific identification of M. tuberculosis complex (MTC) in respiratory specimens. A blind evaluation was carried out in two stages: first, under experimental conditions on convenience samples comprising 20 negative specimens, 44 smear- and culture-positive respiratory specimens, and 11 sputa inoculated with various mycobacterium-related organisms; and second, in the routine workflow of 566 fresh respiratory specimens (4.9% acid-fast bacillus [AFB] smear positives, 7.6% MTC positives, and 1.8% nontuberculous mycobacteria [NTM] culture positives) from two Mycobacterium laboratories. SO-DMT assay showed no reactivity in any of the mycobacterium-free specimens or in those with mycobacterium-related organisms. Compared to culture, the sensitivity in the selected smear-positive specimens was 0.91 (0.92 for MTC and 0.90 for NTM), and there was no molecular detection of NTM in a tuberculosis case or vice versa. With respect to culture and clinical data, the sensitivity, specificity, and positive and negative predictive values for the SO-DMT system in routine specimens were 0.76 (0.93 in smear positives [1.0 for MTC and 0.5 for NTM] and 0.56 in smear negatives [0.68 for MTC and 0.16 for NTM]), 0.99, 0.85 (1.00 in smear positives and 0.68 in smear negatives), and 0.97, respectively. Molecular misidentification of NTM cases occurred when testing 2 gastric aspirates from two children with clinically but not microbiologically confirmed lung tuberculosis. The SO-DMT assay appears to be a fast and easy alternative for detecting mycobacteria and differentiating MTC from NTM in smear-positive respiratory specimens. PMID:23100355

The correlation between effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) with renal scintigraphy 99mTc-DTPA study

NASA Astrophysics Data System (ADS)

Ratnasari, D.; Nazir, F.; Toresano, L. O. H. Z.; Pawiro, S. A.; Soejoko, D. S.

2016-03-01

The prevalence of chronic renal diseases in Indonesia has an increasing annual trend, because it is frequently unrecognized and often co-exists with other disease. GFR and ERPF are parameters currently utilized to estimate renal function at routine renal scintigraphy 99m-Tc DTPA study. This study used 99m-Tc DTPA to measure GFR and ERPF. The purpose of this study was to find the correlation between ERPF and GFR, for ERPF analysis with Schlegel's method, and GFR analysis with Gate's method, as well as to find correction factor between both variables. Analysis of renal scintigraphy has been performed at Department of Nuclear Medicine Pertamina Center Hospital to thirty patient images acquired from 2014 to 2015 which were analyzed retrospectively data, using gamma camera dual head with counting method from renal scintigraphy 99m-Tc DTPA study. The calculation was executed by means of both display and manual calculation. Pearson's statistical analysis resulted on Positive Correlation for all data, with ERPF and GFR (display) showing Strongly Positive Correlation (r = 0.82; p- value < 0.05). Standard deviation was found to be 27.58 and 107.64 for GFR and ERPF (display), respectively. Our result indicated that the use of 99mTc-DTPA measure ERPF was not recommended.

Exploring Mechanisms of Effective Teacher Coaching: A Tale of Two Cohorts From a Randomized Experiment

ERIC Educational Resources Information Center

Blazar, David; Kraft, Matthew A.

2015-01-01

Although previous research has shown that teacher coaching can improve teaching practices and student achievement, little is known about specific features of effective coaching programs. We estimate the impact of MATCH Teacher Coaching (MTC) on a range of teacher practices using a blocked randomized trial and explore how changes in the coaching…

Management of hip fractures pre- and post-Major Trauma Centre activation.

PubMed

Wong, Ken; Rich, James; Yip, Grace; Loizou, Constantinos; Hull, Peter

2015-10-01

In April 2012, the activation of the regional trauma networks in England was carried out to improve the organisation of trauma care. NHS Trusts that could meet the highest standard of care to complex trauma were designated Major Trauma Centres (MTCs). MTCs receive patients fulfilling certain triage criteria, as well as secondary transfers from nearby trauma units. While complex trauma care is streamlined with this new organisation, the impact this would have on the rest of the trauma workload within MTCs as well as non-MTC hospitals is uncertain. We investigate whether the management of hip fracture cases had suffered as a result of a trauma unit becoming a MTC. Summary data was collated from the National Hip Fracture Database website for the periods of April 2011-April 2012 (the 'pre-MTC' activation period) and April 2012-April 2013 (the 'post-MTC' activation period). As our primary outcome, we compared the time to surgery within 36h between MTCs and non-MTCs for the periods detailed above. Other outcome measures were: reasons for delay to surgery, length of acute stay, proportion of cases meeting Best Practice Tariff criteria. A total of 54,897 and 55,998 fNOF patients were included for all hospitals in England in the pre- and post-MTC periods respectively. For MTCs, a weighted mean average of 66.6% patients had surgery within 36h in the pre-MTC period versus 71.4% of patients in the post MTC period (p<0.0001). For non-MTCs, a weighted mean average of 70.0% of patients had surgery within 36h in the pre-MTC period versus 73.8% of patients in the post-MTC period (p<0.0001). Non-MTCs in both pre- and post-MTC activation periods were therefore better in percentage of patients receiving surgery within 36h. The data presented suggests that the creation of MTCs has not had a deleterious effect on the management of hip fracture patients. This paper aims to stimulate the important discussion of maintaining a consistently improving standard throughout the spectrum of trauma care, in conjunction with the development of regional Major Trauma Networks. Copyright © 2015 Elsevier Ltd. All rights reserved.

Epigenetics in Medullary Thyroid Cancer: From Pathogenesis to Targeted Therapy.

PubMed

Vitale, Giovanni; Dicitore, Alessandra; Messina, Erika; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2016-01-01

Medullary thyroid carcinoma (MTC) originates from the parafollicular C cells of the thyroid gland. Mutations of the RET proto-oncogene are implicated in the pathogenesis of MTC. Germline activating mutations of this gene have been reported in about 88-98% of familial MTCs, while somatic mutations of RET gene have been detected in about 23-70% of sporadic forms. Although these genetic events are well characterized, much less is known about the role of epigenetic abnormalities in MTC. The present review reports a detailed description of epigenetic abnormalities (DNA methylation, histone modifications and miRNA profile), probably involved in the pathogenesis and progression of MTC. A systematic review was performed using Pubmed and Google patents databases. We report the current understanding of epigenetic patterns in MTC and discuss the potential use of current knowledge in designing novel therapeutic strategies through epigenetic drugs, focusing on recent patents in this field. Taking into account the reversibility of epigenetic alterations and the recent development in this field, epigenetic therapy may emerge for clinical use in the near future for patients with advanced MTC.

Comparison of internal dose estimates obtained using organ-level, voxel S value, and Monte Carlo techniques

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

Grimes, Joshua, E-mail: grimes.joshua@mayo.edu; Celler, Anna

2014-09-15

Purpose: The authors’ objective was to compare internal dose estimates obtained using the Organ Level Dose Assessment with Exponential Modeling (OLINDA/EXM) software, the voxel S value technique, and Monte Carlo simulation. Monte Carlo dose estimates were used as the reference standard to assess the impact of patient-specific anatomy on the final dose estimate. Methods: Six patients injected with{sup 99m}Tc-hydrazinonicotinamide-Tyr{sup 3}-octreotide were included in this study. A hybrid planar/SPECT imaging protocol was used to estimate {sup 99m}Tc time-integrated activity coefficients (TIACs) for kidneys, liver, spleen, and tumors. Additionally, TIACs were predicted for {sup 131}I, {sup 177}Lu, and {sup 90}Y assuming themore » same biological half-lives as the {sup 99m}Tc labeled tracer. The TIACs were used as input for OLINDA/EXM for organ-level dose calculation and voxel level dosimetry was performed using the voxel S value method and Monte Carlo simulation. Dose estimates for {sup 99m}Tc, {sup 131}I, {sup 177}Lu, and {sup 90}Y distributions were evaluated by comparing (i) organ-level S values corresponding to each method, (ii) total tumor and organ doses, (iii) differences in right and left kidney doses, and (iv) voxelized dose distributions calculated by Monte Carlo and the voxel S value technique. Results: The S values for all investigated radionuclides used by OLINDA/EXM and the corresponding patient-specific S values calculated by Monte Carlo agreed within 2.3% on average for self-irradiation, and differed by as much as 105% for cross-organ irradiation. Total organ doses calculated by OLINDA/EXM and the voxel S value technique agreed with Monte Carlo results within approximately ±7%. Differences between right and left kidney doses determined by Monte Carlo were as high as 73%. Comparison of the Monte Carlo and voxel S value dose distributions showed that each method produced similar dose volume histograms with a minimum dose covering 90% of the volume (D90) agreeing within ±3%, on average. Conclusions: Several aspects of OLINDA/EXM dose calculation were compared with patient-specific dose estimates obtained using Monte Carlo. Differences in patient anatomy led to large differences in cross-organ doses. However, total organ doses were still in good agreement since most of the deposited dose is due to self-irradiation. Comparison of voxelized doses calculated by Monte Carlo and the voxel S value technique showed that the 3D dose distributions produced by the respective methods are nearly identical.« less

Sorafenib in Japanese Patients with Locally Advanced or Metastatic Medullary Thyroid Carcinoma and Anaplastic Thyroid Carcinoma.

PubMed

Ito, Yasuhiro; Onoda, Naoyoshi; Ito, Ken-Ichi; Sugitani, Iwao; Takahashi, Shunji; Yamaguchi, Iku; Kabu, Koki; Tsukada, Katsuya

2017-09-01

Therapeutic options for treating advanced or metastatic medullary thyroid carcinoma (MTC) and anaplastic thyroid carcinoma (ATC) are still limited in Japan, even though vandetanib for MTC and lenvatinib for MTC and ATC have been approved. Sorafenib is an oral multikinase inhibitor approved for the treatment of patients with radioactive iodine-refractory differentiated thyroid cancer (DTC). An uncontrolled, open-label, multicenter, single-arm, Phase 2 clinical study was conducted to evaluate the safety and efficacy of sorafenib in Japanese patients with MTC and ATC. Japanese patients with histologically confirmed ATC and locally advanced or metastatic MTC were enrolled from April to September 2014. The primary endpoint was to evaluate the safety of sorafenib. Treatment efficacy variables including progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and maximum reduction in tumor size were evaluated as secondary endpoints. Patients received sorafenib 400 mg orally twice daily on a continuous basis and then continued treatment until the occurrence of disease progression, unacceptable toxicity, or withdrawal of consent. A total of 20 patients were screened, and 18 (8 with MTC and 10 with ATC) were enrolled. The most common drug-related adverse events were palmar-plantar erythrodysesthesia (72%), alopecia (56%), hypertension (56%), and diarrhea (44%). In the ATC patients, median PFS was 2.8 months [confidence interval 0.7-5.6], and median OS was 5.0 months [confidence interval 0.7-5.7]; ORR and DCR were 0% and 40%, respectively. In the MTC population, neither median PFS nor OS had been reached at the time of this analysis; ORR was 25% and DCR was 75%. The toxicities reported in this study were consistent with the known safety profile of sorafenib. Sorafenib seems to be effective in the treatment of advanced MTC but not ATC, and could be a new treatment option for locally advanced or metastatic MTC and radioactive iodine-refractory DTC.

On-resonance Variable Delay Multi Pulse Scheme for Imaging of Fast-exchanging Protons and semi-solid Macromolecules

PubMed Central

Xu, Jiadi; Chan, Kannie W.Y.; Xu, Xiang; Yadav, Nibhay; Liu, Guanshu; van Zijl, Peter C. M.

2016-01-01

Purpose To develop an on-resonance variable delay multi-pulse (VDMP) scheme to image magnetization transfer contrast (MTC) as well as the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above about 1 kHz. Methods A train of high power binomial pulses was applied at the water resonance. The inter-pulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions due to their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T2 components in MTC and separated out using a variable mixing time. Results Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA) and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method showing strong gray/white matter contrast for the slowly transferring MTC protons while the TFP map was more uniform across the brain but somewhat higher in gray matter. Conclusions The new method provides a simple way of imaging fast-exchanging protons, as well as MTC components with a slow transfer rate. PMID:26900759

Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG-->ATG) mutation.

PubMed

Feldman, G L; Edmonds, M W; Ainsworth, P J; Schuffenecker, I; Lenoir, G M; Saxe, A W; Talpos, G B; Roberson, J; Petrucelli, N; Jackson, C E

2000-07-01

Multiple endocrine neoplasia type 2 (MEN 2) and familial medullary thyroid carcinoma (FMTC) are autosomal dominantly inherited cancer syndromes that predispose to C-cell hyperplasia and MTC. MEN 2A and FMTC are caused by mutations in the RET proto-oncogene. We used a multiplex polymerase chain reaction-based assay to screen exons 10, 11, 13, and 14 of RET for mutations in 2 families with FMTC. We correlated mutation status with calcitonin and pathologic studies to determine genotype-phenotype correlations. We identified a mutation in codon 804 in exon 14 (GTG-->ATG; V804M) in both families. An 86-year-old person who was a gene carrier and other individuals over age 70 who were suspected by pedigree analysis to be gene carriers had no overt clinical evidence of MTC. Four of 21 patients who underwent a thyroidectomy also had papillary thyroid cancer. One individual in each family had metastatic MTC at age 30 and 32 years, and all 26 people having thyroidectomies had either MTC or C-cell hyperplasia, leading us to continue to recommend prophylactic thyroidectomy for all identified patients who were gene carriers. Because of active MTC in younger members of these families, including metastases, we have continued to advocate thyroid surgery in mutation-positive individuals. While DNA diagnosis of gene carriers and subsequent genetic counseling was relatively straightforward, the acceptance of surgical recommendations was more difficult for some individuals. These families demonstrate that the search for RET mutations should include exons 13, 14, 15, and 16 in patients whose studies in exons 10 and 11 are negative.

Basal Serum Calcitonin, After Calcium Stimulation, and in the Needle Washout of Patients with Thyroid Nodules and Mild or Moderate Basal Hypercalcitoninemia.

PubMed

Rosario, P W; Calsolari, M R

2017-02-01

This prospective study evaluated the concentrations of basal serum calcitonin (Ctn), Ctn after stimulation with calcium, and Ctn in the needle washout (FNA-Ctn) as predictors of sporadic medullary thyroid carcinoma (MTC) in patients with thyroid nodules and basal Ctn between 10 and 100 pg/ml. Forty-one patients were included in the study. MTC was diagnosed in only 6 patients (14.6%). None of the patients with basal Ctn≤24.6 pg/ml (n=26) or stimulated Ctn≤186.5 pg/ml (n=21) had MTC. All patients without MTC had basal Ctn<47 pg/ml and stimulated Ctn<655.2 pg/ml. Among patients with basal Ctn between 24.6 and 47 pg/ml (n=12), 3 (25%) had MTC. Among patients with stimulated Ctn between 186.5 and 655.2 pg/ml (n=18), 4 (22.2%) had MTC. FNA-Ctn distinguished nodules that were MTC (n=6) from those that were not (n=60), without overlapping results. In the calcium stimulation test, 19 patients (46.3%) reported some adverse effect, but none of them was severe or required specific treatment. Our results highlight that in patients without a history suspicious for MTC, mild or moderate basal hypercalcitoninemia should not establish the diagnosis of this tumor. Depending on the concentration found, basal Ctn should be sufficient to define patient management. In doubtful cases, FNA-Ctn seems to be the best diagnostic test. Calcium stimulation testing was safe, but more studies are needed to determine the Ctn cutoff after stimulation with calcium. © Georg Thieme Verlag KG Stuttgart · New York.

Impact of Indocyanine Green for Sentinel Lymph Node Mapping in Early Stage Endometrial and Cervical Cancer: Comparison with Conventional Radiotracer (99m)Tc and/or Blue Dye.

PubMed

Buda, Alessandro; Crivellaro, Cinzia; Elisei, Federica; Di Martino, Giampaolo; Guerra, Luca; De Ponti, Elena; Cuzzocrea, Marco; Giuliani, Daniela; Sina, Federica; Magni, Sonia; Landoni, Claudio; Milani, Rodolfo

2016-07-01

To compare the detection rate (DR) and bilateral optimal mapping (OM) of sentinel lymph nodes (SLNs) in women with endometrial and cervical cancer using indocyanine green (ICG) versus the standard technetium-99m radiocolloid ((99m)Tc) radiotracer plus methylene or isosulfan blue, or blue dye alone. From October 2010 to May 2015, 163 women with stage I endometrial or cervical cancer (118 endometrial and 45 cervical cancer) underwent SLN mapping with (99m)Tc with blue dye, blue dye alone, or ICG. DR and bilateral OM of ICG were compared respectively with the results obtained using the standard (99m)Tc radiotracer with blue dye, or blue dye alone. SLN mapping with (99m)Tc radiotracer with blue dye was performed on 77 of 163 women, 38 with blue dye only and 48 with ICG. The overall DR of SLN mapping was 97, 89, and 100 % for (99m)Tc with blue dye, blue dye alone, and ICG, respectively. The bilateral OM rate for ICG was 85 %-significantly higher than the 58 % obtained with (99m)Tc with blue dye (p = 0.003) and the 54 % for blue dye (p = 0.001). Thirty-one women (19 %) had positive SLNs. Sensitivity and negative predictive value of SLN were 100 % for all techniques. SLNs mapping using ICG demonstrated higher DR compared to other modalities. In addition, ICG was significantly superior to (99m)Tc with blue dye in terms of bilateral OM in women with early stage endometrial and cervical cancer. The higher number of bilateral OM may consequently reduce the overall number of complete lymphadenectomies, reducing the duration and additional costs of surgical treatment.

Risk Profile of the RET A883F Germline Mutation: An International Collaborative Study.

PubMed

Mathiesen, Jes Sloth; Habra, Mouhammed Amir; Bassett, John Howard Duncan; Choudhury, Sirazum Mubin; Balasubramanian, Sabapathy Prakash; Howlett, Trevor A; Robinson, Bruce G; Gimenez-Roqueplo, Anne-Paule; Castinetti, Frederic; Vestergaard, Peter; Frank-Raue, Karin

2017-06-01

The A883F germline mutation of the rearranged during transfection (RET) proto-oncogene causes multiple endocrine neoplasia 2B. In the revised American Thyroid Association (ATA) guidelines for the management of medullary thyroid carcinoma (MTC), the A883F mutation has been reclassified from the highest to the high-risk level, although no well-defined risk profile for this mutation exists. To create a risk profile for the A883F mutation for appropriate classification among the ATA risk levels. Retrospective analysis. International collaboration. Included were 13 A883F carriers. The intervention was thyroidectomy. Earliest age of MTC, regional lymph node metastases, distant metastases, age-related penetrance of MTC and pheochromocytoma (PHEO), overall and disease-specific survival, and biochemical cure rate. One and three carriers were diagnosed at age 7 to 9 years (median, 7.5 years) with a normal thyroid and C-cell hyperplasia, respectively. Nine carriers were diagnosed with MTC at age 10 to 39 years (median, 19 years). The earliest age of MTC, regional lymph node metastasis, and distant metastasis was 10, 20, and 20 years, respectively. Fifty percent penetrance of MTC and PHEO was achieved by age 19 and 34 years, respectively. Five- and 10-year survival rates (both overall and disease specific) were 88% and 88%, respectively. Biochemical cure for MTC at latest follow-up was achieved in 63% (five of eight carriers) with pertinent data. MTC of A883F carriers seems to have a more indolent natural course compared with that of M918T carriers. Our results support the classification of the A883F mutation in the ATA high-risk level. Copyright © 2017 Endocrine Society

67 FR 24495 - United States v. Microsoft Corporation; Public Comments; Notice (MTC-00003461 - MTC-00007629)

Federal Register 2010, 2011, 2012, 2013, 2014

2002-05-03

... (web-serving software), Linux, Perl, and those who are building a compatible & free version of MS`s..., Argument from Design Argument from Design-Web & Multimedia [email protected] http://www.ardes.com MTC-00003464... organization could be a good target for this effort. Their web address is http:// www.gnu.org/. This effort...

The tyrosine kinase inhibitor ZD6474 blocks proliferation of RET mutant medullary thyroid carcinoma cells.

PubMed

Vitagliano, Donata; De Falco, Valentina; Tamburrino, Anna; Coluzzi, Sabrina; Troncone, Giancarlo; Chiappetta, Gennaro; Ciardiello, Fortunato; Tortora, Giampaolo; Fagin, James A; Ryan, Anderson J; Carlomagno, Francesca; Santoro, Massimo

2011-02-01

Oncogenic conversion of the RET tyrosine kinase is a frequent feature of medullary thyroid carcinoma (MTC). ZD6474 (vandetanib) is an ATP-competitive inhibitor of RET, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor receptors kinases. In this study, we have studied ZD6474 mechanism of action in TT and MZ-CRC-1 human MTC cell lines, carrying cysteine 634 to tryptophan (C634W) and methionine 918 to threonine (M918T) RET mutation respectively. ZD6474 blunted MTC cell proliferation and RET, Shc and p44/p42 mitogen-activated protein kinase (MAPK) phosphorylation. Single receptor knockdown by RNA interference showed that MTC cells depended on RET for proliferation. Adoptive expression of the ZD6474-resistant V804M RET mutant rescued proliferation of TT cells under ZD6474 treatment, showing that RET is a key ZD6474 target in these MTC cells. Upon RET inhibition, adoptive stimulation of EGFR partially rescued TT cell proliferation, MAPK signaling, and expression of cell-cycle-related genes. This suggests that simultaneous inhibition of RET and EGFR by ZD6474 may overcome the risk of MTC cells to escape from RET blockade through compensatory over-activation of EGFR.

Surgical strategy for the treatment of sporadic medullary thyroid carcinoma: our experience.

PubMed

Lupone, G; Antonino, A; Rosato, A; Zenone, P; Iervolino, E M; Grillo, M; De Palma, M

2012-01-01

Medullary thyroid carcinoma (MTC) is a rare disease which accounts for approximately 5-9% of all thyroid cancers and originates from the calcitonin-screening parafollicular C cells. MTC can be divided into two subgroups: sporadic (75%) or inherited (25%). The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. The purpose of the study is to review our single institution's experience with MTC since 1998 and to evaluate surgical strategy, patterns of lymph node metastases and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent sporadic medullary thyroid carcinoma. A retrospective review of 26 patients treated for MTC at the "Antonio Cardarelli" Hospital referral center, in Naples, between 1998 and 2012. There were 18 female and 8 male patients, median age at presentation was 55 years, and median follow-up for survivors was 5 years. Total thyroidectomy was performed in all 26 patients; central compartment (CC) node dissection (level VI) in 12 (46%) patients; central plus lateral compartment (LC) node dissection (levels II, III, and IV) in 7 (27%) patients. 4 patients (15%) underwent reoperation for loco-regional recurrent/persistent MTC. Results. After a median post-surgical follow-up of 5 years (range 1-10 years), 63 % of patients were living disease-free, 15% were living with disease and/or persistently elevated calcitonin levels after surgery, 11% were deceased due to MTC and 11 % were lost to follow-up. We agree with most authors advocating for a total thyroidectomy and prophylactic central neck dissection in the setting of clinically detected MTC. Lateral neck dissection may be best reserved for patients with positive preoperative imaging. Nevertheless MTC has a high rate of lymph node metastases that are sub optimally detected preoperatively in the central compartment by neck ultrasound or intra-operatively by the surgeon, and reoperation is associated with a higher rate of surgical complications. In our limited experience, patients with thyroid confined nodular pathology, without nodal disease and unknown preoperative diagnosis of MTC, underwent only total thyroidectomy with a good prognosis.

Wild boar tuberculosis in Iberian Atlantic Spain: a different picture from Mediterranean habitats

PubMed Central

2013-01-01

Background Infections with Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex (MTC) are shared between livestock, wildlife and sporadically human beings. Wildlife reservoirs exist worldwide and can interfere with bovine tuberculosis (TB) eradication efforts. The Eurasian wild boar (Sus scrofa) is a MTC maintenance host in Mediterranean Iberia (Spain and Portugal). However, few systematic studies in wild boar have been carried out in Atlantic regions. We describe the prevalence, distribution, pathology and epidemiology of MTC and other mycobacteria from wild boar in Atlantic Spain. A total of 2,067 wild boar were sampled between 2008 and 2012. Results The results provide insight into the current status of wild boar as MTC and Mycobacterium avium complex (MAC) hosts in temperate regions of continental Europe. The main findings were a low TB prevalence (2.6%), a low proportion of MTC infected wild boar displaying generalized TB lesions (16.7%), and a higher proportion of MAC infections (4.5%). Molecular typing revealed epidemiological links between wild boar and domestic – cattle, sheep and goat – and other wildlife – Eurasian badger (Meles meles) and red fox (Vulpes vulpes) – hosts. Conclusions This study shows that the likelihood of MTC excretion by wild boar in Atlantic habitats is much lower than in Mediterranean areas. However, wild boar provide a good indicator of MTC circulation and, given the current re-emergence of animal TB, similar large-scale surveys would be advisable in other Atlantic regions of continental Europe. PMID:24010539

Novel Multiplex Real-Time PCR Diagnostic Assay for Identification and Differentiation of Mycobacterium tuberculosis, Mycobacterium canettii, and Mycobacterium tuberculosis Complex Strains▿†

PubMed Central

Reddington, Kate; O'Grady, Justin; Dorai-Raj, Siobhan; Maher, Majella; van Soolingen, Dick; Barry, Thomas

2011-01-01

Tuberculosis (TB) in humans is caused by members of the Mycobacterium tuberculosis complex (MTC). Rapid detection of the MTC is necessary for the timely initiation of antibiotic treatment, while differentiation between members of the complex may be important to guide the appropriate antibiotic treatment and provide epidemiological information. In this study, a multiplex real-time PCR diagnostics assay using novel molecular targets was designed to identify the MTC while simultaneously differentiating between M. tuberculosis and M. canettii. The lepA gene was targeted for the detection of members of the MTC, the wbbl1 gene was used for the differentiation of M. tuberculosis and M. canettii from the remainder of the complex, and a unique region of the M. canettii genome, a possible novel region of difference (RD), was targeted for the specific identification of M. canettii. The multiplex real-time PCR assay was tested using 125 bacterial strains (64 MTC isolates, 44 nontuberculosis mycobacteria [NTM], and 17 other bacteria). The assay was determined to be 100% specific for the mycobacteria tested. Limits of detection of 2.2, 2.17, and 0.73 cell equivalents were determined for M. tuberculosis/M. canettii, the MTC, and M. canettii, respectively, using probit regression analysis. Further validation of this diagnostics assay, using clinical samples, should demonstrate its potential for the rapid, accurate, and sensitive diagnosis of TB caused by M. tuberculosis, M. canettii, and the other members of the MTC. PMID:21123525

Glucagon-Like Peptide-1 Receptor Imaging with [Lys (40) (Ahx-HYNIC- (99 m) Tc/EDDA)NH 2 ]-Exendin-4 for the Diagnosis of Recurrence or Dissemination of Medullary Thyroid Cancer: A Preliminary Report.

PubMed

Pach, D; Sowa-Staszczak, A; Jabrocka-Hybel, A; Stefańska, A; Tomaszuk, M; Mikołajczak, R; Janota, B; Trofimiuk-Müldner, M; Przybylik-Mazurek, E; Hubalewska-Dydejczyk, A

2013-01-01

Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22-74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys(40)(Ahx-HYNIC-(99m)Tc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent.

Glucagon-Like Peptide-1 Receptor Imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-Exendin-4 for the Diagnosis of Recurrence or Dissemination of Medullary Thyroid Cancer: A Preliminary Report

PubMed Central

Pach, D.; Sowa-Staszczak, A.; Jabrocka-Hybel, A.; Stefańska, A.; Tomaszuk, M.; Mikołajczak, R.; Janota, B.; Trofimiuk-Müldner, M.; Przybylik-Mazurek, E.; Hubalewska-Dydejczyk, A.

2013-01-01

Introduction. Epidemiological studies on medullary thyroid cancer (MTC) have shown that neither a change in stage at diagnosis nor improvement in survival has occurred during the past 30 years. In patients with detectable serum calcitonin and no clinically apparent disease, a careful search for local recurrence, and nodal or distant metastases, should be performed. Conventional imaging modalities will not show any disease until basal serum calcitonin is at least 150 pg/mL. The objective of the study was to present the first experience with labelled glucagon-like peptide-1 (GLP-1) analogue [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 in the visualisation of MTC in humans. Material and Method. Four patients aged 22–74 years (two with sporadic and two with MEN2 syndrome-related disseminated MTC) were enrolled in the study. In all patients, GLP-1 receptor imaging was performed. Results. High-quality images were obtained in all patients. All previously known MTC lesions have been confirmed in GLP-1 scintigraphy. Moreover, one additional liver lesion was detected in sporadic MTC male patient. Conclusions. GLP-1 receptor imaging with [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 is able to detect MTC lesions. GLP-1 scintigraphy can serve as a confirmatory test in MTC patients, in whom other imaging procedures are inconsistent. PMID:23606839

On-resonance variable delay multipulse scheme for imaging of fast-exchanging protons and semisolid macromolecules.

PubMed

Xu, Jiadi; Chan, Kannie W Y; Xu, Xiang; Yadav, Nirbhay; Liu, Guanshu; van Zijl, Peter C M

2017-02-01

To develop an on-resonance variable delay multipulse (VDMP) scheme to image magnetization transfer contrast (MTC) and the chemical exchange saturation transfer (CEST) contrast of total fast-exchanging protons (TFP) with exchange rate above approximately 1 kHz. A train of high power binomial pulses was applied at the water resonance. The interpulse delay, called mixing time, was varied to observe its effect on the water signal reduction, allowing separation and quantification of MTC and CEST contributions as a result of their different proton transfer rates. The fast-exchanging protons in CEST and MTC are labeled together with the short T 2 components in MTC and separated out using a variable mixing time. Phantom studies of selected metabolite solutions (glucose, glutamate, creatine, myo-inositol), bovine serum albumin (BSA), and hair conditioner show the capability of on-resonance VDMP to separate out exchangeable protons with exchange rates above 1 kHz. Quantitative MTC and TFP maps were acquired on healthy mouse brains using this method, showing strong gray/white matter contrast for the slowly transferring MTC protons, whereas the TFP map was more uniform across the brain but somewhat higher in gray matter. The new method provides a simple way of imaging fast-exchanging protons and MTC components with a slow transfer rate. Magn Reson Med 77:730-739, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Developing and Testing a Scale of Moral Thinking and Communication (MTC) Functioning: A Preliminary Study and Its Implications for Moral Development and Education

ERIC Educational Resources Information Center

Lee, Chi-Ming Angela; Thoma, Stephen J.

2018-01-01

The purpose of this study was to develop and test a scale assessing students' moral thinking and communication (MTC) functioning as well as to explore the implications for moral development and education. The rationale of MTC functioning, including interaction of four independent competencies: moral awareness, moral judgement, moral discourse, and…

IDACstar: A MCNP Application to Perform Realistic Dose Estimations from Internal or External Contamination of Radiopharmaceuticals.

PubMed

Ören, Ünal; Hiller, Mauritius; Andersson, M

2017-04-28

A Monte Carlo-based stand-alone program, IDACstar (Internal Dose Assessment by Computer), was developed, dedicated to perform radiation dose calculations using complex voxel simulations. To test the program, two irradiation situations were simulated, one hypothetical contamination case with 600 MBq of 99mTc and one extravasation case involving 370 MBq of 18F-FDG. The effective dose was estimated to be 0.042 mSv for the contamination case and 4.5 mSv for the extravasation case. IDACstar has demonstrated that dosimetry results from contamination or extravasation cases can be acquired with great ease. An effective tool for radiation protection applications is provided with IDACstar allowing physicists at nuclear medicine departments to easily quantify the radiation risk of stochastic effects when a radiation accident has occurred. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Effects of CT-based attenuation correction of rat microSPECT images on relative myocardial perfusion and quantitative tracer uptake

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

Strydhorst, Jared H., E-mail: jared.strydhorst@gmail.com; Ruddy, Terrence D.; Wells, R. Glenn

2015-04-15

Purpose: Our goal in this work was to investigate the impact of CT-based attenuation correction on measurements of rat myocardial perfusion with {sup 99m}Tc and {sup 201}Tl single photon emission computed tomography (SPECT). Methods: Eight male Sprague-Dawley rats were injected with {sup 99m}Tc-tetrofosmin and scanned in a small animal pinhole SPECT/CT scanner. Scans were repeated weekly over a period of 5 weeks. Eight additional rats were injected with {sup 201}Tl and also scanned following a similar protocol. The images were reconstructed with and without attenuation correction, and the relative perfusion was analyzed with the commercial cardiac analysis software. The absolutemore » uptake of {sup 99m}Tc in the heart was also quantified with and without attenuation correction. Results: For {sup 99m}Tc imaging, relative segmental perfusion changed by up to +2.1%/−1.8% as a result of attenuation correction. Relative changes of +3.6%/−1.0% were observed for the {sup 201}Tl images. Interscan and inter-rat reproducibilities of relative segmental perfusion were 2.7% and 3.9%, respectively, for the uncorrected {sup 99m}Tc scans, and 3.6% and 4.3%, respectively, for the {sup 201}Tl scans, and were not significantly affected by attenuation correction for either tracer. Attenuation correction also significantly increased the measured absolute uptake of tetrofosmin and significantly altered the relationship between the rat weight and tracer uptake. Conclusions: Our results show that attenuation correction has a small but statistically significant impact on the relative perfusion measurements in some segments of the heart and does not adversely affect reproducibility. Attenuation correction had a small but statistically significant impact on measured absolute tracer uptake.« less

Clinical effectiveness and cost-effectiveness of interventions for the treatment of anogenital warts: systematic review and economic evaluation.

PubMed

Thurgar, Elizabeth; Barton, Samantha; Karner, Charlotta; Edwards, Steven J

2016-03-01

Typically occurring on the external genitalia, anogenital warts (AGWs) are benign epithelial skin lesions caused by human papillomavirus infection. AGWs are usually painless but can be unsightly and physically uncomfortable, and affected people might experience psychological distress. The evidence base on the clinical effectiveness and cost-effectiveness of treatments for AGWs is limited. To systematically review the evidence on the clinical effectiveness of medical and surgical treatments for AGWs and to develop an economic model to estimate the cost-effectiveness of the treatments. Electronic databases (MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, The Cochrane Library databases and Web of Science) were searched from inception (or January 2000 for Web of Science) to September 2014. Bibliographies of relevant systematic reviews were hand-searched to identify potentially relevant studies. The World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov were searched for ongoing and planned studies. A systematic review of the clinical effectiveness literature was carried out according to standard methods and a mixed-treatment comparison (MTC) undertaken. The model implemented for each outcome was that with the lowest deviance information criterion. A de novo economic model was developed to assess cost-effectiveness from the perspective of the UK NHS. The model structure was informed through a systematic review of the economic literature and in consultation with clinical experts. Effectiveness data were obtained from the MTC. Costs were obtained from the literature and standard UK sources. Of 4232 titles and abstracts screened for inclusion in the review of clinical effectiveness, 60 randomised controlled trials (RCTs) evaluating 19 interventions were included. Analysis by MTC indicated that ablative techniques were typically more effective than topical interventions at completely clearing AGWs at the end of treatment. Podophyllotoxin 0.5% solution (Condyline(®), Takeda Pharmaceutical Company Ltd; Warticon(®) solution, Stiefel Laboratories Ltd) was found to be the most effective topical treatment evaluated. Networks for other outcomes included fewer treatments, which restrict conclusions on the comparative effectiveness of interventions. In total, 84 treatment strategies were assessed using the economic model. Podophyllotoxin 0.5% solution first line followed by carbon dioxide (CO2) laser therapy second line if AGWs did not clear was most likely to be considered a cost-effective use of resources at a willingness to pay of £20,000-30,000 per additional quality-adjusted life-year gained. The result was robust to most sensitivity analyses conducted. Limited reporting in identified studies of baseline characteristics for the enrolled population generates uncertainty around the comparability of the study populations and therefore the generalisability of the results to clinical practice. Subgroup analyses were planned based on type, number and size of AGWs, all of which are factors thought to influence treatment effect. Lack of data on clinical effectiveness based on these characteristics precluded analysis of the differential effects of treatments in the subgroups of interest. Despite identification of 60 studies, most comparisons in the MTC are informed by only one RCT. Additionally, lack of head-to-head RCTs comparing key treatments, together with minimal reporting of results in some studies, precluded comprehensive analysis of all treatments for AGWs. The results generated by the MTC are in agreement with consensus opinion that ablative techniques are clinically more effective at completely clearing AGWs after treatment. However, the evidence base informing the MTC is limited. A head-to-head RCT that evaluates the comparative effectiveness of interventions used in clinical practice would help to discern the potential advantages and disadvantages of the individual treatments. The results of the economic analysis suggest that podophyllotoxin 0.5% solution is likely to represent a cost-effective first-line treatment option. More expensive effective treatments, such as CO2 laser therapy or surgery, may represent cost-effective second-line treatment options. No treatment and podophyllin are unlikely to be considered cost-effective treatment options. There is uncertainty around the cost-effectiveness of treatment with imiquimod, trichloroacetic acid and cryotherapy. This study is registered as PROSPERO CRD42013005457. The National Institute for Health Research Health Technology Assessment programme.

[Somatostatin receptor scintigraphy in medullary thyroid carcinomas, GEP and carcinoid tumors].

PubMed

Eising, E G; Farahati, J; Bier, D; Knust, E J; Reiners, C

1995-02-01

For this study, 24 patients with medullary thyroid cancer (MTC) and 10 with carcinoid-/GEP-tumours underwent scintigraphy with 123I-Tyr3-octreotide or 111In-DTPA-D-Phe1-octreotide (Octreoscan) or 99mTc-V-DMSA. Calcitonin and CEA were elevated in MTC patients, the other had tumour lesions on CT. Octreoscan-scintigraphy was positive in 68% of all suspicious cases. On the other hand, 123I-Tyr3-octreotide showed only rarely positive results. 99mTc-V-DMSA-scans in MTC patients were positive in 23%. Liver metastases could be seen only with Octreoscan in the non-MTC-group. These results showed better sensitivity of 111In-labelled octreotide.

Apatinib-treated advanced medullary thyroid carcinoma: a case report.

PubMed

Chen, Kan; Gao, Yun; Shi, Fei; Cao, Guangqiang; Bao, Jiandong

2018-01-01

Medullary thyroid carcinoma (MTC) is a rare malignancy originating from calcitonin-producing parafollicular C cells of the thyroid. Neither radiotherapy nor chemotherapy has demonstrated durable objective responses in patients with advanced MTC. Vandetanib and cabozantinib are the 2 tyrosine kinase inhibitors recently approved by the US Food and Drug Administration, which are not affordable for most Chinese patients. Herein, we report a case of an MTC patient who responded to apatinib, a Chinese homemade tyrosine kinase inhibitor-targeted vascular endothelial growth factor receptor. The patient was treated with thyroid lobectomy but developed MTC with extensive metastasis. The levels of serum calcitonin and carcino-embryonic antigen were much higher than the normal range. Apatinib was given at a dose of 500 mg daily and adjusted according to tolerance. Sixteen weeks following apatinib administration, the patient achieved a partial response, which lasted more than 9 weeks. No severe toxicity or drug-related side effect was observed during the treatment. Therefore, apatinib could be a new option for the treatment of advanced MTC.

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m.

PubMed

Abreu, P R C; Almeida, M C; Bernardo, R M; Bernardo, L C; Brito, L C; Garcia, E A C; Fonseca, A S; Bernardo-Filho, M

2006-06-01

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m ((99m)Tc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with (99m)Tc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with (99m)Tc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with (99m)Tc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with (99m)Tc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract.

Cytologic aspects of an interesting case of medullary thyroid carcinoma coexisting with Hashimoto's thyroiditis.

PubMed

Patel, Bidish K; Roy, Arun; Badhe, Bhawana A; Siddaraju, Neelaiah

2016-01-01

Among primary thyroid neoplasms, papillary thyroid carcinoma (PTC) and primary thyroid lymphoma (PTL) are known to coexist and are pathogenetically linked with Hashimoto's thyroiditis (HT). However, HT occurring in association with medullary thyroid carcinoma (MTC) is rarely documented. We report here an interesting case. A 34-year-old female with a solitary thyroid nodule underwent fine needle aspiration cytology (FNAC) that was interpreted as "MTC with admixed reactive lymphoid cells, derived possibly from a pretracheal lymph node." Total thyroidectomy specimen showed "MTC with coexisting HT." At a later stage, a follow-up FNAC from the recurrent thyroid swelling showed features consistent with HT. As an academic exercise, the initial smears on which a diagnosis of MTC was offered were reviewed to look for evidence of coexisting HT that showed scanty and patchy aggregates of reactive lymphoid cells without Hürthle cells. Our case highlights an unusual instance of MTC in concurrence with HT that can create a tricky situation for cytopathologists.

Bombesin receptors and transplanted stem cells in rat brain: High-resolution scan with 99mTc BN1.1

NASA Astrophysics Data System (ADS)

Scopinaro, F.; Paschali, E.; Di Santo, G.; Antonellis, T.; Massari, R.; Trotta, C.; Gourni, H.; Bouziotis, P.; David, V.; Soluri, A.; Varvarigou, A. D.

2006-12-01

The aim of this work is to detect the presence of transplanted stem cells (TSC) in rat brain with high-resolution (HR) scintigraphy and labelled bombesin (BN). BN is a morphogen for Central Nervous System (CNS) as well as for other organs: CNS-oriented TSC over-express BN Receptors (BNR). BN is also a neurotransmitter and modulates several functions of CNS. 99mTc labelled BN-like peptide scan of CNS is the ideal method to detect growing TSC once knowing normal distribution of BNRs in CNS. HR Planar and single photon emission computerized tomography (SPECT) images of rat brain were performed with new HR detectors (Li-tech, Italy). Pertechnetate, 99mTc HMPAO and the new 99mTc BN1.1 (patented) were i.v. administered in five rats. HR SPECT of 99mTc BN1.1 detected olfactory tract, fronto-lateral cortex, cerebellum, basal ganglia and amygdale. Results of SPECT were confirmed by bio-distribution study performed after autopsy of three of the five rats. The remaining two rats underwent cerebral lesions followed by transplant of TSC. Three months later, HR scintigraphy was repeated and showed images completely different from previous basal study, with hot spot of 99mTc BN1.1 corresponding to the site of TSC transplant. Immuno-histochemistry confirmed the presence of viable TSC. Not only 99mTc BN1.1 HR scan showed viability of transplanted TSC but also the "background brain" was the still now unknown map of BNR in mammalian brain.

Step-by-step variability of swing phase trajectory area during steady state walking at a range of speeds

PubMed Central

Hurt, Christopher P.; Brown, David A.

2018-01-01

Background Step kinematic variability has been characterized during gait using spatial and temporal kinematic characteristics. However, people can adopt different trajectory paths both between individuals and even within individuals at different speeds. Single point measures such as minimum toe clearance (MTC) and step length (SL) do not necessarily account for the multiple paths that the foot may take during the swing phase to reach the same foot fall endpoint. The purpose of this study was to test a step-by-step foot trajectory area (SBS-FTA) variability measure that is able to characterize sagittal plane foot trajectories of varying areas, and compare this measure against MTC and SL variability at different speeds. We hypothesize that the SBS-FTA variability would demonstrate increased variability with speed. Second, we hypothesize that SBS-FTA would have a stronger curvilinear fit compared with the CV and SD of SL and MTC. Third, we hypothesize SBS-FTA would be more responsive to change in the foot trajectory at a given speed compared to SL and MTC. Fourth, SBS-FTA variability would not strongly co-vary with SL and MTC variability measures since it represents a different construct related to foot trajectory area variability. Methods We studied 15 nonimpaired individuals during walking at progressively faster speeds. We calculated SL, MTC, and SBS-FTA area. Results SBS-FTA variability increased with speed, had a stronger curvilinear fit compared with the CV and SD of SL and MTC, was more responsive at a given speed, and did not strongly co-vary with SL and MTC variability measures. Conclusion SBS foot trajectory area variability was sensitive to change with faster speeds, captured a relationship that the majority of the other measures did not demonstrate, and did not co-vary strongly with other measures that are also components of the trajectory. PMID:29370202

Complete subunit structure of the Clostridium botulinum type D toxin complex via intermediate assembly with nontoxic components.

PubMed

Mutoh, Shingo; Kouguchi, Hirokazu; Sagane, Yoshimasa; Suzuki, Tomonori; Hasegawa, Kimiko; Watanabe, Toshihiro; Ohyama, Tohru

2003-09-23

Clostridium botulinum serotype D strains usually produce two types of stable toxin complex (TC), namely, the 300 kDa M (M-TC) and the 660 kDa L (L-TC) toxin complexes. We previously proposed assembly pathways for both TCs [Kouguchi, H., et al. (2002) J. Biol. Chem. 277, 2650-2656]: M-TC is composed by association of neurotoxin (NT) and nontoxic nonhemagglutinin (NTNHA); conjugation of M-TC with three auxiliary types of hemagglutinin subcomponents (HA-33, HA-17, and HA-70) leads to the formation of L-TC. In this study, we found three TC species, 410, 540, and 610 kDa TC species, in the culture supernatant of type D strain 4947. The 540 and 610 kDa TC species displayed banding patterns on SDS-PAGE similar to that of L-TC but with less staining intensity of the HA-33 and HA-17 bands than those of L-TC, indicating that these are intermediate species in the pathway to L-TC assembly. In contrast, the 410 kDa TC species consisted of M-TC and two molecules of HA-70. All of the TC species, except L-TC, demonstrated no hemagglutination activity. When the intermediate TC species were mixed with an isolated HA-33/17 complex, every TC species converted to 650 kDa L-TC with full hemagglutination activity and had the same molecular composition of L-TC. On the basis of titration analysis with the HA-33/17 complex, the stoichiometry of the HA-33/17 complex molecules in the L-TC, 610 kDa, and 540 kDa TC species was estimated as 4, 3, and 2, respectively. In conclusion, the complete subunit composition of mature L-TC is deduced to be a dodecamer assembled by a single NT, a single NTNHA, two HA-70, four HA-33, and four HA-17 molecules.

Innovative methodology for intercomparison of radionuclide calibrators using short half-life in situ prepared radioactive sources

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

Oliveira, P. A.; Santos, J. A. M., E-mail: joao.santos@ipoporto.min-saude.pt; Serviço de Física Médica do Instituto Português de Oncologia do Porto Francisco Gentil, EPE, Porto

2014-07-15

Purpose: An original radionuclide calibrator method for activity determination is presented. The method could be used for intercomparison surveys for short half-life radioactive sources used in Nuclear Medicine, such as{sup 99m}Tc or most positron emission tomography radiopharmaceuticals. Methods: By evaluation of the resulting net optical density (netOD) using a standardized scanning method of irradiated Gafchromic XRQA2 film, a comparison of the netOD measurement with a previously determined calibration curve can be made and the difference between the tested radionuclide calibrator and a radionuclide calibrator used as reference device can be calculated. To estimate the total expected measurement uncertainties, a carefulmore » analysis of the methodology, for the case of{sup 99m}Tc, was performed: reproducibility determination, scanning conditions, and possible fadeout effects. Since every factor of the activity measurement procedure can influence the final result, the method also evaluates correct syringe positioning inside the radionuclide calibrator. Results: As an alternative to using a calibrated source sent to the surveyed site, which requires a relatively long half-life of the nuclide, or sending a portable calibrated radionuclide calibrator, the proposed method uses a source preparedin situ. An indirect activity determination is achieved by the irradiation of a radiochromic film using {sup 99m}Tc under strictly controlled conditions, and cumulated activity calculation from the initial activity and total irradiation time. The irradiated Gafchromic film and the irradiator, without the source, can then be sent to a National Metrology Institute for evaluation of the results. Conclusions: The methodology described in this paper showed to have a good potential for accurate (3%) radionuclide calibrators intercomparison studies for{sup 99m}Tc between Nuclear Medicine centers without source transfer and can easily be adapted to other short half-life radionuclides.« less

A Survey of Algorithms to Efficiently Reconcile Sets of Infomation

DTIC Science & Technology

2015-08-01

instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing the collection of information. Send... data elements which constitute a Navy Command and Control (C2) data store. The problem is to determine which information must be sent between Host A...components of MTC2 is the data layer which abstracts the implementation of the underlying data store from MTC2 applications. In particular, the MTC2

Experimental study of /sup 99m/Tc pertechnetate abdominal scans in jejunal intussusception: preliminary results

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

James, A.E. Jr.; Strecker, E.P.; Miller, F.J. Jr.

1975-07-01

Recent communications have related the diagnosis of small bowel intussusceptions to abnormal accumulations of the radiopharmaceutical /sup 99m/Tc pertechnetate on abdominal scans. Considering the pathophysiological alterations attendant to intussusceptions, we have attempted an experimental model to examine these changes in temporal sequence. This study was initiated to understand the etiology better and to characterize the abnormalities noted on the /sup 99m/Tc pertechnetate abdominal scans.

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

Yu, S; Green, G; Sehgal, V

Purpose: The purpose of this study is to assess the dose response of radioembolization using yttrium-90 (Y-90) microspheres in patients treated for unresectable cholangiocarcinoma. This study utilized partition dosimetry model for the dose calculation. The results show survival benefit with dose escalation. Methods: Between February 2009 and March 2013, ten patients with pathology proven unresectable cholangiocarcinoma were radioembolized with Y-90 microspheres. Patients underwent initial pre-treatment angiographic assessment for blood flow and 99mTc- MAA for lung shunt evaluation. Activity of Y-90 administration was calculated using the Body Surface Area (BSA) and target volumes which were determined by contouring the pre-treatment MRI/CTmore » images using a radiation therapy treatment planning system. Medical Internal Radiation Dose (MIRD) method was used to assess the dosimetric results of Y90. Partition model based on the tumor to-liver activity uptake estimated from pretreatment 99mTc- MAA study was used to calculate the dose delivered to the target. The variables assessed included: administered dose, toxicity based on clinical changes, imaging based tumor response, and survival. Results: Ten patients were radioembolized with Y-90 microspheres to either one hepatic lobe or both left and right lobes. Patients were stratified by dose. Four patients who received dose greater than 140Gy (p < 0.05) all survived. The corresponding activity they received was greater than 35 mCi. Six out of ten patients died of disease with median survival of 18 weeks (range 12–81wks). Conclusion: Given the growing body of data for Y-90 microspheres in the context of cholangiocarcinoma, radioembolization may become an important treatment modality for an appropriately selected group of patients. Our study further substantiates past studies and shows additional evidence of a survival benefit with dose escalation.« less

Thyroid cancer - medullary carcinoma

MedlinePlus

Thyroid - medullary carcinoma; Cancer - thyroid (medullary carcinoma); MTC; Thyroid nodule - medullary ... in children and adults. Unlike other types of thyroid cancer, MTC is less likely to be caused by ...

Semi-Quantitative Analysis of Post-Transarterial Radioembolization (90)Y Microsphere Positron Emission Tomography Combined with Computed Tomography (PET/CT) Images in Advanced Liver Malignancy: Comparison With (99m)Tc Macroaggregated Albumin (MAA) Single Photon Emission Computed Tomography (SPECT).

PubMed

Rhee, Seunghong; Kim, Sungeun; Cho, Jaehyuk; Park, Jukyung; Eo, Jae Seon; Park, Soyeon; Lee, Eunsub; Kim, Yun Hwan; Choe, Jae-Gol

2016-03-01

The purpose of this study is to evaluate the correlation between pretreatment planning technetium-99m ((99m)Tc) macroaggregated albumin (MAA) SPECT images and posttreatment transarterial radioembolization (TARE) yttirum-90 ((90)Y) PET/CT images by comparing the ratios of tumor-to-normal liver counts. Fifty-two patients with advanced hepatic malignancy who underwent (90)Y microsphere radioembolization from January 2010 to December 2012 were retrospectively reviewed. Patients had undergone (99m)Tc MAA intraarterial injection SPECT for a pretreatment evaluation of microsphere distribution and therapy planning. After the administration of (90)Y microspheres, the patients underwent posttreatment (90)Y PET/CT within 24 h. For semiquantitative analysis, the tumor-to-normal uptake ratios in (90)Y PET/CT (TNR-yp) and (99m)Tc MAA SPECT (TNR-ms) as well as the tumor volumes measured in angiographic CT were obtained and analyzed. The relationship of TNR-yp and TNR-ms was evaluated by Spearman's rank correlation and Wilcoxon's matched pairs test. In a total of 79 lesions of 52 patients, the distribution of microspheres was well demonstrated in both the SPECT and PET/CT images. A good correlation was observed of between TNR-ms and TNR-yp (rho value = 0.648, p < 0.001). The TNR-yp (median 2.78, interquartile range 2.43) tend to show significantly higher values than TNR-ms (median 2.49, interquartile range of 1.55) (p = 0.012). The TNR-yp showed weak correlation with tumor volume (rho = 0.230, p = 0.041). The (99m)Tc MAA SPECT showed a good correlation with (90)Y PET/CT in TNR values, suggesting that (99m)Tc MAA can be used as an adequate pretreatment evaluation method. However, the (99m)Tc MAA SPECT image consistently shows lower TNR values compared to (90)Y PET/CT, which means the possibility of underestimation of tumorous uptake in the partition dosimetry model using (99m)Tc MAA SPECT. Considering that (99m)Tc MAA is the only clinically available surrogate marker for distribution of microsphere, we recommend measurement of tumorous uptake using (90)Y PET/CT should be included routinely in the posttherapeutic evaluation.

Aurora kinases are expressed in medullary thyroid carcinoma (MTC) and their inhibition suppresses in vitro growth and tumorigenicity of the MTC derived cell line TT

PubMed Central

2011-01-01

Background The Aurora kinase family members, Aurora-A, -B and -C, are involved in the regulation of mitosis, and alterations in their expression are associated with cell malignant transformation. To date no information on the expression of these proteins in medullary thyroid carcinoma (MTC) are available. We here investigated the expression of the Aurora kinases in human MTC tissues and their potential use as therapeutic targets. Methods The expression of the Aurora kinases in 26 MTC tissues at different TNM stages was analyzed at the mRNA level by quantitative RT-PCR. We then evaluated the effects of the Aurora kinase inhibitor MK-0457 on the MTC derived TT cell line proliferation, apoptosis, soft agar colony formation, cell cycle and ploidy. Results The results showed the absence of correlation between tumor tissue levels of any Aurora kinase and tumor stage indicating the lack of prognostic value for these proteins. Treatment with MK-0457 inhibited TT cell proliferation in a time- and dose-dependent manner with IC50 = 49.8 ± 6.6 nM, as well as Aurora kinases phosphorylation of substrates relevant to the mitotic progression. Time-lapse experiments demonstrated that MK-0457-treated cells entered mitosis but were unable to complete it. Cytofluorimetric analysis confirmed that MK-0457 induced accumulation of cells with ≥ 4N DNA content without inducing apoptosis. Finally, MK-0457 prevented the capability of the TT cells to form colonies in soft agar. Conclusions We demonstrate that Aurora kinases inhibition hampered growth and tumorigenicity of TT cells, suggesting its potential therapeutic value for MTC treatment. PMID:21943074

Overexpression of L-Type Amino Acid Transporter 1 (LAT1) and 2 (LAT2): Novel Markers of Neuroendocrine Tumors

PubMed Central

Barollo, Susi; Bertazza, Loris; Watutantrige-Fernando, Sara; Censi, Simona; Cavedon, Elisabetta; Galuppini, Francesca; Pennelli, Gianmaria; Fassina, Ambrogio; Citton, Marilisa; Rubin, Beatrice; Pezzani, Raffaele; Benna, Clara; Opocher, Giuseppe; Iacobone, Maurizio; Mian, Caterina

2016-01-01

Background 6-18F-fluoro-L-3,4-dihydroxyphenylalanine (18F-FDOPA) PET is a useful tool in the clinical management of pheochromocytoma (PHEO) and medullary thyroid carcinoma (MTC). 18F-FDOPA is a large neutral amino acid biochemically resembling endogenous L-DOPA and taken up by the L-type amino acid transporters (LAT1 and LAT2). This study was conducted to examine the expression of the LAT system in PHEO and MTC. Methods Real-time PCR and Western blot analyses were used to assess LAT1 and LAT2 gene and protein expression in 32 PHEO, 38 MTC, 16 normal adrenal medulla and 15 normal thyroid tissue samples. Immunohistochemistry method was applied to identify the proteins’ subcellular localization. Results LAT1 and LAT2 were overexpressed in both PHEO and MTC by comparison with normal tissues. LAT1 presented a stronger induction than LAT2, and their greater expression was more evident in PHEO (15.1- and 4.1-fold increases, respectively) than in MTC (9.9- and 4.1-fold increases, respectively). Furthermore we found a good correlation between LAT1/2 and GLUT1 expression levels. A positive correlation was also found between urinary noradrenaline and adrenaline levels and LAT1 gene expression in PHEO. The increased expression of LAT1 is also confirmed at the protein level, in both PHEO and MTC, with a strong cytoplasmic localization. Conclusions The present study is the first to provide experimental evidence of the overexpression in some NET cancers (such as PHEO or MTC) of L-type amino acid transporters, and the LAT1 isoform in particular, giving the molecular basis to explain the increase of the DOPA uptake seen in such tumor cells. PMID:27224648

Mitochondria-Targeted Nitroxide, Mito-CP, Suppresses Medullary Thyroid Carcinoma Cell Survival In Vitro and In Vivo

PubMed Central

Starenki, Dmytro

2013-01-01

Context: Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor mainly caused by mutations in the RET proto-oncogene. For MTC therapy, the U.S. Food and Drug Administration recently approved vandetanib and cabozantinib, multikinase inhibitors targeting RET and other tyrosine kinase receptors of vascular endothelial growth factor, epidermal growth factor, or hepatocyte growth factor. Nevertheless, not all patients with the progressive MTC respond to these drugs, requiring the development of additional therapeutic modalities that have distinct activity. Objective: We aimed to evaluate mitochondria-targeted carboxy-proxyl (Mito-CP), a mitochondria-targeted redox-sensitive agent, for its tumor-suppressive efficacy against MTC. Design: In vitro cultures of 2 human MTC cell lines, TT and MZ-CRC-1, and TT xenografts in mice were treated with Mito-CP in comparison with vandetanib. The effects on cell survival/death, RET expression, mitochondrial integrity, and oxidative stress were determined. Results: Contrary to vandetanib, Mito-CP induced RET downregulation and strong cytotoxic effects in both cell lines in vitro, including caspase-dependent apoptosis. These effects were accompanied by mitochondrial membrane depolarization, decreased oxygen consumption, and increased oxidative stress in cells. Intriguingly, Mito-CP–induced cell death, but not RET downregulation, was partially inhibited by the reactive oxygen species scavenger, N-acetyl-cysteine, indicating that Mito-CP mediates tumor-suppressive effects via redox-dependent as well as redox-independent mechanisms. Orally administered Mito-CP effectively suppressed TT xenografts in mice, with an efficacy comparable to vandetanib and relatively low toxicity to animals. Conclusion: Our results suggest that Mito-CP can effectively suppress MTC cell growth/survival via a mechanism distinct from vandetanib effects. Mitochondrial targeting may be a potential strategy for MTC therapy. PMID:23509102

Radionuclidic purity measurements for cyclotron-produced 99mTc via 100Mo(p,2n) at 18 MeV

NASA Astrophysics Data System (ADS)

Buckley, K.; Tanguay, J.; Hou, X.; Stothers, L.; Vuckovic, M.; Frantzen, K.; Cockburn, N.; Corsaut, J.; Dodd, M.; Goodbody, A.; Hanemaayer, V.; Hook, B.; Klug, J.; Kovacs, M.; Kumlin, J.; McDiarmid, S.; McEwan, J.; Prato, F.; Ruddock, P.; Valiant, J.; Zeisler, S.; Ruth, T.; Celler, A.; Benard, F.; Schaffer, P.

2017-05-01

The radionuclidic purity of cyclotron-produced 99mTc has been measured by gamma ray spectroscopy and compared to the results of a quick release test modeled after the molybdenum breakthrough test performed on generator-derived 99mTc. Excellent radionuclidic purity is reported for samples produced at BCCA during our clinical trial. The quick release test results agree well with the gamma ray analysis.

RET fusion as a novel driver of medullary thyroid carcinoma.

PubMed

Grubbs, Elizabeth G; Ng, Patrick Kwok-Shing; Bui, Jacquelin; Busaidy, Naifa L; Chen, Ken; Lee, Jeffrey E; Lu, Xinyan; Lu, Hengyu; Meric-Bernstam, Funda; Mills, Gordon B; Palmer, Gary; Perrier, Nancy D; Scott, Kenneth L; Shaw, Kenna R; Waguespack, Steven G; Williams, Michelle D; Yelensky, Roman; Cote, Gilbert J

2015-03-01

Oncogenic RET tyrosine kinase gene fusions and activating mutations have recently been identified in lung cancers, prompting initiation of targeted therapy trials in this disease. Although RET point mutation has been identified as a driver of tumorigenesis in medullary thyroid carcinoma (MTC), no fusions have been described to date. We evaluated the role of RET fusion as an oncogenic driver in MTC. We describe a patient who died from aggressive sporadic MTC < 10 months after diagnosis. Her tumor was evaluated by means of next-generation sequencing, including an intronic capture strategy. A reciprocal translocation involving RET intron 12 was identified. The fusion was validated using a targeted break apart fluorescence in situ hybridization probe, and RNA sequencing confirmed the existence of an in-frame fusion transcript joining MYH13 exon 35 with RET exon 12. Ectopic expression of fusion product in a murine Ba/F3 cell reporter model established strong oncogenicity. Three tyrosine kinase inhibitors currently used to treat MTC in clinical practice blocked tumorigenic cell growth. This finding represents the report of a novel RET fusion, the first of its kind described in MTC. The finding of this potential novel oncogenic mechanism has clear implications for sporadic MTC, which in the majority of cases has no driver mutation identified. The presence of a RET fusion also provides a plausible target for RET tyrosine kinase inhibitor therapies.

Mixed-treatment comparison of anabolic (teriparatide and PTH 1-84) therapies in women with severe osteoporosis.

PubMed

Migliore, A; Broccoli, S; Massafra, U; Bizzi, E; Frediani, B

2012-03-01

The recent development of compounds with anabolic action on bone have increased the range of therapeutic options for the treatment of osteoporosis and the prevention of fractures. Two major PTH analogs, the synthetic full-length 1-84 PTH molecule and the recombinant 1-34 N-terminal fragment (teriparatide), are available for the treatment of osteoporosis in many countries. There have bee no comparative trials on the bone anabolic effects of these compounds. In this study we applied a mixed treatment comparison (MTC) to compare the efficacy of teriparatide versus PTH 1-84 for the prevention of vertebral and non-vertebral fractures in women with severe osteoporosis. With this approach the relative treatment effect of one intervention over another can be obtained in the absence of head-to-head comparison. Among the candidate papers selected for analysis, two randomized controlled trials investigating the effects of teriparatide and PTH 1-84 met the selection criteria and underwent MTC analysis. Based on a fixed-effect MTC model analysis of data from two RCTs, teriparatide (20 µg/day) showed a 70% and 94% probability of being the best treatment for the prevention of vertebral and non-vertebral fractures, respectively. Together with a lack of statistical significance, this study has additional limitations. Some differences in trial procedures and populations exist; another limitation concerns the impossibility of carrying out a randomized-effect model MTC, due to sample exiguity. Furthermore, in order to consider unknown or unmeasured differences of covariates across trials, a random-effects approach would be preferred in order to assess the presence of heterogeneity across comparisons. In contrast, in our analysis a fixed-effect MTC model only was used. Teriparatide is expected to provide a greater efficacy over PTH 1-84 with both vertebral and non-vertebral fracture prevention in postmenopausal women with severe osteoporosis.

The effect of the introduction of a regional major trauma network on triage decisions made by a physician-staffed helicopter emergency medical service.

PubMed

Chesters, Adam; Fenton, Ronan

2015-12-01

A major trauma network (MTN) has been in place in the East of England, with a single hospital operating as the major trauma centre (MTC). The primary aim of this retrospective cohort study was to determine whether triage destination decisions with regard to trauma patients made by a helicopter-based doctor-paramedic team are affected by the introduction of a regional trauma network. In addition, we will describe and discuss the logistics of transfer of injured patients attended by the service. This is a retrospective database review that was carried out over two 12-month periods. The first period was before the introduction of an MTN, and the second was after its introduction. All patients who were conveyed to an MTC were identified. Nontrauma patients were excluded. The MTN trauma triage tool was retrospectively applied. A comparative analysis of the two cohorts was carried out. For the group of patients conveyed to the regional MTC, additional follow-up information was obtained. This included patient survival at 30 days and the final injury severity score for each patient. A total of 220 cases were identified in which a major trauma patient was conveyed to an MTC. There were 94 cases in the year before the introduction of the MTN (cohort 1) and 124 in the year during which the MTN was active (cohort 2). There was no significant difference in the number of patients conveyed to each MTC between cohort 1 and cohort 2. The trauma triage tool status was 'positive' in 52.1% of cases in cohort 1 and 55.6% of cases in cohort 2 (P=0.60). Advice of the consultant on call was more commonly used for patients in cohort 2 than for those in cohort 1 (66.9 vs. 40.6%; P<0. 01). The introduction of a regional MTN has not significantly affected the triage decisions made by our physician-paramedic teams.

Assessment of the best N(3-) donors in preparation of [M(N)(PNP)]-based (M=(99m)Tc-; (188)Re) target-specific radiopharmaceuticals: Comparison among succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ).

PubMed

Carta, Davide; Jentschel, Christian; Thieme, Stefan; Salvarese, Nicola; Morellato, Nicolò; Refosco, Fiorenzo; Ruzza, Paolo; Bergmann, Ralf; Pietzsch, Hans-Jurgen; Bolzati, Cristina

2014-08-01

Succinic dihydrazide (SDH), N-methyl-S-methyl dithiocarbazate (HDTCZ) and PEGylated N-methyl-S-methyl dithiocarbazate (HO2C-PEG600-DTCZ) are nitrido nitrogen atom donors employed for the preparation of nitride [M(N)]-complexes (M=(99m)Tc and (188)Re). This study aims to compare the capability and the efficiency of these three N(3-) group donors, in the preparation of [M(N)PNP]-based target-specific compounds (M=(99m)Tc, (188)Re; PNP=aminodiphosphine). For this purpose, three different kit formulations (SDH kit; HO2C-PEG600-DTCZ kit; HDTCZ kit) were assembled and used in the preparation of [M(N)(cys~)(PNP3)](0/+) complexes (cys~=cysteine derivate ligands). For each formulation, the radiochemical yield (RCY) of the [M(N)(~cys)(PNP3)] compounds, was determined by HPLC. The deviation of the percentage of RCY, due to changes in concentration of the N(3-) donors and of the exchanging ligand, was determined. For (99m)Tc, data clearly show that HDTCZ is the most efficient donor of N(3-); however, SDH is the most suitable nitrido nitrogen atom donor for the preparation of [(99m)Tc(N)(PNP)]-based target-specific agents with high specific activity. When HO2C-PEG600-DTCZ or HDTCZ are used in N(3-) donation, high amounts of the exchanging ligand (10(-4)M) were required for the formation of the final complex in acceptable yield. The possibility to use microgram amounts of HDTCZ also in [(188)Re(N)] preparation (0.050mg) reduces its ability to compete in ligand exchange reactions, minimizing the quantity of chelators required to obtain the final complex in high yield. This finding can be exploit for increasing the radiolabeling efficiency in [(188)Re(N)]-radiopharmaceutical preparations compared to the previously reported HDTCZ-based procedure, notwithstanding a purification process could be necessary to improve the specific activity of the complexes. Copyright © 2014 Elsevier Inc. All rights reserved.

Oncogenesis of Thyroid Cancer

PubMed Central

Younis, Enas

2017-01-01

Thyroid neoplasms encompass a variety of lesions that range from benign adenomas to malignancies. These latter can be well-differentiated, poorly differentiated or undifferentiated (anaplastic) carcinomas. More than 95% of thyroid cancers are derived from thyroid follicular cells, while 2-3% (medullary thyroid cancers, MTC) originate from calcitonin producing C-cells. Over the last decade, investigators have developed a clearer understanding of genetic alterations underlying thyroid carcinogenesis. A number of point mutations and translocations are involved, not only in its tumorigenesis, but also as have potential use as diagnostic and prognostic indicators and therapeutic targets. Many occur in genes for several important signaling pathways, in particular the mitogen-activated protein kinase (MAPK) pathway. Sporadic (isolated) lesions account for 75% of MTC cases, while inherited MTC, often in association with multiple endocrine neoplasia (MEN) type 2A and 2B syndromes, constitute the remainder. However, non-MEN familial MTC may also occur. Advances in genetic testing have revolutionized the management of MTC, with prospects of genetic screening, testing and early prophylactic thyroidectomy. Ethical concerns of these advances are addressed. PMID:28610401

Guava extract (Psidium guajava) alters the labelling of blood constituents with technetium-99m*

PubMed Central

Abreu, P.R.C.; Almeida, M.C.; Bernardo, R.M.; Bernardo, L.C.; Brito, L.C.; Garcia, E.A.C.; Fonseca, A.S.; Bernardo-Filho, M.

2006-01-01

Psidium guajava (guava) leaf is a phytotherapic used in folk medicine to treat gastrointestinal and respiratory disturbances and is used as anti-inflammatory medicine. In nuclear medicine, blood constituents (BC) are labelled with technetium-99m (99mTc) and used to image procedures. However, data have demonstrated that synthetic or natural drugs could modify the labelling of BC with 99mTc. The aim of this work was to evaluate the effects of aqueous extract of guava leaves on the labelling of BC with 99mTc. Blood samples of Wistar rats were incubated with different concentrations of guava extract and labelled with 99mTc after the percentage of incorporated radioactivity (%ATI) in BC was determined. The results suggest that aqueous guava extract could present antioxidant action and/or alters the membrane structures involved in ion transport into cells, thus decreasing the radiolabelling of BC with 99mTc. The data showed significant (P<0.05) alteration of ATI in BC from blood incubated with guava extract. PMID:16691636

Evaluation of [99mTc/EDDA/HYNIC0]octreotide derivatives compared with [111In-DOTA0,Tyr3, Thr8]octreotide and [111In-DTPA0]octreotide: does tumor or pancreas uptake correlate with the rate of internalization?

