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Hyponatraemia is the most common electrolyte abnormality, encountered in up to 30% of inpatients. Inappropriate management can have serious implications for patients; including demyelinating disease, coma and death. We have used a case report to identify the common problems, and provide useful strategies in management for which these can be avoided. The aim was to provide a framework which clinicians can adopt, in order to improve clinical practice and provide optimum outcome for the patient.

AMG X, a human neutralizing monoclonal antibody (mAb) against a soluble human protein, caused thrombocytopenia, platelet activation, reduced mean arterial pressure, and transient loss of consciousness in cynomolgus monkeys after first intravenous administration. In vitro, AMG X induced activation in platelets from macaque species but not from humans or baboons. Other similar mAbs against the same pharmacological target failed to induce these in vivo and in vitro effects. In addition, the target protein was known to not be expressed on platelets, suggesting that platelet activation occurred through an off-target mechanism. AMG X bound directly to cynomolgus platelets and required both the Fab and Fc portion of the mAb for platelet activation. Binding to platelets was inhibited by preincubation of AMG X with its pharmacological target or with anti-human Fc antibodies or by preincubation of platelets with AMG X F(ab')(2) or human immunoglobulin (IVIG). AMG X F(ab')(2) did not activate platelets. Thus, platelet activation required both recognition/binding of a platelet ligand with the Fab domain and interaction of platelet Fc receptors (i.e., FcγRIIa) with the Fc domain. These findings reflect the complexity of the mechanism of action of mAbs and the increasing awareness of potential for unintended effects in preclinical species.

Background: Single clinical parameters are inaccurate for diagnostic and prognostic estimation in patients with syncope. The cardiac marker NT-pro-BNP has not thoroughly been evaluated for this application., Methods: NT-pro-BNP was assessed in 161 consecutive patients (median age 69 years, 58% male) hospitalized for syncope in a cardiological university department and association (odds ratio: OR, 95% confidence interval: CI) with diagnosis of cardiac cause and 6-months outcome was analyzed., Results: NT-pro-BNP levels were significantly higher in patients with cardiac (n=78) compared to non-cardiac syncope (n=83). At a cutoff of 156 pg/ml, NT-pro-BNP showed a sensitivity of 89.7%, a specificity of 51.8% and a negative predictive value of 84.3% for the diagnosis of cardiac syncope. Increasing NT-pro-BNP was a significant predictor of cardiac syncope (OR 3.7, 95% CI 2.3-5.8 per standard deviation of Log NT-pro-BNP, p<0.001) and addition of NT-pro-BNP significantly improved a predictive model including heart rate, history of structural heart disease and abnormal ECG. Adding left-ventricular ejection fraction to the model did not change results. Sixty-three patients had an adverse event during hospitalization or 6-months follow-up. NT-pro-BNP>156 pg/ml significantly predicted an adverse outcome (OR 2.7, 95% CI 1.04-6.9, p=0.04) after multivariate adjustment., Conclusions: In patients hospitalized for syncope, NT-pro-BNP was a strong and independent diagnostic and prognostic marker and addition to conventional criteria of history and examination improved the discriminatory performance. Randomized trials must clarify the benefit and position of NT-pro-BNP in the management algorithm of patients with syncope., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Syncope is a common presentation in the neurology clinic and emergency room. However, pulmonary embolism (PE) as a cause of syncope is not common or well recognized. Four aged patients presented to our clinic with episodic syncope, and PE was finally identified as the underlying cause. The significant clinical presentations included transient loss of consciousness and hypoxemia on admission. Syncope with hypoxia should therefore be highlighted as an important clue to the diagnosis of PE in aged patients. A negative D-dimer test will be encountered in patients with a very short history. Repeated D-dimer testing is necessary.

Orthostatic stress activates the coagulation system. The extent of coagulation activation with full orthostatic load leading to presyncope is unknown. We examined in 7 healthy males whether presyncope, using a combination of head up tilt (HUT) and lower body negative pressure (LBNP), leads to coagulation changes as well as in the return to baseline during recovery. Coagulation responses (whole blood thrombelastometry, whole blood platelet aggregation, endogenous thrombin potential, markers of endothelial activation and thrombin generation), blood cell counts and plasma mass density (for volume changes) were measured before, during, and 20 min after the orthostatic stress. Maximum orthostatic load led to a 25% plasma volume loss. Blood cell counts, prothrombin levels, thrombin peak, endogenous thrombin potential, and tissue factor pathway inhibitor levels increased during the protocol, commensurable with hemoconcentration. The markers of endothelial activation (tissue factor, tissue plasminogen activator), and thrombin generation (F1+2, prothrombin fragments 1 and 2, and TAT, thrombin-antithrombin complex) increased to an extent far beyond the hemoconcentration effect. During recovery, the markers of endothelial activation returned to initial supine values, but F1+2 and TAT remained elevated, suggestive of increased coagulability. Our findings of increased coagulability at 20 min of recovery from presyncope may have greater clinical significance than short-term procoagulant changes observed during standing. While our experiments were conducted in healthy subjects, the observed hypercoagulability during graded orthostatic challenge, at presyncope and in recovery may be an important risk factor particularly for patients already at high risk for thromboembolic events (e.g. those with coronary heart disease, atherosclerosis or hypertensives).

Background: Brain natriuretic peptide (BNP) may be a good prognostic marker in syncope. The aim of this study was to establish whether there is any change in BNP in association with an acute presentation., Methods: Patients aged ≥60 years admitted following presentation to the emergency department (ED) with syncope were eligible for prospective enrolment. Serial BNP measurements were performed on admission and at intervals up to 4 weeks after presentation., Results: Between 8 March 2010 and 14 April 2010, 31 patients were recruited and were suitable for analysis, including seven patients who returned to the ED at 4 weeks. Mean BNP rose from a baseline of 167.8 ng/ml to a peak of 303.2 ng/ml at 48 h and then returned to baseline at 4 weeks. BNP ratio reached 2.3 (more than twice admission level) at 18 h and peaked at 2.4 at 1 week before returning to baseline at 4 weeks., Conclusions: BNP seems to rise from baseline to a peak between 18 h and 1 week after an acute syncopal episode in many patients. The reasons for this are not clear.

