No clear trends in expatriation of non-human primate research from -Switzerland between 2004 and 2017.

INTRODUCTION: Animal experimentation is commonly practiced in scientific research worldwide. However, there are no globally accepted standards for regulating the ethical boundaries and accepted practices for animal experimentation. Large differences exist between countries. A report suggested that some researchers, especially from countries with more stringent animal experimentation regulations, may be relocating experimental research to countries with less stringent regulations. We followed a systematic literature review approach to identity publications and determine whether there is an increasing trend in expatriation of non-human primate experimentation by researchers based in Switzerland. We used the Projects People Publications database, which contains projects funded by the Swiss National Science Foundation, to identify researchers conducting experiments using non-human primates. This list of names, together with terms referring to non-human primates were used to search the Web of Science. Publications without an author affiliated to a Swiss institution, no living or only with free non-human primates, and non-original research were excluded. For each publication, we recorded the place of experimentation, funding source, number of animals, species and the statement of ethical approval. We retained 120 publications, involving more than 2,429 non-human primates. Macaca mulatta and Macaca fascicularis were the most common species. We could not confirm an increasing trend in expatriation of non-human primate experimentation outside of Switzerland. Over time, publications appeared to report the ethical approval number more consistently. These results should be interpreted with caution because the sample included only studies that were: 1) published and 2) reported in the Web of Science. Consequently, studies with insignificant results may have been excluded because these studies are rarely published, and studies of poor quality may have been excluded because they are often published in lower quality journals, not indexed by the Web of Science.

INTRODUCTION: L'expérimentation animale est couramment pratiquée dans la recherche scientifique dans le monde entier. Cependant, il n'existe pas de normes mondialement acceptées pour réglementer les limites éthiques et les pratiques acceptées pour cette expérimentation. De grandes différences existent entre les pays. Un rapport récent a suggéré que certains chercheurs, en particulier provenant de pays où la réglementation sur l'expérimentation animale est restrictive, pourraient délocaliser la recherche expérimentale vers des pays où les réglementations sont moins strictes. Nous avons suivi une approche de revue systématique de la littérature pour identifier les publications et déterminer s'il y a une tendance croissante à l'expatriation des expérimentations sur les primates non humains par des chercheurs basés en Suisse. Nous avons utilisé la base de données Projects People Publications, qui contient des projets financés par le Fonds national suisse de la recherche scientifique pour identifier des chercheurs conduisant des expériences sur des primates non humains. Cette liste de noms, ainsi que les termes faisant référence à des primates non humains ont été utilisés pour effectuer des recherches sur le Web of Science. Les publications sans auteur affilié à une institution suisse, non vivant ou consacrées uniquement à des primates non humains libres ainsi que les travaux de recherche non originaux ont été exclus. Pour chaque publication, nous avons enregistré le lieu d'expérimentation, la source de financement, le nombre d'animaux, les espèces et la déclaration d'approbation éthique. Nous avons retenu 120 publications, impliquant plus de 2,429 animaux. Macaca mulatta et Macaca fascicularis étaient les espèces les plus communes. Nous n'avons pas pu confirmer une tendance à la hausse de l'expatriation en dehors de la Suisse des expérimentations sur des primates non humains. Au fil du temps, les publications semblent déclarer le numéro d'approbation éthique de manière plus cohérente. Ces résultats doivent être interprétés avec prudence car l'échantillon ne comprenait que des études 1) publiées et 2) rapportées dans le Web de la science. Par conséquent, les études avec des résultats non significatifs peuvent avoir été exclues car ces études sont rarement publiées et les études de mauvaise qualité peuvent avoir été exclues car elles sont souvent publiées dans des revues de moindre qualité, non indexées par le Web of Science.

Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

BACKGROUND AND PURPOSE: The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). METHODS: From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. RESULTS: Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. CONCLUSIONS: Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE.

Test characteristics of milk amyloid A ELISA, somatic cell count, and bacteriological culture for detection of intramammary pathogens that cause subclinical mastitis.

