S-100B in serum and urine after traumatic head injury in children.

BACKGROUND: Children with head trauma are frequently seen in many emergency units. The clinical evaluation of these patients is difficult for a number of reasons and improved diagnostic tools are needed. S-100B, a protein found in glial cells, has previously been shown to be a sensible marker for brain damage after head injury in adults, but few studies have focused on its use in children. METHODS: In this study, 111 children with head trauma were included and venous blood and urine samples were taken at arrival (S1 and U1) and 6 hours later (S2 and U2). S-100B levels were analyzed. Clinical and radiologic evaluations were performed according to hospital routine. Two groups were identified- group 1: no computed tomography (CT) scan performed ora CT scan without any sign of trauma-related intracranial pathology (n = 105). Group 2: A CT scan with signs of trauma-related intracranial pathology (n = 6). RESULTS: In group 1, the median (inter quartile range) serum S-100B value in S1-samples was 0.111 microg/L (0.086-0.153), and in group 2, it was 0.282 microg/L (0.195-1.44) (p < 0.01). Also, S2 values significantly differed between the two groups. Urine values were, however, not significantly differing between the groups. CONCLUSIONS: Serum S-100B values within 6 hours after head trauma in children were significantly higher in patients with intracranial pathology compared with those without intracranial complications. Identification of these high-risk patients already in the emergency department is of major importance, and we suggest that S-100B could be a valuable diagnostic tool in addition to those used in clinical practice today.

Correlation between catecholamine levels and outcome in patients with severe head trauma.

Some studies have shown that catecholamines and the changes in their levels during and after head trauma can be useful in predicting the outcome in head trauma patients. The goal of this study is to search for a probable relation between urine levels of catecholamines and prognosis in patients with severe head trauma. Fifty four patients with severe head trauma Glasgow Coma Scale (GCS < or = 8) on admission time were recruited in Imam Reza Hospital within one. These patients were included when having no major accompanying trauma in other organs. Twenty four hour urine was collected after admission and levels of metanephrine and nor-metanephrine were measured. The relation between urine levels of these metabolites with final outcome and also with GCS at admission, 24, 48 h and 1 week after admission and discharge time and Glasgow Outcome Scale (GOS) were studied. Fifty two patients, 48 males and 4 females with a mean age of 32.3 +/- 14.7 (3-72) years were included. The main underlying etiologies were motorcycle (46.2%) and car accidents (25%). Diffuse axonal injury, brain contusion and subdural hematoma were three main diagnoses (28.8, 17.3 and 15.4% of the cases, respectively). 19 (36.5%) of the patients expired within the study period. The mean level of metanephrine and normetanephrine in urine were 207.9 +/- 200.5 and 330.2 +/- 218.4 microg in 24 h, respectively. There was no meaningful relation between urine levels of these metabolites and any of GCS and GOS. There was also no meaningful relation between these parameters and final prognosis in patients.

Detection of clenbuterol in heroin users in twelve postmortem cases at the Philadelphia medical examiner's office.

The presence of clenbuterol, a beta2-adrenergic agonist banned for human use in the United States because of its serious side effects, is reported in a series of 12 postmortem cases in which the cause of death was attributed to illicit drug use. During the first three months of 2007, postmortem specimens from cases previously screening positive for opiates or fentanyl were screened specifically for clenbuterol using enzyme-linked immunosorbent assay. Confirmation of clenbuterol was performed using solid-phase extraction, derivatization with trimethylboroxine, and analysis utilizing a gas chromatograph-mass spectrometer (GC-MS) operated in the full-scan mode. The limits of detection and quantitation in blood were 2.5 and 5 ng/mL, respectively. Linearity was from 5 to 100 ng/mL. Clenbuterol was positive in 12/106 (11%) drug-related cases and in 12/575 (2.1%) of the total cases tested. In each of the 12 cases positive for clenbuterol, heroin use was either confirmed by the presence of 6-acetylmorphine or strongly suspected by the presence of morphine with a history of heroin abuse. Because the use of clenbuterol in the United States is restricted to veterinary medicine, its detection is an unexpected finding. Its presence in these cases serves as a caution to emergency room physicians and toxicologists to consider and test for clenbuterol when treating a suspected heroin user who presents atypically. This is the first known series of clenbuterol-positive cases of illicit drug users to be reported from a medical examiner's toxicology laboratory.

