Introdução: A Associação Internacional para o Estudo da Dor (IASP) tem estimulado a organização de Programas de Tratamento de Dor Aguda (SDAP) para um manejo mais efetivo, bem como avaliar seu impacto em desfechos passiveis de mensuração. Estudos têm sido conduzidos para mostrar a necessidade dos hospitais organizarem serviços de dor aguda pós-operatória, com vistas a melhora do tratamento da dor e para avaliar o processo de recuperação do paciente, redução do tempo de internação consequente ao uso de técnicas analgésicas mais eficazes. Então o objetivo deste estudo foi comparar o tempo de internação de pacientes submetidos a cirurgias eletivas com alta probabilidade de apresentarem dor pós operatória intensa sob os cuidados de uma equipe multidisciplinar especializada do SDAP comparado a uma coorte submetida a procedimentos cirúrgicos equivalentes no mesmo período, que tiveram seu tratamento da dor pós-operatório sob o cuidado da cirurgia equipe. Métodos: trata-se de uma coorte naturalista, retrospectiva, que incluiu 1011 pacientes com idade superior a 18 anos, de ambos os sexos submetidos à cirurgia eletiva de grande porte, tais como cirurgias torácicas com toracotomia, cirurgias proctológicas com abertura da cavidade abdominal e cirurgias ortopédicas para prótese de joelho e quadril. Os dados foram obtidos a partir do pontuaria o eletrônico do Hospital de Clinicas de Porto Alegre (HCPA) no período compreendido entre 2011 e 2015. Resultados: Avaliamos retrospectivamente 1050 pacientes assim distribuídos [cirurgia proctológica 506 (50,4%), cirurgia torácica 216 (21,36%) e cirurgia ortopédica 293 (29,17%)]. A média (SD) da internação hospitalar em pacientes sob o atendimento do SDAP foi de 7,84 (4,41) comparado controles correspondentes sob o cuidado da equipe cirúrgica, que apresentaram uma média (SD) de internação de 9,72 (8,64), respectivamente. Foram fatores associados com prolongada internação pós-operatória a mortalidade pós-operatória, reoperação cirúrgica e pacientes que necessitaram de terapia intensiva pós-operatória. Conclusão: Estes resultados sustentam a hipótese de que uma mudança no cuidado pós-operatório de pacientes submetidos a cirurgias com propensão para dor pós-operatória intensa, sob os cuidados de uma equipe multidisciplinar especializada do SDAP reduziu o tempo de internação pós-operatório comparado aos pacientes submetidos a cirurgias equivalentes com o tratamento da dor pós-operatória aos cuidados da equipe assistente. / Background: The American Pain Society stimulate to organize Programs of the Acute Pain Services (APS) fora most efficient pain management, as well to assesses its impact on the measurable outcomes. Studies around the world remind us of the imminent need for hospitals maintain service acute postoperative pain, since it is known that in this way, through better treatment of pain increases the likelihood of establishing strategies to improve patient recovery, coupled with reductions in average length of stay (hospital), more effective analgesic techniques and potential cost savings. Thus, this study compared the long hospital stay between patients underwent to care for a specialized multidisciplinary team of the APS, with a matched cohort suffered to same surgical procedures, during the same period, which had their postoperative pain management under the care of the surgical team. Methods: This is a retrospective naturalistic cohort that included 1011 patients older than 18 years, male and female underwent to elective major surgery, with an open cavity (proctologic and thoracic surgeries) and orthopedic surgeries (knee and hip replacement). The Electronic Information Database, comprehend the years of 2011 through 2015 at a teaching hospital in the south of Brazil. Results: We assessed retrospectively 1050 patients [proctologic surgery 506 (50.4%), thoracic surgery 216 (21.36%) and orthopedic surgery 293 (29.17%)]. The mean (SD) of hospital stay in patients under of the APS care was 7.84 (4.41) compared to their matched controls, which had a mean (SD) of hospital stay of 9.72 (8.64), respectively. Another risk factor for the long hospital stay were the postoperative mortality, surgical re-operation, and patients that needed postoperative intensive care. Conclusion: These findings support the hypothesis that a change in patients undergone to surgeries with a higher propensity to have severe postoperative pain with the postoperative pain management under a specialized multidisciplinary team of APS reduced the postoperative extended hospital stay.

