Urokinase In Patients Research Articles

Relationship Between Circulating Tumor Cells and Tissue Plasminogen Activator in Patients with Early Breast Cancer

Cancer increases the risk of venous thromboembolism (VTE) and circulating tumor cells (CTCs) are associated with an increased risk of VTE and, thus, with increased D-dimers as a product of fibrinolysis. Tissue plasminogen activator (tPA) is one of the key enzymes in the fibrinolytic pathway. Its activity is crucial in maintaining the balance between blood coagulation and fibrinolysis. This study aimed to analyze the association between CTCs and tPA in patients with primary breast cancer before surgery. This prospective study included 110 patients in whom CTCs were detected by quantitative reverse transcription polymerase chain reaction targeted at epithelial (CK19) or epithelial-mesenchymal transition (EMT)-associated genes[TWIST1, SNAI1, SNAI2, zinc finger E-box-binding homeobox 1 (ZEB1), forkhead box protein C2 (FOXC2)]. Plasma tPA protein was detected using enzyme-linked immunosorbent assay (ELISA). CTCs were detected in 31 (28.2%) patients. There was no association between plasma tPA and CTCs. Although on average, higher levels of tPA were detected in patients with CTCs expressing EMT-associated genes, this difference did not reach statistical significance. There was no association of plasma tPA with any of the observed patient or tumor characteristics. Even though the blood coagulation pathway may be activated in more aggressive disease related to an elevated CTC count, in this study, we did not find any association between CTCs and plasma concentrations of tPA.

Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results From a Multicenter Study.

Remote parenchymal hemorrhage (rPH) after intravenous thrombolysis with recombinant tissue-type plasminogen activator may be associated with cerebral amyloid angiopathy, although supportive data are limited. We aimed to investigate risk factors of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator. This is an observational study of patients with ischemic stroke who were treated with intravenous thrombolysis with recombinant tissue-type plasminogen activator and were included in a multicenter prospective registry. rPH was defined as any extraischemic hemorrhage detected in the follow-up computed tomography. We collected demographic, clinical, laboratory, radiological, and outcome variables. In the subset of patients who underwent a magnetic resonance imaging examination, we evaluated the distribution and burden of cerebral microbleeds, cortical superficial siderosis, leukoaraiosis, and recent silent ischemia in regions anatomically unrelated to the ischemic lesion that caused the initial symptoms. We compared patients with rPH with those without rPH or parenchymal hemorrhage. Independent risk factors for rPH were obtained by multivariable logistic regression analyses. We evaluated 992 patients (mean age, 74.0±12.6 years; 52.9% were men), and 408 (41%) of them underwent a magnetic resonance imaging. Twenty-six patients (2.6%) had a rPH, 8 (0.8%) had both rPH and PH, 58 (5.8%) had PH, and 900 (90.7%) had no bleeding complication. Lobar cerebral microbleeds (odds ratio, 8.0; 95% confidence interval, 2.3-27.2) and recent silent ischemia (odds ratio, 4.8; 95% confidence interval, 1.6-14.1) increased the risk of rPH. The occurrence of rPH after intravenous thrombolysis with recombinant tissue-type plasminogen activator in patients with ischemic stroke is associated with lobar cerebral microbleeds and multiple ischemic lesions in different regions.

Abstract WMP34: Use of Intravenous Tissue Plasminogen Activator in Patients Without a Stroke (Stroke Mimics): Findings From the get With the Guidelines Stroke Registry

