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The simultaneous occurrence of subcutaneous emphysema and intravascular air due to an air embolism is a rare condition. Here, we report a patient with COPD who developed a severe episode of hemoptysis due to rupture of a previously undiagnosed lung cavern. Intubation and ventilation led to the development of both massive subcutaneous emphysema and a massive air embolism, resulting from aspiration of air through a torn pulmonary vessel in the cavern. The dramatic amount of intravenous air and subsequent conduction along the venous system to the right heart and pulmonary trunk caused major hemodynamic compromise and ultimately death. The degree of subcutaneous emphysema, especially the massive venous air embolism, was unprecedented.

Background: Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria. Methods: Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome. Results: In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean [SD]). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score: −2.96). Conclusion: Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.

Study design and setting - Two case reports, University Hospital of Antwerp, tertiary referral hospital of the University of Antwerp, Edegem, Belgium. Methods and results - Two women were transferred to our hospital because of acute cardio-respiratory failure due to amniotic fluid embolism during the peripartal period. Both required intensive supportive treatment and invasive monitoring. Haemodynamic data revealed primary left ventricular failure confirming the clinical picture of cardiogenic pulmonary oedema. Review of the literature provides data that do not support obstruction of the pulmonary vasculature by amniotic fluid as the only primary pathophysiological event. However, despite several case reports stressing left ventricular failure as the dominant clinical event, pathophysiological mechanisms are merely speculative. Conclusions - The diagnosis of amniotic fluid embolism remains a clinical challenge, but can be supported by the presence of amniotic cells in the pulmonary artery, aspirated through a pulmonary artery catheter. The treatment is still not causative but supportive. An overview of cases in the literature with predominant left heart failure during amniotic fluid embolism is given.

OBJECTIVE: To report a pediatric case of posttraumatic fungal fasciitis treated successfully with a combination including posaconazole. DESIGN: Case report. SETTING: Pediatric critical care unit at Antwerp University Hospital. PATIENT: A 12-yr-old female polytrauma patient, suffering from extensive skin and muscle injuries, developed fasciitis. Two fungi (Mucor and Trichosporon species) were isolated. The necrotic tissues were aggressively excised, hyperbaric oxygen therapy was applied, and oral posaconazole was added to the initial amphotericin B treatment. The patient made an excellent recovery. CONCLUSIONS: A combination of a high index of suspicion, early aggressive surgery, hyperbaric oxygen, and the association of amphotericin B and posaconazole led to a successful outcome in a case of fungal necrotizing fasciitis. After decades of disappointing amphotericin B treatment in spite of acceptable in vitro activity, the combination with the new triazole posaconazole seems promising.

Objective Intraventricular hemorrhage is associated with a very poor outcome. Simple external ventricular drainage alone has not resulted in a decline of mortality. The aim was to study the effect of direct intraventricular administration of recombinant tissue plasminogen activator (rtPA). Patients and methods A retrospective series of eighteen adult patients with severe intraventricular hemorrhage, admitted to our university hospital, was studied for the effect of direct intraventricular administration of recombinant tissue plasminogen activator (rtPA). rtPA was administered in a dosage of 2 mg. The injection was repeated at 12 h intervals until serial CT scans showed a substantial reduction of intraventricular blood. Results The total of rtPA doses per patient ranged from 2 to 32 mg. Seven out of 18 patients showed good neurological recovery, 4 died. Only one patient had a complication which could be directly attributed to the intraventricular thrombolytic therapy. Conclusion We conclude that the procedure of intraventricular administration of a thrombolytic agent, i.e. rtPA, seems effective in lysis of the intraventricular hematoma and may, therefore, improve outcome.

This study evaluated retrospectively the efficacy of treatment with cefepime vs. a carbapenem, in combination with amikacin or ciprofloxacin, for seriously-ill patients infected with ESBL-producing Enterobacter aerogenes who were admitted to an intensive care unit. Forty-four episodes of infection were investigated in 43 patients: 21 treated with cefepime; 23 with a carbapenem. The two treatment groups did not differ statistically in terms of age, APACHE II scores, and infection sites, but the average duration of antibiotic exposure was significantly shorter in the cefepime group (8.5 days vs. 11.4 days; p 0.04). Clinical improvement was seen in 62% of patients receiving cefepime vs. 70% of patients receiving a carbapenem (p 0.59). Bacteriological eradication was achieved in 14% of patients receiving cefepime vs. 22% of patients receiving a carbapenem (p 0.76). The 30-day mortality rates related to infection were 33% in the cefepime group and 26% in the carbapenem group (p 0.44). Thus, outcome parameters did not differ significantly between the two groups. Nevertheless, a statistically significant increase in failure to eradicate ESBL-producing E. aerogenes was observed as the MICs of cefepime rose (p 0.017). Pulsed-field gel electrophoresis revealed three distinct clones, but one predominant clone harbouring the blaTEM-24 gene was associated with most (42/44) of the episodes of infection. It was concluded that cefepime may be an alternative agent for therapy of severe infections caused by TEM-24 ESBL-producing E. aerogenes, although further studies are required to confirm these observations.

It is unknown whether barbiturates suppress cerebral oxygen metabolism after cerebral trauma as they do in normal individuals. We evaluated the influence of pentobarbital on cerebral oxygen handling of normal rats and rats subjected to non-hemorrhagic closed head injury (CHI). Oxygen delivery was assessed by measuring cerebral perfusion and oxygen extraction, enabling the calculation of cerebral metabolic rate of oxygen (CMRO2). Mitochondrial function was assessed by studying changes in the oxidized cytochrome oxidase concentration. CHI caused changes in both systemic and cerebral hemodynamics. Cerebral blood flow was reduced to 66% of its control value, but the cerebral metabolic rate of oxygen remained unchanged. Pentobarbital administration induced a significant lowering of the cerebral oxygen consumption in normal rats associated with a secondary decrease in cerebral perfusion. In rats subjected to CHI, pentobarbital was unable to lower the cerebral metabolic demand and did not cause a further decrease in perfusion. Pentobarbital was unable to significantly modulate mitochondrial function in traumatized rats, whereas it exerted this effect in all control animals. We therefore conclude that, in rats subjected to CHI, pentobarbital is unable to perform its beneficial effects on the cerebral metabolism.

