Orientador: Maria Elvira Pizzigatti Corrêa / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-28T03:50:50Z (GMT). No. of bitstreams: 1 Vieira_RaizaMeira_M.pdf: 2654950 bytes, checksum: 493dac1ecf0ca2acb92f0ff8829107aa (MD5) Previous issue date: 2015 / Resumo: Complicações orais estão presentes em cerca de 80% dos pacientes durante o Transplante de Células Tronco Hematopoéticas (TCTH), sendo a mucosite oral (MO) e as alterações salivares umas da que possuem maior impacto para a qualidade de vida do paciente. A utilização do perfil proteico salivar (PPS) na abordagem diagnóstica em diversas doenças tem sido frequente. A identificação de um PPS que auxilie o entendimento das manifestações agudas orais do TCTH poderia sobremaneira, influenciar nas decisões terapêuticas visando melhora no manejo do paciente. O objetivo deste trabalho foi identificar alterações do PPS do início do regime do condicionamento pré TCTH até a recuperação medula e correlacioná- las com dados clínicos orais. Para tanto, foi utilizado o banco de dados de proteomica salivar do grupo de Odontologia do Hemocentro, encontrada por Feio et AL (2013). Nesta avaliação foram incluídos 16 pacientes submetidos ao primeiro TCTH alogênico na Unidade de Transplante de Medula Óssea do Hospital de Clínicas da UNICAMP. As amostras de saliva total não estimulada (STNE) foram coletadas em dois momentos: previamente ao condicionamento (coleta A) e a segunda (coleta B), entre os dias D+8 e D+10 pós-TCTH. Dados sobre saúde oral, grau de MO foram coletados, além da avaliação de hiposalivação. O estudo do PPS foi realizado por espectometria de massas no LNBio. Os PPS das duas coletas, A e B foram tabelados no programa Excel® 2007 (Microsoft, WA, EUA), juntamente com os dados clínicos. O teste T pareado foi utilizado para a comparação entre os PPSs com os tempos das coletas. Os critérios clínicos de hiposalivação foram comparados com as divergências proteicas durante as duas coletas por ANOVA. A comparação entre os dados clínicos de cada coleta e seu respectivo PPS, foi feito pelo teste T pareado, sendo considerado significativo p<0,005. Sete proteínas apresentaram intensidades divergentes entre as coletas A e B: Prolactin-inducible protein, Alpha-Amylase 1, Cystatin-SN, Submaxillary gland androgen-regulated protein 3B, Sthaterin, cDNA FLJ60163, highly similar to Carbonic anhydrase 6 apresentaram-se em decréscimo na coleta B comparada a coleta A e a vitamin D-binding protein isoform 1 precursor se apresentou aumentada na coleta B quando comparada a coleta A. A mucosite oral foi correlacionada com as proteinas, Immunoglobulin J chain, Pulative uncharacterized protein DKFZp686N02209 que se demonstraram com intensidade diminuída naqueles pacientes que apresentaram graus III e IV em comparação àqueles com grau 0¿II de MO; a proteína Statherin esteve presente em maior intensidade naqueles pacientes que apresentaram MO com grau III e IV. Esses resultados podem estar relacionados principalmente à toxicidade do regime de condicionamento mieloablativo nas glândulas salivares e sugerem que as proteinas Statherin, Immunoglobulin J chain e Pulative uncharacterized protein DKFZp686N02209 podem ser candidatas a um painel de PPS para a MO no TCTH / Abstract: Hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematological diseases. Oral Complications are present in about 80% of patients who undergo to HSCT. Oral mucositis (OM), oral infections and salivary changes, among others are the most common oral clinical founds in the acute phase of the HSCT. The use of salivary profile as a tool for diagnosis and management of treatment responses has been shown a promising future in different clinical settings. Thus the discovery of a salivary protein profile (SPP) of patients submitted to the allogeneic HSCT during the acute phase of the transplantation may be helpful on the management of the oral effects of the HSCT. The aim of this research was to identify the SPP changes during the acute phase of allogeneic HSCT and correlate them with the oral clinical manifestation of the acute phase of HSCT. This study enrrolled 16 patients with hematological diseases who, underwent to their first allogenic HSCT at the Bone Marrow Transplantation Unit ¿ UNICAMP. Unstimulated salivary samples were collected in two periods: first (collection A), it was performed prior the initiation of the conditioning regimen for the HSCT and collection B; performed between day D+8-10 days after HSCT. Oral health indices were obtained in both moments of the saliva collection. The severity of oral mucositis was collected on the collection B. The PPS analysis was performed by mass spectrometry on a previous study performed by Feio et al (2013). Student T