Background: The necessity for rapid evaluation and treatment with intravenous tissue plasminogen activator (tPA) in acute ischemic stroke may increase the risk of administrating tPA to patients without a stroke (“stroke mimics”). Methods: Using data from the Get With The Guidelines Stroke Registry from 2009 to 2015, we identified 90,746 patients treated with tPA within 4.5 hours of symptom onset. We documented use of tPA in stroke mimics, defined as patients initially thought to have a stroke but without a final diagnosis of one, and compared patient characteristics and outcomes between tPA-treated mimics vs. ischemic strokes. Results: Overall, only 0.8% (728) of all tPA cases were given to stroke mimics, ranging from 0.2% in 2009 Q1 to 1.3% in 2015 Q1. The most common documented diagnoses in tPA-treated mimics were migraine (15.6%), functional disorder (9.4%), and seizure (7.2%). Compared with tPA-treated true stroke patients, tPA-treated mimics were younger (median 52 vs. 72 years), had lower prevalence of atrial fibrillation, coronary artery disease, dyslipidemia, hypertension, heart failure, had less severe National Institute of Health Stroke Scale (median 7 vs. 10), but higher prevalence of prior stroke/transient ischemic attack (34.4% vs. 25.5%), all p<0.001. The door-to-needle times were similar in stroke mimics and true stroke groups (median 68 vs. 68 minutes, p=0.82). Rates of symptomatic intracranial hemorrhage (sICH) were quite rare in stroke mimic patients (0.4%, 3/728) as compared with 4.3% (3846/90018) in patients with an ischemic stroke; adjusted OR for sICH (0.19, 95% CI 0.06-0.58). The in-hospital mortality rate was significantly lower in tPA-treated stroke mimics as compared with ischemic stroke patients (0.6% vs. 7.3%, adjusted OR 0.16, 95% CI 0.06-0.43). Conclusions: In this large nationwide cohort of patients treated with tPA, only 1 in 125 patients who received tPA for presumed stroke was a false positive and complication rates associated with tPA administration to stroke mimics were quite low. Nonetheless, there still may be opportunities to continue to improve the rapid and accurate diagnosis and treatment of ischemic stroke.

Repeated Intravenous Treatment with Recombinant Tissue-Type Plasminogen Activator in Patients with Acute Ischemic Stroke

Objective: Increased use of systemic thrombolysis, demographic changes, and higher chances of surviving first-ever strokes all lead to an increasing number of patients with recurrent stroke. However, data on repeated thrombolysis are limited. Here, we report on the safety and clinical effects of repeated intravenous recombinant tissue-type plasminogen activator (rt-PA) treatment in a large consecutive cohort of stroke patients. Methods: We identified all stroke patients who received repeated thrombolysis. We determined safety and 3-month clinical outcome after the first and second thrombolysis. All patients received follow-up brain imaging. Good clinical outcome was defined as a modified Rankin Scale of 0-2 or recovery to the prestroke status. Results: In total, 24 patients were included (i.e. 1.5% of all stroke patients treated with rt-PA at our center who survived the first treatment; male 45.8%; median age at first event: 74.5 years). No allergic or anaphylactic reactions were recorded after the first time of treatment, but oral angioedema developed once during the second treatment. No symptomatic intracerebral hemorrhage was observed. Clinical outcome was good in 75.0% after the first, but in only 41.7% after the second treatment (p = 0.021). Conclusions: Repeated thrombolysis was not associated with a higher rate of complications. However, the clinical outcome appears to be less satisfactory than after the first treatment.

American Stroke Association Stroke Council Update

This report represents the Spring 2015 update of the Stroke Council. Much has happened in the last 12 months, and we want to particularly focus on the major developments in acute stroke therapy and their implications, progress in the American Stroke Association (ASA)/American Heart Association (AHA) quality initiatives and tiered systems of stroke care, and the approval of a new code for the National Institutes of Health Stroke Scale (NIHSS). Each Stroke Council Update starts with restating our 2020 Goals: to improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%. In December 2014, we had further evidence that our efforts are bearing fruits. In 2011, stroke fell from the number 3 to the number 4 cause of death in the United States, and in December, stroke fell from number 4 to number 5. This development, which reflects the continued decrease in age-adjusted mortality rates for stroke, is a remarkable testament to concerted educational and public health efforts to control blood pressure, decrease tobacco use, appropriately treat atrial fibrillation, educate the public about stroke warning signs, and improve and standardize the neurocritical care of stroke patients. Yet, it is sobering that the actual number of strokes continues to increase as the population ages because the incidence of stroke increases markedly with age. Stroke remains the second leading cause of death worldwide and one of the leading causes of disability worldwide. That is why the ASA/AHA is partnering with the World Stroke Organization and World Health Organization to take best practices and apply them worldwide. We have accomplished much but have more to do. The International Stroke Conference Scientific Sessions and Pre-conference meetings in Nashville was a great success with 4341 attendees, the largest number of attendees ever. The quality of the …

