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| 2. |
- Fläring, Urban
(författare)
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Glutathione during stress in man
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glutathione, a tripeptide (gamma-glutamyl, -cysteinyl, -glycine), is quantitatively the most important antioxidant in man, protecting cells from the toxic effects of reactive oxygen species (ROS). These highly reactive molecules cause tissue damage and are produced at high rates during critical illness including sepsis [1-4]. Glutathione is mainly an intracellular acting substance and is continuously produced in almost all tissues [5]. Besides its antioxidant properties, it also has other important functions such as detoxification and metabolism of xenobiotics and counteracts the effects of radiation [6]. In septic patients, glutathione concentration is decreased in erythrocytes and in skeletal muscle by approximately 40 % within the first 24 hours after admission to the ICU [7]. Muscle glutathione depletion has been shown to correlate with mortality in septic ICU patients [8]. The consequences of glutathione depletion seen in septic patients are not fully understood. In this thesis work new insights into the glutathione status during sepsis are obtained. Study 1. Glutamine is related to glutathione via glutamate which is a direct precursor for glutathione. Both glutathione and glutamine are depleted in skeletal muscle during sepsis and after major surgery. Patients (n = 18) undergoing major abdominal surgery were double blindly randomized to receive either glutamine enriched total parenteral nutrition (TPN) or conventional TPN. The results show that glutamine enriched TPN attenuates the decrease in skeletal muscle glutathione. Study 2. The temporal changes of glutathione status in skeletal muscle were characterized. Samples were taken every 72 hours for 6 days in septic ICU patients (n = 10) with multiple organ failure. The results confirmed the initial glutathione depletion. However total glutathione was spontaneously restituted within a week of ICU treatment, despite low concentration of muscle glutamine. Although total glutathione concentration was restituted, the redox status of glutathione showed an increased oxidized state throughout the study period. Study 3. The temporal changes of glutathione status in whole blood and plasma were investigated in septic ICU patients with multiple organ failure (n = 11), to elucidate whether erythrocytes were representative for skeletal muscle. Samples were taken every 72 hours for 15 days. The results showed an initial depletion of glutathione in whole blood that remained throughout the study, in contrast to what was seen in skeletal muscle. In parallel, the concentration of plasma glutathione increased, indicating a leakage of glutathione from the erythrocytes and/or other tissues via the endothelium. Study 4. The changes occurring in glutathione status in whole blood and plasma during the initial phase (within the first hours) of sepsis have not been characterized in man. Glutathione status in whole blood, muscle and plasma was investigated in healthy volunteers (n = 8) using an endotoxin model, mimicking the physiological and metabolic changes seen in the initial phase of sepsis. The results showed a decrease of total glutathione concentration in plasma. In contrast, the whole blood and muscle concentrations remained unaltered. It was concluded that whole blood and muscle glutathione concentration was maintained in the initial phase of sepsis.
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| 3. |
- Ranta, Susanna, et al.
(författare)
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Extracorporeal Membrane Oxygenation Support in Children With Hematologic Malignancies in Sweden
- 2021
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Ingår i: Journal of Pediatric Hematology/Oncology. - : Wolters Kluwer. - 1077-4114 .- 1536-3678. ; 43:2, s. e272-e275
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Tidskriftsartikel (refereegranskat)abstract
- Background: Extracorporeal membrane oxygenation (ECMO) is used in severe respiratory and/or circulatory failure when conventional critical care fails. Studies on patients with hematologic malignancies on ECMO have shown contradictory results; immunosuppression and coagulopathy are relative contraindications to ECMO.Observations: This nationwide Swedish retrospective chart review identified 958 children with hematologic malignancies of whom 12 (1.3%) required ECMO support. Eight patients survived ECMO, 7 the total intensive care period, and 6 survived the underlying malignancy.Conclusions: ECMO may be considered in children with hematologic malignancy. Short-term and long-term survival, in this limited group, was similar to that of children on ECMO at large.
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- Ranta, Susanna, et al.
(författare)
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Icu admission in children with acute lymphoblastic leukemia in sweden: Prevalence, outcome, and risk factors
- 2021
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Ingår i: Pediatric Critical Care Medicine. - Philadelphia, PA, United States : Lippincott Williams & Wilkins. - 1529-7535 .- 1947-3893. ; 22:12, s. 1050-1060
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVES: Despite progress in the treatment of childhood acute lymphoblastic leukemia, severe complications are common, and the need of supportive care is high. We explored the cumulative prevalence, clinical risk factors, and outcomes of children with acute lymphoblastic leukemia, on first-line leukemia treatment in the ICUs in Sweden.DESIGN: A nationwide prospective register and retrospective chart review study.SETTING: Children with acute lymphoblastic leukemia were identified,and demographic and clinical data were obtained from the Swedish Childhood Cancer Registry. Data on intensive care were collected from the Swedish Intensive Care Registry. Data on patients with registered ICU admission in the Swedish Childhood Cancer Registry were supplemented through questionnaires to the pediatric oncology centers.PATIENTS: All 637 children 0-17.9 years old with acute lymphoblastic leukemia diagnosed between June 2008 and December 2016 in Sweden were included.INTERVENTIONS: None.MEASUREMENTS AND MAIN RESULTS: Twenty-eight percent of the children (178/637) were admitted to an ICU at least once. The Swedish Intensive Care Registry data were available for 96% of admissions (241/252). An ICU admission was associated with poor overall survival (hazard ratio, 3.25; 95% CI, 1.97-5.36; p ≤ 0.0001). ICU admissions occurred often during early treatment; 48% (85/178) were admitted to the ICU before the end of the first month of acute lymphoblastic leukemia treatment (induction therapy). Children with T-cell acute lymphoblastic leukemia or CNS leukemia had a higher risk of being admitted to the ICU in multivariable analyses, both for early admissions before the end of induction therapy and for all admissions during the study period.CONCLUSIONS: The need for intensive care in children with acute lymphoblastic leukemia, especially for children with T cell acute lymphoblastic leukemia and CNS leukemia, is high with most admissions occurring during early treatment.
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