The main problem posed in this thesis is an epistemological one to do with what counts as knowledge in the organisation/management and management accounting areas of scholarship. This question arose regarding discrepancies between an original text, Burns and Stalker's The Management of Innovation (1961, 1966, 1994), and longstanding representations in the mainstream literature. The discrepancies were between the largely objectivist representations focussing on the relationship between organisation structure and environmental contingency, while omitting subjectivist factors and organisational processes, also significant in Burns and Stalker's analysis. The analysis in this thesis is concerned with two main questions: the similarities and differences between The Management of Innovation and mainstream representations; and explanations for these, particularly for the differences. The analytical framework is critical realist theory underpinned by an Hegelian dialectical methodology, looking at phenomena from different perspectives with inconsistencies addressed by a more holistic analysis. This thesis is based on a non-linear, multi-angled approach, which examines each of the two questions from different perspectives through two dialectical circles. A detailed analysis of Burns and Stalker's work and mainstream representations enabled clarity regarding the different foci in the two sets of texts. The absenting of human factors and organisational processes in much mainstream scholarship was found to extend beyond representations of Burns and Stalker's work to orthodox scholarship more widely, despite strong and persistent critiques from within the field. The dialectical opposition constructed between objectivist and subjectivist factors was investigated further and linked to attitudes regarding the commensurability of different approaches in the social sciences, particularly in the organisation/management and management accounting fields. It is suggested that this opposition is based on a particular view of science and scientific method. A broader interpretation however shows that science is also influenced by researchers' subjectivities. This has led to an argument for the complementary, more holistic approaches already present in the field becoming more widespread in the interests of more sustainable and emancipatory knowledge.

This thesis examines the work of reformer Lugenia Burns Hope and her community organization, the Neighborhood Union, as a case study to unpack scholarly characterizations of black elite uplift strategies during the early 20th century. The Neighborhood Union was established in 1908 in Atlanta by Hope and women from the community to build stronger neighborhoods and to combat the deleterious effects of the 1906 Race Riots and Jim Crow laws. Neighborhood Union settlement houses provided basic and extracurricular services, including kindergartens for working mothers, vocational classes, and lecture series. The organization’s exceptional, multi-class leadership structure enabled members of the black poor and working classes to lead their own projects with the assistance of Neighborhood Union resources. Hope’s background provides evidence against broad generalizations of the black elite as paternalistic, and her vision of creating democratic communities that diminished class barriers provides a counter narrative to characterizations of clubwomen and the black elite as engaging in respectability politics in their social work. Understood within its historical and sociopolitical context, Hope’s life and work also challenge mainstream narratives of the Progressive Era and the Social Gospel movement.

Thesis (MA)--University of Stellenbosch, 2001. / ENGLISH ABSTRACT: This study examines the socio-cultural issues in the praise poems of three Xhosa chiefs, namely, Nkosi Whyte Lent Mbali Maqoma of the amaJingqi, Nkosi Doyle Mpuhle Jongilanga of Dushane of Ndlambe and Nkosi Sipho Mangindi Burns-Ncamashe of amaGwali of Tshiwo. What comes out clear in the poems of these chiefs is that they experienced power problems after and before 1994. Their poetry protests about these political influences and calls for the restoration of the dignity of the chieftancy. The socio-cultural aspects of the praise poems of each chief are devoted to a chapter: Nkosi Whyte Lent Mbali Maqoma in Chapter 2, Nkosi Doyle Mpuhle Jongilanga in Chapter 3, and Nkosi Sipho Mangindi Burns-Ncamashe in Chapter 4. Attention is paid to each chiefs genealogy, praise names, names of oxen because of traditional significance in the life of the chief, the chiefs mother, and place names which have historical importance in the life of the chief. As part of the theoretical framework of praise poetry, praise poetry theory is handled in Chapter 1 of the study. It is concluded in Chapter 5 that Xhosa paramount chiefs still play and will playa crucial socio-cultural role in their communities. They are not only concerned about being custodians of culture but also with the development of their nations. / AFRIKAANSE OPSOMMING: Hierdie studie ondersoek sosio-kulturele vraagstukke in die prysgedigte van drie Xhosa opperhoofde, naamlik opperhoof Whyte Lent Mbali Maqoma van die amaJingqi, opperhoof Doyle Mpuhle Jongilanga van die Dushane groep van die Ndlambe en opperhoof Sipho Mangindi Burns-Ncamashe van die amaGwali groep van die Tshiwo. Die beeld wat na vore kom na aanleiding van 'n analise van die opperhoofde se prysgedigte dat hulle 'n magsprobleem ondervind het sowel voor as na 1994. Deur hulle poesie teken hulle protes aan oor bepaalde politieke invloede en hulle doen 'n beroep daarop dat die waardigheid van die hoofmanskap herstel word. Die sosio-kulturele vraagstukke wat na vore kom in die prysgedigte van elke opperhoof word behandel in individuele hoofstukke. Hoofstuk 2 ondersoek die prysgedigte van opperhoof Whyte Lent Mbali Maqoma, Hoofstuk 3 die prysgedigte van opperhoof Doyle Mpuhle Jongilanga, en Hoofstuk 4, die prysgedigte van opperhoof Sipho Mangindi Burns- Ncamashe. Aandag word gegee aan die genealogie van elke opperhoof, prysgroetvorme, die name van beeste, op grond van hulle tradisionele betekenis in die lewe van 'n hoofman, die opperhoof se moeder, asook