PubMed

Storch, Daniel; Béhé, Martin; Walter, Martin A; Chen, Jianhua; Powell, Pia; Mikolajczak, Renata; Mäcke, Helmut R

2005-09-01

Radiolabeled somatostatin analogs are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin receptor-positive tumors. The aim of this study was to compare 3 somatostatin analogs designed for the labeling with (99m)Tc (where HYNIC is 6-hydrazinopyridine-3-carboxylic acid): 6-hydrazinopyridine-3-carboxylic acid(0)-octreotide (HYNIC-OC/(99m)Tc-(1)), [HYNIC(0),Tyr(3)]octreotide (HYNIC-TOC/(99m)Tc-(2)), and [HYNIC(0),Tyr(3),Thr(8)]octreotide (HYNIC-TATE/(99m)Tc-(3)), using ethylenediamine-N,N'-diacetic acid (EDDA) as a coligand. In addition, we compared the (99m)Tc-labeled peptides [(111)In-diethylenetriaminepentaacetic acid(0)]octreotide ([(111)In-DTPA]-OC) and [(111)In-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(0),Tyr(3),Thr(8)]octreotide ([(111)In-DOTA]-TATE) with regard to the rate of internalization and the biodistribution in AR4-2J (expressing the somatostatin receptor subtype 2) tumor-bearing rats. The main attention was directed toward a potential correlation between the rate of internalization and the tumor or pancreas uptake. Synthesis was performed on solid phase using a standard Fmoc strategy. Internalization was studied in cell culture (AR4-2J) and biodistribution was studied using a Lewis rat tumor model (AR4-2J). The 5 radiopeptides showed a specific internalization into AR4-2J cells in culture (as shown by blocking experiments). The rate of internalization of the 5 radiopeptides differed significantly according to the following order: (99m)Tc-(1) approximately = [(111)In-DTPA]-OC < (99m)Tc-(2) < (99m)Tc-(3) approximately = [(111)In-DOTA]-TATE. All radiopeptides displayed a rapid blood clearance and a fast clearance from all somatostatin receptor-negative tissues predominantly via the kidneys. A receptor-specific uptake of radioactivity was observed for all compounds in somatostatin receptor-positive organs such as the pancreas, the adrenals, and the stomach. After 4 h, the uptake in the AR4-2J tumor was comparable for (99m)Tc-(2) (3.85 +/- 1.0 injected dose per gram tissue (%ID/g)), (99m)Tc-(3) (3.99 +/- 0.58%ID/g), and [(111)In-DOTA]-TATE (4.12 +/- 0.74%ID/g) but much lower for [(111)In-DTPA]-OC (0.99 +/- 0.08%ID/g) and (99m)Tc-(1) (0.70 +/- 0.13%ID/g). The specificity was determined by blocking experiments using a large excess of [Tyr(3)]octreotide. (99m)Tc-(3) displayed the highest tumor-to-kidney ratio (2.5:1), followed by (99m)Tc(2) (1.9:1) and [(111)In-DOTA]-TATE (1.7:1). These data show that the 5 radiopeptides are specific radioligands for the somatostatin receptor subtype 2. The rate of internalization correlates with the uptake in the tumor (R(2) = 0.75; P = 0.026) and pancreas (R(2) = 0.98; P = 7.4.10(-5)). [Tyr(3),Thr(8)]octreotide derivatives show superiority over the corresponding octreotide and [Tyr(3)]octreotide derivatives, indicating that [(111)In-DOTA]-TATE and [(99m)Tc/EDDA/HYNIC]-TATE are suitable candidates for clinical studies.

Synthesis and biological evaluation of new diisocyanide- and triisocyanide-99mTc complexes.

PubMed

Chemin, N; du Moulinet d'Hardemare, A; Bouquillon, S; Fagret, D; Vidal, M

1996-01-01

This paper describes the synthesis of four new polyisocyanides (three diisocyanides and one triisocyanide). The complexation of 99mTc with these ligands is also studied through chromatography and revealed the formation of hexacoordinated 99mTc+1 complexes. Finally, biodistributions of these complexes in mice are given and compared. Heart captations are lower than the ones with [99mTc(MIBI)6]+ but remain constant and a satisfactory lungs clearance, probably due to the metabolization of the ligands, is observed.

Ghrelin and obestatin in thyroid gland - immunohistochemical expression in nodular goiter, papillary and medullary cancer.

PubMed

Gurgul, Edyta; Kasprzak, Aldona; Blaszczyk, Agata; Biczysko, Maciej; Surdyk-Zasada, Joanna; Seraszek-Jaros, Agnieszka; Ruchala, Marek

2015-01-01

Previous studies analyzing ghrelin and obestatin expression in thyroid gland tissue are not unanimous and are mostly related to ghrelin. The role of ghrelin and obestatin in the thyroid gland appears very interesting due to their probable involvement in cell proliferation. Furthermore, since the thyroid gland is associated with the maintenance of energy balance, the relationship between ghrelin, obestatin and thyroid function is worthy of consideration. The aim of the study was to assess ghrelin and obestatin immunocytochemical expression in nodular goiter (NG), papillary cancer (PTC) and medullary cancer (MTC). Analyzed samples included 9 cases of NG, 8 cases of PTC and 11 cases of MTC. The analysis of ghrelin and obestatin expression was performed by use of the immunohistochemical (IHC) EnVision system and evaluated with filter HSV software (quantitative morphometric analysis). Quantitative ghrelin expression in MTC cells was higher than in NG (p = 0.013) and correlated negatively with the size of the tumor (r= -0.829, p < 0.05). We did not observe any differences in ghrelin expression neither between MTC and PTC nor between NG and PTC. Obestatin immunoexpression pattern in all analyzed specimens was irregular and poorly accented. The strongest immunoreactivity for obestatin was demonstrated in NG. In MTC obestatin expression was significantly weaker than in NG and PTC (p < 0.05 in both cases). In NG the intensity of obestatin immunostaining was significantly higher than that of ghrelin (p = 0.03). Conversely, ghrelin expression in MTC was definitely more evident than obestatin immunoreactivity (p < 0.01). There was no statistically significant difference between ghrelin and obestatin expression in PTC. No correlations were detected between reciprocal tissue expressions of ghrelin and obestatin in the analyzed specimens of NG, PTC or MTC. The differences between ghrelin expression in NG and MTC suggest that ghrelin may be involved in thyroid cell proliferation. The differences between ghrelin and obestatin immunoreactivity in benign and malignant thyroid tumors could support the theory of alternative transcription of the preproghrelin gene and independent production of ghrelin and obestatin.

[Simplicity or complexity of the radiopharmaceutical production process in the light of optimization of radiation protection of staff - 99mTc vs. 18F].

PubMed

Wrzesień, Małgorzata

2018-05-22

A radiopharmaceutical is a combination of a non-radioactive compound with a radioactive isotope. Two isotopes: technetium-99m (99mTc) and fluorine-18 (18F) are worth mentioning on the rich list of isotopes which have found numerous medical applications. Their similarity is limited only to the diagnostic area of applicability. The type and the energy of emitted radiation, the half-life and, in particular, the production method demonstrate their diversity. The 99mTc isotope is produced by a short-lived nuclide generator - molybdenum-99 (99Mo)/99mTc, while 18F is resulting from nuclear reaction occurring in a cyclotron. A relatively simple and easy handling of the 99Mo/99mTc generator, compared to the necessary use a cyclotron, seems to favor the principle of optimizing the radiological protection of personnel. The thesis on the effect of automation of both the 18F isotope production and the deoxyglucose labelling process on the optimization of radiological protection of workers compared to manual procedures during handling of radiopharmaceuticals labelled with 99Tc need to be verified. Measurements of personal dose equivalent Hp(0.07) were made in 5 nuclear medicine departments and 2 radiopharmaceuticals production centers. High-sensitivity thermoluminescent detectors (LiF: Mg, Cu, P - MCP-N) were used to determine the doses. Among the activities performed by employees of both 18F-fluorodeoxyglucose (18F-FDG) production centers and nuclear medicine departments, the manual quality control procedures and labelling of radiopharmaceuticals with 99mTc isotope manifest the greatest contribution to the recorded Hp(0.07). The simplicity of obtaining the 99mTc isotope as well as the complex, but fully automated production process of the 18F-FDG radiopharmaceutical optimize the radiation protection of workers, excluding manual procedures labelling with 99mTc or quality control of 18F-FDG. Med Pr 2018;69(3):317–327. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Techniques for loading technetium-99m and rhenium-186/188 radionuclides into pre-formed liposomes for diagnostic imaging and radionuclide therapy.

PubMed

Goins, Beth; Bao, Ande; Phillips, William T

2010-01-01

Liposomes can serve as carriers of radionuclides for diagnostic imaging and therapeutic applications. Herein, procedures are outlined for radiolabeling liposomes with the gamma-emitting radionuclide, technetium-99m ((99m)Tc), for non-invasive detection of disease and for monitoring the pharmacokinetics and biodistribution of liposomal drugs, and/or with therapeutic beta-emitting radionuclides, rhenium-186/188 ((186/188)Re), for radionuclide therapy. These efficient and practical liposome radiolabeling methods use a post-labeling mechanism to load (99m)Tc or (186/188)Re into pre-formed liposomes prepared in advance of the labeling procedure. For all liposome radiolabeling methods described, a lipophilic chelator is used to transport (99m)Tc or (186/188)Re across the lipid bilayer of the pre-formed liposomes. Once within the liposome interior, the pre-encapsulated glutathione or ammonium sulfate (pH) gradient provides for stable entrapment of the (99m)Tc and (186/188)Re within the liposomes. In the first method, (99m)Tc is transported across the lipid bilayer by the lipophilic chelator, hexamethylpropyleneamine oxime (HMPAO) and (99m)Tc-HMPAO becomes trapped by interaction with the pre-encapsulated glutathione within the liposomes. In the second method, (99m)Tc or (186/188)Re is transported across the lipid bilayer by the lipophilic chelator, N,N-bis(2-mercaptoethyl)-N',N'-diethylethylenediamine (BMEDA), and (99m)Tc-BMEDA or (186/188)Re-BMEDA becomes trapped by interaction with pre-encapsulated glutathione within the liposomes. In the third method, an ammonium sulfate (pH) gradient loading technique is employed using liposomes with an extraliposomal pH of 7.4 and an interior pH of 5.1. BMEDA, which is lipophilic at pH 7.4, serves as a lipophilic chelator for (99m)Tc or (186/188)Re to transport the radionuclides across the lipid bilayer. Once within the more acidic liposome interior, (99m)Tc/(186/188)Re-BMEDA complex becomes protonated and more hydrophilic, which results in stable entrapment of the (99m)Tc/(186/188)Re-BMEDA complex within the liposomes. Since many commercially available liposomal drugs use an ammonium sulfate (pH) gradient for drug loading, these liposomal drugs can be directly radiolabeled with (99m)Tc-BMEDA for non-invasive monitoring of tissue distribution during treatment or with (186/188)Re-BMEDA for combination chemo-radionuclide therapy.

Configuration of Materially Retained Carbon in Our Society: A WIO-MFA-Based Approach for Japan.

PubMed

Ohno, Hajime; Sato, Hirokazu; Fukushima, Yasuhiro

2018-04-03

To achieve the goals of Paris Agreement, global society is directing much effort in substantially reducing greenhouse gas (GHG) emissions. In addition to energy-related efforts, prevention of carbon release into the atmosphere with carbon capture and storage (CCS) and/or utilization of biomass resources is considered indispensable to achieving the global objective. In this study, considering carbon-containing goods as carbon reservoirs in our society similar to forests and reservoirs enabling CCS, the flow of materially utilized carbon was quantified by input-output-based material flow analysis (IO-MFA). As a result, in 2011, 6.3 Mt-C of petroleum-derived carbon and 7.9 Mt-C of wood-derived carbon were introduced to the Japanese society as end-use products (e.g., automobiles and constructions) in various forms (e.g., plastics and synthetic rubbers). The total amount (14.2 Mt-C) corresponded to 4.1% (52.1 Mt-CO 2 ) of annual CO 2 emission in Japan in 2011. Subsequently, by referring to the technology that can treat carbon in the target forms in end-of-life products, the recoverability of carbon as a material has been discussed with respect to each form and end-use of carbon. By numerically showing the necessity and potential of implementing appropriate technologies, this study provides scientific direction for policymakers to establish a quality carbon cycle in our society.

Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

NASA Astrophysics Data System (ADS)

Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin

2013-09-01

Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

Three-dimensional cytomorphology in fine needle aspiration biopsy of medullary thyroid carcinoma.

PubMed

Chang, T C; Lai, S M; Wen, C Y; Hsiao, Y L; Huang, S H

2001-01-01

To elucidate three-dimensional (3-D) cytomorphology in fine needle aspiration biopsy (FNAB) of medullary thyroid carcinoma (MTC). ENAB was performed on tumors from five patients with MTC. The aspirate was stained and observed under a light microscope (LM). The aspirate was also fixed, dehydrated, critical point dried, spattered with gold ions and observed with a scanning electron microscope (SEM). For transmission electron microscopy (TEM), the specimen was fixed, dehydrated, embedded in an Epon mixture, cut with an ultramicrotome, mounted on copper grids, electron doubly stained with uranium acetate and lead citrate, and observed with TEM. Findings under SEM were correlated with those under LM and TEM. Under SEM, 3-D cytomorphology of MTC displayed a disorganized cellular arrangement with indistinct cell borders in three cases. The cell surface was uneven and had granular protrusions that corresponded to secretory granules observed under TEM. In one case with multiple endocrine neoplasia type IIB, there were abundant granules on the cell surface. In one case of sporadic MTC with multinucleated tumor giant cells and small cells, granular protrusions also were noted on the cell surface. Granular protrusion was a characteristic finding in FNAB of MTC tinder SEM and might be helpful in the differential diagnosis.

Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

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

Hinkle, G.H.; Basmadjian, G.P.; Peek, C.

Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated withmore » other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate.« less

A major trauma course based on posters, audio-guides and simulation improves the management skills of medical students: Evaluation via medical simulator.

PubMed

Cuisinier, Adrien; Schilte, Clotilde; Declety, Philippe; Picard, Julien; Berger, Karine; Bouzat, Pierre; Falcon, Dominique; Bosson, Jean Luc; Payen, Jean-François; Albaladejo, Pierre

2015-12-01

Medical competence requires the acquisition of theoretical knowledge and technical skills. Severe trauma management teaching is poorly developed during internship. Nevertheless, the basics of major trauma management should be acquired by every future physician. For this reason, the major trauma course (MTC), an educational course in major traumatology, has been developed for medical students. Our objective was to evaluate, via a high fidelity medical simulator, the impact of the MTC on medical student skills concerning major trauma management. The MTC contains 3 teaching modalities: posters with associated audio-guides, a procedural workshop on airway management and a teaching session using a medical simulator. Skills evaluation was performed 1 month before (step 1) and 1 month after (step 3) the MTC (step 2). Nineteen students were individually evaluated on 2 different major trauma scenarios. The primary endpoint was the difference between steps 1 and 3, in a combined score evaluating: admission, equipment, monitoring and safety (skill set 1) and systematic clinical examinations (skill set 2). After the course, the combined primary outcome score improved by 47% (P<0.01). Scenario choice or the order of use had no significant influence on the skill set evaluations. This study shows improvement in student skills for major trauma management, which we attribute mainly to the major trauma course developed in our institution. Copyright © 2015 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier Masson SAS. All rights reserved.

Thiocoraline alters neuroendocrine phenotype and activates the Notch pathway in MTC-TT cell line

PubMed Central

Tesfazghi, Sara; Eide, Jacob; Dammalapati, Ajitha; Korlesky, Colin; Wyche, Thomas P; Bugni, Tim S; Chen, Herbert; Jaskula-Sztul, Renata

2013-01-01

Medullary thyroid cancer (MTC) is an aggressive neuroendocrine tumor (NET). Previous research has shown that activation of Notch signaling has a tumor suppressor role in NETs. The potential therapeutic effect of thiocoraline on the activation of the Notch pathway in an MTC cell line (TT) was investigated. Thiocoraline was isolated from a marine bacterium Verrucosispora sp. MTT assay (3-[4, 5-dimethylthiazole-2-yl]-2, 5-diphenyltetrazolium bromide) was used to determine the IC50 value and to measure cell proliferation. Western blot revealed the expression of Notch isoforms, NET, and cell cycle markers. Cell cycle progression was validated by flow cytometry. The mRNA expression of Notch isoforms and downstream targets were measured using real-time PCR. The IC50 value for thiocoraline treatment in TT cells was determined to be 7.6 nmol/L. Thiocoraline treatment decreased cell proliferation in a dose- and time-dependent manner. The mechanism of growth inhibition was found to be cell cycle arrest in G1 phase. Thiocoraline activated the Notch pathway as demonstrated by the dose-dependent increase in mRNA and protein expression of Notch isoforms. Furthermore, treatment with thiocoraline resulted in changes in the expression of downstream targets of the Notch pathway (HES1, HES2, HES6, HEY1, and HEY2) and reduced expression of NET markers, CgA, and ASCL1. Thiocoraline is a potent Notch pathway activator and an inhibitor of MTC-TT cell proliferation at low nanomolar concentrations. These results provide exciting evidence for the use of thiocoraline as a potential treatment for intractable MTC. Thiocoraline is a potent Notch pathway activator and an inhibitor of medullary thyroid cancer cell line (MTC-TT) cell proliferation at low nanomolar concentrations. These results provide evidence for the use of thiocoraline as a potential treatment for intractable MTC. PMID:24403239

Lipid Peroxidation and Antioxidant Status in Patients with Medullary Thyroid Carcinoma: A Case-Control Study.

PubMed

Hosseini-Zijoud, Seyed-Mostafa; Ebadi, Seyed Alireza; Goodarzi, Mohammad Taghi; Hedayati, Mehdi; Abbasalipourkabir, Roghayeh; Mahjoob, Mohammad Parsa; Poorolajal, Jalal; Zicker, Fabio; Sheikh, Nasrin

2016-02-01

Oxidative stress or oxidant/antioxidant imbalance has a crucial role in the pathogenesis of some diseases like cancer. Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and includes 3-4% of the malignant neoplasms that have an effect on this gland. The aetiology of MTC has not been clarified. However, oxidative stress may be one of the factors involved. The aim of the current study was to evaluate the antioxidant enzyme activity of catalase (CAT), Glutathione (GSH), total antioxidant capacity (TAC) and the levels of the lipid peroxidation product malondialdehyde (MDA) in blood samples of MTC patients as compared to healthy controls. A case-control study was designed enrolling patients with confirmed MTC diagnosis and age-and sex group matched healthy volunteers referred to the clinic of the Research Institute for Endocrine Sciences, Tehran, Iran from April 2013 to July 2015. Fasting blood samples were taken for study. Catalase, GSH, MDA and TAC levels were measured by colorimetry using commercial kits (ZellBio GmbH, Germany). Data were analysed using SPSS 17 software, comparing mean±SD through t-test and difference between proportions through chi-square. No statistical difference was observed in the demographic characteristic between cases and controls. The final MTC group included 40 males and 45 females with a mean age of 30±12.9 year, and the control group 40 males and 47 females, with a mean age of 31.2±12.3 year. Anthropometric parameters, dietary and thyroid hormones levels (T3, T4 and TSH) were similar. Serum TAC (p=0.015), GSH (p=0.029) and CAT (p<0.001) levels were found to be significantly lower in the MTC patients, while serum MDA levels were significantly higher in MTC patients than controls (p<0.001). These preliminary findings suggest that oxidant/antioxidant imbalance may be associated with or possibly indicate an increased risk to medullary thyroid carcinoma. Further studies are needed to explore these findings.

Biarsenical labeling of vesicular stomatitis virus encoding tetracysteine-tagged m protein allows dynamic imaging of m protein and virus uncoating in infected cells.

PubMed

Das, Subash C; Panda, Debasis; Nayak, Debasis; Pattnaik, Asit K

2009-03-01

A recombinant vesicular stomatitis virus (VSV-PeGFP-M-MmRFP) encoding enhanced green fluorescent protein fused in frame with P (PeGFP) in place of P and a fusion matrix protein (monomeric red fluorescent protein fused in frame at the carboxy terminus of M [MmRFP]) at the G-L gene junction, in addition to wild-type (wt) M protein in its normal location, was recovered, but the MmRFP was not incorporated into the virions. Subsequently, we generated recombinant viruses (VSV-PeGFP-DeltaM-Mtc and VSV-DeltaM-Mtc) encoding M protein with a carboxy-terminal tetracysteine tag (Mtc) in place of the M protein. These recombinant viruses incorporated Mtc at levels similar to M in wt VSV, demonstrating recovery of infectious rhabdoviruses encoding and incorporating a tagged M protein. Virions released from cells infected with VSV-PeGFP-DeltaM-Mtc and labeled with the biarsenical red dye (ReAsH) were dually fluorescent, fluorescing green due to incorporation of PeGFP in the nucleocapsids and red due to incorporation of ReAsH-labeled Mtc in the viral envelope. Transport and subsequent association of M protein with the plasma membrane were shown to be independent of microtubules. Sequential labeling of VSV-DeltaM-Mtc-infected cells with the biarsenical dyes ReAsH and FlAsH (green) revealed that newly synthesized M protein reaches the plasma membrane in less than 30 min and continues to accumulate there for up to 2 1/2 hours. Using dually fluorescent VSV, we determined that following adsorption at the plasma membrane, the time taken by one-half of the virus particles to enter cells and to uncoat their nucleocapsids in the cytoplasm is approximately 28 min.

Evidence that PC2 is the endogenous pro-neurotensin convertase in rMTC 6-23 cells and that PC1- and PC2-transfected PC12 cells differentially process pro-neurotensin.

PubMed

Rovère, C; Barbero, P; Kitabgi, P

1996-05-10

The neuropeptide precursor proneurotensin/neuromedin N (pro-NT/NN) is mainly expressed and differentially processed in the brain and in the small intestine. We showed previously that rMTC 6-23 cells process pro-NT/NN with a pattern similar to brain tissue and increase pro-NT/NN expression in response to dexamethasone, and that PC12 cells also produce pro-NT/NN but are virtually unable to process it. In addition, PC12 cells were reported to be devoid of the prohormone convertases PC1 and PC2. The present study was designed to identify the proprotein convertase(s) (PC) involved in pro-NT/NN processing in rMTC 6-23 cells and to compare PC1- and PC2-transfected PC12 cells for their ability to process pro-NT/NN. rMTC 6-23 cells were devoid of PC1, PC4, and PC5 but expressed furin and PC2. Stable expression of antisense PC2 RNA in rMTC 6-23 cells led to a 90% decrease in PC2 protein levels that correlated with a > 80% reduction of pro-NT/NN processing. PC2 expression was stimulated by dexamethasone in a time- and concentration-dependent manner. Stable PC12/PC2 transfectants processed pro-NT/NN with a pattern similar to that observed in the brain and in rMTC 6-23 cells. In contrast, stable PC12/PC1 transfectants reproduced the pro-NT/NN processing pattern seen in the gut. We conclude that (i) PC2 is the major pro-NT/NN convertase in rMTC 6-23 cells; (ii) its expression is coregulated with that of pro-NT/NN in this cell line; and (iii) PC2 and PC1 differentially process pro-NT/NN with brain and intestinal phenotype, respectively.

Midwest Transportation Consortium annual progress report : October 2000.

DOT National Transportation Integrated Search

2000-10-01

From the Director: The Midwest Transportation Consortium (MTC), the University Transportation Center serving the states : of Iowa, Kansas, Missouri, and Nebraska, had a very successful first year of operation. The MTC is a : complex partnership invol...

Midwest Transportation Consortium : 2005-2006 annual report.

DOT National Transportation Integrated Search

2006-01-01

Introduction: The Midwest Transportation Consortium (MTC) recently completed its seventh year of : operation. At this point, the MTC has become an established portion of the research and : educational programs at Iowa State University (ISU) and the M...

Fuzzy logic and image processing techniques for the interpretation of seismic data

NASA Astrophysics Data System (ADS)

Orozco-del-Castillo, M. G.; Ortiz-Alemán, C.; Urrutia-Fucugauchi, J.; Rodríguez-Castellanos, A.

2011-06-01

Since interpretation of seismic data is usually a tedious and repetitive task, the ability to do so automatically or semi-automatically has become an important objective of recent research. We believe that the vagueness and uncertainty in the interpretation process makes fuzzy logic an appropriate tool to deal with seismic data. In this work we developed a semi-automated fuzzy inference system to detect the internal architecture of a mass transport complex (MTC) in seismic images. We propose that the observed characteristics of a MTC can be expressed as fuzzy if-then rules consisting of linguistic values associated with fuzzy membership functions. The constructions of the fuzzy inference system and various image processing techniques are presented. We conclude that this is a well-suited problem for fuzzy logic since the application of the proposed methodology yields a semi-automatically interpreted MTC which closely resembles the MTC from expert manual interpretation.

Exposure of wild boar to Mycobacterium tuberculosis complex in France since 2000 is consistent with the distribution of bovine tuberculosis outbreaks in cattle.

PubMed

Richomme, Céline; Boadella, Mariana; Courcoul, Aurélie; Durand, Benoît; Drapeau, Antoine; Corde, Yannick; Hars, Jean; Payne, Ariane; Fediaevsky, Alexandre; Boschiroli, María Laura

2013-01-01

The Eurasian wild boar (Sus scrofa) is increasingly considered as a relevant actor in the epidemiology of animal tuberculosis (TB). Therefore, monitoring TB in wild boar becomes a key tool for establishing comprehensive control schemes for this disease. To estimate the exposure of free living wild boar to Mycobacterium tuberculosis complex (MTC) in France, a bovine-purified protein derivative based ELISA was used to test 2,080 archived serum samples of hunter-harvested animals in 58 French "départements". Two cut-off values were used for diagnostic interpretation: 0.2, recommended by the manufacturer (specificity: 96.43%; sensitivity: 72.6%), and 0.5 (specificity: 100%; sensitivity: 64%). During the same period, at the 0.2 cut-off, global true seroprevalence was 5.9% (IC95%: 4.3%-7.7%) and 76% of the sampled "départements" had seropositive wild boar, including seven cattle TB-free "départements. At the 0.5 cut-off, global true seroprevalence was 2.2% (IC95%: 1.5-3.2) and positive wild boar belonged to 21% of the "départements". All but one of these positive "départements" had reported at least one cattle TB outbreak since 2000. A good consistence between seropositive wild boar and TB outbreaks in cattle was found, especially at the 0.5 cut-off value (the mean distance to the nearest cattle TB outbreak was 13 km and 27 km for seropositive and seronegative wild boar, respectively; P<0.05). The use of an ELISA to detect MTC antibodies in wild boar has permitted the description of the geographic distribution of MTC contact in wild boar in France. Our results suggest that the ELISA could be used as a first screening tool to conduct TB surveillance in wild boar at a population level. High-risk wild boar populations (e.g. overabundant) could be tested and if identified positive by ELISA they should be surveyed in detail by combining pathology and culture.

Exposure of Wild Boar to Mycobacterium tuberculosis Complex in France since 2000 Is Consistent with the Distribution of Bovine Tuberculosis Outbreaks in Cattle

PubMed Central

Richomme, Céline; Boadella, Mariana; Courcoul, Aurélie; Durand, Benoît; Drapeau, Antoine; Corde, Yannick; Hars, Jean; Payne, Ariane; Fediaevsky, Alexandre; Boschiroli, María Laura

2013-01-01

The Eurasian wild boar (Sus scrofa) is increasingly considered as a relevant actor in the epidemiology of animal tuberculosis (TB). Therefore, monitoring TB in wild boar becomes a key tool for establishing comprehensive control schemes for this disease. To estimate the exposure of free living wild boar to Mycobacterium tuberculosis complex (MTC) in France, a bovine-purified protein derivative based ELISA was used to test 2,080 archived serum samples of hunter-harvested animals in 58 French “départements”. Two cut-off values were used for diagnostic interpretation: 0.2, recommended by the manufacturer (specificity: 96.43%; sensitivity: 72.6%), and 0.5 (specificity: 100%; sensitivity: 64%). During the same period, at the 0.2 cut-off, global true seroprevalence was 5.9% (IC95%: 4.3%-7.7%) and 76% of the sampled “départements” had seropositive wild boar, including seven cattle TB-free “départements. At the 0.5 cut-off, global true seroprevalence was 2.2% (IC95%: 1.5-3.2) and positive wild boar belonged to 21% of the “départements”. All but one of these positive “départements” had reported at least one cattle TB outbreak since 2000. A good consistence between seropositive wild boar and TB outbreaks in cattle was found, especially at the 0.5 cut-off value (the mean distance to the nearest cattle TB outbreak was 13km and 27km for seropositive and seronegative wild boar, respectively; P<0.05). The use of an ELISA to detect MTC antibodies in wild boar has permitted the description of the geographic distribution of MTC contact in wild boar in France. Our results suggest that the ELISA could be used as a first screening tool to conduct TB surveillance in wild boar at a population level. High-risk wild boar populations (e.g. overabundant) could be tested and if identified positive by ELISA they should be surveyed in detail by combining pathology and culture. PMID:24167584

Scatter and crosstalk corrections for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging using a CZT SPECT system with pinhole collimators

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

Fan, Peng; Hutton, Brian F.; Holstensson, Maria

2015-12-15

Purpose: The energy spectrum for a cadmium zinc telluride (CZT) detector has a low energy tail due to incomplete charge collection and intercrystal scattering. Due to these solid-state detector effects, scatter would be overestimated if the conventional triple-energy window (TEW) method is used for scatter and crosstalk corrections in CZT-based imaging systems. The objective of this work is to develop a scatter and crosstalk correction method for {sup 99m}Tc/{sup 123}I dual-radionuclide imaging for a CZT-based dedicated cardiac SPECT system with pinhole collimators (GE Discovery NM 530c/570c). Methods: A tailing model was developed to account for the low energy tail effectsmore » of the CZT detector. The parameters of the model were obtained using {sup 99m}Tc and {sup 123}I point source measurements. A scatter model was defined to characterize the relationship between down-scatter and self-scatter projections. The parameters for this model were obtained from Monte Carlo simulation using SIMIND. The tailing and scatter models were further incorporated into a projection count model, and the primary and self-scatter projections of each radionuclide were determined with a maximum likelihood expectation maximization (MLEM) iterative estimation approach. The extracted scatter and crosstalk projections were then incorporated into MLEM image reconstruction as an additive term in forward projection to obtain scatter- and crosstalk-corrected images. The proposed method was validated using Monte Carlo simulation, line source experiment, anthropomorphic torso phantom studies, and patient studies. The performance of the proposed method was also compared to that obtained with the conventional TEW method. Results: Monte Carlo simulations and line source experiment demonstrated that the TEW method overestimated scatter while their proposed method provided more accurate scatter estimation by considering the low energy tail effect. In the phantom study, improved defect contrasts were observed with both correction methods compared to no correction, especially for the images of {sup 99m}Tc in dual-radionuclide imaging where there is heavy contamination from {sup 123}I. In this case, the nontransmural defect contrast was improved from 0.39 to 0.47 with the TEW method and to 0.51 with their proposed method and the transmural defect contrast was improved from 0.62 to 0.74 with the TEW method and to 0.73 with their proposed method. In the patient study, the proposed method provided higher myocardium-to-blood pool contrast than that of the TEW method. Similar to the phantom experiment, the improvement was the most substantial for the images of {sup 99m}Tc in dual-radionuclide imaging. In this case, the myocardium-to-blood pool ratio was improved from 7.0 to 38.3 with the TEW method and to 63.6 with their proposed method. Compared to the TEW method, the proposed method also provided higher count levels in the reconstructed images in both phantom and patient studies, indicating reduced overestimation of scatter. Using the proposed method, consistent reconstruction results were obtained for both single-radionuclide data with scatter correction and dual-radionuclide data with scatter and crosstalk corrections, in both phantom and human studies. Conclusions: The authors demonstrate that the TEW method leads to overestimation in scatter and crosstalk for the CZT-based imaging system while the proposed scatter and crosstalk correction method can provide more accurate self-scatter and down-scatter estimations for quantitative single-radionuclide and dual-radionuclide imaging.« less

Generalized five-dimensional dynamic and spectral factor analysis

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

El Fakhri, Georges; Sitek, Arkadiusz; Zimmerman, Robert E.

2006-04-15

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming thatmore » primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where {sup 99m}Tc and {sup 123}I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary {sup 99m}Tc (bias=6.4%{+-}4.3%) and {sup 123}I (-1.7%{+-}6.9%) time activity curves (TAC) compared to conventional FADS (biases=15.5%{+-}10.6% in {sup 99m}Tc and 8.3%{+-}12.7% in {sup 123}I, p<0.05). Our technique was also validated in two primate dynamic dual isotope perfusion/DAT transporter studies. Biases of {sup 99m}Tc-HMPAO and {sup 123}I-DAT activity estimates with respect to estimates obtained in the presence of only one radionuclide (sequential imaging) were significantly lower with 5D-GFA (9.4%{+-}4.3% for {sup 99m}Tc-HMPAO and 8.7%{+-}4.1% for {sup 123}I-DAT) compared to biases greater than 15% for volumes of interest (VOI) over the reconstructed volumes (p<0.05). 5D-GFA is a novel and promising approach in dynamic SPECT imaging that can also be used in other modalities. It allows accurate and precise dynamic analysis while compensating for Compton scatter and cross-talk.« less

Surgical cure rates of sporadic medullary thyroid cancer in the era of calcitonin screening.

PubMed

Machens, Andreas; Dralle, Henning

2016-09-01

Time trends of the extent of disease at first diagnosis and biochemical cure remain ill-defined for sporadic medullary thyroid cancer (MTC). This investigation aimed to delineate time trends and biochemical cure rates for sporadic MTC. This was an observational study of consecutive patients operated on for sporadic MTC between 1995 and 2015. Time trends of clinical and histopathological variables indicative of the extent of disease and biochemical cure were calculated for 600 patients with sporadic MTC, 322 of whom had initial neck surgery and 278 of whom had neck reoperation at a tertiary surgical center in Germany. From 1995-2000 to 2011-2015, significant declines (all P<0.001) were noted in the percentage of node-positive tumors (from 73 to 49%), mediastinal lymph node metastasis (from 21 to 6%) and distant metastasis (from 23 to 6%). These changes were paralleled by significant increases (all P<0.001) in mean patient age (from 49.1 to 57.3years) and the percentage of MTC ≤10mm (from 19 to 39%) and biochemical cure (from 28 to 62%). When only patients with primary tumors >10mm were considered, the decreasing percentage of mediastinal lymph node metastasis and distant metastasis, and rising mean patient age and biochemical cure rates remained statistically significant. Significant reductions in the extent of the disease and improved biochemical cure rates pointed toward increasing therapeutic control of sporadic MTC. The independent contribution of routine calcitonin screening to these time-dependent changes warrants more research. © 2016 European Society of Endocrinology.

Investigation of SP94 Peptide as a Specific Probe for Hepatocellular Carcinoma Imaging and Therapy

PubMed Central

Li, Yanli; Hu, Yan; Xiao, Jie; Liu, Guobing; Li, Xiao; Zhao, Yanzhao; Tan, Hui; Shi, Hongcheng; Cheng, Dengfeng

2016-01-01

SP94 (SFSIIHTPILPL), a novel peptide, has shown specific binding to hepatocellular carcinoma (HCC) cells. We aimed to investigate the capability of SP94 as a targeting probe for HCC imaging and therapy following labeling with technetium-99m (99mTc) and rhenium-188 (188Re). HYNIC-SP94 was prepared by solid phase synthesis and then labeled with 99mTc. Cell competitive binding, internalization assay, in vitro and in vivo stability, biodistribution and micro-single photon emission computed tomography /computed tomography (SPECT/CT) imaging studies were performed to investigate the capability of 99mTc tricine-EDDA/HYNIC-SP94 as a specific HCC imaging probe. Initial promising targeting results inspired evaluation of its therapeutic effect when labeled by 188Re. HYNIC-SP94 was then labeled again with 188Re to perform cell apoptosis, microSPECT/CT imaging evaluation and immunohistochemistry. Huh-7 cells exhibited typical apoptotic changes after 188Re irradiation. According to 99mTc tricine-EDDA/HYNIC-SP94 microSPECT/CT imaging, tumor uptake was significantly decreased compared with that of pre-treatment with 188Re-HYNIC-SP94. The immunohistochemistry also displayed obvious necrosis and apoptosis as well as inhibition of proliferation in the 188Re-HYNIC-SP94 treatment group. The results supported that 99mTc tricine-EDDA/HYNIC-SP94 is able to target HCC cells and 188Re-HYNIC- SP94 holds potential as a therapeutic agent for HCC, making 99mTc/188Re-HYNIC-SP94 a promising targeting probe for HCC imaging and therapy. PMID:27649935

Hyalinizing Trabecular Tumor of the Thyroid Gland, a Diagnostic Challenge in Fine-Needle Aspiration Cytology: Case Report.

PubMed

Rhee, Ye-Young; Jung, Hong Kyu; Kim, Se Hoon; Kim, Soo Hee

2018-06-11

Hyalinizing trabecular tumor (HTT) is a rare thyroid tumor with low to minimal malignant potential. HTT is often misinterpreted as other thyroid tumors, including papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC), on fine-needle aspiration (FNA) cytology, because of its overlapping cytologic features, such as nuclear grooves and intranulcear pseudoinclusions. Although cytopathologists cannot definitely conclude HTT by FNA cytology, suspicion of HTT is necessary to avoid misdiagnosing HTT as PTC or MTC and to avoid unnecessary aggressive treatment. Here, we report a case of HTT with novel cytologic features in CellPrep liquid based cytology that was diagnosed as suspicious for papillary carcinoma by FNA and finally diagnosed as HTT in the surgical specimen.

Small vessel hematocrit in ischemic myocardium

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

Gumm, D.C.; Cooper, S.M.; Marcus, M.L.

1986-03-01

As blood enters the microvasculature of normally perfused myocardium, there is a progressive decrease in small vessel hematocrit (SV Hct) due to RBC streaming in smaller branching vessels and the Fahraeus-Lindqvist effect. We hypothesized that if the coronary collateral circulation was composed of very small vessels branching from large parent vessels, plasma streaming would result in a further decrease of SV Hct in ischemic myocardium. Six open chest anesthetized dogs were studied. Plasma was labelled with /sup 59/FeCl siderophilin and RBC's with /sup 99/mTc to estimate SV Hct from myocardial biopsies. The LAD was occluded and cannulated for measurement ofmore » retrograde flow (arising presumably from proximal collaterals). The ischemic region was identified using the microsphere shadow technique. Collateral flow after LAD occlusion was 30 +- 12 ml/min 100g (x +- SE). Systemic Hct was 40 +- 1%. The Hct of blood from retrograde flow was 39 +- 1% (p = NS). Activity of /sup 59/FeCl and /sup 99/mTc in known quantities of blood were compared to myocardial biopsies to estimate SV Hct. Ischemic SV Hct was 23 +- 2% and non-ischemic SV Hct was 21 +- 1% (p = NS). We conclude that the size and branching pattern of coronary collaterals is such that plasma streaming in collaterals does not result in an additional decrease in SV Hct in ischemic myocardium.« less

Diversification in the Supply Chain of (99)Mo Ensures a Future for (99m)Tc.

PubMed

Cutler, Cathy S; Schwarz, Sally W

2014-07-01

The uncertain availability of (99m)Tc has become a concern for nuclear medicine departments across the globe. An issue for the United States is that currently it is dependent on a supply of (99m)Tc (from (99)Mo) that is derived solely by production outside the United States. Since the United States uses half the world's (99)Mo production, the U.S. (99)Mo supply chain would be greatly enhanced if a producer were located within the United States. The fragility of the old (99)Mo supply chain is being addressed as new facilities are constructed and new processes are developed to produce (99)Mo without highly enriched uranium. The conversion to low-enriched uranium is necessary to minimize the potential misuse of highly enriched uranium in the world for nonpeaceful means. New production facilities, new methods for the production of (99)Mo, and a new generator elution system for the supply of (99m)Tc are currently being pursued. The progress made in all these areas will be discussed, as they all highlight the need to embrace diversity to ensure that we have a robust and reliable supply of (99m)Tc in the future. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI

PubMed Central

Gao, Shi; Ji, Tiefeng; Wen, Qiang; Song, Yan; Zhu, Lei; Xu, Zheli; Liu, Lin

2014-01-01

Purpose To compare the potential application of 99mTc-3P-Arg-Gly-Asp (99mTc-3P4-RGD2) scintimammography (SMM) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions. Method Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. 99mTc-3P4-RGD2 and 99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases. Results The mean T/NT ratio of 99mTc-3P4-RGD2 in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of 99mTc-3P4-RGD2 SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of 99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of 99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for 99mTc-3P4-RGD2 SMM (area = 0.851) was higher than that for 99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant. Conclusion 99mTc-3P4-RGD2 SMM does not provide any significant advantage over the established 99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of 99mTc-3P4-RGD2 SMM was significantly higher than that of 99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms. PMID:25250628

Development of an Automated Security Incident Reporting System (SIRS) for Bus Transit

DOT National Transportation Integrated Search

1986-12-01

The security incident reporting system (sirs) is a microcomputer-based software program demonstrated at the metropolitan transit commission (mtc) in Minneapolis, mn. Sirs is designed to provide convenient storage, update and retrieval of security inc...

A biokinetic model for systemic technetium in adult humans

DOE PAGES

Leggett, Richard Wayne; Giussani, Augusto

2015-04-10

The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T 1/2=2.1x10 5 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T 1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body formore » use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

Sentinel lymph node status in vulval cancer: systematic reviews of test accuracy and decision-analytic model-based economic evaluation.

PubMed

Meads, C; Sutton, A; Małysiak, S; Kowalska, M; Zapalska, A; Rogozinska, E; Baldwin, P; Rosenthal, A; Ganesan, R; Borowiack, E; Barton, P; Roberts, T; Sundar, S; Khan, K

2013-12-01

Vulval cancer causes 3-5% of all gynaecological malignancies and requires surgical removal and inguinofemoral lymphadenectomy (IFL). Complications affect > 50% of patients, including groin wound infection, lymphoedema and cellulitis. A sentinel lymph node (SLN) is the first groin node with the highest probability of malignancy. SLN biopsy would be useful if it could accurately identify patients in whom cancer has spread to the groin, without removing all groin nodes. SLNs can be identified by isosulfan blue dye and/or technetium-99 ((99m)Tc) radioactive tracer during lymphoscintigraphy. The blue dye/(99m)Tc procedure only detects SLN, not metastases - this requires histological examination, which can include ultrastaging and staining with conventional haematoxylin and eosin (H&E) or immunohistochemistry. To determine the test accuracy and cost-effectiveness of the SLN biopsy with (99m)Tc and/or blue dye compared with IFL or clinical follow-up for test negatives in vulval cancer, through systematic reviews and economic evaluation. Standard medical databases, including MEDLINE, EMBASE, Science Citation Index and The Cochrane Library, medical search gateways, reference lists of review articles and included studies were searched to January 2011. For accuracy and effectiveness, standard methods were used and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were to January 2011, with no language restrictions. Meta-analyses were carried out with Meta-Disc version 1.4 (Javier Zamora, Madrid, Spain) for accuracy; none was appropriate for effectiveness. The economic evaluation from a NHS perspective used a decision-tree model in DATA TreeAge Pro Healthcare 2001 (TreeAge Software, Inc., Williamstown, MA, USA). Six options (blue dye with H&E, blue dye with ultrastaging, (99m)Tc with H&E, (99m)Tc with ultrastaging, blue dye/(99m)Tc with H&E, blue dye/(99m)Tc with ultrastaging) were compared with IFL. Deterministic and probabilistic sensitivity analyses were conducted. For accuracy, of the 26 included studies, most evaluated (99m)Tc/blue dye combined. Four studies had clinical follow-up only for test negatives and five had clinical follow-up for all and IFL for test negatives. Numbers with no SLN found were difficult to distinguish from those with negative SLN biopsies. The largest group of 11 studies using (99m)Tc/blue dye, ultrastaging and immunohistochemistry had a pooled sensitivity of 95.6% [95% confidence interval (CI) 91.5% to 98.1%] and a specificity of 100% (95% CI 99.0% to 100%). Mean SLN detection rates were 94.6% for (99m)Tc, 68.7% for blue dye and 97.7% for both. One study measured global health status quality of life (QoL) and found no difference between SLN biopsy and IFL. One patient preference evaluation showed that 66% preferred IFL rather than a 5% false-negative rate from SLN biopsy. For effectiveness, of 14,038 references, one randomised controlled trial, three case-control studies and 13 case series were found. Approximately 50% died from vulval cancer and 50% from other causes during follow-ups. Recurrences were in the ratio of approximately 4 : 2 : 1 vulval, groin and distant, with more recurrences in node-positive patients. No studies reported QoL. For cost per death averted, IFL was less costly and more effective than strategies using SLN biopsy. For morbidity-free survival and long-term morbidity-free survival, (99m)Tc with ultrastaging was most cost-effective. Strategies with blue dye only and H&E only were never cost-effective. The incremental cost-effectiveness ratio for (99m)Tc with ultrastaging compared with IFL was £4300 per case of morbidity-free survival and £7100 per long-term morbidity-free survival. The main limitations of this study include the lack of good-quality evidence on accuracy, effectiveness and QoL. A large project such as this takes time to publish, so the most recent studies are not included. A sensitive and specific combined metastatic SLN detection test and information on generic QoL in vulval cancer is urgently required. The National Institute for Health Research Health Technology Assessment programme.

Rapid and accurate identification of Mycobacterium tuberculosis complex and common non-tuberculous mycobacteria by multiplex real-time PCR targeting different housekeeping genes.

PubMed

Nasr Esfahani, Bahram; Rezaei Yazdi, Hadi; Moghim, Sharareh; Ghasemian Safaei, Hajieh; Zarkesh Esfahani, Hamid

2012-11-01

Rapid and accurate identification of mycobacteria isolates from primary culture is important due to timely and appropriate antibiotic therapy. Conventional methods for identification of Mycobacterium species based on biochemical tests needs several weeks and may remain inconclusive. In this study, a novel multiplex real-time PCR was developed for rapid identification of Mycobacterium genus, Mycobacterium tuberculosis complex (MTC) and the most common non-tuberculosis mycobacteria species including M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and the M. gordonae in three reaction tubes but under same PCR condition. Genetic targets for primer designing included the 16S rDNA gene, the dnaJ gene, the gyrB gene and internal transcribed spacer (ITS). Multiplex real-time PCR was setup with reference Mycobacterium strains and was subsequently tested with 66 clinical isolates. Results of multiplex real-time PCR were analyzed with melting curves and melting temperature (T (m)) of Mycobacterium genus, MTC, and each of non-tuberculosis Mycobacterium species were determined. Multiplex real-time PCR results were compared with amplification and sequencing of 16S-23S rDNA ITS for identification of Mycobacterium species. Sensitivity and specificity of designed primers were each 100 % for MTC, M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and M. gordonae. Sensitivity and specificity of designed primer for genus Mycobacterium was 96 and 100 %, respectively. According to the obtained results, we conclude that this multiplex real-time PCR with melting curve analysis and these novel primers can be used for rapid and accurate identification of genus Mycobacterium, MTC, and the most common non-tuberculosis Mycobacterium species.

Micronutrient status (calcium, zinc, vitamins D and E) in patients with medullary thyroid carcinoma: A cross-sectional study.

PubMed

Emami, Ali; Nazem, Mohammad Reza; Shekarriz, Reza; Hedayati, Mehdi

2017-09-01

The aim of this study was to evaluate the micronutrient status of Iranian patients with medullary thyroid carcinoma (MTC) and to analyze potential relationships with respect to MTC risk. This was a cross-sectional study (Tehran Thyroid Cancer Survey 2015-2016). We measured and compared preoperative serum calcium, zinc, and vitamins D and E in patients with MTC and healthy controls. Forty cases with MTC and 40 (age-, sex-, and body mass index-matched) healthy controls voluntarily participated in the project. Serum calcium, zinc, and vitamin D and E concentrations were lower in the patients with cancer (P Ca < 0.001, P Zn  = 0.01, P D  = 0.056, P E  = 0.002) than in the healthy controls. We found that serum calcium remarkably associated with enhanced risk for thyroid cancer (odds ratio [OR], 6.5; P = 0.001). Likewise, serum vitamin E was linked to the risk for cancer (OR, 1.31; P = 0.056). Moreover, serum zinc was correlated with vitamin E and calcium (r = +0.23; P = 0.04 and r = +0.25, P = 0.03; respectively). We also observed a correlation between calcium and vitamin E (r = +0.27; P = 0.02). A multiple-micronutrient decrease was confirmed in patients with MTC. A low serum calcium level was a potent risk factor for MTC. Findings from the present study suggest that dietary intake and/or supplementation of micronutrients, especially calcium and vitamin E, may be beneficial in reducing the risk for thyroid cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

The Effect of Mobile Tablet Computer (iPad) Implementation on Graduate Medical Education at a Multi-specialty Residency Institution.

PubMed

Dupaix, John; Chen, John J; Chun, Maria Bj; Belcher, Gary F; Cheng, Yongjun; Atkinson, Robert

2016-07-01

Use of mobile tablet computers (MTCs) in residency education has grown. The objective of this study was to investigate the impact of MTCs on multiple specialties' residency training and identify MTC adoption impediments. To our knowledge, this current project is one of the first multispecialty studies of MTC implementation. A prospective cohort study was formulated. In June 2012 iPad2s were issued to all residents after completion of privacy/confidentiality agreements and a mandatory hard-copy pre-survey regarding four domains of usage (general, self-directed learning, clinical duties, and patient education). Residents who received iPads previously were excluded. A voluntary post-survey was conducted online in June 2013. One-hundred eighty-five subjects completed pre-survey and 107 completed post-survey (58% overall response rate). Eighty-six pre- and post-surveys were linked (response rate of 46%). There was a significant increase in residents accessing patient information/records and charting electronically (26.9% to 79.1%; P<.001), but a significant decrease in looking up drug and treatment reference material (97.0% to 82.1%; P=.0039). There was a significant increase in MTC use as a primary means of charting when conducting rounds (4.9% to 39.5%; P<.001) and a significant decrease in using paper charts (30.1% to 15.7%; P=.0073). There was also a significant increase in MTC use as a primary means for explaining a diagnosis (7.7% to 57.7%; P<.001). The use of MTC has an impact on how residents approach medical education, clinical practice, and patient education. The survey tool may be useful in collecting data on MTC use by other graduate medical education programs.

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours

PubMed Central

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

Objective(s): The objective of this study was to evaluate the performance and utility of 99mTc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). Methods: 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent 99mTc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of 99mTc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with 99mTc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. Results: 99mTc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). Conclusion: 99mTc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options. PMID:27408857

Clinical utility of indigenously formulated single-vial lyophilized HYNIC-TOC kit in evaluating Gastro-entero Pancreatic neuro endocrine tumours.

PubMed

Shinto, Ajit S; Kamaleshwaran, K; Vyshak, K; Sudhakar, Natarajan; Banerjee, Sharmila; Korde, Aruna; Samuel, Grace; Mallia, Madhav

2014-01-01

The objective of this study was to evaluate the performance and utility of (99m)Tc HYNIC-TOC planar scintigraphy and SPECT/CT in the diagnosis, staging and management of gastroenteropancreatic neuroendocrine tumors (GPNETs). 22 patients (median age, 46 years) with histologically proven gastro- entero- pancreatic NETs underwent (99m)Tc HYNIC-TOC whole body scintigraphy and regional SPECT/CT as indicated. Scanning was performed after injection of 370-550 MBq (10-15 mCi) of (99m)Tc HYNIC-TOC intravenously. Images were evaluated by two experienced nuclear medicine physicians both qualitatively as well as semi quantitatively (tumor to background and tumor to normal liver ratios on SPECT -CT images). Results of SPECT/CT were compared with the results of conventional imaging. Histopathology results and follow-up somatostatin receptor scintigraphy with (99m)Tc HYNIC TOC or conventional imaging with biochemical markers were considered to be the reference standards. (99m)Tc HYNIC TOC showed sensitivity and specificity of 87.5% and 85.7%, respectively, for primary tumor and 100% and 86% for metastases. It was better than conventional imaging modalities for the detection of both primary tumor (P<0.001) and metastases (P<0.0001). It changed the management strategy in 6 patients (31.8%) and supported management decisions in 8 patients (36.3%). (99m)Tc HYNIC TOC SPECT/CT appears to be a highly sensitive and specific modality for the detection and staging of GPNETs. It is better than conventional imaging for the evaluation of GPNETs and can have a significant impact on patient management and planning further therapeutic options.

MicroRNA-375/SEC23A as biomarkers of the in vitro efficacy of vandetanib.

PubMed

Lassalle, Sandra; Zangari, Joséphine; Popa, Alexandra; Ilie, Marius; Hofman, Véronique; Long, Elodie; Patey, Martine; Tissier, Frédérique; Belléannée, Geneviève; Trouette, Hélène; Catargi, Bogdan; Peyrottes, Isabelle; Sadoul, Jean-Louis; Bordone, Olivier; Bonnetaud, Christelle; Butori, Catherine; Bozec, Alexandre; Guevara, Nicolas; Santini, José; Hénaoui, Imène Sarah; Lemaire, Géraldine; Blanck, Olivier; Vielh, Philippe; Barbry, Pascal; Mari, Bernard; Brest, Patrick; Hofman, Paul

2016-05-24

In this study, we performed microRNA (miRNA) expression profiling on a large series of sporadic and hereditary forms of medullary thyroid carcinomas (MTC). More than 60 miRNAs were significantly deregulated in tumor vs adjacent non-tumor tissues, partially overlapping with results of previous studies. We focused our attention on the strongest up-regulated miRNA in MTC samples, miR-375, the deregulation of which has been previously observed in a variety of human malignancies including MTC. We identified miR-375 targets by combining gene expression signatures from human MTC (TT) and normal follicular (Nthy-ori 3-1) cell lines transfected with an antagomiR-375 inhibitor or a miR-375 mimic, respectively, and from an in silico analysis of thyroid cell lines of Cancer Cell Line Encyclopedia datasets. This approach identified SEC23A as a bona fide miR-375 target, which we validated by immunoblotting and immunohistochemistry of non-tumor and pathological thyroid tissue. Furthermore, we observed that miR-375 overexpression was associated with decreased cell proliferation and synergistically increased sensitivity to vandetanib, the clinically relevant treatment of metastatic MTC. We found that miR-375 increased PARP cleavage and decreased AKT phosphorylation, affecting both cell proliferation and viability. We confirmed these results through SEC23A direct silencing in combination with vandetanib, highlighting the importance of SEC23A in the miR-375-associated increased sensitivity to vandetanib.Since the combination of increased expression of miR-375 and decreased expression of SEC23A point to sensitivity to vandetanib, we question if the expression levels of miR-375 and SEC23A should be evaluated as an indicator of eligibility for treatment of MTC patients with vandetanib.

The Effect of Mobile Tablet Computer (iPad) Implementation on Graduate Medical Education at a Multi-specialty Residency Institution

PubMed Central

Dupaix, John; Chun, Maria BJ; Belcher, Gary F; Cheng, Yongjun; Atkinson, Robert

2016-01-01

Use of mobile tablet computers (MTCs) in residency education has grown. The objective of this study was to investigate the impact of MTCs on multiple specialties' residency training and identify MTC adoption impediments. To our knowledge, this current project is one of the first multispecialty studies of MTC implementation. A prospective cohort study was formulated. In June 2012 iPad2s were issued to all residents after completion of privacy/confidentiality agreements and a mandatory hard-copy pre-survey regarding four domains of usage (general, self-directed learning, clinical duties, and patient education). Residents who received iPads previously were excluded. A voluntary post-survey was conducted online in June 2013. One-hundred eighty-five subjects completed pre-survey and 107 completed post-survey (58% overall response rate). Eighty-six pre- and post-surveys were linked (response rate of 46%). There was a significant increase in residents accessing patient information/records and charting electronically (26.9% to 79.1%; P<.001), but a significant decrease in looking up drug and treatment reference material (97.0% to 82.1%; P=.0039). There was a significant increase in MTC use as a primary means of charting when conducting rounds (4.9% to 39.5%; P<.001) and a significant decrease in using paper charts (30.1% to 15.7%; P=.0073). There was also a significant increase in MTC use as a primary means for explaining a diagnosis (7.7% to 57.7%; P<.001). The use of MTC has an impact on how residents approach medical education, clinical practice, and patient education. The survey tool may be useful in collecting data on MTC use by other graduate medical education programs. PMID:27437163

99mTc ovalbumin labelled eggs for gastric emptying scintigraphy: in-vitro comparison of solid food markers.

PubMed

Blanc, Frédérique; Salaun, Pierre Y; Couturier, Olivier; Querellou, Solène; Le Duc-Pennec, Alexandra; Mougin-Degraef, Marie; Bizais, Yves; Legendre, Jean M

2005-11-01

The reliability of solid phase gastric emptying measurements by scintigraphy requires a marker that remains within the solid component of the test meal, and which is not degraded by the gastric juice throughout the scintigraphic procedure. In Europe, foods are most often labelled with 99mTc rhenium sulfide macrocolloid (RSMC) but this solid phase marker was withdrawn from the market in January 2004. To test other potential solid phase markers and to compare them to the reference marker RSMC. These markers were rhenium sulfide nanocolloid (RSNC), tin fluoride colloid (TFC), phytates and two albumins (Alb and AlbC). All were radiolabelled with 99mTc. After quality control, each 99mTc marker was incorporated into the albumin of one egg. Then, egg white and yolk were mixed together, and a well-cooked omelette was prepared. Aliquots of the omelette were incubated with an acidic solution of pepsin at 37 degrees C which mimicked gastric juice. Unbound radioactivity in the supernatant fraction was measured at various times up to 3 h. The radiochemical purity was > 95% for all radiopharmaceuticals. During the in-vitro incubation, the percentage of 99mTc labelled colloids released from the omelette increased continuously: after 3 h, 5% for TFC and RSMC, 8% for phytates, and > 9% for the two albumins and RSNC. Considering quality controls and release of 99mTc during in-vitro incubation of the omelette, TFC showed the same behaviour as the reference marker RSMC. Thus, TFC seems to be the best candidate to replace RSMC for the radiolabelling of the solid phase of the gastric emptying test meal.

99mTc-tagged chicken liver as a marker of solid food in the human stomach.

PubMed

Meyer, J H; MacGregor, I L; Gueller, R; Martin, P; Cavalieri, R

1976-04-01

Past measurement of gastric emptying of solid food in man has depended on external counting of surface-absorbed isotopes without verification that isotopic labels remain attached to solid food in the stomach. In this study chicken liver was isotopically labeled with 99mTc incorporated uniformly and intracellularly throughout the liver substance. In vitro studies showed less than 10% loss of 99mTc from liver incubated with pepsin HC1. By contrast, up to 90% of 51Cr absorbed to scrambled eggs became detached under similar conditions. In feeding experiments less than 10% of 99mTc was liberated from fed 99mTc liver, while significantly more 51Cr became detached from egg under identical intragastric conditions. We conclude that 99mTc-tagged chicken liver is an adequate marker of the rate of emptying of solid food and appears to be more reliable than 51Cr-labeled scrambled eggs from which 51Cr dissociates in the stomach.

Mechanics of single cells: rheology, time dependence, and fluctuations.

PubMed

Massiera, Gladys; Van Citters, Kathleen M; Biancaniello, Paul L; Crocker, John C

2007-11-15

The results of mechanical measurements on single cultured epithelial cells using both magnetic twisting cytometry (MTC) and laser tracking microrheology (LTM) are described. Our unique approach uses laser deflection for high-performance tracking of cell-adhered magnetic beads either in response to an oscillatory magnetic torque (MTC) or due to random Brownian or ATP-dependent forces (LTM). This approach is well suited for accurately determining the rheology of single cells, the study of temporal and cell-to-cell variations in the MTC signal amplitude, and assessing the statistical character of the tracers' random motion in detail. The temporal variation of the MTC rocking amplitude is surprisingly large and manifests as a frequency-independent multiplicative factor having a 1/f spectrum in living cells, which disappears upon ATP depletion. In the epithelial cells we study, random bead position fluctuations are Gaussian to the limits of detection both in the Brownian and ATP-dependent cases, unlike earlier studies on other cell types.

WE-AB-204-12: Dosimetry at the Sub-Cellular Scale of Auger-Electron Emitter 99m-Tc in a Mouse Single Thyroid Follicle Model

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

Taborda, A; Benabdallah, N; Desbree, A

2015-06-15

Purpose: To perform a dosimetry study at the sub-cellular scale of Auger-electron emitter 99m-Tc using a mouse single thyroid cellular model to investigate the contribution of the 99m-Tc Auger-electrons to the absorbed dose and possible link to the thyroid stunning in in vivo experiments in mice, recently reported in literature. Methods: The simulation of S-values for Auger-electron emitting radionuclides was performed using both the recent MCNP6 software and the Geant4-DNA extension of the Geant4 toolkit. The dosimetric calculations were validated through comparison with results from literature, using a simple model of a single cell consisting of two concentric spheres ofmore » unit density water and for six Auger-electron emitting radionuclides. Furthermore, the S-values were calculated using a single thyroid follicle model for uniformly distributed 123-I and 125-I radionuclides and compared with published S-values. After validation, the simulation of the S-values was performed for the 99m-Tc radionuclide within the several mouse thyroid follicle cellular compartments, considering the radiative and non-radiative transitions of the 99m-Tc radiation spectrum. Results: The calculated S-values using MCNP6 are in good agreement with the results from literature, validating its use for the 99m-Tc S-values calculations. The most significant absorbed dose corresponds to the case where the radionuclide is uniformly distributed in the follicular cell’s nucleus, with a S-value of 7.8 mGy/disintegration, due mainly to the absorbed Auger-electrons. The results show that, at a sub-cellular scale, the emitted X-rays and gamma particles do not contribute significantly to the absorbed dose. Conclusion: In this work, MCNP6 was validated for dosimetric studies at the sub-cellular scale. It was shown that the contribution of the Auger-electrons to the absorbed dose is important at this scale compared to the emitted photons’ contribution and can’t be neglected. The obtained S-values of Auger-electron emitting 99m-Tc radionuclide will be presented and discussed.« less

Lipid Peroxidation and Antioxidant Status in Patients with Medullary Thyroid Carcinoma: A Case-Control Study

PubMed Central

Hosseini-Zijoud, Seyed-Mostafa; Ebadi, Seyed Alireza; Goodarzi, Mohammad Taghi; Hedayati, Mehdi; Abbasalipourkabir, Roghayeh; Mahjoob, Mohammad Parsa; Poorolajal, Jalal; Zicker, Fabio

2016-01-01

Introduction Oxidative stress or oxidant/antioxidant imbalance has a crucial role in the pathogenesis of some diseases like cancer. Medullary thyroid carcinoma (MTC) originates in the thyroid parafollicular cells and includes 3-4% of the malignant neoplasms that have an effect on this gland. The aetiology of MTC has not been clarified. However, oxidative stress may be one of the factors involved. Aim The aim of the current study was to evaluate the antioxidant enzyme activity of catalase (CAT), Glutathione (GSH), total antioxidant capacity (TAC) and the levels of the lipid peroxidation product malondialdehyde (MDA) in blood samples of MTC patients as compared to healthy controls. Materials and Methods A case-control study was designed enrolling patients with confirmed MTC diagnosis and age-and sex group matched healthy volunteers referred to the clinic of the Research Institute for Endocrine Sciences, Tehran, Iran from April 2013 to July 2015. Fasting blood samples were taken for study. Catalase, GSH, MDA and TAC levels were measured by colorimetry using commercial kits (ZellBio GmbH, Germany). Data were analysed using SPSS 17 software, comparing mean±SD through t-test and difference between proportions through chi-square. Results No statistical difference was observed in the demographic characteristic between cases and controls. The final MTC group included 40 males and 45 females with a mean age of 30±12.9 year, and the control group 40 males and 47 females, with a mean age of 31.2±12.3 year. Anthropometric parameters, dietary and thyroid hormones levels (T3, T4 and TSH) were similar. Serum TAC (p=0.015), GSH (p=0.029) and CAT (p<0.001) levels were found to be significantly lower in the MTC patients, while serum MDA levels were significantly higher in MTC patients than controls (p<0.001). Conclusion These preliminary findings suggest that oxidant/antioxidant imbalance may be associated with or possibly indicate an increased risk to medullary thyroid carcinoma. Further studies are needed to explore these findings. PMID:27042443

Animal tuberculosis maintenance at low abundance of suitable wildlife reservoir hosts: A case study in northern Spain.

PubMed

Gortázar, C; Fernández-Calle, L M; Collazos-Martínez, J A; Mínguez-González, O; Acevedo, P

2017-10-01

Animal tuberculosis (TB), which is caused by infection with members of the Mycobacterium tuberculosis complex (MTC), is a typical multi-host infection that flourishes at the livestock-wildlife interface. TB epidemiology is well characterized in the Mediterranean woodland habitats and Atlantic regions of southwestern Europe. However, much less is known about huge regions that do not form part of the two abovementioned settings, which have a low abundance of wild reservoirs. We hypothesized that MTC would be maintained in multi- rather than single-host communities in which wildlife would make a relatively low contribution to the maintenance of TB. Between 2011 and 2015, 7729 Eurasian wild boar (Sus scrofa) and 1729 wild ruminants were sampled for culture during hunting events on unfenced sites. In addition, 1058 wild ungulates were sampled on 23 fenced hunting estates. Infection prevalence data were modeled along with official data on cattle and goat TB, on livestock distribution and management, and on wild boar abundance. The mean individual MTC infection prevalence was 4.28% in wild boar, while the cattle skin test reactor percent was 0.17%. The prevalence of MTC infection in wild ungulates (mostly wild boar) from the fenced hunting estates was 11.6%. Modeling revealed that the main driver of TB in cattle was their management (beef; communal pastures). However, wild boar abundance, the prevalence of MTC infection in wild boar and the presence of fenced hunting estates also contributed to explaining cattle TB. The model used for goat TB identified communal pastures as a risk factor. The model for the prevalence of MTC infection in wild boar included wild boar abundance and communal pastures. We conclude that the MTC maintenance host community is most likely of a multi-host nature. While cattle and communal pastures pose the main risk regarding TB, it is also necessary to consider increasing wild boar densities and specific risks owing to fenced wildlife. We infer several management implications regarding wildlife management, the wildlife sampling strategy and laboratory testing, the peculiarities of fenced hunting estates, and the wildlife-livestock interface. Copyright © 2017 Elsevier B.V. All rights reserved.

Hydrophobic modification of low molecular weight polyethylenimine for improved gene transfection.

PubMed

Teo, Pei Yun; Yang, Chuan; Hedrick, James L; Engler, Amanda C; Coady, Daniel J; Ghaem-Maghami, Sadaf; George, Andrew J T; Yang, Yi Yan

2013-10-01

Hydrophobic modification of low molecular weight (LMW) polyethylenimine (PEI) is known to increase gene transfection efficiency of LMW PEI. However, few studies have explored how the conjugated hydrophobic groups influence the properties of the modified LMW PEI mainly due to difficulties in obtaining well defined final product compositions and limitations in current chemical synthesis routes. The aim of this study was to modify LMW PEI (Mn 1.8 kDa, PEI-1.8) judiciously with different hydrophobic functional groups and to investigate how hydrophobicity, molecular structure and inclusion of hydrogen bonding properties in the conjugated side groups as well as the conjugation degree (number of primary amine groups of PEI-1.8 modified with hydrophobic groups) influence PEI-1.8 gene transfection efficiency. The modified polymers were characterized for DNA binding ability, particle size, zeta potential, in vitro gene transfection efficiency and cytotoxicity in SKOV-3 human ovarian cancer and HepG2 human liver carcinoma cell lines. The study shows that modified PEI-1.8 polymers are able to condense plasmid DNA into cationic nanoparticles, of sizes ~100 nm, whereas unmodified polymer/DNA complexes display larger particle sizes of 2 μm. Hydrophobic modification also increases the zeta potential of polymer/DNA complexes. Importantly, modified PEI-1.8 shows enhanced transfection efficiency over the unmodified counterpart. Higher transfection efficiency is obtained when PEI-1.8 is modified with shorter hydrophobic groups (MTC-ethyl) as opposed to longer ones (MTC-octyl and MTC-deodecyl). An aromatic structured functional group (MTC-benzyl) also enhances transfection efficiency more than an alkyl functional group (MTC-octyl). An added hydrogen-bonding urea group in the conjugated functional group (MTC-urea) does not enhance transfection efficiency over one without urea (MTC-benzyl). The study also demonstrates that modification degree greatly influences gene transfection, and ~100% substitution of primary amine groups leads to significantly lower gene transfection efficiency. These findings provide insights to modification of PEI for development of effective and non-cytotoxic non-viral vectors. Copyright © 2013 Elsevier Ltd. All rights reserved.

San Francisco Bay Area 1990 Regional Travel Characteristics, Working Paper #4: 1990 MTC Travel Survey

DOT National Transportation Integrated Search

1994-12-01

This working paper is the fourth in a series to document analysis and results : from the 1990 MTC household travel survey. Previous working papers on the 1990 : travel survey covered survey design issues, sample weighting and expansion, and : trip li...

The effect of dimethyl sulfoxide on the induction of DNA strand breaks in plasmid DNA and colony formation of PC Cl3 mammalian cells by alpha-, beta-, and Auger electron emitters (223)Ra, (188)Re, and (99m)Tc.

PubMed

Runge, Roswitha; Oehme, Liane; Kotzerke, Jörg; Freudenberg, Robert

2016-12-01

DNA damage occurs as a consequence of both direct and indirect effects of ionizing radiation. The severity of DNA damage depends on the physical characteristics of the radiation quality, e.g., the linear energy transfer (LET). There are still contrary findings regarding direct or indirect interactions of high-LET emitters with DNA. Our aim is to determine DNA damage and the effect on cellular survival induced by (223)Ra compared to (188)Re and (99m)Tc modulated by the radical scavenger dimethyl sulfoxide (DMSO). Radioactive solutions of (223)Ra, (188)Re, or (99m)Tc were added to either plasmid DNA or to PC Cl3 cells in the absence or presence of DMSO. Following irradiation, single strand breaks (SSB) and double strand breaks (DSB) in plasmid DNA were analyzed by gel electrophoresis. To determine the radiosensitivity of the rat thyroid cell line (PC Cl3), survival curves were performed using the colony formation assay. Exposure to 120 Gy of (223)Ra, (188)Re, or (99m)Tc leads to maximal yields of SSB (80 %) in plasmid DNA. Irradiation with 540 Gy (223)Ra and 500 Gy (188)Re or (99m)Tc induced 40, 28, and 64 % linear plasmid conformations, respectively. DMSO prevented the SSB and DSB in a similar way for all radionuclides. However, with the α-emitter (223)Ra, a low level of DSB could not be prevented by DMSO. Irradiation of PC Cl3 cells with (223)Ra, (188)Re, and (99m)Tc pre-incubated with DMSO revealed enhanced survival fractions (SF) in comparison to treatment without DMSO. Protection factors (PF) were calculated using the fitted survival curves. These factors are 1.23 ± 0.04, 1.20 ± 0.19, and 1.34 ± 0.05 for (223)Ra, (188)Re, and (99m)Tc, respectively. For (223)Ra, as well as for (188)Re and (99m)Tc, dose-dependent radiation effects were found applicable for plasmid DNA and PC Cl3 cells. The radioprotection by DMSO was in the same range for high- and low-LET emitter. Overall, the results indicate the contribution of mainly indirect radiation effects for each of the radionuclides regarding DNA damage and cell survival. In summary, our findings may contribute to fundamental knowledge about the α-particle induced DNA damage.

Assessing activation of hepatic stellate cells by (99m)Tc-3PRGD2 scintigraphy targeting integrin αvβ3: a feasibility study.

PubMed

Zhang, Xin; Xin, Jun; Shi, Yu; Xu, Weina; Yu, Shupeng; Yang, Zhiguang; Liu, Changping; Cao, Li; Guo, Qiyong

2015-03-01

Hepatic stellate cell (HSC) activation, which is accompanied by increased expression of integrin αvβ3, is an important factor in liver fibrogenesis. Molecular imaging targeting the integrin αvβ3 could provide a non-invasive method for evaluating the expression and the function of the integrin αvβ3 on the activated HSCs (aHSCs) in the injured liver, and then provide important prognostic information. (99m)Tc-3PRGD2 is such a radiotracer specific for integrin αvβ3. In this study, we aimed to compare the differences in liver uptake and retention of the (99m)Tc-3PRGD2 between normal liver and injured liver to evaluate the feasibility of (99m)Tc-3PRGD2 scintigraphy for this purpose. We used planar scintigraphy to assess changes in integrin αvβ3 binding of intravenously-administered (99m)Tc-3PRGD2 in the livers of rats with thioacetamide (TAA)-induced liver fibrosis compared with the controls. We co-injected cold c(RGDyK) with (99m)Tc-3PRGD2 to assess the specific binding of the radiotracer. We performed Sirius red staining to assess liver fibrosis, immunofluorescent colocalization to identify the location of integrin αvβ3 expressed in the fibrotic liver, and we measured protein and messenger RNA expression of integrin αvβ3 and alpha smooth muscle actin (α-SMA) in the control and fibrotic livers. The fibrotic livers showed enhanced (99m)Tc-3PRGD2 uptake and retention. The radiotracer was demonstrated to bind specifically with the integrin αvβ3 mainly expressed on the aHSCs. The liver-to-heart ratio at 30 min post-injection was higher in the fibrotic livers than in the control livers (TAA, 1.98±0.08 vs. control, 1.50±0.12, p<0.01). The liver t1/2 was longer than in the controls (TAA, 27.07±10.69 min vs. control, 12.67±4.10 min, p<0.01). The difference of heart t1/2 between the two groups was not statistically significant (TAA, 3.13±0.63 min vs. control, 3.41±0.77 min, p=0.94). (99m)Tc-3PRGD2 molecular imaging can provide a non-invasive method for assessing activation of HSCs. Copyright © 2014 Elsevier Inc. All rights reserved.