Orientador: Suzana Erico Tanni Minamoto / Resumo: Introdução: A exacerbação aguda é uma importante causa de perda de função em pacientes com doença pulmonar obstrutiva crônica (DPOC). Afeta negativamente a qualidade de vida, a função pulmonar, a fraqueza muscular, o uso de recursos de saúde e a sobrevivência. Acredita-se que o exercício físico realizado durante a exacerbação pode melhorar a qualidade de vida e a capacidade física do paciente sem aumento do processo inflamatório. Objetivo: Avaliar a influência do exercício físico aeróbico de curta duração durante a internação em marcadores inflamatórios, qualidade de vida e capacidade física, além de re-hospitalização e taxas de mortalidade seis meses após a alta hospitalar em pacientes com DPOC exacerbada. Pacientes e Métodos: 26 pacientes foram avaliados 24 horas após a hospitalização por características demográficas, história de tabagismo, índice de Charlson, qualidade de vida, marcadores inflamatórios sistêmicos e composição corporal. Após 48 horas de internação, todos os pacientes realizaram o teste de caminhada de 6 minutos e um novo teste de espirometria, sendo calculado o índice BODE. Após 72 horas de internação, os pacientes do grupo de intervenção foram submetidos a exercícios aeróbicos em esteira por 15 minutos, duas vezes ao dia. Por fim, um mês após a alta hospitalar, todos os pacientes foram reavaliados segundo a qualidade de vida, marcadores inflamatórios sistêmicos, composição corporal, espirometria, teste de caminhada de 6 minutos e índice BODE. Resultados: O... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Acute exacerbation is an important cause of loss of function in patients suffering from chronic obstructive pulmonary disease (COPD). It negatively affects the quality of life, lung function, muscle weakness, use of health resources and survival. It is believed that the physical exercise performed during the exacerbation can improve the quality of life and the physical capacity of the patient without an increase in the inflammatory process. Objective: To evaluate the influence of short-term aerobic physical exercise during hospitalization on inflammatory markers, quality of life and physical capacity, as well re-hospitalization and mortality rates six months after hospital discharge in patients with exacerbated COPD. Patients and Methods: 26 patients were evaluated 24 hours after hospitalization for demographic characteristics, smoking history, Charlson index, quality of life, systemic inflammatory markers and body composition. After 48 hours hospitalization, all patients performed a 6-minute walk test and a new spirometry test, and BODE index was calculated. After 72 hours of hospitalization, patients in the intervention group underwent aerobic exercise on a treadmill for 15 minutes twice daily. Finally, a month after hospital discharge, all patients were re-evaluated according to quality of life, systemic inflammatory markers, body composition, spirometry, 6-minute walk test and BODE index. Results: Patients in the intervention and control group did not differ... (Complete abstract click electronic access below) / Doutor

The critical function of the kidney is to regulate the body’s extracellular fluid volume to maintain homeostasis. When insults to the kidney occur, as in the case of kidney ischemia, the function of the kidney to filter metabolic wastes and reabsorb essential solutes is compromised, leading to a variety of clinical manifestations. Current metrics of kidney function are measured by the rise of a single analyte, the serum creatinine, which implies injury of the kidney tubule and its epithelial cells and is encapsulated by the term Acute Kidney Injury (AKI). Yet, creatinine does not specify the etiology, the cell type, or the molecular pathways that are affected by the acute decreases in kidney excretory function. During my thesis work, I hypothesized that there is a pathogenetic heterogeneity of kidney injury and a specificity of location, timing, and molecular mechanisms, unique to each of these three injury models: kidney ischemia, volume depletion, and urinary tract infection. Using genetic mouse models, RNA-sequencing, and a range of molecular biology techniques, I have found (1) kidney ischemia activates inflammatory responses, signal transduction pathways, and epithelial repair and reprogramming, that are not activated in volume depletion, (2) which in contrast, is a transient metabolic condition, inducing genes regulating energy metabolism that were reversible upon rehydration. Lastly, (3) I have found that urinary tract infection, particularly one that invades the kidney, involves a novel heme transport system in the collecting duct of the kidney, that may contribute to nutritional defenses against bacterial pathogens. Each of these findings is explored in specific aims and experiments, which I detail here in my thesis.