[Dynamics of changes in the concentrations of selenium in plasma, urine, and erythrocytes in children with severe brain injury].

The role of selenium in man is diverse. In particular, selenium is a cofactor of the major antioxidative enzyme glutathione peroxidase, which inhibits free radical oxidation reactions and restores the normal vital functions of cells and organs. This study deals with selenium metabolism in severe brain injury and its correction modes.

Emergency department measurement of urinary S100B in children following head injury: can extracranial injury confound findings?

OBJECTIVE: To assess the potential role of urinary S100B as a prognostic biochemical marker following head injury in children in a UK emergency department setting. METHODS: A case-control pilot study was performed in 20 patients with head injury and 15 controls (with extracranial trauma) aged <13 years and within 12 h of their injury recruited over a 4-month period. Urinary S100B levels were measured at presentation to the emergency department. RESULTS: The two groups showed no significant differences in basic characteristics (height, weight, time to sample collection). 50% of the case group had measurable concentrations of S100B following head injury (range 0.02-0.07 microg/l). All patients in the control group had measurable S100B concentrations following extracranial trauma (range 0.02-0.09 microg/l). No significant rise in S100B concentrations occurred in two patients with severe head injuries (Glasgow Coma Score (GCS) <9) and in one patient with a moderate head injury (GCS 10), despite significant injuries on the CT scan. CONCLUSION: Despite detecting measurable S100B levels in urine following head injury, the same levels are measured following extracranial trauma. Urinary S100B is therefore not useful as an early biochemical marker following head injury in children.

Hypothalamic-pituitary-adrenal axis and interleukin-6 activity in children with head trauma and syndrome of inappropriate secretion of antidiuretic hormone.

OBJECTIVE: Arginine vasopressin (AVP; anti-diuretic hormone) and corticotropin-releasing hormone are the two major secretagogues of hypophyseal adrenocorticotropin (ACTH). Interleukin-6 (IL-6) is a potent stimulator of the human hypothalamic-pituitary-adrenal axis (HPA) and a secretagogue of both parvocellular and magnocelullar AVP. We have previously suggested that IL-6-stimulated AVP secretion may be the origin of the syndrome of inappropriate antidiuretic hormone secretion (SIADH) in inflammatory conditions. STUDY DESIGN: To further elucidate the relationship between IL-6 and SIADH as well as IL-6 and HPA axis activity, we studied eight previously healthy children (age 6.3 +/- 4.8 [mean +/- SD] years, weight 23.8 +/- 10.5 kg) who--after sustaining head trauma--presented SIADH during hospitalization (for 7.1 +/- 3.8 days) in the pediatric intensive care unit (P-ICU). Routine blood samples were taken twice daily at 08:00 and 20:00 hours. All children but one survived. Measurements included blood and urine osmolality (BlOsm and UrOsm, respectively), serum cortisol (F) and IL-6, plasma ACTH and AVP. Correlations were assessed with linear regression among the areas under the curve (AUC) of BlOsm, UrOsm, ACTH, F, IL-6 and AVP, separately for BlOsm values <280 mOsm (SIADH phase) and > or = 280 mOsm (non-SIADH phase). RESULTS: During the SIADH phase AVP-AUC correlated positively with IL-6-AUC (r = +0.96, p<0.05), BlOsm-AUC correlated positively with AVP-AUC and F-AUC (r = +0.95 and +0.98, p<0.05, respectively) and F-AUC correlated positively with ACTH-AUC (r = +0.99, p<0.05). During the non-SIADH phase ACTH-AUC correlated positively with BlOsm-AUC (r = +0.96, p<0.05). CONCLUSION: IL-6 secreted during an aseptic inflammatory state, such as sustaining head trauma with SIADH, is quantitatively correlated to AVP, indicating that this cytokine is directly and/or indirectly involved in the pathogenesis of SIADH.

