Avaliação de propriedades físico-químicas e antimicrobianas sobre Enterococcus faecalis do mineral trióxido agregado associado a óleo de melaleuca ou farnesol

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Optimal Timing for Assessment of Tumor Response to Neoadjuvant Chemoradiation in Patients With Rectal Cancer: Do All Patients Benefit From Waiting Longer Than 6 Weeks?

Purpose: To estimate the metabolic activity of rectal cancers at 6 and 12 weeks after completion of chemoradiation therapy (CRT) by 2-[fluorine-18] fluoro-2-deoxy-D-glucose-labeled positron emission tomography/computed tomography ([18 FDG] PET/CT) imaging and correlate with response to CRT. Methods and Materials: Patients with cT2-4N0-2M0 distal rectal adenocarcinoma treated with long-course neoadjuvant CRT (54 Gy, 5-fluouracil-based) were prospectively studied (ClinicalTrials. org identifier NCT00254683). All patients underwent 3 PET/CT studies (at baseline and 6 and 12 weeks fromCRT completion). Clinical assessment was at 12 weeks. Maximal standard uptakevalue (SUVmax) of the primary tumor wasmeasured and recorded at eachPET/CTstudy after 1 h (early) and3 h (late) from 18 FDGinjection. Patientswith an increase in early SUVmax between 6 and 12 weeks were considered " bad" responders and the others as "good" responders. Results: Ninety-one patients were included; 46 patients (51%) were "bad" responders, whereas 45 (49%) patients were " good" responders. " Bad" responders were less likely to develop complete clinical response (6.5% vs. 37.8%, respectively; PZ. 001), less likely to develop significant histological tumor regression (complete or near-complete pathological response; 16% vs. 45%, respectively; PZ. 008) and exhibited greater final tumor dimension (4.3cmvs. 3.3cm; PZ. 03). Decrease between early (1 h) and late (3 h) SUVmax at 6-week PET/CTwas a significant predictor of " good" response (accuracy of 67%). Conclusions: Patients who developed an increase in SUVmax after 6 weeks were less likely to develop significant tumor downstaging. Early-late SUVmax variation at 6-week PET/CT may help identify these patients and allow tailored selection of CRT-surgery intervals for individual patients. (C) 2012 Elsevier Inc.

Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation Long-Term Results of a Prospective Trial (National Clinical Trial 00254683)

BACKGROUND: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. METHODS: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. RESULTS: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. CONCLUSIONS: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;35013511. (C) 2011 American Cancer Society.

Neurovascular anatomical variations in the anterior palate observed on CBCT images

Objective: This study aimed to assess the presence of additional foramina and canals in the anterior palate region, through cone beam computed tomography (CBCT) images, describing their location, direction, and diameter. Materials & Methods: CBCT exams of 178 subjects displaying the anterior maxilla were included and the following parameters were registered: gender; age group; presence of additional foramina in the anterior palate (AFP) with at least 1 mm in diameter; location and diameter of AFP; and direction of bony canals associated with AFP. Results: Twenty-eight patients (15.7%) presented AFP and in total 34 additional foramina were registered. No statistical differences between patients with or without AFP were found for gender or age. The average diameter of AFP was 1.4 mm (range from 1 to 1.9 mm). Their location was variable, with most of the cases occurring in the alveolar process near the incisors or canines (n = 27). In 18 cases, AFP was associated with bony canals with upward or oblique direction toward the anterior nasal cavity floor. In 14 cases, the canal presented as a direct extension of the canalis sinuosus, in an upward direction laterally to the nasal cavity aperture. In two cases, the canal was observed adjacent to the incisive and joined the nasopalatine canal superiorly. Discussion: CBCT images have a crucial role in the recognition of anatomical variations by allowing detailed tridimensional evaluations. Additional foramina and canals in the anterior region of the upper jaw are relatively frequent. Practitioners should be aware and trained to identify these variations. Conclusions: Over 15% of the population studied had additional foramina in the anterior palate, between 1 mm and 1.9 mm wide, with variable locations. In most cases the canals associated with these foramina either presented as a direct extension of the canalis sinuosus, or coursed towards the nasal cavity floor.

