Thesis (Ph.D.)--Hong Kong University of Science and Technology, 2004. / Includes bibliographical references (leaves 212-224). Also available in electronic version. Access restricted to campus users.

Background Nutritional treatment in the intensive care unit (ICU) has evolved from meeting nutritional requirements to manipulating patient outcome. Pharmaconutrition, referring to nutrients that are applied for their pharmacological properties, forms part of the standard nutritional care plan. The most abundant amino acid in the body, glutamine, is also the most-researched pharmaconutrient. It is an independent predictor of mortality in ICU patients, at both deficient and very high levels. Glutamine supplementation is recommended in the ICU setting for its proven outcome benefits. However, recent data showed that glutamine supplementation increases mortality risk in certain patient groups. Moreover, it suggested that not all ICU patients are glutamine deficient. Therefore, the main aim of this study was to investigate the plasma glutamine levels of adult ICU patients, on admission to the ICU. In addition, to elucidate the profile of ICU patients that can be expected to present with a glutamine deficiency or excess, with regards to gender, diagnosis and inflammatory markers. Methods In this observational, cross-sectional study, 60 mixed ICU adult patients admitted to two hospitals in the North West province were included in the study group. Blood sampling was conducted within 24 hours following ICU admission, to determine plasma glutamine, interleukin (IL)-6 and C-reactive protein (CRP) levels. Plasma glutamine levels were compared with those of a control group of healthy individuals, matched by age, race, and gender. Gender-related differences in plasma glutamine levels were investigated, as well as differences between patients with various medical conditions. The relationship between plasma glutamine levels and IL-6 or CRP was examined. Additionally, a CRP concentration cut-off point at which glutamine becomes deficient was determined by means of a receiver operating characteristic (ROC) curve. Results and discussion Intensive care unit patients had significantly lower plasma glutamine levels than healthy individuals on day one of ICU admission (p < 0.0001). However, only 38.3% (n = 23) had deficient plasma glutamine levels (< 420 μmol/L), while 6.7% (n = 4) presented with supra-normal levels (> 930 μmol/L). No significant difference could be detected between the plasma glutamine levels of male and female ICU patients (p = 0.116). Likewise, levels between diagnosis categories were also not significantly different (p = 0.325). There was a significant inverse association between plasma glutamine levels and CRP concentrations (r = -0.44, p < 0.05), and a trend towards an inverse association with IL-6 (r = - 0.23, p = 0.08). A CRP cut-off value of 95.5 mg/L was determined, above which plasma glutamine values became deficient; however, more research is needed to confirm this result. Conclusion and recommendations This research therefore showed that ICU patients, when compared with healthy individuals, had lower plasma glutamine levels on day one of admission to the ICU. However, not all were glutamine deficient, as the majority had normal and some presented with supra-normal plasma glutamine levels. An individualised approach should therefore be followed in identifying candidates for glutamine supplementation. The patients‟ condition alone may not be sufficient to predict glutamine status, but an association between plasma glutamine levels and CRP was firmly established, as well as a cut- off CRP-value above which glutamine can be expected to become deficient, which could be of use in this regard. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2015

