Orientador: Jose Geraldo P. Ferraz / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T17:03:45Z (GMT). No. of bitstreams: 1 Coppi_LucianeCristina_D.pdf: 5991264 bytes, checksum: bbcad7dd36b02092b27ac1c30b751988 (MD5) Previous issue date: 2004 / Resumo: Os eosinófilos estão envolvidos na patogênese de várias doenças inflamatórias crônicas? incluindo doenças inflamatórias intestinais (Dll)? como doença de Crohn (DC) e retocolite ulcerativa inespecífica (RCVI). No entanto? ainda é desconhecido como os eosinófilos contribuem para a patogênese das Dll. Portanto? o objetivo deste estudo foi avaliar a atividade dos eosinófilos isolados de sangue periférico de pacientes com Dll comparada aos voluntários sadios. Eosinófilos dos voluntários sadios (n=5)? com DC (n=5) e RCVI (n=5) foram purificados usando-se um gradiente de Percoll? seguido de separação imunomagnética. A atividade dos eosinófilos foi avaliada usando-se os ensaios de quimiotaxi~ adesão? liberação de peroxidase do eosinófilo (EPO)? citometria de fluxo? contagem histológica e análise morfométrica. A quimiotaxia dos eosinófilos induzida pelo N-formyl-metionyl-Ieucyl-fenilanina(fMLP) foi significativamente maior para as células isoladas de pacientes com DC e RCVI? quando comparada aos voluntários sadios.A adesão basal dos eosinófilos de pacientes com DC aumentou significativamente para fibronectina ou soro? quando comparada aos voluntários sadios e RCVI. A liberação basal e estimulada de EPO foi reduzida em células de pacientes com DC? quando comparada aos voluntários sadios. Entretanto? em células isoladas de pacientes com RCVI? a liberação de EPO basal foi significativamente maior quando comparada aos voluntários sadios. A expressão das moléculas de adesão macrophage-l antigen (Mac-l) e very late antigen 4 (VLA-4) não apresentou diferença em relação aos voluntários sadios. A contagem histológica dos eosinófilos em tecido intestinal e morfométrica dos grânulos destas células mostrar~ respectivamente? aumento significativo do número de eosinófilos e de seus grânulos em pacientes com DC e RCVI quando comparadas aos voluntários sadios. Nossos resultados sugerem que os eosinófilos periféricos estão pré-ativados em pacientes com Dll. A ativação dos eosinófilos periféricos? seguida da migração para o tecido intestinal deve contribuir para a patogênese das Dll / Abstract: Eosinophils are involved in the pathogenesis of several chronic inflammatory diseases, including inflammatory bowel disease (ffiD), as Crohn's disease (CD) and ulcerative colites (DC). However, how activation of intravascular eosinophils contributes to disease activity or ffiD pathogenesis is still unknown. The aim of this study was to investigate if eosinophils isolated ITomperipheral blood ITomffiD patients are activated compared to healthy volunteers. Eosinophils ITomhea1thyvolunteers (n=5), CD (n=5) and DC patients (n=5) were purified using a Percoll gradient followed by immunomagnetic cell separator. Eosinophil activity was investigated using chemotaxis, adhesion and mediator release assays (eosinophil peroxidase, EPO), flow cytometric, histologic counting and morphometric analysis. -formyl-metionyl-Ieucyl-fenilanina (fMLP) induced eosinophil chemotaxis was significandy augmented in cells isolated from CD and DC patients compared to hea1thyvolunteers. Eosinophil basal adhesion of CD significantlyincreased to fibronectin or serum if compared to DC or hea1thyvolunteers. Basal and stimulated EPO release was reduced in cells ITomCD patients compared to hea1thyvolunteers. However, basal EPO release was significantly enhanced in cells isolated from DC patients when compared to hea1thy volunteers. The expression of adhesion molecules macrophage-l antigen (Mac-l) and very late antigen 4 (VLA-4) isn't different in patients with DC and CD compared to hea1thyvolunteers. Histologic counting of eosinophils in intestinal tissue and morphometric analysis of granules of this cells showed, respectively, significant augmentation in the number of eosinophils and its granules in CD and DC patients compared to hea1thy volunteers. Our results suggest that peripheral eosinophils are preactivated in ffiD patients. Activation of peripheral eosinophils followed by migration to intestinal tissue probably contributes to ffiD pathogenesis / Doutorado / Ciencias Basicas / Doutor em Clínica Médica