Evaluation of bone strength: microtomographic tecniques

This thesis is a part of a larger study about the characterization of mechanical and histomorphometrical properties of bone. The main objects of this study were the bone tissue properties and its resistance to mechanical loads. Moreover, the knowledge about the equipment selected to carry out the analyses, the micro-computed tomography (micro-CT), was improved. Particular attention was given to the reliability over time of the measuring instrument. In order to understand the main characteristics of bone mechanical properties a study of the skeletal, the bones of which it is composed and biological principles that drive their formation and remodelling, was necessary. This study has led to the definition of two macro-classes describing the main components responsible for the resistance to fracture of bone: quantity and quality of bone. The study of bone quantity is the current clinical standard measure for so-called bone densitometry, and research studies have amply demonstrated that the amount of tissue is correlated with its mechanical properties of elasticity and fracture. However, the models presented in the literature, including information on the mere quantity of tissue, have often been limited in describing the mechanical behaviour. Recent investigations have underlined that also the bone-structure and the tissue-mineralization play an important role in the mechanical characterization of bone tissue. For this reason in this thesis the class defined as bone quality was mainly studied, splitting it into two sub-classes of bone structure and tissue quality. A study on bone structure was designed to identify which structural parameters, among the several presented in the literature, could be integrated with the information about quantity, in order to better describe the mechanical properties of bone. In this way, it was also possible to analyse the iteration between structure and function. It has been known for long that bone tissue is capable of remodeling and changing its internal structure according to loads, but the dynamics of these changes are still being analysed. This part of the study was aimed to identify the parameters that could quantify the structural changes of bone tissue during the development of a given disease: osteoarthritis. A study on tissue quality would have to be divided into different classes, which would require a scale of analysis not suitable for the micro-CT. For this reason the study was focused only on the mineralization of the tissue, highlighting the difference between bone density and tissue density, working in a context where there is still an ongoing scientific debate.

Ortsaufgelöste Speziation von Schwermetallen in geogenen Proben mit Röntgenabsorptionsspektrometrie (my-XAS)

Die Vergesellschaftung und Bindungsform von Arsen in Düngekalk wurde durch chemische und mineralogische Analysen sowie XANES/EXAFS-Messungen untersucht. Die durch-schnittliche As-Konzentration im Düngekalk (70 mg/kg) überschreitet den Grenzwert der DüMV (40 mg/kg). Arsen ist in Mn- (Romanechit) und Fe-Dendriten (Goethit, Ferrihydrit) angereichert. Seine Oxidationsstufe ist jeweils 5+. µ-EXAFS-Untersuchungen ergaben Hin-weise auf zweizähnige und einzähnige mononukleare Durchdringungskomplexe mit Eisen-oxid. Das Mobilisierungsverhalten von Arsen wurde durch sequentielle Extraktion des Dün-gekalks und Mobilisierungsversuche mit wassergesättigtem Boden untersucht. Die Lösung erfolgte vorwiegend im dritten Extraktionsschritt gemeinsam mit kristallinen Eisenoxiden. Unter moderat anoxischen Bedingungen war im Boden keine zusätzliche Mobilisierung von Arsen aus dem Düngekalk nachweisbar. Erhöhte As-Konzentrationen und As3+-Anteile im Porenwasser traten bei niedrigem Eh unabhängig von Kalkzugabe auf. Eine Kopplung des Arsen-Grenzwerts an den Eisenoxidgehalt erscheint sinnvoll. Ein Messaufbau für Mikro-XAS Imaging wurde in Betrieb genommen. Er ermöglicht die si-multane Erfassung einer Probenfläche von 26,6×6,6 mm² wahlweise im Transmissions- oder Fluoreszenzmodus mit der räumlichen Auflösung 52×52 µm² durch eine CCD-Kamera. Zur Datenverarbeitung wurden IDL-Programme sowie die Fernerkundungssoftware ENVI ver-wendet. Die Messergebnisse zeigen weniger Störungen und Rauschen als die Ergebnisse frü-herer Messungen mit einem Prototyp. Die Ergebnisse und Erfahrungen der Messungen liefern Hinweise für die weitere erfolgreiche Nutzung des Messaufbaus.

Radiomarkierung von HPMA-basierten, funktionalisierten Polymeren mit metallischen Radionukliden für die medizinische Anwendung als Theranostika