Contains fulltext : 48791.pdf (Publisher’s version ) (Closed access) Streptococcus pneumoniae is a common cause of bacterial meningitis but only rarely causes other infections such as brain abscess, encephalitis, encephalomyelitis or meningoencephalitis. We report on three adult patients with meningoencephalitis caused by S. pneumoniae. In all three, CT and MRI revealed widespread brain lesions, suggesting extensive parenchymal injury. Diffusion-weighted MRI showed lesions with restricted diffusion, reflecting local areas of ischaemia with cytotoxic oedema secondary to an immunologically mediated necrotising vasculitis and thrombosis. High levels of markers of neuronal, glial and myelin damage were found in the cerebrospinal fluid. According to the literature, brain parenchyma lesions in adults with pneumococcal meningoencephalitis are often associated with death or severe neurological deficit. Our patients were treated with pulse doses of glucocorticoids: this resulted in dramatic clinical improvement and an excellent final neurological recovery.

It is generally accepted that terms referring to specific craniocerebral injury mechanisms must be replaced by the more general term abusive head trauma (AHT). Although blunt impact trauma remains an essential part of AHT, it has received far less attention in the literature than shaken-impact injuries. The current article presents 19 confessed cases of a series of 47 highly suspected AHT cases. Of these, 13 were confessed shaken-impact cases, and the other 6 confessed blunt trauma cases. There were no significant differences in the appearance of subdural hematoma, which was present in each case. Retinal hemorrhage, which was present in 10 of the 13 shaken-impact cases in which an ophthalmologic examination was conducted, occurred in 2 of the 6 blunt trauma cases. In 1 case, retinal hemorrhage probably had of metabolic origin. Skull fractures with an overlying subgaleal hematoma and a subdural hematoma below the fracture side were found in 5 of the blunt trauma cases but was also seen in the 2 shaken-impact cases with a skull fracture. The most important finding was a lucid interval (LI) in 3 blunt AHT cases. An LI does not seem to occur in shaking injuries because of the immediate and persistent effect of brain damage that such injuries involve. Therefore, LI makes it important to conduct a detailed investigation of the clinical course in time in suspected AHT cases.

The present study validates a method for continuous measurement of intracranial pressure (ICP) in freely moving rats after experimental induction of impact-acceleration injury. Rats subjected to either mild or moderate trauma were individually placed in a Bas-Ratturn system, equipped with a sensor that synchronously turns the cage in response to the locomotor activity of the animal. In this way correct probe positioning is permanently assured and damage due to coiling is avoided. The evolution of ICP and mean arterial blood pressure (MABP) in injured rats was compared with that of a non-traumatized sham group. Since the animals regained consciousness after surgery, interference of anaesthesia on these sensitive parameters should be minimised. The results showed that immediately after induction of neurotrauma, ICP was significantly higher in traumatized rats (sham: 7.7 +/- 0.5 mmHg; mild trauma: 10.4 +/- 0.7 mmHg; moderate trauma: 14.9 +/- 2.4 mmHg; P0.05). Regression analysis showed a stable ICP up to 3 h post-insult for all three conditions. From 4 h onwards till the end of the experiment at 10 h post-insult, a significant increase in ICP was seen for sham-operated and mildly traumatized rats (16.1 +/- 3.4 and 30.5 +/- 6.9 mmHg, respectively; P0.05), but not for moderately traumatized rats (47.3 +/- 11.9 mmHg). The method allows observation of ICP for a critical period up to 3 h. As such the method can be regarded as clinically relevant to study early pathological aspects of intracranial hypertension and to define a therapeutic window for pharmacological intervention after traumatic brain injury (TBI).

Herpes simplex virus (HSV) is occasionally detected in the lower respiratory tract of patients in intensive care, but its clinical importance in such situations remains unclear. We did a prospective cohort study to define the prevalence, origin, risk factors, and clinical relevance of HSV in the respiratory tract of patients undergoing critical care.We tested 764 patients admitted to intensive care for the presence of HSV in the respiratory tract, and assessed statistical relations between this virus and clinical variables.HSV was detected by oropharyngeal swab in the upper respiratory tract of 169 (22%) of 764 patients, within 10 days of admission for 150 (89%) of these individuals. The virus was isolated in 58 (16%) of 361 patients whose lower respiratory tract was sampled. The presence of HSV in the throat was a risk factor for development of HSV infections in the lower respiratory tract (p0.001). HSV was isolated most frequently in patients with severe disease. HSV in the throat was associated with acute respiratory distress syndrome (p0.001) and with increased length of stay in intensive care (p0.001).Our data suggest that HSV reactivation or infection of the upper respiratory tract is frequent among patients in intensive care, and is a risk factor for development of lower respiratory tract infection with this virus, possibly by means of aspiration.

Thrombotic disease of the vertebrobasilar circulation is associated with a poor prognosis. It may occur in trauma patients, especially those with neck injuries and even several months after the initial insult. We report on the case of a young polytrauma patient, victim of a traffic accident, with associated cervical and thoracic spinal injuries resulting in paraplegia. Consciousness was not impaired initially, but during transfer to our hospital he became suddenly unconscious. An occluded basilar artery was found on angiography, but unfortunately we were unable to reopen the vessel with thrombolytic therapy. This case again proves that lesions of the vertebro-basilar system must always be suspected in neck injuries. Even after minor whiplash injuries, fatal basilar thrombosis may occur. A review of all reported cases of traumatic basilar artery thrombosis is given and the use of thrombolytic therapy is discussed.

Unilateral intracarotid injection of contrast agents may considerably destabilize the blood - brain barrier in rats. This leads to vasogenic edema in the ipsilateral hemisphere. Mortality and extravasation increased significantly when administration of these ultrasound contrast agents was followed by mild traumatic brain injury. Direct administration to the cerebral circulation is, therefore, indicative for edema-related pathology and may amplify the consequences of experimental neurotrauma.

We report a case of acute respiratory distress after upper airway obstruction following routine palatoplasty in an otherwise healthy 6-year-old boy. We believe that extreme variation of intrathoracal pressure was the basis of the development of the acute respiratory distress. We recommend after palatoplasty a more than careful postoperative clinical observation to detect and treat postoperative obstruction and hypoxemia.