Porous carbon with a large surface area and an ultrahigh carbon purity via templating carbonization coupling with KOH activation as excellent supercapacitor electrode materials

NASA Astrophysics Data System (ADS)

Sun, Fei; Gao, Jihui; Liu, Xin; Pi, Xinxin; Yang, Yuqi; Wu, Shaohua

2016-11-01

Large surface area and good structural stability, for porous carbons, are two crucial requirements to enable the constructed supercapacitors with high capacitance and long cycling lifespan. Herein, we successfully prepare porous carbon with a large surface area (3175 m2 g-1) and an ultrahigh carbon purity (carbon atom ratio of 98.25%) via templating carbonization coupling with KOH activation. As-synthesized MTC-KOH exhibits excellent performances as supercapacitor electrode materials in terms of high specific capacitance and ultrahigh cycling stability. In a three electrode system, MTC-KOH delivers a high capacitance of 275 F g-1 at 0.5 A g-1 and still 120 F g-1 at a high rate of 30 A g-1. There is almost no capacitance decay even after 10,000 cycles, demonstrating outstanding cycling stability. In comparison, pre-activated MTC with a hierarchical pore structure shows a better rate capability than microporous MTC-KOH. Moreover, the constructed symmetric supercapacitor using MTC-KOH can achieve high energy densities of 8.68 Wh kg-1 and 4.03 Wh kg-1 with the corresponding power densities of 108 W kg-1 and 6.49 kW kg-1, respectively. Our work provides a simple design strategy to prepare highly porous carbons with high carbon purity for supercapacitors application.

Modified TC for MICA offenders: crime outcomes.

PubMed

Sacks, Stanley; Sacks, JoAnn Y; McKendrick, Karen; Banks, Steven; Stommel, Joe

2004-01-01

The study randomly assigned male inmates with co-occurring serious mental illness and chemical abuse (MICA) disorders to either modified therapeutic community (MTC) or mental health (MH) treatment programs. On their release from prison, MICA inmates who completed the prison MTC program could enter the MTC aftercare program. The results, obtained from an intent-to-treat analysis of all study entries, showed that inmates randomized into the MTC group had significantly lower rates of reincarceration compared with those in the MH group. The results also show that differences between the MTC + aftercare and comparison group across a variety of crime outcomes (i.e. any criminal activity, and alcohol or drug related criminal activity) are consistent and significant, and persist after an examination of various threats to validity (e.g. initial motivation, duration of treatment, exposure to risk). This study provides some support for the effectiveness of the prison TC only condition. The findings are encouraging and consonant with other studies of integrated prison and aftercare TC programs for substance abusing non-MICA offenders, although qualified by the possibility that selection bias (i.e. differences in motivation on entry into aftercare) may be operating. Nevertheless, given the available evidence and the need for effective programming for MICA offenders, program and policy makers should strongly consider developing integrated prison and aftercare modified TC programs for MICA offenders. Copyright 2004 John Wiley & Sons, Ltd.

Signature of ocean warming in global fisheries catch.

PubMed

Cheung, William W L; Watson, Reg; Pauly, Daniel

2013-05-16

Marine fishes and invertebrates respond to ocean warming through distribution shifts, generally to higher latitudes and deeper waters. Consequently, fisheries should be affected by 'tropicalization' of catch (increasing dominance of warm-water species). However, a signature of such climate-change effects on global fisheries catch has so far not been detected. Here we report such an index, the mean temperature of the catch (MTC), that is calculated from the average inferred temperature preference of exploited species weighted by their annual catch. Our results show that, after accounting for the effects of fishing and large-scale oceanographic variability, global MTC increased at a rate of 0.19 degrees Celsius per decade between 1970 and 2006, and non-tropical MTC increased at a rate of 0.23 degrees Celsius per decade. In tropical areas, MTC increased initially because of the reduction in the proportion of subtropical species catches, but subsequently stabilized as scope for further tropicalization of communities became limited. Changes in MTC in 52 large marine ecosystems, covering the majority of the world's coastal and shelf areas, are significantly and positively related to regional changes in sea surface temperature. This study shows that ocean warming has already affected global fisheries in the past four decades, highlighting the immediate need to develop adaptation plans to minimize the effect of such warming on the economy and food security of coastal communities, particularly in tropical regions.

EF24 (a Curcumin Analog) and ZSTK474 Emphasize the Effect of Cabozantinib in Medullary Thyroid Cancer.

PubMed

Bertazza, Loris; Sensi, Francesca; Cavedon, Elisabetta; Watutantrige-Fernando, Sara; Censi, Simona; Manso, Jacopo; Vianello, Federica; Casal Ide, Eric; Iacobone, Maurizio; Pezzani, Raffaele; Mian, Caterina; Barollo, Susi

2018-06-01

XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bioavailability, and ZSTK474 is an inhibitor of the phosphatidylinositol 3-kinase signaling pathway. We investigated the effect of these compounds, alone and in combination, in two rearranged during transfection (RET)-mutated TT and MZ-CRC-1 MTC cell lines and in six mostly RET wild-type human MTC primary cultures. Low IC50 values demonstrated the efficacy of the drugs, whereas the combination index revealed an important synergistic effect of combinations of XL184 + ZSTK474 and XL184 + EF24. Cell-cycle changes and the induction of apoptosis or necrosis were modulated by single compounds or combinations thereof. Both XL184 and EF24, alone or combined, were effective in reducing calcitonin secretion. Western blot and in-cell Western analysis showed that the compounds prompted a decrease in general reactivity to phosphorylated antibodies. Our data confirm XL184 alone as the reference drug for RET-mutated MTC, but we also demonstrated that EF24 alone is effective in inhibiting MTC cell viability. We tested the combinations XL184 + ZSTK474 and XL184 + EF24 too, finding that they act synergistically, irrespective of RET mutation status.

Metropolitan Transportation Commission, San Francisco Bay area : developing regional objectives and performance measures to improve system operations

DOT National Transportation Integrated Search

2009-04-01

The Metropolitan Transportation Commission (MTC) uses an objectives-driven, performance-based approach in its transportation planning for the San Francisco Bay Area. This approach focuses attention on transportation investments of highest priority. T...

Revisiting the Evolution of Mycobacterium bovis

PubMed Central

Mostowy, Serge; Inwald, Jackie; Gordon, Steve; Martin, Carlos; Warren, Rob; Kremer, Kristin; Cousins, Debby; Behr, Marcel A.

2005-01-01

Though careful consideration has been placed towards genetic characterization of tubercle bacillus isolates causing disease in humans, those causing disease predominantly among wild and domesticated mammals have received less attention. In contrast to Mycobacterium tuberculosis, whose host range is largely specific to humans, M. bovis and “M bovis-like” organisms infect a broad range of animal species beyond their most prominent host in cattle. To determine whether strains of variable genomic content are associated with distinct distributions of disease, the DNA contents of M. bovis or M. bovis-like isolates from a variety of hosts were investigated via Affymetrix GeneChip. Consistent with previous genomic analysis of the M. tuberculosis complex (MTC), large sequence polymorphisms of putative diagnostic and biological consequence were able to unambiguously distinguish interrogated isolates. The distribution of deleted regions indicates organisms genomically removed from M. bovis and also points to structured genomic variability within M. bovis. Certain genomic profiles spanned a variety of hosts but were clustered by geography, while others associated primarily with host type. In contrast to the prevailing assumption that M. bovis has broad host capacity, genomic profiles suggest that distinct MTC lineages differentially infect a variety of mammals. From this, a phylogenetic stratification of genotypes offers a predictive framework upon which to base future genetic and phenotypic studies of the MTC. PMID:16159772

Chemical Exchange Saturation Transfer (CEST): what is in a name and what isn’t?

PubMed Central

van Zijl, Peter C.M.; Yadav, Nirbhay N.

2011-01-01

Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI contrast approach in which exogenous or endogenous compounds containing either exchangeable protons or exchangeable molecules are selectively saturated and, after transfer of this saturation, detected indirectly through the water signal with enhanced sensitivity. The focus of this review is on basic MR principles underlying CEST and similarities to and differences with conventional magnetization transfer contrast (MTC). In CEST MRI, transfer of magnetization is studied in mobile compounds instead of semisolids. Similar to MTC, CEST has contributions of both chemical exchange and dipolar cross-relaxation, but the latter can often be neglected if exchange is fast. Contrary to MTC, CEST imaging requires sufficiently slow exchange on the MR time scale to allow selective irradiation of the protons of interest. As a consequence, magnetic labeling is not limited to radio-frequency saturation but can be expanded with slower frequency-selective approaches such as inversion, gradient dephasing and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed. A new classification for CEST agents based on exchange type is proposed. The potential of this young field is discussed, especially with respect to in vivo application and translation to humans. PMID:21337419

JSC flight experiment recommendation in support of Space Station robotic operations

NASA Astrophysics Data System (ADS)

Berka, Reginald B.

1993-02-01

The man-tended configuration (MTC) of Space Station Freedom (SSF) provides a unique opportunity to move robotic systems from the laboratory into the mainstream space program. Restricted crew access due to the Shuttle's flight rate, as well as constrained on-orbit stay time, reduces the productivity of a facility dependent on astronauts to perform useful work. A natural tendency toward robotics to perform maintenance and routine tasks will be seen in efforts to increase SSF usefulness. This tendency will provide the foothold for deploying space robots. This paper outlines a flight experiment that will capitalize on the investment in robotic technology made by NASA over the past ten years. The flight experiment described herein provides the technology demonstration necessary for taking advantage of the expected opportunity at MTC. As a context to this flight experiment, a broader view of the strategy developed at the JSC is required. The JSC is building toward MTC by developing a ground-based SSF emulation funded jointly by internal funds, NASA/Code R, and NASA/Code M. The purpose of this ground-based Station is to provide a platform whereby technology originally developed at JPL, LaRC, and GSFC can be integrated into a near flight-like condition. For instance, the Automated Robotic Maintenance of Space Station (ARMSS) project integrates flat targets, surface inspection, and other JPL technologies into a Station analogy for evaluation. Also, ARMSS provides the experimental platform for the Capaciflector from GSPC to be evaluated for its usefulness in performing ORU change out or other tasks where proximity detection is required. The use and enhancement of these ground-based SSF models are planned for use through FY-93. The experimental data gathered from tests in these facilities will provide the basis for the technology content of the proposed flight experiment.

3D dosimetry estimation for selective internal radiation therapy (SIRT) using SPECT/CT images: a phantom study

NASA Astrophysics Data System (ADS)

Debebe, Senait A.; Franquiz, Juan; McGoron, Anthony J.

2015-03-01

Selective Internal Radiation Therapy (SIRT) is a common way to treat liver cancer that cannot be treated surgically. SIRT involves administration of Yttrium - 90 (90Y) microspheres via the hepatic artery after a diagnostic procedure using 99mTechnetium (Tc)-macroaggregated albumin (MAA) to detect extrahepatic shunting to the lung or the gastrointestinal tract. Accurate quantification of radionuclide administered to patients and radiation dose absorbed by different organs is of importance in SIRT. Accurate dosimetry for SIRT allows optimization of dose delivery to the target tumor and may allow for the ability to assess the efficacy of the treatment. In this study, we proposed a method that can efficiently estimate radiation absorbed dose from 90Y bremsstrahlung SPECT/CT images of liver and the surrounding organs. Bremsstrahlung radiation from 90Y was simulated using the Compton window of 99mTc (78keV at 57%). 99mTc images acquired at the photopeak energy window were used as a standard to examine the accuracy of dosimetry prediction by the simulated bremsstrahlung images. A Liqui-Phil abdominal phantom with liver, stomach and two tumor inserts was imaged using a Philips SPECT/CT scanner. The Dose Point Kernel convolution method was used to find the radiation absorbed dose at a voxel level for a three dimensional dose distribution. This method will allow for a complete estimate of the distribution of radiation absorbed dose by tumors, liver, stomach and other surrounding organs at the voxel level. The method provides a quantitative predictive method for SIRT treatment outcome and administered dose response for patients who undergo the treatment.

A cost-effectiveness analysis of lisdexamfetamine dimesylate in the treatment of adults with attention-deficit/hyperactivity disorder in the UK.

PubMed

Zimovetz, Evelina A; Joseph, Alain; Ayyagari, Rajeev; Mauskopf, Josephine A

2018-01-01

Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral disorder in children that may persist into adulthood. Lisdexamfetamine dimesylate (LDX) is approved in many countries for ADHD treatment in children, adolescents, and adults. Estimate the cost-effectiveness of LDX as a first- or second-line treatment for adults with ADHD from the United Kingdom (UK) National Health Service (NHS) perspective compared with methylphenidate extended release (MPH-ER) and atomoxetine (ATX). A 1-year decision-analytic model was developed. Health outcomes included response, non-response and inability to tolerate. Efficacy data were obtained from a mixed-treatment comparison (MTC). Response was a score of 1 or 2 on the Clinical Global Impression-Improvement scale. Tolerability was assessed by discontinuation rates due to adverse events. Utilities were identified via a systematic literature review. Health care resource use estimates were obtained via a survey of clinicians. Daily drug costs were estimated from mean doses reported in the trials used in the MTC. One-way and probabilistic sensitivity analyses (PSAs) were performed. LDX dominated MPH-ER and ATX; reducing mean per-patient annual cost by £5 and £200, and increasing mean quality-adjusted life years (QALYs) by 0.005 and 0.009, respectively. In the PSA, the probability of cost-effectiveness for LDX vs. MPH-ER and ATX at a threshold of £20,000 per QALY was 61% and 80%, respectively. From the perspective of the UK NHS, LDX is likely to provide a cost-effective treatment for adults with ADHD. This conclusion may be drawn with more certainty in comparison with ATX than with MPH-ER.

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

Quigley, Kevin; Chemerisov, Sergey; Tkac, Peter

Through irradiations using our 3 MeV Van de Graaf accelerator, Argonne is testing the radiation stability of components of equipment that are being used to dispense molybdenum solutions for use as feeds to 99mTc generators and in the 99mTc generators themselves. Components have been irradiated by both a direct electron beam and photons generated from a tungsten convertor.

Predominant RET Germline Mutations in Exons 10, 11, and 16 in Iranian Patients with Hereditary Medullary Thyroid Carcinoma

PubMed Central

Hedayati, Mehdi; Zarif Yeganeh, Marjan; Sheikhol Eslami, Sara; Rezghi Barez, Shekoofe; Hoghooghi Rad, Laleh; Azizi, Fereidoun

2011-01-01

Medullary thyroid carcinoma occurs in both sporadic (75%) and hereditary (25%) forms. The missense mutations of RET proto-oncogene in MTC development have been well demonstrated. To investigate the spectrum of predominant RET germline mutations in exons 10, 11, and 16 in hereditary MTC in Iranian population, 217 participants were included. Genomic DNAs were extracted from the leukocytes using the standard Salting Out/Proteinase K method. Mutation detection was performed through PCR-RFLP and DNA sequencing. In 217 participants, 43 missense mutations were identified in exons 10 (6%), 11 (13%), and 16 (0.9%). Moreover, a novel germline mutation was detected in exon 11 (S686N). Also four different polymorphisms were found in intron 16 in eight patients. The obtained data showed the frequency profile of RET mutations in Iranian individuals with MTC (19.8%). The most frequent mutation in our population was C634G whereas in most population it was C634R. Altogether, these results underline the importance of the genetic background of family members of any patient with MTC. PMID:21765987

Role of PET in medullary thyroid carcinoma.

PubMed

Rufini, V; Treglia, G; Perotti, G; Leccisotti, L; Calcagni, M L; Rubello, D

2008-06-01

In the diagnostic assessment of medullary thyroid carcinoma (MTC), nuclear medicine imaging provides its contribution mainly in the postoperative work-up to detect residual or recurrent tumor. With respect to scintigraphy with gamma-emitter radiopharmaceuticals, positron emission tomography (PET) offers interesting perspectives owing to its higher image quality, spatial resolution and speed. Moreover, the recent developments of hybrid machines allow to obtain images that simultaneously hold both anatomic (computed tomography) and functional (PET) information with great impact on diagnostic efficacy. (18)F-fluoro-deoxyglucose ((18)F-FDG) is the most frequently used PET tracer in oncology. Preliminary reports of FDG-PET in MTC patients show encouraging results with a higher sensitivity in detecting local recurrent and metastatic disease when compared with single photon emission tracers. However, (18)F-FDG uptake depends on lesion size and to some extent on the grade of differentiation and biologic aggressiveness of the tumor; so FDG-PET seems useful mainly in patients with very high calcitonin levels and high progression rate. Like other neuroendocrine tumors, MTC is characterized by the presence of amine uptake mechanism and/or peptide receptors at the cell membrane allowing the clinical use of specific radiopharmaceuticals that reflect the different metabolic pathways of MTC, and in particular the synthesis, storage and release of hormones ((18)F-dihydroxyphenilalanine, (18)F-DOPA and (18)F-fluorodopamine, (18)F-FDA) and the expression of receptors ((68)Ga-labeled somatostatin analogs). These tracers are currently under investigation and will further improve the diagnostic approach of MTC.

High-resolution analysis of alterations in medullary thyroid carcinoma genomes.

PubMed

Flicker, Karin; Ulz, Peter; Höger, Harald; Zeitlhofer, Petra; Haas, Oskar A; Behmel, Annemarie; Buchinger, Wolfgang; Scheuba, Christian; Niederle, Bruno; Pfragner, Roswitha; Speicher, Michael R

2012-07-15

Hereditary and sporadic medullary thyroid carcinoma (MTC) are closely associated with RET proto-oncogene mutations. However, the role of additional changes in the tumor genomes remains unclear. Our objective was the identification of chromosomal regions involved in MTC tumorigenesis and to assess their significance by using MTC-derived cell lines. We used array-CGH (comparative genomic hybridization) to map chromosomal imbalances in 52 primary tumors and ten metastases. Eleven tumors (11/52, 21%) were hereditary and 41 (41/52, 79%) were sporadic. Among the latter, 15 tumors (15/41, 37%) harbored RET mutations. Furthermore, we characterized five MTC cell lines in detail and evaluated the tumorigenicity by severe combined immunodeficiency (SCID)-mouse experiments. Most MTCs had only few copy number changes, and losses of chromosomes 1p, 4q, 19p and 22q were observed most frequently. The number of chromosomal aberrations increased in metastases. Twenty-three percent (12/52) of the primary tumors did not even show any chromosomal gains and losses. We injected three cell lines (two of these were without chromosomal changes and pathogenic RET mutations) into immune deficient SCID mice, and in each case, we observed rapid tumor growth at the injection sites. Our data suggest that MTCs--in contrast to most other tumor entities--do not acquire a multitude of genomic imbalances. SCID mouse experiments performed with chromosomally normal cell lines and without RET mutations suggest that presently unknown submicroscopic genomic changes are sufficient in MTC tumorigenesis. Copyright © 2011 UICC.

99mTc Glucarate as a Potential Radiopharmaceutical Agent for Assessment of Tumor Viability: From Bench to the Bed Side

PubMed Central

Choudhury, Partha S.; Savio, E.; Solanki, K. K.; Alonso, O.; Gupta, A.; Gambini, J. P.; Doval, Dinesh; Sharma, P.; Dondi, M.

2012-01-01

Several radiotracers have been used for assessing cell death, whether by necrosis or apoptosis. 99mTc glucarate, which has initially been reported to be concentrating/accumulating in myocardial infarction or zones of cerebral injury, has also shown some tumor-seeking properties in a few preliminary studies. Under International Atomic Energy Agency (IAEA)'s coordinated research program, we report here the standardization, quality control, and clinical evaluation (detection, evaluation of response, and comparison with 18F Fluorodeoxyglucose) of this tracer in well-characterized lung cancer and head neck malignancies in a single-arm prospective observational study. Forty-seven patients (29 inoperable lung carcinoma and 18 head and neck malignancies) were prospectively enrolled and underwent 99mTc glucarate imaging [whole body planar and single-photon emission computed tomography of the region of interest] 4-5 hours after injection of 20 mCi of the radiopharmaceutical. Excellent 99mTc glucarate concentration was noted in the target lesion in lung cancer and head and neck malignancies. The sensitivity was found to be better in lung cancer. Avid concentration of tracer was seen in the metastatic sites. During response evaluation, the glucarate concentration correlated well with the clinical and other radiological findings. 99mTc glucarate showed avid concentration of tracer in the tumor, suggesting it to be a potential tumor imaging agent which can be used for detection and assessment of therapeutic response in malignancy. PMID:23372437

Real medical benefit assessed by indirect comparison.

PubMed

Falissard, Bruno; Zylberman, Myriam; Cucherat, Michel; Izard, Valérie; Meyer, François

2009-01-01

Frequently, in data packages submitted for Marketing Approval to the CHMP, there is a lack of relevant head-to-head comparisons of medicinal products that could enable national authorities responsible for the approval of reimbursement to assess the Added Therapeutic Value (ASMR) of new clinical entities or line extensions of existing therapies.Indirect or mixed treatment comparisons (MTC) are methods stemming from the field of meta-analysis that have been designed to tackle this problem. Adjusted indirect comparisons, meta-regressions, mixed models, Bayesian network analyses pool results of randomised controlled trials (RCTs), enabling a quantitative synthesis.The REAL procedure, recently developed by the HAS (French National Authority for Health), is a mixture of an MTC and effect model based on expert opinions. It is intended to translate the efficacy observed in the trials into effectiveness expected in day-to-day clinical practice in France.

Evaluation of patellar chondromalacia with MR: comparison between T2-weighted FSE SPIR and GE MTC.

PubMed

Macarini, Luca; Perrone, Alessandra; Murrone, Mario; Marini, Stefania; Stefanelli, Michele

2004-09-01

To compare two different MR sequences to tissue signal suppression in the study of patellar cartilage abnormalities. We examined 26 patients with magnetic resonance (MR) imaging: sequences included spectral presaturation with inversion recovery (SPIR), with fat suppression and T2-weighted images, magnetization transfer contrast (MTC) sequences, T1-weighted and T2-weighted spin-echo sequences. All patients underwent conventional knee arthroscopy and in all patients a hyaline cartilage lesion was assessed in three articular zones: the patellar medial facet, the lateral facet and the patellar crista. Was assessed 78 articular facets. The lesions were classified using a standard arthroscopic grading system adapted to MR imaging: normal cartilage that corresponds to the grade 0 according to the Noyes grading system, low grade lesions that correspond to the grade I e IIa and high grade lesions that correspond to grades IIb and III. The arthroscopic results were compared with MR images. We assessed the MR diagnostic accuracy, sensitivity, specificity and MR positive predictive value and negative predictive value of the two sequences taking into consideration total lesions, and high-grade and low grade lesions separately. Twenty-four low grade lesions (16 grade I e 8 grade IIa) and 18 high grade lesions (10 grade IIb e 8 grade III) were diagnosed by arthroscopy. Regarding low grade and high-grade lesions together, the accuracy was 77% for MTC sequences and 90% for SPIR sequences. In identifying low-grade lesions, the sensitivity was 88% for SPIR sequence and 42% for MTC sequences. Specificity for the detection of all lesions was 89% for the SPIR sequences and 94% for the MTC sequences. The SPIR sequence visualised water content abnormalities in degenerating cartilage, which are representative of low-grade lesions. The sensitivity of the sequence enabled us to obtain improved contrast for detecting cartilage surface irregularities. The MTC sequences allowed us to grade high-grade lesions susceptible to surgery and small cartilage defects in the presence of joint fluid. The MTC sequences were insufficient in the diagnosis of early stages of chondromalacia because the suppression of the signal of bonded water reduced the contrast among areas of articular cartilage with different water content. For this reason cartilage oedema and early superficial fibrillation were not identified. In our experience the SPIR sequence proved superior to the MTC sequence in the identification of low grade lesions of the patellar cartilage. The overall value of such sequences in the study of articular pathology also needs to be assessed in the others sites where the articular cartilage is thinner and surfaces more curvilinear.

A Comparative Evaluation of Minimal Therapist Contact and 15-Session Treatment for Female Orgasmic Dysfunction.

ERIC Educational Resources Information Center

Morokoff, Patricia J.; LoPiccolo, Joseph

1986-01-01

Compared a four-session minimal therapist contact (MTC) program for treatment of lifelong global orgasmic dysfunction in women to a 15-session full therapist contact (FTC) program. Both programs were effective in producing female orgasm and in improving satisfaction with the sexual relationship and, for women in MTC treatment, happiness in…

Quality of 99mTcO4- from 99Mo Produced by 100Mo(n,2n)99Mo

NASA Astrophysics Data System (ADS)

Nagai, Yasuki; Nakahara, Yuto; Kawabata, Masako; Hatsukawa, Yuichi; Hashimoto, Kazuyuki; Saeki, Hideya; Motoishi, Shoji; Ohta, Akio; Shiina, Takayuki; Kawauchi, Yukimasa

2017-05-01

The pharmaceutical quality of 99mTc pertechnetate solution obtained from 99Mo, the 100Mo(n,2n) reaction product, was investigated for the first time with an emphasis on the nonradioactive Mo content and endotoxin concentration. They were less than the tolerance dose given in international guidelines and the established upper limit in an international pharmacopoeia, respectively. Four other quality control tests commonly used for a commercially available 99mTc pertechnetate solution also demonstrated to meet the United States Pharmacopeia requirements. The results strongly support that the thermochromatographic separation method used to separate 99mTc from 99Mo can be a promising substitute for the fission product 99Mo.

High-throughput screening of chemical effects on ...

EPA Pesticide Factsheets

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2,060 chemical samples on steroidogenesis via HPLC-MS/MS quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a three stage screening strategy. The first stage established the maximum tolerated concentration (MTC; >70% viability) per sample. The second stage quantified changes in hormone levels at the MTC while the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were pre-stimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2,060 chemical samples evaluated, 524 samples were selected for six-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into five distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A d

High-throughput screening of chemical effects on steroidogenesis using H295R human adrenocortical carcinoma cells

EPA Pesticide Factsheets

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ? 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 00b5M forskolin for 48??h to induce steroidogenesis followed by chemical treatment for 48??h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 1703b2-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mec

[18F]DOPA PET/ceCT in diagnosis and staging of primary medullary thyroid carcinoma prior to surgery.

PubMed

Rasul, Sazan; Hartenbach, Sabrina; Rebhan, Katharina; Göllner, Adelina; Karanikas, Georgios; Mayerhoefer, Marius; Mazal, Peter; Hacker, Marcus; Hartenbach, Markus

2018-05-15

Medullary thyroid carcinoma (MTC) is characterized by a high rate of metastasis. In this study we evaluated the ability of [ 18 F]DOPA PET/ceCT to stage MTC in patients with suspicious thyroid nodules and pathologically elevated serum calcitonin (Ctn) levels prior to total thyroidectomy and lymph node (LN) dissection. A group of 32 patients with sonographically suspicious thyroid nodules and pathologically elevated basal Ctn (bCtn) and stimulated Ctn (sCtn) levels underwent DOPA PET/ceCT prior to surgery. Postoperative histology served as the standard of reference for ultrasonography and DOPA PET/ceCT region-based LN staging. Univariate and multivariate regression analyses as well as receiver operating characteristic analysis were used to evaluate the correlations between preoperative and histological parameters and postoperative tumour persistence or relapse. Primary MTC was histologically verified in all patients. Of the 32 patients, 28 showed increased DOPA decarboxylase activity in the primary tumour (sensitivity 88%, mean SUVmax 10.5). Undetected tumours were exclusively staged pT1a. The sensitivities of DOPA PET in the detection of central and lateral metastatic neck LN were 53% and 73%, in contrast to 20% and 39%, respectively, for neck ultrasonography. Preoperative bCtn and carcinoembryonic antigen levels as well as cN1b status and the number of involved neck regions on DOPA PET/ceCT were predictive of postoperative tumour persistence/relapse in the univariate regression analysis (P < 0.05). Only DOPA PET/ceCT cN1b status remained significant in the multivariate analysis (P = 0.016, relative risk 4.02). This study revealed that DOPA PET/ceCT has high sensitivity in the detection of primary MTC and superior sensitivity in the detection of LN metastases compared to ultrasonography. DOPA PET/ceCT identification of N1b status predicts postoperative tumour persistence. Thus, implementation of a DOPA-guided LN dissection might improve surgical success.

GATE Simulations of Small Animal SPECT for Determination of Scatter Fraction as a Function of Object Size

NASA Astrophysics Data System (ADS)

Konik, Arda; Madsen, Mark T.; Sunderland, John J.

2012-10-01

In human emission tomography, combined PET/CT and SPECT/CT cameras provide accurate attenuation maps for sophisticated scatter and attenuation corrections. Having proven their potential, these scanners are being adapted for small animal imaging using similar correction approaches. However, attenuation and scatter effects in small animal imaging are substantially less than in human imaging. Hence, the value of sophisticated corrections is not obvious for small animal imaging considering the additional cost and complexity of these methods. In this study, using GATE Monte Carlo package, we simulated the Inveon small animal SPECT (single pinhole collimator) scanner to find the scatter fractions of various sizes of the NEMA-mouse (diameter: 2-5.5 cm , length: 7 cm), NEMA-rat (diameter: 3-5.5 cm, length: 15 cm) and MOBY (diameter: 2.1-5.5 cm, length: 3.5-9.1 cm) phantoms. The simulations were performed for three radionuclides commonly used in small animal SPECT studies:99mTc (140 keV), 111In (171 keV 90% and 245 keV 94%) and 125I (effective 27.5 keV). For the MOBY phantoms, the total Compton scatter fractions ranged (over the range of phantom sizes) from 4-10% for 99mTc (126-154 keV), 7-16% for 111In (154-188 keV), 3-7% for 111In (220-270 keV) and 17-30% for 125I (15-45 keV) including the scatter contributions from the tungsten collimator, lead shield and air (inside and outside the camera heads). For the NEMA-rat phantoms, the scatter fractions ranged from 10-15% (99mTc), 17-23% 111In: 154-188 keV), 8-12% (111In: 220-270 keV) and 32-40% (125I). Our results suggest that energy window methods based on solely emission data are sufficient for all mouse and most rat studies for 99mTc and 111In. However, more sophisticated methods may be needed for 125I.

[Restoration filtering based on projection power spectrum for single-photon emission computed tomography].

PubMed

Kubo, N

1995-04-01

To improve the quality of single-photon emission computed tomographic (SPECT) images, a restoration filter has been developed. This filter was designed according to practical "least squares filter" theory. It is necessary to know the object power spectrum and the noise power spectrum. The power spectrum is estimated from the power spectrum of a projection, when the high-frequency power spectrum of a projection is adequately approximated as a polynomial exponential expression. A study of the restoration with the filter based on a projection power spectrum was conducted, and compared with that of the "Butterworth" filtering method (cut-off frequency of 0.15 cycles/pixel), and "Wiener" filtering (signal-to-noise power spectrum ratio was a constant). Normalized mean-squared errors (NMSE) of the phantom, two line sources located in a 99mTc filled cylinder, were used. NMSE of the "Butterworth" filter, "Wiener" filter, and filtering based on a power spectrum were 0.77, 0.83, and 0.76 respectively. Clinically, brain SPECT images utilizing this new restoration filter improved the contrast. Thus, this filter may be useful in diagnosis of SPECT images.

Is basal ultrasensitive measurement of calcitonin capable of substituting for the pentagastrin-stimulation test?

PubMed

Pina, Géraldine; Dubois, Séverine; Murat, Arnaud; Berger, Nicole; Niccoli, Patricia; Peix, Jean-Louis; Cohen, Régis; Guillausseau, Claudine; Charrie, Anne; Chabre, Olivier; Cornu, Catherine; Borson-Chazot, Françoise; Rohmer, Vincent

2013-03-01

To evaluate a second-generation assay for basal serum calcitonin (CT) measurements compared with the pentagastrin-stimulation test for the diagnosis of inherited medullary thyroid carcinoma (MTC) and the follow-up of patients with MTC after surgery. Recent American Thyroid Association recommendations suggest the use of basal CT alone to diagnose and assess follow-up of MTC as the pentagastrin (Pg) test is unavailable in many countries. Multicentric prospective study. A total of 162 patients with basal CT <10 ng/l were included: 54 asymptomatic patients harboured noncysteine 'rearranged during transfection' (RET) proto-oncogene mutations and 108 patients had entered follow-up of MTC after surgery. All patients underwent basal and Pg-stimulated CT measurements using a second-generation assay with 5-ng/l functional sensitivity. Ninety-five per cent of patients with basal CT ≥ 5 ng/l and 25% of patients with basal CT <5 ng/l had a positive Pg-stimulation test (Pg CT >10 ng/l). Compared with the reference Pg test, basal CT ≥ 5 ng/l had 99% specificity, a 95%-positive predictive value but only 35% sensitivity (P < 0.0001). Overall, there were 31% less false-negative results using a 5-ng/l threshold for basal CT instead of the previously used 10-ng/l threshold. The ultrasensitive CT assay reduces the false-negative rate of basal CT measurements when diagnosing familial MTC and in postoperative follow-up compared with previously used assays. However, its sensitivity to detect C-cell disease remains lower than that of the Pg-stimulation test. © 2012 Blackwell Publishing Ltd.

Swing limb mechanics and minimum toe clearance in people with knee osteoarthritis.

PubMed

Levinger, Pazit; Lai, Daniel T H; Menz, Hylton B; Morrow, Adam D; Feller, Julian A; Bartlett, John R; Bergman, Neil R; Begg, Rezaul

2012-02-01

Knee osteoarthritis (OA) has been shown to be a risk factor for falls. Reductions in foot clearance during the swing phase of walking can cause a trip and potentially lead to a fall. This study examined the swing phase mechanics of people with and without knee OA during walking. Minimum toe clearance (MTC) height, joint angles at the time of MTC and the influence of the angular changes of the hip, knee and ankle of the swing leg on foot clearance using sensitivity analysis were investigated in 50 knee OA participants and 28 age-matched asymptomatic controls. Although both groups had a similar MTC height (controls: 12.8±6.7 mm, knee OA: 13.4±7.0 mm), the knee OA group used a different strategy to achieve the same foot clearance, as evidenced by greater knee flexion (52.5±5.3° vs 49.4±4.8°, p=0.007), greater hip abduction (-3.6±3.3° vs -1.8±3.3°, p=0.03) and less ankle adduction (2.8±1.9° vs 4.2±2.1°, p=0.01). MTC height was comparable between the groups, however a different swing phase mechanism was used by the knee OA. Although adequate MTC is an important component of safe locomotion, it does not appear to be impaired in people with knee OA. Other factors, such as inadequate responses to postural perturbation, may be responsible for falls in this group. Copyright © 2011 Elsevier B.V. All rights reserved.

The Development and Validation of a Spanish Elicited Imitation Test of Oral Language Proficiency for the Missionary Training Center

ERIC Educational Resources Information Center

Thompson, Carrie A.

2013-01-01

The Missionary Training Center (MTC), affiliated with the Church of Jesus Christ of Latter-day Saints, needs a reliable and cost effective way to measure the oral language proficiency of missionaries learning Spanish. The MTC needed to measure incoming missionaries' Spanish language proficiency for training and classroom assignment as well as to…

Parallel odor processing by mitral and middle tufted cells in the olfactory bulb.

PubMed

Cavarretta, Francesco; Burton, Shawn D; Igarashi, Kei M; Shepherd, Gordon M; Hines, Michael L; Migliore, Michele

2018-05-16

The olfactory bulb (OB) transforms sensory input into spatially and temporally organized patterns of activity in principal mitral (MC) and middle tufted (mTC) cells. Thus far, the mechanisms underlying odor representations in the OB have been mainly investigated in MCs. However, experimental findings suggest that MC and mTC may encode parallel and complementary odor representations. We have analyzed the functional roles of these pathways by using a morphologically and physiologically realistic three-dimensional model to explore the MC and mTC microcircuits in the glomerular layer and deeper plexiform layer. The model makes several predictions. MCs and mTCs are controlled by similar computations in the glomerular layer but are differentially modulated in deeper layers. The intrinsic properties of mTCs promote their synchronization through a common granule cell input. Finally, the MC and mTC pathways can be coordinated through the deep short-axon cells in providing input to the olfactory cortex. The results suggest how these mechanisms can dynamically select the functional network connectivity to create the overall output of the OB and promote the dynamic synchronization of glomerular units for any given odor stimulus.

Treatment of medullary thyroid carcinoma with apatinib

PubMed Central

Cai, Sina; Deng, Huan; Chen, Yinkui; Wu, Xing; Guan, Xiaoqian

2017-01-01

Abstract Rationale: Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC. Patient concerns: A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016. Diagnoses: A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum. Interventions: This patient was treated with oral apatinib (500 mg daily). Outcomes: The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib. Lessons: Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches. PMID:29390263

New Drug Candidate Targeting the 4A1 Orphan Nuclear Receptor for Medullary Thyroid Cancer Therapy.

PubMed

Zhang, Lei; Liu, Wen; Wang, Qun; Li, Qinpei; Wang, Huijuan; Wang, Jun; Teng, Tieshan; Chen, Mingliang; Ji, Ailing; Li, Yanzhang

2018-03-02

Medullary thyroid cancer (MTC) is a relatively rare thyroid cancer responsible for a substantial fraction of thyroid cancer mortality. More effective therapeutic drugs with low toxicity for MTC are urgently needed. Orphan nuclear receptor 4A1 (NR4A1) plays a pivotal role in regulating the proliferation and apoptosis of a variety of tumor cells. Based on the NR4A1 protein structure, 2-imino-6-methoxy-2H-chromene-3-carbothioamide (IMCA) was identified from the Specs compounds database using the protein structure-guided virtual screening approach. Computationally-based molecular modeling studies suggested that IMCA has a high affinity for the ligand binding pocket of NR4A1. MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide] and apoptosis assays demonstrated that IMCA resulted in significant thyroid cancer cell death. Immunofluorescence assays showed that IMCA induced NR4A1 translocation from the nucleus to the cytoplasm in thyroid cancer cell lines, which may be involved in the cell apoptotic process. In this study, the quantitative polymerase chain reaction results showed that the IMCA-induced upregulation of sestrin1 and sestrin2 was dose-dependent in thyroid cancer cell lines. Western blot showed that IMCA increased phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and decreased phosphorylation of ribosomal protein S6 kinase (p70S6K), which is the key enzyme in the mammalian target of rapamycin (mTOR) pathway. The experimental results suggest that IMCA is a drug candidate for MTC therapy and may work by increasing the nuclear export of NR4A1 to the cytoplasm and the tumor protein 53 (p53)-sestrins-AMPK-mTOR signaling pathway.

Direct Quantification of Post-Stress-Rest Left Ventricular Motion and Thickening Changes for Myocardial Perfusion SPECT

PubMed Central

Karimi-Ashtiani, Shahryar; Arsanjani, Reza; Fish, Mathews; Kavanagh, Paul; Germano, Guido; Berman, Daniel; Slomka, Piotr

2012-01-01

Changes in myocardial wall motion and thickening during myocardial perfusion single-photon emission computed tomography (MPS) are typically assessed separately from gated studies to assess for stress induced functional abnormalities. We sought to develop and validate a novel approach for automatic quantification of post-stress-rest myocardial motion and thickening changes (MTC). Methods Endocardial surfaces at the end-diastolic and end-systolic frames for post-stress and rest studies were registered automatically to each other by matching ventricular surfaces. Myocardial MTCs were computed and normal limits of change were determined as the mean and standard deviation for each polar sample. Normal limits were utilized to quantify the MTCs for each map and the accumulated sample values were used for abnormality assessments in segmental regions. A hybrid method was devised by combining the Total Perfusion Deficit (TPD) and MTC for each vessel territory. Normal limits were obtained from 100 subjects with low likelihood (LLK) of coronary artery disease (CAD). For validation, 623 subjects with correlating invasive angiography were studied. All subjects had a stress/rest 99mTc-sestamibi exercise or adenosine test, and all had coronary angiography within 3 months of MPS. All MTC and TPD measurements were derived automatically. The diagnostic accuracy for detection of coronary artery disease for MTC+TPD was compared to TPD alone. Results Segmental normal values for motion change were between −1.3 and −4.1 mm and between −30.1% and −9.8% for thickening change. MTC combined with TPD achieved 61% sensitivity for 3-vessel disease (3VD), 63% for 2-vessel disease (2VD), and 90% for 1-vessel disease (1VD) detection vs. 32% for 3VD (P <0.0001), 53% for 2VD (P < 0.001), and 90% for 1VD (P = 1.0) detection with TPD alone method. The specificity for the combined method was 71% for 3VD, 72% for 2VD, and 47% for 1 VD detection vs. 90% for 3VD (P < 0.0001), 80% for 2VD (P <0.001), and 50% for 1VD detection (P=0.0625) for TPD alone method. The accuracy of 3VD detection by MTC+TPD was higher (69%) than the accuracy of TPD + change in ejection fraction (63%), (P< 0.004). Conclusion We established normal limits and a novel method for computation of regional functional changes between post-stress and rest. Combination of (TPD) with MTC improved the sensitivity for the detection of 3VD and 2VD as compared to TPD alone. PMID:22872739

Two peptide receptor ligands (99m)Tc-EDDA/HYNIC-Tyr(3)-octreotide and (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin for scintigraphy of medullary thyroid carcinoma.

PubMed

Kosowicz, Jerzy; Mikołajczak, Renata; Czepczyński, Rafał; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy

2007-10-01

Somatostatin and gastrin receptors are overexpressed in medullary thyroid carcinoma (MTC) cells; hence, both of them are potential targets for peptide receptor scintigraphy and radiotherapy. Therefore, the aim of our study was to assess the clinical value of two technetium-99m-labeled peptides, a new gastrin analog, the EDDA/HYNIC-(D)Glu-octagastrin and a somatostatin analog, EDDA/HYNIC-Tyr(3)-octreotide (EDDA/HYNIC-TOC) for scintigraphy in patients with MTC to detect recurrences and metastases and select patients for peptide receptor radiotherapy. Thirty (30) patients, 20 females and 10 males, 22-83 years of age (mean, 52.7) with the diagnosis of MTC in different stages of the disease (preoperative, postsurgery, remission, recurrence, or metastatic disease) were included in this study. Before surgery, in all patients serum calcitonin concentrations were elevated. The diagnosis of MTC was confirmed in all cases by histopathology of the removed tumor and immunohistochemical staining giving positive reactions for calcitonin and chromogranin A. Imaging studies using (99m)Tc-EDDA/HYNIC-TOC and a new minigastrin analog, (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin, were performed in each patient and the results compared with each other and with other imaging methods. Scans of the whole body, head, neck, and chest were performed 2 and 4 hours after injections of the tracer, 500-600 MBq in each case, using a double-head Varicam (Elscint, Israel) gamma camera. (99m)Tc-EDDA/HYNIC-TOC detected somatostatin receptor-positive lesions in 20 patients with MTC, whereas (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin displayed gastrin receptors in 11 patients. In 9 cases, the scans were positive in both methods, although in 2 cases different pathologic foci were visualized. In 12 cases, only (99m)Tc-EDDA/HYNIC-TOC scintigraphy was positive, whereas in 3 other cases only (99m)Tc-EDDA/HYNIC-(D)Glu-octagastrin revealed pathologic lesions. Scintigraphy using (99m)Tc-HYNIC-TOC permits the visualization of somatostatin receptor-positive MTC in the majority of cases. The new gastrin analog, (99m)Tc-HYNIC-(D)Glu-octagastrin, is well tolerated, shows no renal retention, and in some cases of MTC, provides additional information on the expression of gastrin receptors. However, inferior quality of octagastrin scans indicates the need for further improvement of this radiopeptide.

Macro-aggregates (MAA) of albumin for lung imaging. Studies on better tissue to background ratio, on MAA stability and reuse after its first preparation.

PubMed

Malhotra, Anshoo; Kumar, Pardeep; Sharma, Sarika; Dhawan, Davinder K

2010-01-01

The present study was designed to develop stable and economically competitive radioactive technetium-99m macro-aggregates of albumin ((99m)Tc-MAA) which could be used for imaging of lungs. Macro-aggregates were freshly prepared and labeled with (99m)Tc pertechnetate by following the standard protocol which included incubation of formulation at 80(o) C for 10 min. We studied 7 rats in every experiment. The rats were injected intravenously with (99m)Tc MAA and were sacrificed after 10 min to study its distribution in the lungs and other non target tissues using gamma ray spectrometer. This standard protocol was further experimented upon in order to achieve high target to non target ratio. Different formulations were prepared by incubating them at 80 degrees for different incubation times of 5, 10, 15, 20, 25 and 30 min. Formulation of MAA prepared by incubating at 80 degrees for 20 min labeled with (99m)Tc showed the highest target to non target ratio. Another group of rats that received the above formulation were sacrificed after two additional time intervals of 5 and 15 min. The target to non target ratio was high in animals sacrificed after 5 min of injecting them with (99m)Tc the MAA formulation prepared by heating at 80 degrees for 20 min as compared to animals sacrificed after 10 and 15 min. Formulations of MAA following storage at room temperatures which varied from 5(o)C to 18(o)C, for different time durations 1, 2 and 9 days were also evaluated for their ability to be reused after reheating and labeling with (99m)Tc. The formulation of MAA kept for 9 days showed the best target to non-target ratio. The present study suggests that MAA once prepared can be reused following labeling with (99m)Tc even after 9 days of storage with better target to non target ratio as compared to storage timer period of 1 and 2 days.

Disease-modifying polymorphisms and C609Y mutation of RET associated with high penetrance of phaeochromocytoma and low rate of MTC in MEN2A.

PubMed

Speak, Rowena; Cook, Jackie; Harrison, Barney; Newell-Price, John

2016-01-01

Mutations of the rearranged during transfection ( RET ) proto-oncogene, located on chromosome 10q11.2, cause multiple endocrine neoplasia type 2A (MEN2A). Patients with mutations at the codon 609 usually exhibit a high penetrance of medullary thyroid cancer (MTC), but a sufficiently low penetrance of phaeochromocytoma that screening for this latter complication has been called to question. Patients with other RET mutations are at higher risk of younger age onset phaeochromocytoma if they also possess other RET polymorphisms (L769L, S836S, G691S and S904S), but there are no similar data for patients with 609 mutations. We investigated the unusual phenotypic presentation in a family with MEN2A due to a C609Y mutation in RET . Sanger sequencing of the entire RET -coding region and exon-intron boundaries was performed. Five family members were C609Y mutation positive: 3/5 initially presented with phaeochromocytoma, but only 1/5 had MTC. The index case aged 73 years had no evidence of MTC, but presented with phaeochromocytoma. Family members also possessed the G691S and S904S RET polymorphisms. We illustrate a high penetrance of phaeochromocytoma and low penetrance of MTC in patients with a RET C609Y mutation and polymorphisms G691S and S904S. These data highlight the need for life-long screening for the complications of MEN2A in these patients and support the role for the screening of RET polymorphisms for the purposes of risk stratification. C609Y RET mutations may be associated with a life-long risk of phaeochromocytoma indicating the importance of life-long screening for this condition in patients with MEN2A.C609Y RET mutations may be associated with a lower risk of MTC than often quoted, questioning the need for early prophylactic thyroid surgery discussion at the age of 5 years.There may be a role for the routine screening of RET polymorphisms, and this is greatly facilitated by the increasing ease of access to next-generation sequencing.

Implications of uncertainty on regional CO2 mitigation policies for the U.S. onroad sector based on a high-resolution emissions estimate

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

Mendoza, D.; Gurney, Kevin R.; Geethakumar, Sarath

2013-04-01

In this study we present onroad fossil fuel CO2 emissions estimated by the Vulcan Project, an effort quantifying fossil fuel CO2 emissions for the U.S. in high spatial and temporal resolution. This high-resolution data, aggregated at the state-level and classified in broad road and vehicle type categories, is compared to a commonly used national-average approach. We find that the use of national averages incurs state-level biases for road groupings that are almost twice as large as for vehicle groupings. The uncertainty for all groups exceeds the bias, and both quantities are positively correlated with total state emissions. States with themore » largest emissions totals are typically similar to one another in terms of emissions fraction distribution across road and vehicle groups, while smaller-emitting states have a wider range of variation in all groups. Errors in reduction estimates as large as ±60% corresponding to ±0.2 MtC are found for a national-average emissions mitigation strategy focused on a 10% emissions reduction from a single vehicle class, such as passenger gas vehicles or heavy diesel trucks. Recommendations are made for reducing CO2 emissions uncertainty by addressing its main drivers: VMT and fuel efficiency uncertainty.« less

The M-T Hook Structure Is Critical for Design of HIV-1 Fusion Inhibitors*

PubMed Central

Chong, Huihui; Yao, Xue; Sun, Jianping; Qiu, Zonglin; Zhang, Meng; Waltersperger, Sandro; Wang, Meitian; Cui, Sheng; He, Yuxian

2012-01-01

CP621-652 is a potent HIV-1 fusion inhibitor peptide derived from the C-terminal heptad repeat of gp41. We recently identified that its N-terminal residues Met-626 and Thr-627 adopt a unique hook-like structure (termed M-T hook) thus stabilizing the interaction of the inhibitor with the deep pocket on the N-terminal heptad repeat. In this study, we further demonstrated that the M-T hook structure is a key determinant of CP621-652 in terms of its thermostability and anti-HIV activity. To directly define the structure and function of the M-T hook, we generated the peptide MT-C34 by incorporating Met-626 and Thr-627 into the N terminus of the C-terminal heptad repeat-derived peptide C34. The high resolution crystal structure (1.9 Å) of MT-C34 complexed by an N-terminal heptad repeat-derived peptide reveals that the M-T hook conformation is well preserved at the N-terminal extreme of the inhibitor. Strikingly, addition of two hook residues could dramatically enhance the binding affinity and thermostability of 6-helix bundle core. Compared with C34, MT-C34 exhibited significantly increased activity to inhibit HIV-1 envelope-mediated cell fusion (6.6-fold), virus entry (4.5-fold), and replication (6-fold). Mechanistically, MT-C34 had a 10.5-fold higher increase than C34 in blocking 6-helix bundle formation. We further showed that MT-C34 possessed higher potency against T20 (Enfuvirtide, Fuzeon)-resistant HIV-1 variants. Therefore, this study provides convincing data for our proposed concept that the M-T hook structure is critical for designing HIV-1 fusion inhibitors. PMID:22879603

Prevalence and risk factors of Mycobacterium tuberculosis complex infection in slaughtered cattle at Jos South Abattoir, Plateau State, Nigeria.

PubMed

Okeke, Lilian Akudo; Cadmus, Simeon; Okeke, Ikenna Osemeka; Muhammad, Maryam; Awoloh, Oluchi; Dairo, David; Waziri, Endie Ndadilnasiya; Olayinka, Adebola; Nguku, Patrick Mboyo; Fawole, Olufunmilayo

2014-01-01

Bovine tuberculosis (BTB) is widespread yet poorly controlled in Nigeria hence posing a public health threat. This study determined the prevalence of Mycobacterium tuberculosis complex (MTC) and factors associated with MTC among slaughtered cattle at Jos South Abattoir in Plateau State, Nigeria. We conducted a cross sectional study in which we collected 168 lung samples systematically from 485 slaughtered cattle from May-June, 2012, and tested for acid fast bacilli (AFB) using Ziehl-Neelsen test and a duplex polymerase chain reaction technique (PCR) for MTC detection. Data on cattle socio-demographic characteristics and risk factors for zoonotic BTB infection was obtained and analyzed using Epi info version 3.5.3 to determine frequency, proportions, and prevalence odds ratios. Multiple logistic regression was done at 95% Confidence Interval (CI). The mean age of the cattle was 5.6 ± 1.3 years and (108) 64.3% were females. Majority were indigenous White Fulani breed of cattle (58.5%) and about half (54.8%) were slightly emaciated. Prevalence of MTB complex was 21.4% by AFB test and 16.7% by duplex PCR. Of 33 (19.6%) lungs with lesions, 27 (81.8%) were positive for AFB; while of 135 (80.4%) lungs without lesions, 9 (6.7%) were positive for AFB. Lungs with lesions were 52 times more likely to test positive to AFB test compared to tissues without lesions (AOR=52.3; 95% CI: 16.4-191.8). The presence of MTC in cattle signifies its potential risk to public health. Presence of lesions on lungs is a reliable indicator of MTC infection that meat inspectors should look out for.

High-Resolution 4D Imaging of Technetium Transport in Porous Media using Preclinical SPECT-CT

NASA Astrophysics Data System (ADS)

Dogan, M.; DeVol, T. A.; Groen, H.; Moysey, S. M.; Ramakers, R.; Powell, B. A.

2015-12-01

Preclinical SPECT-CT (single-photon emission computed tomography with integrated X-ray computed tomography) offers the potential to quantitatively image the dynamic three-dimensional distribution of radioisotopes with sub-millimeter resolution, overlaid with structural CT images (20-200 micron resolution), making this an attractive method for studying transport in porous media. A preclinical SPECT-CT system (U-SPECT4CT, MILabs BV. Utrecht, The Netherlands) was evaluated for imaging flow and transport of 99mTc (t1/2=6hrs) using a 46,5mm by 156,4mm column packed with individual layers consisting of <0.2mm diameter silica gel, 0.2-0.25, 0.5, 1.0, 2.0, 3.0, and 4.0mm diameter glass beads, and a natural soil sample obtained from the Savannah River Site. The column was saturated with water prior to injecting the 99mTc solution. During the injection the flow was interrupted intermittently for 10 minute periods to allow for the acquisition of a SPECT image of the transport front. Non-uniformity of the front was clearly observed in the images as well as the retarded movement of 99mTc in the soil layer. The latter is suggesting good potential for monitoring transport processes occurring on the timescale of hours. After breakthrough of 99mTc was achieved, the flow was stopped and SPECT data were collected in one hour increments to evaluate the sensitivity of the instrument as the isotope decayed. Fused SPECT- CT images allowed for improved interpretation of 99mTc distributions within individual pore spaces. With ~3 MBq remaining in the column, the lowest activity imaged, it was not possible to clearly discriminate any of the pore spaces.

Plastic surgical operative workload in major trauma patients following establishment of the major trauma network in England: A retrospective cohort study.

PubMed

Hendrickson, S A; Khan, M A; Verjee, L S; Rahman, K M A; Simmons, J; Hettiaratchy, S P

2016-07-01

The introduction of major trauma centres (MTCs) in England has led to 63% reduction in trauma mortality.(1) The role of plastic surgeons supporting these centres has not been quantified previously. This study aimed to quantify plastic surgical workload at an urban MTC to determine the contribution of plastic surgeons to major trauma care. All Trauma Audit and Research Network (TARN)-recorded major trauma patients who presented to an urban MTC in 2013 and underwent an operation were identified retrospectively. Patients who underwent plastic surgery were identified and the type and date of procedure(s) were recorded. The trauma operative workload data of another tertiary surgical specialty and local historical plastics workload data from pre-MTC go-live were collected for comparison. Of the 416 major trauma patients who required surgical intervention, 29% (n = 122) underwent plastic surgery. Of these patients, 43% had open lower limb fractures, necessitating plastic surgical involvement according to British Orthopaedic Association Standards for Trauma (BOAST) 4 guidance. The overall plastic surgery operative workload increased sevenfold post-MTC go-live. A similar proportion of the same cohort required neurosurgery (n = 115; p = 0.589). This study quantifies plastic surgery involvement in major trauma and demonstrates that plastic surgical operative workload is at least on par with other tertiary surgical specialties. It also reports one centre's experience of a significant change in plastic surgery activity following designation of MTC status. The quantity of plastic surgical operative workload in major trauma must be considered when planning major trauma service design and workforce provision, and for plastic surgical postgraduate training. Copyright © 2016 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Surgical management of medullary thyroid cancer.

PubMed

Mazeh, H; Sippel, R S

2012-12-01

Although thyroid cancer accounts for only 1.5% of all malignancies in the US it is the most rapidly increasing cancer in incidence and it is the most common endocrine malignancy that accounts for over 95% of the endocrine malignancies. Medullary thyroid cancer (MTC) originates from the parafollicular C cells and it represents 6-8% of all thyroid cancer cases. As many as 25% of the MTCs are familial and carry a specific germline mutation as compared to only than 10% familial inheritance in non-medullary thyroid cancers. While well-differentiated thyroid malignancies carry a very good prognosis, recurrence and survival rates of patients with MTC are significantly worse. The difference in cell origin and differentiation also results in different available adjunct therapy. The aim of this study is to review in detail the surgical management of patients with MTC.

Validity of /sup 99m/Tc dimercaptosuccinic acid renal uptake for an assessment for individual kidney function

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

Kawamura, J.; Hosakawa, S.; Yoshida, O.

/sup 99m/Tc dimercaptosuccinic acid is a new renal scanning agent that provides a good quality of renal image as a result of preferential cortical accumulation and also makes feasible a quantitative assessment of separate kidney function, correlating well with renal plasma flow obtained from a /sup 131/I hippuran renogram of each kidney. By measuring the dimercaptosuccinic acid uptake, the cortical functioning nephrons can be determined independent of the activity from the urinary outflow tract. Such evaluations may replace the conventional split renal function study in which traumatic procedures, such as cystoscopy and ureteral catheterizations, are required. /sup 99m/Tc dimercaptosuccinic acidmore » scintigraphy causes less discomfort to the patient and can be performed repeatedly and routinely even in children and debilitated geriatric patients.« less

Management of thyroid cancer: United Kingdom National Multidisciplinary Guidelines.

PubMed

Mitchell, A L; Gandhi, A; Scott-Coombes, D; Perros, P

2016-05-01

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. This paper provides recommendations on the management of thyroid cancer in adults and is based on the 2014 British Thyroid Association guidelines. Recommendations • Ultrasound scanning (USS) of the nodule or goitre is a crucial investigation in guiding the need for fine needle aspiration cytology (FNAC). (R) • FNAC should be considered for all nodules with suspicious ultrasound features (U3-U5). If a nodule is smaller than 10 mm in diameter, USS guided FNAC is not recommended unless clinically suspicious lymph nodes on USS are also present. (R) • Cytological analysis and categorisation should be reported according to the current British Thyroid Association Guidance. (R) • Ultrasound scanning assessment of cervical nodes should be done in FNAC-proven cancer. (R) • Magnetic resonance imaging (MRI) or computed tomography (CT) should be done in suspected cases of retrosternal extension, fixed tumours (local invasion with or without vocal cord paralysis) or when haemoptysis is reported. When CT with contrast is used pre-operatively, there should be a two-month delay between the use of iodinated contrast media and subsequent radioactive iodine (I131) therapy. (R) • Fluoro-deoxy-glucose positron emission tomography imaging is not recommended for routine evaluation. (G) • In patients with thyroid cancer, assessment of extrathyroidal extension and lymph node disease in the central and lateral neck compartments should be undertaken pre-operatively by USS and cross-sectional imaging (CT or MRI) if indicated. (R) • For patients with Thy 3f or Thy 4 FNAC a diagnostic hemithyroidectomy is recommended. (R) • Total thyroidectomy is recommended for patients with tumours greater than 4 cm in diameter or tumours of any size in association with any of the following characteristics: multifocal disease, bilateral disease, extrathyroidal spread (pT3 and pT4a), familial disease and those with clinically or radiologically involved nodes and/or distant metastases. (R) • Subtotal thyroidectomy should not be used in the management of thyroid cancer. (G) • Central compartment neck dissection is not routinely recommended for patients with papillary thyroid cancer without clinical or radiological evidence of lymph node involvement, provided they meet all of the following criteria: classical type papillary thyroid cancer, patient less than 45 years old, unifocal tumour, less than 4 cm, no extrathyroidal extension on ultrasound. (R) • Patients with metastases in the lateral compartment should undergo therapeutic lateral and central compartment neck dissection. (R) • Patients with follicular cancer with greater than 4 cm tumours should be treated with total thyroidectomy. (R) • I131 ablation should be carried out only in centres with appropriate facilities. (R) • Serum thyroglobulin (Tg) should be checked in all post-operative patients with differentiated thyroid cancer (DTC), but not sooner than six weeks after surgery. (R) • Patients who have undergone total or near total thyroidectomy should be started on levothyroxine 2 µg per kg or liothyronine 20 mcg tds after surgery. (R) • The majority of patients with a tumour more than 1 cm in diameter, who have undergone total or near-total thyroidectomy, should have I131 ablation. (R) • A post-ablation scan should be performed 3-10 days after I131 ablation. (R) • Post-therapy dynamic risk stratification at 9-12 months is used to guide further management. (G) • Potentially resectable recurrent or persistent disease should be managed with surgery whenever possible. (R) • Distant metastases and sites not amenable to surgery which are iodine avid should be treated with I131 therapy. (R) • Long-term follow-up for patients with differentiated thyroid cancer (DTC) is recommended. (G) • Follow-up should be based on clinical examination, serum Tg and thyroid-stimulating hormone assessments. (R) • Patients with suspected medullary thyroid cancer (MTC) should be investigated with calcitonin and carcino-embryonic antigen levels (CEA), 24 hour catecholamine and nor metanephrine urine estimation (or plasma free nor metanephrine estimation), serum calcium and parathyroid hormone. (R) • Relevant imaging studies are advisable to guide the extent of surgery. (R) • RET (Proto-oncogene tyrosine-protein kinase receptor) proto-oncogene analysis should be performed after surgery. (R) • All patients with known or suspected MTC should have serum calcitonin and biochemical screening for phaeochromocytoma pre-operatively. (R) • All patients with proven MTC greater than 5 mm should undergo total thyroidectomy and central compartment neck dissection. (R) • Patients with MTC with lateral nodal involvement should undergo selective neck dissection (IIa-Vb). (R) • Patients with MTC with central node metastases should undergo ipsilateral prophylactic lateral node dissection. (R) • Prophylactic thyroidectomy should be offered to RET-positive family members. (R) • All patients with proven MTC should have genetic screening. (R) • Radiotherapy may be useful in controlling local symptoms in patients with inoperable disease. (R) • Chemotherapy with tyrosine kinase inhibitors may help in controlling local symptoms. (R) • For individuals with anaplastic thyroid carcinoma, initial assessment should focus on identifying the small proportion of patients with localised disease and good performance status, which may benefit from surgical resection and other adjuvant therapies. (G) • The surgical intent should be gross tumour resection and not merely an attempt at debulking. (G).

Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy to image force responses in living cells.

PubMed

Zhang, Yuejin; Wei, Fuxiang; Poh, Yeh-Chuin; Jia, Qiong; Chen, Junjian; Chen, Junwei; Luo, Junyu; Yao, Wenting; Zhou, Wenwen; Huang, Wei; Yang, Fang; Zhang, Yao; Wang, Ning

2017-07-01

Cells and tissues can undergo a variety of biological and structural changes in response to mechanical forces. Only a few existing techniques are available for quantification of structural changes at high resolution in response to forces applied along different directions. 3D-magnetic twisting cytometry (3D-MTC) is a technique for applying local mechanical stresses to living cells. Here we describe a protocol for interfacing 3D-MTC with confocal fluorescence microscopy. In 3D-MTC, ferromagnetic beads are bound to the cell surface via surface receptors, followed by their magnetization in any desired direction. A magnetic twisting field in a different direction is then applied to generate rotational shear stresses in any desired direction. This protocol describes how to combine magnetic-field-induced mechanical stimulation with confocal fluorescence microscopy and provides an optional extension for super-resolution imaging using stimulated emission depletion (STED) nanoscopy. This technology allows for rapid real-time acquisition of a living cell's mechanical responses to forces via specific receptors and for quantifying structural and biochemical changes in the same cell using confocal fluorescence microscopy or STED. The integrated 3D-MTC-microscopy platform takes ∼20 d to construct, and the experimental procedures require ∼4 d when carried out by a life sciences graduate student.

Clinical efficacy of a 1% Matricaria chamomile L. mouthwash and 0.12% chlorhexidine for gingivitis control in patients undergoing orthodontic treatment with fixed appliances.

PubMed

Goes, Paula; Dutra, Caio S; Lisboa, Mário R P; Gondim, Delane V; Leitão, Renata; Brito, Gerly A C; Rego, Rodrigo O

2016-01-01

This pilot study evaluated the clinical efficacy of a mouthwash containing 1% Matricaria chamomilla L. (MTC) extract in reducing gingival inflammation and plaque formation in patients undergoing orthodontic treatment with fixed appliances. This randomized, double-blind, placebo-controlled study enrolled a total of 30 males and females (age, 10-40 years) with fixed orthodontic appliances and a minimum of 20 natural teeth. The participants were allocated to three groups (n = 10 each) and asked to rinse with 15 mL of a placebo, 0.12% chlorhexidine (CHX), or 1% MTC mouthwash, immediately after brushing for 1 min, in the morning and evening, for 15 days. Data (mean ± SD) on visible plaque index (VPI) and gingival bleeding index (GBI) were recorded on days 1 and 15. The placebo group exhibited increases in VPI and GBI (10.2% and 23.1%, respectively) from day 1 to day 15. As compared with placebo, VPI and GBI significantly decreased in the MTC group (-25.6% and -29.9%, respectively) and the CHX group (-39.9% and -32.0%, respectively). In summary, MTC reduced biofilm accumulation and gingival bleeding in patients with gingivitis, probably because of its antimicrobial and anti-inflammatory activities.(J Oral Sci 58, 569-574, 2016).

Treatment of medullary thyroid carcinoma with apatinib: A case report and literature review.

PubMed

Cai, Sina; Deng, Huan; Chen, Yinkui; Wu, Xing; Guan, Xiaoqian

2017-12-01

Medullary thyroid carcinoma (MTC) is a rare type thyroid carcinoma originating from the thyroid parafollicular cells (C cells). Chemotherapy has a limited efficacy for treating persistent or recurrent MTC. A 46-year-old woman who underwent thyroidectomy for MTC in December 2007. She began experience recurring diarrhea in January 2015 and started to cough and feel shortness of breath in March 2016. A chestcomputed tomography (CT) scan showed metastases in the bilateral lungs, pulmonary hilum, and mediastinal lymph nodes. Percutaneous biopsy of the pulmonary occupying lesions performed on March 21, 2016 indicated medullary carcinoma metastases at the right pulmonary hilum. This patient was treated with oral apatinib (500 mg daily). The patient's symptoms of diarrhea, coughing, and shortness of breath disappeared. CT reexaminations for efficacy assessment at 1, 2, and 3 months after the treatment indicated partial remission. Systemic migrating bone and joint pains occurred during the treatment, which were considered to be adverse events of apatinib. Treatment of MTC with apatinib has been shown to be effective in our case. Tyrosine kinase inhibitors (TKIs) that suppress rearranged during transfection (RET) and vascular endothelial growth factor receptor (VEGFR) should be considered as a effective therapeutic approaches. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

[Situation of supply and boom of PET imaging: what is the future for technetium-99m in nuclear medicine?].

PubMed

Maia, S; Ayachi Hatit, N; Paycha, F

2011-05-01

Molecular imaging has shown its interest in the diagnosis, staging and therapy monitoring of many diseases, especially in the field of cancer. This imaging modality can detect non-invasively early molecular changes specific to these diseases. Its expansion includes two aspects linked firstly with the advanced techniques of imaging modalities and secondly with the development of tracers as radio pharmaceuticals for imaging new molecular targets. Technetium-99m ((99m)Tc), because of its physical characteristics, its widespread availability and low cost, is the most used radionuclide in molecular imaging with the technique of single photon emission computed tomography (SPECT). Nevertheless, the current difficulty concerning the supply and the great interest of Positron Emission Tomography (PET), the "competitor" imaging modality-using molecules labelled with fluorine-18 ((18)F), legitimates the question about the future of (99m)Tc, its supremacy and the emergence of new tracer labelled with (99m)Tc. Focusing on the actual and future supply situation, the place of SPECT imaging in nuclear medicine, as well as the development of new molecules labelled with (99m)Tc is necessary to show that this radionuclide will remain essential for the speciality in the next years. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Interfacing 3D magnetic twisting cytometry with confocal fluorescence microscopy to image force responses in living cells

PubMed Central

Zhang, Yuejin; Wei, Fuxiang; Poh, Yeh-Chuin; Jia, Qiong; Chen, Junjian; Chen, Junwei; Luo, Junyu; Yao, Wenting; Zhou, Wenwen; Huang, Wei; Yang, Fang; Zhang, Yao; Wang, Ning

2017-01-01

Cells and tissues can undergo a variety of biological and structural changes in response to mechanical forces. Only few existing techniques are available for quantification of structural changes at high resolution in response to forces applied along different directions. Three dimensional-Magnetic Twisting Cytometry (3D-MTC) is a technique for applying local mechanical stresses on living cells. Here we describe a protocol for interfacing 3D-MTC with confocal fluorescence microscopy. In 3D-MTC, ferromagnetic beads are bound to the cell surface via surface receptors followed by their magnetization in any desired direction. A magnetic twisting field in a different direction is then applied to generate rotational shear stresses in any desired direction. This protocol describes how to combine magnetic field-induced mechanical stimulation with confocal fluorescence microscopy and provides an optional extension for super resolution imaging using stimulated emission depletion (STED) nanoscopy. This technology allows for rapid real time acquisition of a living cell’s mechanical responses to forces via specific receptors and for quantifying structural and biochemical changes in the same cell using confocal fluorescence microscopy or STED. The integrated 3D-MTC – microscopy platform takes around 20 days to construct and the experimental procedures require ~4 days when carried out by a life sciences graduate student. PMID:28686583

Influence of Bidentate Ligand Donor Types on the Formation and Stability in 2+1 fac-[MI(CO)3]+ (M = Re, 99mTc) Complexes

PubMed Central

Hayes, Thomas R.; Bottorff, Shalina C.; Slocumb, Winston S.; Barnes, Charles L.; Clark, Aurora E.; Benny, Paul D.

2017-01-01

In the last two decades, a number of chelate strategies have been proposed for the fac-[MI(CO)3]+ (M = Re, 99mTc) core in radiopharmaceutical applications. However, the development of new ligands/complexes with improved function and in vivo performance has been limited in recent years. Expanding on our previous studies using the 2+1 labeling strategy, a series of bidentate ligands (neutral vs. anionic) containing an aromatic amine in combination with monodentate pyridine analogs or imidazole were explored to determine the influence of the bidentate and monodentate ligands on the formation and stability of the respective complexes. The 2+1 complexes with Re and 99mTc were synthesized in two steps and characterized by standard radio/chemical methods. X-ray characterization and density functional theory analysis of the Re 2+1 complexes with the complete bidentate series with 4-dimethylaminopyridine were conducted, indicating enhanced ligand binding energies of the neutral over anionic ligands. In the 99mTc studies, anionic bidentate ligands had significantly higher formation yields of the 2+1 product, but neutral ligands appear to have increased stability in an amino acid challenge assay. Both bidentate series exhibited improved stability by increasing the basicity of the pyridine ligands. PMID:28045466

Investigation of activation cross section data of alpha particle induced nuclear reaction on molybdenum up to 40 MeV: Review of production routes of medically relevant 97,103Ru

NASA Astrophysics Data System (ADS)

Tárkányi, F.; Hermanne, A.; Ditrói, F.; Takács, S.; Ignatyuk, A.

2017-05-01

The main goals of this investigations were to expand and consolidate reliable activation cross-section data for the natMo(α,x) reactions in connection with production of medically relevant 97,103Ru and the use of the natMo(α,x)97Ru reaction for monitoring beam parameters. The excitation functions for formation of the gamma-emitting radionuclides 94Ru, 95Ru, 97Ru, 103Ru, 93mTc, 93gTc(m+), 94mTc, 94gTc, 95mTc, 95gTc, 96gTc(m+), 99mTc, 93mMo, 99Mo(cum), 90Nb(m+) and 88Zr were measured up to 40 MeV alpha-particle energy by using the stacked foil technique and activation method. Data of our earlier similar experiments were re-evaluated and resulted in corrections on the reported results. Our experimental data were compared with critically analyzed literature data and with the results of model calculations, obtained by using the ALICE-IPPE, EMPIRE 3.1 (Rivoli) and TALYS codes (TENDL-2011 and TENDL-2015 on-line libraries). Nuclear data for different production routes of 97Ru and 103Ru are compiled and reviewed.