Background: Aim of this study was to test the hypothesis that after presyncope, some blood hormone pools increase while others decrease., Materials and Methods: In twelve healthy male adults, we determined plasma volume changes with plasma mass densitometry and hormone levels. The following were compared: supine rest, presyncope and 20-min post-presyncopal supine rest. We determined plasma renin activity (PRA), aldosterone, adrenocorticotropic hormone (ACTH), adrenomedullin and vasopressin (AVP) from venous blood samples., Results: Using passive 4-min 70° head-up tilt followed by 4-min sequences of additional lower body negative pressure of increasing intensity (15 mmHg steps), presyncope occurred after 11·6 ± 2·8 min, at which time plasma volume was reduced by 15·5 ± 7·4%, aldosterone increased by 37%, ACTH by 75%, PRA by 187% and AVP about 16-fold in average (all P < 0·01); no significant changes in adrenomedullin were seen. Twenty-min post-presyncope, ACTH increased above presyncopal levels (+36%, P < 0·05), aldosterone by 35% (P = 0·07). PRA (-47%, P < 0·01) and AVP (-84%, P < 0·05) decreased below presyncopal but were still above supine control (P < 0·01); similarly, plasma density fell by 2·17 ± 0·97 g L(-1) below presyncopal (P < 0·01), but above supine control (P < 0·05), indicating rapid recovery (83% of initial plasma volume)., Conclusions: We conclude that during the 20-min supine post-syncopal period, plasma volume, PRA and AVP return closer to baseline but aldosterone and ACTH continue increasing. The magnitude of observed concentration changes cannot be explained by haemoconcentration/haemodilution, rather it appears that the observed changes are indicative of hormone-specific endocrine activation patterns in the recovery phase., (© 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: To determine the diagnostic yield of investigations in patients presenting to the emergency department (ED) with syncope. To determine the cause of the syncope., Patients and Methods: We retrospectively identified consecutive patients presenting to the ED who underwent investigations for syncope at a 1900 bed university teaching hospital during 4 months. From the medical records we abstracted clinical information, results of testing and the cause of syncope., Results: A total of 117 patients participated in the study. The mean age was 57 year (range 6-93 year), and 45% were male. Diagnostic procedures most often performed were blood analysis, ECG, chest X-ray and Holter monitoring (respectively in 94.1%, 88.8%, 74.4% and 36,8% of the patients). The corresponding diagnostic yield for these test was 4.5%, 6.7%, 0% and 16.3%. Other procedures were (% of patients; diagnostic yield): Ct scan of the head (35.1%; 0%), transthoracic echocardiogram (24.8%; 6.9%), ECG monitoring (24.8%; 27.6%), EEG (19.7%; 0%), neurovascular imaging (19.7%; 0%), abdominal ultrasound (11.1%; 0%), Ct scan of the chest (11.1%; 23.1%), head up tilt test (7.7%; 11.1%), carotid sinus massage (3.4%; 0%), pulmonary ventilation perfusion scintigraphy (2.6%; 33%) and exercise test (1.7%; 0%). The most common cause of syncope was neurocardiogenic (58,5% of patients), followed by orthostatic (11.1%), cardiac (11.1%), unknown (9.3%), hyperventilation (3.4%), pulmonary embolism (2.5%), drug related (2.5%) and others (1.7%)., Conclusion: Patients admitted in the ED for syncope undergo various investigations. However, the diagnostic yield is poor.The most common cause of syncope is neurocardiogenic, followed by orthostatic and cardiac.

Patients who experience a single generalized tonic-clonic seizure or syncope may have similar clinical symptoms, which can cause difficulty in the differential diagnosis. The aim of this study was to examine whether serum neuron-specific enolase (NSE) has diagnostic relevance as a biochemical marker for these disorders. Serum NSE levels were analyzed following a loss of consciousness in patients who were diagnosed with a seizure (n = 52) and syncope (n = 42) compared with normal controls (n = 91). NSE was 14.97 ± 7.57 ng/dl for the seizure group, 10.15 ± 3.22 ng/dl for the syncope group, and 10.03 ± 1.28 ng/dl for the control group. The seizure group showed a significantly increased serum NSE (p < 0.05) compared to the syncope and control groups. By receiver operating characteristic (ROC) curve analysis, the cut-off value with the highest diagnostic accuracy was defined as 11.5 ng/ml with a sensitivity of 0.58 and specificity of 0.91. The NSE values of the syncope and control groups showed no significant differences. Syncope may not influence diffuse brain damage. Serum NSE measurement may be a helpful test for the identification and diagnosis of a seizure rather than syncope.

Aims: To primarily assess the value of troponin I to identify acute myocardial infarction (AMI), and second, to predict 1-month serious outcome or all-cause death in patients presenting with syncope to the Emergency Department (ED)., Design: Prospective cohort study of all adult patients presenting to the ED after an episode of syncope., Methods: In admitted patients, plasma troponin I was measured 12 h after syncope, and in discharged patients, between 12 h and 7 days following discharge. Primary endpoints were the diagnosis of AMI, and the composite endpoint of serious outcome or all-cause death at 1 month., Results: Over an 8-month period, 289 patients were recruited. Troponin I was obtained in 186 admitted patients and was elevated in 13 (7%), and obtained in 103 discharged patients and was raised in only one (1%). Four patients had an AMI (1.4%) and all had ischaemic electrocardiographic (ECG) changes on their presenting ED ECG (ST segment deviation or pathological Q waves) that were 100% sensitive and 72% specific for AMI with a 100% negative predictive value. Seven of the 14 patients (50%) with a raised troponin I had a serious outcome that did not include AMI, or all-cause death compared with 16 of the 267 patients (6%) without a raised troponin (p<0.0001)., Conclusions: AMI is infrequent (1.4%), and estimation of troponin I provides little additional benefit to the presenting ED ECG in identifying patients with syncope due to AMI. Troponin I should not be used to rule out AMI in adult patients presenting with isolated syncope. Troponin I may predict 1-month serious outcome or all-cause death in syncope.

Introduction: A lack of data exists in the literature evaluating acidemia on admission as a favorable or negative prognostic factor in patients with acute cardiogenic pulmonary edema (ACPE) treated with non-invasive continuous positive airway pressure (CPAP). The objective of the present study was to investigate the impact of acidemia on admission on outcomes of ACPE patients treated with CPAP., Methods: This was a retrospective, observational study of consecutive patients admitted with a diagnosis of ACPE to the Emergency Department of IRCCS Fondazione Cà Granda Ospedale Maggiore Policlinico, Milan, Italy, between January 2003 and December 2006, treated with CPAP on admission. Two groups of patients were identified: subjects with acidemia (acidotic group), and those with a normal pH on admission (controls). The primary endpoint was clinical failure, defined as switch to bi-level ventilation, switch to endotracheal intubation or inhospital mortality., Results: Among the 378 patients enrolled, 290 (77%) were acidotic on admission. A total of 28 patients (9.7%) in the acidotic group and eight patients (9.1%) among controls experienced a clinical failure (odds ratio = 1.069, 95% confidence interval = 0.469 to 2.438, P = 0.875). Survival analysis indicates that, among acidotic patients, the time at which 50% of patients reached the 7.35 threshold was 173 minutes (95% confidence interval = 153 to 193). Neither acidemia (P = 0.205) nor the type of acidosis on admission (respiratory acidosis, P = 0.126; metabolic acidosis, P = 0.292; mixed acidosis, P = 0.397) affected clinical failure after adjustment for clinical and laboratory factors in a multivariable logistic regression model., Conclusions: Neither acidemia nor the type of acidosis on admission should be considered risk factors for adverse outcomes in ACPE patients treated with CPAP.

