Thematic Paper (M.C.T.M. (Clinical Tropical Medicine))--Mahidol University, 2006.

Orientador(a): Prof(a). Dr(a). Juliana Marchi / Tese (doutorado) - Universidade Federal do ABC, Programa de Pós-Graduação em Nanociências e Materiais Avançados, 2016. / A osteomielite e uma inflamacao ossea frequente em traumas diversos, causada por um organismo infectante. O tratamento convencional e o debridamento do osso infectado e dos tecidos moles adjacentes, associado a administracao de antibiotico via sistemica. Este estudo caracterizou o sistema injetavel a base de poloxamer 407 (PL407) . sozinho ou combinado com poloxamer 188 (PL188) . incorporado com o antibiotico teicoplanina e diferentes composicoes de ¿À-TCP (¿À-TCP) dopados com magnesio e/ou zinco, proposto como uma alternativa para o tratamento de osteomielite associada a reparacao ossea. As formulacoes foram caracterizadas por analise estrutural, determinacao da temperatura de transicao sol-gel, avaliacao do perfil de dissolucao das formulacoes e de liberacao da teicoplanina in vitro, e caracterizacao biologica in vitro. Os resultados mostraram que a adicao dos fosfatos tricalcicos e da teicoplanina nao alteraram a reversibilidade termica dos poloxamers, mas a teicoplanina diminuiu as temperaturas de transicao sol-gel. As formulacoes mantiveram uma das caracteristicas vantajosas dos poloxamer: a capacidade de serem injetados na forma liquida na temperatura ambiente e gelificacao proxima a temperatura corporea, ou seja, no local de tratamento. Todas as formulacoes apresentaram baixos valores de tamanho de particulas e reducao da polidispersao apos a adicao da teicoplanina, resultando em formulacoes mais homogeneas. Os fosfatos tricalcicos e a teicoplanina interferiram na agregacao micelar, alterando a entalpia de formacao de micelas e conferindo alta carga de superficie negativa, esta conferindo maior estabilidade ao coloide por repulsao eletrostatica. As formulacoes apresentaram total dissolucao apos 24 horas em contato com o meio de dissolucao e a liberacao da teicoplanina segue o modelo de Higuchi. As formulacoes nao sao citotoxicas e sao positivas para a migracao, proliferacao e diferenciacao celular osteogenica de celulas-tronco de polpa dentaria humana (hDPSCs). Todas as formulacoes apresentaram alta inibicao do crescimento de cepas Gram-positivas, principalmente Staphylococcus aureus, principal agente causador da osteomielite. Os resultados indicaram que as formulacoes a base de poloxamer 407 e 188 (20%:5%, peso/peso) sao promissoras para o carreamento de bioativos, podendo contribuir para um novo material adequado para o tratamento da osteomielite associada a regeneracao ossea. / Osteomyelitis is a inflammation of bone very often in several traumas, caused by an infecting organism. The conventional treatment is the infected bone and adjacente soft tissue debridement, associated with the systemic administration of antibiotic. This study characterized the injectable system based in poloxamer 407 (PL407) - alone or in combination with poloxamer 188 (PL188) - incorporated with the antibiotic teicoplanin and different compositions of â-TCP (â-TCP) doped with magnesium and/or zinc for osteomyelitis treatment associated with bone repair. The formulations were characterized by structural analysis, determination of the sol-gel transition temperature, evaluation of the in vitro dissolution and teicoplanina release profile, and in vitro biological characterization. The results showed that the tricalcium phosphate and teicoplanin did not change the thermal reversibility of poloxamers, but teicoplanin decreased sol-gel transition temperature. The formulations remained one of the advantageous features of poloxamer: the ability to be injected in liquid form at room temperature and near body temperature gelation, in other words, gelation at the treatment site. All formulations showed lower particle size values and decreased of polydispersity after addition of teicoplanin, resulting in more homogeneous formulations. Tricalcium phosphate and teicoplanin interfered in micellar aggregation by changing the micelle formation enthalpy and confering high load negative surface, this resulting in more colloid stability by electrostatic repulsion. The formulations showed complete dissolution after 24 hours in contact with the dissolution medium and teicoplanin release profile follows the Higuchi model. The formulations are non-cytotoxic and are positive for cell migration, proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs). All formulations showed high inhibition of the Gram-positive strains growth, particularly Staphylococcus aureus, the most common organism seen in osteomyelitis. The results indicated the poloxamer 407 and 188 based formulations (20%:5%, w/w) are promising to be a bioactive carrier and can contribute to a new material suitable for the osteomyelitis treatment associated with bone regeneration.