Pharmacokinetics of phenytoin in children with acute neurotrauma.

OBJECTIVE: To determine the pharmacokinetics of intravenous phenytoin in critically ill infants and children with acute neurologic injury. DESIGN: A prospective, descriptive study. SETTING: A pediatric intensive care unit. PATIENTS: Sixteen children, 0.5 to 16 yrs of age (mean 7.6), with various types of acute neurologic injuries, receiving intravenous phenytoin therapy. INTERVENTIONS: Blood samples were collected to measure total and free phenytoin concentrations in plasma. A 24-hr urine collection was made to determine the concentrations of the major metabolite of phenytoin. MEASUREMENTS AND MAIN RESULTS: In 12 children who survived the acute illness, a lower-than-predicted Michaelis-Menten constant (Km) and higher-than-predicted maximum rate of metabolism (Vmax) were observed. Initial free phenytoin fractions ranged between 0.08 and 0.15. In the eight patients who had additional free fractions measured, six patients demonstrated an increase (9.1% to 34% increase) in free fraction, while two patients demonstrated a decrease (1.8% and 19.8% decrease) in free fraction. The ratio of amount of phenytoin to phenytoin plus 5-(p-hydroxyphenyl)-5-phenylhydantoin excreted in the urine in a 24-hr urine collection demonstrated a wide inter-patient variability. There was no correlation in the difference between the predicted and calculated Km and Vmax values and Glasgow Coma Score, circulating albumin concentration, or concomitant medications. CONCLUSION: Based on the average Km and Vmax values of the children enrolled in our study, it appears that children with neurologic injury between the ages of 0.5 and 9 yrs may require dosages of at least 8 to 10 mg/kg/day, and children aged 10 to 16 yrs may require 6 to 8 mg/kg/day to attain therapeutic phenytoin concentrations.

Assessing the validity of adjusted urinary urea nitrogen as an estimate of total urinary nitrogen in three pediatric populations.

Nitrogen excretion is a useful measurement for determining efficiency of protein utilization. Knowledge of nitrogen losses is especially important in the treatment of stressed, postsurgical, or catabolic patients, in whom optimizing the amount of nitrogen intake in the diet may spare visceral and somatic proteins and encourage anabolism. Many methods have been used to estimate total urinary nitrogen (TUN) in different patient populations. Urinary urea nitrogen (UUN) values are routinely adjusted and used by investigators who are not able to measure TUN directly by either Kjeldahl or pyrochemoluminescent methods. The rationale for the use of adjusted UUN concentrations to predict TUN is based on adult experiences. No similar experience in pediatrics has been published. We have compared TUN with adjusted UUN in a study of 250 urine samples from pediatric patients (n = 34) and normal pediatric volunteers (n = 109). Our findings suggest that adjusted UUN (determined by previously established formulas) may be of limited use in estimating TUN in neonates, infants, and critically ill pediatric patients; however, adjusted UUN may be useful in approximating TUN in healthy school-aged children. Good correlations were found between UUN and TUN for critically ill children and postsurgical neonates and infants, suggesting that these newly described regression equations (once validated) may be useful in predicting TUN from a measured UUN.

Coagulopathy and catecholamines in severe head injury.

