Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage.

IMPORTANCE: Although use of oral anticoagulants (OACs) is increasing, there is a substantial lack of data on how to treat OAC-associated intracerebral hemorrhage (ICH). OBJECTIVE: To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAC resumption. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study at 19 German tertiary care centers (2006-2012) including 1176 individuals for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAC resumption. EXPOSURES: Reversal of anticoagulation during acute phase, systolic BP at 4 hours, and reinitiation of OAC for long-term treatment. MAIN OUTCOMES AND MEASURES: Frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP. Incidence analysis of ischemic and hemorrhagic events with or without OAC resumption. Factors associated with favorable (modified Rankin Scale score, 0-3) vs unfavorable functional outcome. RESULTS: Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within 4 hours after admission (43/217 [19.8%]) vs INR of ≥1.3 (264/636 [41.5%]; P < .001) and systolic BP <160 mm Hg at 4 hours (167/504 [33.1%]) vs ≥160 mm Hg (98/187 [52.4%]; P < .001). The combination of INR reversal <1.3 within 4 hours and systolic BP of <160 mm Hg at 4 hours was associated with lower rates of hematoma enlargement (35/193 [18.1%] vs 220/498 [44.2%] not achieving these values; OR, 0.28; 95% CI, 0.19-0.42; P < .001) and lower rates of in-hospital mortality (26/193 [13.5%] vs 103/498 [20.7%]; OR, 0.60; 95% CI, 0.37-0.95; P = .03). OAC was resumed in 172 of 719 survivors (23.9%). OAC resumption showed fewer ischemic complications (OAC: 9/172 [5.2%] vs no OAC: 82/547 [15.0%]; P < .001) and not significantly different hemorrhagic complications (OAC: 14/172 [8.1%] vs no OAC: 36/547 [6.6%]; P = .48). Propensity-matched survival analysis in patients with atrial fibrillation who restarted OAC showed a decreased HR of 0.258 (95% CI, 0.125-0.534; P < .001) for long-term mortality. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%). CONCLUSIONS AND RELEVANCE: Among patients with OAC-associated ICH, reversal of INR <1.3 within 4 hours and systolic BP <160 mm Hg at 4 hours were associated with lower rates of hematoma enlargement, and resumption of OAC therapy was associated with lower risk of ischemic events. These findings require replication and assessment in prospective studies. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01829581.

Improved detection of silent atrial fibrillation using 72-hour Holter ECG in patients with ischemic stroke: a prospective multicenter cohort study.

BACKGROUND AND PURPOSE: Adequate diagnosis of atrial fibrillation (AF), including paroxysmal AF, is an important part of stroke workup. Prolonged ECG monitoring may improve the detection of paroxysmal, previously undiagnosed AF (unknown AF). Therefore, we evaluated systematic 72-hour Holter ECG monitoring to detect unknown AF for the workup of patients with stroke. METHODS: Unselected survivors of a stroke or transient ischemic attack (TIA) without known AF were enrolled in a prospective, multicenter cohort study of 72-hour Holter ECG monitoring in 9 German secondary and tertiary stroke centers between May 2010 and January 2011. In addition to standardized workup of stroke pathogenesis according to the German Stroke Unit protocol, all patients underwent 72-hour Holter ECG monitoring directly after admission. All ECGs were centrally analyzed by 2 independent observers. We determined the proportion of unknown AF and compared the detection rates of 72- and 24-hour monitoring. RESULTS: A total of 1135 patients were enrolled (mean age, 67 years [SD, 13.1 years], 45% women, 29% TIA). Unknown AF was detected in 49 out of 1135 patients (4.3%, [95% confidence interval, 3.4-5.2%]) by 72-hour ECG monitoring. Unknown AF was diagnosed in 29 patients (2.6%) within the first 24 hours of ECG monitoring, and in 20 more patients only by 72 hours of ECG monitoring. The number needed to screen by 72-hour ECG was 55 patients (95% confidence interval [35-123]) for each additional AF diagnosis. Patients with unknown AF were significantly older and had more often a history of previous stroke. Patients with unknown AF were equally distributed within categories of pathogenesis according to Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. CONCLUSIONS: In unselected survivors of stroke or TIA, 72-hour ECG monitoring is feasible and improves the detection rate of silent paroxysmal AF.