Cows’ milk generally contains two types of β-casein, A1 and A2 types. A2 beta-casein is recognized as the original beta-casein variant because it was present before a proline to histidine point mutation occurrence in the polypeptide chain at 67th position. A1 and A2 are processed differently by digestive enzymes, and once milk or milk products are consumed, a seven-amino acid bioactive opioid peptide, beta-casomorphin-7, is released as a result of incomplete digestion of A1-beta-casein. This is a single-dose, randomized and double-blinded study. Participants received four different treatments (Regular milk, A2 milk, Jersey cow milk, and lactose free milk) in a randomized order. The lactose free milk acted as a negative control. This study aimed to evaluate tolerance to milks containing different levels of A2 β-casein (Jersey and A2 milks) as compared to commercial A1 (regularmilk containing both A1 and A2 β-casein) and lactose-free milk controls in lactose digesters and maldigesters. Seven subjects completed this double-blinded, randomized, crossover trial. Lactose malabsorption (LM) was determined by breath hydrogen test and milk intolerance were assessed by validated questionnaires. Treatments were fed as a single dose with a 6-day washout period to minimize any residual effects. Each subject was fed milk containing 0.5 g lactose per kg body weight. The pilot data from the seven subjects does strongly suggest greater hydrogen production from commercial A1 milk as compared to lactose-free, A2 and Jersey milks. Regular milk containing high A1 β-casein produced significantly higher hydrogen compared to lactose-free milk from 2 hours until 5hours. This suggests biologically relevant differences in lactose digestion among these milks. In addition, Jersey milk produced significantly higher hydrogen compared to lactose-free milk similar to regular milk between 2 and 6 hours while A2 milk was acting similar to lactose-free milk and did not result in increased hydrogen throughout the same time intervals. Taken together, these results suggest that the amount of A2 β-casein in Jersey milk was not adequate to attenuate the increased hydrogen concentration while pure A2 milk was effective. In this pilot clinical trial, abdominal pain, bloating, flatulence, diarrhea, fecal urgency and total GI symptoms were reported as measures of digestive discomfort. Although the mean values of total GI symptom scores were numerically lower on the lactose free, pure A2 and Jersey group compared to regular milk group, none were statistically different. With seven subjects reported in this pilot data, and a calculated sample size requirement of 26, we can interpret trends that ultimately could result in significant differences as additional subjects complete this protocol.

INTRODUÇÃO: A angiotomografia computadorizada com múltiplos detectores (ATCMD) apresenta alta acurácia para a detecção de estenose luminal significativa das artérias coronárias ( 50%) quando comparada à angiografia coronária invasiva (ACI). Recentemente, esse método vem sendo investigado na avaliação de pacientes com dor torácica aguda de baixo risco. No entanto, poucos estudos investigaram a capacidade da ATCMD na avaliação de pacientes com maior risco para síndrome coronária aguda (SCA). OBJETIVOS: Investigar a acurácia diagnóstica da ATCMD com 64 colunas de detectores para a detecção de estenose luminal coronária 50% definida pela ACI em indivíduos com suspeita de SCA sem supradesnível do segmento ST e comparar estes resultados com a acurácia encontrada em pacientes com suspeita de doença coronária crônica; avaliar a capacidade da ATCMD em predizer revascularização miocárdica nos 30 primeiros dias de seguimento. Adicionalmente objetivamos verificar a prevalência e a acurácia da presença de