The prospective study reported here evaluated the relationship between coagulopathy, catecholamines, and outcome in severe head trauma. Thirty-six trauma patients (10 with penetrating injuries, 26 with blunt injuries, 50% overall mortality) were evaluated. These patients had severe head trauma (Glasgow Coma Scale score less than 9). Blood was analyzed for platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, D-dimer, antithrombin III, protein C, and protein S levels. A 24-hour urine sample was collected for vanillylmandelic acid (VMA), normetanephrine, and metanephrine determinations. A control group of five patients undergoing elective neurosurgery was also studied. Statistically significant differences between head injury survivors and nonsurvivors were present for platelet count, PT, and fibrinogen activity. There were no differences in the results of the other coagulation tests or in urinary catecholamine levels. The trauma patients differed from the elective neurosurgery patients with regard to D-dimer levels, PT, PTT, protein C levels, and urinary normetanephrine concentrations. Head trauma patients have a coagulopathy that is absent in patients following elective neurosurgical procedures. The coagulopathy may correlate with poor survival in head trauma and may be related to a catecholamine surge.

Substrate oxidation and the contribution of protein oxidation to energy expenditure after severe head injury.

The 'flow' phase response to head injury is characterized by hypermetabolism and catabolism of lean body mass. In order to measure the contribution of protein oxidation (CPO) to resting metabolic expenditure (RME), 11 severely head injured patients (AIS 5) were studied. All patients had 24 h urine collections for at least 10 days after injury and RME was determined at intervals by indirect calorimetry. No patient received exogenous steroids. Peak urinary nitrogen excretion was 11.63 +/- 1.28 g/m2/day occurring between days 6 and 9 after injury. Fat oxidation was the greatest component of the RME at all times after head injury and the CPO to RME was 26.4 +/- 2.9 per cent during days 1-2, 31.8 +/- 3.3 per cent during days 3-5, 28.6 +/- 3.4 per cent during days 6-9 and 23.3 +/- 3.8 per cent during days 10-20 after injury. These figures are higher than those previously reported for burns, musculoskeletal injury or sepsis. The mechanism for the increased CPO is unclear. It may be related to such conditions of management as paralysis and fasting, but more likely it is an idiosyncratic feature of the metabolic response to head injury.

Vasopressin levels and pediatric head trauma.

The syndrome of inappropriate secretion of antidiuretic hormone is associated with head trauma; however, there are no reports concerning vasopressin levels in pediatric patients with head trauma. Urine vasopressin in eight children (mean +/- SEM, age 7.5 +/- 1.6 years, range 1 to 15 years) was measured by radioimmunoassay during their hospitalization for head trauma. Urine vasopressin values for ten healthy children (mean age 5.4 +/- 1.3 years) and for eight children hospitalized for systemic antibiotic treatment of infections (age 5.9 +/- 1.8 years) also were obtained. Urine vasopressin, urine and serum sodium concentration and osmolality, urea nitrogen, creatinine, and fluid intake were measured within 24 hours of admission and daily for the following two days. For the first three days following head trauma, mean urine vasopressin levels in pediatric patients with head trauma were increased (P less than .05) compared with those of healthy children. Despite fluid restriction to 85% of maintenance level, 25% of patients with head trauma exhibited the clinical syndrome of inappropriate secretion of antidiuretic hormone (hyponatremia, increased urinary sodium, diminished serum osmolality, and urine osmolality greater than serum osmolality). Urine osmolality greater than 800 mosm/kg was associated with markedly increased urine vasopressin levels (200 to 1,650 pg/mL); children with this finding may be at particular risk for the syndrome of inappropriate secretion of anti-diuretic hormone without restrictive water intake.

Comparison of urinary urea nitrogen excretion and measured energy expenditure in spinal cord injury and nonsteroid-treated severe head trauma patients.

