Orientador: Brenda Paula Figueiredo de Almeida Gomes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-22T06:43:53Z (GMT). No. of bitstreams: 1 Nobrega_LeticiaMariaMenezes_D.pdf: 2252800 bytes, checksum: 31910f0e934110c7e863efa8d0e293da (MD5) Previous issue date: 2012 / Resumo: Abscessos apicais agudos são condições frequentes na urgência endodôntica. São infecções polimicrobianas que apresentam variações entre indivíduos, e afetam o sistema de canais radiculares e tecidos periapicais. Associações bacterianas podem ser importantes, agindo sinergicamente e aumentando sua virulência, o que agrava os danos causados no hospedeiro. Considerando a etiologia microbiana das alterações pulpares e periapicais, é de fundamental importância identificar corretamente as bactérias presentes nas infecções endodônticas. Métodos moleculares de identificação bacteriana, baseados no sequenciamento do gene 16S rRNA, são importantes e fornecem uma identificação mais fiel que métodos fenotípicos. Estudos metagenômicos são ideais para avaliação da diversidade bacteriana, possibilitando identificação de espécies que se acreditava não estarem sendo cultivadas, ou encontrar espécies que ainda não foram encontradas ou associadas com infecções endodônticas, incluindo espécies ainda não cultiváveis. O objetivo deste estudo foi investigar a diversidade bacteriana de canais radiculares de dentes com abscesso apical agudo por cultura, clonagem e sequenciamento do gene 16S rRNA, compararando a efetividade dos métodos. Foram feitas coletas microbiológicas de 20 canais radiculares utilizando cones de papel absorvente estéreis, transportados em meio VMGA III. Um total de 220 cepas isoladas, identificadas previamente por métodos bioquímicos, foram submetidas à extração de DNA, amplificação do gene 16S rRNA seguido de sequenciamento. Além disso, 10 das 20 amostras coletadas foram também submetidas à clonagem bacteriana através de Escherichia coli DH5? eletrocompetentes. As sequências de nucleotídeos obtidas foram comparadas com o banco de dados do National Center of Biotechnology Information através do BLAST. Trinta e quatro espécies diferentes foram identificadas bioquimicamente e 57 pelo sequenciamento, numa média de 6 espécies por canal. O sequenciamento permitiu identificação de 97% das bactérias isoladas (215), enquanto apenas 70,5% foram identificadas bioquimicamente (155). A concordância entre os métodos de identificação fenotípica e genotípica foi de 49% e as cepas não identificadas bioquimicamente (65/220) foram caracterizadas em 97% (63/65) pelo sequenciamento. As bactérias mais frequentemente identificadas pelo sequenciamento foram Prevotella spp., Pseudoramibacter alactolyticus, Parvimonas micra, Dialister invisus, Filifactor alocis e Peptostreptococcus stomatis. Um total de 689 clones foi analisado e 76 filotipos foram identificados, numa média de 15 por canal. Quarenta e oito espécies diferentes foram identificadas e 28 (36,84%) filotipos representados por espécies ainda não cultivadas ou não caracterizadas. Prevotella spp., Fusobacterium nucleatum, Filifactor alocis e Peptostreptococcus stomatis, foram às espécies mais frequentemente identificadas, seguidas por Dialister invisus, Parvimonas micra, Phocaeicola abscessus, Porphyromonas spp. e Lachnospiraceae oral clone. Nenhuma espécie foi encontrada em todos os casos estudados, e algumas estavam presentes em apenas 1 caso. Métodos que independem da cultura mostram que a microbiota endodôntica pode ser subestimada por estudos cultura-dependentes. Apesar de algumas espécies serem predominantes em infecções endodônticas primárias, como as anaeróbias Gram-negativas, concluímos que esta infecção é bastante complexa e heterogênea, caracterizada por uma grande diversidade bacteriana. A associação de métodos convencionais e moleculares permite um conhecimento mais acurado da microbiota endodôntica / Abstract: Acute apical abscesses are one of the most frequently treated conditions in endodontic emergency. It is a microbiologically heterogeneous disease presenting different bacterial profiles among the patients. Multiple bacterial combinations play a role in disease, acting synergistically and increasing their virulence, which leads to further damage to the host. Considering the microbial etiology of pulp and periapical disease, it is important to identify correctly microorganisms present in acute endodontic infection. Molecular methods of bacterial identification based on the 16S rRNA gene sequencing represent an important tool for identification and determination of the taxonomic position of microorganisms. The assessment of the endodontic microbiota by metagenomic approaches revealed that these techniques are sensitive and specific to evaluate the bacterial diversity of root canal infections, making possible the identification of some unexpected or not often associated with endodontic infection, including as-yet-uncultivated. The aim of this study was to investigate the bacterial diversity in the root canals of teeth with APA by culture, clonal analysis and 16S rRNA sequencing. Microbial samples were taken from 20 root canals using sterile paper points which were immediately placed into the VMGA III transport medium. A total of 220 isolated strains, previously identified by biochemical methods, were submitted to DNA extraction, 16S rRNA gene amplification and sequencing. Ten out of the 20 samples collected were also subjected to the clonal analysis using electrocompetent Escherichia coli DH5?. The nucleotides sequences obtained were compared with the GenBank database from National Center of Biotechnology Information through the BLAST. Thirty-four different bacteria were identified biochemically and 57 by 16S rRNA sequencing, in an average of 6 species per root canal. Sequencing allowed the identification of 97% of isolates against 70.5% identified biochemically. There was an agreement of 49% between the biochemical and 16S rRNA gene sequencing identification. Strains not identified biochemically (65/220) were characterized in 97% (63/65) by sequencing. The most frequently identified bacteria by sequencing were Prevotella spp., Pseudoramibacter alactolyticus, Parvimonas micra, Dialister invisus, Filifactor alocis and Peptostreptococcus stomatis. A total of 689 clones were analyzed and 76 phylotypes identified, of which 48 (63.15%) were different species and 28 (36.84%) were taxa reported as-yet-uncultivable or as yet-uncharacterized species. Prevotella spp., Fusobacterium nucleatum, Filifactor alocis and Peptostreptococcus stomatis, were the most frequently detected species, followed by Dialister invisus, Parvimonas micra, Phocaeicola abscessus, Porphyromonas spp. and the uncharacterized Lachnospiraceae oral clone. No specie was detected in all studied samples and some species were identified in only one case. Culture-independent methods shown that endodontic microbiota was underestimated in culture studies. Although some species predominate in acute primary endodontic infections, it was concluded that this infection is microbiologically heterogeneous, characterized by a wide diversity in which anaerobic gram-negatives are most frequently, and that the association of conventional and molecular approaches allow a better understanding of these microorganisms / Doutorado / Endodontia / Doutora em Clínica Odontológica

No description available.

