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  • 1
    Electronic Resource
    Electronic Resource
    Tissue transition projection (TTP) of the intestines (2000)
    Springer
    European radiology 10 (2000), S. 806-810 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Spiral CT ; Postprocessing ; Small bowel ; Colon ; Translucent imaging
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. Tissue transition projection (TTP) represents a three-dimensional reconstruction technique for volumetric image data sets. To demonstrate the principle characteristics of TTP, a simple phantom consisting of two pipes with a simulated, wall-adherent polyp was scanned with spiral CT, and images were reconstructed by means of volume rendering for both opaque surface reconstructions and TTP. Tissue transition projection was used in 7 patients for reconstruction of the small intestine or the colon. Unlike three-dimensional reconstructions with opaque surfaces, TTP enhances surface transitions while suppressing homogeneous areas, allowing delineation of the bowel wall similar to conventional double-contrast studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300051008
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Virtual endoscopy of the small bowel: phantom study and preliminary clinical results (1998)
    Springer
    European radiology 8 (1998), S. 563-567 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Computed tomography ; Virtual endoscopy ; Lesion detection ; Small bowel
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The purpose of this study was to determine the optimal scanning technique for lesion detection in a small bowel phantom and to evaluate the virtual endoscopy (VE) technique in patients. A small bowel phantom with a fold thickness of 7 mm and length of 115 cm was prepared with nine round lesions (3 × 1 mm, 2 × 2 mm, 2 × 3 mm, 2 × 4 mm). Spiral CT parameters were 7/7/4, 3/5/2, 3/5/1, 1.5/3/1 (slice thickness/table feed/reconstruction interval). VE was done using volume rendering technique with 1 cm distance between images and 120 ° viewing angle. Two masked readers were asked to determine the number and location of the lesions. Seven patients underwent an abdominal CT during one breathhold after placement of a duodenal tube and filling of the small bowel with methyl cellulose contrast solution. VE images were compared with the axial slices with respect to detectability of pathology. With the 7/7/4 protocol only the 4-mm lesions were visualised with fuzzy contours. The 3/5/2 protocol showed both 4-mm lesions, one 3-mm lesion and one false positive lesion. The 3/5/1 protocol showed both 4-mm and both 3-mm (one uncertain) lesions with improved sharpness, and no false positive lesions. One 2-mm and one 1-mm lesion were additionally seen with the 1.5/3/1 protocol. Path definition was difficult in sharp turns or kinks in the lumen. In all patients, no difference was found between VE and axial slices for bowel pathology; however, axial slices showed ’outside' information that was not included in VE. We conclude that the 3/5/2 protocol may be regarded as an optimal compromise between lesion detection, coverage during one breathhold, and number of reconstructed images in patients; round lesions of 4 mm in diameter can be detected with high certainty.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050434
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Virtual endoscopy of the nose and paranasal sinuses (1998)
    Springer
    European radiology 8 (1998), S. 946-950 
    Details
    ISSN: 1432-1084
    Keywords: Key words: Computed tomography ; Virtual endoscopy ; Volume rendering ; Paranasal sinuses
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract. The purpose of this study was to evaluate the applicability of virtual endoscopy (VE) in the region of the nose and paranasal sinuses on the basis of volume-rendered spiral CT data. Forty-five patients underwent a low-dose spiral CT of the sinuses. The data were transferred to a workstation running software for volume rendering (EasyVision, Philips Medical Systems, Eindhoven, The Netherlands). Six orthogonal views of the maxillary sinuses and the nasopharynx and a fly-through movie of the nose were calculated. Two radiologists evaluated the coronal reconstructions and virtual endoscopy with respect to detectability of pathology using a checklist comprising 10 points. In 30 patients who underwent subsequent endoscopic surgery, surgeons were asked to rank the degree of assistance of the preoperative virtual endoscopy. In general, virtual endoscopy was possible in all 45 patients. The mean time required for path definition and movie calculation for virtual endoscopy were 8 ( ± 2) min and 3 ( ± 1) min, respectively. Overall, more anatomical details were depicted on coronal reconstructions; however, a high degree of similarity between virtual endoscopy and the intraoperative impression was reported by the surgeons. We conclude that virtual endoscopy of the nose and paranasal sinuses may develop into a standard means to guide surgeons during endoscopic interventions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s003300050493
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  • 4