Manticore and CS mode : parallelizable encryption with joint cipher-state authentication.

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

Torgerson, Mark Dolan; Draelos, Timothy John; Schroeppel, Richard Crabtree

2004-10-01

We describe a new mode of encryption with inexpensive authentication, which uses information from the internal state of the cipher to provide the authentication. Our algorithms have a number of benefits: (1) the encryption has properties similar to CBC mode, yet the encipherment and authentication can be parallelized and/or pipelined, (2) the authentication overhead is minimal, and (3) the authentication process remains resistant against some IV reuse. We offer a Manticore class of authenticated encryption algorithms based on cryptographic hash functions, which support variable block sizes up to twice the hash output length and variable key lengths. A proof ofmore » security is presented for the MTC4 and Pepper algorithms. We then generalize the construction to create the Cipher-State (CS) mode of encryption that uses the internal state of any round-based block cipher as an authenticator. We provide hardware and software performance estimates for all of our constructions and give a concrete example of the CS mode of encryption that uses AES as the encryption primitive and adds a small speed overhead (10-15%) compared to AES alone.« less

Radionuclide imaging in myocardial sarcoidosis. Demonstration of myocardial uptake of /sup 99m/Tc pyrophosphate and gallium

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

Forman, M.B.; Sandler, M.P.; Sacks, G.A.

1983-03-01

A patient had severe congestive cardiomyopathy secondary to myocardial sarcoidosis. The clinical diagnosis was confirmed by radionuclide ventriculography, /sup 201/Tl, /sup 67/Ga, and /sup 99m/Tc pyrophosphate (TcPYP) scintigraphy. Myocardial TcPYP uptake has not been reported previously in sarcoidosis. In this patient, TcPYP was as useful as gallium scanning and thallium imaging in documenting the myocardial process.

Nurse exposure doses resulted from bone scintigraphy patient

NASA Astrophysics Data System (ADS)

Tunçman, Duygu; Kovan, Bilal; Poyraz, Leyla; ćapali, Veli; Demir, Bayram; Türkmen, Cüneyt

2016-03-01

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It's general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget's disease, investigation of loosening and infection in orthopedic implants. It is applied with using 99mTc labeled radiopharmaceuticals (e.g 99m Tc MDP,99mTc HEDP and 99mTc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. When some patient's situation is not good, patients are hospitalized until the scanning because of patients' close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse's exposure radiations from patient's routine treatment, examination and emergency station.

Knowledge, attitudes and practices of health personnel of maternities in the prevention of mother-to-child transmission of HIV in a sub-Saharan African region with high transmission rate: some solutions proposed.

PubMed

Nkwabong, Elie; Meboulou Nguel, Romuald; Kamgaing, Nelly; Keddi Jippe, Anne Sylvie

2018-06-14

High mother-to-child (MTC) transmission rate of HIV might contribute to the increased pandemic rate. The aim of this study was to identify the knowledge, attitude and practices of health personnel working in maternities in the prevention of MTC transmission of HIV. This cross-sectional descriptive study was carried out from 20th February to 30th April, 2017. All health personnel working in the maternity wards were included in this study. The variables recorded included their age, grade, experience (number of year of practice), gender, educational level, health structure and the training in prevention of MTC transmission of HIV. Analyses were done using SPSS 21.0. The Pearson Chi-square test or Fisher's exact test and logistic regression were used for comparison. The level of significance was P < 0.05. A total of 140 health personnel were recruited. Knowledge was insufficient amongst 73 of them (52.1%). The factors significantly associated with sufficient knowledge were midwifery qualification (aOR 9.01, 95% CI 1.82-48.60) and training in prevention of MTC transmission of HIV (aOR 2.23, 95% CI 1.02-4.81). Regarding attitudes, it was negative in 85 practitioners (60.7%). Only those aged ≥33 years were significantly associated with a positive attitude (aOR 2.34, 95% CI 1.14-4.23). As concerns practices, only 32 practitioners (22.9%) had good practices. Only midwives were associated with good practices (aOR 3.23, 95% CI 1.21-9.95). Insufficient knowledge, attitude and practices in the prevention of MTC transmission of HIV were observed among the majority of health personnel in the region. This lack of knowledge in prevention can therefore contribute to the rise of the mother-to-child transmission rate of HIV. To reduce this rate, more health personnel should be trained, especially midwives, in the prevention of MTC transmission of HIV. Moreover, deliveries of all women living with HIV should be conducted or at least supervised by trained midwives, especially those of at least 33 years of age.

Elastic properties of muscle-tendon complex in long-distance runners.

PubMed

Kubo, K; Kanehisa, H; Kawakami, Y; Fukunaga, T

2000-02-01

The purpose of this study was to investigate the elastic properties of muscle-tendon complex (MTC) in knee extensor muscles and the capacity for elastic energy utilization in long-distance runners (LDR) by comparing with data obtained from untrained individuals (CON). The elongation (L) of the tendon and aponeurosis of vastus lateralis muscle during isometric knee extension was determined by real-time brightness mode ultrasonography, while the subjects developed a gradually increasing torque from 0 (relaxed) to maximal effort (MVC) within 7 s. In addition, performances in two kinds of maximal vertical jumps, i.e. squatting (SJ) and counter-movement jumps (CMJ), were measured. The relationship between L muscle and force (F) was curvilinear and consisted of an initial region (toe region), characterized by a large increase in L with increasing F, immediately followed by a linear region. The slope of the regression equation for the L-F relationship in the range 50%-100% of MVC was defined as an index of MTC compliance, where the rate of the changes in L to that in muscle F at every 10% of MVC became almost constant. The maximal L (Lmax) and MTC compliance were significantly lower in LDR than in CON: 29.9 (SD 3.9) mm in LDR compared to 33.3 (SD 5.5) mm in CON for Lmax and 1.55 (SD 0.25) x 10(-2) mm.N-1 in LDR compared to 1.88 (SD 0.82) x 10(-2) mm.N-1 in CON for MTC compliance. Also, LDR showed significantly less elastic energy absorption (Ee) than CON, defined as the area below the L-F relationship curve from 0 to 100% of MVC. Not only jump heights but also the differences between the heights in SJ and CMJ, expressed as the percentage of the height in SJ, were significantly lower in LDR than in CON. The augmentation with counter-movement was significantly correlated to either MTC compliance (r = 0.554, P < 0.05) or Ee (r = 0.563, P < 0.05). Thus, the present results would indicate that MTC of vastus lateralis muscle is less compliant and its potential for energy storage during MTS lengthening is lower in LDR than untrained individuals. These elastic profiles of vastus lateralis muscle in LDR may be associated with their lower performances during CMJ.

Imaging of spatially extended hot spots with coded apertures for intra-operative nuclear medicine applications

NASA Astrophysics Data System (ADS)

Kaissas, I.; Papadimitropoulos, C.; Potiriadis, C.; Karafasoulis, K.; Loukas, D.; Lambropoulos, C. P.

2017-01-01

Coded aperture imaging transcends planar imaging with conventional collimators in efficiency and Field of View (FOV). We present experimental results for the detection of 141 keV and 122 keV γ-photons emitted by uniformly extended 99mTc and 57Co hot-spots along with simulations of uniformly and normally extended 99mTc hot-spots. These results prove that the method can be used for intra-operative imaging of radio-traced sentinel nodes and thyroid remnants. The study is performed using a setup of two gamma cameras, each consisting of a coded-aperture (or mask) of Modified Uniformly Redundant Array (MURA) of rank 19 positioned on top of a CdTe detector. The detector pixel pitch is 350 μm and its active area is 4.4 × 4.4 cm2, while the mask element size is 1.7 mm. The detectable photon energy ranges from 15 keV up to 200 keV with an energy resolution of 3-4 keV FWHM. Triangulation is exploited to estimate the 3D spatial coordinates of the radioactive spots within the system FOV. Two extended sources, with uniform distributed activity (11 and 24 mm in diameter, respectively), positioned at 16 cm from the system and with 3 cm distance between their centers, can be resolved and localized with accuracy better than 5%. The results indicate that the estimated positions of spatially extended sources lay within their volume size and that neighboring sources, even with a low level of radioactivity, such as 30 MBq, can be clearly distinguished with an acquisition time about 3 seconds.

BAYESIAN META-ANALYSIS ON MEDICAL DEVICES: APPLICATION TO IMPLANTABLE CARDIOVERTER DEFIBRILLATORS

PubMed Central

Youn, Ji-Hee; Lord, Joanne; Hemming, Karla; Girling, Alan; Buxton, Martin

2012-01-01

Objectives: The aim of this study is to describe and illustrate a method to obtain early estimates of the effectiveness of a new version of a medical device. Methods: In the absence of empirical data, expert opinion may be elicited on the expected difference between the conventional and modified devices. Bayesian Mixed Treatment Comparison (MTC) meta-analysis can then be used to combine this expert opinion with existing trial data on earlier versions of the device. We illustrate this approach for a new four-pole implantable cardioverter defibrillator (ICD) compared with conventional ICDs, Class III anti-arrhythmic drugs, and conventional drug therapy for the prevention of sudden cardiac death in high risk patients. Existing RCTs were identified from a published systematic review, and we elicited opinion on the difference between four-pole and conventional ICDs from experts recruited at a cardiology conference. Results: Twelve randomized controlled trials were identified. Seven experts provided valid probability distributions for the new ICDs compared with current devices. The MTC model resulted in estimated relative risks of mortality of 0.74 (0.60–0.89) (predictive relative risk [RR] = 0.77 [0.41–1.26]) and 0.83 (0.70–0.97) (predictive RR = 0.84 [0.55–1.22]) with the new ICD therapy compared to Class III anti-arrhythmic drug therapy and conventional drug therapy, respectively. These results showed negligible differences from the preliminary results for the existing ICDs. Conclusions: The proposed method incorporating expert opinion to adjust for a modification made to an existing device may play a useful role in assisting decision makers to make early informed judgments on the effectiveness of frequently modified healthcare technologies. PMID:22559753

Novel Metal Ion Based Estrogen Mimics for Molecular Imaging

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

Rajagopalan, Raghavan

The overall objective of the SBIR Phase I proposal is to prepare and evaluate a new class of {sup 99m}Tc or {sup 94m}Tc containing estrogen-like small molecules ('estrogen mimics') for SPECT or PET molecular imaging of estrogen receptor positive (ER+) tumors. In this approach, the metal ion is integrated into the estrone skeleton by isosteric substitution of a carbon atom in the steroidal structure to give new class of mimics that are topologically similar to the native estrogen (Fig. 1). Although both N{sub 2}S{sub 2} and N{sub 3}S mimics 1 and 2 were considered as target structures, molecular modeling studymore » revealed that the presence of the acetyl group at position-15 in the N{sub 3}S mimic 2 causes steric hinderance toward binding of 2 to SHBG. Therefore, initial efforts were directed at the synthesis and evaluation of the N{sub 2}S{sub 2} mimic 1.« less

Sorption of99mTc radiopharmaceutical compounds by soils

USGS Publications Warehouse

Jurisson, S.; Gawenis, J.; Landa, E.R.

2004-01-01

Study of the sorption of 99mTc radiopharmaceutical compounds by soils has assessed the fate of these compounds in the event of a surface spill and examined the potential of these compounds as hydrologic tracers. Sorption from deionized water, filtered Missouri River water, and artificial seawater by five surface soils was investigated. For all water types, the Tc radiopharmaceutical compounds showed greater sorption than the uncomplexed pertechnetate. The most lipophilic complexes showed the highest sorption on soils.

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

PubMed

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Omer

2013-12-01

The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. None declared.

LTE-advanced random access mechanism for M2M communication: A review

NASA Astrophysics Data System (ADS)

Mustafa, Rashid; Sarowa, Sandeep; Jaglan, Reena Rathee; Khan, Mohammad Junaid; Agrawal, Sunil

2016-03-01

Machine Type Communications (MTC) enables one or more self-sufficient machines to communicate directly with one another without human interference. MTC applications include smart grid, security, e-Health and intelligent automation system. To support huge numbers of MTC devices, one of the challenging issues is to provide a competent way for numerous access in the network and to minimize network overload. In this article, the different control mechanisms for overload random access are reviewed to avoid congestion caused by random access channel (RACH) of MTC devices. However, past and present wireless technologies have been engineered for Human-to-Human (H2H) communications, in particular, for transmission of voice. Consequently the Long Term Evolution (LTE) -Advanced is expected to play a central role in communicating Machine to Machine (M2M) and are very optimistic about H2H communications. Distinct and unique characteristics of M2M communications create new challenges from those in H2H communications. In this article, we investigate the impact of massive M2M terminals attempting random access to LTE-Advanced all at once. We discuss and review the solutions to alleviate the overload problem by Third Generation Partnership Project (3GPP). As a result, we evaluate and compare these solutions that can effectively eliminate the congestion on the random access channel for M2M communications without affecting H2H communications.

Magnetization transfer contrast-suppressed imaging of amide proton transfer and relayed nuclear overhauser enhancement chemical exchange saturation transfer effects in the human brain at 7T.

PubMed

Xu, Xiang; Yadav, Nirbhay N; Zeng, Haifeng; Jones, Craig K; Zhou, Jinyuan; van Zijl, Peter C M; Xu, Jiadi

2016-01-01

To use the variable delay multipulse (VDMP) chemical exchange saturation transfer (CEST) approach to obtain clean amide proton transfer (APT) and relayed Nuclear Overhauser enhancement (rNOE) CEST images in the human brain by suppressing the conventional magnetization transfer contrast (MTC) and reducing the direct water saturation contribution. The VDMP CEST scheme consists of a train of RF pulses with a specific mixing time. The CEST signal with respect to the mixing time shows distinguishable characteristics for protons with different exchange rates. Exchange rate filtered CEST images are generated by subtracting images acquired at two mixing times at which the MTC signals are equal, while the APT and rNOE-CEST signals differ. Because the subtraction is performed at the same frequency offset for each voxel and the CEST signals are broad, no B0 correction is needed. MTC-suppressed APT and rNOE-CEST images of human brain were obtained using the VDMP method. The APT-CEST data show hyperintensity in gray matter versus white matter, whereas the rNOE-CEST images show negligible contrast between gray and white matter. The VDMP approach provides a simple and rapid way of recording MTC-suppressed APT-CEST and rNOE-CEST images without the need for B0 field correction. © 2015 Wiley Periodicals, Inc.

Inherited medullary thyroid cancer and the duty to warn: revisiting Pate v. Threlkel in light of HIPAA.

PubMed

Rosenthal, M Sara; Pierce, Heather Hanson

2005-02-01

Familial medullary thyroid cancer (FMTC) is one of the few autosomal dominant cancers for which genetic testing provides a clear medical indication for prophylactic and/or curative therapy, and for which prophylactic thyroidectomy, followed by thyroid hormone replacement, presents a relatively low morbidity risk. Medullary thyroid cancer (MTC) is a particularly aggressive type of thyroid cancer, and screening by traditional biochemical markers yields a high proportion of advanced stage diagnoses in individuals from FMTC families. This is particularly hazardous since there are no curative systemic treatments for MTC. Genetic testing for germline mutations of the RET proto-oncogene provides a reliable method of identifying at-risk family members in those FMTC families in which a mutation has been identified in the proband. Prophylactic thyroidectomy in such at-risk family members has significantly reduced the proportion of advanced stage MTC diagnoses in MTC families. Since a clear medical benefit exists for genetic testing in family members, and a clear danger to family members exists in the absence of genetic counseling, establishing genetic diagnosis as standard of care has critical legal and ethical implications for medical providers caring for probands and family members. The "duty to warn," reinforced by the courts in the legal case of Pate v. Threlkel, may override recent confidentiality legislation, known as the HIPAA Privacy Rules, which came into effect April 12, 2003.

Evidence of Mycobacterium tuberculosis complex bacteraemia in intradermal skin test positive cattle detected using phage-RPA.

PubMed

Swift, Benjamin M C; Convery, Thomas W; Rees, Catherine E D

2016-10-02

Bovine tuberculosis is a zoonotic infectious disease caused by Mycobacterium bovis that affects cattle and can cause tuberculosis in a range of wildlife animals. A bacteriophage-based method combined with PCR (phage-PCR) has been recently used to detect and identify viable pathogenic mycobacteria in the peripheral blood mononuclear cells (PBMCs) of animals suffering from paratuberculosis. To adapt this method for the detection of M. bovis in blood, a new isothermal DNA amplification protocol using Recombinase Polymerase Amplification (RPA) was developed and was found to be able to detect M. bovis BCG within 48 h, with a limit of detection of approximately 10 cells per ml of blood for artificially inoculated blood samples. When blood samples (2 ml) from a Single Comparative Cervical Intradermal Tuberculin (SCCIT)- negative beef herd were tested, Mycobacterium tuberculosis complex (MTC) cells were not detected from any (45) of the blood samples. However when blood samples from SCCIT-positive animals were tested, viable MTC bacteria were detected in 66 % (27/41) of samples. Of these 41 animals sampled, 32 % (13) had visible lesions. In the visible lesion (VL) group, 85 % (11/13) had detectable levels of MTC whereas only 57 % (16/28) of animals which had no visible lesions (NVL) were found to have detectable mycobacteraemia. These results indicated that this simple, rapid method can be applied for the study of M. bovis infections. The frequency with which viable mycobacteria were detected in the peripheral blood of SCCIT-positive animals changes the paradigm of this disease.

Dual-Labeled Near-Infrared/99mTc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells

PubMed Central

Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

2016-01-01

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m (99mTc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with 99mTc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner. PMID:27399687

Dual-Labeled Near-Infrared/(99m)Tc Imaging Probes Using PAMAM-Coated Silica Nanoparticles for the Imaging of HER2-Expressing Cancer Cells.

PubMed

Yamaguchi, Haruka; Tsuchimochi, Makoto; Hayama, Kazuhide; Kawase, Tomoyuki; Tsubokawa, Norio

2016-07-07

We sought to develop dual-modality imaging probes using functionalized silica nanoparticles to target human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer cells and achieve efficient target imaging of HER2-expressing tumors. Polyamidoamine-based functionalized silica nanoparticles (PCSNs) for multimodal imaging were synthesized with near-infrared (NIR) fluorescence (indocyanine green (ICG)) and technetium-99m ((99m)Tc) radioactivity. Anti-HER2 antibodies were bound to the labeled PCSNs. These dual-imaging probes were tested to image HER2-overexpressing breast carcinoma cells. In vivo imaging was also examined in breast tumor xenograft models in mice. SK-BR3 (HER2 positive) cells were imaged with stronger NIR fluorescent signals than that in MDA-MB231 (HER2 negative) cells. The increased radioactivity of the SK-BR3 cells was also confirmed by phosphor imaging. NIR images showed strong fluorescent signals in the SK-BR3 tumor model compared to muscle tissues and the MDA-MB231 tumor model. Automatic well counting results showed increased radioactivity in the SK-BR3 xenograft tumors. We developed functionalized silica nanoparticles loaded with (99m)Tc and ICG for the targeting and imaging of HER2-expressing cells. The dual-imaging probes efficiently imaged HER2-overexpressing cells. Although further studies are needed to produce efficient isotope labeling, the results suggest that the multifunctional silica nanoparticles are a promising vehicle for imaging specific components of the cell membrane in a dual-modality manner.

Role of scintigraphy in urinary tract infection

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

Conway, J.J.

1988-10-01

There is controversy regarding the role of radiological imaging for urinary tract infection (UTI). The gold standard has been the intravenous pyelogram (IVP). Yet, the IVP has a very limited value with only about 25% of children with pyelonephritis demonstrating abnormalities. Ultrasound (US) has recently been advocated as a replacement for the poorly sensitive and poorly specific IVP. However, comparative studies between US and IVP indicate only an equivalent sensitivity and specificity. Cortical scintigraphy with Technetium-99m glucoheptonate (99mTc GH) or 99mTc dimercaptosuccinic acid (99mTc DMSA) has also been advocated as a means of differentiating parenchymal (pyelonephritis) from nonparenchymal (lower UTI)more » involvement in UTI. The clinical presentation may be misleading especially in the infant and child in whom an elevated temperature, flank pain, shaking chills, or an elevated sedimentation rate are often lacking. The clinician attempts to localize the site of infection for it has a direct bearing upon the therapy. A collecting system infection can often be eradicated with a single oral dose of an appropriate antibiotic, whereas renal parenchymal involvement requires IV therapy for an extended interval. Cortical scintigraphy can localize the site of infection with a high degree of accuracy. Recent studies report a sensitivity of 86% and specificity of 81% of pyelonephritis. This is in contrast to the IVP with a sensitivity of only 24% and US with a sensitivity of only 42%. The scintigraphic appearance of parenchymal infection of the kidney is a spectrum of minimal to gross defects reflecting the degree of histologic involvement that spans from a mild infection to frank abscess. Cortical scintigraphy can be used to monitor the evolution of scarring following infection. Cortical scintigraphy with 99mTc DMSA or 99mTc GH is the method of choice for the initial evaluation of UTI. 37 references.« less

Carbonate Channel-Levee Systems Influenced by Mass-Transport Deposition, Browse Basin, Australia

NASA Astrophysics Data System (ADS)

Dunlap, D.; Janson, X.; Sanchez-Phelps, C.; Covault, J. A.

2017-12-01

Submarine channels are primary conduits for clastic sediment transport to deep-water basins, thereby controlling the location of marine depocenters and sediment bypass. The evolution and depositional character of submarine channels have broad implications to sediment dispersal, sediment quality, and hydrocarbon exploration potential. Siliciclastic channel systems have been extensively studied in modern environments, seismic and outcrop; however, carbonate channel-levee deposits have only recently been explored. Here we utilize newly released high-resolution (90 Hz) seismic-reflection data from the Australian Browse Basin to document the influence of mass-transport complex (MTC) deposition on the stratigraphic architecture of carbonate channel-levee systems. The 2014 vintage seismic survey is 2500 km2 and hosts numerous large Miocene-age carbonate channel-levee complexes basinward of the shelf edge. Regional horizons and individual channel forms were mapped. Channels range from 200-300 m wide and are bounded by high-relief levee-overbank wedges (>100 ms TWTT). These channels extend across the survey area >70 km. The leveed-channels were sourced from middle and late Miocene slope gullies linked to platform carbonates. Slope-attached and locally derived MTC's are evident throughout the Miocene section likely related to periods of basin inversion and shelf-edge gully incision. We interpret that regionally extensive (>1000 km2) slope-attached MTC's can shut down a channel-levee system and trigger the initiation of a new system, whereas more locally derived (<100 km2) MTC's can promote changes in channel map-view pattern, including avulsion in some cases. The stratigraphic architectures of the carbonate channel-levee systems and their interactions with MTC's are similar to siliciclastic analogs. The similarity in stratigraphic patterns between siliciclastic and carbonate depositional systems suggests similar formative processes related to submarine mass wasting and turbidity currents, which informs depositional models of carbonate slope systems and calls for re-evaluation of the controls on stratigraphic patterns in mixed siliciclastic-carbonate deep-water basins.

Novel mixed ligand technetium complexes as 5-HT1A receptor imaging agents.

PubMed

León, A; Rey, A; Mallo, L; Pirmettis, I; Papadopoulos, M; León, E; Pagano, M; Manta, E; Incerti, M; Raptopoulou, C; Terzis, A; Chiotellis, E

2002-02-01

The synthesis, characterization and biological evaluation of two novel 3 + 1 mixed ligand 99mTc-complexes, bearing the 1-(2-methoxyphenylpiperazine) moiety, a fragment of the true 5-HT1A antagonist WAY 100635, is reported. Complexes at tracer level 99mTcO[(CH3CH2)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N(CH2CH2)2NCH2CH2S], 99mTc-1, and 99mTcO[((CH3)2CH)2NCH2CH2N(CH2CH2S)2][o-CH3OC6H4N (CH2CH2)2NCH2CH2S], 99mTc-2, were prepared using 99mTc-glucoheptonate as precursor. For structural characterization, the analogous oxorhenium complexes, Re-1 and Re-2, were prepared by ligand exchange reaction using ReOCl3(PPh3)2 as precursor, and characterized by elemental analysis and spectroscopic methods. Complex Re-1 was further characterized by crystallographic analysis. Labeling was performed with high yield (>85%) and radiochemical purity (>90%) using very low ligand concentration. The structure of 99mTc complexes was established by comparative HPLC using the well-characterized oxorhenium analogues as references. In vitro binding assays demonstrated the affinity of these complexes for 5-HT1A receptors (IC50 : 67 and 45 nM for Re-1 and Re-2 respectively). Biological studies in mice showed the ability of 99mTc-1 and 99mTc-2 complexes to cross the intact blood-brain barrier (1.4 and 0.9% dose/g, respectively at 1 min post-inj.). The distribution of these complexes in various regions in rat brain is inhomogeneous. The highest ratio between areas reach and poor in 5-HT1A receptors was calculated for complex Tc-1 at 60 min p.i. (hippocampus/cerebellum = 1.7).

Sorafenib for the Treatment of Progressive Metastatic Medullary Thyroid Cancer: Efficacy and Safety Analysis.

PubMed

de Castroneves, Luciana Audi; Negrão, Marcelo Vailati; de Freitas, Ricardo Miguel Costa; Papadia, Carla; Lima, José Viana; Fukushima, Julia T; Simão, Eduardo Furquim; Kulcsar, Marco Aurélio Vamondes; Tavares, Marcos Roberto; Jorge, Alexander Augusto de Lima; de Castro, Gilberto; Hoff, Paulo Marcelo; Hoff, Ana Oliveira

2016-03-01

Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.

Comparison of estimated human dose of (68)Ga-MAA with (99m)Tc-MAA based on rat data.

PubMed

Shanehsazzadeh, Saeed; Lahooti, Afsaneh; Yousefnia, Hassan; Geramifar, Parham; Jalilian, Amir Reza

2015-10-01

(99m)Tc macroaggregated albumin ((99m)Tc-MAA) that had been used as a perfusion agent has been evaluated. In this study, we tried to estimate human absorbed dose of ⁶⁸Ga-MAA via commercially available kit from Pars-Isotopes, based on biodistribution data in wild-type rats, and compare our estimation with the available absorbed dose data from (99m)Tc-MAA. For biodistribution of ⁶⁸Ga-MAA, three rats were sacrificed at each selected times after injection (15, 30, 45, 60, and 120 min) and the percentage of injected dose per gram of each organ was measured by direct counting from rats data from 11 harvested organs. The medical internal radiation dose formulation was applied to extrapolate from rats to human and to project the absorbed radiation dose for various organs in humans. The biodistribution data for ⁶⁸Ga-MAA showed that the most of the activity was taken up by the lung (more than 97 %) in no time. Our dose prediction shows that a 185-MBq injection of ⁶⁸Ga-MAA into humans might result in an estimated absorbed dose of 4.31 mGy in the whole body. The highest absorbed doses are observed in the adrenals, spleen, pancreas, and red marrow with 0.36, 0.34, 0.26, and 0.19 mGy, respectively. Since the (99m)Tc-MAA remains longer than ⁶⁸Ga-MAA in the lung and ⁶⁸Ga-MAA has good image qualities and results in lower amounts of dose delivery to the critical organs such as gonads, red marrow, and adrenals, the use of ⁶⁸Ga-MAA is recommended.

On the possibility of 'real-time' Monte Carlo calculations for the estimation of absorbed dose in radioimmunotherapy.

PubMed

Johnson, T K; Vessella, R L

1989-07-01

Dosimetry calculations of monoclonal antibodies (MABs) are made difficult because the focus of radioactivity is targeted for a nonstandard volume in a nonstandard geometry, precluding straightforward application of the MIRD formalism. The MABDOS software addresses this shortcoming by interactive placement of a spherical perturbation into the Standard Man geometry for each tumor focus. S tables are calculated by a Monte Carlo simulation of photon transport for each organ system (including tumor) that localizes activity. Performance benchmarks are reported that measure the time required to simulate 60,000 photons for each penetrating radiation in the spectrum of 99mTc and 131I using the kidney as source organ. Results indicate that calculation times are probably prohibitive on current microcomputer platforms. Mini and supercomputers offer a realistic platform for MABDOS patient dosimetry estimates.

Nodular Graves' disease with medullary thyroid cancer.

PubMed

Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

2015-01-01

Co-existence of thyroid nodules with Graves' disease has been reported in various studies. 10-15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves' disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves' disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC.

Phaeochromocytoma in multiple endocrine neoplasia type 2: RET codon-specific penetrance and changes in management during the last four decades.

PubMed

Mucha, L; Leidig-Bruckner, G; Frank-Raue, K; Bruckner, Th; Kroiss, M; Raue, F

2017-10-01

We describe phaeochromocytoma (phaeo) penetrance in multiple endocrine neoplasia type 2 (MEN2) according to RET protooncogene-specific mutations and report changes in phaeo diagnosis and management from 1968 to 2015. This retrospective chart review included 309 MEN2 patients from one specialized ambulatory care centre. Phaeo patients were categorized by diagnosis date: early, 1968-1996, n=40, and recent, 1997-2015, n=45. Phaeochromocytoma was diagnosed in 85/309 patients with RET mutations in the following exons (phaeos/all carriers, %): exon 11 (56/120, 46.6%); exon 16 (7/17, 41.2%), exon 10 (14/47, 29.8%), and exon 13-15 (2/116, 1.7%). Age at phaeo diagnosis differed according to affected exon: 21.9±1.5 years, exon 16; 34.1±11.6 years, exon 11; and 41.8±8.8 years, exon 10. Age-related phaeo penetrance differed among five amino acid substitutions at codon 634 and was highest for Cys634Arg and Cys634Tyr. Age at diagnosis was 34.4±11.6 years in the early and recent groups. Phaeochromocytoma and medullary thyroid carcinoma (MTC) were diagnosed synchronously in 21/40 (early) vs 8/45 (recent) and metachronously in 19/40 vs 37/45 cases. Diagnostic methods significantly changed from clinical (22/40 vs 4/45) to biochemical and/or imaging based (14/40 vs 35/45). Phaeochromocytoma diameter at diagnosis was 4.6 vs 2.6 cm. Phaeochromocytoma penetrance and age of diagnosis are highly correlated with MTC aggressiveness based on RET mutation status, with higher penetrance and younger age of diagnosis associated with more aggressive MTC. Penetrance steadily increases with age. At-risk patients require lifelong follow-up. © 2017 John Wiley & Sons Ltd.

Monooxorhenium(V) complexes with 222-N2S2 MAMA ligands for bifunctional chelator agents: Syntheses and preliminary in vivo evaluation

PubMed Central

Demoin, Dustin Wayne; Dame, Ashley N.; Minard, William D.; Gallazzi, Fabio; Seickman, Gary L.; Rold, Tammy L.; Bernskoetter, Nicole; Fassbender, Michael E.; Hoffman, Timothy J.; Deakyne, Carol A.; Jurisson, Silvia S.

2016-01-01

Introduction Targeted radiotherapy using the bifunctional chelate approach with 186/188Re(V) is challenging because of the susceptibility of monooxorhenium(V)-based complexes to oxidize in vivo at high dilution. A monoamine-monoamide dithiol (MAMA)-based bifunctional chelating agent was evaluated with both rhenium and technetium to determine its utility for in vivo applications. Methods A 222-MAMA chelator, 222-MAMA(N-6-Ahx-OEt) bifunctional chelator, and 222- MAMA(N-6-Ahx-BBN(7-14)NH2) were synthesized, complexed with rhenium, radiolabeled with 99mTc and 186Re (carrier added and no carrier added), and evaluated in initial biological distribution studies. Results An IC50 value of 2.0 ± 0.7 nM for natReO-222-MAMA(N-6-Ahx-BBN(7-14)NH2) compared to [125I]-Tyr4-BBN(NH2) was determined through competitive cell binding assays with PC-3 tumor cells. In vivo evaluation of the no-carrier added 99mTc-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed little gastric uptake and blockable pancreatic uptake in normal mice. Conclusions The 186ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex showed stability in biological media, which indicates that the 222-N2S2 chelator is appropriate for chelating 186/188Re in radiopharmaceuticals involving peptides. Additionally, the in vitro cell studies showed that the ReO-222-N2S2(N-6-Ahx-BBN(7-14)NH2) complex (macroscopically) bound to PC3-tumor cell surface receptors with high affinity. The 99mTc analog was stable in vivo and exhibited pancreatic uptake in mice that was blockable, indicating BB2r targeting. PMID:27694058

Nurse exposure doses resulted from bone scintigraphy patient

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

Tunçman, Duygu, E-mail: duygutuncman@gmail.com; Demir, Bayram; Kovan, Bilal

Bone scintigraphy is used for displaying the radiologic undiagnosed bone lesions in nuclear medicine. It’s general indications are researching bone metastases, detection of radiographically occult fractures, staging and follow-up in primary bone tumors, diagnosis of paget’s disease, investigation of loosening and infection in orthopedic implants. It is applied with using {sup 99m}Tc labeled radiopharmaceuticals (e.g {sup 99m} Tc MDP,{sup 99m}Tc HEDP and {sup 99m}Tc HMDP). 20 -25 mCi IV radiotracer was injected into vein and radiotracer emits gamma radiation. Patient waits in isolated room for about 3 hours then a gamma camera scans radiation area and creates an image. Whenmore » some patient’s situation is not good, patients are hospitalized until the scanning because of patients’ close contact care need. In this study, measurements were taken from ten patients using Geiger Muller counter. After these measurements, we calculated nurse’s exposure radiations from patient’s routine treatment, examination and emergency station.« less

[Shielding effect of clinical X-ray protector and lead glass against annihilation radiation and gamma rays of 99mTc].

PubMed

Fukuda, Atsushi; Koshida, Kichiro; Yamaguchi, Ichiro; Takahashi, Masaaki; Kitabayashi, Keitarou; Matsubara, Kousuke; Noto, Kimiya; Kawabata, Chikako; Nakagawa, Hiroto

2004-12-01

Various pharmaceutical companies in Japan are making radioactive drugs available for positron emission tomography (PET) in hospitals without a cyclotron. With the distribution of these drugs to hospitals, medical check-ups and examinations using PET are expected to increase. However, the safety guidelines for radiation in the new deployment of PET have not been adequately improved. Therefore, we measured the shielding effect of a clinical X-ray protector and lead glass against annihilation radiation and gamma rays of (99m)Tc. We then calculated the shielding effect of a 0.25 mm lead protector, 1 mm lead, and lead glass using the EGS4 (Electron Gamma Shower Version 4) code. The shielding effects of 22-mm lead glass against annihilation radiation and gamma rays of (99m)Tc were approximately 31.5% and 93.3%, respectively. The clinical X-ray protector against annihilation radiation approximately doubled the skin-absorbed dose.

Efficient photodegradation of methylthioninium chloride dye in aqueous using barium tungstate nanoparticles

NASA Astrophysics Data System (ADS)

AlShehri, Saad M.; Ahmed, Jahangeer; Ahamad, Tansir; Almaswari, Basheer M.; Khan, Aslam

2017-08-01

BaWO4 nanoparticles were successfully used as the photocatalysts in the degradation of methylthioninium chloride (MTC) dye at different pH levels of aqueous solution. Pure phase of barium tungstate (BaWO4) nanoparticles was synthesized by modified molten salt process at 500 °C for 6 h. Structural and morphological characterizations of BaWO4 nanoparticles (average particle size of 40 nm) were studied in details using powder x-ray diffraction (XRD), FTIR, Raman, energy-dispersive, electron microscopic, and x-ray photoelectron spectroscopy (XPS) techniques. Direct band gap energy of BaWO4 nanoparticles was found to be 3.06 eV from the UV-visible absorption spectroscopy followed by Tauc's model. Photocatalytic properties of the nanoparticles were also investigated systematically for the degradation of MTC dye solution in various mediums. BaWO4 nanoparticles claim the significant enhancement of the photocatalytic degradation of aqueous MTC dye to non-hazardous inorganic constitutes under alkaline, neutral, and acidic mediums. [Figure not available: see fulltext.

Cu-free 1,3-dipolar cycloaddition click reactions to form isoxazole linkers in chelating ligands for fac-[M(I)(CO)3]+ centers (M = Re, 99mTc).

PubMed

Bottorff, Shalina C; Kasten, Benjamin B; Stojakovic, Jelena; Moore, Adam L; MacGillivray, Leonard R; Benny, Paul D

2014-02-17

Isoxazole ring formation was examined as a potential Cu-free alternative click reaction to Cu(I)-catalyzed alkyne/azide cycloaddition. The isoxazole reaction was explored at macroscopic and radiotracer concentrations with the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core for use as a noncoordinating linker strategy between covalently linked molecules. Two click assembly methods (click, then chelate and chelate, then click) were examined to determine the feasibility of isoxazole ring formation with either alkyne-functionalized tridentate chelates or their respective fac-[M(I)(CO)3](+) complexes with a model nitrile oxide generator. Macroscale experiments, alkyne-functionalized chelates, or Re complexes indicate facile formation of the isoxazole ring. (99m)Tc experiments demonstrate efficient radiolabeling with click, then chelate; however, the chelate, then click approach led to faster product formation, but lower yields compared to the Re analogues.

SPECT Imaging of Mice with 99mTc-Radiopharmaceuticals Obtained from 99Mo Produced by 100Mo(n,2n)99Mo and Fission of 235U

NASA Astrophysics Data System (ADS)

Hashimoto, Kazuyuki; Nagai, Yasuki; Kawabata, Masako; Sato, Nozomi; Hatsukawa, Yuichi; Saeki, Hideya; Motoishi, Shoji; Ohta, Masayuki; Konno, Chikara; Ochiai, Kentaro; Kawauchi, Yukimasa; Ohta, Akio; Shiina, Takayuki; Takeuchi, Nobuhiro; Ashino, Hiroki; Nakahara, Yuto

2015-04-01

The distribution of 99mTc-radiopharmaceutical in mouse was determined by single photon emission computed tomography (SPECT) for the first time using 99mTc, which was separated by thermochromatography from 99Mo produced via the 100Mo(n,2n)99Mo reaction with accelerator neutrons. The SPECT image was comparable to that obtained using the fission product 99Mo. Radionuclidic and radiochemical purities of the separated 99mTc and its aluminum concentration met the United States Pharmacopeia regulatory requirements for 99mTc from the fission product 99Mo. These results provide important evidence that the 99mTc-radiopharmaceutical formulated using the (n,2n) 99Mo can be a promising substitute for the fission product 99Mo. The current and forthcoming problem of ensuring a reliable and constant supply of 99Mo in Japan can be partially mitigated.

Rapid detection of Mycobacterium tuberculosis by recombinase polymerase amplification.

PubMed

Boyle, David S; McNerney, Ruth; Teng Low, Hwee; Leader, Brandon Troy; Pérez-Osorio, Ailyn C; Meyer, Jessica C; O'Sullivan, Denise M; Brooks, David G; Piepenburg, Olaf; Forrest, Matthew S

2014-01-01

Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39 °C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays could be of use for integration into a point-of-care test for use in resource constrained settings.

Effect of Thuya occidentalis on the labeling of red blood cells and plasma proteins with technetium-99m.

PubMed Central

Oliveira, J. F.; Braga, A. C.; Avila, A. S.; Fonseca, L. M.; Gutfilen, B.; Bernardo-Filho, M.

1996-01-01

Thuya occidentalis is used in popular medicine in the treatment of condyloma and has antibacterial action. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. This labeling depends on a reducing agent, usually stannous ion. Any drug which alters the labeling of the tracer could be expected to modify the disposition of the radiopharmaceutical. We have evaluated the influence of T. occidentalis extract on the labeling of RBC and plasma proteins with 99mTc. Blood was withdrawn and incubated with T. occidentalis (0.25; 2.5; 20.5; and 34.1 percent v/v). Stannous chloride (1.2 micrograms/ml) was added and then 99mTc was added. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) separated. The analysis of the results shows that there is a decrease in radioactivity (from 97.64 to 75.89 percent) in BC with 34.1 percent of the drug. In the labeling process of RBC with 99mTc, the stannous and pertechnetate ions pass through the membrane, so we suggest that the T. occidentalis effect can be explained (i) by an inhibition of the transport of these ions, (ii) by damage in membrane, (iii) by competition with the cited ions for the same binding sites, or (iv) by possible generation of reactive oxygen species that could oxidize the stannous ion. PMID:9436292

Effect of Thuya occidentalis on the labeling of red blood cells and plasma proteins with technetium-99m.

PubMed

Oliveira, J F; Braga, A C; Avila, A S; Fonseca, L M; Gutfilen, B; Bernardo-Filho, M

1996-01-01

Thuya occidentalis is used in popular medicine in the treatment of condyloma and has antibacterial action. Red blood cells (RBC) labeled with technetium-99m (99mTc) are used for several evaluations in nuclear medicine. This labeling depends on a reducing agent, usually stannous ion. Any drug which alters the labeling of the tracer could be expected to modify the disposition of the radiopharmaceutical. We have evaluated the influence of T. occidentalis extract on the labeling of RBC and plasma proteins with 99mTc. Blood was withdrawn and incubated with T. occidentalis (0.25; 2.5; 20.5; and 34.1 percent v/v). Stannous chloride (1.2 micrograms/ml) was added and then 99mTc was added. Plasma (P) and blood cells (BC) were isolated, also precipitated with trichloroacetic acid and soluble (SF) and insoluble fractions (IF) separated. The analysis of the results shows that there is a decrease in radioactivity (from 97.64 to 75.89 percent) in BC with 34.1 percent of the drug. In the labeling process of RBC with 99mTc, the stannous and pertechnetate ions pass through the membrane, so we suggest that the T. occidentalis effect can be explained (i) by an inhibition of the transport of these ions, (ii) by damage in membrane, (iii) by competition with the cited ions for the same binding sites, or (iv) by possible generation of reactive oxygen species that could oxidize the stannous ion.

Correlation of RET somatic mutations with clinicopathological features in sporadic medullary thyroid carcinomas

PubMed Central

Moura, M M; Cavaco, B M; Pinto, A E; Domingues, R; Santos, J R; Cid, M O; Bugalho, M J; Leite, V

2009-01-01

Screening of REarranged during Transfection (RET) gene mutations has been carried out in different series of sporadic medullary thyroid carcinomas (MTC). RET-positive tumours seem to be associated to a worse clinical outcome. However, the correlation between the type of RET mutation and the patients' clinicopathological data has not been evaluated yet. We analysed RET exons 5, 8, 10–16 in fifty-one sporadic MTC, and found somatic mutations in thirty-three (64.7%) tumours. Among the RET-positive cases, exon 16 was the most frequently affected (60.6%). Two novel somatic mutations (Cys630Gly, c.1881del18) were identified. MTC patients were divided into three groups: group 1, with mutations in RET exons 15 and 16; group 2, with other RET mutations; group 3, having no RET mutations. Group 1 had higher prevalence (P=0.0051) and number of lymph node metastases (P=0.0017), and presented more often multifocal tumours (P=0.037) and persistent disease at last control (P=0.0242) than group 2. Detectable serum calcitonin levels at last screening (P=0.0119) and stage IV disease (P=0.0145) were more frequent in group 1, than in the other groups. Our results suggest that, among the sporadic MTC, cases with RET mutations in exons 15 and 16 are associated with the worst prognosis. Cases with other RET mutations have the most indolent course, and those with no RET mutations have an intermediate risk. PMID:19401695

The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours

PubMed Central

Koçyiğit Deveci, Emel; Ocak, Meltem; Bozkurt, Murat Fani; Türker, Selcan; Kabasakal, Levent; Uğur, Ömer

2013-01-01

Objective: The aim of this study was to assess the diagnostic efficiency of 99mTc-EDDA/HYNIC-Octreotate in comparison with 111Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. Methods: Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both 99mTc- EDDA/HYNIC-octreotate and 111In-pentetrotide. Images were evaluated both visually and semiquantitatively. Results: On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by 99mTc- EDDA/HYNICOctreotate were higher than the number of lesions detected by 111In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT 99mTc- EDDA/HYNIC-Octreotate scans. Conclusion: The results of this study suggested that, 99mTc- EDDA/HYNIC-Octreotate may be a better alternative to 111In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. Conflict of interest:None declared. PMID:24416622

The mechanism of tubulin-colchicine recognition--a kinetic study of the binding of a bicyclic colchicine analogue with a minor modification of the A ring.

PubMed

Dumortier, C; Potenziano, J L; Bane, S; Engelborghs, Y

1997-10-01

2-Methoxy-5-(2',3',4'-trimethoxy)-2,4,6-cycloheptatrien-1-one (MTC) is a colchicine analogue that lacks the B ring. 2-Methoxy-5-(2',4'-dimethoxyphenyl)-2,4,6-cycloheptatrien-1-one (MD) is an A-ring analogue of MTC, in which one methoxy group is replaced by a hydrogen atom. This paper describes the kinetic features of MDC binding to tubulin, and compares its behaviour with MTC to analyse the effect of the A-ring modification on the recognition process by tubulin. Binding is accompanied by a strong enhancement of MDC fluorescence and quenching of protein fluorescence. The kinetic and thermodynamic parameters were obtained from fluorescence stopped-flow measurements. The kinetics are described by a single exponential, indicating that this drug does not discriminate between the different tubulin isotypes. The observed pseudo-first-order rate constant of the fluorescence increase upon binding increases in a non-linear way, indicating that this ligand binds with a similar overall mechanism as colchicine and MTC, consisting of a fast initial binding of low affinity followed by a slower isomerisation step leading to full affinity. The K1 and k2 values for MDC at 25 degrees C were 540 +/- 65 M(-1) and 70 +/- 6 s(-1) respectively. From the temperature dependence, a reaction enthalpy change (deltaH(o)1) of the initial binding of 49 +/- 11 kJ/mol(-1) and an activation energy for the second step of 28 +/- 9 kJ/mol(-1) were calculated. Displacement experiments of bound MDC by MTC allowed the determination of a rate constant of reverse isomerisation of 0.60 +/- 0.07 s(-1) at 25 degrees C and the activation energy of 81 +/- 6 kJ/mol(-1). The overall binding constant was (6.3 +/- 0.2) x 10(4) M(-1) at 25 degrees C. Combination of these results with the kinetic parameters for association gives a full characterisation of the enthalpy pathway for the binding of MDC. The pathway of MDC is shown to differ considerably from that of MTC binding. Since its structural difference is located in ring A, this result indicates the use of ring A in the first step. The kinetics of the binding of MDC in the presence of some A-ring colchicine analogues (podophyllotoxin, 3',4',5'-trimethoxyacetophenone and N-acetylmescaline) and a C-ring analogue (tropolone methyl ether) suggest that the A and C rings are involved in the binding of MDC.

Role of CDKN2C Copy Number in Sporadic Medullary Thyroid Carcinoma.

PubMed

Grubbs, Elizabeth G; Williams, Michelle D; Scheet, Paul; Vattathil, Selina; Perrier, Nancy D; Lee, Jeffrey E; Gagel, Robert F; Hai, Tao; Feng, Lei; Cabanillas, Maria E; Cote, Gilbert J

2016-11-01

The cyclin-dependent-kinase inhibitors (CDKN)/retinoblastoma (RB1) pathway has been implicated as having a role in medullary thyroid carcinoma (MTC) tumorigenesis. CDKN2C loss has been associated with RET-mediated MTC in humans but with minimal phenotypic correlation provided. The objective of this study was to evaluate the association between tumor RET mutation status, CDKN2C loss, and aggressiveness of MTC in a cohort of patients with sporadic disease. Tumors from patients with sporadic MTC treated at a single institution were evaluated for somatic RET M918T mutation and CDKN2C copy number loss. These variables were compared to patient demographics, pathology detail, clinical course, and disease-specific and overall survival. Sixty-two MTC cases with an initial surgery date ranging from 1983 to 2009 met the inclusion criteria, of whom 36 (58%) were male. The median age at initial surgery was 53 years (range 22-81 years). The median tumor size was 30 mm (range 6-145 mm) with 29 (57%) possessing extrathyroidal extension. Nodal and/or distant metastasis at presentation was found in 47/60 (78%) and 12/61 (20%) patients, respectively. Median follow-up time was 10.5 years (range 1.1-27.8 years) for the censored observations. The presence of CDKN2C loss was associated with worse M stage and overall AJCC stage. Median overall survival of patients with versus without CDKN2C loss was 4.14 [confidence interval (CI) 1.93-NA] versus 18.27 [CI 17.24-NA] years (p < 0.0001). Median overall survival of patients with a combined somatic RET M918T mutation and CDKN2C loss versus no somatic RET M918T mutation and CDKN2C loss versus somatic RET M918T mutation and CDKN2C 2N versus no somatic RET M918T mutation and CDKN2C 2N was 2.38 [CI 1.67-NA] years versus 10.81 [CI 2.46-NA] versus 17.24 [CI 9.82-NA] versus not reached [CI 13.46-NA] years (p < 0.0001). The detection of somatic CDKN2C loss is associated with the presence of distant metastasis at presentation as well decreased overall survival, a relationship enhanced by concomitant RET M918T mutation. Further defining the genes involved in the progression of metastatic MTC will be an important step toward identifying pathways of disease progression and new therapeutic targets.

The 'Lumbar Fusion Outcome Score' (LUFOS): a new practical and surgically oriented grading system for preoperative prediction of surgical outcomes after lumbar spinal fusion in patients with degenerative disc disease and refractory chronic axial low back pain.

PubMed

Mattei, Tobias A; Rehman, Azeem A; Teles, Alisson R; Aldag, Jean C; Dinh, Dzung H; McCall, Todd D

2017-01-01

In order to evaluate the predictive effect of non-invasive preoperative imaging methods on surgical outcomes of lumbar fusion for patients with degenerative disc disease (DDD) and refractory chronic axial low back pain (LBP), the authors conducted a retrospective review of 45 patients with DDD and refractory LBP submitted to anterior lumbar interbody fusion (ALIF) at a single center from 2007 to 2010. Surgical outcomes - as measured by Visual Analog Scale (VAS/back pain) and Oswestry Disability Index (ODI) - were evaluated pre-operatively and at 6 weeks, 3 months, 6 months, and 1 year post-operatively. Linear mixed-effects models were generated in order to identify possible preoperative imaging characteristics (including bone scan/99mTc scintigraphy increased endplate uptake, Modic endplate changes, and disc degeneration graded according to Pfirrmann classification) which may be predictive of long-term surgical outcomes . After controlling for confounders, a combined score, the Lumbar Fusion Outcome Score (LUFOS), was developed. The LUFOS grading system was able to stratify patients in two general groups (Non-surgical: LUFOS 0 and 1; Surgical: LUFOS 2 and 3) that presented significantly different surgical outcomes in terms of estimated marginal means of VAS/back pain (p = 0.001) and ODI (p = 0.006) beginning at 3 months and continuing up to 1 year of follow-up. In conclusion,  LUFOS has been devised as a new practical and surgically oriented grading system based on simple key parameters from non-invasive preoperative imaging exams (magnetic resonance imaging/MRI and bone scan/99mTc scintigraphy) which has been shown to be highly predictive of surgical outcomes of patients undergoing lumbar fusion for treatment for refractory chronic axial LBP.

Nodular Graves’ disease with medullary thyroid cancer

PubMed Central

Khan, Shoukat Hussain; Rather, Tanveer Ahmed; Makhdoomi, Rumana; Malik, Dharmender

2015-01-01

Co-existence of thyroid nodules with Graves’ disease has been reported in various studies. 10–15% of such nodules harbor thyroid cancer with papillary thyroid cancer being the commonest. Medullary thyroid cancer (MTC) in nodules associated with Graves’ disease is rare. On literature survey, we came across 11 such cases reported so far. We report a 62-year-old female with Graves’ disease who also had a thyroid nodule that on fine-needle aspiration cytology and the subsequent postthyroidectomy histopathological examination was reported to be MTC. PMID:26430321

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

Harnsberger, H.R.; Datz, F.L.; Knochel, J.Q.

A patient with postpolycythemic myeloid metaplasia developed an enlarging abdominal mass documented on TCT scanning. To distinguish between lymphoma and extramedullary hematopoiesis, marrow elements were imaged with /sup 111/In chloride and /sup 99m/Tc sulfur colloid. Because the mass failed to accumulate either tracer, a presumptive diagnosis of lymphoma was made and exploratory surgery was performed. The excised mass was found to consist of enlarged lymph nodes containing extramedullary hematopoiesis. Caution should be exercised in the use of /sup 111/In or /sup 99m/Tc SC bone-marrow scans to diagnose sites of extramedullary hematopoiesis.

Demonstration of a potent RET transcriptional inhibitor for the treatment of medullary thyroid carcinoma based on an ellipticine derivative

PubMed Central

Kumarasamy, Vishnu Muthuraj; Sun, Daekyu

2017-01-01

Dominant-activating mutations in the RET (rearranged during transfection) proto-oncogene, which encodes a receptor tyrosine kinase, is often associated with the development of medullary thyroid carcinoma (MTC). The proximal promoter region of the RET gene consists of a guanine-rich sequence containing five runs of three consecutive guanine residues that serve as the binding site for transcriptional factors. As we have recently shown, this stretch of nucleotides in the promoter region is highly dynamic in nature and tend to form non-B DNA secondary structures called G-quadruplexes, which suppress the transcription of the RET gene. In the present study, ellipticine and its derivatives were identified as excellent RET G-quadruplex stabilizing agents. Circular dichroism (CD) spectroscopic studies revealed that the incorporation of a piperidine ring in an ellipticine derivative, NSC311153 improves its binding with the G-quadruplex structure and the stability induced by this compound is more potent than ellipticine. Furthermore, this compound also interfered with the transcriptional mechanism of the RET gene in an MTC derived cell line, TT cells and significantly decreased the endogenous RET protein expression. We demonstrated the specificity of NSC311153 by using papillary thyroid carcinoma (PTC) cells, the TPC1 cell line which lacks the G-quadruplex forming sequence in the promoter region due to chromosomal rearrangement. The RET downregulation selectively suppresses cell proliferation by inhibiting the intracellular Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways in the TT cells. In the present study, we also showed that the systemic administration of a water soluble NSC311153 analog in a mouse MTC xenograft model inhibited the tumor growth through RET downregulation. PMID:28498409

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells.

PubMed

Karmaus, Agnes L; Toole, Colleen M; Filer, Dayne L; Lewis, Kenneth C; Martin, Matthew T

2016-04-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. © The Author 2016. Published by Oxford University Press on behalf of the Society of Toxicology.

Characterization of arsenic resistant bacteria from arsenic rich groundwater of West Bengal, India.

PubMed

Sarkar, Angana; Kazy, Sufia K; Sar, Pinaki

2013-03-01

Sixty-four arsenic (As) resistant bacteria isolated from an arsenic rich groundwater sample of West Bengal were characterized to investigate their potential role in subsurface arsenic mobilization. Among the isolated strains predominance of genera Agrobacterium/Rhizobium, Ochrobactrum and Achromobacter which could grow chemolitrophically and utilize arsenic as electron donor were detected. Higher tolerance to As(3+) [maximum tolerable concentration (MTC): ≥10 mM], As(5+) (MTC: ≥100 mM) and other heavy metals like Cu(2+), Cr(2+), Ni(2+) etc. (MTC: ≥10 mM), presence of arsenate reductase and siderophore was frequently observed among the isolates. Ability to produce arsenite oxidase and phosphatase enzyme was detected in 50 and 34 % of the isolates, respectively. Although no direct correlation among taxonomic identity of bacterial strains and their metabolic abilities as mentioned above was apparent, several isolates affiliated to genera Ochrobactrum, Achromobacter and unclassified Rhizobiaceae members were found to be highly resistant to As(3+) and As(5+) and positive for all the test properties. Arsenate reductase activity was found to be conferred by arsC gene, which in many strains was coupled with arsenite efflux gene arsB as well. Phylogenetic incongruence between the 16S rRNA and ars genes lineages indicated possible incidence of horizontal gene transfer for ars genes. Based on the results we propose that under the prevailing low nutrient condition inhabitant bacteria capable of using inorganic electron donors play a synergistic role wherein siderophores and phosphatase activities facilitate the release of sediment bound As(5+), which is subsequently reduced by arsenate reductase resulting into the mobilization of As(3+) in groundwater.

High-Throughput Screening of Chemical Effects on Steroidogenesis Using H295R Human Adrenocortical Carcinoma Cells

PubMed Central

Toole, Colleen M.; Filer, Dayne L.; Lewis, Kenneth C.; Martin, Matthew T.

2016-01-01

Disruption of steroidogenesis by environmental chemicals can result in altered hormone levels causing adverse reproductive and developmental effects. A high-throughput assay using H295R human adrenocortical carcinoma cells was used to evaluate the effect of 2060 chemical samples on steroidogenesis via high-performance liquid chromatography followed by tandem mass spectrometry quantification of 10 steroid hormones, including progestagens, glucocorticoids, androgens, and estrogens. The study employed a 3 stage screening strategy. The first stage established the maximum tolerated concentration (MTC; ≥ 70% viability) per sample. The second stage quantified changes in hormone levels at the MTC whereas the third stage performed concentration-response (CR) on a subset of samples. At all stages, cells were prestimulated with 10 µM forskolin for 48 h to induce steroidogenesis followed by chemical treatment for 48 h. Of the 2060 chemical samples evaluated, 524 samples were selected for 6-point CR screening, based in part on significantly altering at least 4 hormones at the MTC. CR screening identified 232 chemical samples with concentration-dependent effects on 17β-estradiol and/or testosterone, with 411 chemical samples showing an effect on at least one hormone across the steroidogenesis pathway. Clustering of the concentration-dependent chemical-mediated steroid hormone effects grouped chemical samples into 5 distinct profiles generally representing putative mechanisms of action, including CYP17A1 and HSD3B inhibition. A distinct pattern was observed between imidazole and triazole fungicides suggesting potentially distinct mechanisms of action. From a chemical testing and prioritization perspective, this assay platform provides a robust model for high-throughput screening of chemicals for effects on steroidogenesis. PMID:26781511

Optimisation of quantitative lung SPECT applied to mild COPD: a software phantom simulation study.

PubMed

Norberg, Pernilla; Olsson, Anna; Alm Carlsson, Gudrun; Sandborg, Michael; Gustafsson, Agnetha

2015-01-01

The amount of inhomogeneities in a (99m)Tc Technegas single-photon emission computed tomography (SPECT) lung image, caused by reduced ventilation in lung regions affected by chronic obstructive pulmonary disease (COPD), is correlated to disease advancement. A quantitative analysis method, the CVT method, measuring these inhomogeneities was proposed in earlier work. To detect mild COPD, which is a difficult task, optimised parameter values are needed. In this work, the CVT method was optimised with respect to the parameter values of acquisition, reconstruction and analysis. The ordered subset expectation maximisation (OSEM) algorithm was used for reconstructing the lung SPECT images. As a first step towards clinical application of the CVT method in detecting mild COPD, this study was based on simulated SPECT images of an advanced anthropomorphic lung software phantom including respiratory and cardiac motion, where the mild COPD lung had an overall ventilation reduction of 5%. The best separation between healthy and mild COPD lung images as determined using the CVT measure of ventilation inhomogeneity and 125 MBq (99m)Tc was obtained using a low-energy high-resolution collimator (LEHR) and a power 6 Butterworth post-filter with a cutoff frequency of 0.6 to 0.7 cm(-1). Sixty-four reconstruction updates and a small kernel size should be used when the whole lung is analysed, and for the reduced lung a greater number of updates and a larger kernel size are needed. A LEHR collimator and 125 (99m)Tc MBq together with an optimal combination of cutoff frequency, number of updates and kernel size, gave the best result. Suboptimal selections of either cutoff frequency, number of updates and kernel size will reduce the imaging system's ability to detect mild COPD in the lung phantom.

Wear measurement using radioactive tracer technique based on proton, deuteron and α-particle induced nuclear reactions on molybdenum

NASA Astrophysics Data System (ADS)

Ditrói, F.; Tárkányi, F.; Takács, S.

2012-11-01

Excitation functions of light ion induced nuclear reactions on natural molybdenum have been studied in the frame of a systematic investigation of charged particle induced nuclear reactions on metals for various applications. Excitation functions of 93,94g,94m,95g,95m,96,99mTc, 90,93m,99Mo, 90,91m,92m,95m,95g,96Nb and 88,89Zr were measured up to 50 MeV deuteron energy Tárkányi et al., 2012 [1], 93m,93g,94m,94g,95m,95g,96g,99mTc, 90,93m,99Mo, 90,92m,95m,95g,96Nb and 88,89Zr were measured up to 40 MeV proton energy Tárkányi et al., 2012 [2] and 93m,93g,94m,94g,95m,95g,96g,99mTc, 93m,99Mo, 90Nb, 94,95,97,103Ru and 88Zr were measured up to 40 MeV alpha energy Ditrói et al., 2012 [3] by using the stacked foil technique and activation method. The results for 3He induced reactions on natural Mo were taken from the literature Comparetto and Qaim, 1980 [4]. According to their half-lives, from the above listed radionuclides the 95m,96Tc, 91m,92m,95m,95gNb, 99Mo, 103,97Ru and 88Zr are suitable candidates for wear measurement by using thin layer activation (TLA) method. The goal of this work was to determine the necessary nuclear data for TLA of the above radionuclides and to prove their applicability for wear measurements.

Liquid discharges from the use of radionuclides in medicine (diagnosis).

PubMed

Barquero, R; Agulla, M M; Ruiz, A

2008-10-01

The production and discharge of liquid radioactive wastes as excreta from patients undergoing Nuclear Medicine Diagnostic (NMD) in a hospital were studied. Instantaneous and accumulated activity, discharged from the hospital to the sewage system, has been estimated keeping in mind radionuclide decay. This study would enable estimation of the environmental impact due to NMD procedures. Annual accumulated activities of 2.2 GBq (131I), 1.847 GBq (99mTc), 0.743 GBq (123I), 0.337 GBq (67Ga), 0.169 GBq (111In) and 0.033 GBq (201Tl) result from our model when applied to a European hospital. A comparison is made with calculations by other authors that do not consider the radionuclide decay and who overestimate by two orders of magnitude. Doses to critical people as sewage treatment workers are also significantly reduced. So, our results stress the importance of including the decay in the calculations.

Chimeric autologous/allogeneic constructs for skin regeneration.

PubMed

Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

2014-08-01

The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. Reprint & Copyright © 2014 Association of Military Surgeons of the U.S.

The presence of sodium nitrate in generator eluate decreases the radiochemical purity of 99mTc-sestamibi.

PubMed

Métayé, Thierry; Rosenberg, Thierry; Guilhot, Joëlle; Bouin-Pineau, Marie-Hélène; Perdrisot, Rémy

2012-09-01

A high radiochemical purity (RCP) is recommended for radiopharmaceutical compounds used in the clinical practice of nuclear medicine. However, some preparations of (99m)Tc-sestamibi contain excess impurities (>6%). To understand the origin of these impurities, we investigated the effect of sodium nitrate on the RCP of sestamibi preparations by testing eluates from 3 commercially available (99m)Tc generators. The sestamibi kits (Stamicis) were reconstituted with (99m)Tc eluate from nitrate-containing wet-column (NCWC), nitrate-free wet-column (NFWC), and nitrate-free dry-column (NFDC) generators. Sodium nitrate was 0.05 mg/mL in eluates from the NCWC generators. The RCP was determined using aluminum oxide sheets as the stationary phase and absolute ethanol as the mobile phase. Succimer, tetrofosmin, oxidronate, exametazine, albumin nanocolloid, and soluble albumin were also tested for their RCP values with eluates from the 3 different (99m)Tc generators. The RCP assessment of (99m)Tc-sestamibi was performed on 127 Stamicis preparations. Significantly lower RCP values were found for Stamicis kits prepared with the NCWC generator than for Stamicis prepared with the NFWC (P < 0.0001) and NFDC (P < 0.0001) generators. The number of Stamicis preparations with an RCP under 94% was greater with the NCWC generator (32 of 53 kits) than with the NFDC (2 of 51 kits) or NFWC (0 of 23 kits) generator. Furthermore, the addition of a 0.05 mg/mL concentration of nitrate in NFWC generator eluates significantly decreased the RCP of the Stamicis preparation. In the absence of nitrate in (99m)Tc eluate, no difference was observed between the RCP values of Stamicis kits prepared with the NFWC and NFDC generators. The (99m)Tc impurities generated by nitrates did not modify the quality of myocardial imaging (normal heart-to-lung ratio, 2.2), probably because these impurities are not in the heart field of view. No other tested (99m)Tc-radiopharmaceutical interfered with nitrates. We recommend using nitrate-free generator eluates in (99m)Tc-sestamibi preparations to improve the product quality and prevent unnecessary exposure of the patient to radiation.

Prophylactic thyroidectomy for asymptomatic 3-year-old boy with positive multiple endocrine neoplasia type 2A mutation (codon 634).

PubMed

Jesić, Maja D; Tancić-Gajić, Milina; Jesić, Milos M; Zivaljević, Vladan; Sajić, Silvija; Vujović, Svetlana; Damjanović, Svetozar

2014-01-01

The multiple endocrine neoplasia type 2A (MEN 2A) syndrome, comprising medullary thyroid carcinoma (MTC), pheochromocytoma and primary hyperparathyroidism (PHPT) is most frequently caused by codon 634 activating mutations of the RET (rearranged during transfection) proto-oncogene on chromosome 10. For this codon-mutation carriers, earlier thyroidectomy (before the age of 5 years) would be advantageous in limiting the potential for the development of MTC as well as parathyroid adenomas. This is a case report of 3-year-old boy from the MEN 2A family (the boy's father and grandmother and paternal aunt) in which cysteine substitutes for phenylalanine at codon 634 in exon 11 of the RET proto-oncogene, who underwent thyroidectomy solely on the basis of genetic information. A boy had no thyromegaly, thyroidal irregularities or lymphadenopathy and no abnormality on the neck ultrasound examination. The pathology finding of thyroid gland was negative for MTC. Two years after total thyroidectomy, 5-year-old boy is healthy with permanent thyroxine replacement. His serum calcitonin level is < 2 pg/ml (normal < 13 pg/ml), has normal serum calcium and parathyroid hormone levels and negative urinary catecholamines. Long-term follow-up of this patient is required to determine whether very early thyroidectomy improves the long-term outcome of PHPT. Children with familial antecedents of MEN 2A should be genetically studied for the purpose of determining the risk of MTC and assessing the possibilities of making prophylactic thyroidectomy before the age of 5 years.

Rapid diagnosis of occult abscesses using sup 99m Tc-labeled monoclonal antibodies

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

Coons, T.A.; Rhodes, B.A.; Thakur, M.L.

1991-01-01

Acute infections, such as appendicitis and occult infections in AIDS patients, can be diagnosed within two hours by gamma scintigraphy after i.v. administration of {sup 99m}Tc labeled antibodies reactive with human granulocytes. The antibody, murine IgM anti-SSEA-1, is partially reduced using Sn(II) to expose and protect reactive sulfide groups. The antibody is then purified, stannous tartrate and stabilizers are added, and the mixture is lyophilized. To label, sodium pertechnetate is added. After a 15 minute incubation the tracer drug is injected. The rate of accumulation and degree of concentration at the site of infection is presumptively determinative of the severitymore » of the infection. Acceptance criteria and tests for the {sup 99m}Tc labeled antibody product have been established and validated. Greater than 93% of the {sup 99m}Tc is firmly bound to the protein as determined by quantitative HPLC. Radiochemical impurities, colloidal {sup 99m}Tc and free pertechnetate are together less than 4% as determined by thin layer chromatography. The immunoreactive fraction, measured by binding to solid phase antigen, and affinity measured be ELISA, are unchanged by the {sup 99m}Tc-direct labeling process. Two hour blood clearance in rats is within 90% of the value of the {sup 125}I labeled analog. The immunoreactive fraction decreases less than 10% when incubated in human plasma for 24 hours. This method has been compared to other direct labeling methods, and found to give higher radiochemical yields. 5 figs.« less

Use of {sup 99m}Tc 2-methoxyisobutyl isonitrile in minimally invasive radioguided surgery in patients with primary hyperparathyroidism: A narrative review of the current literature

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

Denmeade, Kristie A; Constable, Chris; Reed, Warren M

The use of technetium-99m 2-methoxyisobutyl isonitrile ({sup 99m}Tc MIBI) for assistance in minimally invasive radioguided surgery (MIRS) is growing in popularity as a safe, effective, and proficient technique used for parathyroidectomy in primary hyperparathyroidism (PHPT) treatment. Previously, the preferred treatment for PHPT was bilateral neck exploration (BNE), a very invasive, costly, and lengthy procedure. However, as a large majority (80–85% of cases of PHPT) are attributed to a single parathyroid adenoma (PA), a simpler more direct technique such as MIRS is a far better option. The following article is an exploration of the current literature concerning varied protocols utilizing {supmore » 99m}Tc MIBI for assistance in MIRS for patients undergoing treatment of PHPT. This technique boasts many advantageous outcomes for patients suffering from PHPT. These include a reduction in cost, operating time, and patient recovery; less evidence of post-surgical hypocalcaemia, less pain, and complications; superior cosmetic results; same-day discharge; and the possibility of local anaesthesia which is particularly beneficial in elderly patients. Better outcomes for patients with deep or ectopic PAs, reduced intra-operative complications, and improved cosmetic outcomes for patients who have previously undergone thyroid and/or parathyroid surgery are also advantageous. Of the literature reviewed it was also found that no patients suffered any major surgical complications such as laryngeal nerve palsy or permanent hypoparathyroidism using {sup 99m}Tc MIBI for assistance in MIRS.« less

Goats challenged with different members of the Mycobacterium tuberculosis complex display different clinical pictures.

PubMed

Bezos, J; Casal, C; Díez-Delgado, I; Romero, B; Liandris, E; Álvarez, J; Sevilla, I A; Juan, L de; Domínguez, L; Gortázar, C

2015-10-15

Tuberculosis (TB) in goats (Capra hircus) is due to infection with members of the Mycobacterium tuberculosis complex (MTC), mainly Mycobacterium bovis and Mycobacterium caprae. We report a comparative experimental infection of goats with M. bovis, M. caprae and M. tuberculosis strains. We hypothesized that goats experimentally infected with different members of the MTC would display different clinical pictures. Three groups of goats were challenged with either M. bovis SB0134 (group 1, n=5), M. caprae SB0157 (group 2, n=5) and M. tuberculosis SIT58 (group 3, n=4). The highest mean total lesion score was observed in M. bovis challenged goats (mean 15.2, range 9-19), followed by those challenged with M. caprae (10.8, 2-23). The lowest score was recorded in goats challenged with M. tuberculosis (3, 1-6). Culture results coincided with the lesion scores in yielding more positive pools (7/15) in M. bovis challenged goats. By contrast, only three pools were positive from goats challenged M. tuberculosis (3/12) and with M. caprae (3/15), respectively. Differences in the performance of the intradermal and gamma-interferon (IFN-γ) tests depending of the group were observed since all goats from group 1 were diagnosed using intradermal test and these goats reacted earlier to the IFN-γ assay in comparison to the other groups. This study confirmed that goats experimentally infected with different members of the MTC display different clinical pictures and this fact may have implications for MTC maintenance and bacterial shedding. Copyright © 2015 Elsevier B.V. All rights reserved.

Source Term Estimates of Radioxenon Released from the BaTek Medical Isotope Production Facility Using External Measured Air Concentrations

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

Eslinger, Paul W.; Cameron, Ian M.; Dumais, Johannes R.