Made available in DSpace on 2014-06-11T19:32:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-02-26Bitstream added on 2014-06-13T21:03:22Z : No. of bitstreams: 1 costa_i_dr_araca.pdf: 404352 bytes, checksum: f6cd3645b1babe03a670530063260f21 (MD5) / A osteomielite crônica de maxila e mandíbula é rara em países industrializados e sua ocorrência, nos países em desenvolvimento, está associada a trauma e procedimentos cirúrgicos, sendo que sua etiologia não foi estudada profundamente. O objetivo desse estudo foi avaliar a microbiota associada com a osteomielite de mandíbula e maxila em pacientes brasileiros. Após exames clínicos e radiográficos, amostras de seqüestros ósseos, secreção purulenta e biopsias de tecido granulomatoso de vinte e dois pacientes com osteomielite crônica da mandíbula e maxila foram cultivadas e submetidas à detecção de um conjunto de patógenos através do método do PCR. O isolamento bacteriano foi realizado em ágar “fastidious anaerobe” suplementado com hemina, menadiona e sangue de cavalo, para os microrganismos anaeróbios, e em ágar de tripticaseína de soja suplementado com extrato de levedura e sangue de cavalo, para os aeróbios e anaeróbios facultativos. Cada paciente apresentava uma única lesão. As placas foram incubadas em anaerobiose e aerobiose, a 37oC, por 14 e 3 dias, respectivamente. Bactérias foram cultivadas de 10 amostras de pacientes e os gêneros Actinomyces, Fusobacterium, Parvimonas e Staphylococcus foram os mais freqüentes. Através do PCR, DNA bacteriano foi detectado em amostras de 20 pacientes. Os resultados sugerem que as osteomielites crônicas dos maxilares geralmente são infecções anaeróbias mistas, reforçando o conceito de que estão relacionadas principalmente aos microrganismos do ecossistema bucal e que as infecções periapicais e periodontais podem atuar como fatores predisponentes. / Chronic osteomyelitis of the maxilla and mandible is rare in industrialized countries and its occurrence in developing countries is associated with trauma and surgery, and its microbial etiology has not been studied thoroughly. The aim of this investigation was to evaluate the microbiota associated with osteomyelitis of the mandible and maxilla from some Brazilian patients. After clinical and radiographic evaluation, samples of bone sequestra, purulent secretion, and biopsies of granulomatous tissues from twenty-two patients with chronic osteomyelitis of the mandible and maxilla were cultivated and submitted for pathogen detection by using a PCR method. Each patient harbored a single lesion. Bacterial isolation was performed on fastidious anaerobe agar supplemented with hemin, menadione and horse blood for anaerobes; and on tryptic soy agar supplemented with yeast extract and horse blood for facultative bacteria and aerobes. Plates were incubated in anaerobiosis and aerobiosis, at 37oC during 14 and 3 days, respectively. Bacteria were cultivated from ten patient samples; and genera Actinomyces, Fusobacterium, Parvimonas, and Staphylococcus were the most frequent. By PCR, bacterial DNA was detected from thirteen patient samples. The results suggest that cases of chronic osteomyelitis of the jaws are usually mixed anaerobic infections, reinforcing the concept that osteomyelitis of the jaws are mainly related to microorganisms from the oral environment, and periapical and periodontal infections may act as predisposing factors.

