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Biomedical subjects

Ioanna Dimopoulou

Publications and source records attributed to Ioanna Dimopoulou.

At least 19 recordsLinked to original sources

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators.

OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.

APACHE↗

Pituitary-adrenal responses to human corticotropin-releasing hormone in critically ill patients.

OBJECTIVE: To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome. DESIGN AND SETTING: Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital. PATIENTS: The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years). INTERVENTIONS: A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured over a period of 2 h. MEASUREMENTS AND RESULTS: In the overall patient population baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5 microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors. CONCLUSIONS: Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.

Adolescent↗

Hypothalamic-pituitary dysfunction in critically ill patients with traumatic and nontraumatic brain injury.

BACKGROUND: A significant number of studies have shown that critically ill patients with brain injury (BI) frequently exhibit abnormal pituitary hormonal responses during the immediate postinjury period. DISCUSSION: The elucidation of endocrine alterations depends on the criteria used, the diagnostic tests applied, and the timing of testing in relation to BI. The pattern of the detected hormonal abnormalities shows considerable variability. Altered endocrine responses are due mostly to hypothalamic changes rather than to pituitary dysfunction. Several studies have examined the correlation between hormonal alterations and BI severity, but the results are inconsistent. Furthermore, it remains currently unclear whether and how pituitary abnormalities adversely affect the clinical course of BI patients during the period of critical illness. On the basis of current knowledge, with the exception of clinically significant relative adrenal deficiency and diabetes insipidus, the other endocrine alterations do not seem to require any therapeutic intervention in severely ill BI patients. It is also uncertain whether hormonal abnormalities detected in the early post-BI period persist for the rest of these patients' lives. CONCLUSIONS: In view of current evidence indicating a high incidence of pituitary dysfunction even years following BI it is recommended that repetition of endocrine evaluation should be performed during the rehabilitation phase in all patients.

Brain Injuries↗

Endocrine alterations in critically ill patients with stroke during the early recovery period.

INTRODUCTION: Endocrine abnormalities in critically ill patients with stroke during the early recovery period have not been well characterized. METHODS: To investigate this issue, 33 consecutive mechanically ventilated patients (27 men) with hemorrhagic (n = 21) or ischemic (n = 12) stroke having a mean age of 57 +/- 12 years were studied. Glasgow Coma Scale score on admission in the hospital was 8 +/- 3. The following basal hormones were measured within 72 hours postextubation: cortisol, corticotropin (ACTH), free thyroxine, tri-iodothyronine, thyroid-stimulating hormone, testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, growth hormone, and insulin-like growth factor (IGF)-1. Subsequently, a low-dose (1 microg) ACTH stimulation test was performed. RESULTS: Twenty-six (79%) patients showed endocrine alterations. The most common change was low IGF-1 levels compatible with growth hormone deficiency (45%), followed by hypogonadism (39%), thyroid dysfunction (36%), and cortisol hyporesponsiveness (33%). CONCLUSION: Neuroendocrine changes occur with high frequency in critically ill patients with stroke during the early recovery period. It remains to be determined whether these changes have implications for functional and/or clinical outcome.

Aged↗

High incidence of neuroendocrine dysfunction in long-term survivors of aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: To investigate the incidence, pattern, and magnitude of neuroendocrine changes in long-term survivors of aneurysmal subarachnoid hemorrhage (SAH). METHODS: Thirty patients (16 women) with a mean age of 50+/-13 years underwent endocrine assessment between 12 and 24 months after aneurysmal SAH. SAH severity was graded clinically by the Hunt & Hess scale (median, II) and radiologically by the Fisher classification (median, II). Patients underwent measurement of basal hormone levels and dynamic assessment by the low-dose (1 microg) corticotropin stimulation test. Functional outcome was examined concurrently with endocrine testing by the modified Rankin Scale and the Barthel Index. RESULTS: Of the 30 patients tested, 14 patients (47%) showed isolated or combined endocrine abnormalities. These included low insulin-like growth factor 1 levels compatible with growth hormone deficiency in 37%, hypogonadism in 13%, and cortisol hyporesponsiveness to the low-dose corticotropin stimulation test in 10%; thyroid dysfunction in the form of subclinical hypothyroidism was observed in 7% of patients. Median modified Rankin Scale and Barthel Index at the time of endocrine testing were 1 and 100, respectively. There was no correlation between the presence of endocrine dysfunction and SAH severity indices or functional outcome scores. CONCLUSIONS: Long-term survivors of aneurysmal SAH frequently exhibit endocrine changes, with growth hormone and gonadal deficiencies predominating. Thus, screening of pituitary function is recommended in patients surviving SAH. The relationship between late hormonal alterations and functional outcome in patients with SAH warrants further study.