plekname wat 'n historiese belang het in die lewe van die opperhoof. As deel van die teoretiese raamwerk vir die studie word die teorie van die prysgedig behandel in Hoofstuk 1. Hoofstuk 5 gee 'n samevatting van die belangrikste aspekte van die studie en motiveer die gevolgtrekking dat opperhoofde steeds 'n essenstele sosio-kulturele rol speel en ook in die toekoms sal speel in hulle gemeenskappe. Hulle is nie slegs die bewakers van die kultuurwaardes van hulle gemeenskappe nie, maar is ook fundamenteel betrokke by die ontwikkeling van hulle gemeenskappe. / ISISHWANKATHELO Olu luphando ngemiba yentlalo nenkcubeko kwizibongo zeenkosi zamaXhosa ezintathu, uNkosi uWhyte Lent Mbali Maqoma wamaJingqi, uNkosi uDoyle Mpuhle Jongilanga wemiDushane kaNdlambe noNkosi uSipho Mangindi Burns-Ncamashe wamaGwali kaTshiwo. Into evela ngokucacileyo kwizibongo ezingezi nkosi kukuba ngaphambili komnyaka we-1994 nasemva kwawo zifumene ubunzima ekulawuleni abantu bazo. Kwezi zibongo ukukhalaza ngokuphazamisa kwezopolithiko kulawulo Iwazo nelizwi lokubuyiselwa kwesidima sobukhosi kuvela ngokuthe gca. Iveliswa kwisahluko ngasinye imiba ephathelele kwezentlalo nenkcubeko evela kwizibongo zenkosi nganye: uNkosi Whyte Lent Mbali Maqoma kwisahluko 2, uNkosi Doyle Mpuhle Jongilanga kwisahluko 3, noNkosi uSipho Mangindi Burns-Ncamashe kwisahluko 4. Kuqwalaselwe umlibo wenkosi nganye, izikhahlelo zayo, amagama eenkomo ezinentsingiselo kwinkosi leyo, unina wenkosi namagama eendawo ezinentsingiselo kubomi benkosi nganye. Isikhokhelo esiyithiyori yezibongo sinikwe kwisahluko 1 solu phando. Kwisahluko 5 kuphethwa ngokuba iinkosi zamaXhosa zisenenxaxheba enkulu kwaye zisaya kuhlala zinayo kwimiba yentlalo nenkcubeko yabantu bazo. Aziphelelanga nje ekubeni zigcine inkcubeko yoluntu koko zikwanoxanduva lokunyusa umgangatho wobomi babantu bazo.

INTRODUCTION. La guérison rapide des sites donneurs des greffes cutanées favorise la survie des victimes de brûlures graves (>50 % de superficie brûlée). La mortalité élevée de ces patients est attribuable au fait que la superficie des brûlures excède celle de la peau saine. Des cultures épithéliales autologues (CEA) sont des feuillets de kératinocytes produits en culture à partir de la peau du patient. Cette étude a évalué l’effet des CEA sur l'épithélialisation des sites donneurs chez les grands brûlés. MÉTHODES. Tous les patients recevant des CEA ont été prospectivement inclus. Les plaies des sites donneurs ont été recouvertes de CEA, sauf pour une région contrôle randomisée de 7 x 7 cm. Des biopsies faites sur la greffe de peau ont permis de contrôler la profondeur des plaies sur les sites donneurs. Il y avait deux types de contrôles, avec gaze non adhérente trempée dans le milieu de culture ou dans le salin. L’épithélialisation était quantifiée globalement (% d’épithélialisation par photographie) et histologiquement (par biopsie au poinçon) à simple insu. La guérison des zones de contrôle et CEA était comparée par analyse de variance et par le test de Student. RÉSULTATS. Entre 2008 et 2009, 6 patients furent recrutés avec un total de 11 sites donneurs. Ces patients avaient en moyenne 43.5 ans, 56 % de superficie brûlée, 45% de brûlure pleine épaisseur, 66% avaient une brûlure d’inhalation, 75 jours de séjour. Il n’y a aucune corrélation entre le pourcentage d’épithélialisation et l’épaisseur du prélèvement des greffes (Pearson 0.19). Le score photographique est significativement influencé par le traitement (CEA vs Contrôle; p = 0,039) et par le jour postopératoire (p < 0,001). Le temps moyen pour atteindre un score photographique de guérison pour les zones contrôles fut de 10.2 jours contre 8.6 jours pour le CEA (p = 0,021). A l’évaluation histologique, les sites donneurs traités par le milieu de culture ont évolué aussi favorablement que ceux traités par des feuillets de CEA. CONCLUSION. L’utilisation de CEA sur les sites donneurs semble accélérer leur épithélialisation chez les victimes de brûlures graves. Cet effet est probablement le résultat d’une stimulation de la réépithélialisation innée de la plaie, plutôt que par une adhérence des feuillets de kératinocytes cultivés à la surface de la plaie. / RATIONALE: Prompt healing of split thickness skin graft donor sites is primordial to the survival of severely burned patients. Increased mortality of patients with >50 % TBSA is attributable to the limited availability of donor sites. This study evaluated the effect of Cultured Epithelial Autograft (CEA) application on skin graft donor site healing. METHODS: All burn patients receiving CEA were prospectively included. Donor site wounds were covered with CEA except a randomly designated 7x7 cm control region. Autograft biopsies were taken to document graft harvest thickness. One half of the controls were covered with non-adherent gauze soaked in the culture media and the other controls only received a non-adherent gauze dressing. Epithelialization was objectively evaluated by scoring blinded photographs with an analogue scale. Punch biopsies of the donor sites were evaluated histologically. Repeated measures ANOVA and T-test were used. RESULTS: Between 2008 and 2009, 6 patients were enrolled for a total of 11 donor sites. The patients averaged 43.5 years, 56 % TBSA, 45 % FT-TBSA, 66 % had inhalation injury and mean length of stay was 75 days. As expected, dermatome settings and autograft thickness measured by microscope did not correlate (Pearson 0.19). There was no correlation between the percentage of epithelialization of the punch biopsies of the donor sites and the thickness of the harvest. Photographic score was significantly influenced by its treatment CEA vs Control (p=0.039) and by postoperative day (p<0.001). Mean time to healing was 8.6 days for CEA compared to 10.2 days for controls (p=0.021). Infection was noted on only one donor site. On histologic analysis, the control sites dressed with gauze soaked in the culture media healed as nicely and promptly as the CEA sheet treated region. CONCLUSION: Use of CEA on donor sites appears to stimulate epithelialization. This effect is probably mediated by stimulation of local wound healing processes rather than by engraftment of keratinocytes from the CEA sheets.