Introduction: Competitive breath-hold divers can accomplish previously unbelievable performances; e.g., the current world record for apnea during rest ("static apnea") is 11 min 35 s. However, whether such performances are associated with a risk for hypoxic brain damage has not been established., Case Report: A breath-hold diver's competitive performance resulted in a loss of consciousness, after which he was subjected to a medical examination by the event physician. Blood samples were collected for analysis of the brain damage marker S100B in serum. The S100B in serum was 0.100 microg x L(-1) in the blood sample collected 15 min after the loss of consciousness. At 1 and 5 d after the incident it was 0.097 microg x L(-1) and 0.045 microg x L(-1) respectively., Discussion: The elevated level of S100B, close to the upper reference limit (0.105 microg x L(-1)) indicates that the incident affected the integrity of the central nervous system. Even though this case does not establish that hypoxic brain damage is an inherent risk with loss of consciousness in competitive breathhold diving, the observation raises concerns. We suggest that it should be considered that repetitive exposures to prolonged apneas leading to severe hypoxia may be associated with negative long-term effects.

Background: In animals, the endocannabinoid system is activated during hemodynamic insults and restrains blood pressure in part through sympathetic inhibition., Materials and Methods: We tested the hypothesis that hemodynamic stress elicited by head-up tilt testing increases systemic endocannabinoid concentrations in humans and that excessive endocannabinoid availability predisposes to presyncope., Results: With head-up tilt, 2-arachidonoylglycerol increased, whereas anandamide remained unchanged., Conclusions: In contrast to our expectations, anandamide plasma concentration at rest was directly correlated with orthostatic tolerance, rather than intolerance.

A 79-year-old patient repeatedly presented with chest discomfort and dyspnea on exertion. With echocardiography a prominent left ventricular and septal hypertrophy was detected with reduced left ventricular function. Despite successful revascularization and excellent results after stenting, the patient showed persistently elevated troponin levels. To investigate the abnormal findings of persistent troponin elevation, septal hypertrophy, and heart failure we performed endomyocardial biopsies which showed widespread myocardial amyloidosis. Amyloid subtyping revealed transthyretin amyloidosis. This is the first case showing persistent troponin elevation in a patient with tranthyretin amyloidosis. Very few other cases have been published on the topic of cardiac amyloidosis and troponin elevation so far. Our case serves as an illustrating example in the differential diagnosis of nonischemic causes of persistent troponin elevation. It is important to consider cardiac amyloidosis in patients with troponin elevation and heart failure since the clinical management differs significantly from other causes of heart failure.

Aim: To establish whether D-dimer is an independent predictor of 1-month serious outcome and all-cause death in syncope patients presenting to the emergency department (ED)., Methods: This was a prospective cohort study of all adults presenting with syncope to an ED in the UK. Plasma D-dimer concentrations were determined in citrated plasma obtained at presentation. The primary endpoint was the combination of serious outcome and all-cause death at 1 month., Results: Of 237 patients enrolled, 205 patients had a suitable plasma sample and had complete follow-up. Seventeen patients had a serious outcome or death at 1 month including three patients with a pulmonary embolus and eight with a serious cardiovascular outcome. Nearly a half of all patients (n=94; 46%) had a plasma D-dimer concentration above the upper limit of normal, 10 of whom had a serious outcome or death at 1 month. Receiver-operator characteristic curve analysis showed no relationship between plasma D-dimer concentration and serious outcome or death at 1 month. An elevated plasma D-dimer concentration was found in all patients with a pulmonary embolus., Conclusion: Plasma D-dimer is frequently raised in patients presenting with syncope to the ED and consequently does not predict 1-month serious outcome or death. We conclude that there is no role for the routine measurement of D-dimer in the management of patients presenting to the ED with syncope.

Objectives: To assess in a pediatric emergency care unit (PECU): 1. The frequency of syncope and pre-syncope, 2. The incidence of diagnoses, 3. The value of investigations and cardiology and neurology consultations., Methods: The data of PECU patients aged 2 years to 15 years and 3 months were prospectively collected over 1 year. Standard electrocardiogram and serum glucose were compulsory investigations. Schellong's orthostatic test was performed whenever possible., Results: One hundred and fity-nine children (mean age, 11+/-4 years) were included, accounting for 0.8% of the PECU's visits: 48% had syncope, 52% had pre-syncope. The most common cause was neurally mediated syncope - 98 patients (62%), with vasovagal syncope for 80 patients - followed by neurological causes: 29 patients (18%). Neither cardiac arrhythmia nor obstructive cardiomyopathy was diagnosed. There were discrepancies between cardiologists' and pediatricians' ECG interpretations in 9% of cases. Diagnoses differed between cardiologists and pediatricians in 54% of 41 consultations. Diagnoses differed between neurologists and pediatricians in 54% of 42 consultations. No investigation except Schellong's orthostatic test led to modification of a previous diagnosis., Conclusion: This study emphasizes that the routine workup of pediatric syncope should focus on the patient's history and physical examination. Diagnostic testing should be minimal: ECG and Schellong's orthostatic test. The leading cause was neurocardiogenic syncope.

