Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

Addition of cilostazol reduces biological aspirin resistance in aspirin users with ischaemic stroke: a double-blind randomized clinical trial.

BACKGROUND AND PURPOSE: Biological aspirin resistance (AR) has been recognized as an important cause of clinical AR. Recent studies have reported the beneficial effects of cilostazol for the prevention of cardiovascular diseases. This study investigated whether addition of cilostazol to aspirin in ischaemic stroke patients can reduce AR. METHODS: In this double-blind multicenter trial, 244 aspirin users with ischaemic stroke were randomly assigned to receive cilostazol 100 mg twice daily or to placebo. Antiplatelet function was assessed using the VerifyNow Aspirin system. The primary end-point was the incidence of AR, which was measured as aspirin resistance unit (ARU) > or =550 after 4-week treatment. RESULTS: The incidence of AR after treatment in cilostazol group was not significantly different from that in placebo (8.8% vs. 10.9%, P = 0.578). However, AR decreased from 12.8% to 8.8% in cilostazol group, whereas it was not changed in the placebo group. The mean ARU after treatment were also lower in the cilostazol group (456.9 +/- 56.0 vs. 470.7 +/- 67.2, P = 0.081). Cilostazol addition did not prolong bleeding time. CONCLUSIONS: Although this was a negative study, our findings disclosed a trend toward enhanced antiplatelet effects when cilostazol was added to aspirin in ischaemic stroke patients. Combination of aspirin and cilostazol might be a treatment option in the ischaemic stroke patients with AR.

Pre-hospital notification reduced the door-to-needle time for iv t-PA in acute ischaemic stroke.

BACKGROUND AND PURPOSE: Intrahospital delay is the most serious obstacle in thrombolysis in acute ischaemic stroke (AIS). We implemented the pre-hospital notification system from the emergency medical information system in our metropolitan area to reduce intrahospital delay. METHODS: From October 2007, we implemented a 24-h hotline system between our stroke center and the Korean Emergency Medical Information System in Busan. We compared processing times and clinical outcomes amongst patients after using intravenous tissue type plasminogen activator (iv t-PA) with and without the hotline system. RESULTS: After the pre-hospital notification system was implemented, the rate of iv t-PA use increased from 6.5% to 14.3%. Time of onset in patients with pre-hospital notification was much longer than in patients without (121.5 +/- 34.8 min vs. 74.7 +/- 38.5 min, P < 0.01) notification but door-to-needle time was significantly reduced (28.9 +/- 11.4 min vs. 47.7 +/- 22.8 min, P < 0.01). However, there were no significant differences in 90-day clinical outcomes between the two groups. CONCLUSIONS: The pre-hospital notification system reduced intrahospital processing times which led to increased iv t-PA use after AIS. However, the improvement of clinical outcomes in thrombolysis might require organization of not only intrahospital processes but of outside processes such as the early recognition and rapid dispatch of patients with suspected AIS.

Surgical Therapy of Peri-Implantitis with Local Minocycline: A 6-Month Randomized Controlled Clinical Trial.

The purpose of this study was to determine the clinical, microbial, and radiographic effects of local minocycline combined with surgical treatment of peri-implantitis. Fifty patients with peri-implantitis were recruited, and surgical treatment with the local application of either minocycline or placebo ointment was performed. The application of minocycline was repeated with supragingival debridement at 1, 3, and 6 mo postoperatively. Plaque index, gingival index (GI), probing pocket depth (PPD), and bleeding/suppuration on probing were measured at baseline and 1-, 3-, and 6-mo evaluations. The change in supporting bone level (SBL) measured with cone beam computed tomography was analyzed between baseline and 6 mo. Microbial analysis was performed with real-time polymerase chain reaction. Both groups exhibited improvements in clinical and radiographic measurements after surgical treatment. There was a significant difference in the changes of mean PPD between the test and control groups (2.68 ± 1.73 and 1.55 ± 1.86 mm, respectively, P = 0.039). The changes of mean GI and SBL differed significantly between the groups (ΔGI: 0.83 ± 0.60 and 0.40 ± 0.68; ΔSBL: 0.72 ± 0.56 and 0.31 ± 0.49 mm, respectively, P = 0.026 and 0.014). Treatment success rates (defined as PPD <5 mm, absence of bleeding/suppuration on probing, and no further bone loss) were 66.7% and 36.3% in the test and control groups, respectively. The count of red complex bacteria tended to decrease in both groups until 6 mo; however, no significant intergroup difference was found. None of the patients in the test group carried Porphyromonas gingivalis or Tannerella forsythia at 6 mo. These findings indicate that the repeated local delivery of minocycline combined with surgical treatment provides significant benefits in terms of clinical parameters and radiographic bone fill, with a higher treatment success rate in the short healing period (cris.nih.go.kr KCT0002844).

