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Introduction. The rate of intracerebral hemorrhage following thrombolytic therapy depends on the agent, dose, timing, route of administration, patient population, concomitant treatments, and the definition of hemorrhage used. Prior to the use of intravenous t-PA in stroke, it was found that intracranial hemorrhage occurred 1% or less in patients receiving thrombolytic therapy for myocardial infarction (Hunt et al 1992; Maggioni et al 1992; Simoons et al 1993; Gore et al 1995). Dose-escalation pilot studies demonstrated safety of rt-PA administration in acute ischemic stroke in the late 1980s (Brott et al 1992; del Zoppo et al 1992). The NINDS pilot study reported 3 symptomatic hemorrhages in 74 patients treated with doses of rtPA greater than 0.9 mg/kg within 90 minutes of symptom onset (Brott et al 1992). A great appreciation for hemorrhagic conversion of ischemic stroke following thrombolytic therapy can be accomplished through the following review of selected trials.|{picture:inhemjb1.bmp}{caption:Symptomatic intracerebral parenchymal hematoma after rtPA therapy (CT)}{label:(Left) A 62-year-old man with acute left hemiparesis became obtunded with vomiting and increasing weakness 1 hour after treatment with 0.95 mg/kg rtPA given over 90 minutes, and a right parietal hematoma was detected. Middle: A 65-year-old man developed a Cerebellar hematoma after infusion of 0.95 mg/kg rtPA over 1 hour in the setting of severe hypofibrinogenemia. (Right) A 63-year old woman with acute right hemiparesis and hemisensory loss became drowsy and vomited 1 hour after receiving 0.95 mg/kg of rtPA over 90 minutes, and a left thalamic hematoma was detected. (Used with permission from: Brott TG, Haley EC Jr, Levy DE, et al. Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992;23(5):632-40.)}| Three patients had asymptomatic hemorrhagic transformation.|{picture:inhemjb2.bmp}{caption:Hemorrhagic conversion without hematoma (CT)}{label:CT performed at 18 to 30 hours showed hemorrhagic transformation in 3 of 71 patients without hematoma. CT findings were not associated with neurologic deterioration. Right: Acute infarction involved the deep hemisphere; a well-circumscribed old left hemispheric infarction is also seen. Used with permission (Used with permission from: Brott TG, Haley EC Jr, Levy DE, et al. Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes. Stroke 1992;23(5):632-40.)}| In the Burroughs-Wellcome study treatment had to be started within 8 hours of stroke onset (Wolpert et al 1993). Of the 98 patients treated with varying doses of rtPA, 11 had a symptomatic hemorrhage.|{picture:inhemjb3.bmp}{caption:Parenchymatous hematomas in 11 patients (CT)}{label:In case 2, a hematoma occurred in the occipital lobe on the opposite side from the hemorrhagic infarct. In case 9, a hematoma occurred in the cerebellum, although the infarct involved the temporal lobe and adjacent opercula. Cases 2 and 10 could be classified as either hemorrhagic infarcts or parenchymatous hematomas. (Used with permission from: Wolpert SM, Bruckmann H, Greenlee R, Wechsler L, Pessin MS, del Zoppo GJ. Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rtPA Acute Stroke Study Group. AJNR Am J Neuroradiol 1993;14(1):3-13.)}| The only significant baseline predictor of hemorrhage in this study was treatment greater than 6 hours from symptom onset.