calcificação coronária para detecção de estenose luminal coronária significativa. MÉTODOS: Pacientes que participaram do estudo multicêntrico internacional CorE64 foram classificados nos grupos SCA e não-SCA de acordo com critérios clínicos, incluindo a presença de angina ao repouso, alterações isquêmicas ao ECG e elevação de marcadores de necrose miocárdica. Todos os pacientes foram submetidos à ATCMD e posteriormente à ACI e para a análise primária foram considerados apenas aqueles com escore de cálcio (EC) 600. RESULTADOS: Dos 291 pacientes incluídos, 80 (27%) foram classificados no grupo SCA. A prevalência de estenose coronária 50% foi de 68% neste grupo e de 52% no grupo não-SCA (p=0,015). A acurácia diagnóstica da ATCMD, em análise por paciente, para detecção de estenose coronária significativa demonstrada pela análise da área sob a Curva de Características Operacionais (AUC) foi de 0,95 (IC 95%: 0,90-0,99) e 0,92 (IC 95%: 0,89-0,96) nos grupos SCA e não-SCA, respectivamente (p=0,44). Nos 30 dias de seguimento, 98 pacientes foram submetidos à revascularização miocárdica (48 do grupo SCA e 50 do grupo não-SCA). A AUC da ATCMD e da ACI para predição de revascularização foi de 0,91 (95% IC: 0,83-0,99) e 0,89 (95% IC: 0,80-0,98), respectivamente, no grupo SCA (p=0,61) e 0,80 (95% IC: 0,74-0,86) e 0,79 (95% IC: 0,73-0,85) no grupo não-SCA, p=0,75. Comparando os dois grupos estudados, a ATCMD foi melhor preditora de revascularização no grupo SCA (p=0,035). No grupo SCA, 6 pacientes (7,5%) tinham EC zero e estenose coronária significativa, comparado a 8 indivíduos (3,8%) do grupo não-SCA (p=0,22). Considerando pacientes com EC baixo (0 a 9), 12 (15%) do grupo SCA e 11 (5,2%) do não- SCA apresentaram estenose coronária 50% (p=0,012). A acurácia do EC para detecção de estenose coronária significativa nos grupos SCA e não- SCA foi de 0,73 (IC 95%: 0,63-0,82) e 0,70 (IC 95%: 0,64-0,76), respectivamente (p=0,75), sendo que o valor preditivo negativo no grupo SCA foi estatisticamente menor que no grupo não-SCA [0,63 (IC95%: 0,39- 0,86) e 0,86 (IC 95%: 0,77-0,95), respectivamente, p=0,038]. CONCLUSÕES: A ATCMD apresentou alta acurácia diagnóstica para detecção de estenose coronária significativa nos grupos SCA e não-SCA, não havendo diferença significativa entre ambos. A ATCMD obteve acurácia semelhante à ACI na predição de revascularização, sendo maior no grupo SCA que no não-SCA. A acurácia do EC para a detecção de estenose coronária 50% foi moderada em ambos os grupos, sendo que um EC zero ou baixo não excluiu a ocorrência de estenose significativa, especialmente no grupo SCA / BACKGROUND: Multi-detector computed tomography angiography (MDCTA) has shown high accuracy to detect obstructive coronary luminal stenosis ( 50%) compared to invasive coronary angiography (ICA). Recently, this technology has been investigated in the evaluation of patients with low-risk acute chest pain. However, few studies investigated its diagnostic performance in higher-risk patients with suspected acute coronary syndrome (ACS). OBJECTIVES: To estimate the diagnostic accuracy of 64- row computed tomography angiography to detect significant coronary stenosis defined by ICA in a per-patient analysis and its ability to predict coronary revascularization in patients with suspected acute coronary syndrome and in those with chronic, stable coronary artery disease; to identify the prevalence and the diagnostic accuracy of coronary calcification to detect significant luminal stenosis in both groups. METHODS: Patients included in the international multicenter trial CorE64 were categorized as suspected ACS or non-ACS based on clinical data. A 64-row coronary MDCTA was performed before ICA and both exams were evaluated by blinded, independent core laboratories. RESULTS: From 291 