2015-10-01

Abstract Batan Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies 99mTc for use in medical procedures. Atmospheric releases of Xe-133 in the production process at BaTek are known to influence the measurements taken at the closest stations of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The xenon isotopes released from BaTek are the same as those produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analystsmore » trying to decide whether a specific measurement result came from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84E13 Bq of Xe-133. Concentrations of Xe-133 in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88E13 Bq. The same optimization process yielded a release estimate of 1.70E13 Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10 percent of each other. Weekly release estimates of 1.8E13 Bq and a 40 percent facility operation rate yields a rough annual release estimate of 3.7E13 Bq of Xe-133. This value is consistent with previously published estimates of annual releases for this facility, which are based on measurements at three IMS stations. These multiple lines of evidence cross-validate the stack release estimates and the release estimates from atmospheric samplers.« less

Selective arterial chemoembolization for hepatic metastases from medullary thyroid carcinoma.

PubMed

Lorenz, Kerstin; Brauckhoff, Michael; Behrmann, Curd; Sekulla, Carsten; Ukkat, Jörg; Brauckhoff, Katrin; Gimm, Oliver; Dralle, Henning

2005-12-01

Hepatic metastases from medullary thyroid carcinoma (MTC) may impair quality of life by hypercalcitonemia-associated diarrhea and pain. In this prospective study, the effect of selective arterial chemoembolization (SACE) was evaluated. Eleven patients with hepatic metastases from MTC received 1 to 9 courses of SACE using epirubicine. Symptomatic, biochemical, and morphologic responses on SACE were recorded. Symptomatic response was observed in all symptomatic patients. However, biochemical and radiologic response occurred only in 6 patients. Liver function was not affected by SACE. One patient with unexpected concurrent pheochromocytoma metastases died after the first course. Development of side effects in the course was observed in 8 patients but were only World Health Organization grade 1. Patients' satisfaction with SACE was excellent. Long-term follow-up found 7 patients alive (1-72 months). Three patients died with tumor 6, 12, and 24 months after SACE, respectively. SACE provided good symptom palliation for the majority of patients with hepatic metastases from MTC. However, transient remission or stabilization of hepatic metastases resulted in only 60%. Further studies using a randomized protocol are required.

Invited Article: miniTimeCube

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

Li, V. A., E-mail: vli2@hawaii.edu; Dorrill, R.; Duvall, M. J.

2016-02-15

We present the development of the miniTimeCube (mTC), a novel compact neutrino  detector. The mTC is a multipurpose detector, aiming to detect not only neutrinos but also fast/thermal neutrons. Potential applications include the counterproliferation of nuclear materials and the investigation of antineutrino short-baseline effects. The mTC is a plastic 0.2% {sup 10}B–doped scintillator (13 cm){sup 3} cube surrounded by 24 Micro-Channel Plate (MCP) photon detectors, each with an 8 × 8 anode totaling 1536 individual channels/pixels viewing the scintillator. It uses custom-made electronics modules which mount on top of the MCPs, making our detector compact and able to both distinguishmore » different types of events and reject noise in real time. The detector is currently deployed and being tested at the National Institute of Standards and Technology Center for Neutron Research nuclear reactor (20 MW{sub th}) in Gaithersburg MD. A shield for further tests is being constructed, and calibration and upgrades are ongoing. The mTC’s improved spatiotemporal resolution will allow for determination of incident particle directions beyond previous capabilities.« less

The standardization methods of radioactive sources (125I, 131I, 99mTc, and 18F) for calibrating nuclear medicine equipment in Indonesia

NASA Astrophysics Data System (ADS)

Wurdiyanto, G.; Candra, H.

2016-03-01

The standardization of radioactive sources (125I, 131I, 99mTc and 18F) to calibrate the nuclear medicine equipment had been carried out in PTKMR-BATAN. This is necessary because the radioactive sources used in the field of nuclear medicine has a very short half-life in other that to obtain a quality measurement results require special treatment. Besides that, the use of nuclear medicine techniques in Indonesia develop rapidly. All the radioactive sources were prepared by gravimetric methods. Standardization of 125I has been carried out by photon- photon coincidence methods, while the others have been carried out by gamma spectrometry methods. The standar sources are used to calibrate a Capintec CRC-7BT radionuclide calibrator. The results shows that calibration factor for Capintec CRC-7BT dose calibrator is 1,03; 1,02; 1,06; and 1,04 for 125I, 131I, 99mTc and 18F respectively, by about 5 to 6% of the expanded uncertainties.

A secular technetium-molybdenum generator

NASA Astrophysics Data System (ADS)

Araujo, Wagner L.; Campos, Tarcisio P. R.

2015-05-01

A compact secular molybdenium generator is subject of this paper. This generator represents a nuclear system that comprises a hydrogen-isotopes fusor, moderator, reflector and shield. Deuterium fusion reactions in a tritiated or deuterated target provide the neutron source. A moderation fluid slowdown the neutron energy which increases 98Mo(n,γ)99Mo capture reaction rates. Neutron reflection minimizes the neutron escape and the radiation shield encloses the device. The neutron yield calculation along with electromagnetic and nuclear simulations were addressed. Results revealed the accelerator equipotential surfaces ranging from -30 to 150 kV, the ion trajectories and the energy beam profile define a deuteron current of 1 A with energy of 180 keV at the target, the spatial distribution of the neutron flux, and the 99Mo and 99mTc activities in function of transmuter operation time. The kinetics of the 99mTc correlated to its precursor activity demonstrates a secular equilibrium providing 2 Ci in a operational time of 150 h. As conclusion, the investigated nuclear and electromagnetic features have demonstrated that such generator shall have a notable potential for feeding the 99mTc clinical application.

Development and clinical application of an evidence-based pharmaceutical care service algorithm in acute coronary syndrome.

PubMed

Kang, J E; Yu, J M; Choi, J H; Chung, I-M; Pyun, W B; Kim, S A; Lee, E K; Han, N Y; Yoon, J-H; Oh, J M; Rhie, S J

2018-06-01

Drug therapies are critical for preventing secondary complications in acute coronary syndrome (ACS). The purpose of this study was to develop and apply a pharmaceutical care service (PCS) algorithm for ACS and confirm that it is applicable through a prospective clinical trial. The ACS-PCS algorithm was developed according to extant evidence-based treatment and pharmaceutical care guidelines. Quality assurance was conducted through two methods: literature comparison and expert panel evaluation. The literature comparison was used to compare the content of the algorithm with the referenced guidelines. Expert evaluations were conducted by nine experts for 75 questionnaire items. A trial was conducted to confirm its effectiveness. Seventy-nine patients were assigned to either the pharmacist-included multidisciplinary team care (MTC) group or the usual care (UC) group. The endpoints of the trial were the prescription rate of two important drugs, readmission, emergency room (ER) visit and mortality. The main frame of the algorithm was structured with three tasks: medication reconciliation, medication optimization and transition of care. The contents and context of the algorithm were compliant with class I recommendations and the main service items from the evidence-based guidelines. Opinions from the expert panel were mostly positive. There were significant differences in beta-blocker prescription rates in the overall period (P = .013) and ER visits (four cases, 9.76%, P = .016) in the MTC group compared to the UC group, respectively. We developed a PCS algorithm for ACS based on the contents of evidence-based drug therapy and the core concept of pharmacist services. © 2018 John Wiley & Sons Ltd.

Direct Production of 99mTc via 100Mo(p,2n) on Small Medical Cyclotrons

NASA Astrophysics Data System (ADS)

Schaffer, P.; Bénard, F.; Bernstein, A.; Buckley, K.; Celler, A.; Cockburn, N.; Corsaut, J.; Dodd, M.; Economou, C.; Eriksson, T.; Frontera, M.; Hanemaayer, V.; Hook, B.; Klug, J.; Kovacs, M.; Prato, F. S.; McDiarmid, S.; Ruth, T. J.; Shanks, C.; Valliant, J. F.; Zeisler, S.; Zetterberg, U.; Zavodszky, P. A.

From the efforts of a number of Canadian institutions and private industry collaborations, direct production of 99mTc using medical cyclotrons has recently been advanced from a 1970's academic exercise to a commercial, economically viable solution for regional production. Using GE PETtrace 880 machines our team has established preliminary saturated yields of 2.7 GBq/μA, translating to approximately 174 GBq after a 6 hour irradiation. The team is in the process of assessing the accuracy and reliability of this production value with a goal of optimizing yields by up to 50%.

Phenolic aminocarboxylate chelates of 99mTc as hepatobiliary agents.

PubMed

Hunt, F C; Maddalena, D J; Wilson, J G; Bautovich, G J

1986-01-01

A series of alkyl- and halogen-substituted derivatives of ethylenediamine di[o-hydroxyphenylacetic acid] (EDDHA) and N,N'-bis[2-hydroxybenzyl] ethylenediamine N,N'-diacetic acid (HBED) were complexed with 99mTc and their biodistribution was determined in rats. All complexes displayed substantial hepatobiliary excretion; of each series, 99mTc-Br-EDDHA and 99mTc-di-Cl-HBED had the maximum amount in the gastrointestinal tract. Scintigraphic studies of 99mTc-Cl-EDDHA in dogs revealed prompt imaging of the liver followed by imaging of the gall bladder as the complex was excreted into the bile.

Source term estimates of radioxenon released from the BaTek medical isotope production facility using external measured air concentrations.

PubMed

Eslinger, Paul W; Cameron, Ian M; Dumais, Johannes Robert; Imardjoko, Yudi; Marsoem, Pujadi; McIntyre, Justin I; Miley, Harry S; Stoehlker, Ulrich; Widodo, Susilo; Woods, Vincent T

2015-10-01

BATAN Teknologi (BaTek) operates an isotope production facility in Serpong, Indonesia that supplies (99m)Tc for use in medical procedures. Atmospheric releases of (133)Xe in the production process at BaTek are known to influence the measurements taken at the closest stations of the radionuclide network of the International Monitoring System (IMS). The purpose of the IMS is to detect evidence of nuclear explosions, including atmospheric releases of radionuclides. The major xenon isotopes released from BaTek are also produced in a nuclear explosion, but the isotopic ratios are different. Knowledge of the magnitude of releases from the isotope production facility helps inform analysts trying to decide if a specific measurement result could have originated from a nuclear explosion. A stack monitor deployed at BaTek in 2013 measured releases to the atmosphere for several isotopes. The facility operates on a weekly cycle, and the stack data for June 15-21, 2013 show a release of 1.84 × 10(13) Bq of (133)Xe. Concentrations of (133)Xe in the air are available at the same time from a xenon sampler located 14 km from BaTek. An optimization process using atmospheric transport modeling and the sampler air concentrations produced a release estimate of 1.88 × 10(13) Bq. The same optimization process yielded a release estimate of 1.70 × 10(13) Bq for a different week in 2012. The stack release value and the two optimized estimates are all within 10% of each other. Unpublished production data and the release estimate from June 2013 yield a rough annual release estimate of 8 × 10(14) Bq of (133)Xe in 2014. These multiple lines of evidence cross-validate the stack release estimates and the release estimates based on atmospheric samplers. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comparative Effectiveness of Treatments for Chronic Low Back Pain: A Multiple Treatment Comparison Analysis.

PubMed

Rihn, Jeffrey A; Radcliff, Kristen; Norvell, Daniel C; Eastlack, Robert; Phillips, Frank M; Berland, Daniel; Sherry, Ned; Freedman, Mitchell; Vaccaro, Alexander R

2017-06-01

A systematic review and network meta-analysis. To determine current treatment options of chronic low back pain (LBP) as defined by randomized controlled trials (RCTs) and to compare effectiveness of those treatments using a mixed-treatment comparison (MTC). It is important to provide an evidence-based assessment of the treatment options that exist for LBP. A systematic search of RCTs was conducted in MEDLINE and the Cochrane Collaboration Library from 1990 to 2014. From the selected studies, we extracted preoperative and postoperative ODI and VAS back pain scores, additional surgeries, and complications. Standard and network meta-analytic techniques were used. Twelve RCTs were included in the analysis: 5 total disk replacement (TDR) versus fusion; 1 TDR versus exercise and cognitive behavioral therapy (CBT); 5 fusion versus exercise and CBT; and 1 fusion versus physical therapy (PT). On the basis of MTC, with respect to ODI change scores, the pooled mean difference favoring fusion over exercise and CBT was 2.0 points (95% CI, -1.2 to 4.8). The pooled mean difference favoring TDR over exercise and CBT was 6.4 points (95% CI, 3.2-9.3). The pooled mean difference favoring fusion over PT was 8.8 points (95% CI, 4.1-13.6). The pooled mean differences favoring TDR over fusion was 4.4 points (95% CI, 2.37-6.63). For PT versus structured exercise with CBT, the pooled mean difference favoring exercise with CBT over PT was 6.8 points (95% CI, 1.5-12.8). For TDR versus PT, the pooled mean difference favoring TDR over PT was 13.2 points (95% CI, 8.0-18.4). Additional surgery rates were similar between treatment options. All 4 treatments provided some benefit to patients with chronic LBP. According to the MTC analysis, TDR may be the most effective treatment and PT the least effective treatment for chronic LBP. This review is based on a limited number of RCT studies and does not support any 1 treatment modality for all patients.

Shear wave elastography in medullary thyroid carcinoma diagnostics.

PubMed

Dobruch-Sobczak, Katarzyna; Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-12-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4-15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB.

Pediatric, Adolescent, and Young Adult Thyroid Carcinoma Harbors Frequent and Diverse Targetable Genomic Alterations, Including Kinase Fusions

PubMed Central

Schrock, Alexa B.; Anderson, Peter M.; Morris, John C.; Heilmann, Andreas M.; Holmes, Oliver; Wang, Kai; Johnson, Adrienne; Waguespack, Steven G.; Ou, Sai‐Hong Ignatius; Khan, Saad; Fung, Kar‐Ming; Stephens, Philip J.; Erlich, Rachel L.; Miller, Vincent A.; Ross, Jeffrey S.; Ali, Siraj M.

2017-01-01

Background. Thyroid carcinoma, which is rare in pediatric patients (age 0–18 years) but more common in adolescent and young adult (AYA) patients (age 15–39 years), carries the potential for morbidity and mortality. Methods. Hybrid‐capture‐based comprehensive genomic profiling (CGP) was performed prospectively on 512 consecutively submitted thyroid carcinomas, including 58 from pediatric and AYA (PAYA) patients, to identify genomic alterations (GAs), including base substitutions, insertions/deletions, copy number alterations, and rearrangements. This PAYA data series includes 41 patients with papillary thyroid carcinoma (PTC), 3 with anaplastic thyroid carcinoma (ATC), and 14 with medullary thyroid carcinoma (MTC). Results. GAs were detected in 93% (54/58) of PAYA cases, with a mean of 1.4 GAs per case. In addition to BRAF V600E mutations, detected in 46% (19/41) of PAYA PTC cases and in 1 of 3 AYA ATC cases, oncogenic fusions involving RET, NTRK1, NTRK3, and ALK were detected in 37% (15/41) of PAYA PTC and 33% (1/3) of AYA ATC cases. Ninety‐three percent (13/14) of MTC patients harbored RET alterations, including 3 novel insertions/deletions in exons 6 and 11. Two of these MTC patients with novel alterations in RET experienced clinical benefit from vandetanib treatment. Conclusion. CGP identified diverse clinically relevant GAs in PAYA patients with thyroid carcinoma, including 83% (34/41) of PTC cases harboring activating kinase mutations or activating kinase rearrangements. These genomic observations and index cases exhibiting clinical benefit from targeted therapy suggest that young patients with advanced thyroid carcinoma can benefit from CGP and rationally matched targeted therapy. Implications for Practice. The detection of diverse clinically relevant genomic alterations in the majority of pediatric, adolescent, and young adult patients with thyroid carcinoma in this study suggests that comprehensive genomic profiling may be beneficial for young patients with papillary, anaplastic, or medullary thyroid carcinoma, particularly for advanced or refractory cases for which clinical trials involving molecularly targeted therapies may be appropriate. PMID:28209747

The occurrence and the type of germline mutations in the RET gene in patients with medullary thyroid carcinoma and their unaffected kindred's from Central Poland.

PubMed

Paszko, Z; Sromek, M; Czetwertynska, M; Skasko, E; Czapczak, D; Wisniewska, A; Prokurat, A; Chrupek, M; Jagielska, A; Kozlowicz-Gudzinska, I

2007-12-01

We aimed to investigate the occurrence and types of pathogenic mutations in the RET gene in patients with MTC of the Central Poland population and in their relatives. DNA was extracted from the peripheral blood lymphocytes of a total of 330 persons, including 235 MTC patients and 95 of their unaffected kindred's. Exons 10, 11, 13, 14, 15 and 16 of the RET gene were amplified by PCR and sequenced. Sixty-seven people were found to carry pathogenic, germline mutations in the RET gene. In exon 10, C609F, C609R and C609Y (3 families), C618G, C618F (2 families), and C620G (4 families) mutations were identified. In exon 11, C634R (8 families) and C649L mutations (1 patient) were found. Five families carried Y791F mutation in exon 13. One patient with PTC revealed the presence of a Y791F mutation. In 3 families, exon 14 of the RET gene harbored the following mutations: V804L (1 patient), E819K (1 patient) and R844Q (1 patient). In 1 family, the S891A mutation was identified in exon 15, 3 families were found to carry mutations in exon16, R912P in 1 family and M918T in 2 families. In summary, of the 235 patients affected by MTC, 46 (19.6%) carried pathogenic RET gene mutations, 1 patient with RET mutation had kidney carcinoma, and 1 had PTC. The results show the occurrence of a variety of mutations prevalent in patients with MTC in the population of Central Poland. These results may contribute to a better diagnosis of medullary thyroid carcinoma.

The bone scan.

PubMed

Brenner, Arnold I; Koshy, June; Morey, Jose; Lin, Cheryl; DiPoce, Jason

2012-01-01

Bone imaging continues to be the second greatest-volume nuclear imaging procedure, offering the advantage of total body examination, low cost, and high sensitivity. Its power rests in the physiological uptake and pathophysiologic behavior of 99m technetium (99m-Tc) diphosphonates. The diagnostic utility, sensitivity, specificity, and predictive value of 99m-Tc bone imaging for benign conditions and tumors was established when only planar imaging was available. Currently, nearly all bone scans are performed as a planar study (whole-body, 3-phase, or regional), with the radiologist often adding single-photon emission computed tomography (SPECT) imaging. Here we review many current indications for planar bone imaging, highlighting indications in which the planar data are often diagnostically sufficient, although diagnosis may be enhanced by SPECT. (18)F sodium fluoride positron emission tomography (PET) is also re-emerging as a bone agent, and had been considered interchangeable with 99m-Tc diphosphonates in the past. In addition to SPECT, new imaging modalities, including (18)F fluorodeoxyglucose, PET/CT, CT, magnetic resonance, and SPECT/CT, have been developed and can aid in evaluating benign and malignant bone disease. Because (18)F fluorodeoxyglucose is taken up by tumor cells and Tc diphosphonates are taken up in osteoblastic activity or osteoblastic healing reaction, both modalities are complementary. CT and magnetic resonance may supplement, but do not replace, bone imaging, which often detects pathology before anatomic changes are appreciated. We also stress the importance of dose reduction by reducing the dose of 99m-Tc diphosphonates and avoiding unnecessary CT acquisitions. In addition, we describe an approach to image interpretation that emphasizes communication with referring colleagues and correlation with appropriate history to significantly improve our impact on patient care. Copyright © 2012 Elsevier Inc. All rights reserved.

Fire in Mediterranean climate ecosystems: a comparative overview

USGS Publications Warehouse

Keeley, Jon E.

2012-01-01

Four regions of the world share a similar climate and structurally similar plant communities with the Mediterranean Basin. These five areas, known collectively as "mediterranean-type climate (MTC) regions", are dominated by evergreen sclerophyllous-leaved shrublands, semi-deciduous scrub, and woodlands, all of which are prone to widespread crown fires. Summer droughts produce an annual fire hazard that contributes to a highly predictable fire regime. Fire has been an important factor driving the convergence of these systems and is reflected in plant traits such as lignotubers in resprouting shrubs and delayed reproduction that restricts recruitment to a postfire pulse of seedlings. On fertile soils where postfire resprouting is very rapid, opportunities for postfire seedling recruitment are limited and thus these woody taxa have not opted for delaying reproduction. Such fire-independent recruitment is widespread in the floras of MTC regions of the Mediterranean Basin and California and postfire seeding tends to dominate at the more arid end of the gradient. Due to very different geological histories in South Africa and Western Australia, substrates are nutrient poor and thus postfire resprouters do not pose a similar competitive challenge to seedlings and thus postfire seeding is very widespread in these floras. Although circumstantial evidence suggests that the MTC region of Chile had fire-prone landscapes in the Tertiary, these were lost with the late Miocene completion of the Andean uplift, which now blocks summer lightning storms from moving into the region. Today these five regions pose a significant fire management challenge due to the annual fire hazard and metropolitan centers juxtaposed with highly flammable vegetation. This challenge varies across the five MTC landscapes as a function of differences in regional fuel loads and population density.

Quantitative distribution of radiolabeled 5-aminosalicylic acid enemas in patients with left-sided ulcerative colitis

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

Vitti, R.A.; Meyers, F.; Knight, L.C.

1989-11-01

Rectally administered suspensions of 5-aminosalicylic acid (5-ASA) are topically effective in treating left-sided ulcerative colitis. The extent to which the contents of these enemas are distributed to inflamed mucosal linings has not previously been determined. This study was undertaken to validate a technique for labeling 5-ASA with 99mTc and to quantitate the distribution of (99mTc)5-ASA in eight patients with left-sided ulcerative colitis. Eight patients underwent three colonic scintigraphic exams within five days, receiving a 60-ml radiolabeled 5-ASA enema into the unprepared rectum for each study, with sequential anterior abdominal images obtained for 4 hr. Activity within the rectum, sigmoid, descending,more » transverse, and ascending colon was quantitated. Over 50% of the labeled enema had advanced beyond the rectum in five of eight patients and in six of eight patients by 30 min and 60 min, respectively. The distribution of (99mTc)5-ASA was quantitatively reproducible when repeated in the same patient on different days, despite apparent visual differences. By 2 hr, the amount of the enema present within the rectum decreased significantly (P less than 0.05) compared to the initial distribution. The amount of enema present within the descending colon was increased significantly at 0.5 hr (P less than 0.05) and at 2 hr (P less than 0.01). There were no significant changes in the distribution from initial values for the sigmoid, transverse, or ascending colon at any time. In each of these cases the spread of the enema to or beyond the extent of disease was documented. In patients with left-sided ulcerative colitis, small volume (99mTc)5-ASA enemas reliably reach the area of inflammation.« less

A modified therapeutic community for homeless persons with co-occurring disorders of substance abuse and mental illness in a shelter: an outcome study.

PubMed

Skinner, Darren C

2005-01-01

This article reports on a study conducted to determine the effectiveness of a modified therapeutic community (MTC) shelter on client outcomes. The seven-study hypotheses focused on whether greater effectiveness in the MTC would be demonstrated in longer periods of sobriety, fewer days of psychiatric hospitalization, shorter lengths of stay in a shelter, positive discharge from the shelter, medication compliance, housing placement within the first year, and appropriate housing placement according to level of functioning. The study utilized a quasi-experimental design with two groups: 1) an experimental group (E) homeless persons with co-occurring disorders (COD) of substance abuse/dependence and mental illness who reside in a modified therapeutic community (N = 70); and 2) a comparison group (C) of veterans with CODs living in a general shelter (N = 70). The data collection procedures involved a retrospective review of closed case records for subjects in the facilities from September 1, 1998-June 1, 2000 for the MTC shelter, and from June 1, 1999-June 1, 2000 for the general shelter. Baseline differences between the E and C groups were found in age, length of homelessness, years of education, years of work experience, veteran status, marital status, and psychiatric diagnosis; all except for veteran status were unrelated to outcomes and were controlled in subsequent analyses. Significant difference was found on medication compliance when controlled for both groups. Overall, this study showed some promise for the MTC approach. The study also raised a question as to the contribution of veteran status to the differences between groups and to treatment of CODs.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR.

PubMed

Araújo, Cristina P; Osório, Ana Luiza A R; Jorge, Klaudia S G; Ramos, Carlos A N; Souza Filho, Antonio F; Vidal, Carlos E S; Vargas, Agueda P C; Roxo, Eliana; Rocha, Adalgiza S; Suffys, Philip N; Fonseca, Antônio A; Silva, Marcio R; Barbosa Neto, José D; Cerqueira, Valíria D; Araújo, Flábio R

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis.

Direct detection of Mycobacterium tuberculosis complex in bovine and bubaline tissues through nested-PCR

PubMed Central

Araújo, Cristina P.; Osório, Ana Luiza A.R.; Jorge, Klaudia S.G.; Ramos, Carlos A.N.; Souza Filho, Antonio F.; Vidal, Carlos E.S.; Vargas, Agueda P.C.; Roxo, Eliana; Rocha, Adalgiza S.; Suffys, Philip N.; Fonseca, Antônio A.; Silva, Marcio R.; Barbosa Neto, José D.; Cerqueira, Valíria D.; Araújo, Flábio R.

2014-01-01

Post-mortem bacterial culture and specific biochemical tests are currently performed to characterize the etiologic agent of bovine tuberculosis. Cultures take up to 90 days to develop. A diagnosis by molecular tests such as PCR can provide fast and reliable results while significantly decreasing the time of confirmation. In the present study, a nested-PCR system, targeting rv2807, with conventional PCR followed by real-time PCR, was developed to detect Mycobacterium tuberculosis complex (MTC) organisms directly from bovine and bubaline tissue homogenates. The sensitivity and specificity of the reactions were assessed with DNA samples extracted from tuberculous and non-tuberculous mycobacteria, as well as other Actinomycetales species and DNA samples extracted directly from bovine and bubaline tissue homogenates. Regarding the analytical sensitivity, DNA of the M. bovis AN5 strain was detected up to 1.5 pg by nested-PCR, whereas DNA of M. tuberculosis H37Rv strain was detected up to 6.1 pg. The nested-PCR system showed 100% analytical specificity for MTC when tested with DNA of reference strains of non-tuberculous mycobacteria and closely-related Actinomycetales. A clinical sensitivity level of 76.7% was detected with tissues samples positive for MTC by means of the culture and conventional PCR. A clinical specificity of 100% was detected with DNA from tissue samples of cattle with negative results in the comparative intradermal tuberculin test. These cattle exhibited no visible lesions and were negative in the culture for MTC. The use of the nested-PCR assay to detect M. tuberculosis complex in tissue homogenates provided a rapid diagnosis of bovine and bubaline tuberculosis. PMID:25242951

Osteopontin expression is correlated with differentiation and good prognosis in medullary thyroid carcinoma.

PubMed

Ferreira, Luciana Bueno; Eloy, Catarina; Pestana, Ana; Lyra, Joana; Moura, Margarida; Prazeres, Hugo; Tavares, Catarina; Sobrinho-Simões, Manuel; Gimba, Etel; Soares, Paula

2016-04-01

Osteopontin (OPN) or secreted phosphoprotein 1 (SPP1) is a matricellular glycoprotein whose expression is elevated in various types of cancer and has been shown to be involved in tumourigenesis and metastasis in many malignancies, including follicular cell-derived thyroid carcinomas. Its role in C-cell-derived thyroid lesions and tumours remains to be established. The objective of this study is to clarify the role of OPN expression in the development of medullary thyroid carcinoma (MTC). OPN expression was analysed in a series of 116 MTCs by immunohistochemistry and by qPCR mRNA quantification of the 3 OPN isoforms (OPNa, OPNb and OPNc) in six cases from which fresh frozen tissue was available. Statistical tests were used to evaluate the relationship of OPN expression and the clinicopathological and molecular characteristics of patients and tumours. OPN expression was detected in 91 of 116 (78.4%) of the MTC. We also observed high OPN expression in C-cell hyperplasia as well as in C-cells scattered in the thyroid parenchyma adjacent to the tumours. OPN expression was significantly associated with smaller tumour size, PTEN nuclear expression and RAS status, and suggestively associated with non-invasive tumours. OPNa isoform was expressed significantly at higher levels in tumours than in non-tumour samples. OPNb and OPNc presented similar levels of expression in all samples. Furthermore, OPNa isoform overexpression was significantly associated with reduced growth and viability in the MTC-derived cell line (TT). The expression of OPN in normal C-cells and C-cell hyperplasia suggests that OPN is a differentiation marker of C-cells, rather than a marker of biological aggressiveness in this setting. At variance with other cancers, OPN expression is associated with good prognostic features in MTC. © 2016 European Society of Endocrinology.

A Multicenter Phase 2 Trial of Pazopanib in Metastatic and Progressive Medullary Thyroid Carcinoma: MC057H

PubMed Central

Suman, Vera J.; Molina, Julian R.; Smallridge, Robert C.; Maples, William J.; Menefee, Michael E.; Rubin, Joseph; Karlin, Nina; Sideras, Kostandinos; Morris, John C.; McIver, Bryan; Hay, Ian; Fatourechi, Vahab; Burton, Jill K.; Webster, Kevin P.; Bieber, Carolyn; Traynor, Anne M.; Flynn, Patrick J.; Cher Goh, Boon; Isham, Crescent R.; Harris, Pamela; Erlichman, Charles

2014-01-01

Context: Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). Objective, Design, Setting, Patients, Intervention, and Outcome Measures: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. Results: From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%–27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. Conclusions: Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities. PMID:24606083

Accuracy of 99mTc (V)-Dimercaptosuccinic Acid Scintigraphy and Fecal Calprotectin Compared with Colonoscopy in Localizing Active Lesions in Inflammatory Bowel Disease

PubMed Central

Basirat, Vahid; Azizi, Zahra; Javid Anbardan, Sanam; Taghizadeh Asl, Mina; Farbod, Yasaman; Teimouri, Azam; Ebrahimi Daryani, Nasser

2016-01-01

INTRODUCTION Due to limitation of colonoscopy in assessing the entire bowel and patients’ intolerance in inflammatory bowel disease (IBD), in the current study, we aimed to prospectively compare the accuracy of 99mTc(V)-dimercaptosuccinic acid (DMSA) and fecal calprotectin with ileocolonoscopy as new methods for localizing inflammations. METHODS Current prospective study conducted between 2012 and 2014 on 30 patients with IBD attending Gastroenterology Clinic of Tehran University of Medical Sciences. Fecal calprotectin and disease activity were measured for all participants and all of them underwent 99mTc (V)-DMSA scintigraphy and colonoscopy. The accuracy of 99mTc (V)-DMSA scintigraphy and calprotectin in localizing bowel lesions were calculated. RESULTS A total of 22 patients with ulcerative colitis (UC) and 8 patients with Crohn’s disease (CD) were evaluated in our study. Sensitivity, positive likelihood ratio (PLR), and positive predictive value (PPV) of scintigraphy and calprotectin over colonoscopy in localization of UC lesions were 86.36%, 0.86%, 100.00% and 90.91%, 0.91, and 100.00%, respectively. Meanwhile, it showed 66.67% sensitivity and 81.25% specificity with PLR=3.56, negative likelihood ratio (NLR)=0.41, PPV=84.21%, and negative predictive value (NPV)= 61.90% in localizing lesions in patients with CD. The calprotectin level had sensitivity, PLR, and PPV of 90.00%, 0.90, and 100.00% in detecting active disease over colonoscopy, respectively. CONCLUSION The 99mTc (V)-DMSA scintigraphy would be an accurate method for detecting active inflammation in follow-up of patients with IBD and assessing response to treatment as a non-invasive and complementary method beside colonoscopy for more accurate diagnosis of CD or UC. PMID:27698971

Different digestion enzymes used for human pancreatic islet isolation: A mixed treatment comparison (MTC) meta-analysis

PubMed Central

Rheinheimer, Jakeline; Ziegelmann, Patrícia Klarmann; Carlessi, Rodrigo; Reck, Luciana Ross; Bauer, Andrea Carla; Leitão, Cristiane Bauermann; Crispim, Daisy

2014-01-01

Collagenases are critical reagents determining yield and quality of isolated human pancreatic islets and may affect islet transplantation outcome. Some islet transplantation centers have compared 2 or more collagenase blends; however, the results regarding differences in quantity and quality of islets are conflicting. Thus, for the first time, a mixed treatment comparison (MTC) meta-analysis was carried out to compile data about the effect of different collagenases used for human pancreas digestion on islet yield, purity, viability and stimulation index (SI). Pubmed, Embase and Cochrane libraries were searched. Of 755 articles retrieved, a total of 15 articles fulfilled the eligibility criteria and were included in the MTC meta-analysis. Our results revealed that Vitacyte and Liberase MTF were associated with a small increase in islet yield (islet equivalent number/g pancreas) when compared with Sevac enzyme [standardized mean difference (95% credible interval – CrI) = −2.19 (−4.25 to −0.21) and −2.28 (−4.49 to −0.23), respectively]. However, all other enzyme comparisons did not show any significant difference regarding islet yield. Purity and viability percentages were not significantly different among any of the analyzed digestion enzymes. Interestingly, Vitacyte and Serva NB1 were associated with increased SI when compared with Liberase MTF enzyme [unstandardized weighted mean difference (95% CrI) = −1.69 (−2.87 to −0.51) and −1.07 (−1.79 to −0.39), respectively]. In conclusion, our MTC meta-analysis suggests that the digestion enzymes currently being used for islet isolation works with similar efficiency regarding islet yield, purity and viability; however, Vitacyte and Serva NB1 enzymes seem to be associated with an improved SI as compared with Liberase MTF. PMID:25437379

Multiple endocrine neoplasia type 2 syndromes (MEN 2): results from the ItaMEN network analysis on the prevalence of different genotypes and phenotypes.

PubMed

Romei, Cristina; Mariotti, Stefano; Fugazzola, Laura; Taccaliti, Augusto; Pacini, Furio; Opocher, Giuseppe; Mian, Caterina; Castellano, Maurizio; degli Uberti, Ettore; Ceccherini, Isabella; Cremonini, Nadia; Seregni, Ettore; Orlandi, Fabio; Ferolla, Piero; Puxeddu, Efisio; Giorgino, Francesco; Colao, Annamaria; Loli, Paola; Bondi, Fabio; Cosci, Barbara; Bottici, Valeria; Cappai, Antonello; Pinna, Giovanni; Persani, Luca; Verga, Uberta; Uberta, Verga; Boscaro, Marco; Castagna, Maria Grazia; Cappelli, Carlo; Zatelli, Maria Chiara; Faggiano, Antongiulio; Francia, Giuseppe; Brandi, Maria Luisa; Falchetti, Alberto; Pinchera, Aldo; Elisei, Rossella

2010-08-01

Multiple endocrine neoplasia type 2 (MEN 2) is a genetic disease characterized by medullary thyroid carcinoma (MTC) associated (MEN 2A and 2B) or not familial MTC (FMTC) with other endocrine neoplasia due to germline RET gene mutations. The prevalence of these rare genetic diseases and their corresponding RET mutations are unknown due to the small size of the study population. We collected data on germline RET mutations of 250 families with hereditary MTC followed in 20 different Italian centres. The most frequent RET amino acid substitution was Val804Met (19.6%) followed by Cys634Arg (13.6%). A total of 40 different germline RET mutations were present. Six families (2.4%) were negative for germline RET mutations. The comparison of the prevalence of RET germline mutations in the present study with those published by other European studies showed a higher prevalence of Val804Met and Ser891Ala mutations and a lower prevalence of Leu790Phe and Tyr791Phe (P<0.0001). A statistically significant higher prevalence of mutations affecting non-cysteine codons was also found (P<0.0001). Furthermore, the phenotype data collection showed an unexpected higher prevalence of FMTC (57.6%) with respect to other MEN 2 syndromes (34% MEN 2A and 6.8% of MEN 2B). In conclusion, we observed a statistically significant different pattern of RET mutations in Italian MEN 2 families with respect to other European studies and a higher prevalence of FMTC phenotype. The different ethnic origins of the patients and the particular attention given to analysing apparently sporadic MTC for RET germline mutations may explain these findings.

Single-molecule visualization of Saccharomyces cerevisiae leading-strand synthesis reveals dynamic interaction between MTC and the replisome

PubMed Central

Lewis, Jacob S.; Spenkelink, Lisanne M.; Schauer, Grant D.; Hill, Flynn R.; Georgescu, Roxanna E.; O’Donnell, Michael E.; van Oijen, Antoine M.

2017-01-01

The replisome, the multiprotein system responsible for genome duplication, is a highly dynamic complex displaying a large number of different enzyme activities. Recently, the Saccharomyces cerevisiae minimal replication reaction has been successfully reconstituted in vitro. This provided an opportunity to uncover the enzymatic activities of many of the components in a eukaryotic system. Their dynamic behavior and interactions in the context of the replisome, however, remain unclear. We use a tethered-bead assay to provide real-time visualization of leading-strand synthesis by the S. cerevisiae replisome at the single-molecule level. The minimal reconstituted leading-strand replisome requires 24 proteins, forming the CMG helicase, the Pol ε DNA polymerase, the RFC clamp loader, the PCNA sliding clamp, and the RPA single-stranded DNA binding protein. We observe rates and product lengths similar to those obtained from ensemble biochemical experiments. At the single-molecule level, we probe the behavior of two components of the replication progression complex and characterize their interaction with active leading-strand replisomes. The Minichromosome maintenance protein 10 (Mcm10), an important player in CMG activation, increases the number of productive replication events in our assay. Furthermore, we show that the fork protection complex Mrc1–Tof1–Csm3 (MTC) enhances the rate of the leading-strand replisome threefold. The introduction of periods of fast replication by MTC leads to an average rate enhancement of a factor of 2, similar to observations in cellular studies. We observe that the MTC complex acts in a dynamic fashion with the moving replisome, leading to alternating phases of slow and fast replication. PMID:28923950

Somatostatin receptor scintigraphy using 99mTc-EDDA/HYNIC-TOC in patients with medullary thyroid carcinoma.

PubMed

Czepczyński, Rafał; Parisella, Maria Gemma; Kosowicz, Jerzy; Mikołajczak, Renata; Ziemnicka, Katarzyna; Gryczyńska, Maria; Sowiński, Jerzy; Signore, Alberto

2007-10-01

Several new somatostatin analogues have been developed for the diagnosis and therapy of different tumours. Since somatostatin receptors are often over-expressed in medullary thyroid carcinoma (MTC), the aim of our study was to evaluate the utility of scintigraphy with the somatostatin analogue (99m)Tc-EDDA/HYNIC-TOC in MTC in comparison with other diagnostic techniques. Forty-five patients with MTC, aged 14-83 years, were investigated. Scintigraphy using (99m)Tc-EDDA/HYNIC-TOC (Tektrotyd) was performed 2 and 4 h post injection of 740 MBq (20 mCi) of the tracer. Other imaging techniques were also applied and analysed in individual cases (ultrasonography, computed tomography, (99m)Tc(V)-DMSA, (131)I-MIBG, (99m)Tc-MDP, (111)In-DTPA-octreotide and (18)F-FDG-PET) and compared with (99m)Tc-EDDA/HYNIC-TOC. In group 1 (eight patients before thyroidectomy), uptake of the tracer was found in the primary tumours. In group 2 (six patients with remission), a false positive result was found in one patient; in the remaining five patients, no pathological foci were visualised. In group 3 (31 patients with post-surgical hypercalcitoninaemia), scintigraphy was true positive in 23 patients (74.2%): uptake in the thyroid bed was found in five patients, in the lymph nodes in 18 and in bone metastases in four. Using (99m)Tc-EDDA/HYNIC-TOC scintigraphy, the overall sensitivity was 79.5%, specificity 83.3%, accuracy 80.0%, positive predictive value 96.9% and negative predictive value 38.5%. (99m)Tc-EDDA/HYNIC-TOC is clinically useful for scintigraphy in the follow-up of patients with MTC. It can be used in clinical practice for preoperative evaluation, for localisation of local recurrence or distant metastases and particularly for therapy decision making.

Synthesis and characterization of fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] complexes (M = Re, (99m)Tc) with acetylacetone and curcumin as OO donor bidentate ligands.

PubMed

Triantis, Charalampos; Tsotakos, Theodoros; Tsoukalas, Charalampos; Sagnou, Marina; Raptopoulou, Catherine; Terzis, Aris; Psycharis, Vassilis; Pelecanou, Maria; Pirmettis, Ioannis; Papadopoulos, Minas

2013-11-18

The synthesis and characterization of neutral mixed ligand complexes fac-[M(CO)3(P)(OO)] and cis-trans-[M(CO)2(P)2(OO)] (M = Re, (99m)Tc), with deprotonated acetylacetone or curcumin as the OO donor bidentate ligands and a phosphine (triphenylphosphine or methyldiphenylphosphine) as the monodentate P ligand, is described. The complexes were synthesized through the corresponding fac-[M(CO)3(H2O)(OO)] (M = Re, (99m)Tc) intermediate aqua complex. In the presence of phosphine, replacement of the H2O molecule of the intermediate complex at room temperature generates the neutral tricarbonyl monophosphine fac-[Re(CO)3(P)(OO)] complex, while under reflux conditions further replacement of the trans to the phosphine carbonyl generates the new stable dicarbonyl bisphosphine complex cis-trans-[Re(CO)2(P)2(OO)]. The Re complexes were fully characterized by elemental analysis, spectroscopic methods, and X-ray crystallography showing a distorted octahedral geometry around Re. Both the monophosphine and the bisphosphine complexes of curcumin show selective binding to β-amyloid plaques of Alzheimer's disease. At the (99m)Tc tracer level, the same type of complexes, fac-[(99m)Tc(CO)3(P)(OO)] and cis-trans-[(99m)Tc(CO)2(P)2(OO)], are formed introducing new donor combinations for (99m)Tc(I). Overall, β-diketonate and phosphine constitute a versatile ligand combination for Re(I) and (99m)Tc(I), and the successful employment of the multipotent curcumin as β-diketone provides a solid example of the pharmacological potential of this system.

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance.

PubMed

Honkala, Sanna M; Motiani, Kumail K; Eskelinen, Jari-Joonas; Savolainen, Anna; Saunavaara, Virva; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Kapanen, Jukka; Knuuti, Juhani; Kalliokoski, Kari K; Hannukainen, Jarna C

2017-07-01

Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). A total of 28 healthy men (body mass index = 20.7-30.0 kg·m, age = 40-55 yr) and 16 men with DGT (body mass index = 23.8-33.5 kg·m, age = 43-53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by H-MRS. At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = -42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (-5%) and PAT (-6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC.

The cAMP analogs have potent anti-proliferative effects on medullary thyroid cancer cell lines.

PubMed

Dicitore, Alessandra; Grassi, Elisa Stellaria; Caraglia, Michele; Borghi, Maria Orietta; Gaudenzi, Germano; Hofland, Leo J; Persani, Luca; Vitale, Giovanni

2016-01-01

The oncogenic activation of the rearranged during transfection (RET) proto-oncogene has a main role in the pathogenesis of medullary thyroid cancer (MTC). Several lines of evidence suggest that RET function could be influenced by cyclic AMP (cAMP)-dependent protein kinase A (PKA) activity. We evaluated the in vitro anti-tumor activity of 8-chloroadenosine-3',5'-cyclic monophosphate (8-Cl-cAMP) and PKA type I-selective cAMP analogs [equimolar combination of the 8-piperidinoadenosine-3',5'-cyclic monophosphate (8-PIP-cAMP) and 8-hexylaminoadenosine-3',5'-cyclic monophosphate (8-HA-cAMP) in MTC cell lines (TT and MZ-CRC-1)]. 8-Cl-cAMP and the PKA I-selective cAMP analogs showed a potent anti-proliferative effect in both cell lines. In detail, 8-Cl-cAMP blocked significantly the transition of TT cell population from G2/M to G0/G1 phase and from G0/G1 to S phase and of MZ-CRC-1 cells from G0/G1 to S phase. Moreover, 8-Cl-cAMP induced apoptosis in both cell lines, as demonstrated by FACS analysis for annexin V-FITC/propidium iodide, the activation of caspase-3 and PARP cleavage. On the other hand, the only effect induced by PKA I-selective cAMP analogs was a delay in G0/G1-S and S-G2/M progression in TT and MZ-CRC-1 cells, respectively. In conclusion, these data demonstrate that cAMP analogs, particularly 8-Cl-cAMP, significantly suppress in vitro MTC proliferation and provide rationale for a potential clinical use of cAMP analogs in the treatment of advanced MTC.

Diagnostic and Therapeutic Radiopharmaceutical Agents for Selective Discrimination of Prostate Cancer

DTIC Science & Technology

2008-10-01

complexing a M(CO)3 (Re,99mTc) organometallic species to target prostate cancer for imaging and therapy . The project has been successful in developing and...couple flutamide derivatives with new ligand systems. New methods were investigated on a fundamental level prior to functionalization with the ...based on the current results of the first generation compounds. The 2+1 approach was initially investigated for coupling the Tc(CO)3 to a multi

Radionuclide imaging in herpes simplex encephalitis. [/sup 99m/Tc tracer techniques

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

Karlin, C.A.; Robinson, R.G.; Hinthorn, D.R.

1978-01-01

Eight patients with herpes simplex encephalitis among the 10 cases diagnosed at the University of Kansas Medical Center from 1966 to 1976 were studied with /sup 99m/Tc early in their diagnostic work-up. The images were unilaterally positive in the temporal lobe area in all 8 patients. Radionuclide studies can suggest herpes simplex as the specific etiology in cases of encephalitis and can also indicate the best site for brain biopsy to confirm the diagnosis by fluorescent antibody techniques. Appropriate antiviral therapy should be instituted as soon as possible to alter the course of this destructive form of viral encephalitis.

Design and performance of an automated radionuclide separator: its application on the determination of ⁹⁹Tc in groundwater.

PubMed

Chung, Kun Ho; Choi, Sang Do; Choi, Geun Sik; Kang, Mun Ja

2013-11-01

A modular automated radionuclide separator for (99)Tc (MARS Tc-99) has been developed for the rapid and reproducible separation of technetium in groundwater samples. The control software of MARS Tc-99 was developed in the LabView programming language. An automated radiochemical method for separating (99)Tc was developed and validated by the purification of (99m)Tc tracer solution eluted from a commercial (99)Mo/(99m)Tc generator. The chemical recovery and analytical time for this radiochemical method were found to be 96 ± 2% and 81 min, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

Distinct spatiotemporal activity in principal neurons of the mouse olfactory bulb in anesthetized and awake states

PubMed Central

Blauvelt, David G.; Sato, Tomokazu F.; Wienisch, Martin; Murthy, Venkatesh N.

2013-01-01

The acquisition of olfactory information and its early processing in mammals are modulated by brain states through sniffing behavior and neural feedback. We imaged the spatiotemporal pattern of odor-evoked activity in a population of output neurons (mitral/tufted cells, MTCs) in the olfactory bulb (OB) of head-restrained mice expressing a genetically-encoded calcium indicator. The temporal dynamics of MTC population activity were relatively simple in anesthetized animals, but were highly variable in awake animals. However, the apparently irregular activity in awake animals could be predicted well using sniff timing measured externally, or inferred through fluctuations in the global responses of MTC population even without explicit knowledge of sniff times. The overall spatial pattern of activity was conserved across states, but odor responses had a diffuse spatial component in anesthetized mice that was less prominent during wakefulness. Multi-photon microscopy indicated that MTC lateral dendrites were the likely source of spatially disperse responses in the anesthetized animal. Our data demonstrate that the temporal and spatial dynamics of MTCs can be significantly modulated by behavioral state, and that the ensemble activity of MTCs can provide information about sniff timing to downstream circuits to help decode odor responses. PMID:23543674

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

McAfee, J.G.; Krauss, D.J.; Subramanian, G.

The 3-hour biodistribution of /sup 99m/Tc complexes of five diphosphonates (HMDP, NMMDP, DMAD, DPD, and APD), imidodiphosphonate (IDP), and pyrophosphate (PYP) was compared in rats with segmental renal infarction induced by a 1-hour occlusion of a renal artery branch. /sup 95m/Tc labeled MDP was a reference substance in all animals. Three agents (APD, HMDP and IDP) had a higher infarct/normal kidney concentration ratio than MDP, the latter two by virtue of a lower content in normal kidney. HMDP, DPD, and IDP had very high liver concentrations. DPD showed relatively high concentrations in soft tissues and blood. The blood and kidneymore » levels of PYP were higher than those of MDP but the infarct/normal kidney ratios were similar. None of the agents had a higher uptake in bone than MDP: four had a significantly lower uptake. The increased concentration of /sup 99m/Tc MDP in the infarcts was readily seen in camera images one day after renal artery occlusion, but not at three or seven days. Increased diphosphonate uptake was accompanied by an influx of calcium in both cortex and medulla. The accumulation of diphosphonate in areas of infarction was not modified by infusions of verapamil or Captopril.« less

Child with RET proto-oncogene codon 634 mutation.

PubMed

İnce, Dilek; Demirağ, Bengü; Ataseven, Eda; Oymak, Yeşim; Tuhan, Hale; Karakuş, Osman Zeki; Hazan, Filiz; Abacı, Ayhan; Özer, Erdener; Mutafoglu, Kamer; Olgun, Nur

2017-01-01

İnce D, Demirağ B, Ataseven E, Oymak Y, Tuhan H, Karakuş OZ, Hazan F, Abacı A, Özer E, Mutafoglu K, Olgun N. Child with RET proto-oncogene codon 634 mutation. Turk J Pediatr 2017; 59: 590-593. Herein we reported a 7-year-old child with RET proto-oncogene c634 mutation. Her mother had been diagnosed with medullary thyroid carcinoma (MTC), and treated six years ago. Heterozygous mutation of the RET proto-oncogene at c634 had been detected in her mother. Genetic analysis showed the presence of the same mutation in our patient. Thyroid functions were normal. Serum calcitonin level was found mildly elevated. Parathormone (PTH) and carcinoembrionic antigen (CEA) levels were normal. Prophylactic thyroidectomy and sampling of cervical lymph nodes were performed. Histopathologic examination revealed hyperplasia in thyroid C cells, and reactive lymphadenopathy. The risk of MTC has been reported 100% through the life of patients with RET proto-oncogene mutation. It has been reported that particularly patients with c634 mutation have more risk of occurence of metastatic and progressive/recurrent MTC. Prophylactic `thyroidectomy, cervical lymph node dissection` before 5-years-of-age should be considered for these patients.

Evaluation of 99mTc labeled diadenosine tetraphosphate as an atherosclerotic plaque imaging agent in experimental models.

PubMed

Cao, Wei; Zhang, Yongxue; An, Rui

2006-01-01

The potential of 99mTc labeled P1, P4-di (adenosine-5')-tetraphosphate (Ap4A) for imaging experimental atherosclerotic plaques was evaluated in New Zealand white (NZW) rabbits. To label the 99mTc to Ap4A, stannous tartrate solution was used. 99mTc-Ap4A was purified on a Sephadex G-25 column. The radiochemistry purities of 99mTc-Ap4A were 85% to 91%. Biodistribution study revealed 99mTc-Ap4A cleared from blood rapidly. Thirty min after 99mTc-Ap4A administrated on NZW atherosclerotic rabbits, lesion to blood (target/blood, T/B) ratio was 3.17 +/- 1.27, and lesions to normal (target/non-target, T/NT) ratio was 5.23 +/- 1.87. Shadows of atherosclerotic plaques were clearly visible on radioautographic film. Aortas with atherosclerotic plaques also could be seen on ex vivo gamma camera images. Atherosclerotic abdominal aortas were clearly visible on in vivo images 15 min to 3 h after 99mTc-Ap4A administration. 99mTc-labeled Ap4A can be used for rapid noninvasive detection of experimental atherosclerotic plaque.

Synthesis, characterization and biological evaluation of a novel "3 + 1" mixed ligand 99mTc complex having an aliphatic thiol as coligand.

PubMed

Rey, A; Papadopoulos, M; Leon, E; Mallo, L; Pirmettis, Y; Manta, E; Raptopoulou, C; Chiotellis, E; Leon, A

2001-03-01

A novel "3 + 1" mixed ligand 99mTc complex with N,N-bis(2-mercaptoethyl)-N'N'-diethyl-ethilenediamine as ligand and 1-octanethiol as coligand was prepared and evaluated as potential brain radiopharmaceutical. Preparation at tracer level was accomplished by substitution, using 99mTc-glucoheptonate as precursor and a coligand/ligand ratio of 5. Under these conditions the labeling yield was over 80% and a major product with radiochemical purity >80% was isolated by HPLC methods and used for biological evaluation. Chemical characterization at carrier level was developed using the corresponding rhenium and 99gTc complexes. Results were consistent with the expected "3 + 1" structure and X-ray diffraction study demonstrated that the complex adopted a distorted trigonal bipyramidal geometry. All sulphur atoms underwent ionization leading to the formation of a neutral compound. Biodistribution in mice demonstrated early brain uptake, fast blood clearance and excretion through hepatobiliary system. Although brain/blood ratio increased significantly with time, this novel 99mTc complex did not exhibit ideal properties as brain perfusion radiopharmaceutical since brain uptake was too low.

Small-Animal SPECT/CT of the Progression and Recovery of Rat Liver Fibrosis by Using an Integrin αvβ3-targeting Radiotracer.

PubMed

Yu, Xinhe; Wu, Yue; Liu, Hao; Gao, Liquan; Sun, Xianlei; Zhang, Chenran; Shi, Jiyun; Zhao, Huiyun; Jia, Bing; Liu, Zhaofei; Wang, Fan

2016-05-01

To assess the potential utility of an integrin αvβ3-targeting radiotracer, technetium 99m-PEG4-E[PEG4-cyclo(arginine-glycine-aspartic acid-D-phenylalanine-lysine)]2 ((99m)Tc-3PRGD2), for single photon emission computed tomography (SPECT)/computed tomography (CT) for monitoring of the progression and prognosis of liver fibrosis in a rat model. All animal experiments were performed by following the protocol approved by the institutional animal care and use committee. (99m)Tc-3PRGD2 was prepared and longitudinal SPECT/CT was performed to monitor the progression (n = 8) and recovery (n = 5) of liver fibrosis induced in a rat model by means of thioacetamide (TAA) administration. The mean liver-to-background radioactivity per unit volume ratio was analyzed for comparisons between the TAA and control (saline) groups at different stages of liver fibrosis. Data were compared by using Student t and Mann-Whitney tests. Results:of SPECT/CT were compared with those of ex vivo biodistribution analysis (n = 5). Accumulation of (99m)Tc-3PRGD2 in the liver increased in proportion to the progression of fibrosis and TAA exposure time; accumulation levels were significantly different between the TAA and control groups as early as week 4 of TAA administration (liver-to-background ratio: 32.30 ± 3.39 vs 19.01 ± 3.31; P = .0002). Results of ex vivo immunofluorescence staining demonstrated the positive expression of integrin αvβ3 on the activated hepatic stellate cells, and the integrin αvβ3 levels in the liver corresponded to the results of SPECT/CT (R(2) = 0.75, P < .0001). (99m)Tc-3PRGD2 uptake in the fibrotic liver decreased after antifibrotic therapy with interferon α2b compared with that in the control group (relative liver-to-background ratio: 0.45 ± 0.05 vs 1.01 ± 0.05; P < .0001) or spontaneous recovery (relative liver-to-background ratio: 0.56 ± 0.06 vs 1.01 ± 0.05; P < .0001). (99m)Tc-3PRGD2 SPECT/CT was successfully used to monitor the progression and recovery of liver fibrosis and shows potential applications for noninvasive diagnosis of early stage liver fibrosis. (©) RSNA, 2015 Online supplemental material is available for this article.

Radioactive excretion in human milk following administration of /sup 99m/Tc macroaggregated albumin

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

Pittard, W.B.; Merkatz, R.; Fletcher, B.D.

Albumin-tagged sodium pertechnetate (technetium) is routinely used in nuclear medicine for scanning procedures of the lung. The rate of excretion of this radionuclide into breast milk and the resultant potential radiation hazard to the nursing infant have received little attention. Therefore the milk from a nursing mother who required a lung scan because of suspected pulmonary emboli using an intravenous injection of 4 mCi of /sup 99m/Tc macroaggregated human serum albumin was monitored. Albumin tagging severely limited the entrance of technetium into her milk and the radioactivity of the milk returned to base line by 24 hours. A total ofmore » 2.02 muCi of technetium was measured in the 24-hour milk collection after technetium injection and 94% of this amount was excreted by 15.5 hours. This amount of technetium administered orally to a newborn would deliver a total body radiation dose of .3 mrad. Therefore, an infant would receive trivial doses of radiation if breast-feeding were resumed 15.5 hours after administration of the radionuclide to the mother and nursing can clearly be resumed safely 24 hours after injection.« less

Technetium-99m and rhenium-188 complexes with one and two pendant bisphosphonate groups for imaging arterial calcification.

PubMed

Bordoloi, Jayanta Kumar; Berry, David; Khan, Irfan Ullah; Sunassee, Kavitha; de Rosales, Rafael Torres Martin; Shanahan, Catherine; Blower, Philip J

2015-03-21

The first (99m)Tc and (188)Re complexes containing two pendant bisphosphonate groups have been synthesised, based on the mononuclear M(v) nitride core with two dithiocarbamate ligands each with a pendant bisphosphonate. The structural identity of the (99)Tc and stable rhenium analogues as uncharged, mononuclear nitridobis(dithiocarbamate) complexes was determined by electrospray mass spectrometry. The (99m)Tc complex showed greater affinity for synthetic and biological hydroxyapatite, and greater stability in biological media, than the well-known but poorly-characterised and inhomogeneous bone imaging agent (99m)Tc-MDP. It gave excellent SPECT images of both bone calcification (mice and rats) and vascular calcification (rat model), but the improved stability and the availability of two pendant bisphosphonate groups conferred no dramatic advantage in imaging over the conventional (99m)Tc-MDP agent in which the bisphosphonate group is bound directly to Tc. The (188)Re complex also showed preferential uptake in bone. These tracers and the biological model of vascular calcification offer the opportunity to study the biological interpretation and clinical potential of radionuclide imaging of vascular calcification and to deliver radionuclide therapy to bone metastases.

Synthesis and antimicrobial evaluation of two peptide LyeTx I derivatives modified with the chelating agent HYNIC for radiolabeling with technetium-99m.

PubMed

Fuscaldi, Leonardo Lima; Dos Santos, Daniel Moreira; Pinheiro, Natália Gabriela Silva; Araújo, Raquel Silva; de Barros, André Luís Branco; Resende, Jarbas Magalhães; Fernandes, Simone Odília Antunes; de Lima, Maria Elena; Cardoso, Valbert Nascimento

2016-01-01

Current diagnostic methods and imaging techniques are not able to differentiate septic and aseptic inflammation. Thus, reliable methods are sought to provide this distinction and scintigraphic imaging is an interesting option, since it is based on physiological changes. In this context, radiolabeled antimicrobial peptides have been investigated as they accumulate in infectious sites instead of aseptic inflammation. The peptide LyeTx I, from the venom of Lycosa erythrognatha, has potent antimicrobial activity. Therefore, this study aimed to synthesize LyeTx I derivatives with the chelating compound HYNIC, to evaluate their antimicrobial activity and to radiolabel them with (99m)Tc. Two LyeTx I derivatives, HYNIC-LyeTx I (N-terminal modification) and LyeTx I-K-HYNIC (C-terminal modification), were synthesized by Fmoc strategy and purified by RP-HPLC. The purified products were assessed by RP-HPLC and MALDI-ToF-MS analysis. Microbiological assays were performed against S. aureus (ATCC® 6538) and E. coli (ATCC® 10536) in liquid medium to calculate the MIC. The radiolabeling procedure of LyeTx I-K-HYNIC with (99m)Tc was performed in the presence of co-ligands (tricine and EDDA) and reducing agent (SnCl2 (.) 2H2O), and standardized taking into account the amount of peptide, reducing agent, pH and heating. Radiochemical purity analysis was performed by thin-layer chromatography on silica gel strips and the radiolabeled compound was assessed by RP-HPLC and radioactivity measurement of the collected fractions. Data were analyzed by ANOVA, followed by Tukey test (p-values < 0.05). Both LyeTx I derivatives were suitably synthesized and purified, as shown by RP-HPLC and MALDI-ToF-MS analysis. The microbiological test showed that HYNIC-LyeTx I (N-terminal modification) did not inhibit bacterial growth, whereas LyeTx I-K-HYNIC (C-terminal modification) showed a MIC of 5.05 μmol(.)L(-1) (S. aureus) and 10.10 μmol(.)L(-1) (E. coli). Thus, only the latter was radiolabeled with (99m)Tc. The radiochemical purity analysis of LyeTx I-K-HYNIC-(99m)Tc showed that the optimal radiolabeling conditions (10 μg of LyeTx I-K-HYNIC; 250 μg of SnCl2 (.) 2H2O; pH = 7; heating for 15 min) yielded a radiochemical purity of 87 ± 1 % (n = 3). However, RP-HPLC data suggested (99m)Tc transchelation from LyeTx I-K-HYNIC to the co-ligands (tricine and EDDA). The binding of HYNIC to the N-terminal portion of LyeTx I seems to affect its activity against bacteria. Nevertheless, the radiolabeling of the C-terminal derivative, LyeTx I-K-HYNIC, must be better investigated to optimize the radiolabeled compound, in order to use it as a specific imaging agent to distinguish septic and aseptic inflammation.

Gallium-68 EDTA PET/CT for Renal Imaging.

PubMed

Hofman, Michael S; Hicks, Rodney J

2016-09-01

Nuclear medicine renal imaging provides important functional data to assist in the diagnosis and management of patients with a variety of renal disorders. Physiologically stable metal chelates like ethylenediaminetetraacetic acid (EDTA) and diethylenetriamine penta-acetate (DTPA) are excreted by glomerular filtration and have been radiolabelled with a variety of isotopes for imaging glomerular filtration and quantitative assessment of glomerular filtration rate. Gallium-68 ((68)Ga) EDTA PET usage predates Technetium-99m ((99m)Tc) renal imaging, but virtually disappeared with the widespread adoption of gamma camera technology that was not optimal for imaging positron decay. There is now a reemergence of interest in (68)Ga owing to the greater availability of PET technology and use of (68)Ga to label other radiotracers. (68)Ga EDTA can be used a substitute for (99m)Tc DTPA for wide variety of clinical indications. A key advantage of PET for renal imaging over conventional scintigraphy is 3-dimensional dynamic imaging, which is particularly helpful in patients with complex anatomy in whom planar imaging may be nondiagnostic or difficult to interpret owing to overlying structures containing radioactive urine that cannot be differentiated. Other advantages include accurate and absolute (rather than relative) camera-based quantification, superior spatial and temporal resolution and integrated multislice CT providing anatomical correlation. Furthermore, the (68)Ga generator enables on-demand production at low cost, with no additional patient radiation exposure compared with conventional scintigraphy. Over the past decade, we have employed (68)Ga EDTA PET/CT primarily to answer difficult clinical questions in patients in whom other modalities have failed, particularly when it was envisaged that dynamic 3D imaging would be of assistance. We have also used it as a substitute for (99m)Tc DTPA if unavailable owing to supply issues, and have additionally examined the role of (68)Ga EDTA PET/CT for measuring glomerular filtration rate and split renal function. Copyright © 2016 Elsevier Inc. All rights reserved.

Isothiocyanate-Functionalized Bifunctional Chelates and fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) Complexes for Targeting uPAR in Prostate Cancer.

PubMed

Kasten, Benjamin B; Ma, Xiaowei; Cheng, Kai; Bu, Lihong; Slocumb, Winston S; Hayes, Thomas R; Trabue, Steven; Cheng, Zhen; Benny, Paul D

2016-01-20

Developing new strategies to rapidly incorporate the fac-[M(I)(CO)3](+) (M = Re, (99m)Tc) core into biological targeting vectors in radiopharmaceuticals continues to expand as molecules become more complex and as efforts to minimize nonspecific binding increase. This work examines a novel isothiocyanate-functionalized bifunctional chelate based on 2,2'-dipicolylamine (DPA) specifically designed for complexing the fac-[M(I)(CO)3](+) core. Two strategies (postlabeling and prelabeling) were explored using the isothiocyanate-functionalized DPA to determine the effectiveness of assembly on the overall yield and purity of the complex with amine containing biomolecules. A model amino acid (lysine) examined (1) amine conjugation of isothiocyanate-functionalized DPA followed by complexation with fac-[M(I)(CO)3](+) (postlabeling) and (2) complexation of fac-[M(I)(CO)3](+) with isothiocyanate-functionalized DPA followed by amine conjugation (prelabeling). Conducted with stable Re and radioactive (99m)Tc analogs, both strategies formed the product in good to excellent yields under macroscopic and radiotracer concentrations. A synthetic peptide (AE105) which targets an emerging biomarker in CaP prognosis, urokinase-type plasminogen activator receptor (uPAR), was also explored using the isothiocyanate-functionalized DPA strategy. In vitro PC-3 (uPAR+) cell uptake assays with the (99m)Tc-labeled peptide (8a) showed 4.2 ± 0.5% uptake at 4 h. In a murine model bearing PC-3 tumor xenografts, in vivo biodistribution of 8a led to favorable tumor uptake (3.7 ± 0.7% ID/g) at 4 h p.i. with relatively low accumulation (<2% ID/g) in normal organs not associated with normal peptide excretion. These results illustrate the promise of the isothiocyanate-functionalized approach for labeling amine containing biological targeting vectors with fac-[M(I)(CO)3](+).

Development of Tyrosine-Based Radiotracer 99mTc-N4-Tyrosine for Breast Cancer Imaging

PubMed Central

Kong, Fan-Lin; Ali, Mohammad S.; Rollo, Alex; Smith, Daniel L.; Zhang, Yinhan; Yu, Dong-Fang; Yang, David J.

2012-01-01

The purpose of this study was to develop an efficient way to synthesize 99mTc-O-[3-(1,4,8,11-tetraazabicyclohexadecane)-propyl]-tyrosine (99mTc-N4-Tyrosine), a novel amino acid-based radiotracer, and evaluate its potential in breast cancer gamma imaging. Precursor N4-Tyrosine was synthesized using a 5-step procedure, and its total synthesis yield was 38%. It was successfully labeled with 99mTc with high radiochemical purity (>95%). Cellular uptake of 99mTc-N4-Tyrosine was much higher than that of 99mTc-N4 and the clinical gold standard 18F-2-deoxy-2-fluoro-glucose (18F-FDG) in rat breast tumor cells in vitro. Tissue uptake and dosimetry estimation in normal rats revealed that 99mTc-N4-Tyrosine could be safely administered to humans. Evaluation in breast tumor-bearing rats showed that although 99mTc-N4-Tyrosine appeared to be inferior to 18F-FDG in distinguishing breast tumor tissue from chemical-induced inflammatory tissue, it had high tumor-to-muscle uptake ratios and could detect breast tumors clearly by planar scintigraphic imaging. 99mTc-N4-Tyrosine could thus be a useful radiotracer for use in breast tumor diagnostic imaging. PMID:22496612

Differences between the macroscopic and tracer level chemistry of rhenium and technetium: contrasting cage isomerisation behaviour of Re(I) and Tc(I) carborane complexes.

PubMed

Armstrong, Andrea F; Valliant, John F

2010-09-21

Carboranes form stable complexes with the [M(CO)(3)](+) (M = (99m)Tc, Re) core and are viable ligands for the development of targeted radiopharmaceuticals. (99m)Tc-carborane complexes were found to exhibit substantially different 1,2-->1,7 cage isomerisation behaviour than their Re counterparts, challenging the validity of the routine use of rhenium as a surrogate for the development of technetium-99m based molecular imaging agents.

Producing radiometals in liquid targets: Proof of feasibility with {sup 94m}Tc

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

Hoehr, C.; Badesso, B.; Morley, T.

2012-12-19

{sup 94m}Tc was produced in a liquid target loaded with a molybdenum-salt solution. This novel technique allows for the irradiation of metals dissolved in a liquid solution, normally only available in metal powder or foil form. By using this approach, the existing liquid targets and transfer infrastructure of many PET cyclotrons can be used to produce radiometals, avoiding the need, expense and challenges of operating solid targets. Such an approach allows for rapid testing of new isotopes for proof of feasibility studies. Different concentrations of Mo solution and their effect on the target performance were tested. Sufficient quantities to allowmore » for preclinical studies were produced.« less

[Methodological aspects related to the determination of the relative renal function using 99mTC MAG3].

PubMed

Ladrón De Guevara Hernández, D; Ham, H; Franken, P; Piepsz, A; Lobo Sotomayor, G

2002-01-01

The aim of the study was to evaluate three different methods for calculating the split renal function in patients with only one functioning kidney, keeping in mind that the split function should be zero on the side of the non-functioning kidney. We retrospectively selected 28 99mTc MAG3 renograms performed in children, 12 with unilateral nephrectomy, 4 with unilateral agenesis and 12 with a non-functioning kidney. A renal and perirenal region of interest (ROI) were delineated around the functioning kidney. The ROIs around the empty kidney were drawn symmetrically to the contralateral side. The split renal function was calculated using three different methods, the integral method, the slope method and the Patlak-Rutland algorithm. For the whole group of 28 kidneys as well as for the three categories of patients, the three methods provided a split function on the side of the non-functioning kidney close to the zero value, regardless of whether the empty kidney was the left or the right one. We recommend the use of the integral method for the whole range of split renal function with 99mTc MAG3. No significant improvement was obtained by means of the more sophisticated Patlak-Rutland method.

Effectiveness of medical taping concept in primary dysmenorrhoea: a two-armed randomized trial

PubMed Central

Tomás-Rodríguez, María Isabel; Palazón-Bru, Antonio; Martínez-St. John, Damian Robert James; Toledo-Marhuenda, José Vicente; Asensio-García, María del Rosario; Gil-Guillén, Vicente Francisco

2015-01-01

In 2014, we assessed the effectiveness of Medical Taping Concept (MTC) in Primary Dysmenorrhoea (PD) with a single-blind, two-armed clinical trial (NCT02114723, ClinicalTrials.gov) with a follow-up of 4 menstrual cycles (pre-intervention: 2 months; post-intervention: 2 months) in a sample formed by 129 Spanish women aged 18–30 years with PD. We had two groups: intervention group (75), MTC covering T-11 and T-12 dermatomes; control group (54), another taping in both greater trochanter areas. Our main outcome measures were: pre-intervention and post-intervention increase in pain difference measured 2 hours after commencement (2-h pain — 0-h pain); difference between the number of tablets ingested post-intervention and pre-intervention; and associated symptoms in post-intervention (fatigue, vomiting, diarrhoea, nausea and others). Pain was assessed in: abdomen, legs, head and lower back. We found significant differences (p < 0.05) for number of tablets, abdominal and leg pain. In conclusion, the intervention group had less abdominal and leg pain when pharmacological therapy was not started. Furthermore, the intervention resulted in a lower intake of tablets. Nevertheless, more studies are needed to corroborate our results and to analyze the MTC effectiveness if women do not take any tablets during the entire menstrual period. PMID:26564807

Detection of Myocardial Ischemia-Reperfusion Injury Using a Fluorescent Near-Infrared Zinc(II)-Dipicolylamine Probe and 99mTc Glucarate

PubMed Central

wyffels, Leonie; Gray, Brian D.; Barber, Christy; Pak, Koon Y.; Forbes, Safiyyah; Mattis, Jeffrey A.; Woolfenden, James M.; Liu, Zhonglin

2012-01-01

A fluorescent zinc 2,2′-dipicolylamine coordination complex PSVue®794 (probe 1) is known to selectively bind to phosphatidylserine exposed on the surface of apoptotic and necrotic cells. In this study, we investigated the cell death targeting properties of probe 1 in myocardial ischemia-reperfusion injury. A rat heart model of ischemia-reperfusion was used. Probe 1, control dye, or 99mTc glucarate was intravenously injected in rats subjected to 30-minute and 5-minute myocardial ischemia followed by 2-hour reperfusion. At 90 minutes or 20 hours postinjection, myocardial uptake was evaluated ex vivo by fluorescence imaging and autoradiography. Hematoxylin-eosin and cleaved caspase-3 staining was performed on myocardial sections to demonstrate the presence of ischemiareperfusion injury and apoptosis. Selective accumulation of probe 1 could be detected in the area at risk up to 20 hours postinjection. Similar topography and extent of uptake of probe 1 and 99mTc glucarate were observed at 90 minutes postinjection. Histologic analysis demonstrated the presence of necrosis, but only a few apoptotic cells could be detected. Probe 1 selectively accumulates in myocardial ischemia-reperfusion injury and is a promising cell death imaging tool. PMID:22554483

Evaluation of the efficiency of nested q-PCR in the detection of Mycobacterium tuberculosis complex directly from tuberculosis-suspected lesions in post-mortem macroscopic inspections of bovine carcasses slaughtered in the state of Mato Grosso, Brazil.