ADP-induced platelet aggregation in acute ischemic stroke patients on aspirin therapy.

BACKGROUND AND PURPOSE: Aspirin is an important therapeutic regimen to prevent the recurrent ischemic events or death after acute ischemic stroke. In this study, we evaluated the relationship between the extent of adenosine diphosphate (ADP)-induced platelet aggregation and outcome in acute ischemic stroke patients on aspirin therapy. METHODS: We selected 107 acute ischemic stroke patients who had been prescribed aspirin and evaluated platelet function test by using optic platelet aggregometer test after 5 days of taking it and investigated the prognosis 90 days after ischemic events. Kaplan-Meyer curve was used for survival analysis. RESULTS: After stratification of the subjected patients by tertiles of ADP-induced platelet aggregation, the events rates were 7.4%, 9.3% and 30.8% (P = 0.023). In multiple logistic regression analysis, old age over 70 years (OR, 13.7; 95% CI, 2.14-88.07; P = 0.001) and the increased ADP-induced platelet aggregation had independent significance to the risk of primary end-points after acute ischemic stroke (OR, 1.1; 95% CI 1.01 to 1.20; P = 0.026). CONCLUSIONS: This study showed that the increased ADP-induced platelet aggregation under using aspirin is associated with poor outcome after acute ischemic stroke.

Pre-stroke glycemic control is associated with early neurologic deterioration in acute atrial fibrillation-related ischemic stroke.

BACKGROUND: It has been suggested that AF-related ischemic stroke (IS) that is accompanied by atherosclerotic burden have poorer outcomes. The aim of this study was to investigate the importance of pre-stroke glycemic control (PSGC) on the early neurologic deterioration (END) of patients with acute AF-related IS. METHODS: We retrospectively recruited 121 patients with AF-related IS who also had Diabetes mellitus (DM). The HbA1C level was measured in all subjects. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score of 4 NIHSS points within 7 days of symptom onset compared to the initial NIHSS score. RESULTS: In this study, 20.7% (25 patients) were classified as having a poor PSGC status with a HbA1C level above 8.0%. In the univariate analysis, a poor PSGC status (p < 0.01), smoking (p = 0.01), severe neurologic deficits at admission (p = 0.01), and a larger size of ischemic lesions on DWI (p < 0.01) were associated with the occurrence of END. In the multivariate model, a poor PSGC status (p = 0.02) and larger size of ischemic lesions on MRI (p < 0.01) were independent predictors of END in acute AF-related IS. CONCLUSION: The HbA1c level upon admission was independently associated with significant prediction of END in acute AF-related IS.

Protective effects of swainsonine on murine survival and bone marrow proliferation during cytotoxic chemotherapy.

We have investigated the ability of swainsonine, an indolizidine alkaloid with pleiotropic in vivo effects, to confer protection against the cytotoxic effects of both cell cycle-specific and cell cycle-nonspecific cytotoxic anticancer agents. The intraperitoneal administration of swainsonine decreased the lethality of methotrexate (MTX), fluorouracil (5-FU), cyclophosphamide (CPM), and doxorubicin (DOX) in non-tumor-bearing C57BL/6 mice. The increased survival rate was found to correlate with stimulation of bone marrow cell proliferation, as measured by increases in 1) bone marrow cellularity, 2) in vivo and in vitro colony-forming activity, and 3) engraftment efficiency. These responses were critically dependent on the dose, sequence, and timing of swainsonine administration. If these results are confirmed in humans, swainsonine may offer promise in future intensive chemotherapy programs, allowing increased dosage and/or frequency of administration of cytotoxic agents without increasing toxic effects in bone marrow.