patients with coronary calcium score (CCS) 600 included in the primary analysis, 80 were categorized as suspected ACS. The prevalence of obstructive coronary disease was 68% in suspected ACS and 52% in non-ACS group (p=0.015). Patient-based analysis showed an area under the receiver-operatingcharacteristic curve (AUC) for detecting coronary stenosis 50% of 0.95 (95% CI: 0.90-0.99) in ACS and 0.92 (95% CI: 0.89-0.96) in non-ACS group (p=0.44). After 30 days of follow-up, 98 patients were submitted to coronary revascularization (48 from the ACS and 50 from the non-ACS group). MDCTA was similar to ICA to predict coronary revascularization in both groups with AUC of 0.91 (95% CI: 0.83-0.99) for MDCTA versus 0.89 (95% CI: 0.80-0.98) for ICA in the ACS group (p=0.61) and 0.80 (95% CI: 0.74- 0.86) for MDCTA versus 0.79 (95% CI: 0.73-0.85) for ICA in non-ACS group (p=0.75). MDCTA was better to predict revascularization in ACS than in non- ACS group (p=0.035). In the suspected ACS group, 6 patients (7.5%) had no coronary calcification and coronary stenosis 50%, compared with 8 patients (3.8%) in the non-ACS group (p=0.22). Considering patients with zero or low (0 to 9) CCS, 12 (15%) in the ACS and 11 (5.2%) in the non-ACS group had significant coronary stenosis (p=0.012). The accuracy of CCS to detect obstructive coronary stenosis in the ACS and non-ACS groups were 0.73 (95% CI: 0.63-0.82) e 0.70 (95% CI: 0.64-0.76), p=0.75, and its negative predictive value in the suspected ACS group was lower than in non-ACS patients [0.63 (95% CI: 0.39-0.86) and 0.86 (95% CI: 0.77-0.95), respectively, p=0.038]. CONCLUSIONS: Coronary MDCTA diagnostic accuracy was high and comparable for both ACS and non-ACS patients. MDCTA predicted revascularization similarly to ICA and its prediction ability was significantly better in the ACS than in non-ACS group. The diagnostic accuracy of a positive CCS to detect luminal stenosis 50% was moderate in both groups and a zero or low CCS could not exclude reliably significant coronary stenosis, particularly in suspected ACS patients

The tumour microenvironment consists of an immunosuppressive niche created by the complex interactions between cancer cells and surrounding stromal cells. A critical component of this environment are myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immature myeloid cells arrested at different stages of differentiation and expanded in response to a variety of tumour factors. MDSCs exert diverse effects in modulating the interactions between immune effector cells and malignant cells. An increased presence of MDSCs is associated with tumour progression, poorer outcomes, and decreased effectiveness of immunotherapeutic strategies. In this project, we sought to quantify and characterise MDSC populations in patients with Acute Myeloid Leukaemia (AML) and delineate the mechanisms underlying their expansion. We have demonstrated that immune suppressive MDSCs are expanded in the peripheral blood and bone marrow of patients with AML. Furthermore, AML cells secrete extra-cellular vesicles (EVs) that skew the tumour microenvironment from antigen-presentation to a tumour tolerogenic environment, through the expansion of MDSCs. We then demonstrated that MDSC expansion is dependent on tumour and EV expression of the oncoproteins MUC1 and c-Myc. Furthermore, we determined that MUC1 signalling promotes c-MYC expression in a microRNA (miRNA) dependent mechanism. This observation lead us to elucidate the critical role of MUC1 in suppressing microRNA-genesis in AML, via the down-regulation of the DICER protein, a key component of miRNA processing machinery. Finally, exploiting this critical pathway, we showed that MDSCs can be targeted by MUC1 inhibition or by the use of a novel hypomethylating agent SGI-110.