Objective: To determine if the serum levels of creatine kinase and myoglobin can be used to differentiate the grandmal tonic-clonic seizure and syncope activities in the emergency department (ED)., Methods: Consecutive patients over 16 years old who presented to an ED of a tertiary care hospital with a witnessed tonic-clonic seizure activity and a history of a transient loss of consciousness with normal neurological exams in the ED were selected to either seizure or syncope groups. Patients with an unclear history of seizure or syncope with more than 4 h of the activity and with any conditions that could elevate creatine kinase and myoglobin levels were excluded. Serum samples were drawn at presentation and at the fourth hour of the event., Results: Thirty-seven syncope and 26 generalized tonic-clonic seizure patients with a definite history were assigned to study groups. There was not a statistically significant difference in the time of drawing of the first serum sample among groups. No statistically significant differences were determined with the first samples of creatine kinase and myoglobin for both groups. Serum levels of creatine kinase drawn at the fourth hour of the activity were significantly higher in favor of the seizure group. However, myoglobin levels were insignificant at the fourth hour., Conclusion: Serum creatine kinase measured at the fourth hour of loss of consciousness may be a potentially useful laboratory test to differentiate tonic-clonic seizure from syncope. Patently, it requires and warrants further study.

Objective: To investigate whether neurally mediated syncope (NMS) is associated with low iron storage or serum ferritin (SF)., Study Design: 206 children evaluated between 2000 and 2004 for probable syncope at a tertiary care Pediatric Neurology Clinic were included in a retrospective study. Serum ferritin (SF), iron, total iron binding capacity, and hemoglobin were measured prospectively after initial history taking and physical examination, along with other diagnostic testing. We defined iron deficiency (ID) as SF <12 microg/L, and low iron storage as SF

Aims: To assess the value of a near-patient brain natriuretic peptide (BNP) test to predict medium term (3 month) serious outcome for adult syncope patients presenting to a UK emergency department (ED)., Methods: This was a prospective cohort pilot study. Consecutive patients aged > or = 16 years presenting with syncope over a 3 month period were eligible for prospective enrolment. All patients who were medium or high risk according to our ED's existing syncope guidelines underwent near-patient BNP testing using the Triage point of care machine., Results: 99 patients were recruited. 72 of 82 high and medium risk patients underwent BNP measurement. 11 patients had a serious outcome, 9 of whom had BNP measured. In 25 (35%) patients, BNP was > or = 100 pg/ml, and in 3 of these it was > 1000 pg/ml. 6 of the 25 patients (24%) with a BNP > 100 pg/ml, and all 3 patients with a BNP > 1000 pg/ml, were in the serious outcome group. BNP was raised over 100 pg/ml in 6 of the 9 serious outcome patients having a BNP measured (66%), and over 1000 pg/ml in 3 (33%)., Conclusions: This early work suggests that BNP may have a role in the risk assessment of syncope patients in the ED. Further work is required to see how BNP interacts with other clinical variables. Near-patient BNP testing may be shown to be an independent predictor of adverse outcome either alone or incorporated into existing syncope clinical decision rules and scores in order to improve their sensitivity and specificity. Further studies are required to evaluate this.

Background: Previous studies of patients with postural tachycardia syndrome (POTS) have been hampered by relatively small cohorts, failure to control medications and diet, and inconsistent testing procedures., Methods: The Vanderbilt Autonomic Dysfunction Center Database provided results of posture studies performed in 165 patients and 66 normal controls after dietary and medication restrictions. All posture studies were performed after an overnight fast and > or =30 minutes of supine rest., Results: In both the supine and standing positions, heart rate (HR) and plasma concentrations of norepinephrine (NE), epinephrine, and dopamine were higher in patients with POTS compared with the healthy controls. Supine diastolic blood pressure (BP) was also elevated in POTS, whereas supine plasma l-3,4-dihydroxyphenyalanine was reduced. In an analysis of patient subgroups with either an upright plasma NE > or = 3.54 nM (high NE) or an upright plasma NE < 3.54 nM (normal NE), HR and BP were greater in the patient subgroup with high NE. In addition to these significant differences in hemodynamic and catechol measurements, we demonstrated that supine and standing plasma aldosterone and the aldosterone/renin ratio were decreased in patients with POTS. Plasma renin activity (PRA) tended to be higher in patients, and standing HR for those in the highest PRA quartile was significantly greater than for those in the lowest PRA quartile., Conclusions: Our results from larger cohorts of patients and controls than previously studied confirm published findings and contribute additional evidence of sympathetic activation in postural tachycardia syndrome (POTS). Abnormalities in the renin-angiotensin-aldosterone system may also contribute to the POTS phenotype.

Norepinephrine is frequently elevated in postural tachycardia syndrome (POTS), a syndrome of heterogeneous etiology characterized by a >30 beats/min increase in heart rate with standing. Norepinephrine is synthesized from dopamine by dopamine-beta-hydroxylase (DBH). The results of a preliminary study suggested that the T allele frequency of the DBH -1021C-->T polymorphism is elevated in POTS. This allele correlates with low DBH activity and might predict reduced serum DBH activity in patients with POTS. To test the hypothesis that low DBH activity and the underlying -1021C-->T polymorphism are associated with increased susceptibility to POTS, we measured serum DBH activity in POTS and determined its relationship to the DBH genotype and plasma norepinephrine. Serum DBH was similar for 83 normal volunteers and 42 patients with POTS: median (range) = 22.5 (0.5-94.2) and 19.6 (0.1-68.8) nmol.min(-1).ml(-1), respectively (P = 0.282). The genotype frequencies for 254 control and 157 POTS patients were not different between groups ( approximately 63% CC genotype and approximately 5% TT genotype, P = 0.319). The T allele associated with lower serum DBH in both groups [control serum DBH = 15.7 (SD 12.3) and 35.1 nmol.min(-1).ml(-1) (SD 18.6) for T carriers and noncarriers, respectively; POTS serum DBH = 8.2 (SD 5.6) and 28.5 nmol.min(-1).ml(-1) (SD 14.7) for T carriers and noncarriers, respectively]. High DBH in POTS was linked to elevated plasma levels of norepinephrine. Although DBH activity and genotype are unlikely to be primary determinants of susceptibility to POTS, differences in DBH activity in POTS may reflect differences in the level of sympathetic activation.

Background: Adenosine may play a role in the triggering of neurocardiogenic syncope, but no information on adenosine receptors is available at the present time., Objective: The purpose of this study was to investigate whether adenosine A2A receptors expression is altered in patients with neurocardiogenic syncope., Methods: Adenosine plasma levels (APLs), the expression of A2A receptors, were measured (mean +/- standard error of the mean) during tilt testing. Expression of receptors was assessed on mononuclear cells using a selective receptor ligand., Results: At baseline, the APLs of 16 patients with a positive test were higher than those of 17 patients with a negative test and of those of a control group (2.10 +/- 0.30 vs. 0.40 +/- 0.05 and 0.41 +/- 0.06 muM, respectively; P <.0001). The number of receptors was higher in patients tested positive than in patients tested negative or in the control group (122 +/- 10 vs. 38 +/- 4 and 44 +/- 4 fmol/g of proteins, respectively; P <.0001). No difference was found in the affinity or synthesis among the three groups., Conclusion: This study showed an increased number and an up-regulation of adenosine A2A receptors in patients with spontaneous syncope and a positive head-up tilt, which in the context of high APLs may play a role in the recurrence of syncopal episodes.