Towards a comprehensive hydride donor ability scale.

Rates of hydride transfer from several hydride donors to benzhydrylium ions have been measured at 20 °C and used for the determination of empirical nucleophilicity parameters N and s(N) according to the linear free energy relationship log k(20 °C) = s(N)(N+E). Comparison of the rate constants of hydride abstraction by tritylium ions with those calculated from the reactivity parameters s(N), N, and E showed fair agreement. Therefore, it was possible to convert the large number of literature data on hydride abstraction by tritylium ions into N and s(N) parameters for the corresponding hydride donors, and construct a reactivity scale for hydride donors covering more than 20 orders of magnitude.

Stabilities of trityl-protected substrates: the wide mechanistic spectrum of trityl ester hydrolyses.

Ionization rates of para-substituted triphenylmethyl (trityl) acetates, benzoates, and para-nitrobenzoates have been determined in aqueous acetonitrile and aqueous acetone at 25 degrees C. Conventional and stopped-flow techniques have been used to evaluate rate constants ranging from 1.38 x 10(-5) to 2.15 x 10(2) s(-1) by conductimetry and photospectrometry methods. The varying stabilities of the differently substituted tritylium ions account for a gradual change of reaction mechanism. Poorly stabilized carbocations are generated slowly by the ionization of their covalent precursors and trapped fast by water. Better stabilized carbocations are generated more rapidly and accumulate, so that ionization and trapping by water can be observed as separate steps in a single experiment. Finally, highly stabilized tritylium ions do not react with water, and only the rates of their formation could be measured. The ionization rate constants correlate linearly with Winstein's ionizing powers Y; the low slopes (0.17

Electrophilicity versus electrofugality of tritylium ions in aqueous acetonitrile.

First-order rate constants k(w) for the reactions of a series of donor-substituted triphenylmethylium (tritylium) ions with water in aqueous acetonitrile have been determined photometrically at 20 degrees C using stopped-flow and laser-flash techniques. The rate constants follow the linear free energy relationship log k(20 degrees C)=s(N+E). The reactivities k(w) of the methyl- and methoxy-substituted tritylium ions towards water correlate linearly with the corresponding pK(R(+) ) values with a Leffler-Hammond coefficient alpha=deltaDeltaG(++)/deltaDeltaG(0) of 0.62. The amino-substituted compounds react more slowly than expected from the correlation of the less stabilized systems. Quantum chemical calculations of tritylium ions and the corresponding triarylmethanols and 1,1,1-triarylethanes have been performed at the MP2(FC)/6-31+G(2d,p)//B3LYP/6-31G(d,p) level. The calculated gas-phase hydroxide and methyl anion affinities of the tritylium ions correlate linearly with a slope of unity, indicating that the relative anion affinities do not depend on the nature of the anion. The pK(R(+)) values of the methyl- and methoxy-substituted tritylium ions correlate linearly with the calculated gas-phase hydroxide affinities, and the slope of this correlation shows that the differences in carbocation stabilities in the gas phase are attenuated to 66% in solution. Mono- and bis(dimethylamino)-substituted derivatives deviate from this correlation; their pK(R(+)) values are higher than expected from their calculated gas-phase hydroxide affinities, which is explained by the extraordinary solvation of unsymmetrically amino-substituted tritylium ions. Complete free-energy profiles for the solvolyses of substituted trityl benzoates in 90:10 (v/v) acetonitrile/water have been constructed.

Carbocationic n-endo-trig cyclizations.