Introduction: NKT cells are categorised as borderline between NK and T cells, sharing phenotypic and functional characteristics of both cells, demonstrating their capacity to contritube to both pro- or anti-inflammatory processes. However, the role of these cells among lung transplant recipients remains largely unknown. The aim of this study was to determine the role of NKT cells following lung transplantation. Methods: NKT cells were quantified and characterised according to markers of: activation (CD107a, CD161, NKG2D) and immunomodulation (CD200 and CD200R) in peripheral blood and BALs. NKT cell numbers and phenotypes were correlated to clinical variables: immunosuppression, acute rejection, acute infections (viral, bacterial and fungal), bronchiolitis obliterans syndrome (BOS grade), lung function, and demographic variables. Interactions between NKT cells and the transplanted lung were linked by determining the relative expression of immunomodulatory ligand CD200 in lung biopsies. In vitro models were employed to determine the role of NKT cells to acute lung injury, either alone or in combination with cells of the mononuclear phagocyte system (MPS). Results: Higher numbers of immunomodulatory NKT cells (CD200+ and CD200R+) were found as lung function decreased. Data from peripheral blood indicates that recipients whose donors or themselves had been exposed to CMV infection demonstrated increased numbers of NKT cells. Patients with active EBV infections demonstrated higher NKT cell numbers expressing CD200 and CD200R. Data from BALs, indicates that patients with active fungal infections present higher immunomodulatory (CD200R) NKT cells and lower cytotoxicity marker (CD107a). In peripheral blood, lung recipients demonstrated higher NKT cell numbers compared to healthy volunteers. However, the lower relative mean expression of functional markers in the lung transplant group suggests that cells are less active. In vitro cultures with immunosuppressants demonstrated that cell cycle inhibitors (MMF and AZA) and corticosteroids (Prednisolone) are likely to inhibit NKT cell proliferation, while calcineurin inhibitors (Cyclosporine A and Tacrolimus) decrease the relative mean expression of activation markers. Clinical observations indicate that higher doses of Azathioprine may correlate with increased NKT cell numbers and the relative expression of CD200 and CD200R. However, under these conditions the relative expression of activation marker NKG2D decreases. In vitro data from the acute injury model indicates that NKT cells are capable to migrate into the injured lung and become activated following transmigration which is facilitated by the presence of monocytes. We also observed the interaction of NKT cells with endothelial cells, monocytes and macrophages. Also, the relative mean expression of CD200 and CD200R increased at the capillary layer, regardless of injury while upregulation of activation markers (CD107a, CD161 and NKG2D) was found at the capillary layer, following injury. In contrast, the alveolar layer demonstrated a decrease in both activation and immunomodulatory markers, following acute injury. Conclusions: Despite immunosuppression, NKT cells remain present in peripheral blood and BAL following lung transplantation. NKT cell proliferation is likely to be reduced by effect of cell cycle inhibitors, while calcineurin inhibitors exert an immunomodulatory effect. Our data indicates that NKT cells can participate in inflammatory and immunomodulatory events at the alveolar bilayer. Their capacity to infiltrate the lungs was assisted by cells of the mononuclear phagocyte system (MPS), which play an important role in antigen presentation and modulation of acute injury. Further research is needed to elucidate the signals and mechanisms occurring between NKT and MPS interactions and the outcomes these populations drive in acute lung injury.

Background: In the year 2016 there were over 2 million acute ill adults who visited the emergency department and of those 2 million, 1,3 million were being remitted. The definition of being acute ill is a person who needed emergency care. The nurses' role in the emergency care was to evaluate and prioritize the acute ill medical need. In the acute situation the relatives were often put aside and that would cause a negative wellbeing experience. Aim: The purpose of the study was to investigate the relatives' experiences of having family members who became acute ill. Method: A literature study based on an analysis of eleven qualitative scientific articles was conducted. Results: The analysis resulted in two themes; Mixed feelings and experiences when a family member has become acutely ill and Experience in the meeting with a health professional. The results showed the importance of clear and understandable information from nurses. How the relatives were treated also had a significant impact on how they reacted to the acute situation. Conclusion: When a family member becomes acutely ill the relatives experienced the situation as difficult and were concerned over