Background:Many papers have focused on the importance of granulocytes in the process of reperfusion and ischemia. Most of the clinical studies measured several parameters of this process during and after coronary angiography, without taking into account the effect of the radiographic contrast media (RCM) used during this procedure.Materials and methods:We performed a randomized patient study(n=37)to evaluate the effect of ionic and non-ionic RCM on granulocyte adhesion during coronary angiography. We also evaluated the influence of the ionicity and osmolarity of the different substances on granulocyte adhesion molecules inin vitroexperiments.Results:The osmolarity of patient serum samples increased from 302±1 to 309±1 mOsm/kg(P<0.05)after infusion of RCM. The CD11b expression in the samples of the non-ionic RCM treated group increased from 221±21 MFI to 377±30 MFI(P<0.05)measured as the absolute mean fluorescence intensity (MFI), yet did not alter significantly in the ionic RCM group. In contrast, thein vitroexperiments showed a reduction of the CD11b expression from 360±70 MFI to 149±30 MFI(P<0.05)in the ionic RCM group.Conclusions:The upregulation of adhesion molecules was significantly reducedin vivowith ionic RCM, while ionic substances caused opposite effectsin vitro. This effect should be taken into account when performing leukocyte functional analysis of samples taken during angiography.

Intrathecal administration of ionic contrast media may cause severe and fatal neurotoxic reactions due to their hyperosmolarity and ionic nature. They are therefore strictly contraindicated for all radiologic applications involving the central nervous system (e.g., myelography). We present a case in which ioxitalamate was accidentally injected intrathecally. The patient recovered completely due to a combination of the different therapeutic options reported in the literature, including early mechanical ventilation and neuromuscular paralysis, aggressive control of seizures, elevation of head and trunk to prevent cephalad migration of contrast, steroids, cerebrospinal fluid drainage and lavage and prophylactic antibiotics.

In this study, we evaluated the accuracy of intracranial pressure (ICP) measurement in rats by insertion of a miniature ICP probe in the parenchyma of the cerebellum. A comparison was made between the ICP values measured simultaneously in the parenchyma of the cerebral cortex and the cerebellum. In order to obtain a wide range of ICP, animals were subjected to a severe closed head injury (CHI), a moderate CHI or to a sham operation. ICP values ranged from 0.8 to 43.9 mmHg. After 15 min stabilisation the first measurement was taken and followed by a second measurement 25 min after onset to allow comparison of ICP changes at the two implantation sites. Linear regression analysis showed a highly significant correlation at 15 min: Y = 0.919X + 0.655 (R(2) = 0.977), and at 25 min: Y = 0.931X + 0.698 (R(2) = 0.976). The differences in ICP measurement between cerebellar and cerebral site were not significantly different from zero at both time points. Altman-Bland plots showed that the difference in ICP readings between the two locations could differ maximally by 5.3 mmHg. The largest differences were detected when high ICP values were recorded. We conclude that in rats the ICP measurement in the cerebellum is comparable to the ICP measurement in the cerebral cortex. The cerebellar ICP can be used as a valuable alternative during experimental procedures. ispartof: Journal of Neuroscience Methods vol:119 issue:1 pages:83-8 ispartof: location:Netherlands status: published

The respiratory syncytial virus (RSV) represents the leading cause of viral bronchiolitis and pneumonia in children worldwide and is associated with high morbidity, hospitalization rate, and significant mortality rates. The immune response elicited by RSV is one of the main factors contributing to the pathogenesis of the disease. Two subsets of the cellular immune response, the T helper 17 cell (Th17) and the regulatory T-cell (Treg), and more particularly the balance between these two subsets, might play a significant role in the pathogenesis of the RSV infection. The developmental pathways of Th17 and Treg cells are closely and reciprocally interconnected and plasticity has been demonstrated from Treg toward Th17. During an RSV infection, the functions of both subsets are opposed to one another regarding viral clearance and clinical severity. Th17 and Treg cells offer a promising new view on the pathogenesis of an RSV infection and deserve further exploration.

In recent years, it has been demonstrated that sewage-based epidemiology can deliver interesting information on trends in illicit drug consumption. However, until now, no real evidence exists that the measured concentrations of drugs in sewage can be exactly correlated with the amounts of drugs used by a specific population. This study aimed therefore at correlating detailed monthly prescription figures of 11 pharmaceuticals (atenolol, bisoprolol, citalopram, fluoxetine, venlafaxine, losartan, telmisartan, valsartan, carbamazepine, metformin, and tramadol) with measured concentrations of these compounds in influent sewage from five sewage treatment plants in Belgium. For 7 out of the 11 substances, a ratio between loads calculated from the prescription figures and loads calculated from measured concentrations in the range of 0.303.00 was observed. For four pharmaceuticals (atenolol, bisoprolol, telmisartan, and venlafaxine), the observed relationship was less pronounced. The manuscript gives an overview of the possible uncertainties that are related with the calculated correlations. This study highlights the need for gathering all the necessary information regarding sewage sampling, stability of substances in sewage, pharmacokinetics, and analytical method performance when sewage-based epidemiology studies are performed.

Phthalates are potentially involved in the development of type 2 diabetes mellitus. In a cohort of 123 obese subjects, 10 phthalate metabolites were analyzed. An oral glucose tolerance test was performed and various estimates of insulin resistance and beta-cell function were calculated. After adjustment for age, physical activity level, smoking behavior, medication use and body mass index, several phthalate metabolites were linked to markers of glucose tolerance and insulin resistance. (C) 2015 Elsevier Inc. All rights reserved.