Unsaturated benzyl cations (4-MeOC(6)H(4))CH(+)-(CH(2))(n)-CH=CH(2) (1) have been generated laser-flash photolytically in acetonitrile in the presence of enol ethers or 2-methylfuran. The reactions of the cations 1 (n=2 and 4) with these pi-nucleophiles follow second-order rate laws with rate constants comparable to those of the analogous saturated species (4-MeOC(6)H(4))CH(+)-(CH(2))(3)CH(3). Product studies show the absence of cyclization products. In contrast, the carbocation (4-MeOC(6)H(4))CH(+)-(CH(2))(3)-CH=CH(2) (1 d) undergoes a highly reversible 6-endo-trig cyclization which is approximately 10(7) times faster than the corresponding intermolecular reaction of (4-MeOC(6)H(4))CH(+)-(CH(2))(3)CH(3) with hex-1-ene. This cyclization yields a highly electrophilic, partially bridged carbocation, which accounts for the finding that 1 d is consumed eight times faster in trifluoroethanol solution than all other carbocations of this series. Quantum-chemical calculations (B3LYP/6-311G(d,p) and MP2/6-31+G(2d,p)) have been performed to elucidate the structures of the involved carbocations. Consequences of these findings on the role of pi-participation in solvolysis reactions are discussed.

Organocatalytic activity of cinchona alkaloids: which nitrogen is more nucleophilic?

The cinchona alkaloids 1a-d react selectively at the quinuclidine ring with benzyl bromide and at the quinoline ring with benzhydrylium ions (diarylcarbenium ions). The kinetics of these reactions have been determined photometrically or conductimetrically and are compared with analogous reactions of quinuclidine and quinoline derivatives. Quantum chemical calculations [MP2/6-31+G(2d,p)//B3LYP/6-31G(d)] show that the products obtained by attack at the quinuclidine ring (N(sp3)) of quinine are thermodynamically more stable when small alkylating agents (primary alkyl) are used, while the products arising from attack at the quinoline ring (N(sp2)) are more stable for bulkier electrophiles (Ar(2)CH). In some cases, rate and equilibrium constants for their reactions with benzhydrylium ions could be determined. These data gave access to the Marcus intrinsic barriers, which are approximately 20 kJ mol(-1) lower for attack at the N(sp3)-center than at the N(sp2)-center.

Fischer-344 rats are unsuitable for the MCAO filament model due to their cerebrovascular anatomy.

Middle cerebral artery occlusion (MCAO) in Fischer-344 rats results in a small variance of infarct size. However, complications are frequent especially in aged Fisher-344 rats undergoing endovascular suture occlusion of the middle cerebral artery. Analyzing our experiences with 165 Wistar, 13 Sprague-Dawley and 10 F-344 rats, we compared the incidence of impossible thread advancement and subarachnoid hemorrhage, respectively. Magnetic resonance angiography (MRA) was applied to study the course of the internal carotid artery (ICA) in Fischer and Wistar rats. Finally, we performed a structured review of the literature from 1991 to 2005 evaluating reports on Fischer rats subjected to intraluminal filament MCAO. Complications like fruitless filament advancement or subarachnoid hemorrhage were found to be significantly more frequent in Fischer rats than in other strains. MRA revealed significantly more pronounced kinking of the ICA in F-344 than in Wistar rats. In seven publications available on filament MCAO in F-344 rats, complication rates of 50-100% were reported, corroborating our data. Surgical difficulties accompanied by high complication rates due to their cerebrovascular anatomy make Fischer rats unsuitable for filament MCAO. If the use of Fischer rats for studies on focal cerebral ischemia is indicated, other ischemia models than intraluminal suture occlusion should be chosen.

Long-term outcome after hemicraniectomy for space occupying right hemispheric MCA infarction.