PubMed

Carvalho, Ricardo César Tavares; Furlanetto, Leone Vinícius; Maruyama, Fernanda Harumy; Araújo, Cristina Pires de; Barros, Sílvia Letícia Bomfim; Ramos, Carlos Alberto do Nascimento; Dutra, Valéria; Araújo, Flábio Ribeiro de; Paschoalin, Vânia Margaret Flosi; Nakazato, Luciano; Figueiredo, Eduardo Eustáquio de Souza

2015-08-01

Bovine tuberculosis (BTB) is a zoonotic disease caused by Mycobacterium bovis, a member of the Mycobacterium tuberculosis complex (MTC). The quick and specific detection of this species is of extreme importance, since BTB may cause economic impacts, in addition to presenting imminent risks to human health. In the present study a nested real-time PCR test (nested q-PCR) was used in post-mortem evaluations to assess cattle carcasses with BTB-suspected lesions. A total of 41,193 cattle slaughtered in slaughterhouses located in the state of Mato Grosso, were examined. Of the examined animals, 198 (0.48%) showed BTB-suspected lesions. M. bovis was isolated in 1.5% (3/198) of the samples. Multiplex-PCR detected MTC in 7% (14/198) of the samples. The nested q-PCR test detected MTC in 28% (56/198) of the BTB-suspected lesions, demonstrating higher efficiency when compared to the multiplex-PCR and conventional microbiology. Nested q-PCR can therefore be used as a complementary test in the national program for control and eradication of bovine tuberculosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Restructured Freedom configuration characteristics

NASA Technical Reports Server (NTRS)

Troutman, Patrick A.; Heck, Michael L.; Kumar, Renjith R.; Mazanek, Daniel D.

1991-01-01

In Jan. 1991, the LaRc SSFO performed an assessment of the configuration characteristics of the proposed pre-integrated Space Station Freedom (SSF) concept. Of particular concern was the relationship of solar array operation and orientation with respect to spacecraft controllability. For the man-tended configuration (MTC), it was determined that torque equilibrium attitude (TEA) seeking Control Moment Gyroscope (CMG) control laws could not always maintain attitude. The control problems occurred when the solar arrays were tracking the sun to produce full power while flying in an arrow or gravity gradient flight mode. The large solar array articulations that sometimes result from having the functions of the alpha and beta joints reversed on MTC induced large product of inertia changes that can invalidate the control system gains during an orbit. Several modified sun tracking techniques were evaluated with respect to producing a controllable configuration requiring no modifications to the CMG control algorithms. Another assessment involved the permanently manned configuration (PMC) which has a third asymmetric PV unit on one side of the transverse boom. Recommendations include constraining alpha rotations for MTC in the arrow and gravity gradient flight modes and perhaps developing new non-TEA seeking control laws. Recommendations for PMC include raising the operational altitude and moving to a symmetric configuration as soon as possible.

Effectiveness of medical taping concept in primary dysmenorrhoea: a two-armed randomized trial.

PubMed

Tomás-Rodríguez, María Isabel; Palazón-Bru, Antonio; Martínez-St John, Damian Robert James; Toledo-Marhuenda, José Vicente; Asensio-García, María del Rosario; Gil-Guillén, Vicente Francisco

2015-11-13

In 2014, we assessed the effectiveness of Medical Taping Concept (MTC) in Primary Dysmenorrhoea (PD) with a single-blind, two-armed clinical trial (NCT02114723, ClinicalTrials.gov) with a follow-up of 4 menstrual cycles (pre-intervention: 2 months; post-intervention: 2 months) in a sample formed by 129 Spanish women aged 18-30 years with PD. We had two groups: intervention group (75), MTC covering T-11 and T-12 dermatomes; control group (54), another taping in both greater trochanter areas. Our main outcome measures were: pre-intervention and post-intervention increase in pain difference measured 2 hours after commencement (2-h pain - 0-h pain); difference between the number of tablets ingested post-intervention and pre-intervention; and associated symptoms in post-intervention (fatigue, vomiting, diarrhoea, nausea and others). Pain was assessed in: abdomen, legs, head and lower back. We found significant differences (p < 0.05) for number of tablets, abdominal and leg pain. In conclusion, the intervention group had less abdominal and leg pain when pharmacological therapy was not started. Furthermore, the intervention resulted in a lower intake of tablets. Nevertheless, more studies are needed to corroborate our results and to analyze the MTC effectiveness if women do not take any tablets during the entire menstrual period.

Exercise Training Reduces Intrathoracic Fat Regardless of Defective Glucose Tolerance

PubMed Central

HONKALA, SANNA M.; MOTIANI, KUMAIL K.; ESKELINEN, JARI-JOONAS; SAVOLAINEN, ANNA; SAUNAVAARA, VIRVA; VIRTANEN, KIRSI A.; LÖYTTYNIEMI, ELIISA; KAPANEN, JUKKA; KNUUTI, JUHANI; KALLIOKOSKI, KARI K.; HANNUKAINEN, JARNA C.

2017-01-01

ABSTRACT Purpose Epicardial (EAT) and pericardial (PAT) fat masses and myocardial triglyceride content (MTC) are enlarged in obesity and insulin resistance. We studied whether the high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) similarly decrease ectopic fat in and around the heart and whether the decrease is similar in healthy subjects and subjects with defective glucose tolerance (DGT). Methods A total of 28 healthy men (body mass index = 20.7–30.0 kg·m−2, age = 40–55 yr) and 16 men with DGT (body mass index = 23.8–33.5 kg·m−2, age = 43–53 yr) were randomized into HIIT and MICT interventions for 2 wk. EAT and PAT were determined by computed tomography and MTC by 1H-MRS. Results At baseline, DGT subjects had impaired aerobic capacity and insulin sensitivity and higher levels of whole body fat, visceral fat, PAT, and EAT (P < 0.05, all) compared with healthy subjects. In the whole group, HIIT increased aerobic capacity (HIIT = 6%, MICT = 0.3%; time × training P = 0.007) and tended to improve insulin sensitivity (HIIT = 24%, MICT = 8%) as well as reduce MTC (HIIT = −42%, MICT = +23%) (time × training P = 0.06, both) more efficiently compared with MICT, and without differences in the training response between the healthy and the DGT subjects. However, both training modes decreased EAT (−5%) and PAT (−6%) fat (time P < 0.05) and not differently between the healthy and the DGT subjects. Conclusion Whole body fat, visceral fat, PAT, and EAT masses are enlarged in DGT. Both HIIT and MICT effectively reduce EAT and PAT in healthy and DGT subjects, whereas HIIT seems to be superior as regards improving aerobic capacity, whole-body insulin sensitivity, and MTC. PMID:28628064

Diagnostic impact of PET with 18F-FDG, 18F-DOPA and 3-O-methyl-6-[18F]fluoro-DOPA in recurrent or metastatic medullary thyroid carcinoma.

PubMed

Beuthien-Baumann, B; Strumpf, A; Zessin, J; Bredow, J; Kotzerke, J

2007-10-01

In patients with medullary thyroid carcinoma (MTC), rising levels of the tumour markers calcitonin and CEA after primary surgery indicate tumour recurrence or metastases. The only chance of cure is the resection of localised tumour tissue. For positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) and (18)F-dihydroxyphenylalanine ((18)F-DOPA), sensitivities of 78% and 63% have been reported, but in a considerable percentage of MTC patients the source of tumour marker elevation is not detected. The aim of this retrospective data evaluation was to compare the value of PET with (18)F-FDG, (18)F-DOPA and the amino acid tracer 3-O-methyl-6-[(18)F]fluoro-DOPA ((18)F-OMFD) in the detection of MTC recurrence. Fifteen patients with elevated calcitonin were investigated with PET as part of their individual clinical work-up. All patients underwent (18)F-FDG PET and (18)F-DOPA PET, and ten patients underwent (18)F-OMFD PET. With (18)F-FDG, seven patients showed foci in the neck, mediastinum, upper abdomen or bone. In seven patients, (18)F-DOPA revealed suspicious foci; five of these seven patients showed partially corresponding uptake of (18)F-FDG in the neck and mediastinum. Two of these patients underwent surgery and metastases were verified. With (18)F-OMFD, a small focus in the liver was suspected in one patient without a correlate on (18)F-FDG PET, (18)F-DOPA PET or conventional imaging. (18)F-FDG and (18)F-DOPA showed foci that were highly suspicious for local recurrence or metastasis of MTC, although histological verification in these patients with numerous previous surgical interventions was performed in only two patients. The amino acid tracer (18)F-OMFD had no diagnostic impact in these patients.

Technetium tc 99m-labeled red blood cells in the preoperative diagnosis of cavernous hemangioma and other vascular orbital tumors.

PubMed

Polito, Ennio; Burroni, Luca; Pichierri, Patrizia; Loffredo, Antonio; Vattimo, Angelo G

2005-12-01

To evaluate technetium Tc 99m (99mTc) red blood cell scintigraphy as a diagnostic tool for orbital cavernous hemangioma and to differentiate between orbital masses on the basis of their vascularization. We performed 99mTc red blood cell scintigraphy on 23 patients (8 female and 15 male; mean age, 47 years) affected by an orbital mass previously revealed with computed tomography (CT) and magnetic resonance imaging (MRI) and suggesting cavernous hemangioma. In our diagnosis, we considered the orbital increase delayed uptake with the typical scintigraphic pattern known as perfusion blood pool mismatch. The patients underwent biopsy or surgical treatment with transconjunctival cryosurgical extraction when possible. Single-photon emission tomography (SPET) showed intense focal uptake in the orbit corresponding to radiologic findings in 11 patients who underwent surgical treatment and pathologic evaluation (9 cavernous hemangiomas, 1 hemangiopericytoma, and 1 lymphangioma). Clinical or histologic examination of the remaining 22 patients revealed the presence of 5 lymphoid pseudotumors, 2 lymphomas, 2 pleomorphic adenomas of the lacrimal gland, 1 astrocytoma, 1 ophthalmic vein thrombosis, and 1 orbital varix. The confirmation of the preoperative diagnosis by 99mTc red blood cell scintigraphy shows that this technique is a reliable tool for differentiating cavernous hemangiomas from other orbital masses (sensitivity, 100%; specificity, 86%) when ultrasound, CT, and MRI are not diagnostic. Unfortunately, 99mTc red blood cell scintigraphy results were positive in 1 patient with hemangiopericytoma and 1 patient with lymphangioma, which showed increased uptake in the lesion on SPET images because of the vascular nature of these tumors. Therefore, in these cases, the SPET images have to be integrated with data regarding clinical preoperative evaluation and CT scans or MRI studies. On the basis of our study, a complete diagnostic picture, CT scans or MRI studies, and scintigraphic patterns can establish the preoperative diagnosis of vascular orbital tumors such as cavernous hemangioma, adult-type lymphangioma, and hemangiopericytoma.

Emerging Tuberculosis Pathogen Hijacks Social Communication Behavior in the Group-Living Banded Mongoose (Mungos mungo)

PubMed Central

Sanderson, Claire E.; Larsen, Michelle H.; Robbe-Austerman, Suelee; Williams, Mark C.; Palmer, Mitchell V.

2016-01-01

ABSTRACT An emerging Mycobacterium tuberculosis complex (MTC) pathogen, M. mungi, infects wild banded mongooses (Mungos mungo) in Northern Botswana, causing significant mortality. This MTC pathogen did not appear to be transmitted through a primary aerosol or oral route. We utilized histopathology, spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), quantitative PCR (qPCR), and molecular markers (regions of difference [RDs] from various MTC members, including region of difference 1 [RD1] from M. bovis BCG [RD1BCG], M. microti [RD1mic], and M. pinnipedii [RD1seal], genes Rv1510 [RD4], Rv1970 [RD7], Rv3877/8 [RD1], and Rv3120 [RD12], insertion element IS1561, the 16S RNA gene, and gene Rv0577 [cfp32]), including the newly characterized mongoose-specific deletion in RD1 (RD1mon), in order to demonstrate the presence of M. mungi DNA in infected mongooses and investigate pathogen invasion and exposure mechanisms. M. mungi DNA was identified in 29% of nasal planum samples (n = 52), 56% of nasal rinses and swabs (n = 9), 53% of oral swabs (n = 19), 22% of urine samples (n = 23), 33% of anal gland tissue (n = 18), and 39% of anal gland secretions (n = 44). The occurrence of extremely low cycle threshold values obtained with qPCR in anal gland and nasal planum samples indicates that high levels of M. mungi can be found in these tissue types. Histological data were consistent with these results, suggesting that pathogen invasion occurs through breaks in the nasal planum and/or skin of the mongoose host, which are in frequent contact with anal gland secretions and urine during olfactory communication behavior. Lesions in the lung, when present, occurred only with disseminated disease. No environmental sources of M. mungi DNA could be found. We report primary environmental transmission of an MTC pathogen that occurs in association with social communication behavior. PMID:27165798

Calcitonin assay in wash-out fluid after fine-needle aspiration biopsy in patients with a thyroid nodule and border-line value of the hormone.

PubMed

Massaro, F; Dolcino, M; Degrandi, R; Ferone, D; Mussap, M; Minuto, F; Giusti, M

2009-04-01

Assaying calcitonin (CT) in the wash-out fluid from fine-needle aspiration biopsies (CT-FNAB) could be useful in the diagnosis of medullary thyroid carcinoma (MTC). The aim of this study was to correlate serum CT with cytology and CT-FNAB. Twenty-seven subjects (age range 27-75 yr) were studied. FNAB was performed in a thyroid nodule (no.=16) or lymph-node (no.=1 previously operated on for MTC) or in the prevalent nodule of multinodular goiters (no.=10). CT-FNAB values obtained in 37 subjects with normal serum CT (<10 ng/l) who underwent FNAB for thyroid nodules served as a negative control. In these subjects, CTFNAB values were 8.2+/-6.4 ng/l (range 2-30 ng/l). In patients with a thyroid nodule under evaluation for MTC, serum CT and CT-FNAB values were 14.5+/-3.9 ng/l (range 10-24 ng/l) and 16.4+/-29.8 ng/l (range 2-144 ng/l), respectively. In 4 patients, CT-FNAB values were higher than the highest values found in our negative controls (30 ng/l), but cytology results were compatible with a benign thyroid lesion and pentagastrin testing was negative. In 3 cases with CT-FNAB <30 ng/l, cytology was indicative of an indeterminate or probably follicular malignant lesion and histology was negative for MTC. None of the other subjects in whom pentagastrin testing was conducted showed serum CT values >100 ng/l. Our data do not show any correlation between CT-FNAB and serum CT. In conclusion, borderline CT values in patients with thyroid nodules are not rare. Our experience suggests that CT-FNAB does not have the same importance as that reported in the literature for thyroglobulin and PTH assay in wash-out fluid after FNAB in malignant thyroid and hyperfunctioning parathyroid lesions.

Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

PubMed

Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

2016-01-01

Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

Anthropometric changes in adolescents with anorexia nervosa in response to resistance training.

PubMed

Fernandez-del-Valle, Maria; Larumbe-Zabala, Eneko; Graell-Berna, Montserrat; Perez-Ruiz, Margarita

2015-09-01

The follow-up of anthropometric percentiles such as triceps and mid-thigh skinfold thickness (TSF, MTSF), mid-upper arm and mid-thigh circumferences (MUAC, MTC), and arm and mid-thigh muscle areas (AMA, MTMA) after a resistance training might allow for detecting nutritional progress of fat and muscular tissue during the treatment of anorexia nervosa restricting (AN-R) type patients. A total of 44 AN-R patients were randomized for control (CG 13.0 ± 0.6 years) and intervention (IG 12.7 ± 0.7 years) groups after hospitalization. The intervention group underwent a resistance training program of 8 weeks following the guidelines for healthy adolescents (3 days/week; 70 % of 6 RM). All measurements were obtained prior to starting the program (PRE) and after 8 weeks of training (POST) in both groups. TSF, MTSF, MUAC, and MTC were measured, and AMA and MTMA were calculated. Data were matched with percentile tables for general population. Changes were assessed using statistical tests for categorical data. The distribution of percentile categories within the groups did not differ statistically after 8 weeks (p > 0.05). After training, 73 % of the patients were at the same percentile interval of MUAC, 18 % higher and 9 % lower, while 30 % of CG was at lower percentile categories. Further, 54 % of the IG patients remained at the same percentile interval of MTC after training, and 36 % higher, while 20 % were at lower categories in the CG. The AMA increased (32 %) after training or remained at the same interval (59 %) in the IG, while the IG showed greater frequency of percentile decreases (45 %). Anthropometric measurements could be useful for assessing muscle status in AN-R patients during the treatment process. However, exact standard deviation scores should be used instead of percentile categories to increase the sensitivity to changes in TSF, MTSF, MUAC, MTC or AMA.

Biofeedback training effects on minimum toe clearance variability during treadmill walking.

PubMed

Tirosh, Oren; Cambell, Amity; Begg, Rezaul K; Sparrow, W A

2013-08-01

A number of variability analysis techniques, including Poincaré plots and detrended fluctuation analysis (DFA) were used to investigate minimum toe clearance (MTC) control during walking. Ten young adults walked on a treadmill for 10 min at preferred speed in three conditions: (i) no-intervention baseline, (ii) with biofeedback of MTC within a target range, and (iii) no-biofeedback retention. Mean, median, standard deviation (SD), and inter quartile range of MTC during biofeedback (45.57 ± 11.65, 44.98 ± 11.57, 7.08 ± 2.61, 8.58 ± 2.77 mm, respectively) and retention (56.95 ± 20.31, 56.69 ± 20.94, 10.68 ± 5.41, 15.38 ± 10.19 mm) were significantly greater than baseline (30.77 ± 9.49, 30.51 ± 9.49, 3.04 ± 0.77, 3.66 ± 0.91 mm). Relative to baseline, skewness was reduced in biofeedback and retention but only significantly for retention (0.88 ± 0.51, 0.63 ± 0.55, and 0.40 ± 0.40, respectively). Baseline Poincaré measures (SD1 = 0.25, SD2 = 0.34) and DFA (α1 = 0.72 and α2 = 0.64) were lower than biofeedback (SD1 = 0.58, SD2 = 0.83, DFA α1 = 0.76 and α2 = 0.92) with significantly greater variability in retention compared to biofeedback only in the long-term SD2 and α2 analyses. Increased DFA longer-term correlations α2 in retention confirm that a novel gait pattern was acquired with a longer-term variability structure. Short- and long-term variability analyses were both useful in quantifying gait adaptations with biofeedback. The findings provide evidence that MTC can be modified with feedback, suggesting future applications in gait training procedures for impaired populations designed to reduce tripping risk.

Whole Genome Sequencing of Mycobacterium africanum Strains from Mali Provides Insights into the Mechanisms of Geographic Restriction

PubMed Central

Maiga, Mamoudou; Abeel, Thomas; Shea, Terrance; Desjardins, Christopher A.; Diarra, Bassirou; Baya, Bocar; Sanogo, Moumine; Diallo, Souleymane; Earl, Ashlee M.; Bishai, William R.

2016-01-01

Background Mycobacterium africanum, made up of lineages 5 and 6 within the Mycobacterium tuberculosis complex (MTC), causes up to half of all tuberculosis cases in West Africa, but is rarely found outside of this region. The reasons for this geographical restriction remain unknown. Possible reasons include a geographically restricted animal reservoir, a unique preference for hosts of West African ethnicity, and an inability to compete with other lineages outside of West Africa. These latter two hypotheses could be caused by loss of fitness or altered interactions with the host immune system. Methodology/Principal Findings We sequenced 92 MTC clinical isolates from Mali, including two lineage 5 and 24 lineage 6 strains. Our genome sequencing assembly, alignment, phylogeny and average nucleotide identity analyses enabled us to identify features that typify lineages 5 and 6 and made clear that these lineages do not constitute a distinct species within the MTC. We found that in Mali, lineage 6 and lineage 4 strains have similar levels of diversity and evolve drug resistance through similar mechanisms. In the process, we identified a putative novel streptomycin resistance mutation. In addition, we found evidence of person-to-person transmission of lineage 6 isolates and showed that lineage 6 is not enriched for mutations in virulence-associated genes. Conclusions This is the largest collection of lineage 5 and 6 whole genome sequences to date, and our assembly and alignment data provide valuable insights into what distinguishes these lineages from other MTC lineages. Lineages 5 and 6 do not appear to be geographically restricted due to an inability to transmit between West African hosts or to an elevated number of mutations in virulence-associated genes. However, lineage-specific mutations, such as mutations in cell wall structure, secretion systems and cofactor biosynthesis, provide alternative mechanisms that may lead to host specificity. PMID:26751217

A mixed treatment comparison of gabapentin enacarbil, pramipexole, ropinirole and rotigotine in moderate-to-severe restless legs syndrome.

PubMed

Sun, Ying; van Valkenhoef, Gert; Morel, Thomas

2014-11-01

A mixed treatment comparison (MTC) was performed to investigate the relative efficacy and safety of licensed pharmaceuticals for moderate-to-severe restless legs syndrome (RLS). RLS trials published over the past 10 years were identified via systematic literature searches of MEDLINE, Embase, Cochrane CENTRAL, and manufacturers' websites. MTC was performed with WinBUGS software using a Bayesian approach. Identified primary outcomes: change in International RLS Study Group Rating Scale (IRLS) at week 12 and end of maintenance (EoM). IRLS and Clinical Global Impression - Improvement Scale (CGI-I) responders, RLS-6 items and adverse events (AEs). Twenty-eight clinical trials were identified. Fifteen were included in the primary analysis. Indirect comparisons were established among gabapentin enacarbil, pramipexole, ropinirole, rotigotine and placebo. Overall, the four active treatments showed similar efficacies as assessed by changes in IRLS scores, IRLS responders, CGI-I responders, and RLS-6 scores. The sole exception was change in IRLS at week 12, for which rotigotine was likely more efficacious than ropinirole (mean difference: -2.52 [95% CrI: -4.74, -0.40]). Indirect comparisons on safety endpoints indicated ropinirole was associated with a higher risk of nausea than the other agents, and was more likely to result in discontinuations due to lack of efficacy than pramipexole. Nausea was likely more frequent with pramipexole than gabapentin enacarbil, and rotigotine was more likely to result in discontinuation due to AEs than ropinirole and pramipexole. This MTC confirmed the superiority of gabapentin enacarbil, pramipexole, ropinirole, and rotigotine above placebo in alleviating RLS symptoms. Compared to ropinirole, rotigotine showed some additional benefit in terms of change in IRLS at Week 12. Choice of RLS drugs requires careful evaluation of effectiveness and safety profiles in clinical practice. Due to lack of head-to-head trials, inconsistency could not be assessed in our analysis. Head-to-head trials on a more homogeneous population are needed to validate the MTC results.

Axitinib treatment in advanced RAI-resistant differentiated thyroid cancer (DTC) and refractory medullary thyroid cancer (MTC).

PubMed

Capdevila, Jaume; Trigo, José Manuel; Aller, Javier; Manzano, José Luís; Adrián, Silvia García; Llopis, Carles Zafón; Reig, Òscar; Bohn, Uriel; Cajal, Teresa Ramón Y; Duran-Poveda, Manuel; Astorga, Beatriz González; López-Alfonso, Ana; Martínez, Javier Medina; Porras, Ignacio; Reina, Juan Jose; Palacios, Nuria; Grande, Enrique; Cillán, Elena; Matos, Ignacio; Grau, Juan Jose

2017-10-01

Axitinib, an antiangiogenic multikinase inhibitor (MKI), was evaluated in the compassionate use programme (CUP) in Spain (October 2012-November 2014). 47 patients with advanced radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC, n  = 34) or medullary thyroid cancer (MTC, n  = 13) with documented disease progression were treated with axitinib 5 mg b.i.d. The primary efficacy endpoint was objective response rate (ORR) by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1. Progression-free survival (PFS) and adverse events (AEs) were secondary objectives. Regulatory authorities validated the CUP, and all patients signed informed consent form. Axitinib was administered as first-line therapy in 17 patients (36.2%), as second-line in 18 patients (38.3%) and as third/fourth-line in 12 patients (25.5%). With a median follow-up of 11.5 months (0-24.3), ORR was 27.7% (DTC: 29.4% and MTC: 23.1%) and median PFS was 8.1 months (95% CI: 4.1-12.2) (DTC: 7.4 months (95% CI: 3.1-11.8) and MTC: 9.4 months (95% CI: 4.8-13.9)). Better outcomes were reported with first-line axitinib, with an ORR of 53% and a median PFS of 13.6 months compared with 16.7% and 10.6 months as second-line treatment. Twelve (25.5%) patients required dose reduction to 3 mg b.i.d. All-grade AEs included asthenia (53.2%), diarrhoea (36.2%), hypertension (31.9%) and mucositis (29.8%); grade 3/4 AEs included anorexia (6.4%), diarrhoea (4.3%) and cardiac toxicity (4.3%). Axitinib had a tolerable safety profile and clinically meaningful activity in refractory and progressive thyroid cancer regardless of histology as first-line therapy. To our knowledge, this is the first time that cross-resistance between MKIs is suggested in thyroid cancer, highlighting the importance of prospective sequential clinical studies. © 2017 European Society of Endocrinology.

Dry deposition of reduced and reactive nitrogen: A surrogate surfaces approach

NASA Astrophysics Data System (ADS)

Shahin, Usama Mohammed

Nitrogen deposition constitutes an important component of acidic deposition to terrestrial surfaces. However, deposition flux and ambient concentration measurement methods and are still under development. A new sampler using water as a surrogate surface was developed in the Department of Environmental Engineering at Illinois Institute of Technology. This study investigated nitrate and ammonia dry deposition to the water surface sampler, a Nylasorb filter, a citric acid impregnated filter, and a greased strip on the dry deposition plate. The nitrogen containing species that may be responsible for nitrate dry deposition to the WSS include nitrogen monoxide (NO), nitrogen dioxide (NO2), peroxyacetyl nitrate (PAN), nitrous acid (HNO2), nitric acid (HNO3), and particulate nitrate. The experimental measurements showed that HNO3 and particulate nitrate are the major nitrate contributors to the WSS. Ammonia sources to the water surface are ammonia gas (NH3) and ammonium (NH4+). The experimental results showed that these two species are the sole sources to ammonium deposition. Comparison between the measured deposition velocity of SO2, and HNO3, shows that their dry deposition velocities are statistically the same at the 95% confidence level and NH3 deposition velocity and the water evaporation rate are also the same. It was also shown that the air side MTC of two different compounds were correlated to the square root of the inverse of the molecular weight for compounds. The measured MTC was tested by the application of two models, the resistance model and the water evaporation model. The resistance model prediction of the MTC was very close to the measured value but the evaporation model prediction was not. This result is compatible with the finding of Yi, (1997) who used the same WSS for measurements of SO2. The experimental data collected in this research project was used to develop an empirical model to measure the MTC that is [kl/over D] = 0.0426 ([lv/rho/over /mu])0.8([/mu/over /rho [ D

Radiolabeling of rituximab with (188)Re and (99m)Tc using the tricarbonyl technology.

PubMed

Dias, Carla Roberta; Jeger, Simone; Osso, João Alberto; Müller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert; Schibli, Roger

2011-01-01

The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20(+) B-cell tumors. Rituximab radiolabeled with β(-) emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the (99m)Tc- and (188)Re-tricarbonyl core (IsoLink technology). The native format of the antibody (RTX(wt)) as well as a reduced form (RTX(red)) was labeled with (99m)Tc/(188)Re(CO)(3). The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. The radiolabeling efficiency and kinetics of RTX(red) were superior to that of RTX(wt) ((99m)Tc: 98% after 3 h for RTX(red) vs. 70% after 24 h for RTX(wt)). (99m)Tc(CO)(3)-RTX(red) was used without purification for in vitro and in vivo studies whereas (188)Re(CO)(3)-RTX(red) was purified to eliminate free (188)Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37 °C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of (99m)Tc(CO)(3)-RTX(red) but not with pre-purified (188)Re(CO)(3)-RTX(red). Both conjugates revealed high binding affinity to the CD20 antigen (K(d) = 5-6 nM). Tumor uptake of (188)Re(CO)(3)-RTX(red) was 2.5 %ID/g and 0.8 %ID/g for (99m)Tc(CO)(3)-RTX(red) 48 h after injection. The values for other organs and tissues were similar for both compounds, for example the tumor-to-blood and tumor-to-liver ratios were 0.4 and 0.3 for (99m)Tc(CO)(3)-RTX(red) and for (188)Re(CO)(3)-RTX(red) 0.5 and 0.5 (24 h pi). Rituximab could be directly and stably labeled with the matched pair (99m)Tc/(188)Re using the IsoLink technology under retention of the biological activity. Labeling kinetics and yields need further improvement for potential routine application in radioimmunodiagnosis and therapy. Copyright © 2011 Elsevier Inc. All rights reserved.

Simultaneous acquisition of (99m)Tc- and (123)I-labeled radiotracers using a preclinical SPECT scanner with CZT detectors.

PubMed

Kobayashi, Masato; Matsunari, Ichiro; Nishi, Kodai; Mizutani, Asuka; Miyazaki, Yoshiharu; Ogai, Kazuhiro; Sugama, Jyunko; Shiba, Kazuhiro; Kawai, Keiichi; Kinuya, Seigo

2016-05-01

Simultaneous acquisition of (99m)Tc and (123)I was evaluated using a preclinical SPECT scanner with cadmium zinc telluride (CZT)-based detectors. 10-ml cylindrical syringes contained about 37 MBq (99m)Tc-tetrofosmin ((99m)Tc-TF) or 37 MBq (123)I-15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid ((123)I-BMIPP) were used to assess the relationship between these SPECT radioactive counts and radioactivity. Two 10-ml syringes contained 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP to assess the influence of (99m)Tc upscatter and (123)I downscatter, respectively. A rat-sized cylindrical phantom also contained both 100 or 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. The two 10-ml syringes and phantom were scanned using a pinhole collimator for rats. Myocardial infarction model rats were examined using 300 MBq (99m)Tc-TF and 100 MBq (123)I-BMIPP. Two 1-ml syringes contained 105 MBq (99m)Tc-labeled hexamethylpropyleneamine oxime ((99m)Tc-HMPAO) and 35 MBq (123)I-labeled N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ((123)I-FP-CIT). The two 1-ml syringes were scanned using a pinhole collimator for mice. Normal mice were examined using 105 MBq (99m)Tc-HMPAO and 35 MBq (123)I-FP-CIT. The relationship between SPECT radioactive counts and radioactivity was excellent. Downscatter contamination of (123)I-BMIPP exhibited fewer radioactive counts for 300 MBq (99m)Tc-TF without scatter correction (SC) in 125-150 keV. There was no upscatter contamination of (99m)Tc-TF in 150-175 keV. In the rat-sized phantom, the radioactive count ratio decreased to 4.0 % for 300 MBq (99m)Tc-TF without SC in 125-150 keV. In the rats, myocardial images and radioactive counts of (99m)Tc-TF with the dual tracer were identical to those of the (99m)Tc-TF single injection. Downscatter contamination of (123)I-FP-CIT was 4.2 % without SC in 125-150 keV. In the first injection of (99m)Tc-HMPAO and second injection of (123)I-FP-CIT, brain images and radioactive counts of (99m)Tc-HMPAO with the dual tracer in normal mice also were the similar to those of the (99m)Tc-HMPAO single injection. In the first injection of (123)I-FP-CIT and second injection of (99m)Tc-HMPAO, the brain images and radioactive counts with the dual tracer were not much different from those of the (123)I-FP-CIT single injection. Dual-tracer imaging of (99m)Tc- and (123)I-labeled radiotracers is feasible in a preclinical SPECT scanner with CZT detector. When higher radioactivity of (99m)Tc-labeled radiotracers relative to (123)I-labeled radiotracers is applied, correction methods are not necessarily required for the quantification of (99m)Tc- and (123)I-labeled radiotracers when using a preclinical SPECT scanner with CZT detector.

Shear wave elastography in medullary thyroid carcinoma diagnostics

PubMed Central

Gumińska, Anna; Bakuła-Zalewska, Elwira; Mlosek, Krzysztof; Słapa, Rafał Z.; Wareluk, Paweł; Krauze, Agnieszka; Ziemiecka, Agnieszka; Migda, Bartosz; Jakubowski, Wiesław; Dedecjus, Marek

2015-01-01

Shear wave elastography (SWE) is a modern method for the assessment of tissue stiffness. There has been a growing interest in the use of this technique for characterizing thyroid focal lesions, including preoperative diagnostics. Aim The aim of the study was to assess the clinical usefulness of SWE in medullary thyroid carcinoma (MTC) diagnostics. Materials and methods A total of 169 focal lesions were identified in the study group (139 patients), including 6 MTCs in 4 patients (mean age: 45 years). B-mode ultrasound and SWE were performed using Aixplorer (SuperSonic, Aix-en-Provence), with a 4–15 MHz linear probe. The ultrasound was performed to assess the echogenicity and echostructure of the lesions, their margin, the halo sign, the height/width ratio (H/W ratio), the presence of calcifications and the vascularization pattern. This was followed by an analysis of maximum and mean Young's (E) modulus values for MTC (EmaxLR, EmeanLR) and the surrounding thyroid tissues (EmaxSR, EmeanSR), as well as mean E-values (EmeanLRz) for 2 mm region of interest in the stiffest zone of the lesion. The lesions were subject to pathological and/or cytological evaluation. Results The B-mode assessment showed that all MTCs were hypoechogenic, with no halo sign, and they contained micro- and/ or macrocalcifications. Ill-defined lesion margin were found in 4 out of 6 cancers; 4 out of 6 cancers had a H/W ratio > 1. Heterogeneous echostructure and type III vascularity were found in 5 out of 6 lesions. In the SWE, the mean value of EmaxLR for all of the MTCs was 89.5 kPa and (the mean value of EmaxSR for all surrounding tissues was) 39.7 kPa Mean values of EmeanLR and EmeanSR were 34.7 kPa and 24.4 kPa, respectively. The mean value of EmeanLRz was 49.2 kPa. Conclusions SWE showed MTCs as stiffer lesions compared to the surrounding tissues. The lesions were qualified for fine needle aspiration biopsy based on B-mode assessment. However, the diagnostic algorithm for MTC is based on the measurement of serum calcitonin levels, B-mode ultrasound and FNAB. PMID:26807293

Molecular Imaging Probes for Positron Emission Tomography and Optical Imaging of Sentinel Lymph Node and Tumor

NASA Astrophysics Data System (ADS)

Qin, Zhengtao

Molecular imaging is visualizations and measurements of in vivo biological processes at the molecular or cellular level using specific imaging probes. As an emerging technology, biocompatible macromolecular or nanoparticle based targeted imaging probes have gained increasing popularities. Those complexes consist of a carrier, an imaging reporter, and a targeting ligand. The active targeting ability dramatically increases the specificity. And the multivalency effect may further reduce the dose while providing a decent signal. In this thesis, sentinel lymph node (SLN) mapping and cancer imaging are two research topics. The focus is to develop molecular imaging probes with high specificity and sensitivity, for Positron Emission Tomography (PET) and optical imaging. The objective of this thesis is to explore dextran radiopharmaceuticals and porous silicon nanoparticles based molecular imaging agents. Dextran polymers are excellent carriers to deliver imaging reporters or therapeutic agents due to its well established safety profile and oligosaccharide conjugation chemistry. There is also a wide selection of dextran polymers with different lengths. On the other hand, Silicon nanoparticles represent another class of biodegradable materials for imaging and drug delivery. The success in fluorescence lifetime imaging and enhancements of the immune activation potency was briefly discussed. Chapter 1 begins with an overview on current molecular imaging techniques and imaging probes. Chapter 2 presents a near-IR dye conjugated probe, IRDye 800CW-tilmanocept. Fluorophore density was optimized to generate the maximum brightness. It was labeled with 68Ga and 99mTc and in vivo SLN mapping was successfully performed in different animals, such as mice, rabbits, dogs and pigs. With 99mTc labeled IRDye 800CW-tilmanocept, chapter 3 introduces a two-day imaging protocol with a hand-held imager. Chapter 4 proposed a method to dual radiolabel the IRDye 800CW-tilmanocept with both 68Ga and 99mTc. Chapter 5 introduces a 68Ga metal chelating bioorthogonal tetrazine dextran probe for multistep imaging of a colon cancer. Chapter 6 presents the synthesis and in vivo evaluation of a Hepatocellular Carcinoma targeting PET probe 68Ga-Insulin-Dextran. Chapter 7 discusses a novel method to prepare silicon nanoparticles with great yield and size control. The last chapter 8 concludes all probes developed in this thesis and their clinical relevance.

Magnetic core mesoporous silica nanoparticles doped with dacarbazine and labelled with 99mTc for early and differential detection of metastatic melanoma by single photon emission computed tomography.

PubMed

Portilho, Filipe Leal; Helal-Neto, Edward; Cabezas, Santiago Sánchez; Pinto, Suyene Rocha; Dos Santos, Sofia Nascimento; Pozzo, Lorena; Sancenón, Félix; Martínez-Máñez, Ramón; Santos-Oliveira, Ralph

2018-02-27

Cancer is responsible for more than 12% of all causes of death in the world, with an annual death rate of more than 7 million people. In this scenario melanoma is one of the most aggressive ones with serious limitation in early detection and therapy. In this direction we developed, characterized and tested in vivo a new drug delivery system based on magnetic core-mesoporous silica nanoparticle that has been doped with dacarbazine and labelled with technetium 99 m to be used as nano-imaging agent (nanoradiopharmaceutical) for early and differential diagnosis and melanoma by single photon emission computed tomography. The results demonstrated the ability of the magnetic core-mesoporous silica to be efficiently (>98%) doped with dacarbazine and also efficiently labelled with 99mTc (technetium 99 m) (>99%). The in vivo test, using inducted mice with melanoma, demonstrated the EPR effect of the magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable when injected intratumorally and the possibility to be used as systemic injection too. In both cases, magnetic core-mesoporous silica nanoparticles doped with dacarbazine and labelled with technetium 99 metastable showed to be a reliable and efficient nano-imaging agent for melanoma.

A prototype wireless inertial-sensing device for measuring toe clearance.

PubMed

Lai, Daniel T H; Charry, E; Begg, R; Palaniswami, M

2008-01-01

Tripping and slipping are serious health concerns for the elderly because they result in life threatening injuries i.e., fractures and high medical costs. Our recent work in detection of tripping gait patterns has demonstrated that minimum toe clearance (MTC) is a sensitive falls risk predictor. MTC measurement has previously been done in gait laboratories and on treadmills which potentially imposes controlled walking conditions. In this paper, we describe a prototype design of a wireless device for monitoring vertical toe clearance. The sensors consists of a tri-axis accelerometer and dual-axis gyroscope connected to Crossbow sensor motes for wireless data transmission. Sensor data are transmitted to a laptop and displayed on a Matlab graphic user interface (GUI). We have performed zero base and treadmill experiments to investigate sensor performance to environmental variations and compared the calculated toe clearance against measurements made by an Optotrak motion system. It was found that device outputs were approximately independent of small ambient temperature variations, had a reliable range of 20m indoors and 50m outdoors and a maximum transmission rate of 20 packets/s. Toe clearance measurements were found to follow the Optotrak measurement trend but could be improved further by dealing with double integration errors and improving data transmission rates.

Scintigraphic scoring system for grading severity of gastro-esophageal reflux on 99mTc sulfur colloid gastro-esophageal reflux scintigraphy: A prospective study of 39 cases with pre and post treatment assessment.

PubMed

Puranik, Ameya D; Nair, Gopinathan; Aggarwal, Rajiv; Bandyopadhyay, Abhijit; Shinto, Ajit; Zade, Anand

2013-04-01

The study aimed at developing a scoring system for scintigraphic grading of gastro-esophageal reflux (GER), on gastro-esophageal reflux scintigraphy (GERS) and comparison of clinical and scintigraphic scores, pre- and post-treatment. A total of 39 cases with clinically symptomatic GER underwent 99mTc sulfur colloid GERS; scores were assigned based on the clinical and scintigraphic parameters. Post domperidone GERS was performed after completion of treatment. Follow up GERS was performed and clinical and scintigraphic parameters were compared with baseline parameters. Paired t-test on pre and post domperidone treatment clinical scores showed that the decline in post-treatment scores was highly significant, with P value < 0.001. The scintigraphic scoring system had a sensitivity of 93.9% in assessing treatment response to domperidone, specificity of 83.3% i.e., 83.3% of children with no decline in scintigraphic scores show no clinical response to Domperidone. The scintigraphic scoring system had a positive predictive value of 96.9% and a negative predictive value of 71.4%. GERS with its quantitative parameters is a good investigation for assessing the severity of reflux and also for following children post-treatment.

Current Advances in Thyroid Cancer Management. Are We Ready for the Epidemic Rise of Diagnoses?

PubMed

Rusinek, Dagmara; Chmielik, Ewa; Krajewska, Jolanta; Jarzab, Michal; Oczko-Wojciechowska, Malgorzata; Czarniecka, Agnieszka; Jarzab, Barbara

2017-08-22

A rising incidence of thyroid cancers (TCs) mainly small tumors, observed during recent years, lead to many controversies regarding treatment strategies. TCs represent a distinct molecular background and clinical outcome. Although in most cases TCs are characterized by a good prognosis, there are some aggressive forms, which do not respond to standard treatment. There are still some questions, which have to be resolved to avoid dangerous simplifications in the clinical management. In this article, we focused on the current advantages in preoperative molecular diagnostic tests and histopathological examination including noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). We discussed the controversies regarding the extent of thyroid surgery and adjuvant radioiodine therapy, as well as new treatment modalities for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Considering medullary thyroid cancer (MTC), we analyzed a clinical management based on histopathology and RET (ret proto-oncogene) mutation genotype, disease follow-up with a special attention to serum calcitonin doubling time as an important prognostic marker, and targeted therapy applied in advanced MTC. In addition, we provided some data regarding anaplastic thyroid cancer (ATC), a highly lethal neoplasm, which lead to death in nearly 100% of patients due to the lack of effective treatment options.

Telomere content measurement in human hematopoietic cells: Comparative analysis of qPCR and Flow-FISH techniques.

PubMed

Wand, Taylor; Fang, Mike; Chen, Christina; Hardy, Nathan; McCoy, J Philip; Dumitriu, Bogdan; Young, Neal S; Biancotto, Angélique

2016-10-01

Abnormal telomere lengths have been linked to cancer and other hematologic disorders. Determination of mean telomere content (MTC) is traditionally performed by Southern blotting and densitometry, giving a mean telomere restriction fragment (TRF) value for the total cell population studied. Here, we compared a quantitative Polymerase Chain Reaction approach (qPCR) and a flow cytometric approach, fluorescence in situ hybridization (Flow-FISH), to evaluate telomere content distribution in total patient peripheral blood mononuclear cells or specific cell populations. Flow-FISH is based on in situ hybridization using a fluorescein-labeled peptide nucleic acid (PNA) (CCCTAA) 3 probe and DNA staining with propidium iodide. We showed that both qPCR and Flow-FISH provide a robust measurement, with Flow-FISH measuring a relative content longer than qPCR at a single cell approach and that TRF2 fluorescence intensity did not correlate with MTC. Both methods showed comparable telomere content reduction with age, and the rate of relative telomere loss was similar. Published 2016 Wiley Periodicals Inc. This article is a US government work and, as such, is in the public domain in the United States of America. Published 2016 Wiley Periodicals Inc. This article is a US government work and, as such, is in the public domain in the United States of America.

[Importance of parathyroid SPECT and 99mTc scintigraphy, and of clinical, laboratorial, ultrasonographic and citologic correlation in the pre-operative localization of the parathyroid adenoma - pictorial assay].

PubMed

Oliveira, Marco Antônio Condé de; Maeda, Sérgio Setsuo; Dreyer, Patrícia; Lobo, Alberto; Andrade, Victor Piana de; Hoff, Ana O; Biscolla, Rosa Paula Mello; Smanio, Paola; Brandão, Cynthia M A; Vieira, José G

2010-06-01

In patients with primary hyperparathyroidism, candidates for surgical intervention, the parathyroid pre-operative localization is of fundamental importance in planning the appropriate surgical approach. The additional acquisition of SPECT and Technetium-99m images, during parathyroid scintigraphy with Sestamibi, is not common practice. Usually, only planar image acquisition, 15 minutes prior and 2 hours after radiopharmaceutical administration, is performed. In our experience, the complete protocol in parathyroid scintigraphy increases the accuracy of pre-operative parathyroid localization. The complete utilization of all available nuclear medicine methods (SPECT e 99mTc) and image interpretation in a multidisciplinary context can improve the accuracy of parathyroid scintigraphy.

Recycle of enriched Mo targets for economic production of 99Mo/ 99mTc medical isotope without use of enriched uranium

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

Tkac, Peter; Vandegrift, George F.

2015-08-09

A new recycle process for recovery of enriched 98Mo or 100Mo used for production of 99Mo/ 99mTc medical isotope was developed. In this process, Mo is precipitated from spent NorthStar Mo/Tc generator solution containing ~200 g/L Mo as K 2MoO 4 in 5 M KOH using acetic acid and then washed with nitric acid. High purification factors from potassium were achieved, and typical Mo recovery yields were ~95 %. In conclusion, the recycle process was performed with up to 260 g of Mo per batch and can be easily implemented for processing of up to 400 g of Mo.

Re and 99mTc Tricarbonyl Probes for Target-Specific Detection of Melanoma and Sentinel Lymph Node

NASA Astrophysics Data System (ADS)

Morais, Mauricio da Silva

The work described in this thesis aimed at the development of M(I) (M = 99mTc, Re) specific probes for the detection of malignant melanoma and sentinel lymph node (SLN) through the in vivo targeting of membrane receptors. In the former case we have designed M(CO)3-complexes stabilized by tridentate chelators containing a pyrazolyl-diamine chelating unit (N,N,N donor atom set) and pendant alpha-melanocyte-stimulating hormone (alpha-MSH) derivatives for targeting the melanocortin receptor 1 (MC1R), which is overexpressed in melanotic and amelanotic human melanoma cells. (Abstract shortened by ProQuest.). None None None None None None None None None None None None None None None None None

Attenuation of radionuclide activity by metal-cup arthroplasties

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

Rosenthall, L.; Rosenthall, S.

1985-04-01

The half-value layers of stainless steel, bone cement, and polyethylene were measured for /sup 99m/Tc, /sup 67/Ga, /sup 111/In, and /sup 201/TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in /sup 99m/Tc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. /sup 67/Ga, using the 184 and 300 keV peaks, and /sup 111/In have greater half-value layers than /sup 99m/Tc and are subject to less attenuation bymore » the metallic cup.« less

Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion.

PubMed

Clarke, Charlene; Van Helden, Paul; Miller, Michele; Parsons, Sven

2016-04-26

Members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB) in both animals and humans. In this article, three animal-adapted MTC strains that are endemic to the southern African subregion - that is, Mycobacterium suricattae, Mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. Moreover, factors influencing the transmission and establishment of TB pathogens in novel host populations, including ecological, immunological and genetic factors of both the host and pathogen, are discussed. The risks associated with these infections are currently unknown and further studies will be required for greater understanding of this disease in the context of the southern African ecosystem.

Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion.

PubMed

Clarke, Charlene; Van Helden, Paul; Miller, Michele; Parsons, Sven

2016-04-26

Members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB) in both animals and humans. In this article, three animal-adapted MTC strains that are endemic to the southern African subregion - that is, Mycobacterium suricattae, Mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. Moreover, factors influencing the transmission and establishment of TB pathogens in novel host populations, including ecological, immunological and genetic factors of both the host and pathogen, are discussed. The risks associated with these infections are currently unknown and further studies will be required for greater understanding of this disease in the context of the southern African ecosystem.

Synthesis, Characterization and Biological Studies of 99mTc and 188Re Peptides

NASA Astrophysics Data System (ADS)

Sanders, Vanessa

Radiopharmaceuticals are very powerful diagnostic tools for evaluation of a host of medical conditions. These drugs are labeled with radioactive isotopes, which are utilized to create pictures of areas of interest through absorption of the drug. They are currently in high demand due to their ability to image areas that traditional imaging devices cannot. The radioisotope 99mTc, with a half-life of 6.01 hours and a 140 keV gamma emission, is central to many radiopharmaceutical compounds. This isotope is easily obtained from a 99Mo-99mTc generator, through beta decay and column chromatography separations. Very little technetium, less than 6 ng, is needed to label the pharmaceuticals for use in-vivo. Another radioisotope 188Re is also important due to its ability to be used for therapy while being tracked throughout the body. Radiotherapy gives radiopharmaceuticals a huge advantage by their ability to destroy rapidly growing cells. One of the main reasons there is interest in rhenium pharmaceuticals is the chemical similarity between it and technetium. The 188Re isotope also has a considerably short half-life of approximately 17 hours and has emission energy of 155 keV. The 188Re isotope is separated from 188W-188Re generator, analogously to the 99Mo-99mTc generator. The ligand used in this work is a pentapepetide macrocyclic ligand. This ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for imaging and therapeutic in vivo agents. Ligands are chosen based on their in-situ biological behavior, and are used in the complexation with technetium and rhenium. Understanding and exploiting technetium and rhenium chemistry can provide insight into the reaction mechanisms and coordination chemistry of these compounds. The exploration of various oxidation states as a function of the ligands used and the reaction conditions can help develop novel radiopharmaceuticals. The investigations of the manipulation of oxidation states have the possible application to simplify the synthesis of the pharmaceutical. The versatility of the oxidation states of these metals leads to numerous possibilities in developing new radiopharmaceuticals. The coordination chemistry and reaction mechanisms must be efficiently characterized to ensure the reproducibility of the radiopharmaceutical. The current study focuses on technetium and rhenium complexes with peptides. These complexes have become increasing interesting for their use in diagnostic and therapeutic radiopharmaceuticals. The characterization of the complexation of Tc(V), and Rh(V) with the pentapeptide KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine) will be discussed. Complexes will be characterized by High Performance Liquid Chromatography (HPLC), UV-Visible Spectroscopy, Proton NMR, Circular Dichroism (CD), and Electrospray Ionization Mass Spectroscopy, to compare them to current radiopharmaceuticals. Information on the underlying reactions and coordination will be discussed.

Impact of Gate 99mTc DTPA GFR, Serum Creatinine and Urea in Diagnosis of Patients with Chronic Kidney Failure

PubMed Central

Miftari, Rame; Nura, Adem; Topçiu-Shufta, Valdete; Miftari, Valon; Murseli, Arbenita; Haxhibeqiri, Valdete

2017-01-01

Aim: The aim of this study was determination of validity of 99mTcDTPA estimation of GFR for early detection of chronic kidney failure Material and methods: There were 110 patients (54 males and 56 females) with kidney disease referred for evaluation of renal function at UCC of Kosovo. All patients were included in two groups. In the first group were included 30 patients confirmed with renal failure, whereas in the second group were included 80 patients with other renal disease. In study were included only patients with ready results of creatinine, urea and glucose in the blood serum. For estimation of GFR we have used the Gate GFR DTPA method. The statistical data processing was conducted using statistical methods such as arithmetic average, the student t-test, percentage or rate, sensitivity, specificity and accuracy of the test. Results: The average age of all patients was 36 years old. The average age of female was 37 whereas of male 35. Patients with renal failure was significantly older than patients with other renal disease (p<0.005). Renal failure was found in 30 patients (27.27%). The concentration of urea and creatinine in blood serum of patients with renal failure were significantly higher than in patients with other renal disease (P< 0.00001). GFR in patients with renal failure were significantly lower than in patients with other renal disease, 51.75 ml/min (p<0.00001). Sensitivity of uremia and creatininemia for detection of renal failure were 83.33%, whereas sensitivity of 99mTcDTPA GFR was 100%. Specificity of uraemia and creatininemia were 63% whereas specificity of 99mTcDTPA GFR was 47.5%. Diagnostic accuracy of blood urea and creatinine in detecting of renal failure were 69%, whereas diagnostic accuracy of 99mTcDTPA GFR was 61.8%. Conclusion: Gate 99mTc DTPA scintigraphy in collaboration with biochemical tests are very sensitive methods for early detection of patients with chronic renal failure. PMID:28883673

A gluten-free vegan meal for gastric emptying scintigraphy: establishment of reference values and its utilization in the evaluation of diabetic gastroparesis.

PubMed

Somasundaram, Vijay Harish; Subramanyam, Padma; Palaniswamy, Shanmuga Sundaram

2014-11-01

The aim of this study was to describe the preparation of radiolabeled idli (savory cake) meal for use as an alternate to the egg white sandwich (EWS) meal in gastric emptying scintigraphy (GES). Furthermore, the aim of this study was to establish normal emptying rates for this meal and present our experience in using it in the evaluation of diabetic gastroparesis. The meal was prepared using a universally available packaged mix labeled with 1 mCi 99mTc sulfur colloid, and the stability of labeling was tested up to 4 hours in simulated gastric fluid. One hundred thirteen healthy volunteers (aged 20-78 years; 54 women, 59 men) underwent GES study using the idli meal. Gastric retention at one-half, 1, 2, and 4 hours after ingestion of the meal was estimated, and the normal limits were set using the fifth and 95th percentile values at each period. Having established its normal emptying rates, the idli meal was further used to evaluate 70 patients suspected with diabetic gastroparesis. The idli meal, with a calorific value ≈282 kcal, has a relatively higher fat content (8% of total mass) than EWS. More than 96% of 99mTc sulfur colloid remained bound to the meal after 4 hours suspension in simulated gastric fluid. Gastric retention greater than 30% and greater than 6% at 2 hours and 4 hours, respectively, indicated delayed gastric emptying, whereas retention less than 30% at 1 hour suggested rapid emptying. Among patients suspected with diabetic gastroparesis, delayed gastric emptying was identified in 76%, and rapid emptying was seen in 4.2%. Radiolabeled idli meal is a good alternative to EWS meal for routine GES, especially among patients with specific dietary restrictions.

Long-term climate record inferred from early-middle Pleistocene amphibian and squamate reptile assemblages at the Gran Dolina Cave, Atapuerca, Spain.

PubMed

Blain, Hugues-Alexandre; Bailon, Salvador; Cuenca-Bescós, Gloria; Arsuaga, Juan Luis; Bermúdez de Castro, José Maria; Carbonell, Eudald

2009-01-01

The Gran Dolina cave site is famous for having delivered some of the oldest hominin remains of Western Europe (Homo antecessor, ca. 960 ka). Moreover, the evidence of lithic industries throughout the long vertical section suggests occupation on the part of hominins from the latest early Pleistocene (levels TD3/4, TD5, and TD6) to the late middle Pleistocene (level TD10). The Gran Dolina Sondeo Sur (TDS) has furnished a great number of small-vertebrate remains; among them some 40,000 bones are attributed to amphibians and squamates. Although they do not differ specifically from the extant herpetofauna of the Iberian Peninsula, the overlap of their current distribution areas (= mutual climatic range method) in Spain can provide mean annual temperatures (MAT), the mean temperatures of the coldest (MTC) and warmest (MTW) months, and mean annual precipitation (MAP) estimations for each sub-level, and their change can be studied throughout the sequence. Results from the squamate and amphibian study indicate that during hominin occupation the MAT (10-13 degrees C) was always slightly warmer than at present in the vicinity of the Gran Dolina Cave, and the MAP (800-1000mm) was greater than today in the Burgos area. Climatic differences between "glacial" and "interglacial" phases are poorly marked. Summer temperatures (MTW) show stronger oscillations than winter temperatures (MTC), but seasonality remains almost unchanged throughout the sequence. These results are compared with those for large mammals, small mammals, and pollen analysis, giving a scenario for the palaeoclimatic conditions that occurred during the early to middle Pleistocene in Atapuerca, and hence a scenario for the hominins that once lived in the Sierra de Atapuerca.

Using mixed treatment comparisons and meta-regression to perform indirect comparisons to estimate the efficacy of biologic treatments in rheumatoid arthritis.

PubMed

Nixon, R M; Bansback, N; Brennan, A

2007-03-15

Mixed treatment comparison (MTC) is a generalization of meta-analysis. Instead of the same treatment for a disease being tested in a number of studies, a number of different interventions are considered. Meta-regression is also a generalization of meta-analysis where an attempt is made to explain the heterogeneity between the treatment effects in the studies by regressing on study-level covariables. Our focus is where there are several different treatments considered in a number of randomized controlled trials in a specific disease, the same treatment can be applied in several arms within a study, and where differences in efficacy can be explained by differences in the study settings. We develop methods for simultaneously comparing several treatments and adjusting for study-level covariables by combining ideas from MTC and meta-regression. We use a case study from rheumatoid arthritis. We identified relevant trials of biologic verses standard therapy or placebo and extracted the doses, comparators and patient baseline characteristics. Efficacy is measured using the log odds ratio of achieving six-month ACR50 responder status. A random-effects meta-regression model is fitted which adjusts the log odds ratio for study-level prognostic factors. A different random-effect distribution on the log odds ratios is allowed for each different treatment. The odds ratio is found as a function of the prognostic factors for each treatment. The apparent differences in the randomized trials between tumour necrosis factor alpha (TNF- alpha) antagonists are explained by differences in prognostic factors and the analysis suggests that these drugs as a class are not different from each other. Copyright (c) 2006 John Wiley & Sons, Ltd.

Novel potential diagnostic test for Mycobacterium tuberculosis complex using combined immunomagnetic separation (IMS) and PCR-CTPP.

PubMed

Intorasoot, S; Tharinjaroen, C S; Phunpae, P; Butr-Indr, B; Anukool, U; Intachai, K; Orrapin, S; Apiratmateekul, N; Arunothong, S; Suthachai, V; Saengsawang, K; Khamnoi, P; Pata, S; Kasinrerk, W; Tragoolpua, K

2016-08-01

To exploit immunomagnetic separation combined with PCR with confronting two-pair primers (IMS-PCR-CTPP) as a rapid method for detection of Mycobacterium tuberculosis complex (MTC) and identification of Mycobacterium bovis from sputum specimens. Monoclonal antibody (mAb) against the mycobacterial antigen, 85B (Ag85B), was coupled with magnetic particles for specific immunomagnetic separation (IMS) of Mycobacterium spp. Immunofluorescence assay indicated the capability of mAb to bind to Ag85B in both the recombinant and the native form. The IMS combined with PCR-CTPP targeting the mycobacterial lep B gene was further implemented using 133 sputum samples with acid-fast bacilli grading from negative to 3+. The results showed the sensitivity and specificity of IMS-PCR-CTPP vs gold standard culture method were 89·9 and 88·6% respectively. The IMS-PCR-CTPP method shortens the time for tuberculosis (TB) diagnosis from months to a day. This method is also suitable for investigation of MTC and epidemiological study of Myco. bovis in sputum specimens. This study is the first report emphasizing the combination of IMS and PCR-CTPP for the detection of MTC and simultaneous identification of Myco. bovis from sputum. It could be used for TB diagnosis in resource-limited countries with high TB burden. © 2016 The Society for Applied Microbiology.

Method for generating a crystalline {sup 99}MoO{sub 3} product and the isolation {sup 99m}Tc compositions therefrom

DOEpatents

Bennett, R.G.; Christian, J.D.; Kirkham, R.J.; Tranter, T.J.

1998-09-01

An improved method is described for producing {sup 99m}Tc compositions. {sup 100}Mo metal is irradiated with photons in a particle (electron) accelerator to produce {sup 99}Mo metal which is dissolved in a solvent. A solvated {sup 99}Mo product is then dried to generate a supply of {sup 99}MoO{sub 3} crystals. The crystals are thereafter heated at a temperature which will sublimate the crystals and form a gaseous mixture containing vaporized {sup 99m}TcO{sub 3} and vaporized {sup 99m}TcO{sub 2} but will not cause the production of vaporized {sup 99}MoO{sub 3}. The mixture is then combined with an oxidizing gas to generate a gaseous stream containing vaporized {sup 99m}Tc{sub 2}O{sub 7}. Next, the gaseous stream is cooled to a temperature sufficient to convert the vaporized {sup 99m}Tc{sub 2}O{sub 7} into a condensed {sup 99m}Tc-containing product. The product has high purity levels resulting from the use of reduced temperature conditions and ultrafine crystalline {sup 99}MoO{sub 3} starting materials with segregated {sup 99m}Tc compositions therein which avoid the production of vaporized {sup 99}MoO{sub 3} contaminants. 1 fig.

In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.

PubMed

Dar, Ume-Kalsoom; Khan, Irfanullah; Javed, Muhammad; Ali, Muhammad; Hyder, Syed Waqar; Murad, Sohail; Anwar, Jamil

2013-03-01

In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.

Imaging Lung Clearance of Radiolabeled Tumor Cells to Study Mice with Normal, Activated or Depleted Natural Killer (NK) Cells

NASA Astrophysics Data System (ADS)

Kulkarni, P. V.; Bennett, M.; Constantinescu, A.; Arora, V.; Viguet, M.; Antich, P.; Parkey, R. W.; Mathews, D.; Mason, R. P.; Oz, O. K.

2003-08-01

Lung clearance of 51CR and 125I iododeoxyuridine (IUDR) labeled cancer cells assess NK cell activity. It is desirable to develop noninvasive imaging technique to assess NK activity in mice. We labeled target YAC-1 tumor cells with 125I, 111In, 99mTc, or 67Ga and injected I.V. into three groups of BALB/c mice. Animals were treated with medium (group I), 300mg/kg cyclophosmamide (CY) to kill NK cell (group II), or anti-LY49C/1) (ab')2 mAb to augment NK function (group III). Lungs were removed 15 min or 2 h later for tissue counting. Control and treated mice were imaged every 5 min with a scintillating camera for 1 h after 15 min of infusion of the 111In labeled cells. Lung clearance increased after 15 min (lodging: 60-80%) and (2 h retention: 3-7%). Similar results were obtained with all the isotopes studied. Images distinguished the control and treated mice for lung activity. Cells labeled with 111In, 99mTc or 67Ga are cleared similar to those labeled with 51Cr or 125I. NK cell destruction of tumor cells may be assessed by noninvasive imaging method either by SPECT (99mTc, 111In, 67Ga) or by PET (68Ga).

Initial study : Caldecott improvement project.

DOT National Transportation Integrated Search

2002-11-01

The California Department of Transportation (Caltrans) and the Federal Highway : Administration (FHWA), in cooperation with the Metropolitan Transportation : Commission (MTC), the Alameda County Congestion Management Agency : (ACCMA), and the Contra ...

Prevalence of tuberculous lesion in cattle slaughtered in Mubende district, Uganda.

PubMed

Nalapa, Daniel Pakasi; Muwonge, Adrian; Kankya, Clovice; Olea-Popelka, Francisco

2017-03-21

The aim of this study was to estimate the prevalence of gross pathology suggestive of bovine tuberculosis (TB-like lesions) and evaluate animal's characteristics associated with the risk of having bovine TB-like lesions among cattle slaughtered in Mubende district in the Uganda cattle corridor. We conducted a cross sectional study in which 1,576 slaughtered cattle in Mubende district municipal abattoir underwent post-mortem inspection between August 2013 and January 2014. The presence of bovine TB-like lesions in addition to the animal's sex, age, breed, and sub-county of origin prior to slaughter were recorded. Associations between the presence of bovine TB-like lesions and animal's age, sex, breed, and sub-county of origin prior to slaughter were initially analysed using a univariable approach with the chi-square test, and subsequently with a multivariable logistic regression model to assess the combined impact of these animal characteristics with the risk of having a bovine TB-like lesion. Additionally, and as a secondary objective, tissue samples were collected from all carcases that had a bovine TB-like lesion and were processed using standard Mycobacterium culture and identification methods. The culture and acid fast positive samples were tested using Capilia TB-neo® assay to identify Mycobacterium tuberculosis complex (MTC). Of 1,576 carcasses inspected, 9.7% (153/1,576) had bovine TB-like lesions from which Mycobacterium spp and Mycobacterium Tuberculosis Complex (MTC) were isolated in 13 (8.4%) and 12 (7.8%) respectively. Bovine TB-like lesions were more likely to be found in females (OR = 1.49, OR 95% CI: 1.06-2.13) and in older cattle (OR = 2.5, 95% CI: 1.64-3.7). When compared to Ankole cattle, Cross breed (OR = 6.5, OR 95% CI: 3.37-12.7) and Zebu cattle (OR = 2.57, 95% CI: 1.78-3.72) had higher odds of having bovine TB-like lesions. Animals from Kasanda (OR = 2.5, 95% CI: 1.52-4.17) were more likely to have bovine TB-like lesions than cattle from Kasambya. The findings of study reveals that approximately one in ten slaughtered cattle presents with gross pathology suggestive of bovine TB in Mubende district in the Uganda cattle corridor district, however, we isolated MTC in only 8.4% of these bovine TB-like lesions. Therefore, there is a need to understand the cause of all the other bovine TB-like lesions in order to safe guard diagnostic integrity of meat inspection in Uganda.

SU-F-T-687: Comparison of SPECT/CT-Based Methodologies for Estimating Lung Dose from Y-90 Radioembolization

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

Kost, S; Yu, N; Lin, S

2016-06-15

Purpose: To compare mean lung dose (MLD) estimates from 99mTc macroaggregated albumin (MAA) SPECT/CT using two published methodologies for patients treated with {sup 90}Y radioembolization for liver cancer. Methods: MLD was estimated retrospectively using two methodologies for 40 patients from SPECT/CT images of 99mTc-MAA administered prior to radioembolization. In these two methods, lung shunt fractions (LSFs) were calculated as the ratio of scanned lung activity to the activity in the entire scan volume or to the sum of activity in the lung and liver respectively. Misregistration of liver activity into the lungs during SPECT acquisition was overcome by excluding lungmore » counts within either 2 or 1.5 cm of the diaphragm apex respectively. Patient lung density was assumed to be 0.3 g/cm{sup 3} or derived from CT densitovolumetry respectively. Results from both approaches were compared to MLD determined by planar scintigraphy (PS). The effect of patient size on the difference between MLD from PS and SPECT/CT was also investigated. Results: Lung density from CT densitovolumetry is not different from the reference density (p = 0.68). The second method resulted in lung dose of an average 1.5 times larger lung dose compared to the first method; however the difference between the means of the two estimates was not significant (p = 0.07). Lung dose from both methods were statistically different from those estimated from 2D PS (p < 0.001). There was no correlation between patient size and the difference between MLD from PS and both SPECT/CT methods (r < 0.22, p > 0.17). Conclusion: There is no statistically significant difference between MLD estimated from the two techniques. Both methods are statistically different from conventional PS, with PS overestimating dose by a factor of three or larger. The difference between lung doses estimated from 2D planar or 3D SPECT/CT is not dependent on patient size.« less

Targeted Therapy Shows Benefit in Rare Type of Thyroid Cancer

Cancer.gov

Treatment with the multitargeted agent vandetanib (Caprelsa) improved progression-free survival in patients with medullary thyroid cancer (MTC), according to findings from a randomized clinical trial.

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

Chemerisov, S.; Bailey, J.; Heltemes, T.

A series of four one-day irradiations was conducted with 100Mo-enriched disk targets. After irradiation, the enriched disks were removed from the target and dissolved. The resulting solution was processed using a NorthStar RadioGenix™ 99mTc generator either at Argonne National Laboratory or at the NorthStar Medical Radioisotopes facility. Runs on the RadioGenix system produced inconsistent analytical results for 99mTc in the Tc/Mo solution. These inconsistencies were attributed to the impurities in the solution or improper column packing. During the irradiations, the performance of the optic transitional radiation (OTR) and infrared cameras was tested in high radiation field. The OTR cameras survivedmore » all irradiations, while the IR cameras failed every time. The addition of X-ray and neutron shielding improved camera survivability and decreased the number of upsets.« less

99mTc MDP SPECT-CT-Based Modified Mirels Classification for Evaluation of Risk of Fracture in Skeletal Metastasis: A Pilot Study.

PubMed

Riaz, Saima; Bashir, Humayun; Niazi, Imran Khalid; Butt, Sumera; Qamar, Faisal

2018-06-01

Mirels' scoring system quantifies the risk of sustaining a pathologic fracture in osseous metastases of weight bearing long bones. Conventional Mirels' scoring is based on radiographs. Our pilot study proposes Tc MDP bone SPECT-CT based modified Mirels' scoring system and its comparison with conventional Mirels' scoring. Cortical lysis was noted in 8(24%) by SPECT-CT versus 2 (6.3%) on X-rays. Additional SPECT-CT parameters were; circumferential involvement [1/4 (31%), 1/2 (3%), 3/4 (37.5%), 4/4 (28%)] and extra-osseous soft tissue [3%]. Our pilot study suggests the potential role of SPECT-CT in predicting risk of fracture in osseous metastases.

Targeting hypoxia in tumors using 2-nitroimidazoles with peptidic chelators for technetium-99m: effect of lipophilicity.

PubMed

Zhang, X; Su, Z F; Ballinger, J R; Rauth, A M; Pollak, A; Thornback, J R

2000-01-01

Tumor hypoxia is an important prognostic factor for response to therapy. Radiolabeled 2-nitroimidazoles have been used for imaging hypoxia, and the octanol/water partition coefficient (P) of these compounds appears to play a crucial role in their suitability for imaging. A series of 11 2-nitroimidazoles coupled to peptidic chelators for (99m)Tc with divergent P was developed and evaluated in an in vitro system. Two classes of N(3)S chelators were used: dialkyl-Gly-Ser-Cys-linker-2-nitroimidazole (Class I) and dialkyl-Gly-Lys(2-nitroimidazole)-Cys (Class II). The chelators were prepared by automated solid-phase peptide synthesis. Xanthine oxidase was able to reduce the 2-nitroimidiazole moiety on the ligands, but the rate of reduction varied 5-fold among the different chelators. The chelators were labeled by transchelation from [(99m)Tc]gluconate at temperatures between 22 and 100 degrees C. The reaction mixtures were analyzed by HPLC and their P values determined. The accumulation of each complex in suspension cultures of Chinese hamster ovary cells incubated under aerobic or extremely hypoxic conditions was determined. Radiochemical yields ranged from 5 to 80% for the 11 compounds. HPLC showed that some of the compounds formed two complexes with (99m)Tc, possibly syn and anti conformations with respect to the Tc=O bond. In general, the Class I chelators labeled more readily than the class II chelators. The P values of the (99m)Tc complexes varied from 0.0002 to 5 and were generally in accordance with predictions based on structure. There were also differences in P as a function of pH; the free acids had a lower P at pH 7.4 than at pH 2.0 due to ionization, whereas the amides did not show this effect. Accumulation levels in aerobic cells were related to P but varied over a narrow range. Four of the 11 compounds showed selective accumulation in hypoxic cells. The peptidic class of 2-nitroimidazoles, with flexible design and convenient solid-phase synthesis, deserves further study as agents for imaging hypoxia in tumors.

Tc-labeling of Peptidomimetic Antagonist to Selectively Target alpha(v)beta(3) Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands.

PubMed

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C P; Wood, Bradford; Carrasquillo, Jorge A; Danthi, S Narasimhan; Paik, Chang H

2010-01-01

OBJECTIVES: The aim of this research was to synthesize radiolabeled peptidomimetic integrin alpha(v)beta(3) antagonist with (99m)Tc for rapid targeting of integrin alpha(v)beta(3) receptors in tumor to produce a high tumor to background ratio. METHODS: The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-beta-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with (99m)Tc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N'-diacetic acid (EDDA) as the co-ligand. The products, (99m)Tc EDDA(2)/HYNIC-IAC (P1) and (99m)Tc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. RESULTS: P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 degrees C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 +/- 13.48 vs 51.05 +/- 14.05%) when incubated with alpha(v)beta(3) at a molar excess (0.8 muM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17+/-0.52 and 2.13+/-0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 +/- 3.67% ID at 4 h whereas 54.04 +/- 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by imaging studies showing higher tumor-to-abdominal contrast for P1 than for P2 at 3 h postinjection. CONCLUSIONS: P1 showed good tumor targeting properties with a rapid tumor uptake, prolonged tumor retention and fast whole-body clearance kinetics. These findings warrant further investigation of the HYNIC method of (99m)Tc labeling of other peptidomimetic antagonists using EDDA as a coligand.

