[From stroke to reperfusion : How can we be faster?] / Vom Schlaganfall zur Reperfusion : Wie geht es schneller?

BACKGROUND: During the last two decades major efforts in clinical research have led to the establishment of intravenous thrombolysis as the first line acute therapy for ischemic stroke. More recently, data from successful phase III trials have provided proof of the efficiency of mechanical recanalization in acute stroke. The fact that the efficiency of the available therapies can be increased through faster delivery is well documented; however, many institutions dealing with the emergency care of stroke patients lack organizational or infrastructural arrangements to optimize time efficiency in the diagnostic and therapeutic workup. CONCLUSION: Many of these arrangements have been well evaluated, can be implemented at reasonable costs and have been proven to increase the beneficial effects of thrombolytic therapy.

Effect of thrombus size on recanalization by bridging intravenous thrombolysis.

BACKGROUND AND PURPOSE: Thrombus length has been reported as an important predictor of successful recanalization by intravenous thrombolysis but its influence on bridging thrombolysis has not been investigated yet. The effect of thrombus length on recanalization rates evaluated by catheter angiography early after intravenous bridging thrombolysis was analyzed. METHODS: Ninety-six consecutive patients with acute cerebral artery occlusion were included. Occlusion site and thrombus length on initial computed tomography angiography or magnetic resonance angiography were related to recanalization after intravenous bridging thrombolysis on the initial series of catheter angiography. RESULTS: Eleven of 96 patients (11.5%) showed successful recanalization (TICI 2a, 2b or 3) after intravenous bridging thrombolysis. Mean thrombus length in these patients was 10.8 mm as opposed to 15.6 mm in patients without successful recanalization. No thrombus longer than 16 mm showed complete recanalization. Binary logistic regression demonstrated a significant influence of thrombus length on probability of recanalization (odds ratio 0.78, 95% confidence interval 0.65-0.95; P = 0.014). CONCLUSIONS: Thrombus length is a significant predictor of recanalization rates after bridging thrombolysis. Overall recanalization rate within the time frame until interventional treatment is started was 11.5% after bridging thrombolysis.

Emergency cervical internal carotid artery stenting in combination with intracranial thrombectomy in acute stroke.

BACKGROUND AND PURPOSE: In past years, thrombectomy has become a widely used procedure in interventional neuroradiology for the treatment of acute intracranial occlusions. However, in 10-20% of patients, there are additional occlusions or stenotic lesions of the ipsilateral cervical internal carotid artery. The purpose of this study was to evaluate the feasibility of emergency carotid artery stent placement in combination with intracranial thrombectomy and the clinical outcome of the treated patients. MATERIALS AND METHODS: We analyzed clinical and angiographic data of patients who underwent emergency cervical ICA stent placement and intracranial thrombectomy with stent-retriever devices in our institution between November 2009 and July 2012. Recanalization was assessed according to the Thrombolysis in Cerebral-Infarction score. Clinical outcome was evaluated at discharge (NIHSS) and after 3 months (mRS). RESULTS: Overall, 24 patients were treated. The mean age was 67.2 years; mean occlusion time, 230.2 minutes. On admission, the median NIHSS score was 18. In all patients, the Thrombolysis in Cerebral Infarction score was zero before the procedure. Stent implantation was feasible in all cases. In 15 patients (62.5%), a Thrombolysis in Cerebral Infarction score ≥ 2b could be achieved. Six patients (25%) improved ≥10 NIHSS points between admission and discharge. After 90 days, the median mRS score was 3.0. Seven patients (29.2%) had a good clinical outcome (mRS 0-2), and 4 patients (16.6%) died, 1 due to fatal intracranial hemorrhage. Overall, symptomatic intracranial hemorrhage occurred in 4 patients (16.6%). CONCLUSIONS: Emergency ICA stent implantation was technically feasible in all patients, and the intracranial recanalization Thrombolysis in Cerebral Infarction score of ≥2b was reached in a high number of patients. Clinical outcome and mortality seem to be acceptable for a cohort with severe stroke. However, a high rate of symptomatic intracranial hemorrhage occurred in our study.

Mechanical thrombectomy with stent retrievers in acute basilar artery occlusion.