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / VÃrios distÃrbios neurolÃgicos foram observados em pacientes com doenÃa inflamatÃria intestinal (DII), porÃm sua prevalÃncia exata à desconhecida. Estudamos prospectivamente a incidÃncia e a prevalÃncia das manifestaÃÃes neurolÃgicas em uma coorte de 82 pacientes com DII (protocolo 1) e a presenÃa e gravidade de tremor em pacientes com DII e voluntÃrios sadios (Protocolo 2). Os pacientes do protocolo 1 foram avaliados no ambulatÃrio de DII do Hospital Walter CantÃdio por um perÃodo de pelo menos 1 ano, realizando avaliaÃÃes neurolÃgicas completas periÃdicas. O segundo protocolo consistiu na quantificaÃÃo de tremor em espirais de Arquimedes realizadas por pacientes com doenÃa de Crohn (DC, N=31), retocolite ulcerativa (RCU, N=63) e voluntÃrios sadios (N=41) por um neurologista especializado em distÃrbios de movimento (Dr. Elan Louis, Columbia University, Nova Iorque). Polineuropatia de fibras grossas sensitivas ou sensitivo-motoras foi observada em 16,1% dos pacientes com DC e 19,6% dos pacientes com RCU, sendo usualmente leve, predominantemente simÃtrica, distal e axonal. SÃndrome do tÃnel do carpo foi observada comumente em mulheres com RCU. Sintomas sensitivos sem anormalidades eletromiogrÃficas, sugestivos de neuropatia de pequenas fibras ou mielopatia subclÃnica, foram observados em 29% dos pacientes com DC e 11,8% com RCU. ApÃs excluir outros fatores etiolÃgicos ou contributÃrios para polineuropatia, 13,4% dos pacientes com doenÃa inflamatÃria intestinal apresentaram polineuropatia de fibras grossas ou fibras finas (7,3% com polineuropatia de fibras grossas sensitivo-motoras). CefalÃia nÃo debilitante foi a queixa neurolÃgica mais comum, 3 pacientes apresentaram acidente vascular cerebral isquÃmico, 5 epilepsia e 1 corÃia transitÃria. Pacientes com DII apresentaram menor quantidade de tremor que os voluntÃrios sadios devido ao menor uso de cafeÃna. Nos pacientes com DC, houve correlaÃÃo significativa entre a nota do tremor, uso de medicaÃÃes com aÃÃo sobre o sistema nervoso central, uso e quantidade de cafeÃna e presenÃa de doenÃas neurolÃgicas. Em pacientes com RCU, sà houve correlaÃÃo significativa entre a nota do tremor e idade ou uso/quantidade de cafeÃna ingerida. Em resumo, pacientes com RCU e DC apresentam uma vasta gama de manifestaÃÃes neurolÃgicas que sÃo com freqÃÃncia clinicamente negligenciadas / Several neurological disorders have been described in inflammatory bowel disease (IBD) patients, but their exact prevalence is unknown. We prospectively studied the prevalence and incidence of neurological disorders in a cohort of 82 patients with IBD (protocol 1) and the presence and severity of tremor in patients with IBD or healthy volunteers (Protocol 2). Patients from protocol 1 were evaluated at the IBD Clinic from the Hospital Walter CantÃdio for at least one year, with complete periodic neurological evaluations. The second protocol consisted in quantifying the amount of tremor in Archimedes spirals from patients with CrohnÂs disease (CD, N=31), ulcerative colitis (UC, N=63) and healthy volunteers (N=41) by a neurologist specialized in movement disorders (Dr. Elan Louis, Columbia University, New York City). Sensory or sensorimotor large-fiber polyneuropathy was observed in 16.1% of the patients with CD and 19.6% of the patients with UC. Neuropathy was usually mild, predominantly distal, symmetric, and axonal. Carpal tunnel syndrome was more commonly observed in women with UC. Sensory complaints without electrodiagnostic (EMG) abnormalities suggestive of small fiber neuropathy or subclinical myelopathy were observed in 29% of the patients with CD and 11.8% of the patients with UC. After excluding other etiological or contributory factors for the development of neuropathy, still 13.4% of the IBD patients had large or small fiber neuropathy (7.3% had large-fiber polyneuropathy). Non-debilitating headache was the most common neurological complaint, 3 patients had strokes, 5 were diagnosed with epilepsy and one had transient chorea. Patients with IBD had lower scores of tremor in the Archimedes spiral assessment due to decreased caffeine intake. In patients with CD, there was a significant correlation between tremor grade, use of medications with effect on the central nervous system, use and amount of caffeine intake and presence of other neurological conditions. In patients with UC, there was only a significant correlation between tremor grade, age and use and the amount of caffeine intake prior to the evaluation. In summary, patients with CD and UC exhibit a wide range of neurological manifestations that are frequently neglected clinically

No description available.