Einleitung: Ziel der Arbeit war es, die tiefen Halsinfektionen im Hals-, Nasen- und Ohrenbereich anhand der Ätiologie, diagnostischer Verfahren, Klinik und Therapie mit der aktuellen internationalen Literatur zu vergleichen. Material&Methode: Hierzu erfolgte eine retrospektive Auswertung von 63 Patienten mit tiefen Halsabszessen, die im Zeitraum zwischen Januar 2002 und Dezember 2012 an der Universitätsmedizin Göttingen in der Klinik für HNO-Heilkunde behandelt wurden. Die statistische Asuwertung erfolgte dekriptiv sowie analysierend mit graphischen Darstellungsformen. Die metrischen Variablen wurde mittels Mann-Whitney-U-Test sowie dem Exakte Fisher-Test auf Signifikanz (p=0,05) getestet. Ergebnisse: Tiefe Halsabszesse sind am häufigsten im Spatium parapharygeum anzutreffen. Streptococcus viridans (26,7%), meist als Mischinfektion mit anaeroben Bakterien, ist der häufigste Erreger tiefer Halsinfektionen. Das Keimspektrum unterscheidet sich signifikant beim Krankheitsbild "Diabetes mellitus", bei dem Staphylococcus aureus als häufigster Keim identifiziert wurde (p=0,02). Zusammenfassung: Die Therapie der Wahl bei abszedierenden tiefen Halsinfektionen bleibt die frühzeitige chirurgische Sanierung mit Abszesseröffnung und Drainage sowie die Sicherung der Atemwege in Verbindung mit einer gezielten intravenösen Antibiotikatherapie. Außerdem sollte bei jeder tiefen Halsinfektion eine standardisierte Erreger-bestimmung - inklusive Anitibiogramm- gefordert werden.

Die pyogene Spondylodiszitis als bakterielle Osteomyelitis der Wirbelsäule ist eine seltene Entität der bakteriell-entzündlichen Pathologien des Stütz- und Bewegungsapparates. Trotz adäquater Behandlungsstrategien, wird auch heute noch eine Mortalitätsrate von 5% bis 20% beschrieben. Vor allem die in dem vorwiegend älteren Patientenkollektiv deutlich erhöhte Prävalenz an metabolischen oder kardiopulmonalen Komorbiditäten fordert moderne Therapiekonzepte, die eine risikoarme, jedoch effektive Eradifizierung des bakteriell-entzündlichen Fokus mit schneller Wiederherstellung der prämorbiden Mobilität ermöglichen. Ausgehend von zwei grundlagenwissenschaftlichen Studien, wurden in der vorliegenden Habilitationsschrift zunächst die komplexen Zusammenhänge von lokaler Gewebsveränderungen und systemischer Entzündung erörtert. Hierbei zeigten die Analysen humaner degenerativer und traumatischer Bandscheibenzellen, dass die Apoptose, insbesondere die Herabregulation anti-apoptotischer Schlüsselkomponenten wie das Bcl-2, als mögliche Schnittstelle im katabolen Stoffwechsel der extrazellulären Bandscheibenmatrix diskutiert werden kann. In der generalisierten bakteriellen Entzündung (Sepsis), ließ sich durch die gentherapeutisch gewebsständige Überexpression von antiapoptotischen und antiinflammatorischen Interleukin-10 (IL-10), auch im IL-10-defzienten Organismus, eine deutliche Reduktion der systemischen proinflammatorischen Immunantwort mit verbesserter Überlebensrate septischer Tiere erzielen. Jedoch birgt der substantielle Gewebeschaden bei pyogener Spondylodiszitis nicht selten die Gefahr der konsekutiven Instabilität mit neurologischen Komplikationen und stellt damit eine besondere chirurgische Herausforderung dar. Daher wurden in drei weiteren klinischen Studien unsere, in den letzten 10 Jahren etablierten, lösungsorientierten Strategien erläutert. Zur Überbrückung größerer knöcherner Defekte gelang mit der Implantation expandierbarer Titancages eine sichere knöcherne Durchbauung mit vollständiger Ausheilung des Infektes. Im Beobachtungszeitraum von mehr als 3 Jahren war bei keinem der Patienten ein Infektrezidiv zu verzeichnen. In komplexen Fällen von monosegmentaler Spondylodiszitis der LWS mit multisegmentaler epiduraler Abszedierung, führte die epidurale Katheterspülung über den dorsalen Zugang für die Spondylodese zu einer folgenlosen Ausheilung. Damit konnte ein zusätzliches, iatrogenes Trauma mit multisegmentalen Lamintomien über die Distanz des epiduralen Abszesses vermieden werden. In einer weiteren Studie mit einem Beobachtungszeitraum von bis zu 5 Jahren, erzielte die Implantation von Poly-Ether-Ether-Keton (PEEK) Cages zur dorsalen intersomatischen Fusion bei pyogener Spondylodiszitis eine sehr gute, stabile knöcherne Durchbauung des infizierten Segmentes, ebenfalls ohne Infektrezidiv. Diese Abweichung vom herkömmlichen Standard mit Titanimplantaten erwies sich somit als sichere Alternative mit den für PEEK charakteristischen, verbesserten Eigenschaften. Im Vergleich zu herkömmlichen Operationsverfahren, verspricht die Integration dieser Ergebnisse in die Weiterentwicklung minimal-invasiver Techniken, insbesondere im multimorbiden Patientenklientel, mindestens gleichwertig gute Ergebnisse bei deutlich reduziertem Operationstrauma.