Purpose of review Fluid management is regarded as a cornerstone of successful perioperative care, but fluid prescription is not always treated that way. New insights and guidelines have become available very recently. Recent findings Although most of the recent scientific attention went to resuscitation fluids and the place of hydroxyethyl starches, recent guidelines also emphasize the importance of fluid prescription in a maintenance and a replacement setting. The use of balanced solutions over saline 0.9% gains momentum because recent evidence shows the deleterious effect of chloride-containing solutions on relevant clinical endpoints. Where the debate on the use of starches in septic and critically ill patients seems to be settled after recent trials pointed out several safety issues in the absence of a proven benefit, their intraoperative use is still a matter of debate. A presumably correct use in this setting was proposed recently. Summary The combination of a careful prescription of maintenance fluids, additional replacement solutions tailored to the patient's eventual extra needs and a rational but nonaggressive goal-directed approach to resuscitation fluids seems to be the best practice to avoid fluid-related morbidity. Isotonic balanced crystalloids seem the best pragmatic choice for resuscitation purposes. In certain well defined conditions, colloids can still be used.

OBJECTIVE The contribution of persistent organic pollutants (POPs) to the pandemic of type 2 diabetes mellitus and obesity has been assumed but remains speculative. Our study aimed at investigating the relationship of POP levels with detailed markers of glucose metabolism and body composition. RESEARCH DESIGN AND METHODS Glucose tolerance was determined in a group of normal-weight and obese individuals. Fat distribution was assessed with abdominal computed tomography (CT) scanning, determining subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). Selected POPs (28 polychlorinated biphenyls [PCBs] and the pesticide p,p’-dichlorodiphenyldichloroethylene [p,p’-DDE]) were measured in serum. In a subset of obese individuals undergoing bariatric surgery, POPs were also measured in adipose tissue. RESULTS Among obese participants, serum and adipose tissue levels of POPs were significantly correlated to glucose levels during an oral glucose tolerance test. Logistic regression using a model including age, age2, sex, family history of diabetes, BMI, CT-VAT, smoking behavior, physical activity level score, and a POP level identified serum levels of PCB153, the sum of PCBs and p,p’-DDE as significant predictors of abnormal glucose tolerance (odds ratio 4.6, 4.8, and 3.4, respectively; P < 0.05). Adipose tissue levels of p,p’-DDE were also significant predictors (odds ratio 81.6; P < 0.05). Serum levels of PCBs were inversely related to BMI, while serum and adipose tissue levels of all POPs were positively related to the CT-VAT/SAT ratio, suggesting an important role for the visceral fat compartment in POP dynamics. CONCLUSIONS Our findings further sustain the theory that exposure to environmentally relevant levels of POPs may exert both a diabetogenic and obesogenic effect.

The obesogen hypothesis states that together with an energy imbalance between calories consumed and calories expended, exposure to environmental compounds early in life or throughout lifetime might have an influence on obesity development. In this work, we propose a new approach for obesogen screening, i.e., the use of transcriptomics in the 3T3-L1 pre-adipocyte cell line. Based on the data from a previous study of our group using a lipid accumulation based adipocyte differentiation assay, several human-relevant obesogenic compounds were selected: reference obesogens (Rosiglitazone, Tributyltin), test obesogens (Butylbenzyl phthalate, butylparaben, propylparaben, Bisphenol A), and non-obesogens (Ethylene Brassylate, Bis (2-ethylhexyl)phthalate). The high stability and reproducibility of the 3T3-L1 gene transcription patterns over different experiments and cell batches is demonstrated by this study. Obesogens and non-obesogen gene transcription profiles were clearly distinguished using hierarchical clustering. Furthermore, a gradual distinction corresponding to differences in induction of lipid accumulation could be made between test and reference obesogens based on transcription patterns, indicating the potential use of this strategy for classification of obesogens. Marker genes that are able to distinguish between non, test, and reference obesogens were identified. Well-known genes involved in adipocyte differentiation as well as genes with unknown functions were selected, implying a potential adipocyte-related function of the latter. Cell-physiological lipid accumulation was well estimated based on transcription levels of the marker genes, indicating the biological relevance of omics data. In conclusion, this study shows the high relevance and reproducibility of this 3T3-L1 based in vitro toxicogenomics tool for classification of obesogens and biomarker discovery. Although the results presented here are promising, further confirmation of the predictive value of the set of candidate biomarkers identified as well as the validation of their clinical role will be needed.

Cannabis is a frequently used recreational drug that potentially imposes serious health problems. We report three cases where recent and/or chronic use of marijuana led to severe cardiac dysfunction. All three patients collapsed at home and required cardiopulmonary resuscitation (CPR) with initial restoration of spontaneous circulation (ROSC). The mechanism of the cardiovascular collapse was different in each case. The first case presented with asystole and was found to have diffuse coronary vasospasm on coronary angiography in the hours after acute cannabis abuse. In the second case, an acute anterior infarction with occlusion of both the right coronary artery (RCA) and the left anterior descendens (LAD) was observed in a young patient without known cardiovascular risks but with chronic cannabis abuse. The third case presented at home with ventricular fibrillation presumably caused by an acute coronary syndrome due to left anterior descending (LAD) artery occlusion. The hetero-anamnesis of the family reported that all three patients had recently used cannabis. Toxicological screening also showed no other substance abuse than cannabis. Using these three cases, we would like to illustrate that the widespread use of cannabis is not as innocent as is believed. Cannabis use can lead to severe cardiovascular problems and sudden death, not only in people at increased cardiovascular risk, but also in young people without any medical history or risk factors.

The endotheliumis key in the pathophysiology of numerous diseases as a result of its precarious function in the regulation of tissue homeostasis. Therefore, its clinical evaluation providing diagnostic and prognostic markers, as well as its role as a therapeutic target, is the focus of intense research in patientswith severe illnesses. In the critically ill with sepsis and acute brain injury, the endothelium has a cardinal function in the development of organ failure and secondary ischemia, respectively. Cellular markers of endothelial function such as endothelial progenitor cells (EPC) and endothelialmicroparticles (EMP) are gaining interest as biomarkers due to their accessibility, although the lack of standardization of EPC and EMP detection remains a drawback for their routine clinical use. In this paper we will review data available on EPC, as a general marker of endothelial repair, and EMP as an equivalent of damage in critical illnesses, in particular sepsis and acute brain injury. Their determination has resulted in new insights into endothelial dysfunction in the critically ill. It remains speculative whether their determination might guide therapy in these devastating acute disorders in the near future.