Bovine mastitis is an important disease in the dairy industry, causing economic losses as a result of withheld milk and treatment costs. Several studies have suggested milk amyloid A (MAA) as a promising biomarker in the diagnosis of mastitis. In the absence of a gold standard for diagnosis of subclinical mastitis, we estimated the diagnostic test accuracy of a commercial MAA-ELISA, somatic cell count (SCC), and bacteriological culture using Bayesian latent class modeling. We divided intramammary infections into 2 classes: those caused by major pathogens (e.g., Escherichia coli, Staphylococcus aureus, streptococci, and lacto-/enterococci) and those caused by all pathogens (major pathogens plus Corynebacterium bovis, coagulase-negative staphylococci, Bacillus spp., Streptomyces spp.). We applied the 3 diagnostic tests to all samples. Of 433 composite milk samples included in this study, 275 (63.5%) contained at least 1 colony of any bacterial species; of those, 56 contained major pathogens and 219 contained minor pathogens. The remaining 158 samples (36.5%) were sterile. We determined 2 different thresholds for the MAA-ELISA using Bayesian latent class modeling: 3.9 µg/mL to detect mastitis caused by major pathogens and 1.6 µg/mL to detect mastitis caused by all pathogens. The optimal SCC threshold for identification of subclinical mastitis was 150,000 cells/mL; this threshold led to higher specificity (Sp) than 100,000 cells/mL. Test accuracy for major-pathogen intramammary infections was as follows: SCC, sensitivity (Se) 92.6% and Sp 72.9%; MAA-ELISA, Se 81.4% and Sp 93.4%; bacteriological culture, Se 23.8% and Sp 95.2%. Test accuracy for all-pathogen intramammary infections was as follows: SCC, sensitivity 90.3% and Sp 71.8%; MAA-ELISA, Se 88.0% and Sp 65.2%; bacteriological culture, Se 83.8% and Sp 54.8%. We suggest the use of SCC and MAA-ELISA as a combined screening procedure for situations such as a Staphylococcus aureus control program. With Bayesian latent class analysis, we were able to identify a more differentiated use of the 3 diagnostic tools. The MAA-ELISA is a valuable addition to existing tools for the diagnosis of subclinical mastitis.

Effects of meteorological factors and the lunar cycle on onset of parturition in cows.

The present paper summarizes a comprehensive retrospective study that was undertaken to investigate effects of meteorological factors and lunar cycle on gestation length and daily birth rate in cows. To this end, all cattle births in Switzerland between 2008 and 2010 (n=2,091,159) were related to detailed matched weather recordings. The study revealed some statistically significant effects of climate (temperature, barometric pressure, relative humidity) and weather (thunderstorms, heat index) on gestational length. Thunderstorms on the day before birth reduced the gestation length by 0.5 days. An increase in the birth rate was correlated with the temperature on the day before birth and the barometric pressure 3 days before birth. Differences in the barometric pressure >15hPa increased the birth rate by 4%. Nevertheless, the effects were not consistent and the modeled size of effect was so small that a clinical implication is unlikely. Although the daily birth rate was unevenly distributed across the lunar cycle, no clear pattern could be identified. Compared to the mean birth rate across the lunar cycle the highest daily birth rate was detected on day 4 after new moon (+1.9%) and the lowest on day 20 (-2.1%).

Detection of Chlamydia pneumoniae in a collection of captive snakes and response to treatment with marbofloxacin.

In a collection of 58 snakes comprising predominantly Eurasian vipers in Switzerland, five snakes died unexpectedly during hibernation from 2009 to 2012. In one snake, organisms resembling chlamydiae were detected by immunohistochemistry in multiple histiocytic granulomas. Real-time quantitative PCR and microarray analysis were used to determine the presence of Chlamydia pneumoniae in tissue samples and cloacal/choanal swabs from snakes in the collection; 8/53 (15.1%) of the remaining snakes were positive. Although one infected snake had suppurative periglossitis, infection with C. pneumoniae did not appear to be associated with specific clinical signs in snakes. Of seven snakes treated with 5 mg/kg marbofloxacin IM once daily, five became PCR negative for C. pneumoniae following treatment, whereas one animal remained positive and one snake was lost to follow-up.