test paired was used in order to between the 39 identified proteins equally between the collections A and B. Clinical correlations were also compared to the different PPS using one-way ANOVA analysis. For both comparisons, considered significant p < 0.05. Among the collections A and B, 7 proteins were presented with differing intensities: Prolactin-inducible protein, Alpha-Amylase 1, Cystatin SN, Submaxillary gland androgen-regulated protein 3B, Sthaterin, cDNA FLJ60163 Similar to highly Carbonic anhydrase 6 showed a decrease intensity in the collection B and the vitamin D-binding protein isoform 1 precursor quantity showed a increased in the collection B. Three proteins were shown altered intensity when correlated with the severity of OM: Immunoglobulin J chain, Pulative uncharacterized protein DKFZp686N02209v. These proteins showed a decreased of intensity in those patients grade III-IV OM when compared to patients with grade 0-II OM. The protein Statherin showed in increased intensity in patients with OM grade III-IV. These results indicate the influence of the toxicity of the conditioning regimens on the salivary protein profiles in the acute phase of the HSCT. The proteins: Immunoglobulin J chain, Pulative uncharacterized protein DKFZp686N02209v and Statherin might be a potential candidates for a panel of salivary biomarkers for OM / Mestrado / Estomatologia / Mestra em Estomatopatologia

Les infections fongiques sont une complication fréquente des patients d’hématologie et en particulier des patients ayant reçu un greffe de cellules souches hématopoïétiques (CSH). L’objectif de ce travail était d’identifier les facteurs de risque d’infections fongiques intrinsèques et la transmission.Nous avons d’abord étudié l’aspergillose invasive (AI) qui est l’infection fongique la plus fréquente chez les greffés de CSH en croisant les données du registre européen des greffés ProMise et la base de données de l’étude prospective SAIF. Nous avons mené une étude cas-témoins nichée dans une cohorte de 185 cas et 651 témoins appariés. Les facteurs associés à la survenue d’une aspergillose étaient l’irradiation corporelle totale, une GvH aiguë de grade ≥2 et la rechute de l’hémopathie. Trente-cinq cas étaient précoces (<J40), 33 tardifs (entre J40 et J100) et 117 très tardifs (>J100). Le facteur associé à la survenue d’une AI précoce était l’absence de prise de greffe. Le facteur associé à la survenue d’une AI tardive était la GvH aiguë de grade 3-4. Les facteurs associés à la survenue d’une AI très tardive étaient la GvH aiguë de grade ≥2, la rechute et la neutropénie secondaire. Tous les facteurs pré-greffe étaient effacés par les facteurs post-greffe.Puis nous avons étudié la transmission d’infection fongique par l’étude d’une épidémie de pneumocystose survenue dans le service. Douze cas de pneumocystose sont survenus en 7 mois dans le service soir beaucoup plus qu’au cours des années précédentes. L’analyse moléculaire a permis de montrer que 4 cas appartenaient au même génotype, qui est un génotype rare jamais décrit dans une série de plus de 300 génotypes en Europe. La carte de transmission a permis de constater que ces 4 patients se sont rencontrés uniquement en hôpital de jour. Cette étude est la première démonstration moléculaire d’une épidémie de pneumocystose dans un service d’hématologie. / Fungal infections are a common complication of hematology patients and especially in hematopoietic stem cell transplantation (HSCT) recipients. The objective of this work was to identify intrinsic risk factors for fungal infections and transmission.We first studied invasive aspergillosis (IA), which is the most common fungal infection after HSCT by crossing data from the European HSCT registry ProMise and the prospective study database SAIF. We conducted a nested case-control study in a cohort of 185 cases and 651 matched controls. Factors associated with onset of aspergillosis were total body irradiation, acute GVHD grade ≥2, and relapse of the underlying disease. Thirty-five IA were early (<D40), 33 late (between D40 and D100) and 117 very late (> D100). The factor associated with the occurrence of an early IA was the absence of engraftment. The factor associated with the occurrence of late IA was acute grade 3-4 GvH. Factors associated with the occurrence of very late IA were acute GVHD grade ≥2, relapse, and secondary neutropenia. All pre-transplant factors were supplanted by post-transplant factors.Then we studied the transmission of fungal infection by studying a pneumocystosis outbreak occurring in the hematology department. Twelve cases occurred within 7 months. Molecular analysis showed that 4 of them belonged to the same genotype, which is a rare genotype never described in a series of more than 300 genotypes in Europe. The transmission map permitted to identify that these 4 patients met only in the daycare center. This study is the first molecular demonstration of a pneumocystis outbreak in a hematology ward.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22359号 / 医博第4600号 / 新制||医||1042(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 長尾 美紀, 教授 滝田 順子, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