OBJECTIVE: To examine the long-term prognosis in patients with 'malignant' supratentorial ischemia of the right hemisphere treated with hemicraniectomy, especially in respect to depression, with a focus on age as a possible predictor of outcome. METHODS: We performed a prospective, long-term, follow-up examination in 23 survivors of 32 patients (mortality 28.1%) treated with hemicraniectomy for malignant middle cerebral artery (MCA) infarction of the right hemisphere, who were identified in our data bank since 1993. Long-term was defined as at least 20 months after craniectomy. Outcome data consisted of the items functionality, depression and quality of life. Tests applied included the Barthel Index (BI), the modified Rankin Scale (mRS), Beck Depression Inventory (BDI) and stroke-specific quality of life (QoL) scale. RESULTS: Of the 23 patients 15 (65.2%) had a BI>or=60, 11 (47.8%) a mRS<4 and 9 (39.1%) a SS-QOL>or=60%, each representing a favourable outcome. In retrospect, 14 (60.9%) patients approved the surgery. Depression, i.e. a BDI>9, was diagnosed in 13 (56.5%) patients and 5 (38.5%) of them were treated with antidepressants. In a multiple linear regression analysis age at craniectomy was a predictor of a low BI (beta=-0.863; p=0.031), but not of the other outcome parameters. CONCLUSIONS: Depression is a common and rarely treated long-term complication after 'malignant' right hemispheric ischemia. While high age is a strong predictor of poor functional outcome, it has no impact on depression and retrospective approval of craniectomy.

Telemedicine for safe and extended use of thrombolysis in stroke: the Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria.

BACKGROUND AND PURPOSE: Systemic thrombolysis represents the only proven therapy for acute ischemic stroke, but safe treatment is reported only in established stroke units. One major goal of the ongoing Telemedic Pilot Project for Integrative Stroke Care (TEMPiS) in Bavaria is to extend the use of tissue plasminogen activator (tPA) treatment in nonurban areas through telemedic support. METHODS: The stroke centers in Munich-Harlaching and in Regensburg established a telestroke network to provide consultations for 12 local hospitals in eastern Bavaria. The telemedic system consists of a digital network that includes a 2-way video conference system and CT/MRI image transfer with a high-speed data transmission up to 2 Mb/s. Each network hospital established specialized stroke wards in which qualified teams treat acute stroke patients. Physicians in these hospitals are able to contact the stroke centers 24 hours per day. RESULTS: A total of 106 systemic thrombolyses were indicated via teleconsultations between February 1, 2003, and April 7, 2004. During the first 12 months, the rate of thrombolyses was 2.1% of all stroke patients. Mean age was 68 years, and median National Institutes of Health Stroke Scale score was 13. Mean delay between onset and hospital admission was 65 minutes, and door-to-needle time was on average 76 minutes, which included 15 minutes for the teleconsultation. Symptomatic hemorrhage occurred in 8.5% of patients, and in-hospital mortality was 10.4%. CONCLUSIONS: The present data suggest that systemic thrombolysis indicated via stroke experts in the setting of teleconsultation exhibits similar complication rates to those reported in the National Institute of Neurological Disorders and Stroke trial. Therefore, tPA treatment is also safe in this context and can be extended to nonurban areas.

Predictors of survival after severe dysphagic stroke.