Purpose: Markers for epileptic seizures are rare and their use has not been established in the evaluation of seizures and febrile convulsions (FC). Brain-type natriuretic peptide (BNP) is a natriuretic, diuretic, and vasodilator compound first discovered in the hypothalamus but mainly synthesized in the myocardium. The aim of this study was to assess whether epileptic seizures or FC are related to increased secretion of the N-terminal fragment of BNP (NT-proBNP)., Methods: Sixty-five postictal children (43 boys, 22 girls) and 31 children with epilepsy (20 boys, 11 girls) after a seizure-free period for at least 2 months serving as controls were enrolled. Postictal NT-proBNP levels were analyzed and controlled 24-48 h thereafter., Results: Plasma concentration of NT-proBNP was significantly higher 4 h postictal compared to 24-48 h postictal (p < 0.001). Subgroup analysis revealed increased NT-proBNP levels in children with tonic-clonic seizures and FC compared to children with partial motor seizures (p < 0.001), syncope (SYN; p < 0.01), or control population (p < 0.001)., Conclusions: Our results suggest that elevated plasma NT-proBNP levels are not specific for cardiac dysfunction. Postictal measurement of plasma NT-proBNP seems to be useful in discriminating different types of epilepsy, FC, and SYN in childhood.

Objective: The purpose of this article is to review the use of serum prolactin assay in epileptic seizure diagnosis., Methods: The authors identified relevant studies in multiple databases and reference lists. Studies that met inclusion criteria were summarized and rated for quality of evidence, and the results were analyzed and pooled where appropriate., Results: Most studies used a serum prolactin of at least twice baseline value as abnormal. For the differentiation of epileptic seizures from psychogenic nonepileptic seizures, one Class I and seven Class II studies showed that elevated serum prolactin was highly predictive of either generalized tonic-clonic or complex partial seizures. Pooled sensitivity was higher for generalized tonic-clonic seizures (60.0%) than for complex partial seizures (46.1%), while the pooled specificity was similar for both (approximately 96%). Data were insufficient to establish validity for simple partial seizures. Two Class II studies were consistent in showing prolactin elevation after tilt-test-induced syncope. Inconclusive data exist regarding the value of serum prolactin following status epilepticus, repetitive seizures, and neonatal seizures., Recommendations: Elevated serum prolactin assay, when measured in the appropriate clinical setting at 10 to 20 minutes after a suspected event, is a useful adjunct for the differentiation of generalized tonic-clonic or complex partial seizure from psychogenic nonepileptic seizure among adults and older children (Level B). Serum prolactin assay does not distinguish epileptic seizures from syncope (Level B). The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

Objective: To investigate the utility of both a random troponin T level taken greater than 4 h after a syncopal event and the Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) score in predicting outcome post syncope., Methods: We prospectively enrolled 113 adult patients who presented to our ED after a syncopal event. Each patient had a troponin T level taken at least 4 h after the event. The relevant history of the syncope, background medical history and ECG were collected at presentation. Patients were followed up via telephone after 3-6 months and medical records were also examined. The OESIL risk score was calculated for each patient and the predictive value of both the troponin T and OESIL score were analysed for their utility post syncope., Results: Data were analysed for 100 patients. Twenty percent were believed to have a cardiac cause for their syncope. An elevated troponin T level was found to be highly specific (0.99, 95% confidence interval [CI] 0.96-1.0) for adverse cardiac outcome, but with a very low sensitivity (0.13, 95% CI 0-0.3). The OESIL risk score was found to be predictive of an adverse cardiac outcome (receiver-operating characteristic [ROC] 0.73, 95% CI 0.63-0.84) and return to normal function (ROC 0.74, 95% CI 0.63-0.86)., Conclusions: A normal serum troponin T has a poor negative predictive value for adverse cardiac outcomes following syncope. A simple risk stratification system, such as the OESIL score, can predict those patients most at risk after a syncopal episode.

Paraprostatic pheochromocytoma is a very rare localization of extra-adrenal pheochromocytoma. The clinical and anatomical features of a 41-year-old man are described., (Copyright 2005 S. Karger AG, Basel.)

Objective: A meta-analysis of studies of the usefulness of raised serum prolactin in diagnosing generalised tonic-clonic seizures (GTCS) in patients presenting to the accident and emergency (A&E) department after a single episode of syncope., Methods: A three part question was defined. Medline, EMBASE, PubMed, the Cochrane Library were searched to identify relevant studies. Studies were evaluated for eligibility and quality and data extracted to calculate sensitivity (SN), specificity (SP), and likelihood ratios (LR)., Results: Of 13 relevant studies only three met the criteria for evaluation. If a serum prolactin concentration is greater than three times the baseline when taken within one hour of syncope, then in the absence of test "modifiers": (1) the patient is nine times more likely to have suffered a GTCS as compared with a pseudoseizure positive LR = 8.92 (95% CI (1.31 to 60.91)), SN = 0.62 (95% CI (0.40 to 0.83)), SP = 0.89 (95% CI (0.60 to 0.98)) and (2) five times more likely to have suffered a GTCS as compared with non-convulsive syncope positive LR 4.60 (95% CI (1.25 to 16.90)), SN = 0.71 (95% CI (0.49 to 0.87)), SP = 0.85 (95% CI (0.55 to 0.98))., Conclusion: A positive test result is highly predictive of a GTCS, however a negative test result does not necessarily exclude a seizure. Serum prolactin should be measured in patients presenting to the A&E department within an hour of a syncopal episode, unless the cause is immediately obvious.

The pooling of blood in the limbs is the beginning of a chain of events which brings about the reflex syncope. Observations have confirmed that the reduction of plasma volume is also a factor pathogenetically determinant in the provocation of a faint. During orthostatic stress, plasma volume shifts towards the interstitial spaces of the infra-diaphragmatic vascular network, thus, contributing greatly to the reduction in the circulating volume. The aim of the present study was to calculate whether during orthostasis there was indeed a reduction in plasma volume and to what extent in a population at high risk for fainting. A comparative study of 50 recurrent fainters and 37 controls was performed. Each group was studied both in a supine (before) and orthostatic (after) position. Blood samples were taken to determine the hematocrit and hemoglobin values. The percentage variation of these values was calculated in order to obtain the reduction in plasma volume, i. e., the expression of the amount of plasma accumulated in the interstitial spaces. A significant difference in hematocrit and hemoglobin variation (before vs. after) was found between patients and controls. Plasma volume variation before vs. after (17.1 % in patients vs. 8.6 % in controls) was then calculated using these measurements. The difference in plasma volume variation between patients and controls can be interpreted as a co-factor together with the pooling of plasma in the pathogenesis of reflex fainting. This study illustrates an easy way to evaluate the role of plasma volume reduction in the pathogenesis of vasovagal syncope.