Background Nutritional treatment in the intensive care unit (ICU) has evolved from meeting nutritional requirements to manipulating patient outcome. Pharmaconutrition, referring to nutrients that are applied for their pharmacological properties, forms part of the standard nutritional care plan. The most abundant amino acid in the body, glutamine, is also the most-researched pharmaconutrient. It is an independent predictor of mortality in ICU patients, at both deficient and very high levels. Glutamine supplementation is recommended in the ICU setting for its proven outcome benefits. However, recent data showed that glutamine supplementation increases mortality risk in certain patient groups. Moreover, it suggested that not all ICU patients are glutamine deficient. Therefore, the main aim of this study was to investigate the plasma glutamine levels of adult ICU patients, on admission to the ICU. In addition, to elucidate the profile of ICU patients that can be expected to present with a glutamine deficiency or excess, with regards to gender, diagnosis and inflammatory markers. Methods In this observational, cross-sectional study, 60 mixed ICU adult patients admitted to two hospitals in the North West province were included in the study group. Blood sampling was conducted within 24 hours following ICU admission, to determine plasma glutamine, interleukin (IL)-6 and C-reactive protein (CRP) levels. Plasma glutamine levels were compared with those of a control group of healthy individuals, matched by age, race, and gender. Gender-related differences in plasma glutamine levels were investigated, as well as differences between patients with various medical conditions. The relationship between plasma glutamine levels and IL-6 or CRP was examined. Additionally, a CRP concentration cut-off point at which glutamine becomes deficient was determined by means of a receiver operating characteristic (ROC) curve. Results and discussion Intensive care unit patients had significantly lower plasma glutamine levels than healthy individuals on day one of ICU admission (p < 0.0001). However, only 38.3% (n = 23) had deficient plasma glutamine levels (< 420 μmol/L), while 6.7% (n = 4) presented with supra-normal levels (> 930 μmol/L). No significant difference could be detected between the plasma glutamine levels of male and female ICU patients (p = 0.116). Likewise, levels between diagnosis categories were also not significantly different (p = 0.325). There was a significant inverse association between plasma glutamine levels and CRP concentrations (r = -0.44, p < 0.05), and a trend towards an inverse association with IL-6 (r = - 0.23, p = 0.08). A CRP cut-off value of 95.5 mg/L was determined, above which plasma glutamine values became deficient; however, more research is needed to confirm this result. Conclusion and recommendations This research therefore showed that ICU patients, when compared with healthy individuals, had lower plasma glutamine levels on day one of admission to the ICU. However, not all were glutamine deficient, as the majority had normal and some presented with supra-normal plasma glutamine levels. An individualised approach should therefore be followed in identifying candidates for glutamine supplementation. The patients‟ condition alone may not be sufficient to predict glutamine status, but an association between plasma glutamine levels and CRP was firmly established, as well as a cut- off CRP-value above which glutamine can be expected to become deficient, which could be of use in this regard. / MSc (Dietetics), North-West University, Potchefstroom Campus, 2015

Sepse é um importante problema de saúde pública, uma vez que seu tratamento gera altos custos a um sistema de saúde já sobrecarregado. É uma síndrome de alta mortalidade e morbidade que afeta, em geral, pacientes jovens com plena capacidade produtiva. A identificação e o tratamento precoce desta síndrome reduzem a morbimortalidade, assim como o custo. A proteína C reativa (PCR) e a procalcitonina (PCT) são bem estudadas como ferramentas para diagnóstico de infecção bacteriana em imunocompetentes, mas seu uso como ferramenta diagnóstica ainda não está estabelecido em pacientes imunossuprimidos. Portanto, a proposta deste estudo é avaliar a acurácia diagnóstica destes biomarcadores, em pacientes críticos imunossuprimidos (vírus da imunodeficiência adquirida  HIV positivos, portadores de tuberculose (TBC), cirróticos e transplantados). Como o uso da proteína C ainda não está estabelecido, a primeira questão de pesquisa investigou seu potencial diagnóstico quando comparado ao teste padrão (cultural). O segundo artigo comparou a PCR com a PCT. Para isto foram realizados dois artigos de revisão sistemática com metanálise. O primeiro artigo comparou a acurácia em determinar infecção bacteriana em imunossuprimidos da PCR ao teste padrão-ouro (as culturas). A primeira revisão incluiu 1.418 pacientes e demonstrou uma boa acurácia da PCR como biomarcador no diagnóstico de infecção bacteriana, apresentando sensibilidade de 69% e especificidade de 76% com uma área sob a curva (AUC) de 0,77. Os resultados encontrados são similares aos da literatura para imunocompetentes,(3) sensibilidade de 75%, especificidade de 67% e Área Sob a Curva Receiver Operating Characteristic (AUROC) de 0,92. Quando a PCT foi comparada com a PCR, ambos os biomarcadores mostraram acurácia moderada na utilização como ferrramenta de diagnóstico de infecção bacteriana, com um diagnóstico da razão de chances (DOR) de 7,24 (95% CI (2,83-14,60) para PCT e de 5,56 (95% CI (5,21-10,30) para PCR. A PCT e a PCR apresentaram sensibilidade de 69% e 68% e uma especificidade de 75% e 71%, respectivamente. Ambas mostraram resultados semelhantes, podendo ser utilizadas no diagnóstico de sepse em imunossupressos. / Sepsis is a major public health problem, since its treatment generates high costs, a health system already overburdened. A high mortality and morbidity syndrome affects, in general, young patients with full production capacity. The identification and early treatment of this syndrome reduce morbidity and mortality as well as the cost. C-reactive protein (CRP) and procalcitonin (PCT) are well studied as tools for diagnosis of bacterial infection in immunocompetent patients, but its use as a diagnostic tool is not yet established in immunocompromised patients. Therefore, the purpose of this study is to evaluate the diagnostic accuracy of these biomarkers in immunosuppresses critical patients (human immunodeficiency virus, cirrhotic and transplant). As the use of the c protein is not yet established, the first research question investigated their diagnostic potential when compared to the pattern (cultural). The second article compared to CRP and PCT. For this, there were two articles of a systematic review and meta-analysis. The first article compared the accuracy in determining bacterial infection in immunosuppresses of CRP to the gold standard (cultures). Our first review included 1,418 patients and showed good accuracy of CRP as a biomarker for the diagnosis of bacterial infection presenting a sensibility of 69% and 76% specificity with an area under the curve (AUC) 0.77. The results are similar to those found in the literature for immunocompetent,(3) sensitivity 75%, specificity of 67% and Area Under the Receiver Operating Characteristic Curve (AUROC): 0.92. When the PCT was compared with PCR, both biomarkers showed a moderately accurate for use as tool diagnostic bacterial infection with a Odds ratio diagnostic (DOR) 7.24 (95% CI (2.83-14.60) and PCT to 5:56 (95% CI (5.21-10.30) for CRP. the PCT and CRP had a sensitivity of 69% and 68% and a specificity of 75% and 71%, respectively. Both showed similar results may be used in the diagnosis of sepsis in immunosuppression.