Only a Touch of the Flu? The Simultaneous Manifestation of Acute Necrotizing Encephalopathy in Two Consanguineous Patients.

This case report describes the simultaneous manifestation of acute necrotizing encephalopathy in 2 consanguineous patients after infection with influenza B based on the autosomal dominant missense mutation of the RANBP2-gene. Differential diagnosis of acute encephalopathy, clinical and radiological clues, and treatment strategies are outlined.

Early predictors of refractory status epilepticus: an international two-center study.

BACKGROUND AND PURPOSE: Status epilepticus (SE) refractory to first- and second-line antiepileptic drugs carries high mortality. Little is known on early prediction of refractory SE (RSE)­an essential tool for planning appropriate therapy. Our aim was to identify and validate independent early RSE predictors in adults. METHODS: Clinical and laboratory data on consecutive intensive care unit patients with SE from two academic care centers (a derivation data set from a Swiss center and a validation data set from a US center) were assessed. Multivariable analysis was performed with the derivation set to identify RSE predictors at SE onset. Their external validity was evaluated with an independent validation set. Measures of calibration and discrimination were assessed. RESULTS: In all, 302 patients were analyzed (138 with and 164 without RSE), 171 in the derivation data set and 131 in the validation data set. Acute SE etiology, coma/stupor and serum albumin <35 g/l at SE onset were independent predictors for RSE in the derivation data set [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.01-4.07; OR 4.83, 95% CI 2.42-9.68; OR 2.45, 95% CI 1.16-5.16]. The prediction model showed good measures of calibration (Hosmer-Lemesow goodness-of-fit test P = 0.99) and discrimination (area under the receiver operating characteristic curve 0.8) on the derivation data set­results that were similar in the validation data set (Hosmer-Lemeshow P = 0.24; area under the receiver operating characteristic curve 0.73). CONCLUSIONS: This study confirms the independent prognostic value of readily available parameters for early RSE prediction. Prospective studies are needed to identify additional robust predictors, which could be added to the proposed model for further optimization towards a reliable prediction scoring system.

Reliability of fully automated versus visually controlled pre- and post-processing of resting-state EEG.

OBJECTIVE: To compare the reliability of a newly developed Matlab® toolbox for the fully automated, pre- and post-processing of resting state EEG (automated analysis, AA) with the reliability of analysis involving visually controlled pre- and post-processing (VA). METHODS: 34 healthy volunteers (age: median 38.2 (20-49), 82% female) had three consecutive 256-channel resting-state EEG at one year intervals. Results of frequency analysis of AA and VA were compared with Pearson correlation coefficients, and reliability over time was assessed with intraclass correlation coefficients (ICC). RESULTS: Mean correlation coefficient between AA and VA was 0.94±0.07, mean ICC for AA 0.83±0.05 and for VA 0.84±0.07. CONCLUSION: AA and VA yield very similar results for spectral EEG analysis and are equally reliable. AA is less time-consuming, completely standardized, and independent of raters and their training. SIGNIFICANCE: Automated processing of EEG facilitates workflow in quantitative EEG analysis.

Intranasal midazolam: pharmacokinetics and pharmacodynamics assessed by quantitative EEG in healthy volunteers.

The pharmacokinetics and pharmacodynamics of a highly concentrated cyclodextrin-based intranasal (i.n.) midazolam formulation containing the absorption-enhancer chitosan were studied in 12 healthy volunteers and compared with intravenous (i.v.) midazolam. The pharmacodynamic (PD) effects were assessed using quantitative electroencephalography (EEG). Maximal plasma concentrations of 63 and 110 ng/ml were reached at 8.4 and 7.6 min after 3 and 6 mg i.n. midazolam, respectively. After 5 mg i.v. and 6 and 3 mg i.n. midazolam, the times to onset of significant EEG effects in the ß2 band (18-25 Hz) were 1.2, 5.5, and 6.9 min, respectively, and the times to loss of response to auditory stimuli were 3.0, 8.0, and 15.0 min, respectively. A sigmoid maximum-effect (E(max)) model indicated disequilibrium between plasma and effect-site concentrations, with equilibration half-lives of 2.1-4.8 min. The observed pharmacokinetic-PD (PK-PD) properties suggest that i.n. midazolam deserves to be evaluated as an easy and noninvasive method of administering a first benzodiazepine dose, e.g., in out-of-hospital emergency settings with no immediate i.v. access.