BACKGROUND AND PURPOSE: Dysphagia is estimated to occur in up to 50% of the stroke neurorehabilitation population. Those patients with severe neurogenic oropharyngeal dysphagia (NOD) may receive feeding gastrostomy tubes (FGT) if noninvasive therapies prove ineffective in eliminating aspiration or sustaining adequate nutritional intake. Our aim was to quantify the recovery of swallowing function, and to identify variables predictive of survival after dysphagic stroke requiring FGT placement. METHODS: We identified consecutive stroke patients with severe dysphagic stroke requiring FGT placement admitted to a rehabilitation hospital between May 1998 and October 2001. The medical records were reviewed, and demographic, clinical, videofluoroscopic (VSS) and neuroimaging information were abstracted. A follow-up telephone interview was performed to determine whether the FGT was still in use, had been removed,or if the patient had died. State death certificate records were reviewed to ascertain date of death for subjects who had expired by the time of follow-up. Univariate and multivariate analyses were performed. RESULTS: 11.6 % (77/664) of stroke patients admitted during the study period had severe dysphagic stroke with FGT insertion. Follow-up was available for 66 (85.7 %) of these individuals at a mean of two years after acute stroke. On follow-up 64% (42/66) of the patients were alive and 45 % had had the FGT removed and resumed oral diets. On univariate analysis patients who were alive at the time of follow-up had received FGT feeding for a shorter period of time (p < 0.0003), showed no signs of aspiration on the Clinical Assessment of Feeding & Swallowing (CAFS,p < 0.020) and on the Videofluoroscopic Swallowing Study (VSS, 0.001), had a better discharge FIM-Score (Functional Independence Measure) for eating (p < 0.0002) and cognitive function (p < 0.002) as well as better discharge FCM-Score (Functional Communication Measure) for swallowing (p < 0.0001). On multivariate analysis we developed a model consisting of FGT removal at discharge from the rehabilitation hospital (p < 0.011) and non-aspiration during VSS (p < 0.040) that was significantly associated with longer survival time during follow-up. CONCLUSIONS: Severe dysphagia requiring FGT is common in patients with stroke referred for neurorehabilitation. Patients who had a FGT in place at the time of discharge from the stroke rehabilitation unit or aspirated during VSS were substantially more likely to have died by the time of follow-up compared to those who had had the FGT removed and had no signs of aspiration on VSS. However functional outcome measurements (FIM, FCM) including the cognitive function (attention, concentration etc.) could play an important role for prediction of swallowing regeneration and survival in neurorehabilitation. These findings may have practical utility in guiding physicians and speech language pathologists when advising patients and families about prognosis in stroke survivors with severe dysphagia.

Application of clinical scanners in rats: experimental carotid imaging using magnetic resonance imaging, spiral computed tomography, and color duplex ultrasound.

BACKGROUND AND PURPOSE: Noninvasive small animal imaging allows for reduction of the required numbers of animals in research by providing the possibility of long-term follow-up at various time points. Additionally, correlation to the investigated respective human disease is possible as equivalent equipment is employed. The authors therefore evaluate feasibility and potential of color duplex sonography, computed tomography angiography (CTA), and magnetic resonance angiography (MRA) by the use of clinical scanners for carotid artery imaging in rats. METHODS: Male Wistar rats (n = 17) were subjected to color duplex sonography, CTA, and MRA of the common carotid artery (CCA) and the carotid bifurcation. Clinical scanners were used for the experiments and optimal parameter settings evaluated accounting for the different size of the animals. The applied imaging methods were analyzed in regard to image quality and practicability in laboratory settings. RESULTS: The CCA could be clearly displayed by all imaging modalities in all rats. Duplex sonography provided distinct images and reproducible basic functional information. CTA and MRA provided distinct images of the CCA and the carotid bifurcation in both axial and reconstructed 3-dimensional images. The authors further describe different indications for these imaging methods regarding spatial resolution, acquisition times, possible scanning range, and application of contrast agent. CONCLUSIONS: Color duplex sonography, CTA, and MRA are all feasible methods for imaging of the carotid arteries in rats. Images of sufficient clarity and resolution could be obtained by the use of clinical scanners, yielding information about vessel size, direction of blood flow, and adjacent structures. Further studies need to be performed that address investigations of pathological conditions such as flow disturbances or vessel stenosis.

The relationship between plasma D-dimer concentrations and acute ischemic stroke subtypes.