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    Pharmacodynamics of the Anti-TWEAK mAb RG7212 (2016)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2016-02-16
    Description: Purpose: The TWEAK–Fn14 pathway represents a novel anticancer target that is being actively investigated. Understanding the relationship between pharmacokinetics of anti-TWEAK therapeutics and tumor pharmacodynamics is critical. We investigated exposure-response relationships of RG7212, an anti-TWEAK mAb, in patients with Fn14-expressing tumors. Experimental Design: Patients with Fn14-positive tumors (IHC≥1+) treated in a phase I first-in-human study with ascending doses of RG7212 were the basis for this analysis. Pharmacokinetics of RG7212 and dynamics of TWEAK were determined, as were changes in tumor TWEAK–Fn14 signaling in paired pre- and posttreatment tumor biopsies. The objectives of the analysis were to define exposure-response relationships and the relationship between pretreatment tumor Fn14 expression and pharmacodynamic effect. Associations between changes in TWEAK–Fn14 signaling and clinical outcome were explored. Results: Thirty-six patients were included in the analysis. RG7212 reduced plasma TWEAK to undetectable levels at all observed RG7212 exposures. In contrast, reductions in tumor Fn14 and TRAF1 protein expression were observed only at higher exposure (≥300 mg*h/mL). Significant reductions in tumor Ki-67 expression and early changes in serum concentrations of CCL-2 and MMP-9 were observed exclusively in patients with higher drug exposure who had high pretreatment tumor Fn14 expression. Pretreatment tumor Fn14 expression was not associated with outcome, but a trend toward longer time on study was observed with high versus low RG7212 exposure. Conclusions: RG7212 reduced tumor TWEAK–Fn14 signaling in a systemic exposure-dependent manner. In addition to higher exposure, relatively high Fn14 expression might be required for pharmacodynamic effect of anti-TWEAK monoclonal antibodies. Clin Cancer Res; 22(4); 858–67. ©2015 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 5
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    Individualized Pazopanib Dosing--Response (2016)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2016-12-16
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 6
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    Severe Skin Toxicity in Pediatric Oncology Patients Treated with Voriconazole and Concomitant Methotrexate [Clinical Therapeutics] (2013)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2013-05-15
    Description: We report the occurrence of skin toxicities in pediatric oncology patients on concomitant treatment with voriconazole and methotrexate (MTX). Of 23 patients who received this combination, 11 patients suffered from cheilitis and/or photosensitivity. In contrast, only in 1 of 9 patients who received voriconazole without MTX was photosensitivity observed. A mechanism of action was not able to be identified. We describe two cases with severe skin toxicities. Caution is warranted when using voriconazole and concomitant MTX.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
    Published by The American Society for Microbiology (ASM)
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  • 7
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    Failure of Miltefosine in Visceral Leishmaniasis Is Associated With Low Drug Exposure (2014)
    Oxford University Press
    Details
    Publication Date: 2014-06-13
    Description: Background.  Recent reports indicated high miltefosine treatment failure rates for visceral leishmaniasis (VL) on the Indian subcontinent. To further explore the pharmacological factors associated with these treatment failures, a population pharmacokinetic-pharmacodynamic study was performed to examine the relationship between miltefosine drug exposure and treatment failure in a cohort of Nepalese patients with VL. Methods.  Miltefosine steady-state blood concentrations at the end of treatment were analyzed using liquid chromatography tandem mass spectrometry. A population pharmacokinetic-pharmacodynamic analysis was performed using nonlinear mixed-effects modeling and a logistic regression model. Individual estimates of miltefosine exposure were explored for their relationship with treatment failure. Results.  The overall probability of treatment failure was 21%. The time that the blood concentration was 〉10 times the half maximal effective concentration of miltefosine (median, 30.2 days) was significantly associated with treatment failure: each 1-day decrease in miltefosine exposure was associated with a 1.08-fold (95% confidence interval, 1.01–1.17) increased odds of treatment failure. Conclusions.  Achieving a sufficient exposure to miltefosine is a significant and critical factor for VL treatment success, suggesting an urgent need to evaluate the recently proposed optimal allometric miltefosine dosing regimen. This study establishes the first evidence for a drug exposure-effect relationship for miltefosine in the treatment of VL.
    Print ISSN: 0022-1899
    Electronic ISSN: 1537-6613
    Topics: Medicine
    Published by Oxford University Press on behalf of The Infectious Diseases Society of America (IDSA).