[Primary brain tumors and brain metastases. Symptomatic epilepsy and driving ability - systematic review and expert opinion]. / Primäre Hirntumoren und Hirnmetastasen. Symptomatische Epilepsie und Fahreignung - Expertenumfrage und systematisches Review.

PURPOSE: Primary brain tumors and metastases are common causes of symptomatic epilepsy. Seizures, neurological and neuropsychological deficits can interfere with driving ability. The present paper aims to systematically review the incidence of epileptic seizures in brain tumor patients and to discuss driving ability in the context of the current German guidelines and expert opinions. METHODS: To evaluate the incidence of epileptic seizures which occur at the beginning and in the course of the disease, we performed a systematic literature research in PubMed from 1960 to 2007. Additionally on the basis of this data we performed a survey collecting expert opinions regarding the driving ability of brain tumor patients from members of the German working groups "Arbeitsgemeinschaft für prächirurgische Epilepsiediagnostik und operative Epilepsietherapie" (Working Group for Presurgical Epilepsy Diagnostics and Operative Epileptic Therapy) and "Neuroonkologische Arbeitsgemeinschaft" (Neuro-oncological Working Group). RESULTS: The incidence of epileptic seizures depends on the entity, dignity and localization of the tumor. The driving ability of brain tumor patients is not explicitly regulated in Germany. Of the interviewed experts 72% judged the guidelines to be precise enough and 44% did not want to deprive the patients of their driving ability without a first seizure, independent of the individual risk. DISCUSSION: The available studies are methodologically insufficient and show that a further evaluation is necessary to assess the driving ability. Possible restrictions of the driving ability in patients with a high risk of seizures in the course of the disease have to take into account the balance between individual rights and the interests of the general public.

[Drug treatment of CRPS]. / Medikamentöse Behandlung des CRPS.

The main symptoms of excruciating pain, trophic and inflammatory changes, as well as functional impairment of limbs are the hallmark of the complex regional pain syndrome (CRPS). While functional impairments have to be treated by physical and occupational therapy, the former three symptoms are amendable to drug treatment: antidepressants, antiepileptic drugs and opioids are the most important drug classes for alleviating neuropathic pain whereas acute nociceptive pain may be positively influenced by non-steroidal anti-inflammatory drugs and steroids. In addition, calcitonin and the biphosphonates inhibit osteoclasts and therefore loss of bone mass and may thus also reduce pain. The use of sympatholytic agents beyond locoregional anesthesia techniques (which are covered elsewhere in this issue) is not unequivocal. In general, the evidence level for treatment strategies specifically for the complex regional pain syndrome is very poor; most recommendations and algorithms rely on results derived from studies testing drugs against other conditions where chronic (neuropathic) pain is prevalent, like diabetic polyneuropathy or postherpetic neuralgia, or medications are used on the basis of pathomechanistic considerations.

Control of bovine fasciolosis in dairy cattle in Switzerland with emphasis on pasture management.

Thirty-two dairy cattle farms with fasciolosis as an established herd problem were visited and divided into groups according to the location of the habitats of the intermediate host of Fasciola hepatica. The farms were revisited 4-5 years later and those that had followed the recommended measures were compared to those that had not. Egg shedding and seroprevalence was significantly reduced in cows on farms complying with the control recommendations but was not reduced on farms that had not complied.

Cutaneous silent periods are not affected by the antihistaminic drug cetirizine.