Activities of Daily Living↗

The low-dose corticotropin stimulation test in acute traumatic and non-traumatic brain injury: incidence of hypo-responsiveness and relationship to outcome.

OBJECTIVE: To investigate adrenal responses to the low-dose corticotropin (ACTH) stimulation test in acute traumatic or non-traumatic brain injury (BI) and to assess its value in predicting outcome. DESIGN: Prospective study. SETTING. Intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: Seventy-five patients with acute BI, with a median age of 45 years were investigated. BI was due to trauma ( n=51), ischemic stroke ( n=17), subarachnoid hemorrhage ( n=4) or intracerebral hemorrhage (n=3). INTERVENTIONS: Blood was taken on day 16 (median) after admission to the ICU to determine baseline cortisol and ACTH. Thereafter, a low-dose stimulation test (LDST) was performed: 1 microg of tetracosactrin was injected and 30 min later a second blood specimen was obtained to measure stimulated cortisol. Patients having a stimulated cortisol below 500 nmol/l were defined as non-responders to the LDST. MEASUREMENTS AND RESULTS: Median baseline and stimulated cortisol were 491 nmol/l and 690 nmol/l, respectively. The median increment in cortisol was 154 nmol/l (range 5-579 nmol/l). Mean ACTH was 46+/-21 pg/ml. Ten (13%) patients were non-responders to the LDST; these had a higher mortality rate compared to patients with adequate cortisol production (70 vs 32%, p=0.034). Logistic regression analysis revealed that APACHE II ( p<0.001), Glasgow Coma Scale (GCS) ( p=0.04) and age ( p=0.02) were independent outcome predictors. In contrast, the increment in cortisol ( p=0.26) did not add to outcome prediction. CONCLUSIONS: Adrenal hypo-responsiveness in the setting of acute traumatic or non-traumatic BI is not an independent outcome predictor in the presence of high APACHE II, low GCS and older age.

Adolescent↗

Endocrine abnormalities in critical care patients with moderate-to-severe head trauma: incidence, pattern and predisposing factors.

OBJECTIVE: To investigate the incidence and type of endocrine abnormalities in critical care patients with traumatic brain injury (TBI) and to examine their relationships to possible predisposing factors. DESIGN: Prospective study. SETTING: General intensive care unit in a university hospital. PATIENTS AND PARTICIPANTS: Thirty-four TBI patients (27 men, 7 women), having a mean age of 37+/-16 years, were studied after weaning from mechanical ventilation. INTERVENTIONS: Baseline endocrine assessment was carried out by measuring cortisol, corticotropin, dehydroepiandrosterone sulfate, free thyroxine, thyrotropin (TSH), testosterone, oestradiol, follicle stimulating hormone (FSH), luteinizing hormone, prolactin, growth hormone and insulin-like growth factor I. Dynamic evaluation was performed by human corticotropin releasing hormone and growth hormone releasing hormone in all patients. Male patients underwent additional investigation with gonadotropin-releasing hormone. Severity of neurological derangement was graded according to Glasgow Coma Scale (GCS), Marshall Computerized Tomographic Classification and intracranial pressure (ICP) levels. MEASUREMENTS AND RESULTS: Eighteen of the 34 patients (53%) had an abnormal result in at least one hormonal axis tested, with cortisol hyporesponsiveness and gonadal dysfunction being equally common, affecting 24% of patients. Endocrine abnormalities were associated with a higher brain CT-scan classification score ( p=0.02). The GCS on admission correlated positively with baseline FSH (r=0.37, p=0.03), peak FSH (r=0.41, p=0.03), testosterone (r=0.44, p=0.02) and TSH (r=0.39, p=0.03). There were no relations between ICP(max) and any baseline or dynamic hormone measurements. CONCLUSIONS: Patients with TBI receiving critical care show changes in their neuroendocrine responses, which depend upon clinical and radiological measures of head injury severity. Most common abnormalities include cortisol hyporesponsiveness and hypogonadism.