Safety and Efficacy of Intravenous Tirofiban as Antiplatelet Premedication for Stent-Assisted Coiling in Acutely Ruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Stent-assisted coiling of intracranial aneurysms requires antiplatelet therapy, typically aspirin and clopidogrel to prevent thromboembolic complications. There is a substantial concern that tirofiban may increase the risk of hemorrhage when used as an antiplatelet premedication in ruptured intracranial aneurysms. Our aim was to evaluate the safety and efficacy of intravenous tirofiban administration, instead of oral dual antiplatelet agents, as an antiplatelet premedication for stent-assisted coiling in patients with acutely ruptured intracranial aneurysms. MATERIALS AND METHODS: We conducted a retrospective review of a data base containing a consecutive series of patients who underwent stent-assisted coiling for acutely ruptured intracranial aneurysms between March 2010 and January 2015. Intravenous tirofiban was administered to all patients before stent-assisted coiling, instead of premedication with loading doses of aspirin or clopidogrel. RESULTS: Forty patients with 41 aneurysms received intravenous tirofiban and underwent stent-assisted coiling. None of the patients had a newly developed intracerebral hemorrhage, subarachnoid hemorrhage, or intraventricular hemorrhage. Intraprocedural aneurysmal rupture occurred in 2 patients (5%). Cerebral infarction developed in 2 patients (5%). Ventriculostomy-related hemorrhage was seen in 2 of 10 patients in whom ventriculostomy was performed before or after coiling. Thirty-four (85%) patients had a good outcome (Glasgow Outcome Score of 4 or 5) at the time of discharge, but 1 patient died of cardiac arrest. None of the patients developed thrombocytopenia, retroperitoneal, gastrointestinal, or genitourinary bleeding related to tirofiban administration. CONCLUSIONS: In our study, tirofiban showed a low risk of symptomatic hemorrhagic or thromboembolic complications. Tirofiban may offer a safe and effective alternative as an antiplatelet premedication during stent-assisted coiling of acutely ruptured intracranial aneurysms.

Titanium-mediated alkylative cyclizations of 1,3-diene-tethered esters.

[reaction: see text]. An alkylative titanium-mediated cyclization reaction of 1,3-diene-tethered carboxylic esters has been developed by employing an in situ generated titanacyclopropane intermediate to afford trans-2-alkenyl cyclohexanols.

A new approach to phorbol by [4 + 3] oxyallyl cycloaddition and intramolecular Heck reaction.

[formula: see text] A new synthetic strategy for a functionalized tricyclic core of phorbol has been developed by means of a [4 + 3] oxyallyl cycloaddition and subsequent intramolecular Heck reaction. The [4 + 3] oxyallyl cycloadduct 7 was chosen as the B-ring precursor of phorbol. Subsequent elaboration took advantage of its well-defined diastereofacial bias to afford the tricycle 5. This method should be of general value in the construction of 6,7- or 5,7-fused bicyclic systems.

Electrophilic cyclizations of vinylcyclopropanols to tethered aldehydes.

[reaction: see text]. The intramolecular, stereoselective addition of 1-vinylcyclopropanols to tethered aldehydes has been achieved under mild conditions. Thus, sequential application of the titanium-mediated cyclopropanation of alpha,beta-unsaturated esters and the electrophilic cyclization of the aldehyde-tethered cyclopropanol products provides the facile formation of carbocyclic rings.

[4 + 3] Cycloaddition of cyclopropanone hemiacetals.

[reaction: see text]. Intermolecular and intramolecular [4 + 3] cycloaddition reactions of readily available cyclopropanone hemiacetals with furans are described.

Facile synthesis of the tricyclic core of sarain A. 3-Oxidopyridinium betaine cycloaddition approach.

[formula: see text] A new approach to a suitably functionalized tricyclic core of sarains has been developed by means of Katritzky's cycloaddition using 3-oxidopyridinium betaines. A key step was the regioselective differentiation of the two nearly identical hydroxy groups derived from oxidative cleavage of the double bond in 8 to afford 14. A stereocontrolled construction of the tricyclic core 20 of sarains containing the requisite side chain at C-3' was achieved by an intramolecular conjugate addition.

Pseudochoreoathetosis in four patients with hypesthetic ataxic hemiparesis in a thalamic lesion.

Thalamic lesions give rise to a variety of clinical syndromes including choreoathetotic movements and ataxic hemiparesis as well as sensory deficits. We describe four patients exhibiting pseudochoreoathetosis, hypesthesia, and ataxic hemiparesis in the limbs contralateral to a thalamic lesion. Three of the four patients showed the involuntary movements within 10 days of stroke onset; the remaining patient was not seen until 4 years later. Three had infarction and the other one hemorrhage in the posterior and lateral thalamus. All the patients had both cerebellar and sensory ataxia. These cases suggest that failure to convey proprioceptive information be the basic pathophysiology of pseudochoreoathetosis.

Inhibition of growth of subcutaneous xenografts and metastasis of human breast carcinoma by swainsonine: modulation of tumor cell HLA class I antigens and host immune effector mechanisms.

Swainsonine, an indolizidine alkaloid, can decrease the organ colonization potential of metastatic murine tumor cells by augmentation of host immune effector mechanisms. In this report the above findings were extended by the demonstration that systemic administration of swainsonine strongly suppressed the growth of human breast carcinoma subcutaneous xenografts and experimentally induced lung metastases. This inhibition was not due to a direct effect of swainsonine on cell growth. However swainsonine treatment of tumor cells resulted in enhanced expression of HLA Class I antigens, and HLA class I mRNA. Swainsonine was a potent immunodulator as evidenced by the increased (a) cytotoxicity of splenocytes and macrophages, and, (b) proliferative potential of splenocytes and bone marrow cells. These data suggest that swainsonine-induced inhibition of tumor growth and metastases may be mediated via activation of host effector cells and/or alteration of tumor cell antigenicity.