Serum level of vascular endothelial growth factor is influenced by erythropoietin treatment in peritoneal dialysis patients. (Grupo de Estudios Peritoneales de Madrid).

PubMed

del Peso, G; Selgas, R; Bajo, M A; Fernández de Castro, M; Aguilera, A; Cirugeda, A; Jiménez, C

2000-01-01

Some patients on long-term peritoneal dialysis (PD) develop a hyperpermeability state, owing to peritoneal neoangiogenesis. Vascular endothelial growth factor (VEGF), a potent mitogen for endothelial cells, has been implicated in most diseases characterized by microvascular neoformation. Erythropoietin (EPO) is able to induce endothelial proliferation in vitro. Our aim was to elucidate whether VEGF serum levels are influenced by EPO treatment, and whether VEGF serum level maintains a relationship with peritoneal transport data. We analyzed serum levels of VEGF in 35 PD patients (18 males, 17 females). Mean age was 58 years, with a mean time on PD of 98 +/- 75 months. Of the 35 patients, 19 were on automated peritoneal dialysis, and 16 were on continuous ambulatory peritoneal dialysis. Seven patients had diabetes. Peritoneal transport parameters were: urea mass transfer coefficient (MTC), 19.5 +/- 6.6 mL/min; creatinine MTC, 9.9 +/- 4.7 mL/min; net ultrafiltration, 491 +/- 166 mL per 4-hour dwell. Twenty seven patients were under therapy with recombinant human erythropoietin (rHuEPO). Mean serum VEGF levels were 347 +/- 203 pg/mL (range 66-857 pg/mL), with most patients in the normal range (60-700 pg/mL). VEGF levels did not correlate with age, sex, primary renal disease, diabetes, type of PD, time on PD, peritonitis, and cumulative glucose load. We found no correlation with urea MTC, creatinine MTC, ultrafiltration rate, or protein effluent levels. However, a significant negative correlation with residual renal function was seen (r = -0.39, p < 0.05). Patients treated with rHuEPO showed significantly higher serum levels of VEGF than non treated patients (375 +/- 220 pg/mL vs 251 +/- 75 pg/mL, p < 0.05), although they had similar residual renal function. We conclude that increased serum VEGF levels are associated with EPO treatment. Consequently, VEGF might have a role in the EPO effects found in PD patients. Whether both agents are related to peritoneal neoangiogenesis requires further research.

Predictive and prognostic value of 18F-DOPA PET/CT in patients affected by recurrent medullary carcinoma of the thyroid.

PubMed

Caobelli, Federico; Chiaravalloti, Agostino; Evangelista, Laura; Saladini, Giorgio; Schillaci, Orazio; Vadrucci, Manuela; Scalorbi, Federica; Donner, Davide; Alongi, Pierpaolo

2018-01-01

Medullary thyroid carcinoma (MTC) is a malignancy accounting for about 5-8% of thyroid cancers. Serum calcitonin and carcinoembryonic antigen (CEA) levels are widely used to monitor disease progression. However, prognostic factors able to predict outcomes are highly desirable. We, therefore, aimed to assess the prognostic role of 18 F-DOPA PET/CT in patients with recurrent MTC. 60 patients (mean age 64 ± 13 years, range 44-82) with recurrent MTC were eligible from a multicenter database. All patients underwent a restaging 18 F-DOPA PET/CT, performed at least 6 months after surgery. CEA/calcitonin levels, local recurrences, nodal involvement and metastases at PET/CT were recorded. SUVmax, SUVmean (also normalized to mediastinal uptake) and metabolic tumor volume were automatically calculated for each lesion, by placing a volume of interest around the lesion with 40% of peak activity as threshold for the automatic contouring. The patients were clinically and radiologically followed up for 21 ± 11 months. Rate of progression-free survival (PFS), disease-specific survival (DSS) and incremental prognostic value of 18 F-DOPA PET/CT over conventional imaging modalities were assessed by Kaplan-Meier curves and Log-Rank test. Cox regression univariate and multivariate analyses were performed for assessing predictors of prognosis. 18 F-DOPA PET/CT showed abnormal findings in 27 patients (45%) and resulted unremarkable in 33 (55%). PFS was significantly longer in patients with an unremarkable PET/CT scan (p = 0.018). Similarly, an unremarkable PET/CT study was associated with a significantly longer DSS (p = 0.04). 18 F-DOPA PET/CT added prognostic value over other imaging modalities both for PFS and for DSS (p < 0.001 and p = 0.012, respectively). Neither semiquantitative PET parameters nor clinical or laboratory data were predictive of a worse PFS and DSS in patients with recurrent MTC. 18 F-DOPA PET/CT scan has an important prognostic value in predicting disease progression and mortality rate.

Airport activity and noise trends

DOT National Transportation Integrated Search

1993-10-01

This report is published by the Metropolitan Transportation Commission : (MTC) to provide information concerning local Bay Area airport activity and : airport noise trends. The airport activity data are obtained from published : airline schedules and...

Midwest Transportation Consortium : 2009 annual report.

DOT National Transportation Integrated Search

2009-12-02

In October 2008 the Midwest Transportation Consortium (MTC) began its : second of three years as a Tier I University Transportation Center (UTC). : Its theme, Transportation Safety through Improvements in Management : Information Systems, refle...

Novel Radiolabeled Bisphosphonates for PET Diagnosis and Endoradiotherapy of Bone Metastases

PubMed Central

Pfannkuchen, Nina; Meckel, Marian; Bergmann, Ralf; Bachmann, Michael; Bal, Chandrasekhar; Sathekge, Mike; Mohnike, Wolfgang; Baum, Richard P.; Rösch, Frank

2017-01-01

Bone metastases, often a consequence of breast, prostate, and lung carcinomas, are characterized by an increased bone turnover, which can be visualized by positron emission tomography (PET), as well as single-photon emission computed tomography (SPECT). Bisphosphonate complexes of 99mTc are predominantly used as SPECT tracers. In contrast to SPECT, PET offers a higher spatial resolution and, owing to the 68Ge/68Ga generator, an analog to the established 99mTc generator exists. Complexation of Ga(III) requires the use of chelators. Therefore, DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid), NOTA (1,4,7-triazacyclododecane-1,4,7-triacetic acid), and their derivatives, are often used. The combination of these macrocyclic chelators and bisphosphonates is currently studied worldwide. The use of DOTA offers the possibility of a therapeutic application by complexing the β-emitter 177Lu. This overview describes the possibility of diagnosing bone metastases using [68Ga]Ga-BPAMD (68Ga-labeled (4-{[bis-(phosphonomethyl))carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl)acetic acid) as well as the successful application of [177Lu]Lu-BPAMD for therapy and the development of new diagnostic and therapeutic tools based on this structure. Improvements concerning both the chelator and the bisphosphonate structure are illustrated providing new 68Ga- and 177Lu-labeled bisphosphonates offering improved pharmacological properties. PMID:28524118

Lifetime attributable risk as an alternative to effective dose to describe the risk of cancer for patients in diagnostic and therapeutic nuclear medicine

NASA Astrophysics Data System (ADS)

Andersson, Martin; Eckerman, Keith; Mattsson, Sören

2017-12-01

The aim of this study is to implement lifetime attributable risk (LAR) predictions of cancer for patients of various age and gender, undergoing diagnostic investigations or treatments in nuclear medicine and to compare the outcome with a population risk estimate using effective dose and the International Commission on Radiological Protection risk coefficients. The radiation induced risk of cancer occurrence (incidence) or death from four nuclear medicine procedures are estimated for both male and female between 0 and 120 years. Estimations of cancer risk are performed using recommended administered activities for two diagnostic (18F-FDG and 99mTc-phosphonate complex) and two therapeutic (131I-iodide and 223Ra-dichloride) radiopharmaceuticals to illustrate the use of cancer risk estimations in nuclear medicine. For 18F-FDG, the cancer incidence for a male of 5, 25, 50 and 75 years at exposure is 0.0021, 0.0010, 0.0008 and 0.0003, respectively. For 99mTc phosphonates complex the corresponding values are 0.000 59, 0.000 34, 0.000 27 and 0.000 13, respectively. For an 131I-iodide treatment with 3.7 GBq and 1% uptake 24 h after administration, the cancer incidence for a male of 25, 50 and 75 years at exposure is 0.041, 0.029 and 0.012, respectively. For 223Ra-dichloride with an administration of 21.9 MBq the cancer incidence for a male of 25, 50 and 75 years is 0.31, 0.21 and 0.09, respectively. The LAR estimations are more suitable in health care situations involving individual patients or specific groups of patients than the health detriment based on effective dose, which represents a population average. The detriment consideration in effective dose adjusts the cancer incidence for suffering of non-lethal cancers while LAR predicts morbidity (incidence) or mortality (cancer). The advantages of these LARs are that they are gender and age specific, allowing risk estimations for specific patients or subgroups thus better representing individuals in health care than effective dose.

Midwest Transportation Consortium : 2010-2011 annual report.

DOT National Transportation Integrated Search

2011-01-01

In October 2010, the Midwest Transportation Consortium (MTC) began its fourth : year as a Tier I University Transportation Center (UTC). Our theme, Transportation : Safety through Improvements in Management Information Systems, continues to : r...

Midwest Transportation Consortium : 2009-2010 annual report.

DOT National Transportation Integrated Search

2010-01-01

In October 2009, the Midwest Transportation Consortium (MTC) began its third year : as a Tier I University Transportation Center (UTC). Its theme, Transportation Safety : through Improvements in Management Information Systems, reflects our stro...

Midwest Transportation Consortium : 2007-2008 annual report.

DOT National Transportation Integrated Search

2008-01-01

In October 2007, Iowa State Universitys Midwest Transportation Consortium (MTC) entered its : first year as a Tier I University Transportation Center (UTC) under the theme Transportation : Safety through Improvements in Management Information S...

Midwest Transportation Consortium : 2003-2004 annual report.

DOT National Transportation Integrated Search

2004-01-01

Introduction: The Midwest Transportation Consortium (MTC) recently completed its fifth year : of operation. In doing so, the consortium has established itself as an effective : network that promotes the education of future transportation professional...

Sentinel lymph node detection in early cervical cancer with combination 99mTc phytate and patent blue.

PubMed

Niikura, Hitoshi; Okamura, Chikako; Akahira, Junichi; Takano, Tadao; Ito, Kiyoshi; Okamura, Kunihiro; Yaegashi, Nobuo

2004-08-01

The purpose of this study was to examine sentinel lymph node (SLN) detection in patients with early stage cervical cancer using (99m)Tc phytate and patent blue dye and to compare our method with published findings utilizing other radioisotopic tracers. A total of 20 consecutive patients with cervical cancer scheduled for radical hysterectomy and total pelvic lymphadenectomy at our hospital underwent SLN detection study. The day before surgery, lymphoscintigraphy was performed with injection of 99m-technetium ((99m)Tc)-labeled phytate into the uterine cervix. At surgery, patients underwent lymphatic mapping with a gamma-detecting probe and patent blue injected into the same points as the phytate solution. At least one positive node was detected in 18 patients (90%). A total of 46 sentinel nodes were detected (mean, 2.3; range, 1-5). Most sentinel nodes were in one of the following sites: external iliac (21 nodes), obturator (15 nodes), and parametrial (7 nodes). Eleven (24%) sentinel nodes were detected only through radioactivity and two (4%) were detected only with blue dye. The sensitivity, specificity, and negative predictive value for SLN detection were all 100%. Nine published studies involving 295 patients had a summarized detection rate of 85%. Summarized sensitivity, specificity, and negative predictive value were 93%, 100%, and 99%, respectively. Combination of (99m)Tc phytate and patent blue is effective in SLN detection in early stage cervical cancer.

Bronchoalveolar lavage for diagnosis of tuberculosis infection in elephants.

PubMed

Hermes, R; Saragusty, J; Moser, I; Holtze, S; Nieter, J; Sachse, K; Voracek, T; Bernhard, A; Bouts, T; Göritz, F; Hildebrandt, T B

2018-03-01

Tuberculosis (TB) has been known to affect elephants for thousands of years. It was put into spotlight when few circus elephants were diagnosed carrying Mycobacterium (M.) tuberculosis. Because of the zoonotic risk and high susceptibility to M. tuberculosis, periodic testing was enacted since, in captive breeding programmes. Presently, trunk wash is the recommended diagnostic procedure for TB. Trunk wash, however, puts the operator at risk, has low sensitivity, and is prone to contamination. Here, bronchoalveolar lavage is described for the first time for TB diagnosis in elephants. Bronchial, trunk and mouth fluids were investigated using bacterial culture, M. tuberculosis complex (MTC)-specific real-time quantitative PCR (qPCR) and mycobacterial genus-specific qPCR for overall presence of mycobacteria or mycobacterial DNA including bacteria or DNA of closely related genera, respectively, in 14 elephants. Neither bacteria of the MTC nor their DNA were identified in any of the elephants. Yet, 25% of the cultures grew non-tuberculous mycobacteria (NTM) or closely related bacterial species. Furthermore, 85% of the samples contained DNA of NTM or closely related bacterial genera. This finding might explain continued false-positive results from various serological tests. From a zoonotic point of view, bronchoalveolar lavage is safer for the testing personal, has higher probability of capturing MTC and, through PCR, identifies DNA NTM in elephants. Yet, necessary endoscopic equipment, animal sedation and access to a TB reference laboratory might pose challenging requirements in remote conditions in some elephant range countries.

Assessment of effects of a Cordia salicifolia extract on the radiolabeling of blood constituents and on the morphology of red blood cells.

PubMed

Frydman, Jacques Natan Grinapel; Rocha, Vanessa Camara; Benarroz, Monica Oliveira; Rocha, Gabrielle Souza; Pereira, Márcia Oliveira; de Souza da Fonseca, Adenilson; Bernardo-Filho, Mario

2008-12-01

Effects of a Cordia salicifolia (porangaba) extract on the labeling of blood cells (BCs) with technetium-99m ((99m)Tc) and on the morphology of red BCs were evaluated. Labeling of cellular and molecular structures with (99m)Tc depends on a reducing agent. Some physical characteristics, as visible absorbance spectrum, electric conductivity, and refractive index of this porangaba extract, were also determined. Blood samples from Wistar rats were incubated with porangaba extract or with 0.9% NaCl (control). Labeling of blood constituents with (99m)Tc was performed. Plasma (P) and BCs, both soluble (SF-P and SF-BC) and insoluble (IF-P and IF-BC) fractions, were separated. The radioactivity in each fraction was counted, and the percentage of radioactivity incorporated (%ATI) was calculated. Blood smears were prepared, fixed, and stained, and the morphology of the red BCs was evaluated. Data showed an absorbance peak at 480 nm and electric conductibility and refractive index concentration-dependent. Porangaba extract decreased significantly (P < .05) the BC, IF-P, and IF-BC %ATI, and no modifications were verified on the shape of red BCs. Analysis of the results reveals that some physical parameters could be useful to aid in characterizing the extract studied. Moreover, it is possible that chemical compounds of this extract could have chelating/redox actions or be capable of binding to plasma and/or cellular proteins.

Evaluation of tricine and EDDA as Co-ligands for 99mTc-labeled HYNIC-MSH analogs for melanoma imaging.

PubMed

Garcia, Maria Fernanda; Zhang, Xiuli; Gallazzi, Fabio; Fernandez, Marcelo; Moreno, Maria; Gambini, Juan Pablo; Porcal, Williams; Cabral, Pablo; Quinn, Thomas P

2015-01-01

Several radiolabeled alpha-melanocyte stimulating hormone (α-MSH) analogs have been studied for their abilities to target melanoma tumor cells through specific recognition and binding to the melanocortin receptor 1 (MCR1). In this work, a lactam bridgecyclized α-MSH analog was labeled with (99m) via the hydrazinonicotinamide (HYNIC) chelator and characterized for its melanoma tumor targeting properties. The bifunctional chelating agent HYNIC-Boc was attached to the N-terminus of the MSH peptide followed by the lactam cyclization, resulting in the HYNIC-cyc-MSH analog. The lactam cyclized peptide displayed high affinity and specificity for MC1-receptors present on B16/F1 melanoma tumor cells, exhibiting an IC50 of 6.48 nM. HYNIC-cyc-MSH was radiolabeled with (99m)Tc using two common co-ligands, tricine and EDDA. In vitro, the radiochemical stability, cell binding and efflux properties were similar between the peptides radiolabeled with tricine and EDDA as co-ligands. In vivo, biodistribution studies (n=4) demonstrated that (99m)Tc- HYNIC-cyc-MSH/tricine had superior tumor to muscle and tumor to blood ratios than (99m)Tc-HYNIC-cyc-MSH/EDDA at early time points. Planar gamma imaging of melanoma bearing mice showed that 99mTc-HYNIC-cyc-MSH/tricine was able to clearly visualize tumors, underscoring the potential utility of (99m)Tc labeled lactam cyclized MSH molecules as melanoma imaging agents.

Accelerator-based production of the (99m)Tc-(186)Re diagnostic-therapeutic pair using metal disulfide targets (MoS2, WS2, OsS2).

PubMed

Gott, Matthew D; Hayes, Connor R; Wycoff, Donald E; Balkin, Ethan R; Smith, Bennett E; Pauzauskie, Peter J; Fassbender, Michael E; Cutler, Cathy S; Ketring, Alan R; Wilbur, D Scott; Jurisson, Silvia S

2016-08-01

Novel, natural abundance metal disulfide targets were irradiated for 1h with a 10µA proton beam in a small, medical cyclotron. Osmium disulfide was synthesized by simple distillation and precipitation methods while MoS2 and WS2 were commercially available. The targets dissolved under mild conditions and were analyzed by γ-spectroscopy. Production rates and potential applications are discussed, including target recovery and recycling schemes for OsS2 and WS2. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geospatial and Temporal Analysis of Thyroid Cancer Incidence in a Rural Population

PubMed Central

Hanley, John P.; Jackson, Erin; Morrissey, Leslie A.; Rizzo, Donna M.; Sprague, Brian L.; Sarkar, Indra Neil

2015-01-01

Background: The increasing incidence of thyroid cancer has resulted in the rate tripling over the past 30 years. Reasons for this increase have not been established. Geostatistics and geographic information system (GIS) tools have emerged as powerful geospatial technologies to identify disease clusters, map patterns and trends, and assess the impact of ecological and socioeconomic factors (SES) on the spatial distribution of diseases. In this study, these tools were used to analyze thyroid cancer incidence in a rural population. Methods: Thyroid cancer incidence and socio-demographic factors in Vermont (VT), United States, between 1994 and 2007 were analyzed by logistic regression and geospatial and temporal analyses. Results: The thyroid cancer age-adjusted incidence in Vermont (8.0 per 100,000) was comparable to the national level (8.4 per 100,000), as were the ratio of the incidence of females to males (3.1:1) and the mortality rate (0.5 per 100,000). However, the estimated annual percentage change was higher (8.3 VT; 5.7 U.S.). Incidence among females peaked at 30–59 years of age, reflecting a significant rise from 1994 to 2007, while incidence trends for males did not vary significantly by age. For both females and males, the distribution of tumors by size did not vary over time; ≤1.0 cm, 1.1–2.0 cm, and >2.0 cm represented 38%, 22%, and 40%, respectively. In females, papillary thyroid cancer (PTC) accounted for 89% of cases, follicular (FTC) 8%, medullary (MTC) 2%, and anaplastic (ATC) 0.6%, while in males PTC accounted for 77% of cases, FTC 15%, MTC 1%, and ATC 3%. Geospatial analysis revealed locations and spatial patterns that, when combined with multivariate incidence analyses, indicated that factors other than increased surveillance and access to healthcare (physician density or insurance) contributed to the increased thyroid cancer incidence. Nine thyroid cancer incidence hot spots, areas with very high normalized incidence, were identified based on zip code data. Those locations did not correlate with urban areas or healthcare centers. Conclusions: These data provide evidence of increased thyroid cancer incidence in a rural population likely due to environmental drivers and SES. Geospatial modeling can provide an important framework for evaluation of additional associative risk factors. PMID:25936441

E3 Success Story - E3 Southwest Virginia: Economy, Energy and the Environment

EPA Pesticide Factsheets

E3 Southwest Virginia supports sustainable manufacturing in 17 counties in southwest Virginia. The MTC provides manufacturers with assessments of production processes to reduce their energy consumption and drive innovation.

Film Permeability Determination Using Static Permeability Cells

EPA Pesticide Factsheets

The permeability of tarps to soil fumigant pesticides varies depending on the active ingredient chemical: dimethyl disulfide (DMDS), methyl bromide, chloropicrin, or other. The diffusion rate can be represented by the mass transfer coefficient (MTC).

Investigation of radioactivity concentration in spent technetium generators

NASA Astrophysics Data System (ADS)

Idriss, Hajo; Salih, Isam; Alaamer, Abdulaziz S.; Eisa, M. H.; Sam, A. K.

2014-04-01

This study was carried out to survey and measure radioactivity concentration and estimate radiation dose level at the surface of spent technetium generator columns for the safe final disposal of radioactive waste. High resolution γ-spectrometry with the aid of handheld radiation survey meters has been used. The radioactivity measurements has shown that 238U, 40K and 137Cs were only measurable in one sample whereas 125Sb was found in 14 samples out of total of 20 samples with an activity concentration which ranged from 21 to 7404 with an average value of 1095 Bq/kg. The activity concentration of 125Sb is highly variable indicating that the spent 99mTc generator columns are of different origin. This investigation highlighted the importance of radiation monitoring of spent technetium generators in the country in order to protect workers, and the public from the dangers posed by radioactive waste.

Development of a multispectral autoradiography using a coded aperture

NASA Astrophysics Data System (ADS)

Noto, Daisuke; Takeda, Tohoru; Wu, Jin; Lwin, Thet T.; Yu, Quanwen; Zeniya, Tsutomu; Yuasa, Tetsuya; Hiranaka, Yukio; Itai, Yuji; Akatsuka, Takao

2000-11-01

Autoradiography is a useful imaging technique to understand biological functions using tracers including radio isotopes (RI's). However, it is not easy to describe the distribution of different kinds of tracers simultaneously by conventional autoradiography using X-ray film or Imaging plate. Each tracer describes each corresponding biological function. Therefore, if we can simultaneously estimate distribution of different kinds of tracer materials, the multispectral autoradiography must be a quite powerful tool to better understand physiological mechanisms of organs. So we are developing a system using a solid state detector (SSD) with high energy- resolution. Here, we introduce an imaging technique with a coded aperture to get spatial and spectral information more efficiently. In this paper, the imaging principle is described, and its validity and fundamental property are discussed by both simulation and phantom experiments with RI's such as 201Tl, 99mTc, 67Ga, and 123I.

Robust model predictive control for optimal continuous drug administration.

PubMed

Sopasakis, Pantelis; Patrinos, Panagiotis; Sarimveis, Haralambos

2014-10-01

In this paper the model predictive control (MPC) technology is used for tackling the optimal drug administration problem. The important advantage of MPC compared to other control technologies is that it explicitly takes into account the constraints of the system. In particular, for drug treatments of living organisms, MPC can guarantee satisfaction of the minimum toxic concentration (MTC) constraints. A whole-body physiologically-based pharmacokinetic (PBPK) model serves as the dynamic prediction model of the system after it is formulated as a discrete-time state-space model. Only plasma measurements are assumed to be measured on-line. The rest of the states (drug concentrations in other organs and tissues) are estimated in real time by designing an artificial observer. The complete system (observer and MPC controller) is able to drive the drug concentration to the desired levels at the organs of interest, while satisfying the imposed constraints, even in the presence of modelling errors, disturbances and noise. A case study on a PBPK model with 7 compartments, constraints on 5 tissues and a variable drug concentration set-point illustrates the efficiency of the methodology in drug dosing control applications. The proposed methodology is also tested in an uncertain setting and proves successful in presence of modelling errors and inaccurate measurements. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of five serologic assays for bovine tuberculosis surveillance in domestic free-range pigs from southern Spain.

PubMed

Cardoso-Toset, Fernando; Luque, Inmaculada; Carrasco, Librado; Jurado-Martos, Francisco; Risalde, María Ángeles; Venteo, Ángel; Infantes-Lorenzo, José A; Bezos, Javier; Rueda, Paloma; Tapia, Istar; Gortázar, Christian; Domínguez, Lucas; Domínguez, Mercedes; Gomez-Laguna, Jaime

2017-02-01

In countries where bovine tuberculosis (bTB) is still prevalent the contact among different animal species in extensive systems contributes to the circulation of Mycobacterium bovis (M. bovis) and other members of the Mycobacterium tuberculosis complex (MTC). Thus, free-range pigs can develop subclinical infections and may contribute to disease spread to bovine and wildlife. Serodiagnosis has been proposed as a screening tool for detecting infected pig herds; however, the value of this method to obtain an accurate diagnosis in this species is still not clear. In this study, sensitivity (Se) and specificity (Sp) estimates of four ELISAs and a lateral flow immunochromatographic antibody assay based on different M. bovis antigens, including MPB70 and MPB83 proteins, were evaluated in naturally infected domestic free-range pigs. For this purpose, submandibular lymph nodes and blood samples from 217 pigs from both TB-infected and historically negative farms were sampled at slaughterhouse and analysed by gross examination, histopathology, bacteriological culture and qPCR. Se and Sp estimates of the 5 evaluated assays ranged from 66.1% to 78% (CI 95 from 52.6 to 87.7%) and from 98.9% to 100% (CI 95 from 93.8 to 100%), respectively. Results of our study suggest that all the evaluated assays could be used as a first screening tool to conduct bTB surveillance in domestic pigs at population level; however, animals from seropositive herds should later be surveyed by other methods in order to reduce false negative results. Copyright © 2016 Elsevier B.V. All rights reserved.

Peptide Based Radiopharmaceuticals: Specific Construct Approach

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

Som, P; Rhodes, B A; Sharma, S S

1997-10-21

The objective of this project was to develop receptor based peptides for diagnostic imaging and therapy. A series of peptides related to cell adhesion molecules (CAM) and immune regulation were designed for radiolabeling with 99mTc and evaluated in animal models as potential diagnostic imaging agents for various disease conditions such as thrombus (clot), acute kidney failure, and inflection/inflammation imaging. The peptides for this project were designed by the industrial partner, Palatin Technologies, (formerly Rhomed, Inc.) using various peptide design approaches including a newly developed rational computer assisted drug design (CADD) approach termed MIDAS (Metal ion Induced Distinctive Array of Structures).more » In this approach, the biological function domain and the 99mTc complexing domain are fused together so that structurally these domains are indistinguishable. This approach allows construction of conformationally rigid metallo-peptide molecules (similar to cyclic peptides) that are metabolically stable in-vivo. All the newly designed peptides were screened in various in vitro receptor binding and functional assays to identify a lead compound. The lead compounds were formulated in a one-step 99mTc labeling kit form which were studied by BNL for detailed in-vivo imaging using various animals models of human disease. Two main peptides usingMIDAS approach evolved and were investigated: RGD peptide for acute renal failure and an immunomodulatory peptide derived from tuftsin (RMT-1) for infection/inflammation imaging. Various RGD based metallopeptides were designed, synthesized and assayed for their efficacy in inhibiting ADP-induced human platelet aggregation. Most of these peptides displayed biological activity in the 1-100 µM range. Based on previous work by others, RGD-I and RGD-II were evaluated in animal models of acute renal failure. These earlier studies showed that after acute ischemic injury the renal cortex displays RGD receptor with higher density. The results have indicated good diagnostic potential for their use in this clinical situation, as an imaging agent to diagnose ischemic renal injury and differentiate from other causes. Very promising results were obtained with newly developed tuftsin related metallopeptides. A number of these peptides displayed high potency (nM range) in imaging infection. Antagonists were successfully used to image experimentally induced abscesses in rodents. One of the antagonists, termed 99mTc-RMT-1, was evaluated in rabbits and dogs for its applicability as infection/inflammation imaging agent. Both in dog and rabbit infection/inflammation models 99mTc-RMT-1 could be used for rapid scintigraphic diagnosis. A very high and rapid uptake was observed in both soft tissue and bone infection providing a good target to background contrast. The agent also allowed distinction between bone fracture and osteomyelitis. All these results warrant human clinical trials with 99mTc-RMT-1 which may help replace hazardous ex-vivo WBC labeling procedures that are current clincial modality for imaging infection foci.« less

Emerging Tuberculosis Pathogen Hijacks Social Communication Behavior in the Group-Living Banded Mongoose (Mungos mungo).

PubMed

Alexander, Kathleen A; Sanderson, Claire E; Larsen, Michelle H; Robbe-Austerman, Suelee; Williams, Mark C; Palmer, Mitchell V

2016-05-10

An emerging Mycobacterium tuberculosis complex (MTC) pathogen, M. mungi, infects wild banded mongooses (Mungos mungo) in Northern Botswana, causing significant mortality. This MTC pathogen did not appear to be transmitted through a primary aerosol or oral route. We utilized histopathology, spoligotyping, mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR), quantitative PCR (qPCR), and molecular markers (regions of difference [RDs] from various MTC members, including region of difference 1 [RD1] from M. bovis BCG [RD1(BCG)], M. microti [RD1(mic)], and M. pinnipedii [RD1(seal)], genes Rv1510 [RD4], Rv1970 [RD7], Rv3877/8 [RD1], and Rv3120 [RD12], insertion element IS1561, the 16S RNA gene, and gene Rv0577 [cfp32]), including the newly characterized mongoose-specific deletion in RD1 (RD1(mon)), in order to demonstrate the presence of M. mungi DNA in infected mongooses and investigate pathogen invasion and exposure mechanisms. M. mungi DNA was identified in 29% of nasal planum samples (n = 52), 56% of nasal rinses and swabs (n = 9), 53% of oral swabs (n = 19), 22% of urine samples (n = 23), 33% of anal gland tissue (n = 18), and 39% of anal gland secretions (n = 44). The occurrence of extremely low cycle threshold values obtained with qPCR in anal gland and nasal planum samples indicates that high levels of M. mungi can be found in these tissue types. Histological data were consistent with these results, suggesting that pathogen invasion occurs through breaks in the nasal planum and/or skin of the mongoose host, which are in frequent contact with anal gland secretions and urine during olfactory communication behavior. Lesions in the lung, when present, occurred only with disseminated disease. No environmental sources of M. mungi DNA could be found. We report primary environmental transmission of an MTC pathogen that occurs in association with social communication behavior. Organisms causing infectious disease evolve modes of transmission that exploit environmental and host conditions favoring pathogen spread and persistence. We report a novel mode of environmental infectious disease transmission that occurs in association with olfactory secretions (e.g., urine and anal gland secretions), allowing pathogen exposure to occur within and between social groups through intricate social communication behaviors of the banded mongoose host. The presence of M. mungi in these environmentally deposited secretions would effectively circumvent natural social barriers (e.g., territoriality), facilitating between-group pathogen transmission in the absence of direct physical contact, a rare occurrence in this highly territorial species. This work identifies an important potential mechanism of pathogen transmission of epidemiological significance in social species. We also provide evidence of a novel mechanism of pathogen transmission for the MTC complex, where pathogen movement in the environment and host exposure dynamics are driven by social behavior. Copyright © 2016 Alexander et al.

99mTc-labeling of Peptidomimetic Antagonist to Selectively Target αvβ3 Receptor-Positive Tumor: Comparison of PDA and EDDA as co-Ligands

PubMed Central

Shin, In Soo; Maeng, Jin Soo; Jang, Beom-Su; You, Eric; Cheng, Kenneth; Li, King C.P; Wood, Bradford; Carrasquillo, Jorge A.; Danthi, S. Narasimhan; Paik, Chang H.

2010-01-01

Objectives The aim of this research was to synthesize radiolabeled peptidomimetic integrin αvβ3 antagonist with 99mTc for rapid targeting of integrin αvβ3 receptors in tumor to produce a high tumor to background ratio. Methods The amino terminus of 4-[2-(3,4,5,6-tetra-hydropyrimidin-2-ylamino)-ethyloxy]benzoyl-2-(S)-[N-(3-amino-neopenta-1-carbamyl)]-aminoethylsulfonyl-amino-β-alanine hydrochloride (IAC) was conjugated with N-hydroxysuccinimide ester of HYNIC and labeled with 99mTc using tricine with either 1,5-pyridinedicarboxylic acid (PDA) or ethylenediamine-N,N′-diacetic acid (EDDA) as the co-ligand. The products, 99mTc EDDA2/HYNIC-IAC (P1) and 99mTc PDA (tricin)/HYNIC-IAC (P2) were subjected to in vitro serum stability, receptor-binding, biodistribution and imaging studies. Results P1 and P2 were synthesized with an overall yield of >80%. P1 was slightly more stable than P2 when incubated in serum at 37 °C for 18 hrs (84 vs 77% intact). The In vitro receptor-binding of P1 was higher than that of P2 (78.02 ± 13.48 vs 51.05 ± 14.05%) when incubated with αvβ3 at a molar excess (0.8 μM). This receptor binding was completely blocked by a molar excess of an unlabeled peptidomimetic antagonist. Their differences shown in serum stability and the receptor-binding appeared to be related to their biological behaviors in tumor uptake and retention; the 1 h tumor uptakes of P1 and P2 were 3.17±0.52 and 2.13±0.17 % ID/g, respectively. P1 was retained in the tumor longer than P2. P1 was excreted primarily through the renal system whereas P2 complex was excreted equally via both renal and hepatobiliary systems. Thus, P1 was retained in the whole-body with 27.25 ± 3.67% ID at 4 h whereas 54.04 ± 3.57% ID of P2 remained in the whole-body at 4 h. This higher whole-body retention of P2 appeared to be resulted from a higher amount of radioactivity retained in liver and intestine. These findings were supported by imaging studies showing higher tumor-to-abdominal contrast for P1 than for P2 at 3 h postinjection. Conclusions P1 showed good tumor targeting properties with a rapid tumor uptake, prolonged tumor retention and fast whole-body clearance kinetics. These findings warrant further investigation of the HYNIC method of 99mTc labeling of other peptidomimetic antagonists using EDDA as a coligand. PMID:20556233

Midwest Transportation Consortium : 2006-2007 annual report.

DOT National Transportation Integrated Search

2007-01-01

Introduction: The Midwest Transportation Consortium (MTC) began year 8 by having the funding it receives from the Research and Innovative Technology Administration doubled, and by losing its regional grant to a consortium led by the University of Neb...

Using LabVIEW for Telemetry Monitoring and Display

NASA Technical Reports Server (NTRS)

Wells, G.; Baroth, E.

1994-01-01

Part of the Jet Propulsion Laboratory's (JPL's) Instrumentation Section, the Measurement Technology Center (MTC) evaluates data acquisition hardware and software products for inclusion into the Instrument Loan Pool, which are the made available to JPL experimenters.

Bay Area transportation : state of the system 2002

DOT National Transportation Integrated Search

2002-12-01

The Metropolitan Transportation Commission (MTC) and Caltrans District 4 have engaged in a collaborative effort to assemble key facts and performance indicators of interest to Bay Area commuters and other travelers. The publication of this report, Ba...

Straight and chopped dc performance data for a Prestolite MTC-4001 motor and a general electric EV-1 controller

NASA Technical Reports Server (NTRS)

Edie, P. C.

1981-01-01

Performance data on the Prestolite MTC-4001 series wound dc motor and General Electric EV-1 Chopper Controller is supplied for the electric vehicle manufacturer. Data are provided for both straight and chopped dc input to the motor, at 2 motor temperature levels. Testing was done at 6 voltage increments to the motor, and 2 voltage increments to the controller. Data results are presented in both tabular and graphical forms. Tabular information includes motor voltage and current input data, motor speed and torque output data, power data and temperature data. Graphical information includes torque-speed, motor power output-speed, torque-current, and efficiency-speed plots under the various operating conditions. The data resulting from this testing show the speed-torque plots to have the most variance with operating temperature. The maximum motor efficiency is between 76% and 82%, regardless of temperature or mode of operation.

Polymorphisms of 20 regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis.

PubMed

Bigi, María M; Blanco, Federico Carlos; Araújo, Flabio R; Thacker, Tyler C; Zumárraga, Martín J; Cataldi, Angel A; Soria, Marcelo A; Bigi, Fabiana

2016-08-01

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans and animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and other members of the MTC evolved. The genome of M. bovis is over >99.95% identical to that of M. tuberculosis but with seven deletions ranging in size from 1 to 12.7 kb. In addition, 1200 single nucleotide mutations in coding regions distinguish M. bovis from M. tuberculosis. In the present study, we assessed 75 M. tuberculosis genomes and 23 M. bovis genomes to identify non-synonymous mutations in 202 coding sequences of regulatory genes between both species. We identified species-specific variants in 20 regulatory proteins and confirmed differential expression of hypoxia-related genes between M. bovis and M. tuberculosis. © 2016 The Societies and John Wiley & Sons Australia, Ltd.

(99m)Tc-3PRGD 2 SPECT/CT predicts the outcome of advanced nonsquamous non-small cell lung cancer receiving chemoradiotherapy plus bevacizumab.

PubMed

Ma, Qingjie; Min, Kaiyin; Wang, Ting; Chen, Bin; Wen, Qiang; Wang, Fan; Ji, Tiefeng; Gao, Shi

2015-07-01

Functional imaging can help clinicians assess the individual response of advanced nonsquamous non-small cell lung cancer (NSCLC) to chemoradiation therapy plus bevacizumab. Our purpose is to investigate the ability of (99m)Tc-3PRGD2 single photon emission computed tomography/computed tomography (SPECT/CT) in predicting the early response to treatment. Patients with advanced nonsquamous NSCLC diagnosed by histological or cytological examination were imaged with (99m)Tc-3PRGD2 SPECT/CT at 3 time points: 1-3 days before the start of treatment (SPECT1), 40 Gy radiotherapy with 2 cycles of chemotherapy plus bevacizumab (SPECT2) and 4 weeks after chemoradiotherapy plus bevacizumab (SPECT3). The images were evaluated semiquantitatively by measuring the tumor to non-tumor ratio (T/N) and calculating the percentage change in T/N ratio. Short-term outcome was assessed by the treatment response evaluation according to the Response Evaluation Criteria in Solid Tumors criteria as: complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients were divided two groups: responders (CR and PR) and nonresponders (SD and PD). To determine a threshold for percent reduction in T/N ratios, receiver-operating characteristic (ROC) curve analysis was used. Patients were grouped again based on the threshold of P1 (the change percentage from SPECT1 to SPECT2) and P2 (the change percentage from SPECT1 to SPECT3): P1 responders and P1 nonresponders; P2 responders and P2 nonresponders. Patients were followed up starting 4 weeks after completion of therapy and then every 3 months for the first 2 years and every 6 months after 2 years. OS of P1 responders, P1 nonresponders, P2 responders and P2 nonresponders was estimated and graphically illustrated using the Kaplan-Meier method and the log-rank test was used to test the null hypotheses of equal OS in subgroups of patients. A total of 28 patients completed all imaging and treatment. All primary lung tumors were well visualized on SPECT1. The mean T/N ratio of SPECT1 in responders and nonresponders was not statistically different (2.73 ± 0.59 vs. 2.59 ± 0.52, p > 0.05). At SPECT2 and SPECT3, the mean T/N ratios were both lower in the responders compared with the nonresponders and had statistical significance (p < 0.05). P1 and P2 in the responders was larger than the nonresponders with significant difference (P1: 34.18 ± 21.55 % vs. 9.02 ± 14.02 %, p < 0.05; P2: 53.02 ± 15.50 % vs. 7.74 ± 37.95 %, p < 0.05). The optimal threshold of P1 that can discriminate between P1 responders and P1 nonresponders was greater than 25.9 % reduction, and that of P2 that can discriminate between P2 responders and P2 nonresponders was 34.0 % reduction. The area under the ROC curve (AUC) of P1 and P2 for determining residual disease was 0.856 and 0.909, respectively; but there was no statistical significance between them (p > 0.05). There was a significant difference for OS between P1 responders and P1 nonresponders (p < 0.05), and also for OS between P2 responders and P2 nonresponders (p < 0.05). But there was no difference between the P1 responders and P2 responders (p > 0.05), or between the P1 nonresponders and P2 nonresponders (p > 0.05). A (99m)Tc-3PRGD2 SPECT/CT after two cycles of chemoradiotherapy plus bevacizumab can predict patients who will have a better response to treatment and survival.

Kit preparation and biokinetics in women of 99mTc-EDDA/HYNIC-E-[c(RGDfK)]2 for breast cancer imaging.

PubMed

Ortiz-Arzate, Zareth; Santos-Cuevas, Clara L; Ocampo-García, Blanca E; Ferro-Flores, Guillermina; García-Becerra, Rocío; Estrada, Gisela; Gómez-Argumosa, Edgar; Izquierdo-Sánchez, Vanessa

2014-04-01

In breast cancer, α(ν)β(3) and/or α(ν)β(5) integrins are overexpressed in both endothelial and tumour cells. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence are radiopharmaceuticals with high affinity and selectivity for these integrins. The RGD-dimer peptide (E-[c(RGDfK)]2) radiolabelled with (99m)Tc has been reported as a radiopharmaceutical with a 10-fold higher affinity for the α(ν)β(3) integrin compared with the RGD-monomer. Ethylenediamine-N,N'-diacetic acid (EDDA) is a hydrophilic molecule that may favour renal excretion when used as coligand in the (99m)Tc labelling of hydrazinonicotinamide (HYNIC) peptides and can easily be formulated in a lyophilized kit. The aim of this study was to establish a biokinetic model for (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 prepared from lyophilized kits and evaluate its dosimetry as a tumour-imaging agent in seven healthy women and three breast cancer patients. (99m)Tc labelling was performed by adding sodium pertechnetate solution and 0.2 mol/l phosphate buffer (pH 7.0) to a lyophilized formulation containing E-[c(RGDfK)]2, EDDA, tricine, mannitol and stannous chloride. The radiochemical purity was evaluated using reverse-phase high-performance liquid chromatography and instant thin-layer chromatography on silica gel analyses. Stability studies in human serum were carried out using size-exclusion high-performance liquid chromatography. In-vitro cell uptake was tested using breast cancer cells (MCF7, T47D and MDA-MB-231) with blocked and nonblocked receptors. Biodistribution and tumour uptake were determined in MCF7 tumour-bearing nude mice with blocked and nonblocked receptors, and images were obtained using a micro-SPECT/PET/CT. Whole-body images from seven healthy women were acquired at 0.5, 1, 3, 6 and 24 h after (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 administration with radiochemical purities greater than 94%. Regions of interest were drawn around the source organs at each time frame. Each region of interest was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate the (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 time-activity curves of each organ to adjust the biokinetic model and calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. In three breast cancer patients with histologically confirmed cancer, static images were obtained at 1 h in the supine position with hands placed behind the head. (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained from lyophilized kits demonstrated high stability in human serum and specific cell receptor binding. The biodistribution data from mice showed rapid blood clearance, with both renal and hepatobiliary excretion, and specific binding towards α(ν)β(3) integrins in the MCF7 tumours. In women, the blood activity showed a half-life value of 1.60 min for the fast component (T1/2α = ln2/26.01) and half-life values of 1.0 h for the first slow component (T1/2β = ln2/0.69) and 4.03 h for the second slow component (T1/2γ = ln2/0.16). Images from patients showed an average tumour/heart (blood) ratio of 3.61 ± 0.62 at 1 h. The average equivalent doses calculated for a study using 740 MBq were 4.9, 6.2, 20.7, 34.5 and 57.0 mSv for the liver, intestines, spleen, kidneys and thyroid, respectively, and the effective dose was 6.1 mSv. All absorbed doses were comparable to those known from most of the (99m)Tc studies. (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2 obtained from kit formulations showed high tumour uptake in patients with malignant lesions, making it a promising imaging radiopharmaceutical for targeting site-specific breast cancer. The results obtained in this study warrant further clinical studies to determine the specificity and sensitivity of (99m)Tc-EDDA/HYNIC-E-[c(RGDfK)]2.

Real-time gamma imaging of technetium transport through natural and engineered porous materials for radioactive waste disposal.

PubMed

Corkhill, Claire L; Bridge, Jonathan W; Chen, Xiaohui C; Hillel, Phil; Thornton, Steve F; Romero-Gonzalez, Maria E; Banwart, Steven A; Hyatt, Neil C

2013-12-03

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of (99)Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in (99m)Tc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ~20 MBq (99m)Tc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min(-1). Changes in calibrated mass distribution of (99m)Tc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection-dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that (99)Tc in the pertechnetate form (Tc(VII)O4(-)) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments.

Real-Time Gamma Imaging of Technetium Transport through Natural and Engineered Porous Materials for Radioactive Waste Disposal

PubMed Central

2013-01-01

We present a novel methodology for determining the transport of technetium-99m, a γ-emitting metastable isomer of 99Tc, through quartz sand and porous media relevant to the disposal of nuclear waste in a geological disposal facility (GDF). Quartz sand is utilized as a model medium, and the applicability of the methodology to determine radionuclide transport in engineered backfill cement is explored using the UK GDF candidate backfill cement, Nirex Reference Vault Backfill (NRVB), in a model system. Two-dimensional distributions in 99mTc activity were collected at millimeter-resolution using decay-corrected gamma camera images. Pulse-inputs of ∼20 MBq 99mTc were introduced into short (<10 cm) water-saturated columns at a constant flow of 0.33 mL min–1. Changes in calibrated mass distribution of 99mTc at 30 s intervals, over a period of several hours, were quantified by spatial moments analysis. Transport parameters were fitted to the experimental data using a one-dimensional convection–dispersion equation, yielding transport properties for this radionuclide in a model GDF environment. These data demonstrate that 99Tc in the pertechnetate form (Tc(VII)O4–) does not sorb to cement backfill during transport under model conditions, resulting in closely conservative transport behavior. This methodology represents a quantitative development of radiotracer imaging and offers the opportunity to conveniently and rapidly characterize transport of gamma-emitting isotopes in opaque media, relevant to the geological disposal of nuclear waste and potentially to a wide variety of other subsurface environments. PMID:24147650

Adverse events and treatment failure leading to discontinuation of recently approved antipsychotic drugs in schizophrenia: A network meta-analysis.

PubMed

Tonin, Fernanda S; Piazza, Thais; Wiens, Astrid; Fernandez-Llimos, Fernando; Pontarolo, Roberto

2015-12-01

Objective:We aimed to gather evidence of the discontinuation rates owing to adverse events or treatment failure for four recently approved antipsychotics (asenapine, blonanserin, iloperidone, and lurasidone).Methods: A systematic review followed by pairwise meta-analysis and mixed treatment comparison meta analysis(MTC) was performed, including randomized controlled trials (RCTs) that compared the use of the above-mentioned drugs versus placebo in patients with schizophrenia. An electronic search was conducted in PubMed, Scopus, Science Direct, Scielo, the Cochrane Library, and International Pharmaceutical Abstracts(January 2015). The included trials were at least single blinded. The main outcome measures extracted were discontinuation owing to adverse events and discontinuation owing to treatment failure.Results: Fifteen RCTs were identified (n = 5400 participants) and 13 of them were amenable for use in our meta-analyses. No significant differences were observed between any of the four drugs and placebo as regards discontinuation owing to adverse events, whether in pairwise meta-analysis or in MTC. All drugs presented a better profile than placebo on discontinuation owing to treatment failure, both in pairwise meta-analysis and MTC. Asenapine was found to be the best therapy in terms of tolerability owing to failure,while lurasidone was the worst treatment in terms of adverse events. The evidence around blonanserin is weak.Conclusion: MTCs allowed the creation of two different rank orders of these four antipsychotic drugs in two outcome measures. This evidence-generating method allows direct and indirect comparisons, supporting approval and pricing decisions when lacking sufficient, direct, head-to-head trials.

Management of treatment-related toxicities in advanced medullary thyroid cancer.

PubMed

Brose, Marcia S; Bible, Keith C; Chow, Laura Q M; Gilbert, Jill; Grande, Carolyn; Worden, Francis; Haddad, Robert

2018-05-01

Progress in the treatment of advanced medullary thyroid cancer (MTC) has resulted from the approval of 2 drugs within the past 5 years, vandetanib and cabozantinib. These multikinase inhibitors (MKIs) possess overlapping specificities for multiple kinase targets implicated in the progression of MTC. Both drugs are associated with toxicities, including hypertension, hemorrhage/perforation, diarrhea and other gastrointestinal events, several dermatologic events, and hypothyroidism. In addition, vandetanib is uniquely associated with QTc prolongation through interaction with myocardial potassium channels, and cabozantinib is uniquely associated with hand-foot skin reaction. Treatment-related toxicities occur frequently and can be severe or life-threatening, and patients undergoing long-term treatment will likely experience adverse events (AEs). Here we offer specific practical recommendations for managing AEs commonly occurring with vandetanib and cabozantinib. The recommended approach relies on early recognition and palliation of symptoms, dose interruption, and dose reduction as necessary in order for the patient to maintain the highest tolerable dose for as long as possible and optimal quality of life. Treatment guidelines do not specify a recommended sequence for treating with vandetanib and cabozantinib; however, most patients will receive both drugs during their lifetime. The choice for first-line therapy is individualized after a risk-benefit assessment and depends on physician preference and patient-related factors, such as comorbid conditions. Because most generalist practices may not be familiar with the intricacies of agents such as vandetanib and cabozantinib, we commend that patients with advanced MTC be managed and treated by a thyroid cancer specialist with coordination of care within a multidisciplinary team. Copyright © 2018. Published by Elsevier Ltd.

Cost-benefit of the telecardiology service in the state of Minas Gerais: Minas Telecardio Project.

PubMed

Andrade, Mônica Viegas; Maia, Ana Carolina; Cardoso, Clareci Silva; Alkmim, Maria Beatriz; Ribeiro, Antônio Luiz Pinho

2011-10-01

Telecardiology is a tool that can aid in cardiovascular care, mainly in towns located in remote areas. However, economic assessments on this subject are scarce and have yielded controversial results. To evaluate the cost-benefit of implementing a Telecardiology service in remote, small towns in the state of Minas Gerais, Brazil. The study used the database from the Minas Telecardio (MTC) Project, developed from June 2006 to November 2008, in 82 towns in the countryside of the state. Each municipality received a microcomputer with a digital electrocardiograph, with the possibility of transmitting ECG tracings and communicating with the on-duty cardiologist at the University hospital. The cost-benefit analysis was carried out by comparing the cost of performing an ECG in the project versus the cost of performing it by patient referral to another city. The average cost of an ECG in the MTC project was R$ 28.92, decomposed into R$ 8.08 for the cost of implementation and R$ 20.84 for maintenance. The cost simulation of the ECG with referral ranged from R$ 30.91 to R$ 54.58, with the cost-benefit ratio being always favorable to the MTC program, regardless of the type of calculation used for referral distance. The simulations considered the financial sponsor's and society's points-of-view. The sensitivity analysis with variation of calibration parameters confirmed these results. The implementation of a Telecardiology system as support to primary care in small Brazilian towns is feasible and economically beneficial, and can be used as a regular program within the Brazilian public health system.

Magnetic Transfer Contrast Accurately Localizes Substantia Nigra Confirmed by Histology

PubMed Central

Bolding, Mark S.; Reid, Meredith A.; Avsar, Kathy B.; Roberts, Rosalinda C.; Gamlin, Paul D.; Gawne, Timothy J.; White, David M.; den Hollander, Jan A.; Lahti, Adrienne C.

2012-01-01

Background Magnetic Resonance Imaging (MRI) has multiple contrast mechanisms. Like various staining techniques in histology, each contrast type reveals different information about the structure of the brain. However, it is not always clear how structures visible in MRI correspond to structures previously identified by histology. The purpose of this study was to determine if magnetic transfer contrast (MTC) or T2 contrast MRI was better at delineating the substantia nigra. Methods MRI scans were acquired in-vivo from two non-human primates (NHPs). The NHPs were subsequently euthanized, perfused, and their brains sectioned for histological analyses. Each slice was photographed prior to sectioning. Each brain was sectioned into approximately 500, 40-micron sections, encompassing most of the cortex, midbrain, and dorsal parts of the hindbrain. Levels corresponding to anatomical MRI images were selected. From these, adjacent sections were stained using Kluver Barrera (myelin and cell bodies) or tyrosine hydroxylase (TH) (dopaminergic neurons) immunohistochemistry. The resulting images were coregistered to the block-face images using a moving least squares algorithm with similarity transformations. MR images were similarly coregistered to the block-face images, allowing the structures in the MRI to be identified with structures in the histological images. Results We found that hyperintense (light) areas in MTC images were coextensive with the SN as delineated histologically. The hypointense (dark) areas in T2-weighted images were not coextensive with the SN, but extended partially into the SN and partially into the cerebral peduncles. Conclusions MTC is a more accurate contrast mechanism than T2-weighting for localizing the SN in vivo. PMID:22981657

Rapid noninvasive detection of experimental atherosclerotic lesions with novel 99mTc-labeled diadenosine tetraphosphates

PubMed Central

Elmaleh, David R.; Narula, Jagat; Babich, John W.; Petrov, Artiom; Fischman, Alan J.; Khaw, Ban-An; Rapaport, Eliezer; Zamecnik, Paul C.

1998-01-01

The development of a noninvasive imaging procedure for identifying atherosclerotic lesions is extremely important for the clinical management of patients with coronary artery and peripheral vascular disease. Although numerous radiopharmaceuticals have been proposed for this purpose, none has demonstrated the diagnostic accuracy required to replace invasive angiography. In this report, we used the radiolabeled purine analog, 99mTc diadenosine tetraphosphate (Ap4A; AppppA, P1,P4-di(adenosine-5′)-tetraphosphate) and its analogue 99mTc AppCHClppA for imaging experimental atherosclerotic lesions in New Zealand White rabbits. Serial gamma camera images were obtained after intravenous injection of the radiolabeled dinucleotides. After acquiring the final images, the animals were sacrificed, ex vivo images of the aortas were recorded, and biodistribution was measured. 99mTc-Ap4A and 99mTc AppCHClppA accumulated rapidly in atherosclerotic abdominal aorta, and lesions were clearly visible within 30 min after injection in all animals that were studied. Both radiopharmaceuticals were retained in the lesions for 3 hr, and the peak lesion to normal vessel ratio was 7.4 to 1. Neither of the purine analogs showed significant accumulation in the abdominal aorta of normal (control) rabbits. The excised aortas showed lesion patterns that were highly correlated with the in vivo and ex vivo imaging results. The present study demonstrates that purine receptors are up-regulated in experimental atherosclerotic lesions and 99mTc-labeled purine analogs have potential for rapid noninvasive detection of plaque formation. PMID:9435254

Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft-poly(ethylene glycol): in vitro and in vivo studies.

PubMed

Kim, Eun-Mi; Jeong, Hwan-Jeong; Park, In-Kyu; Cho, Chong-Su; Moon, Hyung-Bae; Yu, Dae-Yeul; Bom, Hee-Seung; Sohn, Myung-Hee; Oh, In-Joon

2005-11-28

The asialoglycoprotein receptor (ASGP-R) on the hepatocyte membrane is a specific targeting marker for gene and drug delivery. Polyethylenimine (PEI) is a polycationic nonviral vector that is used for gene transfer. We have synthesized galactosylated polyethylenimine-graft-poly(ethylene glycol) (GPP) for performing gene delivery to the hepatocytes. The present study reports on the in vitro and in vivo data that was achieved in hepatoma bearing transgenic mice. The cytotoxicity was decreased with the increasing PEG content. The particle size of the complex was increased with the increasing PEG at an N/P ratio of 3.0, while the zeta potentials were decreased. The (99m)Tc labeled complexes were transfected into HepG2 and HeLa cells, while the GFP reporter genes were mainly expressed in the HepG2 cells. The in vivo data was achieved in ALB/c-Ha-ras transgenic mice. (99m)Tc labeled GPP(50)/DNA was injected into the mice via the tail vein, and the gamma images were acquired at 5, 15 and 30 min. The (99m)Tc labeled complexes were mainly localized in the heart and liver, and they were excreted through the kidneys. The GFP gene was mainly expressed in the proliferating cells at the tumor periphery. This result was confirmed by PCNA staining. The GPP(50)/DNA complexes were bound to ASGP-R of the proliferating hepatocytes in vitro and in vivo. The present results demonstrate the feasibility of nonviral gene transfer using galactosylated PEI-PEG in vivo.

Improved synthesis and biological evaluation of Tc-99m radiolabeled AMO for miRNA imaging in tumor xenografts.

PubMed

Kang, Lei; Fan, Zhongyi; Sun, Hongwei; Feng, Yingying; Ma, Chao; Yan, Ping; Zhang, Chunli; Ma, Huan; Hao, Pan; Chen, Xueqi; Zheng, Zhibing; Xu, Xiaojie; Wang, Rongfu

2015-01-01

MicroRNAs (miRNAs) have been considered as important biomarkers for malignant tumors. In this study, we introduced an improved (99m)Tc labeling method for noninvasive visualization of overexpressed miRNAs in tumor-bearing mice. Anti-miRNA-21 oligonucleotide (AMO) with partial 2'-O-methyl and phosphorothioate modification was designed and chemically synthesized. After conjugated with NHS-MAG3, AMO was labeled with (99m)Tc. Optimization was made to shorten reaction time and to improve labeling efficiency. Labeling efficiency was 97%, and specific activity was 2.78 MBq/ng. During 12 h, (99m)Tc-AMO showed no significant degradation by gel electrophoresis. Its radiochemical purity was stable, between 95.8% and 99.1%. Further, (99m)Tc-AMO decreased the level of miR-21 and increased the expression of PTEN protein at cellular level, shown by qRT-PCR and Western blot. Fluorescent protein labeled AMO displayed specific distribution and good stability in tumor cells. After the administration in tumor-bearing mice, (99m)Tc-AMO showed more radioactive uptake in the miR-21 over-expressed tumors than scramble control. Biodistribution results further proved the significant difference of tumor uptake between (99m)Tc-AMO and (99m)Tc-control. Therefore, this study presents an improved method with shorten time to prepare a (99m)Tc radiolabeled AMO. In addition, it supports the role of (99m)Tc-AMO for noninvasive visualization of miR-21 in malignant tumors. Copyright © 2015 John Wiley & Sons, Ltd.

Respiration Gates Sensory Input Responses in the Mitral Cell Layer of the Olfactory Bulb

PubMed Central

Short, Shaina M.; Morse, Thomas M.; McTavish, Thomas S.; Shepherd, Gordon M.; Verhagen, Justus V.

2016-01-01

Respiration plays an essential role in odor processing. Even in the absence of odors, oscillating excitatory and inhibitory activity in the olfactory bulb synchronizes with respiration, commonly resulting in a burst of action potentials in mammalian mitral/tufted cells (MTCs) during the transition from inhalation to exhalation. This excitation is followed by inhibition that quiets MTC activity in both the glomerular and granule cell layers. Odor processing is hypothesized to be modulated by and may even rely on respiration-mediated activity, yet exactly how respiration influences sensory processing by MTCs is still not well understood. By using optogenetics to stimulate discrete sensory inputs in vivo, it was possible to temporally vary the stimulus to occur at unique phases of each respiration. Single unit recordings obtained from the mitral cell layer were used to map spatiotemporal patterns of glomerular evoked responses that were unique to stimulations occurring during periods of inhalation or exhalation. Sensory evoked activity in MTCs was gated to periods outside phasic respiratory mediated firing, causing net shifts in MTC activity across the cycle. In contrast, odor evoked inhibitory responses appear to be permitted throughout the respiratory cycle. Computational models were used to further explore mechanisms of inhibition that can be activated by respiratory activity and influence MTC responses. In silico results indicate that both periglomerular and granule cell inhibition can be activated by respiration to internally gate sensory responses in the olfactory bulb. Both the respiration rate and strength of lateral connectivity influenced inhibitory mechanisms that gate sensory evoked responses. PMID:28005923

Study of axial mixing, holdup and slip velocity of dispersed phase in a pulsed sieve plate extraction column using radiotracer technique.

PubMed

Ghiyas Ud Din; Imran Rafiq Chughtai; Hameed Inayat, Mansoor; Hussain Khan, Iqbal

2009-01-01

Axial mixing, holdup and slip velocity of dispersed phase which are parameters of fundamental importance in the design and operation of liquid-liquid extraction pulsed sieve plate columns have been investigated. Experiments for residence time distribution (RTD) analysis have been carried out for a range of pulsation frequency and amplitude in a liquid-liquid extraction pulsed sieve plate column with water as dispersed and kerosene as continuous phase using radiotracer technique. The column was operated in emulsion region and (99m)Tc in the form of sodium pertechnetate eluted from a (99)Mo/(99m)Tc generator was used to trace the dispersed phase. Axial dispersed plug flow model with open-open boundary condition and two points measurement method was used to simulate the hydrodynamics of dispersed phase. It has been observed that the axial mixing and holdup of dispersed phase increases with increase in pulsation frequency and amplitude until a maximum value is achieved while slip velocity decreases with increase in pulsation frequency and amplitude until it approaches a minimum value. Short lived and low energy radiotracer (99m)Tc in the form of sodium pertechnetate was found to be a good water tracer to study the hydrodynamics of a liquid-liquid extraction pulsed sieve plate column operating with two immiscible liquids, water and kerosene. Axial dispersed plug flow model with open-open boundary condition was found to be a suitable model to describe the hydrodynamics of dispersed phase in the pulsed sieve plate extraction column.

Scintigraphic diagnosis of gastric carcinoma (in Hebrew)

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

Czerniak, D.

1972-09-01

During the past 10 years efforts have been made to develop a radioisotope test for gastric malignancy. Phosphorus-32 was used by intracavity procedures (gastric tube-detector; autoradiography) but the procedures were difficult. In 1961 the first scintillographic assays with scanners and then with scintillation cameras were performed. Iodine-131 was used at first and since 1965 /sup 99m/Tc, which is superior from a physical point of view. It was established that a cold space-occupying lesion in the gastroscan indicates malignancy and that a foggy scan, general or local, may also indicate a neoplastic lesion. All other conditions, including peptic ulcer and gastritis,more » give a normal scan. In the dog, injection of /sup 99m/Tc indicated a turnover of the isotope in the body, and that it is concentrated in the gastric mucosa and excreted in the gastric juice. A gastroscintillographic study in 220 patients showed that 54 of them had stomach malignancies (51 carcinoma and 3 sarcoma). Only neoplasms at least 2 cm in diameter were visualized. In all the patients, clinical, radiological, and biochemical examinations were performed and in most, pathological examinations as well. There was correspondence with the final diagnosis in 80% of the scintillographed cancers and in 92% of those studied roentgenologically. The false scinttllographic diagnosed conclusions were mostly in diffurent patients than in those with false roentgenological diagnoses. It can therefore be concluded that the two methods are complementary. The radiological exposure due to /sup 99m/Tc scintivisualization is low, 200 mrad to the stomach and l5 mrad to the whole body. (INIS)« less

Anelastic spherical dynamos with radially variable electrical conductivity

NASA Astrophysics Data System (ADS)

Dietrich, W.; Jones, C. A.

2018-05-01

A series of numerical simulations of the dynamo process operating inside gas giant planets has been performed. We use an anelastic, fully nonlinear, three-dimensional, benchmarked MHD code to evolve the flow, entropy and magnetic field. Our models take into account the varying electrical conductivity, high in the ionised metallic hydrogen region, low in the molecular outer region. Our suite of electrical conductivity profiles ranges from Jupiter-like, where the outer hydrodynamic region is quite thin, to Saturn-like, where there is a thick non-conducting shell. The rapid rotation leads to the formation of two distinct dynamical regimes which are separated by a magnetic tangent cylinder - mTC. Outside the mTC there are strong zonal flows, where Reynolds stress balances turbulent viscosity, but inside the mTC Lorentz force reduces the zonal flow. The dynamic interaction between both regions induces meridional circulation. We find a rich diversity of magnetic field morphologies. There are Jupiter-like steady dipolar fields, and a belt of quadrupolar dominated dynamos spanning the range of models between Jupiter-like and Saturn-like conductivity profiles. This diversity may be linked to the appearance of reversed sign helicity in the metallic regions of our dynamos. With Saturn-like conductivity profiles we find models with dipolar magnetic fields, whose axisymmetric components resemble those of Saturn, and which oscillate on a very long time-scale. However, the non-axisymmetric field components of our models are at least ten times larger than those of Saturn, possibly due to the absence of any stably stratified layer.

Performance Analysis of Millimeter-Wave Multi-hop Machine-to-Machine Networks Based on Hop Distance Statistics

PubMed Central

2018-01-01

As an intrinsic part of the Internet of Things (IoT) ecosystem, machine-to-machine (M2M) communications are expected to provide ubiquitous connectivity between machines. Millimeter-wave (mmWave) communication is another promising technology for the future communication systems to alleviate the pressure of scarce spectrum resources. For this reason, in this paper, we consider multi-hop M2M communications, where a machine-type communication (MTC) device with the limited transmit power relays to help other devices using mmWave. To be specific, we focus on hop distance statistics and their impacts on system performances in multi-hop wireless networks (MWNs) with directional antenna arrays in mmWave for M2M communications. Different from microwave systems, in mmWave communications, wireless channel suffers from blockage by obstacles that heavily attenuate line-of-sight signals, which may result in limited per-hop progress in MWNs. We consider two routing strategies aiming at different types of applications and derive the probability distributions of their hop distances. Moreover, we provide their baseline statistics assuming the blockage-free scenario to quantify the impact of blockages. Based on the hop distance analysis, we propose a method to estimate the end-to-end performances (e.g., outage probability, hop count, and transmit energy) of the mmWave MWNs, which provides important insights into mmWave MWN design without time-consuming and repetitive end-to-end simulation. PMID:29329248

Performance Analysis of Millimeter-Wave Multi-hop Machine-to-Machine Networks Based on Hop Distance Statistics.

PubMed

Jung, Haejoon; Lee, In-Ho

2018-01-12

As an intrinsic part of the Internet of Things (IoT) ecosystem, machine-to-machine (M2M) communications are expected to provide ubiquitous connectivity between machines. Millimeter-wave (mmWave) communication is another promising technology for the future communication systems to alleviate the pressure of scarce spectrum resources. For this reason, in this paper, we consider multi-hop M2M communications, where a machine-type communication (MTC) device with the limited transmit power relays to help other devices using mmWave. To be specific, we focus on hop distance statistics and their impacts on system performances in multi-hop wireless networks (MWNs) with directional antenna arrays in mmWave for M2M communications. Different from microwave systems, in mmWave communications, wireless channel suffers from blockage by obstacles that heavily attenuate line-of-sight signals, which may result in limited per-hop progress in MWNs. We consider two routing strategies aiming at different types of applications and derive the probability distributions of their hop distances. Moreover, we provide their baseline statistics assuming the blockage-free scenario to quantify the impact of blockages. Based on the hop distance analysis, we propose a method to estimate the end-to-end performances (e.g., outage probability, hop count, and transmit energy) of the mmWave MWNs, which provides important insights into mmWave MWN design without time-consuming and repetitive end-to-end simulation.

Midwest Transportation Consortium annual progress report : October 2002.

DOT National Transportation Integrated Search

2002-10-01

From the Director: For the past three years, the Midwest Transportation Consortium (MTC) has focused its efforts in : supporting the development and use of asset management systems in transportation. The MTCs main : focus is on human capital devel...

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

Jones, D.K.; Higenbottam, T.W.

Despite no radiographic change, a patient with Pneumocystis pneumonia showed increased clearance of inhaled /sup 99m/Tc DTPA from lung to blood. Gas transfer for carbon monoxide was also reduced, but improved with treatment. This was paralleled by serial increase in the t1/2 LB.

Mass Transportation in Massachusetts : demonstration project progress report no. 4

DOT National Transportation Integrated Search

1963-09-01

This fourth Progress Report presents the results of the first eight months of the program of demonstration experiments which the MTC is conducting in cooperation wit the Office of Transportation of the Housing and Home Finance Agency.

PEGylated N-methyl-S-methyl dithiocarbazate as a new reagent for the high-yield preparation of nitrido Tc-99m and Re-188 radiopharmaceuticals.

PubMed

Boschi, Alessandra; Massi, Alessandro; Uccelli, Licia; Pasquali, Micol; Duatti, Adriano

2010-11-01

A novel nitrido nitrogen atom donor for the preparation of (99m)Tc and (188)Re radiopharmaceuticals containing a metal-nitrogen multiple bond is presented. HO(2)C-PEG(600)-DTCZ was obtained by conjugation of N-methyl-S-methyl dithiocarbazate [H(2)N-N(CH(3))-C(S)SCH(3), HDTCZ] with polyethylene glycol 600 (PEG(600)). Asymmetrical heterocomplexes of the type [M(N)(PNP)(B)](0/+) (M=(99m)Tc, (188)Re; PNP=diphosphine ligands, B=DBODC, DEDC, NSH, H(2)OS, CysNAc, HDTCZ) and symmetrical nitride compounds of the type [M(N)(L)(2)] (L=DEDC, DPDC) have been prepared in high yield by using the newly designed nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ. A two-step procedure was applied for preparing the above symmetrical and asymmetrical complexes. The first step involved the preliminary formation of a mixture of nitride Tc-99m or Re-188 precursors, which contained the [M≡N](2+) core, through reduction of generator-eluted (99m)Tc-pertechnetate or (188)Re-perrhenate with thin (II) chloride in the presence of HO(2)C-PEG(600)-DTCZ. In the second step, the intermediate mixture was converted either in the final mixed asymmetrical complex by the simultaneous addition of diphosphine ligand and the suitable bidentate ligand B, or in the final symmetrical complex by the only addition of the bidentate ligand L. It was also demonstrated that the novel water-soluble nitride nitrogen atom donor HO(2)C-PEG(600)-DTCZ did not show coordinating properties toward the M≡N ((99m)Tc, (188)Re) core. Biodistribution studies in rats of the hitherto unreported [(99m)Tc(N)(PNP(3))DTCZ](+) and [(99m)Tc(N)(PNP(5))DTCZ](+) complexes showed that they selectively localize in the myocardium of rats with a favourable heart-to-lung and heart-to-liver uptake ratios. In particular, the heart-to-lung and heart-to-liver uptake ratios dramatically increased in the interval between 60 and 120 min postinjection. Hence, the combination of the favourable chemical and biological properties of HO(2)C-PEG(600)-DTCZ might confer to this novel compound an important role for the development of new (99m)Tc and (188)Re-nitrido radiopharmaceuticals. Copyright © 2010 Elsevier Inc. All rights reserved.

A-site deficiency effects on the critical behavior of La0.6Ca0.15·0.05Ba0.2MnO3

NASA Astrophysics Data System (ADS)

Debbebi, I. Sfifir; Omrani, H.; Cheikhrouhou-Koubaa, W.; Cheikhrouhou, A.

2018-02-01

The aim of the present work is to study the critical behavior of calcium deficient La0.6Ca0.15·0.05Ba0.2MnO3 (LCBMO), synthetized by the conventional solid-state reaction method, around the paramagnetic (PM)-ferromagnetic (FM) phase transition. X-ray diffraction revealed that these manganites crystallized in the orthorhombic structure with Pbnm space group. Then, the magnetic properties of this compound are discussed in detail, building on the magnetization and the susceptibility. The temperature dependence of magnetic susceptibility at higher temperature confirms the presence of the Griffiths phase above the Curie temperature which proves the existence of ferromagnetic clusters in the paramagnetic domain. Experimental results revealed that our sample exhibit a second-order magnetic phase transition. The estimated critical exponents derived from the magnetic data were estimated using various techniques such as modified Arrott plot, Kouvel-Fisher method, and critical magnetization isotherms M(TC, H). The obtained values are very close to those representative of the mean-field model (β = 0.547, γ = 1.23, and δ = 3.092 at an average TC = 201.74 K).