Adult↗

Hypothalamic-pituitary-adrenal axis dysfunction in critically ill patients with traumatic brain injury: incidence, pathophysiology, and relationship to vasopressor dependence and peripheral interleukin-6 levels.

OBJECTIVE: To investigate hypothalamic-pituitary-adrenal axis function in patients requiring mechanical ventilation for traumatic brain injury and to assess the relation of hypothalamic-pituitary-adrenal axis abnormalities with vasopressor dependence and peripheral cytokine levels. DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: Forty patients (33 men and 7 women) with moderate to severe traumatic brain injury (mean age, 37 +/- 16 yrs) were studied the day after termination of mechanical ventilation (7-60 days after trauma). INTERVENTIONS: First, a morning blood sample was obtained to measure baseline cortisol, corticotropin, interleukin-6, and tumor necrosis factor alpha. Subsequently, 1 microg of synthetic corticotropin was injected intravenously, and 30 mins later, a second blood sample was drawn to determine stimulated plasma cortisol. Based on data derived from healthy volunteers, patients having stimulated cortisol levels <18 microg/dL were defined as nonresponders to the low-dose stimulation test. Thirty-one patients underwent also a human corticotropin releasing hormone test. MEASUREMENTS AND MAIN RESULTS: In traumatic brain injury patients, mean baseline and low-dose stimulation test-stimulated cortisol levels were 17.2 +/- 5.4 microg/dL and 24.0 +/- 6.6 microg/dL, respectively. The median increment in cortisol was 5.9 microg/dL. Basal corticotropin levels ranged from 3.9 to 118.5 pg/mL. Six of the 40 patients (15%) failed the low-dose stimulation test. The human corticotropin releasing hormone test (performed in 26 responders and five nonresponders) revealed diminished cortisol release only in the low-dose stimulation test nonresponder patients. Corticotropin responses to corticotropin releasing hormone were consistent with both primary (three patients) and/or secondary (two patients) adrenal dysfunction. In retrospect, nonresponders to the low-dose stimulation test more frequently required vasopressors (6/6 [100%] vs. 16/34 [47%]; p =.02) and for a longer time interval (median, 0 vs. 293 hrs; p =.006) compared with responders. Furthermore, nonresponders had higher interleukin-6 levels compared with responders (56.03 vs. 28.04 pg/mL; p =.01), whereas tumor necrosis factor alpha concentrations were similar in the two groups (2.42 vs. 1.55 pg/mL; p =.53). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a subset of critically ill patients with moderate to severe head injury. This disorder is associated with prior vasopressor dependency and higher interleukin-6 levels.

Adrenocorticotropic Hormone↗

Health-related quality of life and disability in survivors of multiple trauma one year after intensive care unit discharge.

OBJECTIVE: To evaluate health-related quality of life and disability in multiple-trauma patients requiring intensive care unit management. DESIGN: A total of 87 survivors of multiple trauma, with a median age of 31 yrs and a median Injury Severity Score of 22, were enrolled in the present study. The Nottingham Health Profile, Glasgow Outcome Scale, and Rosser Disability Scale were used to assess the functional consequences of trauma 1 yr after intensive care unit discharge. RESULTS: A total of 64 of 87 patients had a problem in at least one of the six domains related to subjective health status. The most prevalent complaint was related to somatic subdimensions, but emotional functioning was also affected. Nottingham Health Profile part 2 showed that 63 of the survivors experienced problems in at least one of the daily activities. Of particular importance, inability to work was reported by 47% of the patients. Fifty-nine percent experienced moderate-to-severe disability as evaluated by Glasgow Outcome Scale and Rosser Disability Scale. High aggregate injury severity score along with severe head trauma were independent predictors of poor health-related quality of life and disability. CONCLUSIONS: The majority of survivors of major trauma exhibit considerable levels of disability and impairment in health-related quality of life. Global injury severity score and degree of brain trauma determine functional limitations. This information may help in organizing long-term rehabilitation of multiple-trauma patients.