The incidence of stroke and re-infarction is noticeably high in the first few days following acute myocardial infarction. This finding has raised questions whether the systemic inflammatory reaction secondary to myocardial necrosis is involved. The inflammation might affect the activation of platelets leading to insufficient effect of the antiplatelet treatment given. Furthermore, the importance of platelet reactivity and inflammation in terms of long-term prognosis is not fully understood. The prognostic importance of C-reactive protein (CRP) in relation to clinical variables also needs to be clarified. The present studies are aimed at describing the dynamics of platelet function during the first days of an acute myocardial infarction, in relation to diabetes and inflammation. We also investigated whether increased platelet reactivity or the increased concentration of CRP in blood were related to a worse outcome. Finally, we examined if CRP levels contributed to a predictive model using clinical variables known to affect outcome in patients with AMI.  We used two novel platelet function tests to measure platelet reactivity; the PA-200 (a laser light aggregometer) and the PFA-100 (measures primary haemostasis in whole blood). Platelet aggregation increased during the initial course of an acute myocardial infarction. The increase in platelet aggregation was most pronounced in diabetics and in patients showing higher systemic inflammatory reaction, assessed by measuring the concentration of CRP in blood. The pronounced platelet aggregation occurred despite ongoing antiplatelet and antithrombotic treatment. There was a significant association between the levels of CRP and the degree of platelet reactivity. However, while the CRP levels were associated with a worse outcome (AMI, stroke and death), the results of the platelet function tests were not. The importance of CRP in predicting prognosis depended on which adjustments were made for confounding factors. CRP and prognostic variables in a statistical model predicting death, however, showed that CRP was excluded. Thus CRP did not predict outcome beyond clinical prognostic variables. The results of these studies reinforce the importance of clinical variables such as heart failure, age, atrial fibrillation, smoking status, diabetes and impaired kidney function - all of which were associated with worse prognosis in multivariable analysis.

Thesis (Ph. D.)--Case Western Reserve University, 2008. / [School of Medicine] Department of Biochemistry. Includes bibliographical references.

Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine] Department of Biochemistry. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Thesis (M.S.)--Brigham Young University. Dept. of Exercise Sciences, 2005. / Includes bibliographical references.

Thesis (M.S.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains v, 82 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 33-35).

Thesis (M.S.)--Brigham Young University. Dept. of Exercise Sciences, 2006. / Includes bibliographical references.