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  • 8
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    Molecular Imaging of ABCB1 and ABCG2 Inhibition at the Human Blood-Brain Barrier Using Elacridar and 11C-Erlotinib PET (2018)
    The Society of Nuclear Medicine (SNM)
    Details
    Publication Date: 2018-06-02
    Description: Transporters such as ABCB1 and ABCG2 limit the exposure of several anticancer drugs to the brain, leading to suboptimal treatment in the central nervous system. The purpose of this study was to investigate the effects of the ABCB1 and ABCG2 inhibitor elacridar on brain uptake using 11 C-erlotinib PET. Methods: Elacridar and cold erlotinib were administered orally to wild-type (WT) and Abcb1a/b;Abcg2 knockout mice. In addition, brain uptake was measured using 11 C-erlotinib imaging and ex vivo scintillation counting in knockout and WT mice. Six patients with advanced solid tumors underwent 11 C-erlotinib PET scans before and after a 1,000-mg dose of elacridar. 11 C-erlotinib brain uptake was quantified by pharmacokinetic modeling using volume of distribution (V T ) as the outcome parameter. In addition, 15 O-H 2 O scans to measure cerebral blood flow were acquired before each 11 C-erlotinib scan. Results: Brain uptake of 11 C-erlotinib was 2.6-fold higher in Abcb1a/b;Abcg2 knockout mice than in WT mice, measured as percentage injected dose per gram of tissue ( P = 0.01). In WT mice, the addition of elacridar (at systemic plasma concentrations of ≥200 ng/mL) resulted in an increased brain concentration of erlotinib, without affecting erlotinib plasma concentration. In patients, the V T of 11 C-erlotinib did not increase after intake of elacridar (0.213 ± 0.12 vs. 0.205 ± 0.07, P = 0.91). 15 O-H 2 O PET showed no significant changes in cerebral blood flow. Elacridar exposure in patients was 401 ± 154 ng/mL. No increase in V T with increased elacridar plasma exposure was found over the 271–619 ng/mL range. Conclusion: When Abcb1 and Abcg2 were disrupted in mice, brain uptake of 11 C-erlotinib increased both at a tracer dose and at a pharmacologic dose. In patients, brain uptake of 11 C-erlotinib was not higher after administration of elacridar. The more pronounced role that ABCG2 appears to play at the human blood–brain barrier and the lower potency of elacridar to inhibit ABCG2 may be an explanation of these interspecies differences.
    Print ISSN: 0022-3123
    Topics: Medicine
    Published by The Society of Nuclear Medicine (SNM)
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  • 9
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    New Therapy for Epstein-Barr Virus-Driven Tumors (2012)
    The American Association for Cancer Research (AACR)
    Details
    Publication Date: 2012-09-18
    Description: Purpose: Nasopharyngeal carcinoma (NPC) is causally linked to Epstein–Barr virus (EBV) infection. Because all tumor cells carry EBV, the virus itself is a potential target for therapy. In these tumor cells, EBV hides in a latent state and expresses only a few non-immunogenic proteins for EBV maintenance and contributes to tumor growth. We developed a cytolytic virus activation (CLVA) therapy for NPC treatment, reactivating latent EBV, triggering immune recognition, and inducing susceptibility to antiviral therapy. Experimental Design: CLVA therapy combines gemcitabine (GCb) and valproic acid (VPA) for virus activation and tumor clearance with (val)ganciclovir (GCV) as the antiviral drug to block virus replication and kill proliferating virus-infected cells. CLVA treatment was optimized and validated in NPC cell lines and subsequently tested in 3 Dutch patients with NPC that was refractory to conventional treatment. Results: In NPC cell lines, both GCb and VPA can induce the lytic cycle of EBV. Their combination resulted in a strong synergistic effect. The addition of GCV resulted in higher cytotoxicity compared with chemotherapy alone, which was not observed in EBV-negative cells. CLVA therapy was analyzed in 3 patients with end-stage NPC. Patients developed increased levels of viral DNA in the circulation originating from apoptotic tumor cells, had disease stabilization, and experienced improved quality of life. Conclusions: Our results in the initial CLVA-treated patients indicate that the therapy had a biological effect and was well tolerated with only moderate transient toxicity. This new virus-specific therapy could open a generic approach for treatment of multiple EBV-associated malignancies. Clin Cancer Res; 18(18); 5061–70. ©2012 AACR .
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Published by The American Association for Cancer Research (AACR)
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  • 10
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    Optimal Dosing of Miltefosine in Children and Adults with Visceral Leishmaniasis [Pharmacology] (2012)
    The American Society for Microbiology (ASM)
    Details
    Publication Date: 2012-06-15
    Description: Only anecdotal data are available on the pharmacokinetics (PK) of miltefosine in children suffering from visceral leishmaniasis (VL). While failure rates were higher in children with VL, steady-state concentrations appeared lower than those seen with adults. We hypothesized that the current linear dosage (in milligrams per kilogram of body weight) is too low for children and that a new dosing algorithm based on an appropriate body size model would result in an optimal exposure. A population PK analysis was performed on three historic pooled data sets, including Indian children, Indian adults, and European adults. Linear and allometric scaling of PK parameters by either body weight or fat-free mass (FFM) was evaluated for body size models. Based on the developed PK model, a dosing algorithm for miltefosine in children and adults was proposed and evaluated in silico . The population PK model employing allometric scaling fitted best to the pooled miltefosine data. Allometric scaling by FFM reduced between-subject variability, e.g., for drug clearance, from 49.6% to 32.1%. A new allometric miltefosine dosing algorithm was proposed. Exposure to miltefosine was lower in children than adults receiving 2.5 mg/kg/day: a C max of 18.8 μg/ml was reached by 90% of adults and 66.7% of children. The allometric daily dose resulted in similar levels of exposure to miltefosine for adults and children. The use of a new allometric dosing algorithm for miltefosine in VL patients results in optimal exposure to miltefosine in both adults and children and might improve clinical outcome in children.
    Print ISSN: 0066-4804
    Electronic ISSN: 1098-6596
    Topics: Biology , Medicine
    Published by The American Society for Microbiology (ASM)
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