OBJECTIVE: Noxious digital nerve stimulation leads to transient suppression of the electromyographic activity in isometrically contracted hand muscles, known as the "cutaneous silent period" (CSP). To date, neurotransmitters potentially involved in mediating this electromyographic (EMG) suppression remain unknown. Anecdotal observation lead to the hypothesis that antihistaminic medication may counteract nociceptive EMG suppression, as CSPs in one male subject who was accustomed to CSP recordings were temporarily lost following ingestion of an antihistaminic drug for acute rhinitis. A second otherwise healthy male subject, who was on long-term cetirizine for allergic rhinitis, presented without clearly defined CSPs when volunteering for normal values. METHODS: We undertook a systematic study in five healthy subjects (including the one with temporarily lost CSPs) who underwent serial CSP testing after ingestion of 10 mg cetirizine. CSPs were elicited in thenar muscles following digit II and digit V stimulation (20 times sensory threshold, 100 sweeps rectified and averaged) before and 90, 180, and 360 min following intake of medication. RESULTS: CSP onset latency, CSP end latency and CSP duration, as well as the index of suppression did not change significantly following ingestion of 10 mg cetirizine. Repeat study in the subject with no clearly defined CSPs on long-term treatment revealed persistently absent CSPs after a 5-week withdrawal from cetirizine. CONCLUSION: CSPs are not affected by therapeutic doses of the H1 antihistaminic cetirizine. SIGNIFICANCE: Our findings suggest that histamine plays no major role as a neurotransmitter of CSPs.

Use of a palliative care order set to improve resident comfort with symptom management in palliative care.

Although one-fourth of all medicare dollars are spent during the last year of life, symptom management for terminal hospitalized patients has continued to be inadequate. Quality end-of-life care is often overlooked, seldom taught and rarely measured within Internal Medicine Residency Programmes. We studied the effects of a palliative care order set and educational e-mail on resident comfort. Survey of residents showed that only 54% were comfortable across nine aspects of palliative care. Three months after release, 88% of residents were using the order set and 63% believed it increased their comfort with palliative care. Resident comfort managing palliative symptoms increased an average 10% (P = 0.02). First-year residents exposed to this order set increased in comfort from 40% to 65% (P < 0.0001), which significantly surpassed the 48% of second-year residents who reported being comfortable (P = 0.002). Introducing a palliative care order set improves resident comfort with symptom management in dying patients.

Estimation of the transmission dynamics of Theileria equi and Babesia caballi in horses.

For the evaluation of the epidemiology of Theileria equi and Babesia caballi in a herd of 510 horses in SW Mongolia, several mathematical models of the transmission dynamics were constructed. Because the field data contain information on the presence of the parasite (determined by PCR) and the presence of antibodies (determined by IFAT), the models cater for maternal protection with antibodies, susceptible animals, infected animals and animals which have eliminated the parasite and also allow for age-dependent infection in susceptible animals. Maximum likelihood estimation procedures were used to estimate the model parameters and a Monte Carlo approach was applied to select the best fitting model. Overall, the results are in line with previous experimental work, and add evidence that the epidemiology of T. equi differs from that of Babesia spp. The presented modelling approach provides a useful tool for the investigation of some vector-borne diseases and the applied model selection procedure avoids asymptotical assumptions that may not be adequate for the analysis of epidemiological field data.

Intracranial pressure in patients with sepsis.

INTRODUCTION: In sepsis the brain is frequently affected although there is no infection of the CNS (septic encephalopathy). One possible cause of septic encephalopathy is failure of the blood-brain barrier. Brain edema has been documented in animal models of sepsis. Aggressive fluid resuscitation in the early course of sepsis improves survival and is standard practice. We hypothesized that aggressive fluid administration will increase intracranial pressure (ICP) and may cause critical reductions in cerebral perfusion pressure (CPP). MATERIALS AND METHODS: Patients with sepsis were investigated daily on up to four consecutive days in the intensive care unit. Mean arterial blood pressure (MAP) and blood flow velocity in the middle cerebral artery were monitored for one hour each day. ICP was calculated non-invasively from MAP and flow velocity data. S-100beta was determined daily. FINDINGS: Fifty-two measurements were performed in 16 patients. ICP could be determined in 45 measurements in 15 patients. Seven patients had an ICP > 15 mmHg and 11 patients had a CPP < 60 mmHg on at least 1 day. We found no significant correlation between ICP and fluid administration, but low CPP was significantly correlated with elevated S-100beta (r = -0.47, p = 0.001). CONCLUSIONS: Further research is needed to determine the role of ICP/CPP monitoring in patients with sepsis.