Introdução: as sequelas de queimaduras na morfologia, mobilidade das estruturas motoras orais e nas funções orofaciais, como mastigação, deglutição e fala, são frequentes em pacientes com queimaduras graves na região de cabeça e pescoço. Objetivo: verificar a efetividade de um programa de reabilitação fonoaudiológica da motricidade orofacial em pacientes com queimaduras em cabeça e pescoço. Método: participaram da pesquisa 29 indivíduos encaminhados para avaliação e reabilitação ao Ambulatório de Funções da Face da Divisão de Fonoaudiologia do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de abril de 2016 a abril de 2018. Os critérios inclusão adotados na pesquisa foram: idade > = 6 anos; queimadura de terceiro grau caracterizada por perda epidérmica e dérmica em áreas de cabeça e pescoço; realização de tratamento cirúrgico prévio da ferida; ausência de falhas dentárias; presença de queixas relacionadas às alterações motoras orais; quadro clínico estável (conforme registros em prontuários médicos); alimentação por via oral exclusiva. Os pacientes foram divididos em dois grupos considerando o tempo da queimadura: Grupo 1 (G1) - pacientes com até um ano após a queimadura; Grupo 2 (G2) - pacientes com mais de um ano após a queimadura. A gravidade da queimadura foi determinada pela escala ABSI (The Abbreviated Burn Severity Index), aplicada no primeiro atendimento hospitalar do paciente. Todos os participantes foram submetidos à avaliação fonoaudiológica em dois momentos distintos, pré e pós-programa terapêutico. A avaliação foi composta pelos seguintes protocolos clínicos: Avaliação Miofuncional Orofacial com Escores Expandido (AMIOFE-E), verificação da amplitude mandibular (abertura oral máxima, lateralização para a direita e esquerda e protrusão mandibular) e medida antropométrica do canto de olho à comissura labial. O programa terapêutico adotado foi composto por 8 sessões semanais individuais, com duração de trinta minutos cada. O programa terapêutico foi composto por: manobras de compressão e alongamento em tecido cicatricial, manobras de alongamento intra e extra orais dos músculos da face, exercícios para mobilidade da musculatura da face e região cervical e exercícios para a adequação das funções de mastigação e deglutição. Resultados: a análise estatística evidenciou que o G2 apresentou idade significativamente maior que o G1. Nas análises intragrupos, tanto G1 quanto G2 apresentaram diferenças estatísticas para todos os itens do AMIOFE-E: aparência e condição postural; mobilidade e funções orofaciais (mastigação e deglutição). Quanto às medidas de amplitude mandibular, ambos os grupos apresentaram aumento significativo da medida de abertura oral máxima. Nas análises intergrupos, não foram observadas diferenças significativas entre G1 e G2, indicando que a melhora foi semelhante para ambos os grupos. Conclusão: a pesquisa comprova a eficácia do programa fonoaudiológico, baseado em evidências e com controle de resultados, em pacientes com queimaduras de terceiro grau em cabeça e pescoço. Os resultados demonstraram que ambos os grupos apresentaram melhora significativa na atividade miofuncional oral e na amplitude mandibular. Quando comparados os resultados obtidos entre G1 e G2, não foi observada diferença relevante, indicando que o tratamento proposto foi eficiente, independentemente do tempo entre a queimadura e o início do tratamento / Introduction: alterations in the morphology and mobility of the oral motor structures, and orofacial functions (i.e. mastication, swallowing and speech) are often observed in patients who suffered severe head and neck burns. Purpose: the purpose of the present study was to verify the effectiveness of a myofunctional orofacial rehabilitation program for patients with head and neck burns. Method: participants of this study were 29 individuals referred to the Division of Orofacial Myology of Instituto Central do Hospital das Clínicas of the School of Medicine, University of São Paulo, between April 2016 and April 2018, for oral motor assessment and rehabilitation. Inclusion criteria were as follows: age >= 6 years; third degree burns to the head and neck (i.e. epidermal and dermal loss); previous surgical treatment to the wound; complete dentition; oral motor alterations deficits; medical stability (according to medical records); receiving all nutrition by mouth. Patients were divided in two groups according to the onset of the injury: Group 1 (G1) - patients with injuries less than a year old; Group 2 (G2) - patients with injuries more than a year old. Burn severity was determined by the ABSI (The Abbreviated Burn Severity Index) according to the patient\'s first hospital record. All participants underwent clinical assessment that involved an oral motor evaluation (Expanded Protocol of Orofacial Myofunctional Evaluation with Scores - OMES-E), the assessment of the mandibular range of movements (maximal incisor distance, right and left lateral excursions and protrusion) and an anthropometric assessment (measurement of the distance between the commissures of mouth and the corners of the eyes). For comparison purposes, assessments were performed pre and post-treatment. The rehabilitation program involved 8 individual 30 minute weekly sessions. The rehabilitation program involved: compression and stretching maneuvers on the scar tissue; intra and extra oral stretching maneuvers of the facial muscles; facial and cervical muscles mobility exercises; mastication and swallowing exercises. Results: the statistical analysis indicated that G2 was significantly older than G1. When comparing pre and post-treatment results, both group of patients presented significant differences considering the items on the OMES-E (i.e. appearance and posture, mobility and orofacial functions), and the maximal incisor opening. The analysis comparing the performance of G1 and G2 did not indicate differences between the groups. Conclusion: The results of the study indicated that the rehabilitation program was effective for third degree burns on the head and neck, demonstrating significant improvement of the oral myofunctional parameters and of the maximal incisor opening. The results also suggest that the maturation of the scar tissue did not have an influence on the results of the treatment program