Intravenous thrombolytic therapy. The NINDS rtPA Stroke Study formed the basis for FDA approval of intravenous rtPA for acute ischemic stroke within 3 hours of symptom onset (National Institute of Neurological Disorders and Stroke r-TPA Stroke Study Group 1995). In this study, the total dose of rtPA was 0.9 mg/kg, with 10% of the dose given as an initial bolus, followed by the remaining 90% via intravenous infusion over one hour. All patients were treated within 3 hours of symptom onset, with half receiving treatment within 90 minutes. Symptomatic intracerebral hemorrhage attributable to study drug was defined as a CT-documented hemorrhage, which was temporally related to a change in the patient's clinical condition in the judgment of the clinical investigator within 36 hours from treatment onset. Of the 312 patients treated with rtPA, 6.4% of patients had a symptomatic intracerebral hemorrhage compared to 0.6% of placebo-treated patients. An additional 4.2% of patients treated with rtPA had an asymptomatic hemorrhage on a protocol-mandatory CT scan at 24 hours as compared to 2.8% of placebo patients. These rates of hemorrhage are very similar to the rates in the pilot NINDS studies in which patients were treated within 3 hours, but lower than in the other randomized thrombolytic studies in which the large majority of patients were treated after 3 hours (Table 1). A severe baseline neurologic deficit, as measured by the NIHSS, and the presence of edema or mass effect on the baseline CT scan were independently associated with an increased risk of symptomatic intracerebral hemorrhage in the NINDS trial (NINDS t-PA Stroke Study Group 1997). However, these patients were still likely to benefit from use of the medication.
Table 1. Incidence of Symptomatic Intracerebral Hemorrhage in Randomized Clinical Trials Using Thrombolytic Therapy in Acute Ischemic Stroke
No. of
Drug and dose
in treatment
in control
3 hours
rtPA 0.9 mg/kg
6 hours
1.5 million units
6 hours
rtPA 1.1 mg/kg
Australian Streptokinase Study**
4 hours
1.5 million units
6 hours
1.5 million units
0-3 hours
3-6 hours
rtPA 0.9 mg/kg
6 hours
6 mg +
500 IU/hr
for 4 hrs
6 hours
9 mg
3-5 hours
0.9 mg/kg
6 hours
0.9 mg/kg
3 hours
72 hour infusion
6 hours
72-hour infusion
3 to 4.5 hours
0.9 mg/kg
3 to 9 hours
6 hours
3 hours
8 hours
90 ìg/kg
125 ìg/kg
0.1 mg/kg in 25 patients
0.25 mg/kg in 25 patients
0.9 mg/kg in IV group vs. 0.6 mg/kg EV
Standard treatment vs. merci
* Symptomatic hemorrhage was defined as a CT-documented hemorrhage that was temporarily related to a change in the patient's clinical condition in the judgment of the clinical investigator.
** Parenchymal hemorrhage type 2 is considered symptomatic/major hemorrhage and is defined as greater than 30% of the infarcted area affected by hemorrhage with mass effect or extension outside the infarct.
*** Parenchymal hematoma-homogenous area of circumscribed hyperdensity, usually with a mass effect and sometimes with ventricular extension.
**** Hemorrhagic transformation associated with neurologic deterioration of 4 or more points on the NIHSS or 1 point deterioration in level of consciousness.
***** Hemorrhagic transformation associated with neurologic deterioration of 4 or more points on the NIHSS at 72 hours or causing death by 90 days.
‡ Streptokinase and aspirin in the treatment group and aspirin alone in the control group.
† The percentages reflect the parenchymal hematoma of larger extent in the intention-to-treat population.
Table 2 lists the most important potential risk factors for intracerebral hemorrhage associated with the use of thrombolytic therapy in stroke based on the various studies that are summarized in this review. Risks most frequently found to predict symptomatic intracerebral hemorrhage across multiple studies are early CT hypodensity, elevated serum glucose or history of diabetes mellitus, and severe baseline neurologic deficit, as measured by the NIHSS (Lansberg et al 2007a).