Background: Water ingestion raises blood pressure substantially in patients with perturbed autonomic control and more modestly in older subjects. It is unclear whether prophylactic water drinking improves orthostatic tolerance in normal healthy adults., Methods and Results: Twenty-two healthy subjects, 18 to 42 years of age, with no history of syncope underwent head-up tilt-table testing at 60 degrees for 45 minutes or until presyncope or syncope occurred. In their initial test, participants were randomized to either 16 oz (473 mL) of water drinking 5 minutes before tilt-table testing or tilt-table testing alone, with the alternative in a second test on a different day. During the first 30 minutes of tilt, 8 of 22 subjects without water experienced presyncope but only 1 of 22 who had ingested water (P=0.016). Water drinking attenuated the heart rate increase associated with tilt (P<0.001) while accentuating the increase in total peripheral resistance (P=0.012). The average time study participants tolerated head-up tilt was 26% longer after water (41.1+/-8.1 versus 32.6+/-14.3 minutes, mean+/-SD), with a pairwise mean difference of 8.5+/-14.0 minutes (95% CI, 2.3 to 14.7 minutes; P=0.011)., Conclusions: Water enhances tolerance of upright posture. The effect of water is mediated by increased peripheral vascular resistance. Water ingestion may constitute a simple and effective prophylaxis against vasovagal reactions in healthy subjects, such as those associated with blood donation.

Background and Objectives: von Willebrand factor (VWF) is stored in the Weibel-Palade bodies of endothelial cells and may be released in response to different secretion stimuli such as stress, physical exercise, adrenaline, DDAVP and thrombin., Design and Methods: We found that fainting can also induce an acute increase in plasma VWF and factor FVIII (FVIII) concentrations, following observations in two patients with von Willebrand's disease (VWD) who experienced a fainting episode during venipuncture for blood collection., Results: One patient was classified as having type Vicenza VWD, the other as type 1 VWD; both had normal platelet VWF content. After the fainting episode, FVIII and VWF levels were significantly higher than the levels in blood samples collected without stress; mean increases were 4.35-fold for FVIII, 4-fold for VWF:Ag and 5.3-fold for VWF:RCo, with values overshooting the upper limit of the normal range. Moreover, the post-fainting plasma VWF multimer pattern was characterized by a significant increase in all oligomers with the appearance of unusually large VWF multimers, similar to those observed following DDAVP infusion., Interpretation and Conclusions: These findings demonstrate that fainting acts as a stimulus capable of inducing the release of VWF from endothelial cells, and further highlight the role of stress in determining hemostatic states potentially favorable to the development of thrombotic complications.

Background: The onset of symptoms is a critical point in the natural history of aortic stenosis and the cardinal indication for valve replacement. This study assessed the associations between natriuretic peptide levels, disease severity, and cardiac symptoms in aortic stenosis., Methods and Results: Seventy-four patients with isolated aortic stenosis underwent independent assessment of symptoms, transthoracic echocardiography, and measurement of plasma levels of atrial natriuretic peptide, brain natriuretic peptide (BNP), and N-BNP. Natriuretic peptide levels were also measured in 100 clinically normal control subjects. The aortic valve area was smaller in symptomatic patients (n=45) than in asymptomatic patients (n=29; mean, 0.71+/-0.23 cm2 and 0.99+/-0.31 cm2, respectively; P<0.0001). Plasma natriuretic peptide levels were higher in symptomatic patients than in asymptomatic patients (for N-BNP: median, 112 versus 33 pmol/L; interquartile range, 70 to 193 versus 16 to 58 pmol/L, respectively; P=0.0002). After adjustment for age, sex, serum creatinine, aortic valve area, and left ventricular ejection fraction, N-BNP levels were 1.74 times higher (95% confidence interval, 1.12 to 2.69) for symptomatic than asymptomatic patients with aortic stenosis (P=0.014). Natriuretic peptide levels increased with the New York Heart Association class (for N-BNP median values were 13, 34, 105, and 202 pmol/L for normal control subjects, class I, class II, and class III/IV patients, respectively; interquartile ranges for the same patients were 8 to 21, 16 to 58, 57 to 159, and 87 to 394 pmol/L; P<0.0001). Similar associations were observed for BNP and atrial natriuretic peptide., Conclusions: Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis.

Purpose: An attenuated baroreflex response and orthostatic intolerance have been reported in endurance-trained male athletes; however, it is still unknown whether this occurs also in females. The purpose of the present study was to examine whether endurance exercise-trained women had a predisposition to orthostatic compromise, and if so, what causative factor(s) may induce orthostatic intolerance., Methods: We studied cardiovascular and hormonal responses to graded lower body negative pressure (LBNP) (0 to -60 mm Hg) in 26 middle-distance female runners (18.6 +/- 0.1 yr) as the exercise-trained (ET) subjects and 23 age-matched untrained (UT) control subjects. On the basis of the occurrence of syncope episodes during LBNP, ET and UT subjects were further allocated to two groups; ET with presyncope (ET+syncope) and without presyncope (ET-syncope) and UT with presyncope (UT+syncope) and without presyncope (UT-syncope)., Results: Occurrence of presyncope episodes during LBNP was higher in ET (65.4%, P < 0.05) than that for UT (34.8%). Leg compliance was higher (P < 0.05) in ET than in UT. LBNP reduced stroke volume (SV) more (P < 0.05), increased heart rate (HR) higher (P < 0.05), and increased forearm vascular resistance (FVR) more in ET+syncope as compared with the other groups. Response of vasoactive hormones to LBNP was higher in ET+syncope (P < 0.05) than that of the other groups except for norepinephrine (NE); high in both ET+syncope and UT+syncope. The relationship between SV and NE, an index of sympathetic neuronal response, had no training-related changes during LBNP., Conclusion: We conclude that exercise-trained females have a high incidence of orthostatic intolerance during LBNP, with a greater reduction of SV independent of changes in baroreflex and neurohumoral function. A lower incidence of LBNP intolerance in UT may be accounted for by a lower reduction of SV during LBNP. An increase in leg compliance in the exercise-trained females may play an important role in inducing pronounced reduction of SV and hence the intolerance to LBNP.