Introdução: A sepse é a maior causa de morbidade e mortalidade em pacientes queimados, uma vez que profundas alterações ocorrem na farmacocinética de agentes antimicrobianos prescritos para o controle das infecções. Além disso, pacientes queimados podem apresentar quadro de infecção por germes da comunidade, numa fase precoce de internação na UTI, e devem receber antimicrobianos que diferem daqueles indicados na sepse. Na vigência de infecção fúngica, o quadro se torna ainda mais grave para os pacientes queimados de prolongada internação e imunocomprometidos. Objetivo: Realizar o monitoramento plasmático de oito antimicrobianos largamente prescritos na UTI, a investigação da farmacocinética e a modelagem PK-PD para o ajuste do regime de dose e controle das infecções em pacientes queimados. Casuística: Investigaram-se 32 pacientes queimados internados na UTI/Unidade de Queimados - Divisão de Cirurgia Plástica do HC FMUSP, portadores de infecção recebendo pela via sistêmica sete antimicrobianos e um antifúngico. Métodos- Etapa Clinica: Os pacientes receberam os antimicrobianos geralmente em associação para o controle das infecções seguindo as recomendações da CCIH do hospital relativas ao regime de dose empírica inicial do controle de infecção na UTI de Queimados, na fase precoce e tardia da internação. Realizou-se o monitoramento plasmático do fluconazol, para a infecção fúngica, e dos sete antimicrobianos mais prescritos na UTI para os germes da comunidade e hospitalares (cefepime, ciprofloxacino, imipenem, oxacilina, piperacilina, sulfametoxazol e vancomicina) através das coletas de amostras sanguíneas de pico (termino da infusão) e vale (imediatamente antes da dose subseqüente). Complementarmente, a critério Clínico, foram colhidas amostras seriadas de sangue (pico, 1ª, 2ª, 4ª, 6ª e vale), totalizando seis coletas, para investigação da farmacocinética do agente que requereu ajuste de dose e individualização de terapia no paciente queimado. As coletas de sangue foram realizadas através de cateter venoso (2mL/coleta em tubos contendo EDTA sódico) pelo médico intensivista de plantão na UTI; o plasma foi obtido pela centrifugação para análise do fármaco de interesse ou então armazenado no congelador (-80o C) até o ensaio. Métodos - Etapa Analítica: Previamente à realização da Etapa Clínica, foi realizado no Laboratório o desenvolvimento, validação e otimização de método bioanalítico para quantificação dos oito antimicrobianos no plasma. Preferencialmente, as análises foram realizadas no dia da coleta de sangue do paciente, e o \"Laudo de Exame\" contendo os resultados foi expedido no mesmo dia ou na manhã do dia subseqüente possibilitando a intervenção precoce da Equipe Clínica e se necessária a substituição do regime empírico pela terapia individualizada dose ajustada. Métodos- Etapa estatística: A estatística propriamente dita foi realizada pelo tratamento estatístico com utilização do software GraphPad Instat 4.0., GraphPad Prism 4.0, pela utilização de testes paramétricos e não paramétricos. A modelagem farmacocinética foi realizada através da aplicação do software NonCompartmental Analysis, PK Solutions 2.0, aos pares de dados (C vs T) para cada antimicrobiano. Adicionalmente, aplicou-se o software GraphPad Prism 4.0 para a modelagem PK-PD, ferramenta importante na tomada de decisão relativa à alteração do regime empírico dos antimicrobianos. Resultados: Os pacientes queimados incluídos no protocolo eram adultos de ambos os sexos 23F/9M, 39,6 anos, 69,5 kg, 33,9% SCQ, e os agentes da queimadura foram para 27 pacientes/ térmico-fogo e para três pacientes/trauma elétrico; a lesão inalatória foi registrada em 11/32 pacientes. Foram realizados 303 seguimentos farmacoterapêuticos com a emissão de laudos de exame para os antimicrobianos prescritos aos pacientes nas fases precoce e tardia da internação. O ajuste de dose foi requerido para a vancomicina em 88% das solicitações de exame, cefepime (65%), sulfametozaxol (52%), fluconazol (74%) e imipenem (19%). Registrou-se alta variabilidade na farmacocinética para todos os antimicrobianos investigados. Adicionalmente, registrou-se alteração significativa dos parâmetros farmacocinéticos do imipenem, fluconazol, sulfametoxazol e vancomicina nos seguimentos de pacientes queimados com disfunção renal dialítica relativamente aqueles em que se registrou função renal preservada. A modelagem PK-PD para os diversos antimicrobianos se baseou nos parâmetros de predição de eficácia recomendados tais como o intervalo de tempo em que a concentração plasmática permaneceu acima da concentração inibitória mínima (%&#916; T> CIM) para o cefepime, imipenem, oxacilina e piperacilina, ASCss0-24/CIM + Cssmax/CIM para o ciprofloxacino, ASCss0-24/CIM para o fluconazol e para a vancomicina e ASCss0-24/CIM +%&#916; T> CIM para a sulfametoxazol. Conclusões: Registrou-se alta variabilidade na farmacocinética dos agentes investigados e a modelagem PK-PD justificou plenamente a substituição da terapia empírica inicial pela dose ajustada para a cobertura dos germes sensíveis, daqueles apresentando sensibilidade dose dependente ao antimicrobiano, além daqueles com alto CIM, pouco sensíveis as