Introduction: Inflammatory bowel disease (IBD), Crohn’s Disease and ulcerative colitis, are long term conditions which follow a relapsing and remitting pattern. The rising incidence of IBD in adults and children has implications for the lifelong burden of disease and the provision of specialist services. Patients are predominantly managed by secondary care and follow a traditional, scheduled follow-up cycle, which is unsustainable and unsatisfactory. Patients with IBD should have access to specialist care which is delivered according to their values and needs. However few studies have examined patients’ views of follow-up care. There is also concern in the UK that services for patients with long term conditions are not orgnised to promote independence with silo working in primary and secondary care.These may be brought together formally through the development of models of care. Utilization of current out-patient spaces to regularly review stable patients is inappropriate and is challenged by commissioners. The question remains as to what models of follow-up are we able to offer patients which are acceptable and what is the role of the general practitioner (GP) and primary care within this. The aim of this study was to develop an integrated, acceptable, model of follow-up care for patients with IBD.Methods The study follows the development phase of the MRC Framework for complex interventions. A best evidence synthesis was undertaken to identify the follow-up care models in IBD. A meta-synthesis of the health and social care needs of patients with IBD was conducted to explore the impact of living with IBD. Qualitative interviews with 24 IBD patients (18 patients had CD, and 6 UC, age range 27-72 years, disease duration range 2 – 40yr) and 20 GPs purposively selected from across NW England were carried out. Patients were asked about their experience, values and preference of follow-up care. The GPs were questioned about their current and potential role in IBD. Analysis was undertaken using Framework Analysis. The best evidence synthesis, meta-synthesis and interviews were synthesised by an expert panel, Consultant Gastroenterologist, patient, GP, IBD Nurse, to develop the model of follow-up care.Results There were similarities and commonalities between the patient and general practitioner interviews. Patients did not want to be seen when well, GPs wanted more involvement in care and there is scope for an IBD outreach nurse at the interface of primary/secondary care. Discharging quiescent patients into enhanced GP care, to ensure equitable treatment, was acceptable to all, as was the concept of ‘virtual’ clinics. Patients would initiate self referral within the ‘virtual’ arm whilst patients under GP care would be referred back into secondary care as a rapid referral < 7days and not using a new patient tariff. Complex IBD patients would remain under secondary care. A stratified model of follow-up care was developed.Conclusion This study provides an acceptable integrated model of follow-up for patients with IBD. It takes into account the growing incidence of IBD and UK policy to reduce inappropriate follow-up. It emphasises role of self management, the integration of primary and secondary care, placing the patient closer to home whilst allowing secondary care to concentrate on complex patient management.

Introduction: Inflammatory bowel disease is a common, complex relapsing disorder characterised by immune dysregulation, altered intestinal permeability and microbial insult. Limited knowledge is available regarding the metabolic changes observed during progression of the disease, and limited biomarkers of disease available that have been validated and shown to be of sound clinical value. Aim of Study: A two stage metabolomics approach was adopted to determine if metabolic signature profiles, could distinguish inflammatory bowel disease Crohn’s disease (CD) patients from ulcerative colitis (UC) patients and from healthy controls. Methods: A serum metabolomics approach was undertaken to define metabolic changes associated with UC and CD. Serum samples from a discovery study of 30 UC, 30 CD and 29 ethnically, age and gender matched controls were analysed by ultra-performance liquid chromatography mass spectrometry. A subsequent validation study was preformed using 28UC, 31CD, and 29 gender matched controls were also analysed using UPLC-MS.ResultsClasses of metabolites, identified as biologically interesting and at significantly different levels (p<0.05) in comparisons of control and CD and UC cohorts included: steroids and steroid derivatives, phosphocholine, Vitamin D metabolites, fatty acids and conjugates, glycerolipids, isoprenoids, amino acids, and phosphosphingolipids. There were fewer discriminatory metabolites differentiating the CD and UC cohorts. Conclusion: Serum Metabolomic profiling may represent a novel technology which could be used to distinguish individuals with CD from those with UC and healthy controls.