Elevated concentrations of D-dimers (DDs) in patients with acute ischemic stroke may cause differential diagnostic problems with regard to pulmonary or deep venous thrombosis. The true relationship between plasma DDs and acute ischemic stroke remains uncertain. We studied acute stroke patients admitted to a single acute neurology department with a specialized stroke unit. As part of our clinical protocol, blood samples of each patient had been taken within the first 24 hours after the onset of stroke symptoms and before anticoagulant treatment had been started, to evaluate the coagulation profile. Each patient's medical record was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Univariate and multivariate statistical analyses were performed. A total of 59 patients admitted to our stroke unit between October 2003 and March 2004 with different stroke subtypes according to the TOAST criteria were evaluated to characterize the impact of stroke category on DD concentration. Family members (n = 23) served as controls in this study. Multivariate regression analysis revealed that patients who sustained cardioembolic stroke had significantly higher DD concentrations than controls and patients who sustained transient ischemic attacks. We identified a correlation between plasma DD levels and different acute ischemic stroke subtypes before any stroke treatment was started. Thus DD concentrations may be considered a direct consequence of marked cerebral infarction and may be useful for physicians when making decisions on treatment for acute ischemic stroke.

External carotid artery territory ischemia impairs outcome in the endovascular filament model of middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: Middle cerebral artery occlusion (MCAO) by an intraluminal filament is a widely accepted animal model of focal cerebral ischemia. In this procedure, cutting of the external carotid artery (ECA) is a prerequisite for thread insertion. However, the implications of ECA transsection have not yet been described. METHODS: After 90 minutes of filament MCAO or sham surgery, rats were evaluated for up to 14 days in terms of body weight development, core temperature, and motor performance. Repeated in vivo MRI of the head and neck was performed for quantification of brain edema and infarct volume. The temporal muscles were histologically analyzed postmortem. RESULTS: In 47% of all rats, ischemic tissue damage to the ipsilateral ECA area, including temporal, lingual, and pharyngeal musculature, was detectable by MRI. Histology of temporal muscles confirmed acute ischemic myopathy. Animals with ECA territory ischemia (ECA-I) showed delayed body weight development and poorer recovery of motor function. There was no difference in the extent of brain edema or final cerebral lesion size between ECA-I-affected and unaffected rats. CONCLUSIONS: Filament MCAO was complicated by the consequences of ECA ischemia in approximately half of all rats. Impaired mastication and swallowing functions restricted ingestion and resulted in postsurgical body weight loss and worse motor performance. Impaired cerebral microperfusion resulting from dehydration and reduced spontaneous motor activity resulting from reduced food and water uptake might have contributed to poorer neurological recovery in ECA ischemic rats. Thus, adverse effects caused by extracerebral ischemia with potential impact on outcome have to be considered in this stroke model.

Preoperative evaluation of carotid artery stenosis: comparison of contrast-enhanced MR angiography and duplex sonography with digital subtraction angiography.

BACKGROUND AND PURPOSE: Contrast-enhanced MR angiography and extracranial color-coded duplex sonography are noninvasive, preoperative imaging modalities for evaluation of carotid artery stenosis. Innovative techniques and improvements in image quality require frequent reassessment of accuracy, reliability, and diagnostic value compared with those of digital subtraction angiography (DSA). We evaluated contrast-enhanced MR angiography and duplex sonography compared with DSA for detection of high-grade carotid artery stenoses. METHODS: Four readers, blinded to clinical symptoms and the outcome of other studies, independently evaluated stenoses on contrast-enhanced MR angiograms in 71 vessels of 39 symptomatic patients. Duplex sonography was also performed in all vessels. The severity of stenosis was defined according to North American Symptomatic Carotid Endarterectomy Trial criteria (0-29%, 30-69%, 70-99%, 100%). Results of both modalities were compared with the corresponding DSA findings. RESULTS: Contrast-enhanced MR angiography had a sensitivity and specificity of 94.9% and 79.1%, respectively, for the identification of carotid artery stenoses of 70% or greater. Sensitivity and specificity of duplex sonography were 92.9% and 81.9%, respectively. Combining data from both tests revealed a sensitivity and specificity of 100% and 81.4%, respectively, for concordant results (80% of vessels). CONCLUSION: Concordant results of contrast-enhanced MR angiography and duplex sonography increase the diagnostic sensitivity to 100%. The reliability of MR angiography is comparable to that of DSA. The combination of contrast-enhanced MR angiography and duplex sonography might be preferable over DSA for preoperative evaluation in most patients, thus reducing the risk of perioperative morbidity and improving the overall outcome.