doses usuais. Finalmente, a modelagem PK-PD mostrou-se definitiva e ferramenta indispensável na manutenção desses agentes no arsenal terapêutico, garantindo terapia eficaz ao paciente queimado, evitando a emergência bacteriana e o desenvolvimento de resistência. / Introduction: Sepsis is a main cause of morbidity and mortality in burn patients, once pharmacokinetics of antimicrobials prescribed for the control of infections are significantly altered in those patients. In addition, burn patients in the ICU, initially can present infections by community microbial and must receive different antimicrobials than those prescribed for sepsis. On the other hand, burn immunocompromized patients with prolonged staying in the ICU, re-incidence of sepsis and fungal infection requires an effective antifungal agent that must be associated to the antimicrobials prescription. Objective: Therapeutic plasma monitoring of eight antimicrobials largely prescribed to burn patients from the ICU, Pharmacokinetic and PK-PD modeling for dose adjustment and for the control of infections. Study design: Thirty two burn inpatients with infections from the ICU Burns- Division of Plastic Surgery of Clinics Hospital Medical School University of Sao Paulo received systemically antimicrobials/ antifungal agents. Methods - Clinical Procedures: In general burn patients received several antimicrobial agents as recommended by the Control of Hospital Infection Committee as empirical dose at the beginning of therapy and also afterwards in the ICU. The control of infections by community microbials or yet by hospital microbials, and also for fungal infection, was performed by drug plasma monitoring of cefepime, ciprofloxacin, imipenem, oxacillin, piperacillin, sulphamethoxazole, vancomycin and fluconazole after blood sample collection at the peak and at the trough. Complementary, usually by clinical criteria, six blood sample collections were performed at time dose interval (end of drug infusion, 1st, 2nd, 4th, 6th and at the trough) for pharmacokinetic purposes, dose adjustment and individualization of drug therapy for burn patients. Blood sample collection was done by the physician from the ICU by venous catheter (2mL/each into blood collection tubes sodium EDTA); plasma obtained by centrifugation of blood tubes were analyzed in the same day or in a deep freezer to storage (-80o C) until assay. Methods - Analytical Procedures: Previously to the clinical study, in the Laboratory School of Pharmaceutical Sciences was performed the development, validation and optimization of bioanalytical methods for drug plasma monitoring of eight antimicrobial/antifungal agents by HPLC-UV. Drug measurements were performed on the day of blood collection and data were preferentially informed to the physician at the same day or at the early morning of the following day to facilitate the therapeutic intervention and changes on the morning prescription to guarantee drug efficacy. Methods Statistics Procedures: Descriptive statistics was performed by applying the software GraphPad Instat v 4.0., GraphPad Prism v.4.0 by parametric and non parametric tests. Pharmacokinetics was estimated by applying the software NonCompartmental Analysis, PK Solutions 2.0, to data (C vs T) for each antimicrobial agent. Additionally, the software GraphPad Prism v 4.0 was applied to PK-PD modeling, an important tool related to dilemma decision about changes on empirical dose of an antimicrobial agent and obviously helps the physician in the rationalization of drug therapy in severe burns. Results: Burn patients included in the protocol were of both genders 23F/9M, 39.6 yrs, 69.5 kg, 33.9% TBSA; agents of the accident were fire/ alcohol for 27 patients and electrical trauma for three patients; inhalation injury were described for 11/32 patients. Approximately 1500 drug plasma measurements for all antimicrobials prescribed to burn patients for the control of infection in the ICU were performed totalizing 303 follow up for pharmacokinetic purposes during the period in the ICU for 32 burn patients. Dose adjustment was required in 88% of vancomycin prescription, 65% for cefepime, 52% for sulphamethoxazole, 74% for fluconazole e 19% for imipenem. High pharmacokinetic variability was registered for all agents investigated. In addition, significant changes on pharmacokinetic parameters were described for imipenem, fluconazole, sulphamethoxazole and vancomycin for burn patients with dialytic renal dysfunction compared to those with renal function preserved. PK-PD modeling applied to antimicrobials investigated in the present study was based on predictive parameters recommended like time interval to maintain drug plasma concentration higher than the minimum effective concentration (%&#916; T> MIC) for cefepime and also for imipenem, oxacillin and piperacillin; AUCss0-24/MIC plus Cssmax/MIC for ciprofloxacin, AUCss0-24/MIC for fluconazole and vancomycin, and finally, AUCss0-24/MIC plus %&#916; T> MIC for sulphamethoxazole. Conclusions: High pharmacokinetic variability was obtained for all investigated agents. PK-PD modeling applied could justify definitively the antimicrobial therapy dose adjustment instead the empirical dose regimen. Then, drug efficacy was guaranteed against susceptible microbial, spreading to susceptible to antimicrobial dose dependent and also those presenting high value for MIC related to microbial resistance to empiric dose regimen. In conclusion, it was demonstrated that PK-PD modeling of antimicrobials with basis on predictive drug efficacy parameter is definitively an important tool to preserve and safeguard these agents for the control of severe infection in burn patients, to avoid the bacterial emergency and microbial resistance.

