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Biomedical subjects

Else Tønnesen

Publications and source records attributed to Else Tønnesen.

12 recordsLinked to original sources

[Operative risk in patients with pulmonary disease].

Surgical patients with pulmonary disease are at increased risk of developing postoperative pulmonary complications and some patients may need postoperative ventilatory support. Stratifying and planning the right strategies for these patient categories are important since complications increase morbidity and mortality. Predictive tests, however, are few and preoperative interventions are of limited value. This brief review summarizes the current knowledge on perioperative measures to reduce pulmonary complications.

Anesthesia↗

[Postoperative analgesia following total knee arthroplasty].

Total knee arthroplasty (TKA) is associated with considerable postoperative pain which may be difficult to manage. This article describes advantages and disadvantages of the different analgesic techniques used for pain treatment after TKA, for example i.v. patient-controlled analgesia, epidural pain treatment, and peripheral nerve blocks (especially femoral and sciatic blocks). Randomised studies suggest that peripheral nerve blocks have the best effect and have fewest side effects. Intra-articular administration of analgesics is the most recently introduced technique.

Analgesia↗

Endotoxemia-induced lymphocyte apoptosis is augmented by a hyperinsulinemic-euglycemic clamp.

BACKGROUND: Sepsis and endotoxemia are associated with lymphocyte apoptosis. This has been regarded as harmful, contributing to further immune suppression in already immune-compromised patients. Because normalization of blood glucose improves outcome in critically ill patients, the authors hypothesized that one of the effects of insulin and normoglycemia would be inhibition of lymphocyte apoptosis. Therefore, in this experimental study in pigs, the authors examined the separate and combined effects of acute endotoxemia and a hyperinsulinemic-euglycemic clamp (HEC) on lymphocyte apoptosis. METHODS: After 60 min of stabilization, 38 anesthetized and mechanically ventilated pigs (weight, 35-40 kg) were divided (by randomization performed before the experiment) into four groups and were then studied for 570 min. Group 1 received no intervention. Group 2 received a HEC (5 mm p-glucose, insulin infusion rate of 0.6 mU . kg (-1). min(-1)) for 570 min. Group 3 received a lipopolysaccharide infusion for 180 min. Group 4 was given a combination of a HEC and a lipopolysaccharide infusion. After the 570-min study period, the pigs were killed, and tissue was sampled from the spleen and frozen. In four sections of each sample, the apoptosis of B and T lymphocytes were analyzed using stereologic methods: The number of apoptotic B and T cells was estimated by fluorescence immunohistochemistry with anti-active caspase-3 and either anti-CD21 (B lymphocytes) or anti-CD3epsilon (T lymphocytes). The number of apoptotic B and T lymphocytes was then compared using two-way analysis of variance, and the interaction between endotoxemia and the clamp (hyperinsulinemia and euglycemia) was investigated. RESULTS: Endotoxemia induced apoptosis of B (P < 0.001) and T lymphocytes (P = 0.016) in the spleen, and this effect was independent of the clamp. The ratios of apoptotic cells in the spleen tissue of pigs with and without endotoxemia were 2.4 (confidence interval, 1.7-3.4) and 1.6 (confidence interval, 1.1-2.2) for B and T lymphocytes, respectively. Independent of endotoxin infusion, HEC increased the number of apoptotic lymphocytes (P = 0.029 and P = 0.038 for B and T lymphocytes, respectively). The ratios of the number of apoptotic spleen cells in pigs treated and not treated with HEC were 1.5 (confidence interval, 1.0-2.1) and 1.5 (confidence interval, 1.0-2.1) for B and T lymphocytes, respectively. CONCLUSION: In this porcine model, both endotoxemia and a HEC increased the number of apoptotic B and T lymphocytes in the spleen. Contrary to our hypothesis, lymphocyte apoptosis during acute endotoxemia was augmented by a HEC.

Algorithms↗

Hyperglycaemia and mortality in critically ill patients. A prospective study.

