BackgroundIndocyanine green (ICG)-enhanced fluorescence optical imaging (FOI) is an established technology for imaging of inflammation in animal models. In experimental models of arthritis, FOI findings corresponded to histologically proven synovitis. This is the first comparative study of FOI with other imaging modalities in humans with arthritis.Methods252 FOI examinations (Xiralite system, mivenion GmbH, Berlin, Germany; ICG bolus of 0.1 mg/kg/body weight, sequence of 360 images, one image per second) were compared with clinical examination (CE), ultrasonography (US) and MRI of patients with arthritis of the hands.ResultsIn an FOI sequence, three phases could be distinguished (P1–P3). With MRI as reference, FOI had a sensitivity of 76% and a specificity of 54%, while the specificity of phase 1 was 94%. FOI had agreement rates up to 88% versus CE, 64% versus greyscale US, 88% versus power Doppler US and 83% versus MRI, depending on the compared phase and parameter. FOI showed a higher rate of positive results compared to CE, US and MRI. In individual patients, FOI correlated significantly (p<0.05) with disease activity (Disease Activity Score 28, r=0.41), US (r=0.40) and RAMRIS (Rheumatoid Arthritis MRI Score) (r=0.56). FOI was normal in 97.8% of joints of controls.ConclusionICG-enhanced FOI is a new technology offering sensitive imaging detection of inflammatory changes in subjects with arthritis. FOI was more sensitive than CE and had good agreement with CE, US in power Doppler mode and MRI, while showing more positive results than these. An adequate interpretation of an FOI sequence requires a separate evaluation of all phases. For the detection of synovitis and tenosynovitis, FOI appears to be as informative as 1.5 T MRI and US.
Objective. Indocyanine green-enhanced fluorescence optical imaging (FOI) is a novel diagnostic tool for the assessment of inflammation in arthritis. We undertook this study to compare FOI with magnetic resonance imaging (MRI) in 32 patients with early and very early untreated arthritis (mean disease duration 7.1 months).Methods. FOI images were acquired with the commercially available Xiralite system. Image interpretation was done for an early phase (phase 1), an intermediate phase (phase 2), and a late phase (phase 3), and for an electronically generated composite image. The results were compared with those of clinical examination (960 joints) and contrast (gadolinium)-enhanced 1.5T MRI (382 joints) of the clinically more affected hand. Additionally, we evaluated FOI in a control group of 46 subjects without any signs of inflammatory joint disease (1,380 joints).Results. With MRI as the reference method, the sensitivity of FOI was 86% and the specificity was 63%, while the composite image, phase 1, and phase 3 reached high specificities (87%, 90%, and 88%, respectively). The results differed considerably between the composite image and the phases. FOI did not detect inflammation in 11 joint regions that showed palmar tenosynovitis on MRI. Intrareader and interreader agreements were moderate to substantial ( ؍ 0.55-0.73). In the control group, FOI showed positive findings in 5% of normal joints in phase 2.Conclusion. Further multicenter studies will address the question of whether FOI allows sensitive and reliable detection of inflammatory changes in early arthritis, as suggested by our initial findings. If this is confirmed, FOI has the potential to be a sensitive and valuable tool for monitoring disease activity on site in clinical settings and for serving as an outcome parameter in clinical trials.
Adverse tissue reactions of the gingiva and the periodontium close to dental cast alloys may be caused by the effects of released metal elements. Tissue reactions depend upon the amounts of elements available which are a function of corrosion rates. Since pH values of standard corrosion solutions are as low as 2.3, such extracts are a priori not biocompatible. In the present study, elements released from dental cast alloys into cell-culture media were determined, and the cytotoxicity of these medium extracts was compared with the effectiveness of metal salt solutions prepared according to the metal elements found in extracts. The elements Ag, Cu, Ni, and Zn were detected in extracts of dental alloys and copper (positive control) by inductively coupled plasma atomic emission spectrometry (ICP-AES). Medium extracts of dental alloys were non-toxic in mouse fibroblasts (L929 cells). However, the amounts of elements found in these extracts were weakly cytotoxic when tested as salt solutions prepared from chloride (Cu2+, Zn2+, Ni2+) or sulfate (Ag1+) salts. When the test specimens were heat-treated before extraction, extracts were clearly cytotoxic in a dose-related manner. Again, the amounts of elements that caused 50% cell death (TC50) were slightly lower in corresponding salt solutions than in extracts. In general, cytotoxicity of medium extracts consistently proved to be slightly less than that of the corresponding salt solutions, probably due to the limitations of the chemical analysis of extracts. This should be taken into account if salt solutions are used instead of the medium extract.
The relative stabilities of the six lowest energy tautomers of the DNA base guanine have been investigated in the first excited singlet state, S1, employing the restricted open-shell Kohn–Sham (ROKS) method. Comparison of the S1 optimized geometries to the respective ground-state structures reveals large distortions for the keto tautomers, whereas the enol tautomers remain essentially planar. Harmonic vibrational spectra in the S1 state have been calculated using the ROKS potential energy surfaces. Adiabatic excitation energies together with characteristic vibrational features of the individual guanine tautomers enable us to unambiguously assign recent experimental IR-UV spectra. Velocity autocorrelation functions obtained from adiabatic excited state Car–Parrinello molecular dynamics simulations demonstrate that anharmonic effects only play a minor role.
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