Background: Exploration of the impact of severe hypotension on the evolution of acute kidney injury in septic patients. Methods and Results: We reviewed the hemodynamic parameters of 137 adults with septic shock and proven blood stream infection in the ICU. Severe hypotension was defined as a mean arterial blood pressure (MAP)

Despite their frequent use, allergy to illicit drugs and narcotics is rarely reported in literature. We present a review of the different classes of drugs of abuse that might be involved in allergies: central nervous system (CNS) depressants (such as cannabis, opioids and kava), CNS stimulants (cocaine, amphetamines, khat and ephedra) and hallucinogens such as ketamine and nutmeg. Diagnosis of drug and narcotic allergy generally relies upon careful history taking, complemented with skin testing eventually along with quantification of sIgE. However, for various reasons, correct diagnosis of most of these drug allergies is not straightforward. For example, the native plant material applied for skin testing and sIgE antibody tests might harbour irrelevant IgE-binding structures that hamper correct diagnosis. Diagnosis might also be hampered due to uncertainties associated with the non-specific histamine releasing characteristics of some compounds and absence of validated sIgE tests. Whether the introduction of standardized allergen components and more functional tests, that is, basophil activation and degranulation assays, might be helpful to an improved diagnosis needs to be established. It is anticipated that due to the rare character of these allergies further validation is although necessary.

Objectives: To illustrate that acute, even dramatic, demyelination of the central nervous system and encephalitis can occur after viral i.e. influenza A/H1N1 vaccination or infection. Patients and methods: We describe a case of encephalitis/acute disseminated encephalomyelitis associated with vaccination against influenza A/H1N1 and review the available literature. Results: We report a case of a 26-year-old female who developed symptoms of acute encephalitis 5 days after vaccination against the pandemic 2009 A/H1N1 influenza. MRI of the brain showed confluent T2-hyperintense signal intensity changes in the deep white matter which further confirmed the diagnosis of encephalitis/acute disseminated encephalomyelitis. Despite therapy with immunoglobulins and corticosteroids, her persistent vegetative state continued. In light of the dramatic cause of this case, we reviewed all 21 other previously reported cases of central nervous system demyelination related to H1N1 vaccination and/or infection. Conclusions: The available data suggest that even severe central nervous system demyelination i.e. acute encephalitis/disseminated encephalomyelitis and transverse myelitis may very rarely be associated with vaccination against novel influenza A/H1N1 or with A/H1N1 infection itself. (C) 2014 Elsevier B.V. All rights reserved.

Objectives: To review clinical and radiological findings in patients with Duret hemorrhages and to discuss the pathophysiology and differential diagnosis of these lesions. Patients and methods: We reviewed the case records of four patients with Duret hemorrhages who had been admitted to the neurological intensive care unit with supratentorial mass lesions. Results: Descending transtentorial and subfalcine herniations were present in all cases. Three patients were admitted with acute subdural hematoma and one with intraparenchymal hemorrhage. Computed tomography revealed the presence of blood in the mesencephalon and upper pons. Three patients died; one survived with severe disabilities. Discussion: Duret hemorrhages are typically located in the ventral and paramedian aspects of the upper brainstem (mesencephalon and pons). The pathophysiology of Duret hemorrhage remains under debate: arterial origin (stretching and laceration of pontine perforating branches of the basilar artery), versus venous origin (thrombosis and venous infarction). Multifactorial causation seems likely. Conclusion: Duret hemorrhages are delayed, secondary brainstem hemorrhages. They occur in craniocerebral trauma victims with rapidly evolving descending transtentorial herniation. Diagnosis is made on computed tomography of the brain. In most cases the outcome is fatal. On the basis of our observations we believe that arterial hypertension and advanced age are risk factors for the development of Duret hemorrhage.

Central venous catheters are widely used in clinical practice. Air embolism is a rare, but potentially life threatening complication of central venous catheterisation. We describe a case of collapse and transient hemiplegia after removal of central venous catheter. This was accidentally performed with the patient in upright position. A CT scan of the brain demonstrated air in the sinus cavernosus bilaterally and at the posterior wall of the foramen magnum.

We present a case of a 3-year-old boy with neurodegeneration. Family history reveals Rendu-Osler-Weber disease. Magnetic resonance imaging (MRI) of the spinal cord and spinal angiography showed a spinal arteriovenous fistula with venous aneurysm, causing compression of the lumbar spinal cord. Embolisation of the fistula was executed, resulting in clinical improvement. A week after discharge he was readmitted with neurologic regression. A second MRI scan revealed an intraspinal epidural haematoma and increase in size of the aneurysm with several new arterial feeders leading to it. Coiling of the aneurysm and fistulas was performed. Postoperative, the spinal oedema increased despite corticoids, causing more extensive paraplegia of the lower limbs and a deterioration of his mental state. A laminectomy was performed and the aneurysm was surgically removed. Subsequently, the boy recovered gradually. A new MRI scan after two months showed less oedema and a split, partly affected spinal chord. This case shows the importance of excluding possible arteriovenous malformations in a child presenting with progressive neurodegeneration. In particular when there is a family history for Rendu-Osler-Weber disease, scans should be performed instantly to rule out this possibility. The case also highlights the possibility of good recovery of paraplegia in paediatric Rendu-Osler-Weber patients.

The only way to rescue ischaemic tissue is to re-instate the oxygen supply to the tissue. However reperfusion of the ischaemic area not only oxygenates the tissue but also initiates a cascade of processes, which may in some cases result in temporary dysfunction of the myocardium. In order to devise protective measures, it is essential to understand the mechanisms and the triggers of this reperfusion phenomenon. In this review we will mainly focus on the inflammatory response caused by reperfusion. We will cover the different steps of polymorphonuclear leukocyte activation and will briefly discuss the molecular biology of the receptors involved. The currently used pharmacological medications in acute cardiology will be reviewed and in particular their actions on polymorphonuclear leukocyte activation, adhesion and degranulation. This review is a compilation of the current knowledge in the field and the therapeutic progress in the prevention of reperfusion injury made today.