O objetivo deste estudo foi avaliar os fatores de risco, aspectos clínicos, imagenológicos e terapêuticos da osteonecrose dos maxilares associada ao uso dos bisfosfontos (ONMAB), bem como compará-los com o estado atual da doença, na busca de parâmetros que favoreceram o reparo tecidual. Foram avaliados retrospectivamente 40 casos de ONMAB de pacientes oncológicos encaminhados para avaliação estomatológica. Os dados demográficos, clínicos, imagenológicos, laboratoriais, histopatológicos e terapêuticos foram analisados. Foi realizada análise descritiva dos dados e para associar o estado atual da osteonecrose com as demais variáveis foi utilizado o teste exato de Fisher. O nível de significância estabelecido foi de 5% (p0,05). A ONMAB se mostrou mais comum em mulheres, com idade média de 59 anos e associadas mais freqüentemente ao de câncer de mama, seguido de câncer de próstata e do mieloma múltiplo. O principal bisfosfonato utilizado foi o ácido zoledrônico com média de uso de 23,54 meses. A exodontia, o tratamento quimioterápico e com corticóides foram associados com mais da metade dos casos. O aspecto clínico principal foi a exposição óssea com sintomatologia dolorosa associados ou não à drenagem de secreção, principalmente em mandíbula. Modificações no trabeculado ósseo, erosão da cortical e osteoesclerose foram os principais achados de imagem. Dentre todos os tratamentos realizados, a associação de cirurgia com plasma rico em plaquetas (PRP) e laser de diodo foi a mais utilizada (52,5%) e que mostrou alto índice de sucesso clínico (62,96%). A evolução dos casos tratados mostrou que 67,5% apresentaram reparo tecidual e mesmo aqueles que mantiveram a exposição óssea não mostraram sintomatologia dolorosa. A classificação clínica e o tipo de tratamento empregado influenciaram de forma significante a resolução da ONMAB. Conclui-se que medidas de controle local de infeccção, antibioticoterapia e pequenos debridamentos ósseos devem ser adotadas nos quadros de ONMAB, porém em conjunto com a utilização de bioestimuladores teciduais como o PRP e laser de diodo que promovem de forma mais eficiente o reparo tecidual. / The aim of this study was to evaluate the risk factors, clinical, radiological and treatment aspects of bisphosphonate-associated osteonecrosis of the jaws (BONJ) in cancer patients. Likewise, comparing the current state of the disease with the different variables in the search for parameters that favored the tissue repair. We evaluated retrospectively 40 cases of BONJ of cancer patients referred for stomatology evaluation. Demographic data, clinical, radiographic, laboratory, histopathological and treatment were analyzed. We performed descriptive analysis of data and to associate the current state of the osteonecrosis with the other variables we used Fisher\'s exact test. The level of significance established was 5% (p 0.05). The BONJ was more common in women, the mean age was 59 years and was more frequently associated to the breast cancer followed by prostate and multiple myeloma. Zoledronic acid was the main bisphosphonate used with average use of 23.54 months. The dental tooth, chemotherapy and corticosteroids history were associated with more than half of the cases. The clinical aspect was the main bone exposure associated with painful symptoms or drainage of secretions, especially in mandible. Structural alteration of trabecular bone, cortical bone erosion and osteosclerosis were the main radiological findings. Among all the treatments performed, the therapy combining bone resection, diode laser and platelet-rich plasma (PRP) was the most used (52.5%) which showed high rate of clinical success (62.96%). The evolution of treated cases showed that 67.5% had tissue repair and only 32.5% maintained the bone exposure, but all without painful symptoms. The clinical classification and type of treatment used significantly influence the outcome of BONJ . It is concluded that measures of infection local control, antibiotics and small bone debridement should be adopted in the BONJ but with the use of tissue stimulation using PRP and diode laser helps to promote more effective tissue repair.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19558号 / 医博第4065号 / 新制||医||1013(附属図書館) / 32594 / 京都大学大学院医学研究科医学専攻 / (主査)教授 平岡 眞寛, 教授 福原 俊一, 教授 一山 智 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

INTRODUCTION: The treatment of chronic intramedullary infection of the long bones relies on microbe-specific antibiotics in conjunction with surgical removal of infected necrotic material. We discuss the use of reamer-irrigator-aspirator(RIA) for debridement of the intramedullary canal instead of conventional reaming techniques. This is the first case report to explore the use of RIA for osteomyelitis. CASE REPORT: We discuss the use of the RIA in treatment of a 26-year-old female presenting with chronic osteomyelitis of the left distal femoral shaft. She had normalization of infection laboratories at 6 weeks and complete resolution of symptoms at 3 months and was released at 6 months. CONCLUSION: Recent exploration of the RIA system's (Synthes®, Inc. West Chester, Philadelphia) multipurpose applications has indicated use in long bone debridement. While further exploration and high-quality studies are needed to make robust claims of efficacy, we believe that the use of RIA in the context of chronic osteomyelitis is a superior alternative to conventional reaming techniques.