the family member's health. Despite that they were grateful for the opportunity to be present because they experienced that they were comforted and calmed. To have access to professional support and company helps the relatives to control and react to the situation. / I Sverige anländer ett stort antal personer till sjukhus som är i behov av akut omhändertagande och det är vanligt att dessa personer har med sig anhöriga. Sjuksköterskans ansvar är att bemöta och stötta både den sjuke familjemedlemmen och anhöriga i det akuta omhändertagandet. När anhöriga är närvarande upplever de blandade känslor. De känslor som dominerar är rädsla och oro. Anhöriga kan mötas av ett bristfälligt bemötande av sjuksköterskan samt uppleva att informationen som ges är oklar och svårförståelig. Det kan leda till att anhöriga känner att de blir åsidosatta vilket skapar känslor som övergivenhet, ångest och osäkerhet. Att bemöta anhöriga på rätt sätt kan göras genom att utgå från familjefokuserad omvårdnad, där sjuksköterskan ska se varje familj som en helhet. Vid rätt bemötande och information upplever anhöriga tacksamhet över att få möjlighet att vara nära sin sjuke familjemedlem. Detta skapar förtroende för vården och känslan av att få verktyg att hantera situationen. Vid en akut situation används anhörigstödjare som en resurs där deras uppgift är att förklara vad som händer/pågår och stödja anhöriga. När en familjemedlem blir akut sjuk kan anhöriga uppleva en förlust av kontroll över situationen och på detta sätt förändras deras livsvärld. Ett sätt att få tillbaka kontrollen är att få tillgång till rätt förmedlad information. Författarna väljer att göra ett litteraturbaserat examensarbete där 11 kvalitativa artiklar granskas. I examensarbetet framkommer det 2 teman och 4 underteman. Resultatet visar att anhöriga upplever blandade känslor när deras familjemedlem blir akut sjuk. Anhöriga upplever det viktigt att få möjlighet att ge stöd till sin sjuke familjemedlem. Dessutom minskar anhörigas stress om de får stöd från övrig familj och vänner. I mötet med vårdpersonalen har många anhöriga positiva känslor medan vissa anhöriga uppger negativa känslor såsom övergivenhet, osäkerhet, frustration och en känsla av att skapa obehag hos vårdpersonalen. Examensarbetets resultat ger sjuksköterskan en förståelse om vikten av ett bra bemötande och förmedlandet av förståelig information i mötet med anhöriga.

Background: Hepatic ischemia reperfusion injury (IRI) results from the interruption and then reinstatement of the liver’s blood supply. IRI involves both an ischemic and an immune-mediated reperfusion phase of tissue injury; similar inflammatory events are seen in other forms of acute (sterile) liver injury (ALI), including paracetamol toxicity. Hypothesis Irrespective of the primary insult, common pathways exist in the pathophysiology of the lymphocyte-mediated secondary liver injury. Natural mechanisms exist to limit lymphocyte function and these pathways can be targeted therapeutically by immunomodulatory agents. Aims: 1. To assess the relative importance of different lymphocyte subsets in IRI. 2. To correlate observations in IRI with other models of ALI. 3. To identify possible pharmacological targets. Materials and Methods Three experimental murine models of acute liver injury were utilised to test this hypothesis: murine model of warm hepatic IRI, concanavalin A (con A) hepatitis and paracetamol-induced liver injury. These models were interrogated with a combination of (transgenic and knockout) mouse lines, in vivo antibody depletion and small molecule inhibition. Injury was evaluated primarily in terms of the biochemical marker of liver injury alanine aminotransferase (ALT). Data were correlated with human tissue where possible. Results: T cells (CD3εKO vs WT p=0.010), but not other lymphocyte populations (B cells, NK cells, or other innate lymphoid cells), play a central role in warm hepatic IRI. Programmed Death Receptor-1 (PD-1) is a negative regulator of pro-inflammatory cytokine production by T cells and the absence of PD-1 was associated with significantly worse hepatic IRI (p=0.034), con A hepatitis (p=0.00020) and paracetamol-induced liver injury (p=0.0050). Interferon-γ (IFNγ) and T-box expressed in T cells (T-bet) are important mediators of hepatic IRI (p=0.017) and paracetamol induced liver injury (p=0.0007). The absence of IL-6 was associated with significant protection in paracetamol induced liver injury (p=0.006). The infiltrates within the recipient liver of patients transplanted following paracetamol overdose stain positively for PD-1, IFNγ and T-bet. The Janus family of kinases (JAK) play an important role in the common pathways of cytokine signal transduction. In vivo use of a selective JAK1/JAK2 inhibitor is protective in hepatic IRI (p=0.0014), con A hepatitis (p=0.019) and paracetamol-induced liver injury (p=0.0045). Conclusions: Common pathways appear to exist in the immune-mediated secondary phase of injury in ALI. Targeting these pathways will complement existing (cytoprotective) treatment strategies.