Coral reefs are in decline worldwide and coral disease is a significant contributing factor. However, etiologies of coral diseases are still not well understood. In contrast with the Caribbean, extremely little is known about coral diseases in the Philippines. In 2005, off Southeast Negros Island, Philippines, I investigated relationships between environmental parameters and prevalence of the two most common coral diseases, ulcerative white spot (UWS) and massive Porites growth anomalies (MPGAs). Samples were collected along a disease prevalence gradient 40.5 km long. Principal component analyses showed prevalence of MPGAs was positively correlated with water column nitrogen, organic carbon of surface sediments, and colony density. UWS was positively correlated with water column phosphorus. This is the first quantitative evidence linking anthropogenically-impacted water and sediment to a higher prevalence of these diseases. Histological and cytological alterations were investigated by comparing tissues from two distinct types of MPGA lesions (types 1 and 2) and healthy coral using light and electron microscopy. Skeletal abnormalities and sloughing, swelling, thinning, and loss of tissues in MPGAs resembled tissues exposed to bacterial or fungal toxins. Both lesion types had decreases in symbiotic zooxanthellae, which supply nutrients to corals. Notable alterations included migrations of chromophore cells (amoebocytes) (1) nocturnally to outer epithelia to perform wound-healing, including plugging gaps and secreting melanin in degraded tissues, and (2) diurnally to the interior of the tissue possibly to prevent shading zooxanthellae in order to maximize photosynthate production. Depletion of melanin (active in wound healing) in type 2 lesions suggested type 2 tissues were overtaxed and less stable. MPGAs contained an abundance of endolithic fungi and virus-like particles, which may result from higher nutrient levels and play roles in disease development. Swollen cells and mucus frequently blocked gastrovascular canals (GVCs) in MPGAs. Type 1 lesions appeared to compensate for impeded flow of wastes and nutrients through these canals with proliferation of new GVCs, which were responsible for the observed thickened tissues. In contrast, type 2 tissues were thin and more degraded. Dysplasia and putative neoplasia were also observed in MPGAs which may result from the tissue regeneration capacity being overwhelmed.

INTRODUCTION: The inflammation observed in patients with IBD can negatively impact the intake or absorption of vitamin D. This can increase the risk of disease relapse, impact patients’ quality of life, and increase the risk of IBD related surgeries. In addition to the traditional observation that vitamin D deficiency may be a comorbid manifestation of IBD, there is now growing evidence pointing to serum vitamin D levels as a pathogenic factor contributing to the initiation and propagation of mucosal inflammation in patients with IBD. It is well-established that variation in clinical practice leads to less optimal outcomes in any clinical setting. The relative scarcity of clinical and translational studies is even more pronounced in the pediatric population. OBJECTIVES: The primary objective of this study is to quantify the prevalence of clinician assessment of vitamin D levels in pediatric patients with IBD. We will also look at this behavior in subpopulations and compare their vitamin D status. It is secondary for this study to also describe variations in physician practices with respect to the testing and treatment of vitamin D deficiency at a single tertiary care IBD Center. METHODS: We conducted a retrospective cohort study on consecutive patients with UC, CD, and ID, that were followed in the ambulatory program in the Center for Inflammatory Bowel Disease at Boston Children’s Hospital from 1/1/2014 to 12/31/2014. We identified 498 patients and collected their demographic information, serologic testing, and physician prescribing behavior. RESULTS: Out of the entire population, 64% of the patients were vitamin D deficient (vitamin D level below 32 ng/ml). 24% of the patients received vitamin D supplementation. Vitamin D deficiency was less prevalent in patients with UC than those with CD, with an OR of 0.64 (95% CI 0.43-0.94). Out of the ones receiving supplementation, 37% of them were deficient. In terms of physician practice trends, 62% of the patients were not formally prescribed supplementation. 14.5% of those who were prescribed supplementation were receiving 50,000 IU weekly, and the rest receiving 400 – 2,000 IU daily. Patients with vitamin D levels below 20 ng/ml were more likely to receive the high dose vitamin D prescription (OR 11.5) than those with levels between 20 and 30 ng/ml (OR 5.7). CONCLUSIONS: Our study suggests that despite high prevalence of vitamin D deficiency in pediatric patients with IBD, there is a lack of consensus with respect to the assessment of vitamin D levels and consistency in prescribing vitamin D supplementation. With the potential role that vitamin D plays in IBD pathology and suggestions of the therapeutic effects of vitamin D supplementation, further studies are needed to explore this area.