Antibiotic resistant strains of bacteria continue to increase in prevalence, hindering the ability of clinicians to treat infection. One disease exacerbated by this trend is osteomyelitis, or bone infection. When osteomyelitis is induced by these antibiotic resistant strains, patients can experience prolonged hospital visits, greater economic burdens, amputation, and even death. Due to the limitations of antibiotics to clear these infections, we sought to identify new therapeutic options for osteomyelitis. Our aim was to first develop an in vivo implant-related model of osteomyelitis. We then wanted to explore the potential of novel CRISPR-Cas9 modified bacteriophage to treat infection. In vitro and in vivo investigations demonstrated that bacteriophage therapeutic may be a viable option for infection mitigation. Furthermore, our in vivo model of osteomyelitis proved to be reliable, consistent, and challenging. Future research will utilize this model as a platform for optimizing therapeutic regimen and delivery vehicle(s) for antimicrobial therapeutics.

No description available.

Le traitement antibiotique local de l'infection osseuse par le polyméthacrylate de méthyle (PMMA), chargé de gentamicine ou de tobramycine, montre actuellement des limites. Ses inconvénients sont liés à la non résorbabilité du PMMA et à la rétention d'une grande partie de l'antibiotique intégré au PMMA. L’association fréquente à l’infection de pertes de substance osseuse a favorisé la recherche de vecteurs d’antibiothérapie locale, alternative au PMMA, parmi les substituts de comblement osseux résorbables et ostéoconducteurs. Les ciments phosphocalciques (CPC) pourraient devenir parmi les plus performants dans cette utilisation. Ils sont biocompatibles et offrent avec le Dicalcium Phosphate-ß-Tricalcium Phosphate (DCPD-ß-TCP), un CPC, la possibilité d'obtention d'un mélange DCPD-ß-TCP-gentamicine à une température de 43°C n'altérant pas l'antibiotique, contrairement aux céramiques phosphocalciques qui sont fabriquées par frittage à très haute température. Le but de notre travail était de tester in vitro (élution d’antibiotique) et in vivo (essai de traitement d'ostéite expérimentale) le DCPD-ß-TCP-gentamicine comme alternative possible au PMMA-gentamicine. [...] / Local antibiotic treatment of osteomyelitis is based on the use of gentamicin- (or tobramycin-) loaded polymethylmethacrylate (PMMA). These two aminoglycosides are effective against most cultured orthopedic microorganisms, including Staphylococcus aureus, the most frequent cause of infection. The extensive use of PMMA as a Local Antibiotic Delivery System (LADS) has various disadvantages. Firstly, only a small proportion (about 5 to 17%) of the antibiotic is released by the cement (trapping effect). Secondly, the most significant problem is that PMMA is not resorbable and presents a physical obstacle to osteogenesis. A second surgical operation is therefore always required to remove the PMMA and to fill the cavity caused by bone loss with a bone graft or a synthetic substitute. Several absorbable synthetic substitutes, such as calcium phosphate ceramics, calcium sulfate, and polymers of polylactic-polyglycolic acids, have been investigated as antibiotic carriers. These synthetic substitutes are largely underused as LADS in clinical practice. Polymers are not perfectly biocompatible, and ceramics provide a burst release of antibiotics as a consequence of their manufacturing techniques (Antibiotic adsorption onto the carrier, after sintering of the carrier at high temperature, 1000-1200°C). We have developed a possible alternative to gentamicin loaded-PMMA for local treatment of osteomyelitis in the form of novel calcium phosphate cement (CPC): dicalcium phosphate dihydrate-β-tricalcium phosphate (DCPD-β-TCP). The biocompatibility of such a cement has been demonstrated experimentally and has been clinically confirmed for the treatment of burst fractures and for filling bone cavities in osteoporotic fractures. DCPD-ß-TCP is made in granules from 2 to 3 mm in diameter to avoid the superficial ―creeping substitution‖ observed when DCPD-β-TCP is used as a cement block. [...]