Objetivos: Avaliar o manejo da dor em Endodontia por meio de dois estudos: Artigo 1 – um ensaio clínico randomizado comparando a eficácia analgésica de duas associações de opioide e não opioide no controle da dor do Abscesso Dentoalveolar Agudo (ADA) em evolução; Artigo 2 – uma revisão sistemática investigando a eficácia e segurança de terapia sistêmica para o tratamento da dor de origem endodôntica. Métodos: No Artigo 1, foram incluídos 24 pacientes que procuraram atendimento em serviço odontológico universitário do sul do Brasil. Após o atendimento de urgência, os pacientes foram alocados em dois grupos: Co/Pa – prescrição da associação de codeína (30 mg) e paracetamol (500 mg), por via oral, a cada 4 h, por 3 dias; Tr/Pa - prescrição da associação de cloridrato de tramadol (37,5 mg) e paracetamol (500 mg), na mesma posologia do grupo anterior. Os escores de dor foram registrados pelo próprio paciente, nos tempos 6, 12, 24, 48 e 72 h após o atendimento, em diário específico de evolução da dor, por meio da Escala Analógica Visual (EAV). No Artigo 2, foi realizada uma revisão sistemática, por meio de buscas conduzidas nas bases de dados: MEDLINE, registro de ensaios clínicos da Cochrane Library, LILACS, SciELO, banco de teses/dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e referências dos artigos encontrados. Para serem incluídos, os artigos deveriam ser ensaios clínicos randomizados (ECRs), controlados e cegos, ou revisões sistemáticas com ou sem metanálise. Deveriam ter um dos braços de terapia constituído por analgésico ou anti-inflamatório, administrado por via oral, para controle da dor moderada a intensa, de origem endodôntica, mensurada por meio da Escala Analógica Visual, em adultos. Foram coletados dados referentes às características da amostra, escores de dor pré-tratamento, características dos grupos em comparação, aspectos de qualidade metodológica, frequência de uso de analgésico adicional e a frequência de eventos adversos. Foram realizadas análises descritiva e inferencial. Resultados: No Artigo 1, em ambos os grupos, houve redução dos escores de dor ao longo do tempo. No grupo Co/Pa, houve redução significativa dos escores em 12, 24, 48 e 72 horas, em comparação com aos iniciais (P<0,05). Os escores em 48 e 72 horas foram menores, em relação aos iniciais e aos escores das 6 horas (P<0,05). No grupo Tr/Pa, houve redução dos escores de todos os tempos experimentais, em relação aos iniciais (P<0,05). Para todos os intervalos de tempo analisados, os grupos não foram diferentes entre si (P>0,05). Ambos os tratamentos foram eficazes no controle da dor provocada pelo ADA em evolução. Porém, a associação Tr/Pa apresentou-se menos segura. No Artigo 2, de um total de 431 referências, 419 resumos foram analisados e 14 artigos foram lidos na íntegra. Após a exclusão de 5 artigos, 9 ensaios clínicos preencheram os critérios de inclusão. Os estudos compararam paracetamol, AINE (ibuprofeno, flurbiprofeno, cetorolaco de trometamina, etodolaco, tenoxicam), prednisolona, tramadol e associações analgésicas no tratamento da dor endodôntica moderada a intensa. Foi observado que os medicamentos foram administrados antes ou após a intervenção endodôntica. Em 8 estudos, o grupo controle foi placebo e 8 estudos utilizaram o esquema de dose única para avaliar o controle da dor. Em todos os ensaios clínicos, o desfecho primário analisado foi a redução dos escores de dor e os desfechos secundários, uso de medicamento adicional e ocorrência de reações adversas. Foi possível estabelecer uma relação significativa entre uso de analgésico adicional e diagnóstico periapical. Quando a administração ocorreu antes do procedimento endodôntico, não foi observada a ocorrência de eventos adversos. Quando a administração ocorreu após o procedimento, foram relatadas reações adversas em dois dos três estudos incluídos na análise. Conclusão: O Artigo 1 sugere que, em função de eficácia analgésica e segurança, a associação codeína/paracetamol seja mais efetiva para o controle da dor aguda de moderada a intensa, no tratamento da ADA em evolução. O Artigo 2 aponta carência de ECRs em Endodontia, que utilizem um mesmo padrão metodológico, para definição de um protocolo de tratamento sistêmico na dor de origem endodôntica. / Aim: To evaluate the management of pain in Endodontics by two studies: Article 1 - a randomized clinical trial comparing the analgesic efficacy of two opioids and non-opioid associations in the pain control of Acute Dentoalveolar Abscess (ADA); Article 2 - a systematic review investigating the efficacy and safety of analgesic therapy in the management endodontic pain.Methodology: The Article 1 included 24 patients that looked for emergency treatment in a university dental clinic. These patients were divided into two groups: Co / Pa - prescription of codeine (30 mg) + acetaminophen (500 mg) oral, every 4 h, during 3 days; Tr / Ac - prescription of tramadol hydrochloride (37.5 mg) + acetaminophen (500 mg) as the previous group. Pain scores were recorded by the patient at 6, 12, 24, 48, and 72 h after treatment, in a pain diary, using the Visual Analogue Scale (VAS). The Article 2 was conducted in electronic databases, gray literature, and references of retrieved articles to analyze randomized clinical trials or systematic reviews with