We investigated the dynamics of several organohalogenated contaminants (OHCs) and their metabolites in an obese population during weight loss. Serum samples from obese individuals were taken before patients lost weight and after three, six, and twelve months. Samples were also collected from a matched lean control population. Analyzed OHCs were polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (HO-PCBs), pentachlorophenol (PCP), polybrominated diphenyl ethers, and organochlorine pesticides (OCPs). Significantly lower concentrations of major PCBs, their metabolites, and PCP were measured in obese individuals at the initial moment of their enrolling in the project. While dilution differences might be responsible for the lower concentrations in the neutral OHCs, we suggest that a lower CYP-mediated metabolic activity can partially explain the data for the HO-PCBs. Additionally, lower chlorinated substituted PCBs had a higher percentage contribution to the sum PCBs in obese individuals, while higher chlorinated PCBs had a higher contribution for the controls. Increasing serum levels for all OHCs were observed during weight loss. The release from adipose tissue seemed dependent on the octanol-water partition coefficient, since OHCs with higher log K-ow values displayed a higher release in serum. This also influenced the HO-PCBs profile after weight loss with lower chlorinated HO-PCBs increasingly gaining importance. Although weight loss is beneficial, it also influences the release of OHCs from adipose tissue and their metabolism. Therefore, the increase in the levels of compounds with endocrine effects might be of concern.

Delirium is a serious and frequent disorder in ICU patients. The aim of this study was to internationally validate the existing Prediction of Delirium ICU (PREDELIRIC) model to predict delirium in ICU patients.

Recently the environmental obesogen hypothesis has been formulated, proposing a role for endocrine disrupting compounds (EDCs) in the development of obesity. To evaluate this hypothesis, a screening system for obesogenic compounds is urgently needed. In this study, we suggest a standardised protocol for obesogen screening based on the 3T3-L1 cell line, a well-characterised adipogenesis model, and direct fluorescent measurement using Nile red lipid staining technique. In a first phase, we characterised the assay using the acknowledged obesogens rosiglitazone and tributyltin. Based on the obtained dose-response curves for these model compounds, a lipid accumulation threshold value was calculated to ensure the biological relevance and reliability of statistically significant effects. This threshold based method was combined with the well described strictly standardized mean difference (SSMD) method for classification of non-, weak- or strong obesogenic compounds. In the next step, a range of EDCs, used in personal and household care products (parabens, musks, phthalates and alkylphenol compounds), were tested to further evaluate the obesogenicity screening assay for its discriminative power and sensitivity. Additionally, the peroxisome proliferator activated receptor γ (PPARγ) dependency of the positive compounds was evaluated using PPARγ activation and antagonist experiments. Our results showed the adipogenic potential of all tested parabens, several musks and phthalate compounds and bisphenol A (BPA). PPARγ activation was associated with adipogenesis for parabens, phthalates and BPA, however not required for obesogenic effects induced by Tonalide, indicating the role of other obesogenic mechanisms for this compound.

A seven-month-old baby was admitted to a hospital emergency department after collapsing suddenly while staying with his nanny. The baby displayed classic symptoms of shaken baby syndrome, including subdural haemorrhage, cytotoxic cerebral oedema, and bilateral retinal hemorrhages. Child protection services were informed, but both the parents and the nanny denied any involvement. In the subsequent weeks, the baby developed three other episodes of new subdural bleeding and a medico-legal investigation was started into the origin of the repeated subdural bleeding. Eventually, platelet aggregation tests and electron microscopy diagnosed a delta-storage pool disease; that is, a haemostatic disorder involving dense granules of the platelets. Initial minor blunt trauma may have resulted in subdural bleeding, while subsequent retinal haemorrhage could have been facilitated by the underlying haemostatic disorder. Delta-storage pool disease should be considered as a possible mimic of abusive head trauma similar to other rare conditions such as Menkes disease and type 1 glutaric aciduria.

Background: The metabolic disruptor hypothesis postulates that environmental pollutants may be risk factors for metabolic diseases. Because insulin resistance is involved in most metabolic diseases and current health care prevention programs predominantly target insulin resistance or risk factors thereof, a critical analysis of the role of pollutants in insulin resistance might be important for future management of metabolic diseases. Objectives: We aimed to critically review the available information linking pollutant exposure to insulin resistance and to open the discussion on future perspectives for metabolic disruptor identification and prioritization strategies. Methods: We searched PubMed and Web of Science for experimental studies reporting on linkages between environmental pollutants and insulin resistance and identified a total of 23 studies as the prime literature. Discussion: Recent studies specifically designed to investigate the effect of pollutants on insulin sensitivity show a potential causation of insulin resistance. Based on these studies, a summary of viable test systems and end points can be composed, allowing insight into what is missing and what is needed to create a standardized insulin resistance toxicity testing strategy. Conclusions: It is clear that current research predominantly relies on top-down identification of insulin resistance–inducing metabolic disruptors and that the development of dedicated in vitro or ex vivo screens to allow animal sparing and time- and cost-effective bottom-up screening is a major future research need. Citation: Hectors TL, Vanparys C, Van Gaal LF, Jorens PG, Covaci A, Blust R. 2013. Insulin resistance and environmental pollutants: experimental evidence and future perspectives. Environ Health Perspect 121:1273–1281; http://dx.doi.org/10.1289/ehp.1307082

Conclusion: This study showed that GABAB agonist baclofen (10 mg) affects the semicircular canals (SCCs), both centrally and peripherally, but does not influence the otolithic function. Objectives: The aim of the study was to identify the effects of baclofen on the complete vestibular system, i.e. semicircular canals, saccules and utricles. Methods: The study had a double-blind, placebo-controlled, repeated measures design and was conducted on healthy male volunteers. With electronystagmography (ENG), the SCC function was evaluated, whereas utricular function was determined by means of unilateral centrifugation (UC). Cervical vestibular evoked myogenic potentials (cVEMPs) tested saccular integrity. Results: Baclofen caused a significant increase of the vestibulo-ocular reflex (VOR) phase and a significant decrease of the total caloric response (TCR), both measured during ENG. The drug also decreased the maximal contribution of the SCCs to ocular counter-rolling (OCR) evaluated during UC. No effects on saccules and utricules were observed.