Severe head trauma patients (HT) exhibit markedly elevated energy expenditure and 24-hr urinary urea nitrogen excretion (UUN) values. The objective of this study was to compare seven spinal cord injured patients (SCI) to seven HT for changes in UUN and measured energy expenditure (MEE) over the first 18 days following injury. Energy expenditure was measured by indirect calorimetry and compared to values predicted by the Harris Benedict Equation (PEE). There were six quadriplegics and one paraplegic in the SCI group. HT patients had peak Glasgow Coma Scale scores of 3 to 10 for the first 24 hr postinjury. Patients were studied prospectively and matched for age, sex, and admitting weight Week 1 following the injury, SCI had mean UUN values of 0.18 +/- 0.04 g/kg/day vs 0.18 +/- 0.01 for HT patients. The mean MEE/PEE ratio was 0.56 for the SCI and 1.4 for HT (p less than 0.01). Over the entire study period the mean UUN value for SCI was 0.23 +/- 0.03 g/kg vs 0.21 +/- 0.01 for HT. The mean MEE/PEE ratio for SCI was 0.94 while HT remained elevated at 1.5 (p less than 0.05). Although the UUN was comparable in SCI vs HT, there was a significant difference in MEE/PEE between the groups. The elevation in UUN observed in SCI is not due to a hypermetabolic state. This suggests that different mechanisms promote the increased nitrogen excretion observed in these two populations.

Steroid administration potentiates urinary nitrogen losses in head-injured children.

Exogenous steroid administration has been shown to increase post-traumatic nitrogen excretion in adults. Children sustaining head injuries and treated with steroids have previously been shown to have markedly increased total urinary nitrogen levels; the amount of nitrogen excreted is also directly related to the degree of injury, as evidenced by the Modified Injury Severity Score (MISS). It is unclear whether the increased protein breakdown in these patients is a result of the head injury or a result of the catabolic effects of steroids. Nineteen children aged 4-14 years, suffering head injuries, were prospectively studied. In ten children, management included steroid administration (1-1.5 mg/kg/day dexamethasone X 3-5 days); the remaining nine were similarly managed; however, without steroids. The groups were matched for age, weight, MISS, and Glasgow Coma Scale Score. The steroid-treated group showed a significantly higher urinary nitrogen excretion (mean, 256 +/- 24 mg/kg/day) than the nonsteroid-treated group (mean, 172 +/- 29 mg/kg/day) (p less than 0.02). These data suggest that steroids potentiate an already accelerated post-traumatic catabolic response seen in children with head injuries. Our data suggest that steroid use, which is common, mandates aggressive nutritional support in the management of children with head injuries.

[Cranio-cerebral trauma and circadian rhythms of activity of several functions of the hypothalamo-hypophyseo-adrenal system in patients of different age groups]. / Cherepno-mozgovaia travma i tsirkadnye ritmy aktivnosti nekotorykh funktsii gipotalamo-gipofizarno-nadpochechnikovoi sistemy u bol'nykh razlichnykh vozrastnykh grupp

The circadian rhythms of the androgenic and glucocorticoid activity of the adrenal cortex were examined in 7 patients with concussions of the brain, and in 22 -- with contusions. The excretion of 17-ketosteroids and of total 17-oxycorticosteroids was determined dynamically in separate 6-hour portions of the urine. In cases of brain concussions, both in the initial period of the trauma, and 10--12 days therafter, only a tendency towards increased excretion of corticosteroids during the night and decreased excretion in the morning hours was observed. In brain contusions the rhythm of andorgenic activity was altered. The most significant alterations caused by a severe trauma were observed in the rhythm of the glucocorticoid function of the adrenal cortex: its reduction in the morning hours, and increase during the night. Some 10--12 days after the brain contusions the rhythm of the hormonal activity remained altered, especially in young and middle-aged patients. These peculiarities of the rhythms should be taken into account when prescribing replacement corticosteroid therapy.

Initial effect of injury on ketone bodies and other blood metabolites.

The arterial and venous concentrations of ketone bodies and other metabolites were measured in twelve adults, from 2 to 24 hours after injury. Two groups could be distinguished, with or without hyperketonaemia (defined as more than 0.2 mmol per litre) in the 2-hour blood-sample. In the hyperdetonaemic group the concentrations of alanine, pyruvate, and lactate and the urinary nitrogen excretion were lower throughout the first 24 hours than in the non-hyperdetonaemic group. These preliminary results indicate that hyperketonaemia after trauma is associated with decreased protein breakdown.