Für eine erfolgreiche Behandlung bösartiger Tumore ist eine frühzeitige Diagnose, aber auch eine effektive und effiziente Therapie essentiell. In diesem Zusammenhang sind Nanomaterialien in den Fokus der Arzneimittelentwicklung gerückt, welche für Diagnostik und Therapie genutzt werden könnten.rnSystematische Studien zur Radiometallmarkierung von Nanopartikeln und deren Stabilität in vitro im Zusammenhang mit der Struktur des Linkers und dem Anteil an Chelator wurden anhand verschiedener HPMA-DOTA-Konjugate durchgeführt. Es konnte gezeigt werden, dass die Linkerstruktur und der Belegungsgrad sowohl die Markierung als auch die in vitro -Stabilität von radiometallmarkierten HPMA-rnDOTA-Konjugaten beeinflussen.rnFür die Markierung selbst stehen mehrere Generator-produzierte metallische Positronenemitter zur Verfügung. Infolge der gesetzlichen Bestimmungen muss das Eluat der Generatoren bestimmte Spezifikationen (Elutionsausbeute, Durchbruch des Mutternuklids, Gehalt an Fremdionen, pH-Wert etc.) erfüllen, um für die Darstellung von Radiopharmaka verwendet werden zu können.rnFür das bereits etablierte PET-Nuklid 68Ga konnte eine Ethanol-basierte Aufreinigung entwickelt werden, welche hohe Elutions- und Markierungsausbeuten sowie Radionuklidreinheit garantiert und damit einen wichtigen Schritt für die Entwicklung von Kit-Formulierungen repräsentiert. Ausserdem konnten zwei Methoden zur Qualitätskontrolle entwickelt werden, welche es ermöglichen die Radionuklidreinheit des initialen 68Ga-Eluats, aber auch des finalen 68Ga-Radiopharmakons innerhalb einer Stunde ohne γ–Spektroskopie zu bestimmen.rnWährend mit 68Ga die Pharmakokinetik markierter Derivate für einen Zeitraum von bis 3 Stunden zugänglich ist, deckt das Generator-produzierte 44Sc eine Periode von bis zu einem Tag ab. Damit lässt sich die Pharmakokinetik markierter polymerer Drug Carrier-Systeme – von der frühen Ausscheidungsphase bis hin zu organspezifischen Akkumulationen durch passives und aktives Targeting – gut beschreiben.rnFür 44Sc konnte anhand der Modellverbindung DOTATOC gezeigt werden, dass das aufgereinigte Generatoreluat für die Markierung mit hohen radiochemischen Ausbeuten geeignet ist und etablierte Markierungsmethoden übertragbar sind. In weiterführenden Studien zur molekularen Bildgebung könnte das Potential dieses PET-Nuklids für die Langzeitbildgebung gezeigt werden.

Valutazione dell'accuratezza e della precisione di un algoritmo di correlazione digitale di volumi applicato a vertebre naturali e trattate

La Digital Volume Correlation (DVC) è una tecnica di misura a tutto campo, non invasiva, che permette di misurare spostamenti e deformazioni all’interno della struttura ossea in esame. Mediante la comparazione d’immagini con provino scarico e con provino carico, ottenute attraverso sistemi di tomografia computerizzata, si può ottenere la mappa degli spostamenti per ogni direzione e la mappa di deformazione per ogni componente di deformazione. L’obiettivo di questo lavoro di tesi è la validazione della DVC, attraverso la determinazione dell’errore sistematico (accuratezza) e dell’errore casuale (precisione), in modo da poter valutare il livello di affidabilità della strumentazione. La valutazione si effettua su provini di vertebre di maiale, aumentate e non, sia a livello d’organo, sia a livello di tessuto. The Digital Volume Correlation (DVC) is a full field and contact less measurement technique that allowed estimating displacement and strain inside bone specimen. Images of the unloaded and loaded specimen were obtained from micro-CT and compared in order to obtain the displacement map and, differentiating, the strain map. The aim of this work is the validation of the approach, estimating the lack of accuracy (systematic error) and the lack of precision (random error) on different kinds of porcine vertebra, augmented and not, analysing the specimen on tissue level and on organ level.

The use of mobile single-sided NMR for the diagnosis of osteoporosis: a preliminary study