BACKGROUND AND PURPOSE: Basilar artery occlusion remains one of the most devastating subtypes of ischemic stroke. The prognosis is poor if early recanalization is not achieved. The purpose of this study was to evaluate the safety and technical feasibility of self-expanding retrievable stents in the endovascular treatment of acute basilar artery occlusion. MATERIALS AND METHODS: Twenty-four patients with acute basilar artery occlusion were treated with Solitaire FR or Revive SE devices between December 2009 and May 2012. Additional treatment included intravenous and/or intra-arterial thrombolysis (21/24) and percutaneous transluminal angioplasty/permanent stent placement (7/24). Recanalization was assessed by means of the TICI score. Clinical outcome was determined at discharge (NIHSS), and at 3 months (mRS). RESULTS: Median NIHSS score on admission was 24; median duration of symptoms was 254 minutes. Successful recanalization (TICI 2b +3) by thrombectomy only was achieved in 18 patients (75%). Intracranial stent deployment after thrombectomy caused by underlying atherosclerotic stenosis was performed in 7 patients. If these patients with intracranial stent placement are included, successful recanalization was achieved in 21 of 24 patients (87.5%). NIHSS improvement ≥10 points was reached in 54% of patients (n = 13/24). Mortality during the first 3 months was 29% (7/24). After 3 months, 8 patients (33%) had a favorable clinical outcome (mRS 0-2). CONCLUSIONS: In our series, application of self-expanding retrievable stents in acute basilar artery occlusion resulted in a high recanalization rate without procedural complications and good clinical outcome in one-third of patients.

Prolonged low-dose thrombolysis in posterior circulation stroke.

BACKGROUND: We aimed to investigate the feasibility, preliminary safety, and efficacy of prolonged low-dose intravenous thrombolysis in posterior circulation stroke patients with a thrombus lodged in the basilar artery who were ineligible for standard rtPA administration. METHODS: We retrospectively analyzed consecutively collected patients in our stroke database who suffered from a basilar artery thrombosis and were treated with prolonged (>1 h), intravenous, low-dose (≤20 mg) rtPA between 01/2005 and 11/2012. RESULTS: Patients included in this study (n = 14) were 68.5 years (IQR 55.5; 72.75) of age and presented with a median NIHSS of 2 (1; 5.25). Median time from symptom onset to treatment was 63 h (33; 141). A median dose of 5.21 µg/kg h (4.46; 6.25) rtPA was administered over 24 h (min 10; max 48). No patient experienced symptomatic intracerebral hemorrhage, one patient developed a spinal epidural hematoma, and two elderly patients were switched to comfort care and died. In eight patients (57%) a decrease in thrombus size or no thrombus at all was detected on control imaging. Nine patients (64%) had a favorable outcome (mRS 0-2) at day 90. CONCLUSIONS: Prolonged low-dose thrombolysis with rtPA may be considered as individual treatment option in selected high-risk patients with basilar artery thrombosis. Presented data may lay the groundwork to further investigate safety and efficacy in a prospective trial.

Hepatic gene expression involved in glucose and lipid metabolism in transition cows: effects of fat mobilization during early lactation in relation to milk performance and metabolic changes.

Insufficient feed intake during early lactation results in elevated body fat mobilization to meet energy demands for milk production. Hepatic energy metabolism is involved by increasing endogenous glucose production and hepatic glucose output for milk synthesis and by adaptation of postcalving fuel oxidation. Given that cows differ in their degree of fat mobilization around parturition, indicated by variable total liver fat concentration (LFC), the study investigated the influence of peripartum fat mobilization on hepatic gene expression involved in gluconeogenesis, fatty acid oxidation, ketogenesis, and cholesterol synthesis, as well as transcriptional factors referring to energy metabolism. German Holstein cows were grouped according to mean total LFC on d 1, 14, and 28 after parturition as low [<200mg of total fat/g of dry matter (DM); n=10], medium (200-300 mg of total fat/g of DM; n=10), and high (>300 mg of total fat/g of DM; n=7), indicating fat mobilization during early lactation. Cows were fed total mixed rations ad libitum and held under equal conditions. Liver biopsies were taken at d 56 and 15 before and d 1, 14, 28, and 49 after parturition to measure mRNA abundances of pyruvate carboxylase (PC); phosphoenolpyruvate carboxykinase; glucose-6-phosphatase; propionyl-coenzyme A (CoA) carboxylase α; carnitine palmitoyl-transferase 1A (CPT1A); acyl-CoA synthetase, long chain 1 (ASCL1); acyl-CoA dehydrogenase, very long chain; 3-hydroxy-3-methylglutaryl-CoA synthase 1 and 2; sterol regulatory element-binding factor 1; and peroxisome proliferator-activated factor α. Total LFC postpartum differed greatly among cows, and the mRNA abundance of most enzymes and transcription factors changed with time during the experimental period. Abundance of PC mRNA increased at parturition to a greater extent in high- and medium-LFC groups than in the low-LFC group. Significant LFC × time interactions for ACSL1 and CPT1A during the experimental period indicated variable gene expression depending on LFC after parturition. Correlations between hepatic gene expression and performance data and plasma concentrations of metabolites and hormones showed time-specific relations during the transition period. Elevated body fat mobilization during early lactation affected gene expression involved in gluconeogenesis to a greater extent than gene expression involved in lipid metabolism, indicating the dependence of hepatic glucose metabolism on hepatic lipid status and fat mobilization during early lactation.