Table 2. Risk Factors for Intracerebral Hemorrhage in Patients with Acute Ischemic Stroke
Use of a thrombolytic agent
Dose of thrombolytic agent
Type of thrombolytic agent
CT findings of early infarction prior to treatment
Deeply ischemic brain tissue prior to treatment
Hyperglycemia or history of diabetes mellitus
High severity of stroke as determined by the NIHSS score
Longer time to treatment
Concomitant antithrombotic drug use
Older age
Deviation from established treatment protocols
Elevated systolic blood pressure prior to treatment
Prior antithrombotic drug use
Prior stroke
History of cardiac disease
History of hypertension
Non-smoking status
Magnetic resonance imaging characteristics
CT with leukoaraiosis
Increased matrix metalloproteinase -9 levels
Low platelet count
Low LDL levels
Low plasminogen activator inhibitor levels
In the European Acute Stroke Study (ECASS), where intravenous rtPA (1.1mg/kg) was provided within 6 hours of symptom onset, the risk of intracerebral hemorrhage was increased by 8.8% in the treatment group in the intention-to-treat analysis (Hacke et al 1995). Moderate to large regions of early cerebral infarction or a severe clinical deficit led to an increased risk of hemorrhagic transformation, whereas advanced age increased the risk of parenchymal hematoma (Hacke et al 1995; Larrue et al 1997). The rate of hemorrhage in ECASS was much higher than in the NINDS rtPA study, which may well be related to the rtPA dose (1.1 mg/kg, 100 mg maximum) that was substantially higher than in the NINDS rtPA study and most trials that followed. In the ECASS II, 800 patients were randomized to placebo or the current accepted 0.9 mg/kg dose of intravenous rtPA within a 6-hour time window (Larrue et al 2001). The rate of parenchymal hemorrhage was increased significantly in the treatment group as compared to the placebo group (8.1% vs. 0.8%); however, only 158 of the 800 patients were randomized in the 0 to 3 hour time window. Risk factors for intracerebral hemorrhage in ECASS II included large areas of hypodensity on the baseline CT scan, congestive heart failure, advanced age, and aspirin use prior to thrombolysis (Larrue et al 2001). The search for a longer treatment time window following stroke symptom onset was evaluated in the Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) studies. ATLANTIS-A and ATLANTAS-B evaluated the safety and efficacy of rtPA given between 0 and 6 hours after stroke onset, and between 0 and 5 hours post stroke onset respectively (Clark et al 1999; Clark et al 2000). An unacceptable rate of symptomatic intracerebral hemorrhage, which was as high as 11% in the treatment group, was found without clear benefit from treatment at 90 days. The relatively high hemorrhage rate in this study has been attributed to the prolonged treatment window (Clark et al 1999; Clark et al 2000).
A pooled analysis including 2775 patients from the above mentioned randomized placebo-controlled trials of intravenous rtPA indicated that there may be a clinical benefit up to 4.5 hours from symptom onset (Hacke et al 2004). This was put to the test in the ECASS III trial where efficacy and safety of intravenous rtPA between 3 and 4.5 hours after stroke symptom onset were evaluated (Hacke et al 2008). Treatment with rtPA significantly increased odds of a favorable outcome at 3 months (odds ratio 1.34, 95% confidence interval 1.02 to 1.76). Symptomatic intracerebral hemorrhage, defined as hemorrhage causally associated with a clinical deterioration of 4 or more points on the NIHSS or death, was 2.4% in the rtPA treatment arm and 0.2% in the placebo arm. Using the NINDS trial definition, the rate of symptomatic intracerebral hemorrhage in ECASS was 7.9% and 3.5% in the treatment and placebo arms, respectively. Of note, ECASS III also excluded patients older than 80 years, on oral anticoagulants, with NIHSS greater than 25, or with a history of diabetes and prior stroke. An observational study of patients treated with intravenous rtPA between 3 and 4.5 hours reported a 2.2% rate of symptomatic intracerebral hemorrhage at 7 days using the ECASS III definition (Wahlgren et al 2008a). Based on these trials, the American Heart Association/American Stroke Association (AHA/ASA) updated its guidelines in 2009 recommending intravenous rtPA for eligible patients with acute ischemic stroke up to 4.5 hours after symptom onset (del Zoppo et al 2009).