Amiloride lowers blood pressure and attenuates urine plasminogen activation in patients with treatment–resistant hypertension

In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria/proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase–type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen–to–plasmin activation; and (3) inhibits urine urokinase–type plasminogen activator in patients with resistant hypertension and type 2 diabetes mellitus (T2DM).In an open–label, non–randomized, 8–week intervention study, a cohort (n = 80) of patients with resistant hypertension and T2DM were included. Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin–angiotensin–aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks. Complete dataset for urine analysis was available in 60 patients. Systolic and diastolic BP measured by ambulatory BP monitoring and office monitoring were significantly reduced. Average daytime BP was reduced by 6.3/3.0 mm Hg. Seven of 80 cases (9%) discontinued amiloride due to hyperkalemia >5.5 mol/L, the most frequent adverse event. Urinary plasmin(ogen) and albumin excretions were significantly reduced after amiloride treatment (P < .0001). Urokinase activity was detectable in macroalbuminuric urine, with a tendency toward reduction in activity after amiloride treatment. Amiloride lowers BP, urine plasminogen excretion and activation, and albumin/creatinine ratio, and is a relevant add–on medication for the treatment of resistant hypertension in patients with T2DM and microalbuminuria.

Salvage of a free flap using postoperative percutaneous angioplasty in patients with diabetic foot ulcers.

Salvage of a free flap using postoperative percutaneous angioplasty in patients with diabetic foot ulcers.

No exacerbation of perihematomal edema with intraclot urokinase in patients with spontaneous intracerebral hemorrhage.

Perihematomal edema (PHE) can worsen patient outcomes after spontaneous intracerebral hemorrhage (ICH). Minimally invasive surgery (MIS) in combination with thrombolytic removal of hematoma has been proven to be a promising treatment strategy. However, preclinical studies have suggested that intraclot thrombolysis may exacerbate PHE after ICH. Herein, we investigated the effects of MIS and urokinase on PHE. ICH patients were retrospectively identified from our institutional ICH database. Computerized volumetric analysis was applied to assess changes in both ICH and PHE volumes using computed tomographic (CT) scans of T1 (pre-MIS) and T2 (post-MIS) time points. Relative PHE (rPHE) was calculated as a ratio of PHE and T1 ICH volume. Data from 60 MIS plus urokinase (MIS + U), 20 MIS aspiration only (MO), and 30 control patients were analyzed. The ICH volume, PHE volume and rPHE on T2 CT in both MIS + U and MO groups significantly decreased as compared with the control group (ICH volume, 13.7 ± 5.7 ml, 17.0 ± 10.5 ml vs. 30.5 ± 10.3 ml, P < 0.01; PHE volume, 36.5 ± 18.9 ml, 32.2 ± 17.5 ml vs. 45.4 ± 16.0 ml, P < 0.01; rPHE, 0.9 ± 0.4, 0.8 ± 0.4 vs.1.4 ± 0.5, P < 0.01). Between the MIS + U and MO groups, the ICH volume, PHE volume and rPHE at T2 trended towards similarity, but was not significant (P = 0.09, P = 0.40, P = 0.43). Furthermore, we found a significant correlation between the percent of ICH removal and PHE reduction (r = 0.59, P < 0.01). There was no correlation between the cumulative dose of urokinase and either T2 PHE volume (r = 0.19; P = 0.16) or T2 rPHE (r = -0.12; P = 0.37). Hematoma evacuation using MIS leads to a significant reduction in PHE. Furthermore, the use of urokinase does not exacerbate PHE, making its hypothesized proedematous effects unlikely when the thrombolytic is administered directly into the clot.