or without meta-analysis. One arms of the therapy should have comprised an anti-inflammatory or analgesic drugs, orally administered by adults, in order to control moderate to severe pain, measured by Visual Analogue Scale, cause by endodontic problems . Data were collected regarding the characteristics of the sample, scores of pretreatment pain, characteristics of compared groups, methodological quality aspects, additional analgesic use, and frequency of adverse events. Descriptive and inferential analyzes were performed. Results: In Article 1, in both groups there was a reduction in the pain scores over time. For Co/Ac group, it was found a significant reduction in the scores at 12, 24, 48, and 72 hours after treatment (P <0.05). The scores at 48 and 72 hours were lower, compared to immediate treatment and scores at 6 hours after treatment (P <0.05). In the Tr/ Ac group, the scores decreased as the time is increasing (P <0.05). For all time intervals tested, the groups were not significantly different (P> 0.05). Both treatments were effective in controlling pain caused by ADA. The association Tr/ Ac presented itself less secure. In Article 2, a total of 431 references and 419 abstracts were reviewed, then only 14 articles were read in full. From these articles it was excluded 5 and 9 trials met the inclusion criteria. These studies compared acetaminophen, NSAIDs (ibuprofen, flurbiprofen, ketorolac tromethamine, etodolac, and tenoxicam), prednisolone, and analgesic tramadol associations for treating moderate to severe endodontic pain. It was observed that drugs were administered before or after endodontic therapy. In 8 studies, the control group was placebo and 8 studies used single dose regimen to assess pain control. In all clinical trials, the primary outcome analyzed was the reduction of scores in pain and secondary outcomes were the utilization of additional medication and adverse reactions. It was possible to establish a significant relationship between use of additional analgesics and periapical diagnosis. When the administration occurred before the endodontic procedure no adverse events were observed. When it was administered after the procedure, adverse reactions were reported in 2 of 3 trials included in the analysis. Conclusion: The Article 1 suggests that, considering analgesic efficacy and safety function, the association codeine/ acetaminophen is more effective for the control moderate to severe pain, at the treatment of ADA in evolution. The Article 2 found that there is a lack of RCTs in Endodontics using the same methodological standard to define a systemic treatment protocol of endodontic pain.

Objetivos: Avaliar o manejo da dor em Endodontia por meio de dois estudos: Artigo 1 – um ensaio clínico randomizado comparando a eficácia analgésica de duas associações de opioide e não opioide no controle da dor do Abscesso Dentoalveolar Agudo (ADA) em evolução; Artigo 2 – uma revisão sistemática investigando a eficácia e segurança de terapia sistêmica para o tratamento da dor de origem endodôntica. Métodos: No Artigo 1, foram incluídos 24 pacientes que procuraram atendimento em serviço odontológico universitário do sul do Brasil. Após o atendimento de urgência, os pacientes foram alocados em dois grupos: Co/Pa – prescrição da associação de codeína (30 mg) e paracetamol (500 mg), por via oral, a cada 4 h, por 3 dias; Tr/Pa - prescrição da associação de cloridrato de tramadol (37,5 mg) e paracetamol (500 mg), na mesma posologia do grupo anterior. Os escores de dor foram registrados pelo próprio paciente, nos tempos 6, 12, 24, 48 e 72 h após o atendimento, em diário específico de evolução da dor, por meio da Escala Analógica Visual (EAV). No Artigo 2, foi realizada uma revisão sistemática, por meio de buscas conduzidas nas bases de dados: MEDLINE, registro de ensaios clínicos da Cochrane Library, LILACS, SciELO, banco de teses/dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e referências dos artigos encontrados. Para serem incluídos, os artigos deveriam ser ensaios clínicos randomizados (ECRs), controlados e cegos, ou revisões sistemáticas com ou sem metanálise. Deveriam ter um dos braços de terapia constituído por analgésico ou anti-inflamatório, administrado por via oral, para controle da dor moderada a intensa, de origem endodôntica, mensurada por meio da Escala Analógica Visual, em adultos. Foram coletados dados referentes às características da amostra, escores de dor pré-tratamento, características dos grupos em comparação, aspectos de qualidade metodológica, frequência de uso de analgésico adicional e a frequência de eventos adversos. Foram realizadas análises descritiva e inferencial. Resultados: No Artigo 1, em ambos os grupos, houve redução dos escores de dor ao longo do tempo. No grupo Co/Pa, houve redução significativa dos escores em 12, 24, 48 e 72 horas, em comparação com aos iniciais (P<0,05). Os escores em 48 e 72 horas foram menores, em relação aos iniciais e aos escores das 6 horas (P<0,05). No grupo Tr/Pa, houve redução dos escores de todos os tempos experimentais, em relação aos iniciais (P<0,05). Para todos os intervalos de tempo analisados, os grupos não foram diferentes entre si (P>0,05). Ambos os tratamentos foram eficazes no controle da dor provocada pelo ADA em evolução. Porém, a