Ketamine/xylazine anesthesia for radiologic imaging of neurologically impaired rats: dose response, respiratory depression, and management of complications.

In vivo imaging of rats represents an important tool for outcome evaluation in research on stroke, brain trauma, and other neurologic diseases. Since sedation of animals is necessary to avoid artifacts, a mixture of ketamine and xylazine is frequently used for anesthesia. We assessed the suitable dosage of narcotics and its correlation to severe respiratory adverse events in 269 cases of ketamine/xylazine anesthesia in male Wistar rats for performance of magnetic resonance imaging after middle cerebral artery occlusion (MCAO) or sham surgery. Anesthesia depth was not measured. Anesthesia was efficacious in avoiding movement artifacts during imaging. Necessary dosage was lower if rodents were subjected to MCAO instead of sham surgery, if body weight was below baseline, and if time since surgery was short. If anesthesia was induced during the first 2 days after surgery in animals with body weight loss, necessary dose rates were 27% below doses required for rats more than 10 days post-surgery with body weight above baseline (91.4/8.3 versus 125.1/11.3 mg of ketamine/xylazine/kg). A dose adaptation scale for the prediction of necessary dose rates was developed. Apnea developed in 3.3% of all animals. Use of ketamine/xylazine anesthesia for imaging procedures is feasible and safe, though it is associated with a small risk of respiratory arrest. In case of apnea, inspiration can be provoked by a puff of air into the rat's pelt. If unsuccessful, endotracheal intubation and mechanical ventilation are needed until spontaneous breathing is restored or xylazine effects are antagonized.

N-Heterocyclic carbene boranes are good hydride donors.

The nucleophilicity parameters (N) of 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene borane and 1,3-dimethylimidazol-2-ylidene borane are 9.55 and 11.88. This places N-heterocyclic carbene boranes (NHC-boranes) among the most nucleophilic classes of neutral hydride donors. Reductions of highly electron-poor C═N and C═C bonds provide hydrogenation products along with new, stable borylated products. The results suggest that NHC-boranes have considerable untapped potential as neutral organic reductants.

Depressive symptoms and quality of life after thrombolysis in stroke: the TEMPiS study.

Intravenous thrombolysis leads to a reduction of post-stroke disability. No data exist about whether depression and poor quality of life (QoL) remain relevant problems in patients with good functional outcome. We assessed mood and QoL at 3 and 6 months after stroke in consecutive patients who received intravenous thrombolysis in stroke centers and telemedicine hospitals within the TEMPiS network. The Beck Depression Inventory (BDI) was used with BDI ≥18 indicating clinically relevant depressive symptoms. Stroke specific quality of life (SSQOL) was used for QoL assessment with the definition of SSQOL total score <60% for poor QoL. Associations of BDI and SSQOL with baseline parameters and modified Rankin scale (mRS) in follow-up were analyzed. In patients with known mRS 0-4 at 3 months (N = 213), BDI was available in 74% and SSQOL in 77%. At 3 and 6 months, 23 and 18% of patients had clinically relevant depressive symptoms; 25 and 24% reported a poor QoL. The mRS at 3 months correlated with BDI (r = 0.43, p < 0.01) and SSQOL (r = -0.75, p < 0.01). BDI ≥18 was observed in 11% of patients with mRS 0-1 and 16% in mRS 0-2. Severe stroke (NIHSS ≥12) at admission (OR 1.23, 0.57-2.66; p = 0.57) was not predictive for depressive symptoms but for poor QoL (OR 2.77, 95%CI 1.34-5.74). Depressive symptoms and impaired QoL are observed in a substantial proportion of stroke patients at 3 months after intravenous thrombolysis. Health professionals should be aware that thrombolysed patients may have relevant mood disorders despite good functional outcome.