Third International Stroke Trial 3

The third International Stroke Trial (IST-3) was a randomized controlled trial of thrombolysis with intravenous recombinant tissue plasminogen activator in patients with acute ischemic stroke within 6 h of onset. It sought to determine whether a wider variety of patients might benefit from treatment than were eligible under the prevailing European Union approval for the drug, especially among those aged over 80 years. The entry criteria were broad, and there was no upper age limit for inclusion; over half the 3035 patients were aged over 80 years. For the types of patient recruited in IST-3, despite the early hazards (chiefly of fatal intracerebral hemorrhage), thrombolysis within 6 h did not affect longer-term survival and improved functional outcome. Benefit was greatest among patients treated within 3 h, and benefit did not appear to be diminished among elderly patients or those with severe stroke. These results should, therefore, encourage clinicians to: consider thrombolytic treatment for a wider variety of patients (particularly those aged over 80 years); treat those with more severe strokes; reinforce their efforts to increase the proportion of ischemic strokes treated within 3 h; and, have greater confidence that mortality is not increased by treatment. http://links.lww.com/CONR/A23.

Fibrinolytic agents for peripheral arterial occlusion

Peripheral arterial thrombolysis is used in the management of peripheral arterial ischaemia. Streptokinase was originally used but safety concerns led to a search for other agents. Urokinase and recombinant tissue plasminogen activator (rt-PA) have increasingly become established as first line agents for peripheral arterial thrombolysis. Potential advantages of these agents include improved safety, greater efficacy and a more rapid response. Recently drugs such as pro-urokinase, recombinant staphylokinase and alfimperase have been introduced. This is an update of a review first published in 2010. To determine which fibrinolytic agents are most effective in peripheral arterial ischaemia. For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator (TSC) searched the Specialised Register (last searched March 2013) and CENTRAL (2013, Issue 3) for randomised controlled trials (RCTs) comparing fibrinolytic agents to treat peripheral arterial ischaemia. RCTs comparing fibrinolytic agents to treat peripheral arterial occlusion. Data were analysed for the outcomes vessel patency, time to lysis, limb salvage, amputation, death, complications including major haemorrhage, stroke, and distal embolization. Five RCTs involving a total of 687 participants with a range of clinical indications were included. No new studies were included in this update. In one three-pronged study, vessel patency was greater with intra-arterial recombinant tissue plasminogen activator (rt-PA) than with intra-arterial streptokinase (P < 0.04) or intravenous rt-PA (P < 0.01). In participants with peripheral arterial occlusion there was no statistically significant difference in limb salvage at 30 days with either urokinase or rt-PA, though this may reflect the small numbers in the studies. Incidences of haemorrhagic complications varied with fibrinolytic regime but there was no statistically significant difference between intra-arterial urokinase and intra-arterial rt-PA. In the three-pronged study intravenous rt-PA and intra-arterial streptokinase were associated with a significantly higher risk of haemorrhagic complications than with intra-arterial rt-PA (P < 0.05). There is some evidence to suggest that intra-arterial rt-PA is more effective than intra-arterial streptokinase or intravenous rt-PA in improving vessel patency in people with peripheral arterial occlusion. There was no evidence that rt-PA was more effective than urokinase for patients with peripheral arterial occlusion and some evidence that initial lysis may be more rapid with rt-PA, depending on the regime. Incidences of haemorrhagic complications were not statistically significantly greater with rt-PA than with other regimes. However, all of the findings come from small studies and a general paucity of results means that it is not possible to draw clear conclusions.

Use of intravenous recombinant tissue plasminogen activator in patients outside the defined criteria: safety and feasibility issues

Currently, intravenous thrombolysis is by far the most effective treatment of acute ischemic stroke, and its use can independently strongly increase the proportion of stroke patients surviving. While the use of recombinant tissue plasminogen activator in accordance to licensed criteria has continuously risen, off-label use is also frequent. In this review the most important reasons to transcend current license criteria are discussed and evidence is summarized from new studies, such as IST-3, contributing to the balance of increased benefit as opposed to possible harm in situations of off-label use of recombinant tissue plasminogen activator in stroke. In addition, several scores to predict risk and outcome in patients undergoing thrombolysis are compared.