Matrix formalism of electromagnetic wave propagation through multiple layers in the near-field region: application to the flat panel display.

We have developed an electromagnetic (EM) wave propagation theory through a single layer and multiple layers in the near-field and far-field regions, and have constructed a matrix formalism in terms of the boundary conditions of the EM waves. From the shielding efficiency (SE) against EM radiation in the near-field region calculated by using the matrix formalism, we propose that the effect of multiple layers yields enhanced shielding capability compared to a single layer with the same total thickness in conducting layers as the multiple layers. We compare the intensities of an EM wave propagating through glass coated with conducting indium tin oxide (ITO) on one side and on both sides, applying it to the electromagnetic interference (EMI) shielding filter in a flat panel display such as a plasma display panel (PDP). From the measured intensities of EMI noise generated by a PDP loaded with ITO coated glass samples, the two-side coated glass shows a lower intensity of EMI noise compared to the one-side coated glass. The result confirms the enhancement of the SE due to the effect of multiple layers, as expected in the matrix formalism of EM wave propagation in the near-field region. In the far-field region, the two-side coated glass with ITO in multiple layers has a higher SE than the one-side coated glass with ITO, when the total thickness of ITO in both cases is the same.

Acute ophthalmoplegia (without ataxia) associated with anti-GQ1b antibody.

BACKGROUND: Anti-GQ1b antibody has been found in Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff brainstem encephalitis (BBE), and acute ophthalmoplegia without ataxia (AO). The aim of this study was to determine the clinical features of AO associated with anti-GQ1b antibody. METHODS: We retrospectively collected 34 patients with anti-GQ1b antibody syndrome. Of these patients, 31 patients had ophthalmoplegia. The patients with ophthalmoplegia were classified into MFS (n = 13), AO (n = 11), GBS with ophthalmoplegia (n = 6), and BBE (n = 1). We analyzed clinical features and patterns of external and internal ophthalmoplegia of AO, and neuro-ophthalmologic findings were compared with those of other anti-GQ1b syndromes with ophthalmoplegia. RESULTS: AO was observed in 11 (32.4%) of the 34 patients with anti-GQ1b antibody. External ophthalmoparesis was present in all the patients and included mixed horizontal-vertical (n = 7), pure horizontal (n = 3), and pure vertical gaze palsy (n = 1). Binocular involvement was common, but unilateral ophthalmoparesis was also observed in 27.3%. Other findings included ptosis (n = 5, 45.5%) and internal ophthalmoplegia (n = 6, 54.5%). Other anti-GQ1b antibody syndromes had prominent neurologic signs including ataxia, weakness, and facial palsy in addition to ophthalmoplegia. The patterns of neuro-ophthalmologic findings did not differ between AO and other anti-GQ1b antibody syndromes with ophthalmoplegia. CONCLUSIONS: Acute ophthalmoplegia (AO) commonly occurs in anti-GQ1b antibody syndrome and manifests as various combinations of external and internal ophthalmoplegia. Internal ophthalmoplegia is fairly common and unilateral involvement may occur in AO.

Total synthesis of tropoloisoquinolines: imerubrine, isoimerubrine, and grandirubrine.

A unified, ready access to the tropoloisoquinoline alkaloids imerubrine (1), grandirubrine (2), and isoimerubrine (3) is delineated and features sequential application of the intramolecular Diels-Alder reaction of an acetylene-tethered oxazole and the [4 + 3] cycloaddition of an oxyallyl. A regioselective synthesis of 1 was achieved by stereo- and regioselective oxidation of an 8-oxabicyclo[3.2.1]oct-6-en-3-one cycloadduct by means of the Moriarty method. Such a post-cycloaddition functionalization complements the synthetic utility of an alpha-alkoxy-substituted oxyallyl so as to broaden the scope of the oxyallyl [4 + 3] cycloaddition reaction.

Two cases of suspected arteriosclerotic optical chiasmal syndrome.

Optic chiasmal syndrome due to arteriosclerotic vascular changes is rate. To our knowledge, there has been no report of arteriosclerotic chiasmal syndrome in Korea. In our two cases, other causes of chiasmal syndrome were not detected by MRI, four-vessel cerebral angiography, CSF study, and special laboratory examinations including ANA test, RA factor, and LE cell. With conservative treatment, the visual fields of the two patients are showing progressive improvement. We report here two cases of suspected arteriosclerotic optic chiasmal syndrome.