Purpose: To get a more complete picture of cardiovascular regulation after postural changes, this investigation directly monitored volume-related, hemodynamic, and endocrine variables during and after 30 min of passive head-up tilt (HUT) of various degrees. It was hypothesized that the return of variables to pre-tilt control level is of system-specific duration and different from what is found after lower body negative pressure (LBNP)., Design: We tested 7 persons on 5 different days using, in random order, no (HUT0) or different intensity (12 degrees , 30 degrees , 53 degrees , and 70 degrees ) of passive orthostasis (HUT12, HUT30, HUT53, HUT70). Data were collected before (supine), during, and after (supine) HUT and compared with synchronous data from HUT0., Results: There was graded alteration with the sine of tilt angle for all hormones and directly volume-related variables. The effects of HUT70 were of the same magnitude as previously documented by others. After HUT, hemodynamic variables and catecholamines returned to control levels most rapidly. Heart rate depression, as observed in a companion LBNP study in the same subjects, did not occur. Vasopressin, PRA, plasma volume and Z0 returned to nominal values more slowly. Plasma aldosterone was still elevated 50 min after reassuming supine posture., Conclusion: Besides specific dose-responses within hemodynamic, volume-dependent, and hormonal variables after orthostatic loading of different degree, the return to control levels after HUT occurs with distinctly different time-courses, which are not identical with those seen after LBNP-simulated orthostasis.

Background and Hypothesis: Previous research has failed to document temporal changes in epinephrine levels in patients with neurally mediated syncope associated with exercise. The purpose of this study was to investigate the role of circulatory catecholamines in exercise-induced neurally mediated syncope, specifically focusing on epinephrine levels., Methods: The present study deals with temporal changes of circulatory catecholamine levels during head-up tilt tests (40 min, 80 degree tilt) in 62 patients with syncope of unknown origin, 7 of whom had syncope associated with exercise (exercise-induced group, 19+/-3 years). Data were compared with 10 control subjects (control group, 45+/-23 years). Of the 55 patients with syncope not associated with exercise, 32 tested positive for the head-up tilt tests (positive group, 31+/-16 years) and 23 patients tested negative (negative group, 46+/-19 years). Blood samples for circulatory catecholamine assay were obtained from the antecubital vein in the baseline supine position 2 min after the tilt started, every 10 min during tilt, and at the time of the onset of symptoms or the end of tilt. Levels of norepinephrine and epinephrine were determined using the high-pressure liquid chromatography (HPLC) method (pg/ml)., Results: Plasma norepinephrine levels among the four groups were similar at the supine position and during tilt testing. In contrast, patients in the exercise-induced group had significantly higher maximum epinephrine levels during head-up tilt testing than the other three groups (288+/-191 vs. 148+/-117, 66+/-31, and 54+/-27 pg/ml, respectively, p < 0.05). Patients in the positive group had higher maximum epinephrine levels than those in the negative group (p <0.05). Also, patients in the exercise-induced group and those in the positive group had a significantly shorter tilt-testing time than patients in the negative and control groups., Conclusions: A marked increase of epinephrine was observed during head-up tilt testing in patients with neurally mediated syncope associated with exercise. The present findings further accelerate the identification of the role of epinephrine in the mechanisms behind neurally mediated syncope associated with exercise.

Two-site immunoassay methods have become the standard technique for measurement of a wide variety of drugs, hormones, and cell proteins. One limitation of these methods is their susceptibility to interference from heterophilic antibodies present in the sera of some patients. Human anti-murine antibodies represent a common heterophile antibody that can bind to mouse immunoglobulin and as well as to immunoglobulin from other species. While the mechanism of human anti-murine antibody interference has been well characterized, the time course over which this interference occurs and the susceptibility of different immunoassay procedures to human anti-murine antibody interference from patients with human anti-murine antibody have not been as well described. We report on the time course of interference in assays for cardiac markers for two patients with human anti-murine antibodies. We measured creatine kinase MB isoenzyme (CKMB) and troponins I and T using three different vendors' immunoassay procedures. Our results demonstrate that assay interference due to human anti-murine antibody interference is a transient phenomenon. In one of our patients, human anti-murine antibody interference appeared suddenly, peaked approximately 9 days following its appearance, and gradually resolved over the next 3 weeks. In addition, we found that immunoassay methods from different vendors can show highly variable interference effects when human anti-murine antibody-containing specimens are analyzed.

Background: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities., Methods: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion., Results: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling., Conclusions: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

A 61-year-old woman developed hypokalemia, atrioventricular block and ventricular tachycardia with syncope after habitual drinking 2 to 3 liters of oolong tea per day. She had been suffering from rheumatoid arthritis and Sjögren's syndrome and her serum albumin was decreased (2.9 g/dl). Oolong tea contains caffeine at approximately 20 mg/dl. Great quantities of caffeine can induce hypokalemia. The serum protein binding caffeine is albumin. Accordingly, in patients with hypoalbuminemia, caffeine is apt to induce hypokalemia. This case suggested that great quantities of oolong tea, one of the so-called "healthy" drinks, result in serious symptoms for patients with hypoalbuminemia.

Objectives: We studied the triggering mechanism for neurally mediated syncope., Background: Although increased transient sympathetic tone is thought to be necessary for the development of neurally mediated syncope, little is known about the triggering mechanism for neurally mediated syncope., Methods: Plasma epinephrine (EP) and norepinephrine (NE) levels were assessed in 20 syncope patients during tilt test (80 degrees, 15 min) with and without isoproterenol (ISP, 0.01, 0.02 microg/kg/min). If syncope occurred, propranolol (0.1 mg/kg) was injected., Results: Eight patients experienced syncope during tilting alone, and 9 patients required ISP for syncope. In the negative response without ISP, NE showed a small statistical 1.7-fold increase at end of tilting and EP did not change during tilting. When syncope occurred during tilting alone, a significant 11.7-fold increase in EP at syncope was registered concomitant with a small 2.5-fold increase in NE. When patients experienced syncope during tilting with ISP, a significant 5.0-fold increase in EP at syncope was registered concomitant with a small 1.7-fold increase in NE. In patients without ISP, propranolol did not interrupt syncope. In patients with ISP, six of eight receiving propranolol responded to tilting negatively., Conclusions: An increase of NE levels may result in inhibition of syncope and an EP surge may be a triggering mechanism for neurally mediated syncope. Comparatively low levels of EP may be enough to induce syncope during tilting with ISP compared with tilting alone. Propranolol is not effective in patients without ISP, but it frequently inhibits syncope in patients with ISP. Propranolol (0.1 mg/kg) may be insufficient to block the actions of high levels of circulating EP.