Una nuova ed originale tecnica è stata messa a punto, finalizzata alla realizzazione di una procedura per la diagnosi dell’osteoporosi, mediante l’utilizzo di scanner low field single-sided NMR. Tre differenti scanner (NMR MOLE, MOUSE PM 10 e MOUSE PM5) sono stati usati per determinare il Bone Volume-to-Total Volume ratio (BV/TV), parametro che fornisce indicazioni sulla microstruttura dell’osso. I risultati sono stati confrontati con le analisi micro-CT. Gli esperimenti sono stati condotti nel Lab. NMR del dipartimento DIFA di UNIBO e nel Lab. NMR della Victoria University di Wellington (NZ), durante un periodo di visita di cinque mesi, supportato da una borsa di studio della “Facoltà di Scienze” di UNIBO. Le analisi micro-CT sono state condotte presso il Lab. di Tecnologie Mediche dell’Istituto Ortopedico Rizzoli, Bologna. La ricerca è stata parzialmente finanziata dalla “Fondazione del Monte di Bologna e Ravenna”. La caratterizzazione dell’osso trabecolare di campioni animali e dei tessuti che lo circondano (come cartilagine e muscolo) è stata condotta tramite mappe di correlazione T1-T2 e D-T2 , dove T1 e T2 sono, rispettivamente, il tempo di rilassamento longitudinale e trasversale del nucleo 1H, e D è il coefficiente di autodiffusione molecolare. E’ stata sviluppata una sequenza di impulsi (Diffusion-Weighted T1-T2) per ottenere mappe T1-T2 pesate in diffusione. I risultati hanno consentito di mettere a punto una procedura che elimina il segnale NMR proveniente da cartilagine e muscolo, rendendo più realistico lo scenario di applicazione in-vivo. I tre diversi dispositivi NMR hanno dato risultati consistenti tra loro e con le immagini micro-CT. L’intera catena di esperimenti condotti ha mostrato che dispositivi NMR single-sided possono essere usati per valutare il BV/TV di ossa trabecolari, con il vantaggio di essere portatili, a basso costo e non invasivi, permettendo campagne di screening della popolazione a rischio osteoporosi.

Multi-slice computed tomography (MSCT) of mountaineering casualties in the Swiss Alps - Advantages and limitations

As an Alpine country, Switzerland has not only a thriving mountaineering tourist industry, but also many mountaineering casualties. At the request of the state attorney, most of the victims undergo only an external inspection without autopsy. One of the main tasks of the forensic pathologist under these circumstances is the correct identification of the deceased for a fast release to their kin. Nevertheless, detailed knowledge of the injuries sustained may lead to improved safety measures, such as better protective equipment. In this study, we examined the feasibility of using cross-sectional imaging with postmortem multi-slice computed tomography (MSCT) to detect lesions of the skeletal structures and internal organs. For this purpose, we used whole-body MSCT to examine 10 corpses that suffered fatal falls from great height while climbing in the Swiss part of the European Alps from the years 2007 to 2009. We conclude that postmortem CT imaging is a valuable tool for dental identification and is superior to plain X-rays as a viable compromise between a solely external legal inspection and an autopsy because it delivers otherwise irretrievable additional internal findings non-invasively. This fact is of great importance in cases where an autopsy is refused.

18F-fluorodeoxyglucose uptake of bone and soft tissue sarcomas in pediatric patients

A high (18)F-fluorodeoxyglucose (FDG) uptake by positron emission tomography/computed tomography (PET/CT) imaging in sarcomas of adults has been reported. The current study aimed at defining the degree of (18)F-FDG uptake of pediatric sarcomas. This retrospective study included 29 patients (23 males, 6 females; mean age 14 ± 5 years) with soft tissue (n = 9) or bone (n = 20) sarcomas. Twenty-two patients (76%) underwent (18)F-FDG PET/CT and 7 (24%) had dedicated (18)F-FDG PET studies. Tumor (18)F-FDG uptake was quantified by standard uptake value (SUV)(max) and tumor-to-liver ratios (SUV ratios; tumor SUV(max)/liver SUV(mean)). Tumor SUV(max) and SUV ratios were correlated with tumor Ki-67 expression. SUV(max) ranged from 1.4 to 24 g/mL (median 2.5 g/mL) in soft tissue sarcomas and 1.6 to 20.4 g/mL (median 6.9 g/mL) in bone sarcomas (P = .03), and from 1.6 to 9.2 g/mL (median 3.9 g/mL) and 3.5 to 20.4 g/mL (median 12 g/mL) in Ewing sarcoma and osteosarcoma, respectively (P = .009). Tumor SUV ratios ranged from 0.8 to 8.7 (median 1.9) in soft tissue sarcomas and 1.4 to 8.9 (median 3.8) in bone sarcomas (P = .08). Ewing sarcoma had a significantly lower tumor SUV ratio than osteosarcoma (P = .01). Ki-67 expression correlated significantly with the (18)F-FDG uptake in bone but not in soft tissue sarcomas. All sarcomas were visualized by (18)F-FDG PET/CT imaging. A higher (18)F-FDG uptake was observed in osteosarcoma than in Ewing and soft tissue sarcomas. The results of this study suggest that the degree of tumor (18)F-FDG uptake is sufficient to allow for monitoring of therapeutic responses in pediatric sarcomas.