Variation in fat mobilization during early lactation differently affects feed intake, body condition, and lipid and glucose metabolism in high-yielding dairy cows.

Fat mobilization to meet energy requirements during early lactation is inevitable because of insufficient feed intake, but differs greatly among high-yielding dairy cows. Therefore, we studied milk production, feed intake, and body condition as well as metabolic and endocrine changes in high-yielding dairy cows to identify variable strategies in metabolic and endocrine adaptation to overcome postpartum metabolic load attributable to milk production. Cows used in this study varied in fat mobilization around calving, as classified by mean total liver fat concentrations (LFC) postpartum. German Holstein cows (n=27) were studied from dry off until d 63 postpartum in their third lactation. All cows were fed the same total mixed rations ad libitum during the dry period and lactation. Plasma concentrations of metabolites and hormones were measured in blood samples taken at d 56, 28, 15, and 5 before expected calving and at d 1 and once weekly up to d 63 postpartum. Liver biopsies were taken on d 56 and 15 before calving, and on d 1, 14, 28, and 49 postpartum to measure LFC and glycogen concentrations. Cows were grouped accordingly to mean total LFC on d 1, 14, and 28 in high, medium, and low fat-mobilizing cows. Mean LFC (±SEM) differed among groups and were 351±14, 250±10, and 159±9 mg/g of dry matter for high, medium, and low fat-mobilizing cows, respectively, whereas hepatic glycogen concentrations postpartum were the highest in low fat-mobilizing cows. Cows in the low group showed the highest dry matter intake and the least negative energy balance postpartum, but energy-corrected milk yield was similar among groups. The decrease in body weight postpartum was greatest in high fat-mobilizing cows, but the decrease in backfat thickness was greatest in medium fat-mobilizing cows. Plasma concentrations of nonesterified fatty acids and ß-hydroxybutyrate were highest around calving in high fat-mobilizing cows. Plasma triglycerides were highest in the medium group and plasma cholesterol concentrations were lowest in the high group at calving. During early lactation, the decrease in plasma glucose concentrations was greatest in the high group, and plasma insulin concentrations postpartum were highest in the low group. The revised quantitative insulin sensitivity check index values decreased during the transition period and postpartum, and were highest in the medium group. Plasma cortisol concentrations during the transition period and postpartum period and plasma leptin concentrations were highest in the medium group. In conclusion, cows adapted differently to the metabolic load and used variable strategies for homeorhetic regulation of milk production. Differences in fat mobilization were part of these strategies and contributed to the individual adaptation of energy metabolism to milk production.

Recanalization with stent-retriever devices in patients with wake-up stroke.

BACKGROUND AND PURPOSE: Stent-retriever devices play an increasing role in the interventional treatment of acute stroke patients, because fast recanalization can be achieved. The purpose of this study was to evaluate the feasibility of stent-retriever recanalization in patients with wake-up stroke in the anterior circulation. MATERIALS AND METHODS: We retrospectively analyzed clinical and angiographic data of 19 consecutive patients with wake-up stroke who were treated with stent-retriever devices between 2009 and October 2011. Recanalization was assessed by using the Thrombolysis in Cerebral Infarction score. Clinical outcome was evaluated at discharge and after 90 days by using the modified Rankin Scale. RESULTS: Median NIHSS score at admission was 17 (IQR, 15-20). Before the procedure, the TICI score was 0 in 18 patients and 1 in 1 patient. Recanalization with stent-retriever devices was successful (TICI ≥ 2) in 94.7%. Mean time to flow restoration was 36.7 minutes and to complete recanalization 83.7 minutes. Symptomatic intracranial hemorrhage occurred in 4 patients (21.1%). Eight patients had an NIHSS improvement of ≥4 points between admission and discharge. After 90 days, 2 (10.5%) of our patients presented with mRS 0-2; seven (36.8%) died. CONCLUSIONS: Despite successful and rapid recanalization with stent-retriever devices, good clinical outcome in patients with wake-up stroke is achieved in a minority of patients. Clinical outcome remains poor. Bleeding rates were higher compared with recanalization procedures within 6 hours after stroke onset.

Detection of paroxysmal atrial fibrillation in acute stroke patients.

BACKGROUND: Atrial fibrillation (AF) is a frequent cause of stroke, but detecting paroxysmal AF (pAF) poses a challenge. We investigated whether continuous bedside ECG monitoring in a stroke unit detects pAF more sensitively than 24-hour Holter ECG, and tested whether examining RR interval dynamics on short-term ECG recordings using an automated screening algorithm (ASA) for pAF detection is a useful tool to predict the risk of pAF outside periods of manifest AF. METHODS: Patients >60 years with acute ischemic stroke or transient ischemic attacks (TIA) were prospectively enrolled unless initial ECG revealed AF or they had a history of paroxysmal or persistent AF. ASA was performed on 1- to 2-hour ECG recordings in the emergency room and patients were classified into 5 risk categories for pAF. All patients underwent continuous bedside ECG monitoring for >48 h. Additionally, 24-hour Holter ECG was performed. RESULTS: 136 patients were enrolled (median age: 72 years, male: 58.8%). In 29 (21.3%), pAF was newly diagnosed by continuous bedside ECG monitoring. pAF increased with age (p = 0.031). Median time to first pAF detection on continuous bedside ECG monitoring was 36 h. In 16 patients, pAF was detected by continuous bedside ECG monitoring prior to the performance of 24-hour Holter ECG. Thirteen of the remaining patients were pAF positive on continuous bedside ECG monitoring, but 24-hour Holter detected only 3 patients. Accordingly, the sensitivity of 24-hour Holter was 0.23. Sensitivity of higher-risk categories of ASA compared to continuous bedside ECG monitoring was 0.72, and specificity 0.63. CONCLUSION: Continuous bedside ECG monitoring is more sensitive than 24-hour Holter ECG for pAF detection in acute stroke/TIA patients. Screening patients for pAF outside AF episodes using ASA requires further development.

Preparation and characterization of the conjugated Fusarium mycotoxins zearalenone-4O-beta-D-glucopyranoside, alpha-zearalenol-4O-beta-D-glucopyranoside and beta-zearalenol-4O-beta-D-glucopyranoside by MS/MS and two-dimensional NMR.

Glucosides of several Fusarium mycotoxins occur in naturally infected cereals and may contribute to an increased content to the total mycotoxin load of food and feed. The paper presents the results of a fermentation procedure to produce zearalenone-4O-beta-D-glucopyranoside from zearalenone using an engineered Saccharomyces cerevisiae strain, expressing the Arabidopsis thaliana UDP-glucosyltransferase UGT73C6. About 24 mg of zearalenone-4O-beta-D-glucopyranoside was obtained from 50 mg of zearalenone and further purified. A total of 10 mg of the glucoside were reduced with sodium borohydride, yielding 4.1 mg alpha-zearalenol-4O-beta-D-glucopyranoside and 4.5 mg beta-zearalenol-4O-beta-D-glucopyranoside at purities higher than 99%. To confirm the identities of the three produced glucosides, MS and MS/MS spectra were acquired using negative electrospray ionization. Besides the deprotonated ions at m/z 479 or 481, respectively, in full-scan mode, fragments, adducts, and dimers were recorded and assigned. MS/MS spectra of the glucosylated substances yielded the deprotonated ions of the mycotoxins zearalenone, alpha-zearalenol, beta-zearalenol and their fragments, respectively. Unambiguous structural assignment of the three substances was achieved using two-dimensional NMR methods. This way, the glucose attachment to position C-4, the beta-configuration of the sugar unit and the stereo-chemical assignment of the zearalenol hydroxyl group at C-6' were proven.