rtPA in clinical practice. Despite early concerns of a potentially higher risk of intracerebral hemorrhage associated with intravenous rtPA outside the clinical trial setting, several studies support a safety profile of rtPA in clinical practice that is comparable to the NINDS rtPA trial (Albers et al 2000; Tanne et al 2002). Following FDA approval of rtPA for ischemic stroke, Standard Treatment with Alteplase to Reverse Stroke study (STARS) and the Canadian Alteplase for Stroke Effectiveness Study (CASES), both aiming to show safety and efficacy of rtPA in clinical practice, found symptomatic intracranial hemorrhage (sICH) rates of 3.3% and 3.8%, respectively (Albers et al 2000; Shobha et al 2010). The SITS-MOST registry also reported that patients treated with intravenous rtPA 0 to 3 hours following onset of acute ischemic stroke in clinical practice were similar to those enrolled in clinical trials, with a rate of symptomatic intracerebral hemorrhage (using the NINDS rtPA trial definition) of 7.3% at 7 days (Wahlgren et al 2007).
Results from ECASS III also translate well to the community setting as seen in 104 patients treated with rtPA in the 3 to 4.5 hour window at one community hospital, giving rise to a 2.4% rate of sICH (Montano et al 2013). In a study of 50 stroke patients treated in 10 acute-care hospitals in Indianapolis, the authors found that sICH following rtPA occurred more often when protocol violations occurred (Lopez-Yunez et al 2001). A meta-analysis published by the Cochrane Database of Systematic Reviews in 2009 summarized the data of 26 randomized controlled trials completed by 2009 in 7152 acute stroke patients (Wardlaw 2009). Most of these trials tested intravenous thrombolysis up to 6 hours after symptom onset. Fifty-five percent of trials tested rtPA. Four trials evaluated intra-arterial thrombolysis. Overall, the odds of symptomatic intracranial hemorrhage were increased 3-fold (odds ratio 3.49, 95% confidence interval 2.81 to 4.33) in patients who received thrombolysis. In spite of this, there was a significantly reduced chance of poor outcome (combined death and dependency) during follow-up in patients who received thrombolytic therapy.
Multiple other thrombolytic agents – streptokinase, desmoteplase, tenecteplase, and ancrod – have been studied in randomized trials (Candelise et al 1995; Hommel et al 1995; Donnan et al 1996; Sherman et al 2000; Hacke et al 2005; Haley et al 2005; Furlan et al 2006; Hennerici et al 2006; Hacke et al 2009). However, these medications have not been approved for use in stroke patients because of safety concerns or a lack of established efficacy. Tenecteplase deserves special mention following recent completion of its phase 2B trial. After thrombolysis treatment of ischemic stroke, patients were carefully selected based on CT perfusion imaging (Parsons et al 2012). Tenecteplase was associated with significantly better reperfusion, improved clinical outcomes, and reduced symptomatic hemorrhagic conversion when compared to alteplase.