INTRODUCTION: Anemia is a frequent complication in patients with inflammatory bowel disease (IBD). The inflammation observed in IBD negatively impact absorption of iron. This could lead to increased hospitalizations, affect growth and development, and decrease overall quality of life. This is especially pronounced in the pediatric population. The screening and treatment of iron deficiency anemia (IDA) varies between centers, and as a result, roughly 40-60% of pediatric IBD patients are iron deficient. OBJECTIVES: The objective of this study is to assess the efficacy and safety profile of intravenous and enteral iron therapy in a population of iron deficient patients with IBD. The secondary aim of this study is to determine if oral or intravenous iron therapy can improve hematologic and iron parameters. We will also examine the longitudinal changes in gastrointestinal (GI) symptoms and quality of life in patients receiving oral and intravenous iron supplementation. METHODS: We conducted a prospective cohort study in pediatric patients with IBD admitted to the inpatient GI service at Boston Children’s Hospital from 09/05/2017 to 03/05/2018. Forty-six IBD patients were screened, and twenty-nine (63%) were identified as iron deficient and were consented for data collection through chart review and administration of the IMPACT-III quality of life questionnaire. RESULTS: Out of the twenty-nine IBD patients, eighteen (62%) received intravenous iron, seven (24%) received oral iron, and four (14%) were untreated and served as controls. The mean change in hemoglobin in patients receiving parenteral, oral, or no iron therapy was 1.6g/dl±0.5, 1.1g/dl±0.4, and 0.2g/dl±0.5, respectively. The change in hemoglobin was significant between the parenteral and oral iron group (P<0.05). The mean change in health-related quality of life scores in patients receiving parenteral or oral iron therapy was 11.6±11.4 and 3.8l±7.5, respectively. CONCLUSION: Our study demonstrates that intravenous iron therapy was more efficacious than oral iron in improving hematologic and iron parameters in IBD patients. This improvement was concomitant with higher scores on the IMPACT-III quality of life questionnaire, suggesting that iron supplementation improves health-related quality of life in IBD patients with iron deficiency anemia.

Bakgrund: Ulcerös kolit är en kronisk sjukdom som orsakar inflammation i tjockoch ändtarm och karakteriseras av att gå i skov. Botemedel finns ännu inte och symtom är något många upplever trots medicinsk behandling. Syfte: Att belysa hur det är att leva med ulcerös kolit. Metod: Tidigare vetenskaplig forskning har samlats in via vårdvetenskapliga databaser och en induktiv ansats har använts. Artiklar granskades och tio stycken valdes ut. Innehållsanalys utfördes genom att meningsbärande enheter kodades med hjälp av kategorier. Resultat: Fyra teman bildades: Oro och rädsla på grund av ovisshet, Oförmåga att delta i fritids- och arbetsaktiviteter, Påverkan på livskvalité och livsstil samt Påfrestningar och utmaningar för barn med ulcerös kolit. Resultatet visade att både vuxna och barn kunde känna sig både psykiskt och fysiskt nedsatta och led av bland annat oro och rädsla. Konklusion: Det behövs mer kommunikation, information och stöd från vården för att minska oron bland patienter med ulcerös kolit. / Background: Ulcerative colitis is a chronic disease that causes inflammation of the colon and rectum and is characterized by relapses. There is no cure yet and symptoms are something many people experience despite medical treatment. Aim: To shed light on what it is like to live with ulcerative colitis. Method: Previous scientific research has been collected via caring science databases and an inductive approach has been used. Articles were reviewed and ten were selected. Content analysis was performed by coding meaningful units using categories. Results: Four themes were formed: Anxiety and fear due to uncertainty, Inability to participate in leisure and work activities, Impact on quality of life and lifestyle and Stress and challenges for children with ulcerative colitis. The results showed that both adults and children could feel both mentally and physically impaired and suffered from, among other things, anxiety and fear. Conclusion: More communication, information and support from healthcare is needed to reduce the anxiety among patients with ulcerative colitis.

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第22364号 / 医博第4605号 / 新制||医||1043(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 濵﨑 洋子, 教授 松田 文彦, 教授 遊佐 宏介 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM