Prevalência das manifestações neuropsiquiátricas em pacientes com lúpus eritematoso sistêmico.

Trabalho de Conclusão de Curso - Universidade Federal de Santa Catarina. Curso de Medicina. Departamento de Clínica Médica

Comparison of Two Digital Stethoscopes with the Traditional Stethoscope Used on International Space Station

A traditional stethoscope is currently flown on the International Space Station (ISS). The background noise on the ISS is much higher than a normal exam room, and the literature shows that traditional stethoscopes are unable to function effectively in high noise environments. Digital stethoscopes provide amplification which improves the audibility in a quiet environment. This study is designed to determine if digital stethoscopes offer any advantage over traditional stethoscopes in being able to identify normal and abnormal sounds in the ISS noise environment. Methods: An ISS noise simulation facility was created to reproduce ISS noise profiles by modifying pink noise with a software-based graphic equalizer. The files were played in a continuous loop on a computer, amplified through a high-end stereo system and adjusted using a sound level meter. Nine caregiver analogues were given the same auscultation lesson received by astronauts. They began testing by becoming familiar with normal and abnormal sounds on a Student Auscultation Manikin . They then used two digital stethoscopes and a traditional stethoscope identical to the one flown on the ISS to auscultate the manikin sounds in the noise facility. They identified the sounds on a questionnaire and picked which of the three stethoscopes they preferred. Results: Evaluators displayed equivalent accuracy in sound identification when using either the 3M model 4000 digital stethoscope or traditional stethoscope. However, the 3M was preferred 2 to 1 by the evaluators, primarily because of additional amplification of the sounds. Discussion: Although our results show that the current ISS stethoscope and the "best-of-breed" digital stethoscope provide essentially the same auscultation utility, the latter has the advantage of recording and transmitting sounds to a remote physician. Since the astronaut caregivers are non-physiCians, this capability may be worth the additional expense and effort needed to certify the digital stethoscope for flight

Vandetanib-eluting Radiopaque Beads: <i>In vivo</i> Pharmacokinetics, Safety and Toxicity Evaluation following Swine Liver Embolization.

To evaluate the plasma and tissue pharmacokinetics, safety and toxicity following intra-arterial hepatic artery administration of Vandetanib (VTB)-eluting Radiopaque Beads (VERB) in healthy swine. In a first phase, healthy swine were treated with hepatic intra-arterial administration of VERB at target dose loading strengths of 36 mg/mL (VERB36), 72 mg/mL (VERB72) and 120 mg/mL (VERB120). Blood and tissue samples were taken and analysed for VTB and metabolites to determine pharmacokinetic parameters for the different dose forms over 30 days. In a second phase, animals were treated with unloaded radiopaque beads or high dose VTB loaded beads (VERB100, 100 mg/mL). Tissue samples from embolized and non-embolized areas of the liver were evaluated at necropsy (30 and 90 days) for determination of VTB and metabolite levels and tissue pathology. Imaging was performed prior to sacrifice using multi-detector computed tomography (MDCT) and imaging findings correlated with pathological changes in the tissue and location of the radiopaque beads. The peak plasma levels of VTB (C &lt;sub&gt;max&lt;/sub&gt; ) released from the various doses of VERB ranged between 6.19-17.3 ng/mL indicating a low systemic burst release. The plasma profile of VTB was consistent with a distribution phase up to 6 h after administration followed by elimination with a half-life of 20-23 h. The AUC of VTB and its major metabolite N-desmethyl vandetanib (NDM VTB) was approximately linear with the dose strength of VERB. VTB plasma levels were at or below limits of detection two weeks after administration. In liver samples, VTB and NDM VTB were present in treated sections at 30 days after administration at levels above the &lt;i&gt;in vitro&lt;/i&gt; IC &lt;sub&gt;50&lt;/sub&gt; for biological effectiveness. At 90 days both analytes were still present in treated liver but were near or below the limit of quantification in untreated liver sections, demonstrating sustained release from the VERB. Comparison of the reduction of the liver lobe size and associated tissue changes suggested a more effective embolization with VERB compared to the beads without drug. Hepatic intra-arterial administration of VERB results in a low systemic exposure and enables sustained delivery of VTB to target tissues following embolization. Changes in the liver tissue are consistent with an effective embolization and this study has demonstrated that VERB100 is well tolerated with no obvious systemic toxicity

Long-term biocompatibility, imaging appearance and tissue effects associated with delivery of a novel radiopaque embolization bead for image-guided therapy

The objective of this study was to undertake a comprehensive long-term biocompatibility and imaging assessment of a new intrinsically radiopaque bead (LC Bead LUMI™) for use in transarterial embolization. The sterilized device and its extracts were subjected to the raft of ISO10993 biocompatibility tests that demonstrated safety with respect to cytotoxicity, mutagenicity, blood contact, irritation, sensitization, systemic toxicity and tissue reaction. Intra-arterial administration was performed in a swine model of hepatic arterial embolization in which 0.22–1 mL of sedimented bead volume was administered to the targeted lobe(s) of the liver. The beads could be visualized during the embolization procedure with fluoroscopy, DSA and single X-ray snapshot imaging modalities. CT imaging was performed before and 1 h after embolization and then again at 7, 14, 30 and 90 days. LC Bead LUMI™ could be clearly visualized in the hepatic arteries with or without administration of IV contrast and appeared more dense than soluble contrast agent. The CT density of the beads did not deteriorate during the 90 day evaluation period. The beads embolized predictably and effectively, resulting in areas devoid of contrast enhancement on CT imaging suggesting ischaemia-induced necrosis nearby the sites of occlusion. Instances of off target embolization were easily detected on imaging and confirmed pathologically. Histopathology revealed a classic foreign body response at 14 days, which resolved over time leading to fibrosis and eventual integration of the beads into the tissue, demonstrating excellent long-term tissue compatibility

Radiopaque drug-eluting embolisation beads as fiducial markers for stereotactic liver radiotherapy

OBJECTIVE: To determine the feasibility of using radiopaque (RO) beads as direct tumour surrogates for image-guided radiotherapy (IGRT) in patients with liver tumours after transarterial chemoembolisation (TACE). METHODS: A novel vandetanib-eluting RO bead was delivered via TACE as part of a first-in-human clinical trial in patients with either hepatocellular carcinoma or liver metastases from colorectal cancer. Following TACE, patients underwent simulated radiotherapy imaging with 4-dimensional computed tomography (4D-CT) and cone-beam CT (CBCT) imaging. RO beads were contoured using automated thresholding, and feasibility of matching between the simulated radiotherapy planning dataset (AVE-IP image from 4D data) and CBCT scans assessed. Additional kV, MV, helical CT and CBCT images of RO beads were obtained using an in-house phantom. Stability of RO bead position was assessed by comparing 4D-CT imaging to CT scans taken 6-20 days following TACE. RESULTS: Eight patients were treated and 4D-CT and CBCT images acquired. RO beads were visible on 4D-CT and CBCT images in all cases and matching successfully performed. Differences in centre of mass of RO beads between CBCT and simulated radiotherapy planning scans (AVE-IP dataset) were: 2.0 mm mediolaterally, 1.7 mm anteroposteriorally, 3.5 mm craniocaudally. RO beads in the phantom were visible on all imaging modalities assessed. RO bead position remained stable up to 29 days post-TACE. CONCLUSION: RO beads are visible on IGRT imaging modalities, showing minimal artefact. They can be used for on-set matching with CBCT and remain stable over time. ADVANCES IN KNOWLEDGE: The role of RO beads as fiducial markers for stereotactic liver radiotherapy is feasible and warrants further exploration as a combination therapy approach

VEROnA Protocol: A Pilot, Open-Label, Single-Arm, Phase 0, Window-of-Opportunity Study of Vandetanib-Eluting Radiopaque Embolic Beads (BTG-002814) in Patients With Resectable Liver Malignancies

BACKGROUND: Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and is also a treatment option for patients with liver metastases from colorectal cancer. However, TACE is not a curative treatment, and tumor progression occurs in more than half of the patients treated. Despite advances and technical refinements of TACE, including the introduction of drug-eluting beads-TACE, the clinical efficacy of TACE has not been optimized, and improved arterial therapies are required. OBJECTIVE: The primary objectives of the VEROnA study are to evaluate the safety and tolerability of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies and to determine concentrations of vandetanib and the N-desmethyl metabolite in plasma and resected liver following treatment with BTG-002814. METHODS: The VEROnA study is a first-in-human, open-label, single-arm, phase 0, window-of-opportunity study of BTG-002814 (containing 100 mg vandetanib) delivered transarterially, 7 to 21 days before surgery in patients with resectable liver malignancies. Eligible patients have a diagnosis of colorectal liver metastases, or HCC (Childs Pugh A), diagnosed histologically or radiologically, and are candidates for liver surgery. All patients are followed up for 28 days following surgery. Secondary objectives of this study are to evaluate the anatomical distribution of BTG-002814 on noncontrast-enhanced imaging, to evaluate histopathological features in the surgical specimen, and to assess changes in blood flow on dynamic contrast-enhanced magnetic resonance imaging following treatment with BTG-002814. Exploratory objectives of this study are to study blood biomarkers with the potential to identify patients likely to respond to treatment and to correlate the distribution of BTG-002814 on imaging with pathology by 3-dimensional modeling. RESULTS: Enrollment for the study was completed in February 2019. Results of a planned interim analysis were reviewed by a safety committee after the first 3 patients completed follow-up. The recommendation of the committee was to continue the study without any changes to the dose or trial design, as there were no significant unexpected toxicities related to BTG-002814. CONCLUSIONS: The VEROnA study is studying the feasibility of administering BTG-002814 to optimize the use of this novel technology as liver-directed therapy for patients with primary and secondary liver cancer. TRIAL REGISTRATION: ClinicalTrial.gov NCT03291379; https://clinicaltrials.gov/ct2/show/NCT03291379. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13696

Studies on the biology and pharmacology of avian medullary bone osteoclasts in vitro

SIGLEAvailable from British Library Document Supply Centre- DSC:DX179643 / BLDSC - British Library Document Supply CentreGBUnited Kingdo

Spectroscopy Of Unstable Molecules

The {dollar}\rm B\sp2\Sigma\sp{lcub}+{rcub}{dollar} ion-pair excited states for the unstable group IIB metal monohalide radicals have acquired eminence as the upper levels for the potentially important blue/green lasers. In this work, the metal monohalide radicals were produced by exciting a corona excited electrical discharge in a supersonic gas expansion. The ion-pair-valence {dollar}\rm B\sp2\Sigma\sp{lcub}+{rcub}\gets X\sp2\Sigma\sp{lcub}+{rcub}{dollar} transitions for several of these species were recorded by the method of laser induced fluorescence excitation spectroscopy. For HgCl the resultant spectra recorded over the 368-267nm range reveal an extensive vibrationally and isotopically resolved structure due to transitions between {dollar}\rm X\sp2\Sigma\sp{lcub}+{rcub}\ (2\ge v\sp{lcub}\prime\prime{rcub}\ge0){dollar} and {dollar}\rm B\sp2\Sigma\sp{lcub}+{rcub}\ (75\ge v\sp\prime\ge21){dollar}. The {dollar}\rm B\sp2\Sigma\sp{lcub}+{rcub}\gets X\sp2\Sigma\sp{lcub}+{rcub}{dollar} fluorescence excitation spectrum for HgI extending from 322nm to 367nm shows that transitions from the lowest ground state levels {dollar}\rm (v\sp{lcub}\prime\prime{rcub}=0-2){dollar} excite the ion-pair state over a wide range of high vibrational levels {dollar}\rm (v\sp\prime=30-70).{dollar} The HgBr vibrational progressions {dollar}\rm B\sp2\Sigma\sp{lcub}+{rcub}(v\sp\prime=62-54)\gets X\sp2\Sigma\sp{lcub}+{rcub} (v\sp{lcub}\prime\prime{rcub}=0-1){dollar} were also recorded. Franck-Condon factor calculations were carried out to estimate the equilibrium bond lengths of the excited states.;High quality spectra for the heteronuclear rare gas excimers have long eluded experimentalists since these molecules are physically unstable. Recently, our group recorded single isotopomer resonantly enhanced {dollar}(2+1){dollar} multiphoton ionization spectra of jet cooled ArKr and NeXe using time-of-flight mass detection. In this thesis the findings of the vibrational analyses for several transitions of these two molecules are presented.;Excited state equilibrium bond lengths for all of the Rydberg states observed were estimated using Franck-Condon factor calculations. Four band systems of ArKr were observed in the energy region 94825-92012 cm{dollar}\sp{lcub}-1{rcub}{dollar} whose exerted states dissociate to {dollar}\rm Ar+Kr\sp{lcub}*{rcub}(5p){dollar} or{dollar}\rm Kr+Ar\sp{lcub}*{rcub}(4s){dollar}. Eight Rydberg state-ground state transitions of NeXe were identified whose upper states dissociate to {dollar}\rm Ne+Xe\sp{lcub}*{rcub}(6p{dollar} or 5d) in the region between 80073-78546 cm{dollar}\sp{lcub}-1{rcub}{dollar}. To aid in the electronic symmetry assignments all spectra were recorded separately with linearly and circularly polarized radiation. A model is presented to explain the trends of the excited states dissociation energies and vibrational frequencies in terms of the relative importance of covalent bonding versus long range interactions