associação Tr/Pa apresentou-se menos segura. No Artigo 2, de um total de 431 referências, 419 resumos foram analisados e 14 artigos foram lidos na íntegra. Após a exclusão de 5 artigos, 9 ensaios clínicos preencheram os critérios de inclusão. Os estudos compararam paracetamol, AINE (ibuprofeno, flurbiprofeno, cetorolaco de trometamina, etodolaco, tenoxicam), prednisolona, tramadol e associações analgésicas no tratamento da dor endodôntica moderada a intensa. Foi observado que os medicamentos foram administrados antes ou após a intervenção endodôntica. Em 8 estudos, o grupo controle foi placebo e 8 estudos utilizaram o esquema de dose única para avaliar o controle da dor. Em todos os ensaios clínicos, o desfecho primário analisado foi a redução dos escores de dor e os desfechos secundários, uso de medicamento adicional e ocorrência de reações adversas. Foi possível estabelecer uma relação significativa entre uso de analgésico adicional e diagnóstico periapical. Quando a administração ocorreu antes do procedimento endodôntico, não foi observada a ocorrência de eventos adversos. Quando a administração ocorreu após o procedimento, foram relatadas reações adversas em dois dos três estudos incluídos na análise. Conclusão: O Artigo 1 sugere que, em função de eficácia analgésica e segurança, a associação codeína/paracetamol seja mais efetiva para o controle da dor aguda de moderada a intensa, no tratamento da ADA em evolução. O Artigo 2 aponta carência de ECRs em Endodontia, que utilizem um mesmo padrão metodológico, para definição de um protocolo de tratamento sistêmico na dor de origem endodôntica. / Aim: To evaluate the management of pain in Endodontics by two studies: Article 1 - a randomized clinical trial comparing the analgesic efficacy of two opioids and non-opioid associations in the pain control of Acute Dentoalveolar Abscess (ADA); Article 2 - a systematic review investigating the efficacy and safety of analgesic therapy in the management endodontic pain.Methodology: The Article 1 included 24 patients that looked for emergency treatment in a university dental clinic. These patients were divided into two groups: Co / Pa - prescription of codeine (30 mg) + acetaminophen (500 mg) oral, every 4 h, during 3 days; Tr / Ac - prescription of tramadol hydrochloride (37.5 mg) + acetaminophen (500 mg) as the previous group. Pain scores were recorded by the patient at 6, 12, 24, 48, and 72 h after treatment, in a pain diary, using the Visual Analogue Scale (VAS). The Article 2 was conducted in electronic databases, gray literature, and references of retrieved articles to analyze randomized clinical trials or systematic reviews with or without meta-analysis. One arms of the therapy should have comprised an anti-inflammatory or analgesic drugs, orally administered by adults, in order to control moderate to severe pain, measured by Visual Analogue Scale, cause by endodontic problems . Data were collected regarding the characteristics of the sample, scores of pretreatment pain, characteristics of compared groups, methodological quality aspects, additional analgesic use, and frequency of adverse events. Descriptive and inferential analyzes were performed. Results: In Article 1, in both groups there was a reduction in the pain scores over time. For Co/Ac group, it was found a significant reduction in the scores at 12, 24, 48, and 72 hours after treatment (P <0.05). The scores at 48 and 72 hours were lower, compared to immediate treatment and scores at 6 hours after treatment (P <0.05). In the Tr/ Ac group, the scores decreased as the time is increasing (P <0.05). For all time intervals tested, the groups were not significantly different (P> 0.05). Both treatments were effective in controlling pain caused by ADA. The association Tr/ Ac presented itself less secure. In Article 2, a total of 431 references and 419 abstracts were reviewed, then only 14 articles were read in full. From these articles it was excluded 5 and 9 trials met the inclusion criteria. These studies compared acetaminophen, NSAIDs (ibuprofen, flurbiprofen, ketorolac tromethamine, etodolac, and tenoxicam), prednisolone, and analgesic tramadol associations for treating moderate to severe endodontic pain. It was observed that drugs were administered before or after endodontic therapy. In 8 studies, the control group was placebo and 8 studies used single dose regimen to assess pain control. In all clinical trials, the primary outcome analyzed was the reduction of scores in pain and secondary outcomes were the utilization of additional medication and adverse reactions. It was possible to establish a significant relationship between use of additional analgesics and periapical diagnosis. When the administration occurred before the endodontic procedure no adverse events were observed. When it was administered after the procedure, adverse reactions were reported in 2 of 3 trials included in the analysis. Conclusion: The Article 1 suggests that, considering analgesic efficacy and safety function, the association codeine/ acetaminophen is more effective for the control moderate to severe pain, at the treatment of ADA in evolution. The Article 2 found that there is a lack of RCTs in Endodontics using the same methodological standard to define a systemic treatment protocol of endodontic pain.