Análise semiquantitativa do parênquima distal de pulmões obtidos em autópsia de vítimas de morte por ação do fogo e por sufocação, foi feita para avaliar as alterações em bronquíolos e tecido alveolar (ductos e alvéolos). A análise discriminante dos parâmetros obtidos permitiu classificação de 74% / A semiquantitative analysis of the distal parenchyma in lung autopsies of victims of death by fire and death by suffocation, was done to evaluate the changes in membranous bronchiolar and alveolar tissue (alveolar ducts and alveoli). The discriminant parameters obtained permitted classification of 74% of cases

Ainda que resulte na sobrevida do paciente, o tratamento atual de queimaduras profundas e extensas é imperfeito. A contratura cicatricial e o aspecto rendilhado persistentes na área enxertada produzem resultados estéticos e funcionais pobres. A principal dificuldade no adequado restabelecimento do tegumento destes pacientes é o déficit de derme, decorrente da reposição das perdas com enxertos relativamente finos. Neste trabalho são relatados quatro casos, decorrentes da familiaridade obtida em nossa prática clínica com o emprego de pele preservada em glicerol, nos quais foi utilizada a enxertia combinada, isto é, derme alógena residual sobreposta por enxertos de espessura parcial autógenos, como forma de reposição de matriz dérmica. Os tegumentos resultantes da enxertia combinada mostraram-se estáveis e duráveis, dentro do período de seguimento dos casos apresentados. / Although it results in the patient\'s survival, the current treatment of deep and extensive burns is imperfect. Scar contracture and the persistent lacy aspect in the grafted area produce aesthetic and functional poor results. The main difficulty in the appropriate re-establishment of the tegument of these patients is the deficit of dermis, due to the replacement of the skin losses with relatively thin grafts. In this work, decurrent of the familiarity obtained in our clinical practice with glycerol preserved cadaver skin, four cases are reported, which the combined grafting was used, that is, residual allogeneous dermis put upon by split thickness autogenous grafts, as form of replacement of dermal matrix. The resulting teguments of the combined grafting were shown stable and durable, inside the follow-up period of the presented cases.

Introdução: as sequelas de queimaduras na morfologia, mobilidade das estruturas motoras orais e nas funções orofaciais, como mastigação, deglutição e fala, são frequentes em pacientes com queimaduras graves na região de cabeça e pescoço. Objetivo: verificar a efetividade de um programa de reabilitação fonoaudiológica da motricidade orofacial em pacientes com queimaduras em cabeça e pescoço. Método: participaram da pesquisa 29 indivíduos encaminhados para avaliação e reabilitação ao Ambulatório de Funções da Face da Divisão de Fonoaudiologia do Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, no período de abril de 2016 a abril de 2018. Os critérios inclusão adotados na pesquisa foram: idade > = 6 anos; queimadura de terceiro grau caracterizada por perda epidérmica e dérmica em áreas de cabeça e pescoço; realização de tratamento cirúrgico prévio da ferida; ausência de falhas dentárias; presença de queixas relacionadas às alterações motoras orais; quadro clínico estável (conforme registros em prontuários médicos); alimentação por via oral exclusiva. Os pacientes foram divididos em dois grupos considerando o tempo da queimadura: Grupo 1 (G1) - pacientes com até um ano após a queimadura; Grupo 2 (G2) - pacientes com mais de um ano após a queimadura. A gravidade da queimadura foi determinada pela escala ABSI (The Abbreviated Burn Severity Index), aplicada no primeiro atendimento hospitalar do paciente. Todos os participantes foram submetidos à avaliação fonoaudiológica em dois momentos distintos, pré e pós-programa terapêutico. A avaliação foi composta pelos seguintes protocolos clínicos: Avaliação Miofuncional Orofacial com Escores Expandido (AMIOFE-E), verificação da amplitude mandibular (abertura oral máxima, lateralização para a direita e esquerda e protrusão mandibular) e medida antropométrica do canto de olho à comissura labial. O programa terapêutico adotado foi composto por 8 sessões semanais individuais, com duração de trinta minutos cada. O programa terapêutico foi composto por: manobras de compressão e alongamento em tecido cicatricial, manobras de alongamento intra e extra orais dos músculos da face, exercícios para mobilidade da musculatura da face e região cervical e exercícios para a adequação das funções de mastigação e deglutição. Resultados: a análise estatística evidenciou que o G2 apresentou idade significativamente maior que o G1. Nas análises intragrupos, tanto G1 quanto G2 apresentaram diferenças estatísticas para todos os itens do AMIOFE-E: aparência e condição postural; mobilidade e funções orofaciais (mastigação e deglutição). Quanto às medidas de amplitude mandibular, ambos os grupos apresentaram aumento significativo da medida de abertura oral máxima. Nas análises