OBJECTIVE: To describe hyperglycaemia as a possible marker of morbidity and mortality in critically ill medical and surgical patients admitted to a multidisciplinary ICU. DESIGN: Prospective cohort study. SETTING: A 13-bed non-cardiac multidisciplinary ICU in a university hospital. PATIENTS AND PARTICIPANTS: Adult patients consecutively admitted to the ICU in a 6-month period. Patients with fewer than 2 days' stay in the ICU and patients with known diabetes were excluded. MEASUREMENTS AND RESULTS: At admission a registration form was filled in including demographic data, first and second day APACHE II scores, infections and daily maximum blood glucose level. In surgical patients, high maximum blood glucose level during the stay in ICU was correlated with increased mortality, morbidity and frequency of infection. In medical patients, we found a non-significant trend towards a correlation between hyperglycaemia and morbidity and mortality, respectively. CONCLUSIONS: High blood glucose level during the stay in ICU was a marker of increased morbidity and mortality in critically ill surgical patients. In medical patients the same trend was found, but non-significant. The population of patients in the present study are heterogeneous and the results from surgical critically ill patients should not be generalised to medical patients.

APACHE↗

Acute hyperinsulinemia restrains endotoxin-induced systemic inflammatory response: an experimental study in a porcine model.

BACKGROUND: Intensive insulin therapy in critically ill patients reduces morbidity and mortality. The current study elucidates whether acute hyperinsulinemia per se could attenuate the systemic cytokine response and improve neutrophil function during endotoxin (lipopolysaccharide)-induced systemic inflammation in a porcine model. METHODS: Pigs were anesthetized, mechanically ventilated, randomized into four groups, and followed for 570 min: group 1 (anesthesia solely, n = 10), group 2 (hyperinsulinemic euglycemic clamp [HEC], n = 9), group 3 (lipopolysaccharide, n = 10), group 4 (lipopolysaccharide-HEC, n = 9). Groups 3 and 4 were given a 180-min infusion of lipopolysaccharide (total, 10 microg/kg). Groups 2 and 4 were clamped (p-glucose: 5 mM/l, insulin 0.6 mU.kg(-1).min(-1)) throughout the study period. Changes in pulmonary and hemodynamic function, circulating cytokines, free fatty acids, glucagon, and neutrophil chemotaxis were monitored. RESULTS: Tumor necrosis factor alpha and interleukin 6 were significantly reduced in the lipopolysaccharide-HEC group compared with the lipopolysaccharide group (both P = 0.04). In the lipopolysaccharide-HEC group, the glucagon response was diminished compared with the lipopolysaccharide group (P < 0.05). Serum free fatty acid concentrations were decreased in animals exposed to HEC. Animals receiving lipopolysaccharide showed an increase in pulmonary pressure (P < 0.001), but otherwise, there were no major changes in pulmonary or hemodynamic function. Neutrophil function was impaired after lipopolysaccharide administration. CONCLUSION: Hyperinsulinemia concomitant with normoglycemia reduces plasma concentrations of tumor necrosis factor alpha and the catabolic hormone glucagon in lipopolysaccharide-induced systemic inflammation in pigs. The finding strongly supports the role of insulin as an antiinflammatory hormone. Whether the effect to some extent operates via a reduced free fatty acid concentration is unsettled.

Acute Disease↗

The roles of insulin and hyperglycemia in sepsis pathogenesis.

Hyperglycemia is a risk marker of morbidity and mortality in acute critical illness, and insulin therapy seems to be beneficial in this patient group. Whether this is true for a population of sepsis patients, as such, has not been investigated in clinical trials, but evidence from in vitro studies and experimental sepsis suggests that this may be the case. The endocrinology of septic patients is characterized by a shift in the balance between insulin and its counter-regulatory hormones favoring the latter. This leads to prominent metabolic derangements composed of high release and low use of glucose, amino acids, and free fatty acids (FFA), resulting in increased blood levels of these substrates. Circulating, proinflammatory mediators further enhance this state of global catabolism. Increased levels of glucose and FFA have distinct effects on inflammatory signaling leading to additional release of proinflammatory mediators and endothelial and neutrophil dysfunction. Insulin has the inherent capability to counteract the metabolic changes observed in septic patients. Concomitantly, insulin therapy may act as a modulator of inflammatory pathways inhibiting the unspecific, inflammatory activation caused by metabolic substrates. Given these properties, insulin could conceivably be serving a dual purpose for the benefit of septic patients.

Endocrine System↗

Phenotypic characterisation of porcine counterparts of human NK cell populations--implications for pre-clinical studies.