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This article provides a brief review of the pathophysiology of osteoarthritis and the ontogeny of chondrocytes and details how physical exercise improves the health of osteoarthritic joints and enhances the potential of autologous chondrocyte implants, matrix-induced autologous chondrocyte implants, and mesenchymal stem cell implants for the successful treatment of damaged articular cartilage and subchondral bone. In response to exercise, articular chondrocytes increase their production of glycosaminoglycans, bone morphogenic proteins, and anti-inflammatory cytokines and decrease their production of proinflammatory cytokines and matrix-degrading metalloproteinases. These changes are associated with improvements in cartilage organization and reductions in cartilage degeneration. Studies in humans indicate that exercise enhances joint recruitment of bone marrow-derived mesenchymal stem cells and upregulates their expression of osteogenic and chondrogenic genes, osteogenic microRNAs, and osteogenic growth factors. Rodent experiments demonstrate that exercise enhances the osteogenic potential of bone marrow-derived mesenchymal stem cells while diminishing their adipogenic potential, and that exercise done after stem cell implantation may benefit stem cell transplant viability. Physical exercise also exerts a beneficial effect on the skeletal system by decreasing immune cell production of osteoclastogenic cytokines interleukin-1β, tumor necrosis factor-α, and interferon-γ, while increasing their production of antiosteoclastogenic cytokines interleukin-10 and transforming growth factor-β. In conclusion, physical exercise done both by bone marrow-derived mesenchymal stem cell donors and recipients and by autologous chondrocyte donor recipients may improve the outcome of osteochondral regeneration therapy and improve skeletal health by downregulating osteoclastogenic cytokine production and upregulating antiosteoclastogenic cytokine production by circulating immune cells.

Granulocyte colony-stimulating factor (GCSF) is currently the most widely used cytokine for stem cell mobilization. There are few studies suggesting GCSF administration may induce activation of both coagulation and endothelial cells that could favor the developing of thrombotic events. We report a 58-year-old female with vasculitis and renal impairment. She was found to have an underlying monoclonal gammopathy of unknown significance (MGUS). The monoclonal protein was felt to play a role in her underlying renal disease and peripheral neuropathy. She was considered a candidate for peripheral blood stem cell transplantation to manage the monoclonal protein. During stem cell mobilization with GCSF, she developed worsening of anemia; thrombocytopenia and worsening of renal function. She was diagnosed with thrombotic microangiopathy (TMA) which was successfully treated with therapeutic plasma exchange and rituximab. It is possible that GCSF may have directly (activating endothelial cells) or indirectly (activation of underlying autoimmune disorder) contributed to TMA in this patient.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18857号 / 医博第3968号 / 新制||医||1008(附属図書館) / 31808 / 京都大学大学院医学研究科医学専攻 / (主査)教授 前川 平, 教授 江藤 浩之, 教授 河本 宏 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第20618号 / 医博第4267号 / 新制||医||1023(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 髙折 晃史, 教授 羽賀 博典, 教授 江藤 浩之 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Introduktion: Patienter med hematologisk cancer kan genomgå en stamcellstransplantation som behandling för att få nya blodbildande stamceller. Målet med transplantationen samt cytostatikabehandling är överlevnad för patienten och att bota malignitet.  Syfte: Att studera patienter med hematologisk cancer och deras upplevelser av att genomgå stamcellstransplantation.  Metod: En deskriptiv litteraturöversikt där 11 kvalitativa studier har granskats. Litteratursökningen gjordes via databaserna CINAHL och PubMed. Kvalitetsanalysen genomfördes med hjälp av SBU:s kvalitetsgranskningsmall. Resultatanalysen genomfördes enligt Fribergs femstegsmodell.  