Objetivos: Avaliar o manejo da dor em Endodontia por meio de dois estudos: Artigo 1 – um ensaio clínico randomizado comparando a eficácia analgésica de duas associações de opioide e não opioide no controle da dor do Abscesso Dentoalveolar Agudo (ADA) em evolução; Artigo 2 – uma revisão sistemática investigando a eficácia e segurança de terapia sistêmica para o tratamento da dor de origem endodôntica. Métodos: No Artigo 1, foram incluídos 24 pacientes que procuraram atendimento em serviço odontológico universitário do sul do Brasil. Após o atendimento de urgência, os pacientes foram alocados em dois grupos: Co/Pa – prescrição da associação de codeína (30 mg) e paracetamol (500 mg), por via oral, a cada 4 h, por 3 dias; Tr/Pa - prescrição da associação de cloridrato de tramadol (37,5 mg) e paracetamol (500 mg), na mesma posologia do grupo anterior. Os escores de dor foram registrados pelo próprio paciente, nos tempos 6, 12, 24, 48 e 72 h após o atendimento, em diário específico de evolução da dor, por meio da Escala Analógica Visual (EAV). No Artigo 2, foi realizada uma revisão sistemática, por meio de buscas conduzidas nas bases de dados: MEDLINE, registro de ensaios clínicos da Cochrane Library, LILACS, SciELO, banco de teses/dissertações da Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) e referências dos artigos encontrados. Para serem incluídos, os artigos deveriam ser ensaios clínicos randomizados (ECRs), controlados e cegos, ou revisões sistemáticas com ou sem metanálise. Deveriam ter um dos braços de terapia constituído por analgésico ou anti-inflamatório, administrado por via oral, para controle da dor moderada a intensa, de origem endodôntica, mensurada por meio da Escala Analógica Visual, em adultos. Foram coletados dados referentes às características da amostra, escores de dor pré-tratamento, características dos grupos em comparação, aspectos de qualidade metodológica, frequência de uso de analgésico adicional e a frequência de eventos adversos. Foram realizadas análises descritiva e inferencial. Resultados: No Artigo 1, em ambos os grupos, houve redução dos escores de dor ao longo do tempo. No grupo Co/Pa, houve redução significativa dos escores em 12, 24, 48 e 72 horas, em comparação com aos iniciais (P<0,05). Os escores em 48 e 72 horas foram menores, em relação aos iniciais e aos escores das 6 horas (P<0,05). No grupo Tr/Pa, houve redução dos escores de todos os tempos experimentais, em relação aos iniciais (P<0,05). Para todos os intervalos de tempo analisados, os grupos não foram diferentes entre si (P>0,05). Ambos os tratamentos foram eficazes no controle da dor provocada pelo ADA em evolução. Porém, a associação Tr/Pa apresentou-se menos segura. No Artigo 2, de um total de 431 referências, 419 resumos foram analisados e 14 artigos foram lidos na íntegra. Após a exclusão de 5 artigos, 9 ensaios clínicos preencheram os critérios de inclusão. Os estudos compararam paracetamol, AINE (ibuprofeno, flurbiprofeno, cetorolaco de trometamina, etodolaco, tenoxicam), prednisolona, tramadol e associações analgésicas no tratamento da dor endodôntica moderada a intensa. Foi observado que os medicamentos foram administrados antes ou após a intervenção endodôntica. Em 8 estudos, o grupo controle foi placebo e 8 estudos utilizaram o esquema de dose única para avaliar o controle da dor. Em todos os ensaios clínicos, o desfecho primário analisado foi a redução dos escores de dor e os desfechos secundários, uso de medicamento adicional e ocorrência de reações adversas. Foi possível estabelecer uma relação significativa entre uso de analgésico adicional e diagnóstico periapical. Quando a administração ocorreu antes do procedimento endodôntico, não foi observada a ocorrência de eventos adversos. Quando a administração ocorreu após o procedimento, foram relatadas reações adversas em dois dos três estudos incluídos na análise. Conclusão: O Artigo 1 sugere que, em função de eficácia analgésica e segurança, a associação codeína/paracetamol seja mais efetiva para o controle da dor aguda de moderada a intensa, no tratamento da ADA em evolução. O Artigo 2 aponta carência de ECRs em Endodontia, que utilizem um mesmo padrão metodológico, para definição de um protocolo de tratamento sistêmico na dor de origem endodôntica. / Aim: To evaluate the management of pain in Endodontics by two studies: Article 1 - a randomized clinical trial comparing the analgesic efficacy of two opioids and non-opioid associations in the pain control of Acute Dentoalveolar Abscess (ADA); Article 2 - a systematic review investigating the efficacy and safety of analgesic therapy in the management endodontic pain.Methodology: The Article 1 included 24 patients that looked for emergency treatment in a university dental clinic. These patients were divided into two groups: Co / Pa - prescription of codeine (30 mg) + acetaminophen (500 mg) oral, every 4 h, during 3 days; Tr / Ac - prescription of tramadol hydrochloride (37.5 mg) + acetaminophen (500 mg) as the previous group. Pain scores were recorded by the patient at 6, 12, 24, 48, and 72 h after treatment, in a pain diary, using the Visual Analogue Scale (VAS). The Article 2 was conducted in electronic databases, gray literature, and references of retrieved articles to analyze randomized clinical trials or systematic reviews with or without meta-analysis. One arms of the therapy should have comprised an anti-inflammatory or analgesic drugs, orally administered by adults, in order to control moderate to severe pain, measured by Visual Analogue Scale, cause by endodontic problems . Data were collected regarding the characteristics of the sample, scores of pretreatment pain, characteristics of compared groups, methodological quality aspects, additional analgesic use, and frequency of adverse events. Descriptive and inferential analyzes were performed. Results: In Article 1, in both groups there was a reduction in the pain scores over time. For Co/Ac group, it was found a significant reduction in the scores at 12, 24, 