Human exposure to chemicals commonly encountered in our environment, like phthalates, is routinely assessed through urinary measurement of their metabolites. A particular attention is given to the specific population groups, such as obese, for which the dietary intake of environmental chemicals is higher. To evaluate the exposure to phthalates, nine phthalate metabolites (PMs) were analyzed in urine collected from obese individuals and a control population. Obese individuals lost weight through either bariatric surgery or a conservative weight loss program with dietary and lifestyle counseling. Urine samples were also collected from the obese individuals after 3, 6 and 12 months of weight loss. Individual daily intakes of the corresponding phthalate diesters were estimated based on the urinary PM concentrations. A high variability was recorded for the levels of each PM in both obese and control urine samples showing the exposure to high levels of PMs in specific subgroups. The most important PM metabolite as percentage contribution to the total PM levels was mono-ethyl phthalate followed by the metabolites of di-butyl phthalate and di 2-ethyl-hexyl phthalate (DEHP). No differences in the PM levels and profiles between obese entering the program and controls were observed. Although paralleled by a significant decrease of their weight, an increase in the urinary PM levels after 3 to 6 months loss was seen. Constant figures for the estimated phthalates daily intake were observed over the studied period, suggesting that besides food consumption, other human exposure sources to phthalates (e.g. air, dust) might be also important. The weight loss treatment method followed by obese individuals influenced the correlations between PM levels, suggesting a change of the intake sources with time. Except for few gender differences recorded between the urinary DEHP metabolites correlations, no other differences were observed for the urinary PM levels as a function of age, body mass index or waist circumference. Linear regression analysis showed almost no significance of the relationship between measured urinary PMs and serum free thyroxine, thyroid-stimulating hormone (TSH) for all obese individuals participating to the study, while for the control samples, several PMs were significantly associated with the serum TSH levels. Keywords: Intake estimation, Phthalates, Phthalate metabolites, Obesity, Urine, Weight loss

A new analytical method was developed for the determination of dialkyl and diaryl phosphates (DAPs), which are metabolites of organophosphate triesters (PFRs), in human urine. Target DAPs included dibutyl phosphate (DBP), diphenyl phosphate (DPHP), bis(2-butoxyethyl) phosphate (BBOEP), bis(2-chloroethyl) phosphate (BCEP), bis(1-chloro-2-propyl) phosphate (BCPP), and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP). Sample preparation was based on solid phase extraction using a weak anion exchange sorbent (Oasis WAX). Although several instrumental techniques have been tested, best results were obtained with reversed phase liquid chromatography-negative electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS) taking the total analysis time into account. Method accuracy at 3 ng/mL in pooled urine ranged between 69 and 119% (recovery), while inter-day imprecision (as relative standard deviation) was

A case of oral ingestion of large doses of both the amphetamine-derivative 3,4-methylene dioxyethamphetamine (MDEA) and heroin is reported. Despite high serum levels of both drugs, the patient did not present with the classic signs and symptoms normally seen during intoxication with these drugs. The patient recovered after symptomatic treatment. The possibility that opposite pharmacological properties of the two drugs prevented the patients death is discussed.

Oxidized low-density lipoprotein (LDL) is currently regarded as a tentative key player in atherosclerosis by virtue of its ability to induce intracellular lipid accumulation and to modulate cell functions in the vessel wall. We previously demonstrated that inducible nitric oxide (NO) synthase activity is attenuated in lipid-laden J774 macrophages obtained by incubation with oxidized LDL 200 micrograms ml-1 for 24 h. In the present study we investigated the effect of oxidized LDL in a lower concentration (20 micrograms ml-1) or for a shorter time (6 h) and the possible mediator role of prostaglandin E2 and prostacyclin. Prostaglandins and the NO synthase metabolites citrulline and nitrite were elevated in the 24 h supernatant after immune stimulation with interferon-gamma 100 U ml-1 with or without lipopolysaccharide 10 micrograms ml-1. Pretreatment with oxidized LDL 20 micrograms ml-1 for 18 h decreased nitrite release by 31 +/- 2%, whereas prostaglandin production was not affected. A 6 h pre-exposure to 200 micrograms ml-1 had an opposite effect: it significantly potentiated interferon-gamma-stimulated prostaglandin E2 (10-fold), prostacyclin (7-fold), nitrite (1.5-fold), and citrulline (2.4-fold) release. Indomethacin 10 microM abolished the prostaglandin production and largely prevented the oxidized LDL-dependent increase in NO synthase activity. Acetylated LDL was without effect. The data show that the immune-induced release of NO is potentiated or suppressed, depending on the conditions of exposure to oxidized LDL. The potentiation due to short, high-dose exposure is partly mediated by prostaglandins since indomethacin inhibited both processes.

By the simultaneous measurement of acetylcholine release and smooth muscle contraction in rabbit tracheal segments with and without epithelium, pre- as well as postsynaptic effects of this cell layer were studied on cholinergic neurotransmission. The epithelial cell layer exerted a presynaptic inhibitory influence on acetylcholine release, induced by KCl and electrical stimulation, with a concomitant decrease in the smooth muscle contractions. The responses elicited by exogenous acetylcholine, acting postsynaptically, were also inhibited in the presence of the epithelium. The epithelial effect was not accounted for by the production of inhibitory prostaglandins or a nitric oxide-synthase product. Furthermore, the epithelium did not function as a metabolic site for the degradation of acetylcholine. Phosphoramidon, an inhibitor of neutral endopeptidase, mimicked the effects of epithelium removal on the cholinergic responses to high frequency stimulation and on the acetylcholine-induced effects. Neutral endopeptidase inhibition did not further enhance the responses in epithelium-denuded segments. We therefore suggest that the inhibitory function of the epithelium can be partly explained by the activity of neutral endopeptidase, limiting the excitatory effects of tachykinins on cholinergic responses. An alteration in the neutral endopeptidase activity as a result of inflammatory responses and epithelial damage can contribute to the mechanism of airway hyperreactivity in asthma.

We report the isolation of the aquatic gram-negative bacterium Shewanella putrefaciens from the bronchoalveolar lavage in a case of ventilator-associated pneumonia. To our knowledge, this species has never been isolated from the lower respiratory tract before as a potential pathogen.