As fraturas de mandíbula são freqüentes e o seu tratamento é por meio de fixação interna rígida. Complicações podem ocorrer após o tratamento das fraturas mandibulares levando a necessidade de reabordagem cirúrgica, havendo poucos estudos a esse respeito na literatura. A proposta deste estudo retrospectivo foi avaliar as características, os possíveis fatores de risco e os tipos de tratamento realizado em pacientes que necessitaram de reabordagem cirúrgica de fraturas de mandíbula tratadas com fixação interna rígida (FIR). Dentre 364 pacientes tratados por fraturas de mandíbula com FIR, houve 17 pacientes (4,7%) que necessitaram de reabordagem cirúrgica, tendo sido incluídos três pacientes provenientes de outros serviços, totalizando 20 casos com necessidade de nova cirurgia. Houve predomínio do gênero masculino, com idade média de 31,4 anos, sendo freqüentes o tabagismo e o etilismo. Foram freqüentes fraturas múltiplas e cominutivas nas regiões de corpo e ângulo mandibular, dente no traço e exposição intraoral da fratura. O tempo de espera para primeira cirurgia foi alto e o acesso extraoral e o sistema de fixação menos rígido 2.0 mm foram freqüentes. As complicações mais comuns foram dor, infecção e mobilidade anormal. Nas culturas bacterianas houve predomínio do Staphylococcus aureus e a imagem mais freqüente foi de reabsorção óssea difusa, seguida por parafuso solto, seqüestro ósseo, traço de fratura visível, fixação solta e placa fraturada. A reabordagem cirúrgica ocorreu em média de 7,5 meses após a primeira cirurgia e constou de remoção dos meios de fixação associada ou não a nova fixação ou ainda a remoção de seqüestro ósseo, sendo que apenas um caso necessitou de refratura. Histologicamente houve predomínio de osteomielite crônica. Os diagnósticos em ordem decrescente foram infecção, pseudoartrose, osteomielite e placa exposta, sendo que muitos pacientes tiveram mais de um diagnóstico. Foi destacada a freqüência de tabagismo e etilismo, fraturas múltiplas e cominutivas na região de corpo e ângulo mandibular, dente no traço, exposição intraoral, tempo de espera alto e acesso extraoral predispondo complicações das fraturas mandibulares e exames de imagem de reabsorção óssea, fixação e parafusos solto e seqüestro ósseo e diagnóstico histológico de osteomielite como característica dos casos requerendo nova cirurgia. / Mandibular fractures are frequent and their treatment is through rigid internal fixation (RIF). Complications can occur after treatment of the mandibular fractures which may require a new surgical procedure, and there are a few studies about that in the literature. The purpose of this retrospective study was to evaluate the characteristics, possible risk factors, and the kinds of treatment did in patients which needed another surgery after treatment of mandibular fracture with RIF. From 364 patients with mandibular fractures treated by RIF, there were 17 patients (4.7%) with need of a new surgery, and 3 patients coming from another city were included, comprising a total of 20 patients who needed a new surgery. There was predominance of the male gender, with a mean age of 31.4 years, being frequent smoking and alcohol abuse. Multiple and comminuted fractures on the body and angle sites, teeth in the fracture line, and intraorally exposed fractures were frequent. Delay time to the first surgery was high, and extraoral approaches and system 2.0mm were predominant. The most common complications were pain, infection and abnormal mobility. In the bacterial culture there was predominance of Staphylococcus aureus, and the most frequent radiographic images were of diffuse bone resorption, loosening of screws, bone sequestration, fracture line visible, loose fixation, and fractured plate. A new surgery occurred with a mean of 7.5 months after the first intervention and comprised plate and screws removal associated or not to a new fixation or bone sequestra removal, and only a case the fracture needed to be osteotomized. Histologically there was predominance of chronic osteomyelitis. The diagnoses in decreasing order were infection, nonunion, osteomyelitis and exposed plate, although many patients had more than one diagnosis. It was evidenced the frequency of smoking and alcohol abuse, multiple and comminuted fracture on the body and angle regions, teeth in the fracture line, intraoral fracture exposition, high delay time and extraoral approaches predisposing complications of the mandibular fractures, and images showing bony resorption, loose hardware and bone sequestra, as well as histological diagnosis of osteomyelitis as characteristic of the cases requiring a new surgery.