Adolescent↗

Relationship of thyroid function to post-traumatic S-100b serum levels in survivors of severe head injury: preliminary results.

OBJECTIVE: To assess thyroid function abnormalities in survivors of severe head trauma and to examine their relationship with indices of brain injury severity. DESIGN: Prospective study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS AND PARTICIPANTS: Twenty-two (21 men) head-injured patients, with a median age of 25.5 years at the time of injury, were investigated. Severity of brain trauma was assessed by Glasgow Coma Scale (GCS) score, Marshall Computerized Tomographic Classification, intracranial pressure levels and serum S-100b concentrations measured over a 6-day period. INTERVENTIONS: Thyroid function testing was performed 1 year after ICU discharge and included the measurement of free thyroxine, triiodothyronine and thyrotropin. MEASUREMENTS AND RESULTS: On admission to the ICU, GCS ranged from 3 to 8. Peak S-100b was 1.49 microg/l (range: 0.37-5.26 microg/l). Median triiodothyronine and thyrotropin were 123 ng/dl and 1.60 microIU/ml, respectively. Free thyroxine was 1.08+/-0.22 ng/dl (range: 0.7-1.5 ng/dl). Overall, 7 of the 22 patients (32%) had thyroid dysfunction. Four patients had central hypothyroidism and three patients had subclinical hypothyroidism. Peak S-100b correlated negatively with free thyroxine (r=-0.47, p=0.02). There were no correlations between other brain injury severity indices and thyroid hormone levels. CONCLUSIONS: A significant subset of brain injury patients presents with changes in thyroid function 1 year after ICU discharge; these depend upon biochemical serum markers of head trauma severity.

Adolescent↗

Prediction of prolonged ventilatory support in blunt thoracic trauma patients.

OBJECTIVE: To identify predictors of prolonged (>7 days) mechanical ventilation (MV) in patients with blunt thoracic trauma. DESIGN: Prospective analysis of consecutive patients. SETTING: Adult intensive care unit (ICU) in a teaching, tertiary-care hospital. PATIENTS AND PARTICIPANTS: Sixty-nine patients (53 men, 16 women) with thoracic trauma having a median age of 35 (range 17-85) years and a median injury severity score (ISS) of 29 (range 14-41) were enrolled in the present study. Associated injuries included head-neck (77%), extremities (72%), external (67%), abdomen-pelvis (67%), and face (55%). INTERVENTIONS: Patient surveillance and data collection. MEASUREMENTS AND RESULTS: Thirty-three (48%) of the 69 patients required prolonged ventilatory support, ranging in duration from 8 to 38 (median 18) days. Logistic regression analysis revealed that advancing age (odds ratio=1.04, p=0.04), severity of head injury (odds ratio=1.92, p=0.008), and bilateral thoracic injuries (odds ratio=12.80, p<0.0001) were significant and independent predictors of long-lasting MV. In contrast, gender, injuries affecting the other body regions (face, abdomen-pelvis, extremities, and external), laparotomy in patients with abdominal injury, or PaO(2)/FIO(2) on admission in the ICU, were unrelated to prolonged MV. CONCLUSIONS: In thoracic trauma patients admitted in the ICU, prolonged mechanical ventilation was primarily determined by presence of bilateral chest injuries, age, and degree of neurotrauma. This information may help in planning the long-term care of such patients.

Adolescent↗

High prevalence of decreased cortisol reserve in brain-dead potential organ donors.

OBJECTIVE: To investigate the adrenocortical function in brain-dead patients, potential organ donors. DESIGN: Prospective study. SETTING: Intensive care units in two teaching hospitals. PATIENTS: A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 +/- 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. INTERVENTIONS: In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 microg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 microg/dL after the administration of adrenocorticotropic hormone were defined as responders. MEASUREMENTS AND MAIN RESULTS: After the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 +/- 6.2 vs. 17.0 +/- 6.6 microg/dL, p <.001) and stimulated (16.9 +/- 6.3 vs. 23.9 +/- 5.7 microg/dL, p =.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p <.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r =.71, p =.001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p =.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 +/- 11.4 vs. 6.8 +/- 4.2 microg/dL, p =.003) and stimulated serum cortisol (28.8 +/- 9.9 vs. 16.3 +/- 4.3 microg/dL, p =.008). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.

Adolescent↗