An analysis of the methyl rotation dynamics in the So (x' A) and T (a A) states of thioacetaldehyde from Pyrolysis jet spectra /

Jet-cooled, laser-induced phosphorescence excitation spectra (LIP) of thioacetaldehyde CH3CHS, CH3CDS, CD3CHS and CD3CDS have been observed over the region 15800 - 17300 cm"^ in a continuous pyrolysis jet. The vibronic band structure of the singlet-triplet n -* n* transition were attributed to the strong coupling of the methyl torsion and aldehydic hydrogen wagging modes . The vibronic peaks have been assigned in terms of two upper electronic state (T^) vibrations; the methyl torsion mode v^g, and the aldehydic hydrogen wagging mode v^^. The electronic origin O^a^ is unequivocally assigned as follows: CH3CHS (16294.9 cm"'' ), CH3CDS (16360.9 cm"'' ), CD3CHS (16299.7 cm"^ ), and CD3CDS (16367.2 cm"'' ). To obtain structural and dynamical information about the two electronic states, potential surfaces V(e,a) for the 6 (methyl torsion) and a (hydrogen wagging) motions were generated by ab initio quantum mechanical calculations with a 6-3 IG* basis in which the structural parameters were fully relaxed. The kinetic energy coefficients BQ(a,e) , B^(a,G) , and the cross coupling term B^(a,e) , were accurately represented as functions of the two active coordinates, a and 9. The calculations reveal that the molecule adopts an eclipsed conformation for the lower Sq electronic state (a=0°,e=0"') with a barrier height to internal rotation of 541.5 cm"^ which is to be compared to 549.8 cm"^ obtained from the microwave experiment. The conformation of the upper T^ electronic state was found to be staggered (a=24 . 68° ,e=-45. 66° ) . The saddle point in the path traced out by the aldehyde wagging motion was calculated to be 175 cm"^ above the equilibrium configuration. The corresponding maxima in the path taken by methyl torsion was found to be 322 cm'\ The small amplitude normal vibrational modes were also calculated to aid in the assignment of the spectra. Torsional-wagging energy manifolds for the two states were derived from the Hamiltonian H(a,e) which was solved variationally using an extended two dimensional Fourier expansion as a basis set. A torsionalinversion band spectrum was derived from the calculated energy levels and Franck-Condon factors, and was compared with the experimental supersonic-jet spectra. Most of the anomalies which were associated with the interpretation of the observed spectrum could be accounted for by the band profiles derived from ab initio SCF calculations. A model describing the jet spectra was derived by scaling the ab initio potential functions. The global least squares fitting generates a triplet state potential which has a minimum at (a=22.38° ,e=-41.08°) . The flatter potential in the scaled model yielded excellent agreement between the observed and calculated frequency intervals