48, and 72 hours after treatment (P <0.05). The scores at 48 and 72 hours were lower, compared to immediate treatment and scores at 6 hours after treatment (P <0.05). In the Tr/ Ac group, the scores decreased as the time is increasing (P <0.05). For all time intervals tested, the groups were not significantly different (P> 0.05). Both treatments were effective in controlling pain caused by ADA. The association Tr/ Ac presented itself less secure. In Article 2, a total of 431 references and 419 abstracts were reviewed, then only 14 articles were read in full. From these articles it was excluded 5 and 9 trials met the inclusion criteria. These studies compared acetaminophen, NSAIDs (ibuprofen, flurbiprofen, ketorolac tromethamine, etodolac, and tenoxicam), prednisolone, and analgesic tramadol associations for treating moderate to severe endodontic pain. It was observed that drugs were administered before or after endodontic therapy. In 8 studies, the control group was placebo and 8 studies used single dose regimen to assess pain control. In all clinical trials, the primary outcome analyzed was the reduction of scores in pain and secondary outcomes were the utilization of additional medication and adverse reactions. It was possible to establish a significant relationship between use of additional analgesics and periapical diagnosis. When the administration occurred before the endodontic procedure no adverse events were observed. When it was administered after the procedure, adverse reactions were reported in 2 of 3 trials included in the analysis. Conclusion: The Article 1 suggests that, considering analgesic efficacy and safety function, the association codeine/ acetaminophen is more effective for the control moderate to severe pain, at the treatment of ADA in evolution. The Article 2 found that there is a lack of RCTs in Endodontics using the same methodological standard to define a systemic treatment protocol of endodontic pain.

BACKGROUND: Drug abuse is a social problem with psychosocial and physical complications. The lifestyle of injection drug users (IUD) increases the risk of infectious as well as of non-infectious diseases. The workers of low-threshold programmes are often the first ones to encounter the physical complications of injection drug users, and the workers are accordingly often the ones who take the initiative in dealing with those complications. Mapping the possible solutions of injection drug users' complications by the workers of low-threshold programmes would respond to the needs for methodological approach widely available to the workers of low-threshold programmes. AIMS: The present thesis aims to describe the possible solutions to physical complications of injection drug users through mapping the solutions in the practice of the low-threshold programmes workers for drug users in Prague. SAMPLE: All the seven low-threshold programmes facilities based in Prague were appealed to participate on the research. Thirty eight respondents participated in the study (39 % outreach programs, 53 % drop-in centre, 8 % combined services) METHODS: The present research was carried out via questionnaire research. The output data was analysed through descriptive statistics. The standardized questions of the...

Doctor of Philosophy / Department of Diagnostic Medicine/Pathobiology / Daniel U. Thomson / A series of studies were conducted in order to develop, test, implement, and utilize an objective and comprehensive gross pathology scoring system for cattle at slaughter. Individual lung, liver, and rumen gross pathology data was collected from 19,229 head of cattle and corresponding individual pre-harvest and carcass data for a subset of 13,226 head.. Across the entire population 22.6% and 9.8% of cattle displayed mild and severe lesions, respectively. Severe lung lesions at the time of slaughter were associated with a decreased ADG of 0.07 kg/ day and a carcass weight 7.1 kg less than that of their cohorts with no visible signs of pulmonary BRDC lesions (P < 0.01). Overall, 68.6 % of cattle observed had normal livers, free from abscesses and other abnormalities. Cattle with a severe liver abscess at the time of slaughter were associated with a 0.10 kg/day during the feeding period (P < 0.01). Of cattle severely affected by liver abscesses (A+, 4.6%), 14.9% also displayed severe BRDC lung lesions and 28.3 % of cattle displayed mild BRDC lung lesions. Rumenitis lesions were observed in 24.1% of the overall study population. Severe rumenitis lesions were associated with a significant decrease in average daily gain and carcass weight (0.03kg/day and 2.20 kg, respectively, P < 0.01). The system was also implemented on a population of cull cows at a commercial abattoir in the Great Lakes region of the U.S. (n=1,461; 87% Holstein, 13% other cows). Severe liver abscesses, were observed in 18.5% of cull cows at slaughter. Severe rumenitis lesions or rumenitis scars were observed in 10% and severe BRDC lesions were observed in 10.3% o of the population. A prospective study of a commercially available, direct fed microbial oral drench of Megasphaera elsdenii (NCIMB 41125) was conducted in 4,863 head of yearling feeder cattle. No significant effects of treatment were detected for final live weight (599 vs. 601 kg; P=0.79) or hot carcass weight (386 vs. 387 kg P=0.81) for Con and M.e., respectively. Fourteen point two percent and 14.0% of Con and M.e., respectively displayed a liver abscess of varying severity at the time of slaughter. Overall, 8.27 and 7.96% % of Con and M.e. cattle were observed with an altered rumen epithelial health status. The ordinal odds ratio of a M.e. treated animal having a more severe liver abscess score or rumen health score was not significant (Estimate: 0.96, 95% C.L. 0.733-1.259, P=0.771; Estimate: 1.01, 95% C.L. 0.625-1.63 P=0.96, respectively.) Comprehensive monitoring of gross pathology at slaughter is commercially plausible and provides valuable data for veterinarians, nutritionists and management personnel.