Resonance frequency analysis in relation to jawbone characteristics and during early healing of implant installation

OBJECTIVES: To monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics and during the early phases of healing and incorporation of Straumann dental implants with an SLA surface. MATERIAL AND METHODS: 17 Straumann 4.1 mm implants (10 mm) and 7 Straumann 4.8 mm implants (10 mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1 mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). RESULTS: Pocket probing depths ranged from 2-4 mm and bleeding on probing from 5-20%. At baseline, BVD varied between 24% and 65% and BTC between 4.9 and 25.4 for the 4.1 mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8 mm diameter implants baseline ISQ values ranged from 57-70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1 mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. CONCLUSION: ISQ values of 57-70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since the decrease occurred after the fact.

Resonance Frequency Analysis (RFA) during early healing

Objectives: - to monitor resonance frequency analysis (RFA) in relation to the jawbone characteristics during the early phases of healing and incorporation of Straumann® dental implants with an SLA surface. Material and methods: 17 Straumann 4.1mm implants (10mm) and 7 Straumann 4.8mm implants (10mm) were installed and ISQ determined at baseline and after 1, 2, 3, 4, 5, 6, 8 and 12 weeks. Central bone cores were analyzed from the 4.1mm implants using micro CT for bone volume density (BVD) and bone trabecular connectivity (BTC). Results: Pocket probing depths ranged between 2-4mm and bleeding on probing between 5-20%. At baseline, BVD varied between 24 and 65% and BTC between 4.9 and 25.4 for the 4.1mm implants. Baseline ISQ varied between 55 and 74 with a mean of 61.4. No significant correlations were found between BVD or BTC and ISQ Values. For the 4.8mm diameter implants baseline ISQ values ranged from 57 – 70 with a mean of 63.3. Over the healing period ISQ values increased at 1 week and decreased after 2-3 weeks. After 4 weeks ISQ values, again increased slightly, no significant differences were noted over time. One implant (4.1mm) lost stability at 3 weeks. Its ISQ value had dropped from 68 to 45. However the latter value was determined after the clinical diagnosis of instability. Conclusion: ISQ values of 57 – 70 represented homeostasis and implant stability. However no predictive value for loosing implant stability can be attributed to RFA since decease occurred after the fact.

Differential distribution of vasa vasorum in different vascular beds in humans

OBJECTIVE: Vasa vasorum (VV) have been implicated to play a role in the pathogenesis of atherosclerosis. This study was designed to describe the distribution of VV density in different vascular beds in humans and to investigate the association between VV density and the known distribution of atherosclerosis in human arteries. METHODS: Forty-two human arteries, harvested at autopsy or after explantation, were analyzed by three-dimensional microscopic-computed tomography (micro-CT). VV density, endothelial-surface-fraction (Sigma VV endothelial-surface-area/vessel-wall-volume) and vascular-area-fraction (Sigma VV area/vessel-wall-area) were calculated for coronary, renal and femoral arteries. Representatively five coronary, renal and femoral arteries were stained for endothelial cells (von Willebrand-Factor), macrophages (CD68), vascular endothelial growth factor (VEGF) and collagen (Sirius Red). RESULTS: Coronary arteries showed a higher VV density compared to renal and femoral arteries (2.12+/-0.26 n/mm(2) versus 0.61+/-0.06 n/mm(2) and 0.66+/-0.11 n/mm(2); P<0.05 for both) as well as a higher endothelial-surface-fraction and vascular-area-fraction. Histology showed a positive correlation between histologically derived VV density and CD68-positive cells/area (r=0.54, P<0.01), VEGF-immunoreactivity/area (r=0.55, P<0.01) and a negative correlation between VV density and collagen I content (r=0.66, P<0.05). CONCLUSION: This micro-CT study highlights a higher VV density in coronary than in peripheral arteries, supporting the relation between VV density and the susceptibility to atherosclerosis in different vascular beds in humans.

An integrated approach for reconstructing surface models of the proximal femur from sparse input data for surgical navigation

A patient-specific surface model of the proximal femur plays an important role in planning and supporting various computer-assisted surgical procedures including total hip replacement, hip resurfacing, and osteotomy of the proximal femur. The common approach to derive 3D models of the proximal femur is to use imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). However, the high logistic effort, the extra radiation (CT-imaging), and the large quantity of data to be acquired and processed make them less functional. In this paper, we present an integrated approach using a multi-level point distribution model (ML-PDM) to reconstruct a patient-specific model of the proximal femur from intra-operatively available sparse data. Results of experiments performed on dry cadaveric bones using dozens of 3D points are presented, as well as experiments using a limited number of 2D X-ray images, which demonstrate promising accuracy of the present approach.