Atrial fibrillation predicts good functional outcome following intravenous tissue plasminogen activator in patients with severe stroke

ObjectiveAtrial fibrillation (AF) is associated with poor outcome after intravenous thrombolysis probably due to greater pretreatment stroke severity. We conducted this retrospective study to determine whether AF is an independent predictor for clinical outcome in patients stratified by initial stroke severity. MethodsA total of 143 acute ischemic stroke patients who received intravenous thrombolysis within 3h after onset were enrolled. The patients were categorized according to the baseline stroke severity by National Institute of Health Stroke Scale (NIHSS) score (≤10 vs. >10) and the presence of AF or not. Favorable 90-day outcome was defined as a modified Rankin Scale (mRS) score<2. ResultsAmong the 100 patients with severe stroke (NIHSS>10), those with AF (n=52) had a higher proportion of favorable 90-day outcome than those without AF (31% vs. 8%, P=0.005). After adjustment for age, baseline glucose level, and onset to treatment time, the difference remained significant (odds ratio 5.80, 95% confidence interval 1.63–20.68). In patients with mild stroke (NIHSS≤10), no difference in clinical outcome was found between AF (n=20) and non-AF (n=23) groups. ConclusionPresence of AF was associated with favorable 90-day outcome following intravenous thrombolysis in patients with severe stroke at baseline, while the association did not exist in patients with mild stroke.

Treatment of acute ischemic stroke: systemic or local?

Systemic treatment of acute ischemic stroke currently means intravenous infusion of plasminogen activator in patients with the stroke syndrome after exclusion of brain hemorrhage irrespective of whether thrombotic arterial obstruction is present or not. In contrast, local intra-arterial treatment requires digital subtraction angiography and means direct treatment of the arterial pathology with the aim of recanalization and brain tissue reperfusion. Randomized controlled trials that test these two treatment approaches are missing. This paper discusses whether the time-saving systemic treatment approach is more promising for acute ischemic stroke patients than is the time-consuming endovascular local approach.

Admission Leukocytosis Is Not Associated with Early Response to Tissue Plasminogen Activator in Patients with Acute Ischemic Stroke (P02.198)

Objective: We examined the relationships between admission leukocytosis and clinical response to intravenous tissue plasminogen activator (rt-PA) and early clinical outcomes in patients with acute ischemic stroke (AIS) receiving rt-PA. Background In patients with acute coronary events treated with IV rt-PA, the presence of leukocytosis is associated with impaired microvascular perfusion and increased re-occlusion rates. Within 24hr of an ischemic event, neutrophils and other acute-phase mediators invade the ischemic tissue releasing pro-inflammatory cytokines promoting endothelial damage. The degree of acute-phase response is related to infarct size and functional outcome. Design/Methods: We undertook a single-center retrospective analysis of patients treated with IV rt-PA for AIS between July 2008 and June 2010. Patients were excluded for in-hospital strokes, infections within 72hr of admission, and for corticosteroids taken in the month before admission or during hospitalization. Leukocyte counts were considered elevated if it exceeded our laboratory reference range for normal ( Results: Eighty-five patients met inclusion criteria; 20% had leukocytosis. Age, race, glucose, and NIHSS were similar, but patients with leukocytosis were more likely to be female (p=0.049). No difference in ΔNIHSS from admission to 24hr post-tPA was detected in patients with leukocytosis (or elevated neutrophils or lymphocytes) compared to those with normal WBC counts. Patients with leukocytosis had similar frequencies of sICH, neurological deterioration, and length of stay and similar median mRS scores. The ΔNIHSS from admission to discharge was significantly greater (p=0.0044) in patients with leukocytosis, but other outcomes were similar (sICH, neurological deterioration, length of stay, and mRS). Conclusions: At our center, patients with AIS and leukocytosis at the time of IV rt-PA had similar improvement in NIHSS when compared to those with normal WBC counts, arguing against a deleterious interaction. The improvement in NIHSS score by discharge and higher frequency of favorable discharge disposition requires validation and further exploration. Disclosure: Dr. Gillette has received research support from the Infectious Disease Society of America. Dr. Siegler has nothing to disclose. Dr. Kumar has nothing to disclose. Dr. Boehme has nothing to disclose. Dr. Martin-Schild has nothing to disclose. Dr. Albright has nothing to disclose.