Resultat: Många negativa aspekter framkom men även positiva upplevelser inom några underkategorier. Många av deltagarna upplevde biverkningarna som begränsande, däribland fatigue som även kunde påverka dem en tid efter behandlingens slut. Flertalet kände sig rädda för att dö och återinsjukna i sjukdomen. Stöd från anhöriga, vårdpersonal och patienter var viktigt för att orka ta sig igenom behandlingsperioden. Skyddsisoleringen upplevdes av de flesta som jobbig, men kunde även kännas som en säker miljö för vissa. En övervägande andel av deltagarna var i behov av mycket information såväl inför som under stamcellstransplantationen. Slutsats: Personer som genomgår en stamcellstransplantation på grund av hematologisk cancer kan påverkas på många olika sätt, mestadels negativt där rädsla var förekommande. Biverkningar påverkade även återgången till vardagen. Skyddsisoleringen upplevdes av många som påfrestande och begränsande. Behovet av information var individuellt. Stöd var för många patienter det som underlättade behandlingen mest. Sjuksköterskan behöver därför individanpassa vården utifrån patientens behov och resurser. / Introduction: Patients with hematological cancer can undergo stem cell transplantation as a treatment to get new blood-forming stem cells. The goal with transplantation and chemotherapy is survival and to cure malignancy.  Purpose: To study the experience of patients with hematological cancer undergoing hematopoietic stem cell transplantation.  Method: A descriptive literature review where 11 qualitative studies have been reviewed. The literature search was made via the databases CINAHL and PubMed. The quality analysis is based on the quality review template by SBU. The result analysis was conducted according to Friberg’s five-step model.  Results: Many negative aspects emerged, but there were also positive experiences in some of the subcategories. Many of the participants experienced that side effects were limiting, including fatigue that could remain and affect them months after treatment. Several participants felt scared of dying or falling ill again. Support from relatives, nursing staff and patients was an important part to cope with treatment. Protective isolation was experienced by most as difficult, but could for some feel like a safe environment. A predominant part of the participants had the need of being well informed before and during stem cell transplantation.  Conclusion: Patients undergoing stem cell transplantation because of hematological cancer are affected by the treatment in several ways, mostly negative and fear was common. Side effects also affected returning to everyday life. Protective isolation was experienced as stressful and limiting. The need of information was individual. Social support was for many patients what helped to ease treatment most. Nurses therefore need to personalize the care of these patients, from their needs and resources.

Aim: To determine if a significant relationship exists between bloodless medicine practices and decreased infection rates in oncology patients following hematopoietic stem cell transplantation by performing a literature review. Background: It is not uncommon for healthcare professionals to encounter Jehovah's Witnesses (JW) seeking medical treatment in the acute care hospital setting and outpatient clinics alike. However, JW's pose a unique challenge to healthcare providers. Their refusal of blood transfusions makes them a population of interest within the medical community. The refusal of blood transfusions also poses a serious challenge to successful treatment in oncology JW patients, and many hospitals will refuse to perform a procedure as complex yet beneficial as a hematopoietic stem cell transplant in this population. Methods: An extensive electronic literature search in the CINAHL Plus database was completed and included the keywords infection, blood transfusion, stem cell transplant, bloodless medicine, Jehovah's Witnesses, and transfusion reactions. The available literature was carefully examined for interventions performed and compared for ultimate results to be finalized as a written report. Significance: The results of this research can not only optimize healthcare for the population of Jehovah's Witnesses, but also assist in reduced blood transfusions and improved cost management in all patients with a cancer diagnosis. Conclusions: All studies concluded that autologous hematopoietic stem cell transplantation can be performed safely without the use of blood products. Their conclusion was based off of the data they collected following patients post-stem cell transplant. More research is needed to explore outcomes in this population as a result of blood transfusion refusal following stem cell transplantation in comparison with those who receive blood transfusion support.