Einleitung: Die Implantation kryokonservierter allogener Aortenklappen stellt heutzutage eine effektive operative Technik dar, um in schweren Fällen einer floriden Aortenklappenendokarditis exzellente postoperative Ergebnisse zu erzielen. Diese Studie demonstriert die Langzeitergebnisse im Deutschen Herzzentrum Berlin über einen Zeitraum von 17 Jahren. Material und Methoden: Zwischen dem 1.Januar 1987 und 31.Dezember 2003 wurden bei 203 Patienten mit florider Aortenklappenendokarditis kryokonservierte Aortenklappenallografts implantiert (in subkoronarer Implantationstechnik n=107 und durch totalen Aortenwurzelersatz n=96). Das mittlere Alter der Patienten betrug 51,3 Jahre (2-82 Jahre). Darunter waren 42 Frauen und 161 Männer. 161 Patienten zeigten präoperativ eine anuläre Aortenwurzelabszeßbildung. Ergebnisse: Die 30-Tage-Mortalität (mit Anulusabszeß) betrug insgesamt 21,1% (23,6%): bei nativer Aortenklappenendokarditis 14,9% (17,5%) und bei Prothesen-endokarditis 29,2% (29,6%). Nach 17 Jahren waren 70,4+3,6% und 78,6+6,3% (p=0,24) der Patienten mit und ohne präoperativem Anulusabszeß am Leben. Bei 12 Patienten mit Anulusabszeß trat eine Allograft-Re-Infektion auf, die aktualisierte Freiheit von Reinfektion betrug 91,6+2,4% nach 17 Jahren. Insgesamt wurden 37 Patienten reoperiert, die aktualisierte Freiheit von Reoperation betrug 75,0+3,7% nach 17 Jahren. Die aktualisierte Freiheit von Explantation der Allografts wegen Strukturalteration betrug bei den Patienten mit Anulusabszeß nach 17 Jahren 96,0+2,0%. Thrombembolische Ereignisse traten nicht auf. Die Univarianzanalyse identifizierte die Allograft-Re-Infektion (p=0,0001) und zu klein bemessene Allografts (p=0,001) als Risikofaktoren für eine Reoperation sowohl bei nativer als auch Prothesenendokarditis. Schlußfolgerung: Aortenklappenallografts zeigen bei florider Aortenklappenendokarditis mit Anulusabszeß exzellente Langzeitresultate. Die 30-Tage–Mortalität wird hinsichtlich der Schwere der Erkrankung akzeptiert und Re-Infektionen sind selten. Zu klein bemessene Allografts und Re-Infektionen sind Risikofaktoren für Reoperationen. / Objective: Cryopreserved aortic valve homografts have become an accepted valve substitute in acute aortic valve endocarditis, but long-term studies of valve function are largely unavailable. This survey represents our observations over a period of 17 years. Material and methods: Between February 9, 1987 and October 30, 2003, 203 patients with infective aortic valve endocarditis underwent allograft replacement of the aortic valve (free-hand subcoronary technique, n=107 and root replacement, n=96). The patients’ age ranged between 2 and 82 years with a mean age of 51.3 years. The survey included 42 females and 161 males. 161 had infected aortic root with ring abscesses. Results: The hospital mortality of patients with native and prosthetic endocarditis complicated by periannular abscess was 14.9% (17.5%) and 29.2 % (29.6%) respectively making an overall hospital mortality of 21.2% (23.6%). 17 years patient survival in patients with and without periannular abscess was 70.4+3.6% and 78.6+6.3% (p=0,24) respectively. There were 12 events of recurrent endocarditis in patients with periannular abscess, giving an actuarial freedom of 91.6+2.4% at 17 years. Reoperation was performed in 37 patients for a variety of reasons, and overall freedom from reoperation was 75.0+3.7% at 17 years. Freedom from explantation for structural valve deterioration was 96.0+2.0% at 17 years for patients with periannular abcess. No thrombembolic event was evident. Univariable analysis identified recurrent endocarditis (p=0.0001) and undersized allograft (p=0.001) as risk factors for reoperation for both native and prosthetic aortic valve endocarditis. No risk factors for hospital mortality were found. Conclusion: Aortic allograft offers an excellent long-term clinical result in patients with infective aortic valve endocarditis with associated periannular abscess. Operative mortality is acceptable based on the severity of aortic pathology, with low evidence of recurrent endocarditis and no thrombembolic events. Undersized allograft and recurrent infection are risk factors for reoperation.