intergrupos, não foram observadas diferenças significativas entre G1 e G2, indicando que a melhora foi semelhante para ambos os grupos. Conclusão: a pesquisa comprova a eficácia do programa fonoaudiológico, baseado em evidências e com controle de resultados, em pacientes com queimaduras de terceiro grau em cabeça e pescoço. Os resultados demonstraram que ambos os grupos apresentaram melhora significativa na atividade miofuncional oral e na amplitude mandibular. Quando comparados os resultados obtidos entre G1 e G2, não foi observada diferença relevante, indicando que o tratamento proposto foi eficiente, independentemente do tempo entre a queimadura e o início do tratamento / Introduction: alterations in the morphology and mobility of the oral motor structures, and orofacial functions (i.e. mastication, swallowing and speech) are often observed in patients who suffered severe head and neck burns. Purpose: the purpose of the present study was to verify the effectiveness of a myofunctional orofacial rehabilitation program for patients with head and neck burns. Method: participants of this study were 29 individuals referred to the Division of Orofacial Myology of Instituto Central do Hospital das Clínicas of the School of Medicine, University of São Paulo, between April 2016 and April 2018, for oral motor assessment and rehabilitation. Inclusion criteria were as follows: age >= 6 years; third degree burns to the head and neck (i.e. epidermal and dermal loss); previous surgical treatment to the wound; complete dentition; oral motor alterations deficits; medical stability (according to medical records); receiving all nutrition by mouth. Patients were divided in two groups according to the onset of the injury: Group 1 (G1) - patients with injuries less than a year old; Group 2 (G2) - patients with injuries more than a year old. Burn severity was determined by the ABSI (The Abbreviated Burn Severity Index) according to the patient\'s first hospital record. All participants underwent clinical assessment that involved an oral motor evaluation (Expanded Protocol of Orofacial Myofunctional Evaluation with Scores - OMES-E), the assessment of the mandibular range of movements (maximal incisor distance, right and left lateral excursions and protrusion) and an anthropometric assessment (measurement of the distance between the commissures of mouth and the corners of the eyes). For comparison purposes, assessments were performed pre and post-treatment. The rehabilitation program involved 8 individual 30 minute weekly sessions. The rehabilitation program involved: compression and stretching maneuvers on the scar tissue; intra and extra oral stretching maneuvers of the facial muscles; facial and cervical muscles mobility exercises; mastication and swallowing exercises. Results: the statistical analysis indicated that G2 was significantly older than G1. When comparing pre and post-treatment results, both group of patients presented significant differences considering the items on the OMES-E (i.e. appearance and posture, mobility and orofacial functions), and the maximal incisor opening. The analysis comparing the performance of G1 and G2 did not indicate differences between the groups. Conclusion: The results of the study indicated that the rehabilitation program was effective for third degree burns on the head and neck, demonstrating significant improvement of the oral myofunctional parameters and of the maximal incisor opening. The results also suggest that the maturation of the scar tissue did not have an influence on the results of the treatment program

Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgico / Queimaduras podem causar substancial morbidade e contraturas devido à hiperproliferaÃÃo fibroblÃstica. O imiquimode, imunomodulador utilizado em doenÃas virais e neoplasias cutÃneas, promove resposta imune inata e adaptativa, interagindo com Toll-Like Receptors, permitindo reconhecer antÃgenos e cÃlulas invasoras, ativando cÃlulas de Langerhans e citocinas endÃgenas capazes de suprimir a hiperproliferaÃÃo fibroblÃstica, mostrando-se Ãtil no tratamento de cicatrizes hipertrÃficas e quelÃides. Inexistiam trabalhos sobre o imiquimode em queimaduras cutÃneas. Avaliou-se os efeitos do imiquimode na cicatrizaÃÃo de queimaduras utilizando-se mÃtodos macroscÃpicos, microscÃpicos e computacionais. Produziram-se queimaduras dÃrmicas profundas de cada lado da linha mÃdia dorsal em 32 ratos Wistar utilizando um ferro-de-solda modificado aplicado a pele por 9s. Instituiram-se tratamentos 3X/semana a partir do segundo dia pÃs-queimadura (D2PQ). No lado direito (controle) utilizou-se soluÃÃo salina isotÃnica (SAL). à esquerda utilizou-se imiquimode (IMQ) tÃpico 5%. Oito animais foram eutanasiados nos D4, D7, D14 e D21PQ, obtendo-se fotografias digitais e amostras teciduais. Na anÃlise macroscÃpica utilizou-se escala visual analÃgica (EVA), escala de exame clÃnico (EEC) e planimetria digital. Para anÃlises microscÃpicas utilizaram-se amostras coradas pela hematoxilina-eosina (HE) ou picrosirius-red (PR). Nas amostras