The phenotype of cryopreserved crossbred porcine PBMC, with special emphasis on NK cell related surface markers, was characterised. The phenotype expressed prior to stimulation with rHu IL2 and rHu IL12 was related to the in vitro cytotoxic capacity estimated in a 4-h or 21-h 51Cr-release assay. PBMC incubated in growth medium without addition of cytokines were used to investigate the spontaneous cytotoxic capacity. The results of this study suggest that crossbred porcine PBMC comprise a specific subset expressing the phenotype CD2+CD3-CD4-CD8+SWC3-CD16+CD21-. No spontaneous cytotoxicity of the PBMC could be estimated, but the expression of CD16 seems to be a basic marker of the cytokine induced cytotoxic activity. This study suggests that cryopreserved porcine PBMC can be used when possible influences on the porcine NK cell system are investigated in relation to disease models conducted experimentally in crossbred pigs.

Animals↗

Neutrophils and platelets accumulate in the heart, lungs, and kidneys after cardiopulmonary bypass in neonatal pigs.

OBJECTIVE: Cardiac surgery with cardiopulmonary bypass elicits a systemic inflammatory response. An exaggerated response is associated with organ dysfunction and increased morbidity and mortality. DESIGN: The aim of the present study was to investigate whether the cardiopulmonary bypass procedure in itself results in accumulation of isotope-labeled platelets, polymorphonuclear neutrophils, and fibrinogen at organ levels in neonatal pigs and to monitor changes in organ function. SETTING: Pediatric cardiopulmonary bypass setup with 60 mins of aortic cross-clamp time and 120 mins of hypothermic cardiopulmonary bypass time. SUBJECTS: Thirty piglets were allocated to sternotomy alone (sham group, n = 15) or to sternotomy and cardiopulmonary bypass (n = 15). MEASUREMENTS AND MAIN RESULTS: Isotope-labeled autologous polymorphonuclear neutrophils, platelets, and commercially available fibrinogen were infused, and the specific accumulation at organ level was measured in a gamma counter 4 hrs after termination of cardiopulmonary bypass. Concomitant changes in oxygenation index and cardiac output were registered. Animals exposed to cardiopulmonary bypass showed a significantly higher technetium-99m-polymorphonuclear neutrophil accumulation in the lungs and kidneys, whereas indium-111-platelets accumulated in the heart and kidneys compared with the sham group. There was a significantly larger increase in oxygenation index and significantly larger decrease in cardiac output between the pre- and postcardiopulmonary bypass period in the cardiopulmonary bypass group compared with the sham group. CONCLUSIONS: The cardiopulmonary bypass procedure without cardiac surgery elicits organ dysfunction in terms of impaired respiratory and hemodynamic function. Platelets and polymorphonuclear neutrophils were entrapped in the heart, lungs, and kidneys of cardiopulmonary bypass animals, indicating that cell accumulation may contribute to the developing organ dysfunction.

Animals↗

Effect of modified ultrafiltration on the inflammatory response in paediatric open-heart surgery: a prospective, randomized study.

Modified ultrafiltration (MUF) is often used in conjunction with paediatric cardiac surgery with cardiopulmonary bypass (CPB) and is thought to improve clinical outcome. It is unclear whether these improvements (if any) are due to the removal of inflammatory mediators. In this prospective study, 18 children aged 12-24 months undergoing uncomplicated cardiac surgery with methylprednisolone added in the pump prime were randomized to receive CPB with (n = 10) and without (n = 8) MUF. Cytokines (TNFalpha, IL-6, IL-1beta, IL-10, IL-1ra), complement split products (C3d, C4d) and coagulation system activation (F1 + 2, ATIII) were measured pre-, peri- and up to 48 h postoperatively. For clinical outcome, the alveolar-arterial oxygen (A-a) gradient, transfusion requirement, drain loss, mean blood pressure and requirement for inotropic support were registered up to 24 h postoperatively. Our results show an improvement in postoperative oxygenation as well as a tendency towards decreased drain loss and improved haemodynamics in the MUF group. There were no intergroup differences detectable for TNFalpha, IL-1beta, IL-1ra, complement and coagulation markers. We conclude that MUF in itself does not significantly influence TNFalpha, IL-1beta, IL-1ra and the complement and coagulation profiles in children undergoing cardiac surgery with CPB. Despite this, there was some evidence for improved clinical outcome. Our results do not support that MUF improves postoperative organ function by modulation of the measured markers of inflammation.

Biomarkers↗

Effects of morphine on tumour growth.

Endogenous opiate alkaloids, such as morphine, and their peptide counterparts have been implicated in a wide variety of pharmacological and physiological functions. In addition to their use in the treatment of pain, opioids, appears to be important in the growth regulation of normal and neoplastic tissue. This review will focus on the influence of endogenous and exogenous opioids on tumour growth, with emphasis on immunoregulatory and antiproliferative mechanisms.

Analgesics, Opioid↗