There are only few studies defining persistent organic pollutant (POP) concentrations in various fat compartments from living obese individuals. The present study has therefore determined the concentrations of various classes of organohalogenated compounds, such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and hexabromocyclododecanes (HBCDs) in visceral fat (VF: n = 52) and subcutaneous abdominal fat (SF: n = 52) samples collected in 2010–2012 from obese individuals in Belgium. Organohalogen compounds were detected in all fat samples in the decreasing order of their concentrations: PCBs > DDTs > HCHs > CHLs > HCB > HBCDs > PBDEs, suggesting that Belgians have been widely exposed to these contaminants. The levels and the patterns of POP distribution in VF and SF tissue depots were not significantly different. Concentrations of PCBs (VF/SF; median: 285/275 ng/g lw) and DDTs (VF/SF; median: 150/155 ng/g lw) were the major POPs in all fat samples. Concerning PCBs, PCB 153 (VF/SF: 27/26%) was the most dominant congener, followed by PCB 180 (VF/SF: 17/18%), PCB 138 (VF/SF: 15/14.5%) and PCB 170 (VF/SF: 8.1/8.4%) to the sum PCBs, respectively. Levels of HBCDs (VF/SF; median: 4.0/3.7 ng/g lw) and PBDEs (VF/SF; median: 2.6/2.7 ng/g lw) were 1–2 orders of magnitude lower than those of PCBs and DDTs. Among PBDEs, BDE 153 (VF/SF: 31/34%) was the dominant congener, followed by BDE 47 (VF/SF: 26/23%), BDE 154 (VF/SF: 16/16%), BDE 100 (VF/SF: 10/11%) and BDE 99 (VF/SF: 9/9%). To our knowledge, this is the first report on HBCD concentrations in Belgian human fat tissues. Total PBDE and HBCD levels in human fat samples could not be correlated with age. In agreement with the literature, a significant correlation (p

Recently it was demonstrated that the analysis of drugs of abuse (DOA) in wastewater can be used to track their use in communities. This paper presents the optimization, validation, and application of an analytical procedure based on solid-phase extraction (SPE) and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of some emerging drugs in influent wastewater. The compounds of interest were the cathinone derivatives methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone (MEPH)), ketamine (KET) and its metabolites norketamine (NK) and dehydronorketamine (DHNK), as well as the major metabolite of cannabis, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH). Except for DHNK, deuterated analogues were used as internal standards for quantification. The use of a short C18 column (50 mm x 2 mm, 3 µm) allowed a good separation for the compounds analyzed in positive ionization mode (KET, NK, DHNK, MDPV, and MEPH) and for THC-COOH, which was analyzed in negative ionization mode, with a total run time of 13 min. Sample preparation using SPE was optimized by comparing Oasis HLB and Oasis MCX sorbents. The method was validated for each compound by assessing the following parameters: linearity, accuracy, precision, recovery, and relative process efficiency. The lowest calibration level was considered as the lower limit of quantification (LLOQ) and was 5 ng/l for KET, NK, DHNK, MDPV, and MEPH and 20 ng/l for THC-COOH. KET, and THC-COOH could be quantified in the majority of wastewater samples from three large wastewater treatment plants in Belgium. The other compounds were below the LLOQ or could not be detected.

Introduction Thiopental is a cornerstone in the treatment of refractory status epilepticus and intractable intracranial hypertension. In our center we observed that thiopental might cause falsely elevated serum sodium levels. Methods Triggered by a recent case experience of extremely elevated serum sodium levels during thiopental treatment, we retrospectively identified 53 patients treated with thiopental in our intensive care unit between 2007 and 2011 and evaluated electrolyte changes. We differentiated the analysis before and after introduction of a new device for sodium assays (Dimension Vista, Siemens) in the central laboratory in April 2010. Standardized in vitro laboratory tests were performed to study the effect of thiopental on sodium analysis. Results Before April 2010, serum sodium levels determined in the central laboratory showed a good agreement with the bedside point-of-care (POC) device during thiopental therapy with [sodium]laboratory − [sodium]POC of only 1.08 mmol/L (P = .0517). After April 2010, a strong discrepancy between laboratory values and POC values was observed with [sodium]laboratory − [sodium]POC = 11.57 mmol/L (P < .0001). Standardized in vitro testing confirmed that thiopental induced a dose-dependent false hypernatremia (P = .002). Conclusions Thiopental treatment can result in falsely elevated serum sodium. This is a critical finding since high sodium levels preclude administrating mannitol or hypertonic saline for the treatment of elevated intracranial pressure. Moreover, a false high sodium level might lead to the inappropriate administration of hypotonic fluids potentially resulting in increased brain edema and even higher intracranial pressure. To our knowledge, this is the first paper describing this clinically relevant phenomenon.

Despite the development of new antiepileptic drugs, Dravet syndrome frequently remains therapy resistant and is a catastrophic epilepsy syndrome. Fenfluramine is an amphetamine-like drug that has been used in the past as a part of antiobesity treatments. Because of the possible cardiac adverse effects (valve thickening, pulmonary hypertension) associated with use of fenfluramine, it was withdrawn from the market in 2001. In Belgium, a Royal Decree permitted examination of the potential anticonvulsive effects of fenfluramine in a clinical trial consisting of a small group of patients diagnosed with Dravet syndrome.Herein, we report 12 patients, 7 female and 5 male, with a genetically proven (11 of 12) diagnosis of Dravet syndrome who received fenfluramine as add-on therapy.Their ages at their last evaluation ranged from 3-35 years. The mean dosage of fenfluramine was 0.34 (0.12-0.90) mg/kg/day. Exposure duration to fenfluramine ranged from 1-19 years. Seven of the patients who were still receiving the fenfluramine treatment at the time of the last visit had been seizure-free for at least 1 year. In total, patients had been seizure-free for a mean of 6 (1-19) years. In seven patients, the fenfluramine treatment was interrupted once during the follow-up; seizures reappeared in three of the seizure-free patients. Subsequent reintroduction of fenfluramine controlled the seizures in these three patients again. Only two patients exhibited a mild thickening of one or two cardiac valves without clinical significance.Compared with a recent long-term follow-up series in which a maximum of 16% of patients with Dravet syndrome were seizure-free, our result of 70% of patients with Dravet syndrome remaining seizure-free is noteworthy. Given the limitations of this observational study, a larger prospective study should be undertaken to confirm these promising results.