[Subtherapeutic blood levels of phenytoin due to a medication error]. / Subtherapeutische Phenytoinspiegel infolge eines Medikationsfehlers.

We report a female patient who was admitted to the emergency ward with suspected cerebral ischemia and in whom transvenous clot lysis was performed. Following lysis the patient developed recurrent complex partial seizures and treatment with intravenous phenytoin was started. Initial phenytoin serum levels were within the therapeutic range. During the course of the in-hospital treatment a sudden fall of phenytoin serum levels was detected and could not be explained by pharmacokinetic changes. Only when the drug application process was further analysed the reason for the fall in serum levels became obvious. Phenytoin sodium injections had not been administered directly into the veins but had been diluted in 0.9% saline infusions. As a result phenytoin sodium injections precipitated and were retained by the particle filter, thus leading to subtherapeutic phenytoin serum levels.

Age-dependent dynamics of Theileria equi and Babesia caballi infections in southwest Mongolia based on IFAT and/or PCR prevalence data from domestic horses and ticks.

Epidemiological factors of tick-borne equine piroplasmoses, caused by Theileria equi and Babesia caballi, were investigated using logistic regression (GLM) and general additive models (GAM) based on the prevalences determined in 510 domestic horses and in ticks in S.W. Mongolia by indirect immunofluorescence antibody test (IFAT) and/or multiplex PCR. Prevalences of T. equi and B. caballi in horses were 66.5% (95% CI: 62.1-70.7) and 19.1% (15.6-22.9), respectively by PCR and 78.8% (74.9-82.3) and 65.7% (61.3-69.9) by IFAT. Of 166 ticks analysed from PCR- and IFAT-negative horses 1 was PCR positive for B. caballi and none for T. equi. GAM demonstrated non-linear increasing proportions of T. equi-PCR and -IFAT positive horses with age suggesting persistent infection. In contrast, the B. caballi-PCR prevalence decreased with age despite a concurrent increase in the proportion of IFAT-positive animals suggesting parasite elimination. The tick (Dermacentor nuttalli) burden of the horses increased with age and decreased with advancing season. Geldings were more likely to be infected with, and seroconvert to, T. equi. Neither herd affiliation, date of sample collection nor abundance of tick infestation had a significant influence on parasite prevalence.

Life-threatening orolingual angioedema during thrombolysis in acute ischemic stroke.

BACKGROUND: Orolingual angioedema can occur during thrombolysis with alteplase in stroke patients. However, data about its frequency, severity and the significance of concurrent use of angiotensin-converting-enzyme inhibitors (ACEi) are sparse. OBJECTIVE: (1), to alert to the potentially life-threatening complication of orolingual angioedema. (2), to present CT-scans of the tongue which exclude lingual hematoma. (3), to estimate the frequency of orolingual angioedema. (4), to evaluate the risk associated with the concurrent use of ACEi. METHODS: Single center, databank-based observational study on 120 consecutive patients with i. v. alteplase for acute stroke. Meta-analysis of all stroke studies on alteplase-associated angioedema, which provided detailed information about the use of ACE-inhibitors. Across studies, the Peto odds ratio of orolingual angioedema for "concurrent use of ACEi" was calculated. RESULTS: Orolingual angioedema occurred in 2 of 120 patients (1.7%, 95% CI 0.2-5.9 %). Angioedema was mild in one, but rapidly progressive in another patient. Impending asphyxia prompted immediate intubation. CT showed orolingual swelling but no bleeding. One of 19 (5%) patients taking ACEi had orolingual angioedema, compared to 1 of 101 (1%) patients without ACEi. Medline search identified one further study about the occurrence of alteplase-associated angioedema in stroke patients stratified to the use of ACEi. Peto odds ratio of 37 (95 % CI 8-171) indicated an increased risk of alteplasetriggered angioedema for patients with ACEi (p <0.001). CONCLUSION: Orolingual angioedema is a potentially life-threatening complication of alteplase treatment in stroke patients, especially in those with ACEi. Orolingual hematoma as differential diagnosis can be excluded by CT-scan.