In recent years peripheral blood stem cell (PBSC) collection for allogeneic or autologous transplantation has experienced an increased use in the onco-hematological setting. The latest generation cell separators allow a satisfactory and safe PBSC collection. Nevertheless, as in all therapeutic apheresis procedures, patients may experience procedure-related side-effects, mainly vasovagal reactions or symptoms related to hypocalcemia and/or hypomagnesemia. We investigated electrolyte changes in 18 patients, with a median age of 46 years (range 7-62), undergoing PBSC collection from January to April 1998. A significant decrease in total calcium in the final sample (9.65 +/- 0.7 mg/dL) with respect to the basal one (9.2 +/- 0.6 mg/dL, P < 0.05) was observed; also ionized calcium decreased markedly from the first sample drawn at +30 minutes: 1.22 +/- 0.14 vs. 1.03 +/- 0.15 mmol/L (P < 0.05), and a highly significant difference emerged when basal value were compared to the final value: 1.22 +/- 0.14 vs. 0.94 +/- 0.13 mmol/L (P < 0.0001). Similar findings affected potassium concentration: 4.1 +/- 0.4 vs. 3.3 +/- 0.3 mEq/L (P < 0.0001). Three out of eighteen patients (16.7%) reached a final potassium level <3.0 mEq/L, and eight out of eighteen (44.5%) showed a potassium concentration decrease >20% with respect to the basal value. A mild metabolic alkalosis occurred during the procedure: pH increased from 7.35 +/- 0.02 to 7.43 +/- 0.028 (P < 0.001), and plasma bicarbonate concentration increased from 27.48 +/- 2.21 to 32.44 +/- 2.52 mmol/L (P < 0.01). Sodium and chloride did not differ in the final sample with respect to the basal sample. None of our patients experienced clinically relevant side effects related to severe electrolyte changes (i.e., >20% with respect to the basal value). Because our current therapeutic schedules include patients older than 50 years in the PBSC collection and transplantation program and since it is well known that subclinical myocardial disease may occur in up to 4% of middle-aged males, we suggest that patients aged 50 or older undergoing PBSC collection procedures be carefully monitored in order to identify significant electrolyte variation, especially if they present with low serum potassium levels. However, further investigation of larger patient series are needed to determine the clinical relevance of serum potassium changes during apheresis.

Background: The purpose of this study was to study the effect of enalapril on neurally mediated syncope (NMS). Several agents (except for angiotensin-converting enzyme [ACE] inhibitors) have been used to treat patients with NMS. It is unknown whether ACE inhibitors have beneficial effects on NMS., Methods and Results: Thirty subjects who had reproducible NMS induced with head-up tilt table test (HUT) were randomly assigned and divided in double-blind fashion into placebo and enalapril (an ACE inhibitor) groups. Hemodynamics and plasma catecholamine concentrations were studied. Before administration of enalapril, syncope induced by HUT was associated with vigorous hypotension and bradycardia. Plasma catecholamine concentrations were significantly elevated during NMS compared with the supine position before tilt. Oral enalapril rather than placebo produced a marked reduction in diastolic blood pressure during supine positioning before tilt. Administration of enalapril prevented HUT-induced NMS and increase of plasma catecholamine concentrations in all patients examined. Conversely, placebo had no effect in the majority of patients with NMS (12 of 15 subjects). Follow-up data showed that NMS disappeared in 14 (93%) of 15 patients treated with enalapril., Conclusions: This study demonstrates that ACE inhibitors may efficiently prevent NMS, presumably through inhibition of sympathetic system activation and peripheral hypotensive effect.

Objectives: This prospective study was conducted to evaluate the usefulness of venous lactate assay in the diagnosis of generalized seizures., Patients and Methods: Over a three month period, 78 consecutive adults admitted to the emergency unit for unconsciousness were included in the study. Three study groups were defined: patients with generalized seizures (n = 22), unconscious patients without seizure (n = 34) and known epileptic patients with unexplained malaises (n = 22). Patients with a disease susceptible of increasing lactate levels were excluded. Peripheral venous blood was drawn to determine lactates, bicarbonates and pH on a blood gas analyzer. All determinations were performed within 5 minutes of blood withdrawal. CPK level was also determined with an enzymatic method., Results: In patients who had seizures, venous lactate levels were higher than those in patients who had no seizures: 4.3 +/- 0.5 mmol/l in generalized seizure patients versus 1.64 +/- 0.1 and 2.2 +/- 1.39 in unconscious patients without seizure and known epileptic patients with unexplained malaise respectively. The threshold lactate level of 2.5 mmol/l given by ROC curves gave a 0.97 specificity and a 0.73 sensitivity., Discussion: The acidosis observed in patients with generalized seizures results from the combined effects of respiratory and metabolic acidosis. High lactate level would be a consequence of hypoxemia, per seizure rise in catecholamines, and aerobic and anaerobic metabolism in muscles during the tonic-clonic phase. In patients presenting in an unconscious state, increased lactate levels, even when determined up to 2 hours after venous blood withdrawal, could be a useful parameter for the diagnosis of epileptic seizure.

A dramatic increase in catecholamine (CA) concentration is believed to be a primary trigger of the neurally mediated syncope (NMS) in elderly subjects. The hypercontractile state of the heart might be alleviated by angiotensin-converting enzyme (ACE) inhibitor through depression of CA release from the sympathetic nerve ending. Thus ACE inhibitor might have positive effect on the prevention of NMS. In this study, 24 elderly subjects who had reproducible NMS induced with head-up tilt test (HUT) were randomized and double-blind divided into placebo and ACE-inhibitor groups. The plasma CA concentration [norepinephrine (NE) and epinephrine (E)] were measured during HUT, and the effects of enalapril on NMS were observed in the two groups. Before administration of enalapril, plasma CA concentrations were significantly increased during HUT compared with those in the supine position; In contrast, administration of the enalapril (10 mg/day) for >1 year inhibited the concentration of plasma CA increase and prevented syncope in all 12 patients (p < 0.05); however, placebo had no effect on plasma CA concentrations and syncope disappeared in only two of 12 patients after administration of placebo. From this study, we conclude that enalapril can prevent NMS in patients, presumably because of its part in the inhibition of CA release from sympathetic nerve endings.