Orientador: Silvio Luis de Oliveira / Banca: Marcelo De Franco / Banca: Angela Maria Victoriano de Campos Soares / Resumo: Camundongos selecionados para a máxima (AIRmax) ou mínima (AIRmin) reação inflamatória aguda apresentam desvio de freqüência do gene Slc11a1. Este gene está envolvido no transporte de íons divalentes no compartimento endossomal/lisossomal de macrófagos e neutrófilos, interferindo na sua ativação e suscetibilidade a infecções. Neste estudo, nós investigamos a interação dos alelos Slc11a1 R (Slc11a1rGly169) e S (expressão nula da proteína Slc11a1, Slc11a1sAsp169) com os loci de características quantitativas (QTL) moduladores da inflamação, durante a paracoccidioidomicose (PCM) em linhagens AIRmaxRR, AIRmaxSS, AIRminRR and AIRminSS homozigotas para o gene Slc11a1, produzidas por acasalamentos assistidos por genotipagem. Nós verificamos que o alelo R em homozigose foi responsável por um maior influxo neutrofílico em camundongos com background AIRmax. Observamos ainda, que as linhagens AIRmaxRR e AIRmaxSS foram mais resistentes enquanto a linhagem AIRmin portadora do alelo R foi implicada em uma maior recuperação de UFC de P. brasiliensis. Desta forma, apesar de não observarmos diferença na recuperação de UFC entre as sublinhagens AIRmax, um aumento no influxo de neutrófilos para o pulmão dos animais AIRmaxRR pode ter compensado a influência do alelo Slc11a1 R na multiplicação do fungo. Nós também mostramos que o número de UFC nos pulmões foi relacionado a síntese de IL-4 e IL-10 neste órgão, mas a produção de óxido nítrico foi semelhante em ambas as linhagens mostrando que este metabólito não foi o fator determinante de resistência/suscetibilidade nas linhagens analisadas. Quanto a análise de diferentes citocinas em sobrenadante de cultura de células do baço e no pulmão das linhagens utilizadas, mostramos que o gene modula a síntese de várias citocinas, porém... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Mice selected for the maximum (AIRmax) or minimum (AIRmin) acute inflammatory reaction show disequilibrium of the Slc11a1 gene. This gene is involved in the transport of divalent ions at the endosomal/lysosomal compartment within macrophages and neutrophils, interfering in their activation and susceptibility to infections. In this study, we investigated the interaction of the Slc11a1 R (Slc11a1rGly169) and S (null Slc11a1 protein expression, Slc11a1sAsp169) alleles with the Quantitative Trait Loci (QTL) modulated-inflammation during paracoccidioidomycosis in homozygous AIRmaxRR, AIRmaxSS, AIRminRR and AIRminSS lines produced by genotype-assisted breedings. It could be verified that R allele in homozygosis is associated with a more intense neutrophil influx in AIRmax background. The AIRmax lines showed to be more resistant wile AIRmin bearing allele R implicated in a higher recovered P. brasiliensis CFU. Although, the increase of neutrophil influx to the lungs in AIRmaxRR mice can be compensating the influence of Slc11a1 R allele in P. brasilinsis multiplication. We have also observed that the number of CFU in lungs was not related to NO production but instead to modulation of IL-4 and IL-10 synthesis in the lungs. Moreover, we present the effect of Slc11a1 modulating the release of differents cytokines in both supernatant of spleen cells and lungs, but this effect was time-dependent and change in accordance of host genetic background and microenviroment produced by immune response during P. brasiliensis infection. In conclusion, these findings suggest that the lower PMN leukocyte infiltration to the lungs and Slc11a1 R genotype seemed to be a decisive factor in determining the susceptibility profiles in P.brasiliensis infection. / Mestre