HE, sob microscopia Ãtica, quantificou-se o tipo e a intensidade da reaÃÃo inflamatÃria e a involuÃÃo temporal do dano tecidual pela atribuiÃÃo de escores. Amostras PR foram analisadas à microscopia de luz polarizada, quantificando-se a densidade do colÃgeno tipo I e tipo III e razÃo colÃgeno I: colÃgeno III (RazÃo I:III). NÃo houve mortes, infecÃÃo nem autocanibalismo. Os parÃmetros biomÃtricos nÃo evidenciaram efeitos deletÃrios sobre o estado nutricional. A EVA favoreceu discretamente o grupo SAL (P=0,0491). A EEC nÃo mostrou diferenÃas significativas. A planimetria digital evidenciou menor velocidade de reparaÃÃo nas feridas do grupo IMQ (P<0,05). A quantificaÃÃo da Ãrea de lesÃo mostrou involuÃÃo similar, exceto no D14PQ onde a Ãrea de necrose era maior no grupo IMQ (P<0,05). A anÃlise histolÃgica qualitativa mostrou um processo reparatÃrio mais lentificado no grupo IMQ em todos os tempos. No D7PQ, a intensidade da reaÃÃo inflamatÃria foi classificada como discreta em 50% das feridas do grupo SAL e intensa ou moderada em 75% do grupo IMQ (P<0,005). No D21PQ a inflamaÃÃo foi mais extensa no grupo IMQ (P<0,005). Observou-se que 50% das feridas do grupo SAL exibiam reaÃÃo inflamatÃria subaguda e 37,5% crÃnica, enquanto nenhuma ferida do grupo IMQ mostrava inflamaÃÃo crÃnica no D7PQ (P<0,005). No D21PQ a inflamaÃÃo no grupo IMQ era subaguda (68,75%) e no grupo SAL 56,25% era crÃnica (P<0,05). A morfometria do colÃgeno evidenciou aumento do colÃgeno tipo I e diminuiÃÃo do colÃgeno tipo III nos dois grupos. A razÃo colÃgeno I: colÃgeno III foi menor no grupo IMQ em D4 e D21PQ (P<0,05). O modelo reproduziu queimaduras dÃrmicas, preservando anexos essenciais à reepitelizaÃÃo. A picrossirius-polarizaÃÃo foi eficaz no reconhecimento do colÃgeno e os mÃtodos computacionais foram eficientes, identificando diferenÃas mÃnimas no processo lesÃo-reparaÃÃo. O imiquimode foi eficaz em promover o processo inflamatÃrio e retardar a maturaÃÃo, gerando menor quantidade de fibrose / Burns can result in substantial morbidity because of fibroblastic hyperproliferation and contracture. Imiquimod is a immunomodifier -TLR-7 agonist used in viral diseases and in neoplastic conditions like actinic keratosis, melanoma, and non-melanoma skin cancer. It acts by promoting endogenous cytokines known to suppress fibroblast proliferation. A new recent use is in treating keloids and hypertrophic scars to reduce scarring. No study of the effect of imiquimod on cutaneous burns has been performed. This study examined burn healing in the presence of topical imiquimod by evaluation of wound appearance, computer-aided image analysis, and histology in a rat model. Standardized partial-thickness burns were produced on the dorsum of thirty-two Wistar rats. Right-sided wounds received therapy with isotonic saline (sham). Left-sided wounds were treated with imiquimod cream at 5% (IMQ). This was repeated 3 times/week after injury. Euthanasia was performed at 4th, 7th, 14th and 21st Postburn days (PBD). Wounds were harvested for histological analysis. Evaluation of wound appearance was performed using clinical assessment scale (CAS) and a visual analogue scale (VAS). Scars area and perimeter were measured using digital planimetry to assess wound edge migration by Gilmanâs modified Equation. Inflammation type and intensity was graded by histological scale. Collagen type was identified by picrosirius-polarization and morphometric analysis was performed. VAS scores showed discretally improved appearance in the imiquimod-treated wounds versus the saline-treated control at PBD21 (P=0.0491). There was no difference in CAS scores. Wound edge migration was significantly slowest in imiquimod-treated wounds (p<0.05). Histological evidence of partial thickness dermal injury with sparing of dermal appendage epithelial cells was seen in all wounds. Histologic characteristics of gradually diminished injured area between groups were similar except in imiquimod-treated wounds at PBD14 (p<0.05). Inflamattory state was bigger in imiquimod-treated wounds at PBD7 and PBD21 (p<0.005). At PBD7 there was no chronic-type of inflammatory reaction in imiquimod-treated group, although in saline-treated group chronic plus sub-acute type was present in 87.5% (p<0.005). At PBD21 68.75% of imiquimod-treated group showed acute plus subacute inflammatory state, and saline-treated group displayed chronic-type in 56.25% of the wounds. The total amount of collagen increased in both groups throughout all time points. Morphometry showed an inversed ratio type I to type III collagen. Ratios of type I collagen to type III collagen was much lower in imiquimod-treated wounds at PBD4 and PBD21. Topical treatment with Imiquimod 5% cream for partial-thickness burn wounds 3 times/week courses do not improve clinical appearance and scarring during late healing. There is no difference in histology during the short-term healing process. Computer-aided image proccessing was efficient to evaluate burned-wound healing. Wound healing and fibrosis was impaired in imiquimod- treated wound group