Characterization of (13C24) T-2 toxin and its use as an internal standard for the quantification of T-2 toxin in cereals with HPLC-MS/MS.

In this paper, the structure and the identity of fully 13C-substituted T-2 toxin were confirmed using high-resolution mass spectrometry, 1H-NMR, 13C-NMR, tandem mass spectrometry and HPLC-DAD. The purity of this compound was estimated to be at least 98.8% according to UV data. The isotopic distribution of (13C(24)) T-2 toxin indicated a total isotopic enrichment of 98.2 +/- 1.0 atom% 13C, and the application of different MS measurement modes revealed the MS/MS fragmentation pattern of T-2 toxin. Furthermore, a stable isotope dilution mass spectrometry method for the quantification of T-2 toxin was developed using (13C(24)) T-2 toxin as internal standard. The method was evaluated with and without conventional clean-up and validated for maize and oats. Both cereals showed strong matrix enhancement effects, which could be compensated for through the application of the isotope-substituted internal standard.

Production of zearalenone-4-glucoside, a-zearalenol-4-glucoside and ß-zearalenol-4-glucoside.

The work at hand describes the production of the zearalenone (ZON) metabolites zearalenone-4-glucoside (ZON-4G), a-zearalenol-4-glucoside (oc-ZOL-4G) and ß-zearalenol-4-glucoside (ß-ZOL-4G). In a first step a genetically modified yeast strain, expressing theArabidopsis thaliana UDP-glu-cosyltransferase UGT73C6, was treated with ZON to produce ZON-4G. The substance was purified by solid phase extraction and subsequent reversed phase preparative HPLC prior to the reduction with sodium borohydride to yield 0C-ZOL-4G and ß-ZOL-4G. The identity and purity of the substances were confirmed by(13)C-and(1)H-NMR as well as by HPLC-UV. In total, 50 mg of ZON were used to produce 5 mg of a-ZOL-4G with a purity of 98%, 6 mg of ß-ZOL-4G with a purity of 99% and 5 mg of ZON-4G with a purity of 99%.

Determination of microbial contamination of plastic cups for dairy products and utilization of electron beam treatment for sterilization.

Packaging materials are often considered a critical control point in HACCP systems of food companies. Methods for the determination of the microbial contamination rate of plastic cups, especially for dairy products, must reliably detect single moulds, yeasts or coliforms. In this study, a comparison of a specially adapted coating method, impedance method, direct inoculation and membrane filter technique was carried out to determine contamination with yeasts, moulds, coliforms and total bacterial counts using the appropriate agar in each case. The coating method is recommended for determining yeasts, moulds and coliforms as it allows the localization of the microorganisms as well as the determination of single microorganisms. For total bacterial count, a direct inoculation technique is proposed. The employing of simple measures in the production and during transport of packaging materials, such as dust-prevention or tight sealing in polyethylene bags, heavily reduces microbial contamination rates of packaging material. To reduce contamination rates further, electron beam irradiation was applied: plastic cups sealed in polyethylene bags were treated with 4-5 kGy, a dose that already leads to sterile polystyrene and polypropylene cups without influencing mechanical characteristics of the packaging material.

Allergologically relevant rubber accelerators in single-use medical gloves.

To prevent contact with specific rubber accelerators, sensitized patients have to know in which glove brands these accelerators are present. Additionally, quantitative measurements of the bioavailable amounts of accelerators are needed to assist consumers in selecting gloves with the lowest possible amount of residual rubber accelerators. The aim of the study was to develop an analytical method by which residuals of rubber accelerators in single-use medical gloves could be determined qualitatively and quantitatively. 19 different glove brands were analysed for content of accelerators, and the results were compared to manufacturers' ingredient claims of the identical gloves. ZDEC, ZDBC, ZMBT and ZPC were the most frequently detected chemicals. In 9 of 15 gloves discrepancies were found, usually minor, between content of accelerators declared by manufacturers to be present and accelerators detected by analysis. Both phosphate buffer and acetone were tested as extraction media. No accelerators were detectable with the described chemical analysis in phosphate extracts, whereas acetone was demonstrated to be a technically suitable medium for extraction. However, more kinetic studies of the extraction procedure and studies of skin penetration are needed to document that the extraction procedure simulates the clinical situation.