Systemic Hematologic Status Following Intraventricular Recombinant Tissue-Type Plasminogen Activator for Intraventricular Hemorrhage

Background and Purpose— This is the first prospective evaluation of changes in systemic hematologic status following administration of intraventricular recombinant tissue-type plasminogen activator in patients with intraventricular hemorrhage (IVH). Methods— Laboratory data from subjects enrolled onto the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) Trials were analyzed. We analyzed pre- and post- recombinant tissue-type plasminogen activator dosing coagulation parameters. Longer-term changes in hematologic status were studied in subjects who received the study agent after blood clot in the third/fourth ventricles had resolved radiologically. Results— Plasma fibrinogen increased significantly in both treatment groups. Dosing did not have a significant impact on any systemic coagulation parameters in either treatment group. Conclusions— Intraventricular recombinant tissue-type plasminogen activator is unlikely to impact systemic coagulation or to compound the effects of systemic anticoagulation for deep venous thrombosis prophylaxis. Clinical Trial Registration— URL: http://clinicaltrials.gov . Unique identifier: NCT00650858.

Low-Dose Intravenous Recombinant Tissue-Type Plasminogen Activator Therapy for Patients With Stroke Outside European Indications

The purpose of this study was to determine the safety and efficacy of intravenous recombinant tissue-type plasminogen activator (0.6 mg/kg alteplase) within 3 hours of stroke onset in Japanese patients outside the indications in the European license. Of the 600 patients who were treated with recombinant tissue-type plasminogen activator, 422 met the inclusion criteria of the European license (IN group) and 178 did not (OUT group). The OUT group was inversely associated with any intracerebral hemorrhage (adjusted OR, 0.50; 95% CI, 0.29-0.84), positively associated with an unfavorable outcome (2.48; 1.55-3.94) and mortality (2.04; 1.02-4.04), and not associated with symptomatic intracerebral hemorrhage (0.53; 0.11-1.79) or complete independency (0.65; 0.40-1.03) after multivariate adjustment. Functional and vital outcomes 3 months after low-dose recombinant tissue-type plasminogen activator in patients outside the European indications were less favorable compared with those included in the indications; however, the risk of intracerebral hemorrhage was not.

Tissue Plasminogen Activator for Stroke and Concomitant Influenza Infection

See related article, pages 783–791. In individuals with a given vascular risk profile, the occurrence of stroke is not equally distributed over time. In fact, there are trigger factors that temporarily increase the risk of stroke. Acute and exacerbating chronic infections are among such trigger factors. Mainly respiratory tract infections and both bacterial and viral infection appear to be important in this respect.1 Influenza virus infection is among the infections that play a relevant role, probably not only by direct viral infection, but also through bacterial superinfections. Large epidemiological surveys had shown that the mortality from cardiovascular disease and stroke increases in temporal association with influenza epidemics and that vascular disease contributes to a large degree to influenza-related mortality.2 Furthermore, case–control and large observational studies reported that influenza vaccination is associated with reduced hospitalization for and mortality of stroke and myocardial infarction.3,4 Although causality is not firmly proven, it is very likely that influenza vaccination exerts protective effects regarding vascular diseases and therefore recent guidelines on secondary prevention for cardiovascular diseases have included influenza infection.5 Infection, thrombosis, and ischemic stroke are potentially linked with each other by a multitude of connective …

Interleukin-1β, Calcium-Sensing Receptor, and Urokinase Gene Polymorphisms in Korean Patients with Urolithiasis

PurposeThere are various causes of ureter calculi, and genetic factors are known to play a role. Interleukin-1β (IL-1β) and calcium-sensing receptor (CaSR) genes are related to hypercalciuria, and urokinase is related to the formation of calcium oxalate stones. This study investigated polymorphisms in IL-1β, CaSR, and urokinase in patients with urolithiasis and healthy controls.Materials and MethodsUrolithiasis patients treated at Chung-Ang University Hospital were enrolled from January 2007 to December 2008. The control group of volunteers displayed normal urinalysis findings in the health screening, no stones identified by ultrasonography, and no history of urolithiasis. DNA extracted from peripheral blood was analyzed by the polymerase chain reaction. Patients were genetically screened for mutations in IL-1β (484 urolithiasis patients, 208 controls), CaSR (433 urolithiasis patients, 197 controls), and urokinase (370 urolithiasis patients, 167 controls). Stone metabolic study was done to see the differences between the metabolic factors and to discern normal genes from polymorphic genes.ResultsAccording to the genotype frequency and allele frequency analysis, there were no statistically significant differences between IL-1β, CaSR, and urokinase genes. Also, the analysis between genotypes and metabolic factors did not show statistically significant differences between the three genes.ConclusionsIn Korean urolithiasis patients, IL-1β, CaSR, and urokinase gene polymorphisms do not differ from those of healthy individuals. A larger-scale study is needed to confirm the need for other genetic markers of urolithiasis.

Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L)

Induced hypothermia is a promising neuroprotective therapy. We studied the feasibility and safety of hypothermia and thrombolysis after acute ischemic stroke. Intravenous Thrombolysis Plus Hypothermia for Acute Treatment of Ischemic Stroke (ICTuS-L) was a randomized, multicenter trial of hypothermia and intravenous tissue plasminogen activator in patients treated within 6 hours after ischemic stroke. Enrollment was stratified to the treatment time windows 0 to 3 and 3 to 6 hours. Patients presenting within 3 hours of symptom onset received standard dose intravenous alteplase and were randomized to undergo 24 hours of endovascular cooling to 33°C followed by 12 hours of controlled rewarming or normothermia treatment. Patients presenting between 3 and 6 hours were randomized twice: to receive tissue plasminogen activator or not and to receive hypothermia or not. Results- In total, 59 patients were enrolled. One patient was enrolled but not treated when pneumonia was discovered just before treatment. All 44 patients enrolled within 3 hours and 4 of 14 patients enrolled between 3 to 6 hours received tissue plasminogen activator. Overall, 28 patients randomized to receive hypothermia (HY) and 30 to normothermia (NT). Baseline demographics and risk factors were similar between groups. Mean age was 65.5±12.1 years and baseline National Institutes of Health Stroke Scale score was 14.0±5.0; 32 (55%) were male. Cooling was achieved in all patients except 2 in whom there were technical difficulties. The median time to target temperature after catheter placement was 67 minutes (Quartile 1 57.3 to Quartile 3 99.4). At 3 months, 18% of patients treated with hypothermia had a modified Rankin Scale score of 0 or 1 versus 24% in the normothermia groups (nonsignificant). Symptomatic intracranial hemorrhage occurred in 4 patients (68); all were treated with tissue plasminogen activator <3 hours (1 received hypothermia). Six patients in the hypothermia and 5 in the normothermia groups died within 90 days (nonsignificant). Pneumonia occurred in 14 patients in the hypothermia and in 3 of the normothermia groups (P=0.001). The pneumonia rate did not significantly adversely affect 3 month modified Rankin Scale score (P=0.32). This study demonstrates the feasibility and preliminary safety of combining endovascular hypothermia after stroke with intravenous thrombolysis. Pneumonia was more frequent after hypothermia, but further studies are needed to determine its effect on patient outcome and whether it can be prevented. A definitive efficacy trial is necessary to evaluate the efficacy of therapeutic hypothermia for acute stroke.

Efficacy of anterior inferior cerebellar artery infusion of urokinase in sudden vascular deafness

Objective To observe the efficacy of superselective trans⁃microcatheter intra⁃anterior inferior cerebellar artery thrombolytic therapy with urokinase for patients with sudden vascular deafness. Methods Seventy ⁃ four cases of sudden vascular deafness were randomly treated by transarterial or transvenous urokinase thrombolytic therapy. After thrombolysis, low molecular weight heparin subcutaneous injection of 0.40 ml (2 times/d) and aspirin 100 mg oral (1 time/d) were given continuously for 7 days. Electric audiometry was performed at day 1, 3, 6, 10 to assess the efficacy. Results At day 10, the total effective rate of patients given with transarterial thrombolysis (intra⁃arterial group) was 84.21% (32/38), and the patients given with transvenous thrombolysis (intra⁃venous group) was 58.33% (21/36), the difference between two groups was significant (χ2 = 6.091, P = 0.014). The results of electric audiometry at different time points in intra⁃arterial group were all better than those in intra⁃venous group, the differences were all significant (P < 0.01, for all). Conclusion Superselective intra⁃arterial urokinase thrombolysis is probably an effective therapy for sudden vascular deafness. DOI：10.3969/j.issn.1672-6731.2010.02.017