Preclinical molecular imaging: development of instrumentation for translational research with small laboratory animals.

PubMed

Mejia, Jorge; Miranda, Ana Claudia Camargo; Durante, Ana Claudia Ranucci; Oliveira, Larissa Rolim de; Barboza, Marycel Rosa Felisa Figols de; Rosell, Katerin Taboada; Jardim, Daniele Pereira; Campos, Alexandre Holthausen; Reis, Marilia Alves Dos; Catanoso, Marcela Forli; Galvis-Alonso, Orfa Yineth; Cabral, Francisco Romero

2016-01-01

To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99mTc-Sestamibi), technetium-labeled dimercaptosuccinic acid (99mTc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99mTc-HMPAO). This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others. Apresentar o resultado da adaptação de uma gama câmara clínica para uso dedicado na obtenção de imagens tomográficas in vivo de órgãos de pequenos animais de experimentação, e de sua aplicação na obtenção de imagens cardíacas, renais e neurológicas. Foi construída uma versão atualizada do dispositivo de adaptação miniSPECT, composto por três subsistemas: mecânico, eletrônico e de software. O dispositivo foi montado em uma câmara Discovery VH da General Electric Healthcare, retirada do serviço clínico e instalada no Centro de Imagem Pré-Clínica do Hospital Israelita Albert Einstein. O sistema combinado foi caracterizado, determinando parâmetros de funcionamento como resolução espacial, magnificação, limites de tamanho dos alvos de estudo, número de projeções, tempo de registro e tempo de reconstrução das imagens tomográficas. Foram obtidas imagens com resolução espacial de até 0,5mm, com tempos de registro e reconstrução de 30 a 45 minutos, utilizando reconstrução iterativa com 10 a 20 iterações e 4 subconjuntos de projeções. O sistema foi validado obtendo imagens tomográficas in vivo do coração, dos rins e do cérebro de animais normais (camundongos e ratos adultos), utilizando os radiofármacos hexaquis-2-metoxi-isobutil-isonitrila marcado com 99mTc (Sestamibi-99mTc), ácido dimercaptosuccínico marcado com 99mTc (DMSA-99mTc) e hexametil-propileno-amina-oxima marcada com 99mTc (HMPAO-99mTc). Este tipo de aplicação, que consiste na adaptação para um objetivo alternativo de instrumentação já existente, constituiu-se em uma opção de infraestrutura de baixo custo, que permite realizar estudos in vivo em larga escala, com qualidade aprimorada, em áreas diversas, como neurologia, nefrologia, cardiologia, entre outras.

A Generator-Produced Gallium-68 Radiopharmaceutical for PET Imaging of Myocardial Perfusion

PubMed Central

Sharma, Vijay; Sivapackiam, Jothilingam; Harpstrite, Scott E.; Prior, Julie L.; Gu, Hannah; Rath, Nigam P.; Piwnica-Worms, David

2014-01-01

Lipophilic cationic technetium-99m-complexes are widely used for myocardial perfusion imaging (MPI). However, inherent uncertainties in the supply chain of molybdenum-99, the parent isotope required for manufacturing 99Mo/99mTc generators, intensifies the need for discovery of novel MPI agents incorporating alternative radionuclides. Recently, germanium/gallium (Ge/Ga) generators capable of producing high quality 68Ga, an isotope with excellent emission characteristics for clinical PET imaging, have emerged. Herein, we report a novel 68Ga-complex identified through mechanism-based cell screening that holds promise as a generator-produced radiopharmaceutical for PET MPI. PMID:25353349

The slightly-enriched spectral shift control reactor. Final report, September 30, 1988--September 30, 1991

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

Martin, W.R.; Lee, J.C.; Larsen, E.W.

1991-11-01

An advanced converter reactor design utilizing mechanical spectral shift control rods in a conventional pressurized water reactor configuration is under investigation. The design is based on the principle that a harder spectrum during the early part of the fuel cycle will result in large neutron captures in fertile {sup 238}U, which can then be burned in situ in a softer spectrum later in the cycle. Preliminary design calculations performed during FY 89 showed that the slightly-enriched spectral shift reactor design offers the benefit of substantially increased fuel resource utilization with the proven safety characteristics of the pressurized water reactor technologymore » retained. Optimization of the fuel design and development of fuel management strategies were carried out in FY 90, along with effort to develop and validate neutronic methodology for tight-lattice configurations with hard spectra. During FY 91, the final year of the grant, the final Slightly-Enriched Spectral Shift Reactor (SESSR) design was determined, and reference design analyses were performed for the assemblies as well as the global core configuration, both at the beginning of cycle (BOC) and with depletion. The final SESSR design results in approximately a 20% increase in the utilization of uranium resources, based on equilibrium fuel cycle analyses. Acceptable pin power peaking is obtained with the final core design, with assembly peaking factors equal to less than 1.04 for spectral shift control rods both inserted and withdrawn, and global peaking factors at BOC predicted to be 1.4. In addition, a negative Moderation Temperature Coefficient (MTC) is maintained for BOC, which is difficult to achieve with conventional advanced converter designs based on a closed fuel cycle. The SESSR design avoids the need for burnable poison absorber, although they could be added if desired to increase the cycle length while maintaining a negative MTC.« less

The slightly-enriched spectral shift control reactor

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

Martin, W.R.; Lee, J.C.; Larsen, E.W.

1991-11-01

An advanced converter reactor design utilizing mechanical spectral shift control rods in a conventional pressurized water reactor configuration is under investigation. The design is based on the principle that a harder spectrum during the early part of the fuel cycle will result in large neutron captures in fertile {sup 238}U, which can then be burned in situ in a softer spectrum later in the cycle. Preliminary design calculations performed during FY 89 showed that the slightly-enriched spectral shift reactor design offers the benefit of substantially increased fuel resource utilization with the proven safety characteristics of the pressurized water reactor technologymore » retained. Optimization of the fuel design and development of fuel management strategies were carried out in FY 90, along with effort to develop and validate neutronic methodology for tight-lattice configurations with hard spectra. During FY 91, the final year of the grant, the final Slightly-Enriched Spectral Shift Reactor (SESSR) design was determined, and reference design analyses were performed for the assemblies as well as the global core configuration, both at the beginning of cycle (BOC) and with depletion. The final SESSR design results in approximately a 20% increase in the utilization of uranium resources, based on equilibrium fuel cycle analyses. Acceptable pin power peaking is obtained with the final core design, with assembly peaking factors equal to less than 1.04 for spectral shift control rods both inserted and withdrawn, and global peaking factors at BOC predicted to be 1.4. In addition, a negative Moderation Temperature Coefficient (MTC) is maintained for BOC, which is difficult to achieve with conventional advanced converter designs based on a closed fuel cycle. The SESSR design avoids the need for burnable poison absorber, although they could be added if desired to increase the cycle length while maintaining a negative MTC.« less

NOTE: Acceleration of Monte Carlo-based scatter compensation for cardiac SPECT

NASA Astrophysics Data System (ADS)

Sohlberg, A.; Watabe, H.; Iida, H.

2008-07-01

Single proton emission computed tomography (SPECT) images are degraded by photon scatter making scatter compensation essential for accurate reconstruction. Reconstruction-based scatter compensation with Monte Carlo (MC) modelling of scatter shows promise for accurate scatter correction, but it is normally hampered by long computation times. The aim of this work was to accelerate the MC-based scatter compensation using coarse grid and intermittent scatter modelling. The acceleration methods were compared to un-accelerated implementation using MC-simulated projection data of the mathematical cardiac torso (MCAT) phantom modelling 99mTc uptake and clinical myocardial perfusion studies. The results showed that when combined the acceleration methods reduced the reconstruction time for 10 ordered subset expectation maximization (OS-EM) iterations from 56 to 11 min without a significant reduction in image quality indicating that the coarse grid and intermittent scatter modelling are suitable for MC-based scatter compensation in cardiac SPECT.

High efficiency microfluidic beta detector for pharmacokinetic studies in small animals

NASA Astrophysics Data System (ADS)

Convert, Laurence; Girard-Baril, Frédérique; Renaudin, Alan; Grondin, Étienne; Jaouad, Abdelatif; Aimez, Vincent; Charette, Paul; Lecomte, Roger

2011-10-01

New radiotracers are continuously being developed to improve diagnostic efficiency using Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET). The characterization of their pharmacokinetics requires blood radioactivity monitoring over time during the scan and is very challenging in small animals because of the low volume of blood available. In this work, a prototype microfluidic blood counter made of a microchannel atop a silicon substrate containing PIN photodiodes is proposed to improve beta detection efficiency in a small volume by eliminating unnecessary interfaces between fluid and detector. A flat rectangular-shaped epoxy channel, 36 μm×1.26 mm cross section and 31.5 mm in length, was microfabricated over a die containing an array of 2×2 mm 2 PIN photodiodes, leaving only a few micrometers of epoxy floor layer between the fluid and the photodiode sensitive surface. This geometry leads to a quasi 2D source, optimizing geometrical detection efficiency that was estimated at 41% using solid angle calculation. CV- IV measurements were made at each fabrication step to confirm that the microchannel components had no significant effects on the diodes' electrical characteristics. The chip was wire-bonded to a PCB and connected to charge sensitive preamplifier and amplifier modules for pulse shaping. Energy spectra recorded for different isotopes showed continuous beta distribution for PET isotopes and monoenergetic conversion electron peaks for 99mTc. Absolute sensitivity was determined for the most popular PET and SPECT radioisotopes and ranged from 26% to 33% for PET tracers ( 18F, 13N, 11C, 68Ga) and more than 2% for 99mTc. Input functions were successfully simulated with 18F, confirming the setup's suitability for pharmacokinetic modeling of PET and SPECT radiotracers in animal experiments. By using standard materials and procedures, the fabrication process is well suited to on-chip microfluidic functionality, allowing full characterization of new radiotracers.

Diuretic 99mTc DTPA renography in assessment of renal function and drainage in infants with antenatally detected hydronephrosis.

PubMed

Radulović, Marija; Pucar, Dragan; Jauković, Ljiljana; Sisić, Marija; Krstić, Zoran; Ajdinović, Boris

2015-12-01

The controversy over the postnatal management of infants with antenataly detected hydronephrosis (ANH) still exists. We presented the results of diuretic 99mTc diethylenetriamine pentaacetic acid (DTPA) renography in 30 infants with the antenatal diagnosis of unilateral renal pelvic dilatation. The aim of this study was to assess the renal function determined by the pattern of drainage and split renal function (SRF) on diuretic renography and to correlate these findings with anteroposterior pelvic diameter (APD) estimated by ultrasonography. A total of 30 infants with 60 renal units (RU) (25 boys and 5 girls, median age 6.0 months, range 2-24) presented with unilateral hydronephrosis on ultrasound in the newborn period, underwent DTPA diuretic renal scintigraphy (F+15 protocol). The median APD evaluated on perinatal ultrasound was 15 mm (range 5-30). The postnatal associated clinical diagnosis were pelviureteric junction obstruction (PUJ), simple hydronephrosis, megaureter, vesicoureteral reflux (VUR) and posterior urethral valves in 11, 10, 6, 2 and 1 infant, respectively. Images and Tmax/2 after diuretic stimulation on the background subtracted renographic curves were used as the criteria for classifying the drainage as good, partial, and poor or no drainage. The SRF was calculated with the integral method. Good drainage was shown in 36/60, partial drainage in 13/60 and poor or no drainage in 11/60 RU. The SRF > 40% was observed in 55/60 RU, with no RU showing SRF lower than 23.5%. In infants with severe ANH the obstruction was not excluded in 94.1%. Diuretic renography in antenatally detected hydronephrosis should be a useful tool in postnatal follow up, especially in differentiating nonobstructive hydronephrosis from obstructive. It is also importanat to assess and monitor the SRF. Our results suggest that even in the presence of partial or no drainage, SRF may not be significantly impaired.

Radiolabelling of glycosylated MFE-23::CPG2 fusion protein (MFECP1) with 99mTc for quantitation of tumour antibody-enzyme localisation in antibody-directed enzyme pro-drug therapy (ADEPT).

PubMed

Francis, R J; Mather, S J; Chester, K; Sharma, S K; Bhatia, J; Pedley, R B; Waibel, R; Green, A J; Begent, R H J

2004-08-01

MFECP1 is a glycosylated recombinant fusion protein composed of MFE-23, a high-affinity anti-carcinoembryonic antigen (CEA) single chain Fv (scFv), fused to the enzyme carboxypeptidase G2 (CPG2), and has been constructed for use in antibody-directed enzyme pro-drug therapy (ADEPT). Radiolabelling of glycosylated MFECP1 with technetium-99m was developed for the purpose of determining tumour localisation of MFECP1 in a phase I ADEPT clinical study. The method used was 99mTc-carbonyl [99mTc(H2O)3(CO)3]+ (abbreviated to TcCO) mediated labelling of 99mTc to the hexahistidine (His) tag of MFECP1. MFECP1 fusion protein was labelled with TcCO under a variety of conditions, and this was shown to be a relatively simple and robust method. Tissue biodistribution was assessed in a CEA-expressing LS174T (human colon carcinoma) nude mouse xenograft model. Tissues were taken at 1, 4 and 6 h for assessment of distribution of radioactivity and for measurement of CPG2 enzyme levels. The amount of radioactivity retained by the tumour proved to be an accurate estimation of actual measured enzyme activity, indicating that this radiolabelling method does not appear to damage the antibody-antigen binding or the enzyme activity of MFECP1. However, correlation between CPG2 enzyme activity and measured radioactivity in liver, spleen and kidney was poor, indicating retention of radioactivity in non-tumour sites but loss of enzyme activity. The high retention of technetium radioisotope in normal tissues may limit the clinical applicability of this radiolabelling method for MFECP1; however, these results suggest that this technique does have applicability for measuring the biodistribution of His-tagged recombinant proteins.

A fast and simple dose-calibrator-based quality control test for the radionuclidic purity of cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Tanguay, J.; Hou, X.; Esquinas, P.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2015-11-01

Cyclotron production of {{}99\\text{m}} Tc through the 100Mo(p,2n){{}99\\text{m}} Tc reaction channel is actively being investigated as an alternative to reactor-based 99Mo generation by nuclear fission of 235U. Like most radioisotope production methods, cyclotron production of {{}99\\text{m}} Tc will result in creation of unwanted impurities, including Tc and non-Tc isotopes. It is important to measure the amounts of these impurities for release of cyclotron-produced {{}99\\text{m}} Tc (CPTc) for clinical use. Detection of radioactive impurities will rely on measurements of their gamma (γ) emissions. Gamma spectroscopy is not suitable for this purpose because the overwhelming presence of {{}99\\text{m}} Tc and the count-rate limitations of γ spectroscopy systems preclude fast and accurate measurement of small amounts of impurities. In this article we describe a simple and fast method for measuring γ emission rates from radioactive impurities in CPTc. The proposed method is similar to that used to identify 99Mo breakthrough in generator-produced {{}99\\text{m}} Tc: one dose calibrator (DC) reading of a CPTc source placed in a lead shield is followed by a second reading of the same source in air. Our experimental and theoretical analysis show that the ratio of DC readings in lead to those in air are linearly related to γ emission rates from impurities per MBq of {{}99\\text{m}} Tc over a large range of clinically-relevant production conditions. We show that estimates of the γ emission rates from Tc impurities per MBq of {{}99\\text{m}} Tc can be used to estimate increases in radiation dose (relative to pure {{}99\\text{m}} Tc) to patients injected with CPTc-based radiopharmaceuticals. This enables establishing dosimetry-based clinical-release criteria that can be tested using commercially-available dose calibrators. We show that our approach is highly sensitive to the presence of {{}93\\text{g}} Tc, {{}93\\text{m}} Tc, {{}94\\text{g}} Tc, {{}94\\text{m}} Tc, {{}95\\text{m}} Tc, {{}95\\text{g}} Tc, and {{}96\\text{g}} Tc, in addition to a number of non-Tc impurities.

Assessment of the viability of skin grafts

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

Wahner, H.W.

1988-07-01

A number of tests are available to monitor the blood flow in free and distant pedicle skin grafts. The information from these tests aids in the development of measures to enhance vascularization and is occasionally needed to make clinical decisions in patients with distant pedicle grafts. Measurements of the disappearance of an intradermally injected small amount of /sup 133/Xe allows determination of a clearance rate and blood flow before and after clamping the original blood supply through the base. With /sup 99m/Tc, which is generally more readily available, a flow index and block index can be determined. Clinically both proceduresmore » give equally good results in determining a safe time for pedicle base separation. The fluorescein test allows assessment of regional blood flow distribution within the pedicle.« less

Establishing a legal service for major trauma patients at a major trauma centre in the UK.

PubMed

Seligman, William H; Thompson, Julian; Thould, Hannah E; Tan, Charlotte; Dinsmore, Andrew; Lockey, David J

2017-09-01

Major trauma causes unanticipated critical illness and patients have often made few arrangements for what are sudden and life-changing circumstances. This can lead to financial, housing, insurance, legal and employment issues for patients and their families.A UK law firm worked with the major trauma services to develop a free and comprehensive legal service for major trauma patients and their families at a major trauma centre (MTC) in the UK. In 2013, a legal service was established at North Bristol NHS Trust. Referrals are made by trauma nurse practitioners and it operates within a strict ethical framework. A retrospective analysis of the activity of this legal service between September 2013 and October 2015 was undertaken. 66 major trauma patients were seen by the legal teams at the MTC. 535 hours of free legal advice were provided on non-compensation issues-an average of 8 hours per patient. This initiative confirms a demand for the early availability of legal advice for major trauma patients to address a range of non-compensation issues as well as for identification of potential compensation claims. The availability of advice at the MTC is convenient for relatives who may be spending the majority of their time with injured relatives in hospital. More data are needed to establish the rehabilitation and health effects of receiving non-compensation advice after major injury; however, the utilisation of this service suggests that it should be considered at the UK MTCs. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Performance evaluation of Xpert MTB/RIF in a moderate tuberculosis incidence compared with TaqMan MTB and TRCRapid M.TB.

PubMed

Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi

2017-02-01

Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.

Radiofrequency ablation, an effective modality of treatment in tumor-induced osteomalacia: a case series of three patients.

PubMed

Jadhav, Swati; Kasaliwal, Rajeev; Shetty, Nitin S; Kulkarni, Suyash; Rathod, Krantikumar; Popat, Bhavesh; Kakade, Harshal; Bukan, Amol; Khare, Shruti; Budyal, Sweta; Jagtap, Varsha S; Lila, Anurag R; Bandgar, Tushar; Shah, Nalini S

2014-09-01

Tumor-induced osteomalacia is curable if the tumors can be totally excised. However, when the tumors are present in locations that make surgery disproportionately risky, the need for less invasive strategies like radiofrequency ablation (RFA) is realized. We describe three patients with suspected tumor-induced osteomalacia who were treated in our department between 2006 and 2013 with tumors in surgically difficult locations and were subjected to single or multiple sessions of RFA. The response was documented in terms of symptomatic improvement, phosphorus normalization, and follow-up (99m)Technitium-labelled hydrazinonicotinyl-Tyr3-octreotide ((99m)Tc HYNIC TOC) scan. Two of the three individuals, patient A (with a 1.5 × 1.2-cm lesion in the head of the right femur) and patient B (with a 1.3 × 1.2-cm lesion on the endosteal surface of the shaft of the left femur), achieved complete remission with single sessions of RFA. Three months after the procedure, (99m)Tc HYNIC TOC scans revealed the absence of uptake at the previous sites, corroborating with the clinical improvement and phosphorus normalization. Patient C had a large 5.6 × 6.5-cm complex lesion in the lower end of the left femur with irregular margins, loculations, and bone grafts placed in previous surgery. He failed to achieve remission after multiple sessions of RFA due to the complex nature of the lesion, although the tumor burden was reduced significantly as documented on serial (99m)Tc HYNIC TOC scans. Although surgery remains the treatment of choice, RFA could be an effective, less invasive, and safe modality of treatment in judiciously selected patients.

Overexpression of genes involved in miRNA biogenesis in medullary thyroid carcinomas with RET mutation.

PubMed

Puppin, Cinzia; Durante, Cosimo; Sponziello, Marialuisa; Verrienti, Antonella; Pecce, Valeria; Lavarone, Elisa; Baldan, Federica; Campese, Antonio Francesco; Boichard, Amelie; Lacroix, Ludovic; Russo, Diego; Filetti, Sebastiano; Damante, Giuseppe

2014-11-01

Abnormal expression of non-coding micro RNA (miRNA) has been described in medullary thyroid carcinoma (MTC). Expression of genes encoding factors involved in miRNA biogenesis results often deregulated in human cancer and correlates with aggressive clinical behavior. In this study, expression of four genes involved in miRNA biogenesis (DICER, DROSHA, DCGR8, and XPO5) was investigated in 54 specimens of MTC. Among them, 33 and 13 harbored RET and RAS mutations, respectively. DICER, DGCR8, and XPO5 mRNA levels were significantly overexpressed in MTC harboring RET mutations, in particular, in the presence of RET634 mutation. When MTCs with RET and RAS mutations were compared, only DGCR8 displayed a significant difference, while MTCs with RAS mutations did not show significant differences with respect to non-mutated tumors. We then attempted to correlate expression of miRNA biogenesis genes with tumor aggressiveness. According to the TNM status, MTCs were divided in two groups and compared (N0 M0 vs. N1 and/or M1): for all four genes no significant difference was detected. Cell line experiments, in which expression of a RET mutation is silenced by siRNA, suggest the existence of a causal relationship between RET mutation and overexpression of DICER, DGCR8, and XPO5 genes. These findings demonstrate that RET- but not RAS-driven tumorigenic alterations include abnormalities in the expression of some important genes involved in miRNA biogenesis that could represent new potential markers for targeted therapies in the treatment of RET-mutated MTCs aimed to restore the normal miRNA expression profile.

Synthesis and preliminary evaluation of a new (99m)tc labeled substance p analogue as a potential tumor imaging agent.

PubMed

Mozaffari, Saeed; Erfani, Mostafa; Beiki, Davood; Johari Daha, Fariba; Kobarfard, Farzad; Balalaie, Saeed; Fallahi, Babak

2015-01-01

Neurokinin 1 receptors (NK1R) are overexpressed on several types of important human cancer cells. Substance P (SP) is the most specific endogenous ligand known for NK1Rs. Accordingly,a new SP analogue was synthesized and evaluated for detection of NK1R positive tumors.[6-hydrazinopyridine-3-carboxylic acid (HYNIC)-Tyr(8)-Met(O)(11)-SP] was synthesized and radiolabeled with (99m)Tc using ethylenediamine-N,N'-diacetic acid (EDDA)and Tricine as coligands. Common physicochemical properties of radioconjugate were studied and in-vitro cell line biological tests were accomplished to determine the receptor mediated characteristics. In-vivo biodistribution in normal and tumor bearingnude mice was also assessed. The cold peptide was prepared in high purity (>99%) and radiolabeled with (99m)Tc at high specific activities (84-112GBq/µmol) with an acceptable labeling yield (>95%). The radioconjugate was stable in-vitro in the presence of human serum and showed 44% protein binding to human serumalbumin. In-vitro cell line studies on U373MG cells showed an acceptable uptake up to 4.91 ± 0.22% with the ratio of 60.21 ± 1.19% for its specific fraction and increasing specific internalization during 4 h. Receptor binding assays on U373MG cells indicated a mean Kd of 2.46 ± 0.43 nM and Bmax of 128925 ± 8145 sites/cell. In-vivo investigations determined the specific tumor uptake in 3.36 percent of injected dose per gram (%ID/g) for U373MG cells and noticeable accumulations of activity in the intestines and lung. Predominant renal excretion pathway was demonstrated. Therefore, this new radiolabeled peptide could be a promising radiotracer for detection of NK1R positive primary or secondary tumors.

A newly detected mutation of the RET protooncogene in exon 8 as a cause of multiple endocrine neoplasia type 2A.

PubMed

Bethanis, Sotirios; Koutsodontis, George; Palouka, Theodosia; Avgoustis, Christos; Yannoukakos, Drakoulis; Bei, Thalia; Papadopoulos, Savas; Linos, Dimitrios; Tsagarakis, Stylianos

2007-01-01

Multiple endocrine neoplasia type 2A (MEN2A) is a syndrome of familial neoplasias characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperplasia of the parathyroid glands. RET protooncogene mutations are responsible for MEN 2A. Mutations in exons 10 or 11 have been identified in more than 96% of patients with MEN 2A. We herein report for the first time a patient with MEN 2A harboring a mutation (Gly(533)Cys) in exon 8. A 66-year old male patient was referred to our department for bilateral adrenal nodules. The patient's family history was remarkable in that his mother had pheochromocytoma. Biochemical evaluation and findings of the magnetic resonance imaging of the adrenals were compatible with the diagnosis of bilateral pheochromocytomas. The patient underwent laparoscopic bilateral adrenalectomy and histological examination confirmed the preoperative diagnosis of pheochromocytoma. Absence of phenotypic characteristics of VHL or NF1 and elevated calcitonin levels both basal and post pentagastrin stimulation, raised the possibility of MEN 2A syndrome. Total thyroidectomy was performed and histological examination showed the presence of MTC. Direct sequencing of exon 8 from the patient's genomic DNA revealed the mutation c.1,597G-->T (Gly533Cys). Although this missense point mutation has been associated with familial MTC (FMTC), to the best of our knowledge mutations in exon 8 have not previously been identified in patients with MEN 2A. In conclusion, in patients with clinical suspicion of MEN 2A syndrome, analysis of RET exon 8 should be considered when the routine evaluation of MEN 2A-associated mutations is negative. Furthermore, patients with FMTC and exon 8 mutations should also be screened for pheochromocytoma.

Degenerative effects in rat eyes after experimental ocular hypertension.

PubMed

Scarsella, G; Nebbioso, M; Stefanini, S; Pescosolido, N

2012-10-08

This study was used to evaluate the degenerative effects on the retina and eye-cup sections after experimental induction of acute ocular hypertension on animal models. In particular, vascular events were directly focused in this research in order to assess the vascular remodeling after transient ocular hypertension on rat models. After local anaesthesia by administration of eye drops of 0.4% oxibuprocaine, 16 male adult Wistar rats were injected in the anterior chamber of the right eye with 15 µL of methylcellulose (MTC) 2% in physiological solution. The morphology and the vessels of the retina and eye-cup sections were examined in animals sacrificed 72 h after induction of ocular hypertension. In retinal fluorescein angiographies (FAGs), by means of fluorescein isothiocyanate-coniugated dextran (FITC), the radial venules showed enlargements and increased branching, while the arterioles appeared focally thickened. The length and size of actually perfused vessels appeared increased in the whole superficial plexus. In eye-cup sections of MTC-injected animals, in deep plexus and connecting layer there was a bigger increase of vessels than in controls. Moreover, the immunolocalization of astrocytic marker glial fibrillary acidic protein (GFAP) revealed its increased expression in internal limiting membrane and ganglion cell layer, as well as its presence in Müller cells. Finally, the pro-angiogenic factor vascular endothelial growth factor (VEGF) was found to be especially expressed by neurones of ganglion cell layer, both in control and in MTC-injected eyes. The data obtained in this experimental model on the interactions among glia, vessels and neurons should be useful to evaluate if also in glaucomatous patients the activation of vessel-adjacent glial cells might play key roles in following neuronal dysfunction.

Bone scintigraphy of the aged patient. 1. /sup 99m/Tc-polyphosphate bone scintigraphy (in Japanese)

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

Yamamoto, M.; Chiba, K.; Tanno, M.

Application and evaluation of a new bone-seeking radiopharmaceuticai, / sup 99m/Tc-polyphosphate are reported. Analysis of the image by digital color display data analyzer (Phosdac) was performed. The subjects of the study were cases at Tokyo Metropolitan Geriatric Hospital ranging from 63 to 85 years old with several kinds of bone diseases. Polyphosphate kits (Diagnostic Isotopes, Inc.) were used to prepare /sup 99m/Tc, and a Rho/gamma HP gamma-camera was used for scintigraphy. The images obtained were analyzed by Phosdac to obtain clear image of the bone system. In the final preparation, presence of approximately 30% of free /sup 99m/Tc was noticedmore » by paper chromatography. /sup 99m/Tc- polyphosphate was cleared from the blood with a half time of about 60 min. Urinary excretion proved to be 40 to 60% within 24 hrs. The bone system was visualized rather clearly with high accumulation of the label in the diseased region in spite of the fact that geriatric cases had marked general osteoporotic tendencies. In some cases, ribs were clearly visualized, and different information from that of x-ray was obtained by scanning images. Data processing by Phosdac increased diagnostic accuracy by enhancing the difference of the density of the image as well as eliminating the background caused by free /sup 99m/TcO/sub 4/. In conclusion, /sup 99m/Tc-polyphosphate was proved to be useful for bone scanning in geriatric cases. A digital color display data analyzer was successfully applied for the processing of the original data. (auth)« less

Cost-utility of First-line Disease-modifying Treatments for Relapsing-Remitting Multiple Sclerosis.

PubMed

Soini, Erkki; Joutseno, Jaana; Sumelahti, Marja-Liisa

2017-03-01

This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting). Markov cohort modeling with a 15-year time horizon was employed. During each 1-year modeling cycle, patients either maintained the Expanded Disability Status Scale (EDSS) score or experienced progression, developed secondary progressive MS (SPMS) or showed EDSS progression in SPMS, experienced relapse with/without hospitalization, experienced an adverse event (AE), or died. Patients׳ characteristics, RRMS progression probabilities, and standardized mortality ratios were derived from a registry of patients with MS in Finland. A mixed-treatment comparison (MTC) informed the treatment effects. Finnish EuroQol Five-Dimensional Questionnaire, Three-Level Version quality-of-life and direct-cost estimates associated with EDSS scores, relapses, and AEs were applied. Four approaches were used to assess the outcomes: cost-effectiveness plane and efficiency frontiers (relative value of efficient treatments); cost-effectiveness acceptability frontier, which demonstrated optimal treatment to maximize net benefit; Bayesian treatment ranking (BTR); and an impact investment assessment (IIA; a cost-benefit assessment), which increased the clinical interpretation and appeal of modeled outcomes in terms of absolute benefit gained with fixed drug-related budget. Robustness of results was tested extensively with sensitivity analyses. Based on the modeled results, teriflunomide was less costly, with greater QALYs, versus glatiramer acetate and the IFNs. Teriflunomide had the lowest ICER (24,081) versus BSC. DMF brought marginally more QALYs (0.089) than did teriflunomide, with greater costs over the 15 years. The ICER for DMF versus teriflunomide was 75,431. Teriflunomide had >50% cost-effectiveness probabilities with a willingness-to-pay threshold of <€77,416/QALY gained. According to BTR, teriflunomide was first-best among the disease-modifying therapies, with potential willingness-to-pay thresholds of up to €68,000/QALY gained. In the IIA, teriflunomide was associated with the longest incremental quality-adjusted survival and time without cane use. Generally, primary outcomes results were robust, based on the sensitivity analyses. The results were sensitive only to large changes in analysis perspective or mixed-treatment comparison. The results were sensitive only to large changes in analysis perspective or MTC. Based on the analyses, teriflunomide was cost-effective versus BSC or DMF with the common threshold values, was dominant versus other first-line RRMS treatments, and provided the greatest impact on investment. Teriflunomide is potentially the most cost-effective option among first-line treatments of RRMS in Finland. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The carbon stock of harvested wood products in US residential houses is substantial

NASA Astrophysics Data System (ADS)

Xie, S. H.; Kurz, W. A.; McFarlane, P. N.

2016-12-01

Harvested wood products (HWP) provide humans with services that can substitute for emissions-intensive products, while storing carbon sequestered from the atmosphere by forests. Nearly half of HWP in the US have been used for construction purposes. Due to the long-lived nature of houses, the wood within these buildings can store carbon for many decades. This study developed a new methodology to model the decay and half-lives based on national census data. Six different models were evaluated and the inverse sigmoidal decay pattern of houses was best represented using a Gamma distribution model. It adequately modelled the decay pattern of houses from the US, Canada and Norway and enabled the quantification of structural HWP carbon stocks in residential houses. For the US, it was estimated that residential houses would take about 140 years to reach 50% removal of the housing number initially constructed and 390 years to reach 95% removal. At the end of 2009, the carbon stock of structural HWP in US residential houses was estimated to be 668 MtC and the average rate of carbon storage from 1990 to 2006 was 44.7 Mt CO2e yr-1. The utilization of HWP for long-lived uses has the potential to make a major contribution to mitigating greenhouse gas emissions through carbon storage and substitution of emissions from other products such as concrete and steel. With a same amount of HWP input, structural wood use can produce a carbon pool that is 48 times larger than pulp and paper use, or 3 times larger than furniture use. In addition, this pool takes much longer to saturate. Accurate quantification of the structural HWP pool is therefore an important topic worthy of detailed investigation.

Midlands Teaching Factory, LTD.

ERIC Educational Resources Information Center

Midlands Technical Coll., Columbia, SC.

In 1987, Midlands Technical College (MTC), in Columbia, South Carolina, initiated a Computer Integrated Manufacturing (CIM) project, the Midlands Teaching Factory, LTD, which integrated various college departments with the goal of manufacturing a high quality, saleable product. The faculty developed a teaching factory model which was designed to…

Feasibility study of medical isotope production at Sandia National Laboratories

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

Massey, C.D.; Miller, D.L.; Carson, S.D.

1995-12-01

In late 1994, Sandia National Laboratories in Albuquerque, New Mexico, (SNL/NM), was instructed by the Department of Energy (DOE) Isotope Production and Distribution Program (IPDP) to examine the feasibility of producing medically useful radioisotopes using the Annular Core Research Reactor (ACRR) and the Hot Cell Facility (HCF). Los Alamos National Laboratory (LANL) would be expected to supply the targets to be irradiated in the ACRR. The intent of DOE would be to provide a capability to satisfy the North American health care system demand for {sup 99}Mo, the parent of {sup 99m}Tc, in the event of an interruption in themore » current Canadian supply. {sup 99m}Tc is used in 70 to 80% of all nuclear medicine procedures in the US. The goal of the SNL/NM study effort is to determine the physical plant capability, infrastructure, and staffing necessary to meet the North American need for {sup 99}Mo and to identify and examine all issues with potential for environmental impact.« less

Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging

NASA Astrophysics Data System (ADS)

Singh, Sweta; Tiwari, Anjani K.; Varshney, Raunak; Mathur, R.; Shukla, Gauri; Bag, N.; Singh, B.; Mishra, Anil K.

2016-01-01

2,2‧,2″-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11-tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N-methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2-ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized and evaluated for imaging application. The pharmacokinetics of these ligands were determined by tracer methods. In vitro human serum stability of 99mTc Met-ac-TE3A/99mTc Bis(thiosemicarbazone)-Biotin after 24 h was found to be 96.5% and 97.0% respectively. Blood kinetics of both ligands in normal rabbits showed biphasic clearance pattern. Ex vivo biodistribution study revealed significant initial tumor uptake and high tumor/muscles ratio which is a pre-requisite condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging.

New multifunctional ligands for potential use in the design therapeutic or diagnostic radiopharmaceutical imaging agents

DOEpatents

Katti, K.V.; Volkert, W.A.; Ketring, A.R.; Singh, P.R.

1997-02-11

A class of diagnostic and therapeutic compounds are derived from phosphinimines that include ligands containing either a single phosphinimine functionality or both a phosphinimine group and a phosphine or arsine group, or an aminato group, or a second phosphinimine moiety. These phosphinimine ligands are complexed to early transition metal radionuclides (e.g., {sup 99m}Tc or {sup 186}Re/{sup 188}Re) or late transition metals (e.g., {sup 105}Rh or {sup 109}Pd). The complexes with these metals {sup 186}Re/{sup 188}Re, {sup 99m}Tc and {sup 109}Pd exhibit a high in vitro and high in vivo stability. The complexes are formed in high yields and can be neutral or charged. These ligands can also be used to form stable compounds with paramagnetic transition metals (e.g., Fe and Mn) for potential use as MRI contrast agents. Applications for the use of ligands and making the ligands are also disclosed.

Bilateral pheochromocytoma during the postpartum period.

PubMed

Wattanachanya, Lalita; Bunworasate, Udomsak; Plengpanich, Wanee; Houngngam, Natnicha; Buranasupkajorn, Patinut; Sunthornyothin, Sarat; Shotelersuk, Vorasuk; Snabboon, Thiti

2009-12-01

Pheochromocytoma manifesting during pregnancy is uncommon but it is responsible for a high maternal and fetal mortality rate, especially when unrecognized. Most cases of pheochromocytoma are sporadic but they can be part of hereditary autosomal dominant syndromes. We describe a case of bilateral pheochromocytoma in a term-pregnant patient with a previous history of medullary thyroid carcinoma (MTC). Her genetic study revealed a heterozygous mutation, c.1900T>C, in the RET proto-oncogene which confirmed the diagnosis of multiple endocrine neoplasia type 2A (MEN2A). Unrecognized, the tumors caused a crisis with fatal outcome in the mother during the postpartum period. This event might have been prevented if the tumor had been detected previously. MEN2A affected pregnancy is an unusual condition. This syndrome should be suspected when a pregnant patient has a history of MTC. Early detection and appropriate management can prevent serious maternal and fetal complications. We also reviewed the literature of MEN2A-affected pregnancies.

⁹⁹mTc/Re complexes bearing bisnitroimidazole or mononitroimidazole as potential bioreductive markers for tumor: synthesis, physicochemical characterization and biological evaluation.

PubMed

Mei, Lei; Wang, Yue; Chu, Taiwei

2012-12-01

Four monoamine-monoamide dithiol (MAMA) ligands containing two or one nitroimidazole moieties were synthesized and labeled with (99m)Tc (labeling yield > 95%). The proposed structures of (99m)Tc-complexes are identified by comparison with analogous Re-MAMA complexes. (99m)Tc-MAMA complexes show better physicochemical characters than (99m)TcO-(PnAO-1-(2-nitroimidazole)). Reduction potentials of nitro groups of the rhenium complexes are within the range for bioreductive compounds. As expected, biodistribution studies demonstrate that the 2-nitroimidazole complex shows better tumor-to-tissue ratios than 4-nitroimidazole analog for mononitroimidazole complexes, but not for MAMA-bisnitroimidazoles due to higher lipophilicity. Both the bisnitroimidazole compounds show rapider excretion, lower background activity in liver and higher tumor-to-tissue ratios than the mononitroimidazoles. Better biodistribution characteristic makes both the MAMA-bisnitroimidazole complexes, especially (99m)Tc-15, be potential tumor hypoxia marker. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Evaluation of a 99mTc-tricine Vascular Disrupting Agent as an In-vivo Imaging in 4T1 Mouse Breast Tumor Model

PubMed Central

Erfani, Mostafa; Shirmardi, Seyed Pezhman; Shafiei, Mohammad

2017-01-01

Colchicine as a vascular disrupting agent creates microtubule destabilization which induces vessel blockage and consequently cell death. Accordingly, colchicines and its analogues radiolabeled with 99mTc may have potential for visualization of tumor. In this work, deacetylcolchicine a colchicine analogue was labeled with 99mTc via tricine as a coligand and characterized for its tumor targeting properties. The in-vitro radiochemical stability and the biodistribution were studied in 4T1 breast tumor model bearing mice. Labeling yield of more than 90% was obtained corresponding to a specific activity of 46 MBq/µmol. In-vivo biodistribution studies demonstrated that radiocomplex had high tumor to muscle and tumor to blood ratios at early time points. Planer gamma imaging of tumor bearing mice showed that this radioconjugate was able to clearly visualize tumors. According to high tumor uptake, presented radiocomplex may have a potential for targeted imaging studies. PMID:29201088

Space station freedom resource nodes internal thermal control system

NASA Technical Reports Server (NTRS)

Merhoff, Paul; Dellinger, Brent; Taggert, Shawn; Cornwell, John

1993-01-01

This paper presents an overview of the design and operation of the internal thermal control system (ITCS) developed for Space Station Freedom by the NASA-Johnson Space Center and McDonnell Douglas Aerospace to provide cooling for the resource nodes, airlock, and pressurized logistics modules. The ITCS collects, transports and rejects waste heat from these modules by a dual-loop, single-phase water cooling system. ITCS performance, cooling, and flow rate requirements are presented. An ITCS fluid schematic is shown and an overview of the current baseline system design and its operation is presented. Assembly sequence of the ITCS is explained as its configuration develops from Man Tended Capability (MTC), for which node 2 alone is cooled, to Permanently Manned Capability (PMC) where the airlock, a pressurized logistics module, and node 1 are cooled, in addition to node 2. A SINDA/FLUINT math model of the ITCS is described, and results of analyses for an MTC and a PMC case are shown and discussed.

[Nuclear cardiology with new radiopharmaceuticals].

PubMed

Bunko, H

1994-08-01

In the field of nuclear cardiology, 99mTc labeled myocardial perfusion agents such as MIBI, Tetrofosmin and Teboroxime, 111In-antimyosin for imaging of myocardial necrosis, 123I-betamethyl-iodophenylpentadecanoic acid (BMIPP) for imaging of myocardial fatty acid metabolism and 123I-metaiodobenzylguanidine (MIBG) for imaging of myocardial adrenergic function are introduced recently in Japan. Improved image quality and simultaneous evaluation of myocardial perfusion, function and wall motion can be obtained with use of 99mTc labeled myocardial perfusion agents. 111In-antimyosin enables specific imaging of myocardial necrosis which leads to the use for wide variety of heart diseases. Discrepancy of the myocardial perfusion and metabolism in case of stunned myocardium or cardiomyopathy can be evaluated by 123I-BMIPP in conjunction with perfusion agent. Recently wide variety of diseases which may have cardiac adrenergic abnormality are targeted for 123I-MIBG imaging. These new radiopharmaceuticals are expected to be powerful tool for evaluation of the pathophysiology including severity and prognosis and evaluation of the etiology of the various heart diseases.

What helps or hinders the transformation from a major tertiary center to a major trauma center? Identifying barriers and enablers using the Theoretical Domains Framework.

PubMed

Roberts, Neil; Lorencatto, Fabiana; Manson, Joanna; Brundage, Susan I; Jansen, Jan O

2016-03-12

Major Trauma Centers (MTCs), as part of a trauma system, improve survival and functional outcomes from injury. Developing such centers from current teaching hospitals is likely to generate diverse beliefs amongst staff. These may act as barriers or enablers. Prior identification of these may make the service development process more efficient. The importance of applying theory to systematically identify barriers and enablers to changing clinical practice in emergency medicine has been emphasized. This study systematically explored theory-based barriers and enablers towards implementing the transformation of a tertiary hospital into a MTC. Our goal was to demonstrate the use of a replicable method to identify targets that could be addressed to achieve a successful transformation from an organization evolved to provide a particular type of clinical care into a clinical system with different demands, requirements and expectations. The Theoretical Domains Framework (TDF) is a tool designed to elicit and analyze beliefs affecting behavior. Semi-structured interviews based around the TDF were conducted in a major tertiary hospital in Scotland due to become a MTC with a purposive sample of major stakeholders including clinicians and nurses from specialties involved in trauma care, clinical managers and administration. Belief statements were identified through qualitative analysis, and assessed for importance according to prevalence, discordance and evidence base. 1728 utterances were recorded and coded into 91 belief statements. 58 were classified as important barriers/enablers. There were major concerns about resource demands, with optimism conditional on these being met. Distracting priorities abound within the Emergency Department. Better communication is needed. Staff motivation is high and they should be engaged in skills development and developing performance improvement processes. This study presents a systematic and replicable method of identifying theory-based barriers and enablers towards complex service development. It identifies multiple barriers/enablers that may serve as a basis for developing an implementation intervention to enhance the development of MTCs. This method can be used to address similar challenges in developing specialist centers or implementing clinical practice change in emergency care across both developing and developed countries.

Global socioeconomic carbon stocks in long-lived products 1900-2008

NASA Astrophysics Data System (ADS)

Lauk, Christian; Haberl, Helmut; Erb, Karl-Heinz; Gingrich, Simone; Krausmann, Fridolin

2012-09-01

A better understanding of the global carbon cycle as well as of climate change mitigation options such as carbon sequestration requires the quantification of natural and socioeconomic stocks and flows of carbon. A so-far under-researched aspect of the global carbon budget is the accumulation of carbon in long-lived products such as buildings and furniture. We present a comprehensive assessment of global socioeconomic carbon stocks and the corresponding in- and outflows during the period 1900-2008. These data allowed calculation of the annual carbon sink in socioeconomic stocks during this period. The study covers the most important socioeconomic carbon fractions, i.e. wood, bitumen, plastic and cereals. Our assessment was mainly based on production and consumption data for plastic, bitumen and wood products and the respective fractions remaining in stocks in any given year. Global socioeconomic carbon stocks were 2.3 GtC in 1900 and increased to 11.5 GtC in 2008. The share of wood in total C stocks fell from 97% in 1900 to 60% in 2008, while the shares of plastic and bitumen increased to 16% and 22%, respectively. The rate of gross carbon sequestration in socioeconomic stocks increased from 17 MtC yr-1 in 1900 to a maximum of 247 MtC yr-1 in 2007, corresponding to 2.2%-3.4% of global fossil-fuel-related carbon emissions. We conclude that while socioeconomic carbon stocks are not negligible, their growth over time is not a major climate change mitigation option and there is an only modest potential to mitigate climate change by the increase of socioeconomic carbon stocks.

Abnormal regional cerebral blood flow in systemic lupus erythematosus patients with psychiatric symptoms.

PubMed

Oda, Kenji; Matsushima, Eisuke; Okubo, Yoshiro; Ohta, Katsuya; Murata, Yuji; Koike, Ryuji; Miyasaka, Nobuyuki; Kato, Motoichiro

2005-07-01

Single-photon emission computed tomography (SPECT) studies have demonstrated decreased regional cerebral blood flow (rCBF) in systemic lupus erythematosus (SLE) patients. However, no study has done voxel-based analysis using statistical parametric mapping (SPM) that can evaluate rCBF objectively, and the relationship between rCBF and psychiatric symptoms has not been well investigated. Using L,L-ethyl cysteinate dimer (99mTc ECD) SPECT and SPM, we aimed to clarify the association of rCBF changes with psychiatric symptoms in SLE patients whose magnetic resonance imaging (MRI) showed no morphological abnormalities. Twenty SLE patients and 19 healthy volunteers underwent 99mTc ECD SPECT. Data were collected from August 2000 to March 2003. SLE was diagnosed according to American College of Rheumatology criteria, and psychiatric symptoms were diagnosed according to ICD-10 criteria. On the basis of the modified Carbotte, Denburg, and Denburg method, the patients were classified into 3 groups: a group with major psychiatric symptoms (hallucinosis, delusional disorder, and mood disorder), a group with minor psychiatric symptoms (anxiety disorder, dissociative disorder, and emotionally labile disorder), and a group without psychiatric symptoms. Gross organic lesions were ruled out by brain MRI. Group comparisons of rCBF were performed with analysis using SPM99. SLE patients without MRI lesions showed decreased rCBF in the posterior cingulate gyrus and thalamus. The reduction in rCBF was overt in patients with major psychiatric symptoms. Our study indicated that SLE patients may have dysfunction in the posterior cingulate gyrus and thalamus and that this may be associated with the severity of psychiatric symptoms.

Mass Transportation in Massachusetts : demonstration project progress report no. 5 - tentative conclusions

DOT National Transportation Integrated Search

1963-11-22

This fifth progress report is submitted twelve months after the initiation of the first MTC-HHFA experiment, and ten months after the start of the large Boston and Maine Railroad. Because of the urgent need to present comprehensive analyses in some d...

Impact of thiocyanate salts on zein properties

USDA-ARS?s Scientific Manuscript database

A new class of zein plasticizer was investigated, thiocyanate salts. Ammonium (ATC), potassium (KTC), guanidine (GTC) and magnesium thiocyanate (MTC) salts were added to solutions of zein in 90% ethanol/10% water with various amounts of tri(ethylene glycol) (TEG), cast as films and then tested to de...

Comparative genomics of archived pyrazinamide resistant Mycobacterium tuberculosis complex isolates from Uganda

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis is a ‘neglected zoonosis’ and its contribution to the proportion of Mycobacterium tuberculosis complex infections in humans is unknown. A retrospective study on archived Mycobacterium tuberculosis complex (MTC) isolates from a reference laboratory in Uganda was undertaken to iden...

Mass Transportation in Massachusetts : demonstration project progress report no. 6 - bus and parking experiments

DOT National Transportation Integrated Search

1964-04-10

This sixth progress report, as with all previous such reports, has been prepared by the MTC staff to disseminate the results of the individual experiments and tentative preliminary conclusions so that the full Commission might have the benefit of wid...

Polymorphisms of twenty regulatory proteins between Mycobacterium tuberculosis and Mycobacterium bovis

USDA-ARS?s Scientific Manuscript database

Mycobacterium tuberculosis and Mycobacterium bovis are responsible for tuberculosis in humans or animals, respectively. Both species are closely related and belong to the Mycobacterium tuberculosis complex (MTC). M. tuberculosis is the most ancient species from which M. bovis and the other members o...

Hypothyroidism presenting as reversible renal impairment: an interesting case report.

PubMed

Vikrant, Sanjay; Chander, Subhash; Kumar, Satish; Gupta, Dalip

2013-10-01

We describe an interesting case of reversible renal impairment secondary to hypothyroidism. A 57-years-old man was referred from peripheral institution for evaluation of elevated serum creatinine. He had vague complaints of weakness, lethargy and muscle ache but no urinary symptoms. He was found to have hypothyroidism, and thyroid hormone replacement therapy (THRT) was started which resulted in reversal of the renal dysfunction. There was marked improvement in estimated glomerular filtration rate. 99mTc DTPA renal scans done before and after THRT suggested hypothyroidism responsible for this reversible renal impairment. Several studies have described the pathophysiology of diminished renal function in hypothyroidism. Few studies or case reports have shown total amelioration of renal impairment as seen in our patient. The etiology is presumed to be multifactorial, in which hemodynamic effects and a direct effect of thyroid hormone on the kidney play an important role. We suggest that patients with renal impairment of unknown cause have thyroid function tests undertaken as part of routine investigation.

Analysis Of Leakage In Carbon Sequestration Projects In Forestry:A Case Study Of Upper Magat Watershed, Philippines

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

Lasco, Rodel D.; Pulhin, Florencia B.; Sales, Renezita F.

2007-06-01

The role of forestry projects in carbon conservation andsequestration is receiving much attention because of their role in themitigation of climate change. The main objective of the study is toanalyze the potential of the Upper Magat Watershed for a carbonsequestration project. The three main development components of theproject are forest conservation, tree plantations, and agroforestry farmdevelopment. At Year 30, the watershed can attain a net carbon benefit of19.5 M tC at a cost of US$ 34.5 M. The potential leakage of the projectis estimated using historical experience in technology adoption inwatershed areas in the Philippines and a high adoption rate.more » Two leakagescenarios were used: baseline and project leakage scenarios. Most of theleakage occurs in the first 10 years of the project as displacement oflivelihood occurs during this time. The carbon lost via leakage isestimated to be 3.7 M tC in the historical adoption scenario, and 8.1 MtC under the enhanced adoption scenario.« less

Calcitonin estimation in patients with nodular goiter and its significance for early detection of MTC: european comments to the guidelines of the American Thyroid Association.

PubMed

Elisei, Rossella; Romei, Cristina

2013-03-14

One of the most discussed and controversial issue in the management of thyroid nodules is the need to perform a routine measurement of serum Calcitonin (Ct) in all cases. The American Thyroid Association guidelines do not recommend in favor or against this procedure since they retain that there are not enough evidences that it can determine an advantage to the health outcomes of these patients. This is not the view of many European experts who met in Lisbon in 2009 at the European Thyroid Association-Cancer Research Network meeting to discuss all the still open controversial issues on the management of medullary thyroid cancer patients.This paper is focused on the routine measurement of serum Ct in all patients with thyroid nodule(s): the evidences, the rational and the benefits of this procedure are deeply analysed following the discussion that was done in Lisbon. The conclusions reached at that time are reported in detail.

Diagnostic value of (99m)Tc-3PRGD2 scintimammography for differentiation of malignant from benign breast lesions: Comparison of visual and semi-quantitative analysis.

PubMed

Chen, Qianqian; Xie, Qian; Zhao, Min; Chen, Bin; Gao, Shi; Zhang, Haishan; Xing, Hua; Ma, Qingjie

2015-01-01

To compare the diagnostic value of visual and semi-quantitative analysis of technetium-99m-poly-ethylene glycol, 4-arginine-glycine-aspartic acid ((99m)Tc-3PRGD2) scintimammography (SMG) for better differentiation of benign from malignant breast masses, and also investigate the incremental role of semi-quantitative index of SMG. A total of 72 patients with breast lesions were included in the study. Technetium-99m-3PRGD2 SMG was performed with single photon emission computed tomography (SPET) at 60 min after intravenous injection of 749 ± 86MBq of the radiotracer. Images were evaluated by visual interpretation and semi-quantitative indices of tumor to non-tumor (T/N) ratios, which were compared with pathology results. Receiver operating characteristics (ROC) curve analyses were performed to determine the optimal visual grade, to calculate cut-off values of semi-quantitative indices, and to compare visual and semi-quantitative diagnostic values. Among the 72 patients, 89 lesions were confirmed by histopathology after fine needle aspiration biopsy or surgery, 48 malignant and 41 benign lesions. The mean T/N ratio of (99m)Tc-3PRGD2 SMG in malignant lesions was significantly higher than that in benign lesions (P<0.05). When grade 2 of the disease was used as cut-off value for the detection of primary breast cancer, the sensitivity, specificity and accuracy were 81.3%, 70.7%, and 76.4%, respectively. When a T/N ratio of 2.01 was used as cut-off value, the sensitivity, specificity and accuracy were 79.2%, 75.6%, and 77.5%, respectively. According to ROC analysis, the area under the curve for semi-quantitative analysis was higher than that for visual analysis, but the statistical difference was not significant (P=0.372). Compared with visual analysis or semi-quantitative analysis alone, the sensitivity, specificity and accuracy of visual analysis combined with semi-quantitative analysis in diagnosing primary breast cancer were higher, being: 87.5%, 82.9%, and 85.4%, respectively. The area under the curve was 0.891. Results of the present study suggest that the semi-quantitative and visual analysis statistically showed similar results. The semi-quantitative analysis provided incremental value additive to visual analysis of (99m)Tc-3PRGD2 SMG for the detection of breast cancer. It seems from our results that, when the tumor was located in the medial part of the breast, the semi-quantitative analysis gave better diagnostic results.

Dual-modality imaging with 99mTc and fluorescent indocyanine green using surface-modified silica nanoparticles for biopsy of the sentinel lymph node: an animal study

PubMed Central

2013-01-01

Background We propose a new approach to facilitate sentinel node biopsy examination by multimodality imaging in which radioactive and near-infrared (NIR) fluorescent nanoparticles depict deeply situated sentinel nodes and fluorescent nodes with anatomical resolution in the surgical field. For this purpose, we developed polyamidoamine (PAMAM)-coated silica nanoparticles loaded with technetium-99m (99mTc) and indocyanine green (ICG). Methods We conducted animal studies to test the feasibility and utility of this dual-modality imaging probe. The mean diameter of the PAMAM-coated silica nanoparticles was 30 to 50 nm, as evaluated from the images of transmission electron microscopy and scanning electron microscopy. The combined labeling with 99mTc and ICG was verified by thin-layer chromatography before each experiment. A volume of 0.1 ml of the nanoparticle solution (7.4 MBq, except for one rat that was injected with 3.7 MBq, and 1 μg of an ICG derivative [ICG-sulfo-OSu]) was injected submucosally into the tongue of six male Wistar rats. Results Scintigraphic images showed increased accumulation of 99mTc in the neck of four of the six rats. Nineteen lymph nodes were identified in the dissected neck of the six rats, and a contact radiographic study showed three nodes with a marked increase in uptake and three nodes with a weak uptake. NIR fluorescence imaging provided real-time clear fluorescent images of the lymph nodes in the neck with anatomical resolution. Six lymph nodes showed weak (+) to strong (+++) fluorescence, whereas other lymph nodes showed no fluorescence. Nodes showing increased radioactivity coincided with the fluorescent nodes. The radioactivity of 15 excised lymph nodes from the four rats was assayed using a gamma well counter. Comparisons of the levels of radioactivity revealed a large difference between the high-fluorescence-intensity group (four lymph nodes; mean, 0.109% ± 0.067%) and the low- or no-fluorescence-intensity group (11 lymph nodes; mean, 0.001% ± 0.000%, p < 0.05). Transmission electron microscopy revealed that small black granules were localized to and dispersed within the cytoplasm of macrophages in the lymph nodes. Conclusion Although further studies are needed to determine the appropriate dose of the dual-imaging nanoparticle probe for effective sensitivity and safety, the results of this animal study revealed a novel method for improved node detection by a dual-modality approach for sentinel lymph node biopsy. PMID:23618132

Pathology of the emerging Mycobacterium tuberculosis complex pathogen, M. mungi in the banded mongoose (Mungos mungo)

USDA-ARS?s Scientific Manuscript database

Wild banded mongooses (Mungos mungo) in northeastern Botswana and Northwest Zimbabwe are infected with a novel Mycobacterium tuberculosis complex pathogen (MTC), M. mungi. This pathogen is transmitted environmentally between mongoose hosts through exposure to infected scent marks used in olfactory c...

A Bayesian Missing Data Framework for Generalized Multiple Outcome Mixed Treatment Comparisons

ERIC Educational Resources Information Center

Hong, Hwanhee; Chu, Haitao; Zhang, Jing; Carlin, Bradley P.

2016-01-01

Bayesian statistical approaches to mixed treatment comparisons (MTCs) are becoming more popular because of their flexibility and interpretability. Many randomized clinical trials report multiple outcomes with possible inherent correlations. Moreover, MTC data are typically sparse (although richer than standard meta-analysis, comparing only two…

Aerospace Materials and Process Technology Reinvestment Workshop Held in Dayton, Ohio on 18-19 May 1993.

DTIC Science & Technology

1993-05-19

The Laboratories Theory, Modeling and Simulation , • ATP Characterization J Education and Human Resources • MTC Facilities -- NBSR and CNRF MISSION...34 Automiated System for Composite Analysis (ASCA).Y -Basis for usefri(eadly numerical methods to describe composite laminates and predict ?heir response

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

Basinger, G.T.; McCullough, D.L.; McLaughlin, A.P.

Eleven patients with urologic cancer had an abnormal /sup 99m/Tc (technetium-99m) bone scan as the sole evidence of metastatic disease. Potentially curative therapy should not be withheld on the basis of a ''positive'' bone scan if such an area is accessible to selected bone biopsy and proves to be negative for tumor histologically.

Parameters leading to a successful radiographic outcome following surgical treatment for Lenke 2 curves.

PubMed

Koller, Heiko; Meier, Oliver; McClung, Anna; Hitzl, Wolfgang; Mayer, Michael; Sucato, Daniel

2015-07-01

In Lenke 2 curves, there are conflicting data when to include the PTC into the fusion. Studies focusing on Lenke 2 curves are scant. The number of patients with significant postoperative shoulder height difference (SHD) or trunk shift (TS) is as high as 30 % indicating further research. Therefore, the purpose of the current study was to improve understanding of curve resolution and shoulder balance following surgical correction of Lenke 2 curves as well as the identification of radiographic parameters predicting postoperative curve resolution, shoulder and trunk balance in perspective of inclusion/exclusion of the proximal thoracic curve (PTC). This is a retrospective study of a 158 Lenke 2 curves. Serial radiographs were analyzed for the main thoracic curve (MTC), PTC, and lumbar curve (LC), SHD, clavicle angle (CA), T-1 tilt, deviation of the central sacral vertical line (CSVL) off the C7 plumb line.Patients were stratified whether the PTC was included in the fusion (+PTC group, n = 60) or not (-PTC group, n = 98). Intergroup results were studied. Compensatory mechanisms for SHD were studied in detail. Adding-on distally was defined as an increase of the lowest instrumented vertebra adjacent disc angle (LIVDA) >3°. Stepwise regression analyses were performed to establish predictive radiographic parameters. At follow-up averaging 24 months significant differences between the +PTC and -PTC group existed for the PTC (24° vs 28°, p < .01), PTC correction (42 vs 29 %, p < .01), rate of MTC-loss >5° (27 vs 53 %, p < .01), and spontaneous LC correction in patients with a selective thoracic fusion (STF) (80/93 %, p = .04). The number of patients with a new trunk shift (CSVL > 2 cm) was 9 (6 %): 7 in the -PTC vs 2 in the +PTC group (p = .03). Utilization of compensatory mechanisms (99 vs 83 %, p < .01) and adding-on (35 vs 20 %, p < .05) occurred more often in the +PTC vs the -PTC groups. Statistics showed postoperative SHD improvement in both the +PTC and -PTC groups. There were no significant differences regarding SHD, CA and T1-Tilt between groups. However, only in the -PTC group, a significant change between postoperative and follow-up SHD existed (p = .02). Statistics identified a preoperative 'left shoulder up' (p < .01) and CSVL (p = .03) predictive for follow-up SHD ≥1.5 cm. A statistical model only for the -PTC group showed 9 parameters highly predictive for a follow-up SHD ≥1.5 cm with highest prediction strength for a PTC >40° (p = .01), a preoperative 'left shoulder up' (p < .01) and anterior fusion (p = .02). To account for baseline differences between the +PTC and -PTC groups, 49 matched-pairs were studied. Postoperative differences remained significant between the +PTC and -PTC groups for the PTC (p < .01), MTC (p = .03) and the rate of loss of MTC >5° (p < .01). Prediction of a successful surgical outcome for Lenke 2 curves depends on multiple variables, in particular a preoperative left shoulder up, preoperative PTC >40°, MTC correction, and surgical approach. Shoulder balance is not significantly different whether the PTC is included in the fusion or not. But, powerful compensation mechanisms utilized to balance shoulder in the -PTC group can impose changes of trunk alignment, main and compensatory lumbar curves.

Thyroid uptake of (/sup 99m/Tc) pertechnetate during in vivo RBC labeling: incidental diagnosis of hypothyroidism

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

Holmes, K.A.; Ponto, J.A.

1981-09-01

Increased thyroid activity was incidentally observed during an in vivo labeled Tc-99m blood pool scan and subsequent evaluation resulted in a diagnosis of hypothyroidism. Alternate explanations of abnormal thyroid uptake on in vivo labeled blood pool scans were considered and are discussed briefly.

Radioisotope imaging for the evaluation of thyroid neoplasia and hypothyroidism in a dog

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

Branam, J.E.; Leighton, R.L.; Hornof, W.J.

1982-05-01

An 11-year-old dog was diagnosed as having concurrent unilateral follicular thyroid carcinoma and hypothyroidism. Radioisotope imaging with /SUP 99m/Tc as sodium pertechnatate identified the extent of thyroid tissue involvement. A combination of surgical resection and hormonal supplementation resulted in a favorable clinical response.

Extravasation of contrast material from vascular ectasia of the cecum detected with /sup 99m/Tc-pertechnetate

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

Tavormina, A.; Mousavi, A.; Gordon, D.H.

A case of vascular ectasia of the cecum is presented. The isotopic pattern did not differ from that of Meckel's diverticulum. The authors suggest that studies with /sup 99m/Tc may be helpful in screening for areas of pathology in cases of lower gastrointestinal bleeding.

Partial growth plate closure: apex view on bone scan

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

Howman-Giles, R.; Trochei, M.; Yeates, K.

1985-01-01

A new technique of using /sup 99m/Tc bone scan to assess partial closure of the growth plate is described. The site and degree of osseous fusion can be obtained by using the apex view. The technique has the potential of assessing serially the growth of a plate before and after surgery.

Bone scan findings in hypervitaminosis D: case report. [/sup 99m/Tc tracer technique

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

Fogelman, I.; McKillop, J.H.; Cowden, E.A.

1977-12-01

Bone scans in three patients showed generalized symmetrical increased uptake of radiopharmaceutical by the skeleton and absent or faint kidney images. It is thought that these appearances may be attributable to excess vitamin D, and other possible contributing factors, including the presence of renal osteodystrophy, are discussed.

Cancer imaging with CEA antibodies: historical and current perspectives.

PubMed

Goldenberg, D M

1992-01-01

This article reviews the history and status of cancer imaging with radiolabeled antibodies against carcinoembryonic antigen (CEA). Although CEA and many other cancer-associated antigens are not distinct for neoplasia, the quantitative increase of these markers in malignant tissues provides a sufficient differential for selective antibody targeting. Animal studies with xenografted human tumors provided the first evidence of the prospects of this technology, followed by initial clinical success with purified goat whole IgG antibodies to CEA, labeled with 131I and with the use of dual-isotope subtraction methods. Subsequently, improved and earlier imaging could be accomplished with monoclonal antibody fragments, which then would permit the use of shorter-lived radionuclides, such as 111In, 123I, and 99mTc. The preferred use of a monoclonal anti-CEA IgG Fab' fragment, labeled with 99mTc by a recently developed, simple and rapid kit, has enabled the detection of small lesions, including those in the liver, within 4 h of injection. By means of SPECT imaging, a high sensitivity and specificity for RAID could be achieved.

Synthesis of tripeptide derivatized cyclopentadienyl complexes of technetium and rhenium as radiopharmaceutical probes.

PubMed

Nadeem, Qaisar; Can, Daniel; Shen, Yunjun; Felber, Michael; Mahmood, Zaid; Alberto, Roger

2014-03-28

We describe the syntheses of half-sandwich complexes of the type [(η(5)-Cp(CONH-R))M(CO)3] with M = Re or (99m)Tc. The R group represents different tri-peptides (tpe) which display high binding affinities for oligopeptide transporters PEPT2. The (99m)Tc complexes were prepared directly from [(99m)Tc(OH2)3(CO)3](+) and Diels-Alder dimerized, cyclopentadienyl derivatized peptides in water. This approach corroborates the feasibility of metal-mediated retro Diels-Alder reactions for the preparation of not only small molecules but also peptides carrying a [(η(5)-Cp)(99m)Tc(CO)3] tag. We synthesized the Diels-Alder product [(HCpCONH-tpe)2] from Thiele's acid [(η(5)-HCpCOOH)2] via double peptide coupling. The Re-complexes [(η(5)-CpCONH-tpe)Re(CO)3] were obtained by attaching [(Cp-COOH)Re(CO)3] directly to the N-terminus of peptides as received from SPPS. The authenticity of the (99m)Tc-complexes is confirmed by chromatographic comparison with the corresponding rhenium complexes, fully characterized by spectroscopic techniques.

A 3D Computational fluid dynamics model validation for candidate molybdenum-99 target geometry

NASA Astrophysics Data System (ADS)

Zheng, Lin; Dale, Greg; Vorobieff, Peter

2014-11-01

Molybdenum-99 (99Mo) is the parent product of technetium-99m (99mTc), a radioisotope used in approximately 50,000 medical diagnostic tests per day in the U.S. The primary uses of this product include detection of heart disease, cancer, study of organ structure and function, and other applications. The US Department of Energy seeks new methods for generating 99Mo without the use of highly enriched uranium, to eliminate proliferation issues and provide a domestic supply of 99mTc for medical imaging. For this project, electron accelerating technology is used by sending an electron beam through a series of 100Mo targets. During this process a large amount of heat is created, which directly affects the operating temperature dictated by the tensile stress limit of the wall material. To maintain the required temperature range, helium gas is used as a cooling agent that flows through narrow channels between the target disks. In our numerical study, we investigate the cooling performance on a series of new geometry designs of the cooling channel. This research is supported by Los Alamos National Laboratory.

A decision support system using combined-classifier for high-speed data stream in smart grid

NASA Astrophysics Data System (ADS)

Yang, Hang; Li, Peng; He, Zhian; Guo, Xiaobin; Fong, Simon; Chen, Huajun

2016-11-01

Large volume of high-speed streaming data is generated by big power grids continuously. In order to detect and avoid power grid failure, decision support systems (DSSs) are commonly adopted in power grid enterprises. Among all the decision-making algorithms, incremental decision tree is the most widely used one. In this paper, we propose a combined classifier that is a composite of a cache-based classifier (CBC) and a main tree classifier (MTC). We integrate this classifier into a stream processing engine on top of the DSS such that high-speed steaming data can be transformed into operational intelligence efficiently. Experimental results show that our proposed classifier can return more accurate answers than other existing ones.

Molecular epidemiology of HIV-1 among the HIV infected people of Manipur, Northeastern India: Emergence of unique recombinant forms.

PubMed

Sharma, Adhikarimayum Lakhikumar; Singh, Thiyam Ramsing; Devi, Khuraijam Ranjana; Singh, Lisam Shanjukumar

2017-06-01

According to the Joint National Programme on HIV/AIDS (UNAIDS), the northeastern region of India has the highest HIV prevalence in the country. This study was conducted to determine the current HIV-1 molecular epidemiology of Manipur, a state in northeast India. Blood samples from HIV-1 seropositive subjects were collected between June 2011 and February 2014. The partial regions of HIV-1 genes; pol and tat-vpu-env were independently amplified, sequenced, analyzed, and genotyped. Based on all sequences generated from 110 samples using pol and/or tat-vpu-env gene, the overall HIV-1 genotypes distribution of Manipur was as follows: 65.45% (72/110) subtype C, 32.73% (36/110) unique recombinant forms (URFs), and 1.82% (2/110) subtype B. The distribution of HIV-1 genotypes among the risk groups was: heterosexual: 58.33% (35/60) subtype C, 38.33% (23/60) URFs, and 3.34% (2/60) subtype B; intravenous drug users (IDUs): 85.36% (35/41) subtype C, 9.76% (4/41) URFs, and 4.88% (2/41) subtype B; mother to child (MTC): 50% (3/6) URFs and 50% (3/6) subtype C and blood transfusion: 100% (3/3) subtype C. The findings for the first time revealed the emergence of URFs of HIV-1 in Manipur which is predominant among the sexual and MTC risk groups as compared to IDUs. Taking together, this study illustrated that Manipur is the "recombinant hotspot of HIV" of India. The results will provide the clinical importance for continuous monitoring of HIV-infections in order to design appropriate prevention measures to limit the spread of new HIV infections. © 2016 Wiley Periodicals, Inc.

Advanced Cardiac Life Support (ACLS) utilizing Man-Tended Capability (MTC) hardware onboard Space Station Freedom

NASA Technical Reports Server (NTRS)

Smith, M.; Barratt, M.; Lloyd, C.

1992-01-01

Because of the time and distance involved in returning a patient from space to a definitive medical care facility, the capability for Advanced Cardiac Life Support (ACLS) exists onboard Space Station Freedom. Methods: In order to evaluate the effectiveness of terrestrial ACLS protocols in microgravity, a medical team conducted simulations during parabolic flights onboard the KC-135 aircraft. The hardware planned for use during the MTC phase of the space station was utilized to increase the fidelity of the scenario and to evaluate the prototype equipment. Based on initial KC-135 testing of CPR and ACLS, changes were made to the ventricular fibrillation algorithm in order to accommodate the space environment. Other constraints to delivery of ACLS onboard the space station include crew size, minimum training, crew deconditioning, and limited supplies and equipment. Results: The delivery of ACLS in microgravity is hindered by the environment, but should be adequate. Factors specific to microgravity were identified for inclusion in the protocol including immediate restraint of the patient and early intubation to insure airway. External cardiac compressions of adequate force and frequency were administered using various methods. The more significant limiting factors appear to be crew training, crew size, and limited supplies. Conclusions: Although ACLS is possible in the microgravity environment, future evaluations are necessary to further refine the protocols. Proper patient and medical officer restraint is crucial prior to advanced procedures. Also emphasis should be placed on early intubation for airway management and drug administration. Preliminary results and further testing will be utilized in the design of medical hardware, determination of crew training, and medical operations for space station and beyond.