Endovascular therapy. Intra-arterial delivery of thrombolytic therapy and clot extraction would theoretically increase cerebral artery recanalization and decrease the likelihood of hemorrhage due to a lower required total tPA dose and less widespread effects of the agent. Although the reported lysis rates using endovascular delivery are higher than those reported for patients treated with intravenous thrombolytic agents, the rates of hemorrhage are similar to or greater than those in studies using intravenous rtPA within 3 hours of onset, even when performed by experienced individuals (Meyers et al 2011). A retrospective multicenter analysis comparing stroke patients treated with intravenous tPA to those treated with either intra-arterial thrombolysis or bridging intravenous plus intra-arterial therapy found an increased odds of sICH in patients receiving endovascular treatment (OR 3.47; 95% CI 1.19–10.01, p<0.05) after adjusting for baseline age, stroke severity, and stroke location (Singer et al 2009). Early studies looked at intra-arterial t-PA alternative therapy, such as Pro-urokinase in the Prolyse in Acute Cerebral Thromboembolism Trial Study I and II (PROACT I and PROACT II). PROACT I provided patients intra-arterial pro-urokinase (6 mg) and high-dose heparin (100 units/kg bolus followed by 1000 units/hour for 4 hours) and compared the results to a placebo group receiving high-dose heparin alone, resulting in an unacceptable 27% symptomatic intracerebral hemorrhage rate in the combined group and 20% for high-dose heparin alone (del Zoppo et al 1998). The PROACT II study randomized 180 patients with an acute middle cerebral artery occlusion of less than 6 hours duration (Furlan et al 1999). The treatment group received 9 mg intra-arterial pro-urokinase over 2 hours plus intravenous heparin 2000 units bolus and 500 units per hour infusion for 4 hours, whereas the placebo group received heparin only. A 15% absolute increase in favorable clinical outcome was found in the treatment group; however, an increased sICH rate was observed in 10% of the treatment group compared with 2% in the control group. Neither pro-urokinase nor urokinase are commercially available, resulting in use of tPA at many centers when intra-arterial administration is chosen as treatment for acute ischemic stroke due to large artery occlusion. Until recently, other than the early IMS trials, no published randomized controlled trials were available in the management of acute ischemic stroke comparing FDA approved intravenous tPA to more aggressive treatments such as intra-arterial (IA) tPA, mechanical devices, or combination intravenous t-PA with endovascular therapy.
The Interventional Management of Stroke Study evaluated intra-arterial rtPA given after a reduced "bridging" dose (0.6 mg/kg) of intravenous rtPA (IMS Study Investigators 2004). Eighty subjects were enrolled, and comparisons were made to match controls and rtPA-treated patients from the NINDS stroke study. The 6.6% rate of symptomatic intracerebral hemorrhage in treated patients was similar to those treated with intravenous rtPA in the NINDS trial. A second study evaluated this combined intravenous and intra-arterial approach to treatment of moderate to severe strokes within 3 hours of symptom onset (IMS II Trial Investigators 2007). Eighty-one patients were treated and compared to historical controls from the NINDS trial. This trial reported a symptomatic intracerebral hemorrhage rate of 9.9%, similar to other studies. A large multicenter study retrospectively analyzed data from 645 stroke patients treated with intravenous, intra-arterial, and intravenous plus intra-arterial thrombolysis (Singer et al 2009). This study reported DWI lesion volume on pretreatment MRI, and intra-arterial or intravenous plus intra-arterial thrombolysis independently predicted symptomatic intracerebral hemorrhage. Patients treated with intra-arterial or intravenous plus intra-arterial were 3.5 times more likely to develop symptomatic intracerebral hemorrhage than those treated with intravenous alone (Singer et al 2009). The IMS-3 trial randomized acute stroke patients within 3 hours of symptom onset to intravenous tPA alone or intravenous tPA followed by endovascular therapy. Surprisingly, clinical outcomes were similar in both groups, as were sICH rates of 5.9% and 6.2% in the placebo and study groups respectively (Broderick et al 2013). The Synthesis Expansion trial attempted to randomize patients within 4.5 hours of stroke onset into either an endovascular group where any type of accepted intervention was allowed or a control group where intravenous t-PA alone was provided. Results of this trial surprisingly showed no difference in outcome nor in sICH rates (6% in both groups) (Ciccone et al 2013).
Mechanical thrombolysis and thrombectomy have historically been shown in several uncontrolled trials to promote arterial recanalization. These endovascular techniques may be used alone or in combination with intravenous or intra-arterial administration of thrombolytic drugs. Currently, there are 2 catheter systems, the Merci Retriever® (Concentric Medical, Inc., Mountain View, CA) and the Penumbra System® (Penumbra, Inc., Alameda, CA), as well as 2 retrievable stents, Solitaire™ FR Revascularization Device and Trevo Device retrievable stents, which are often used for revascularization of patients with acute ischemic stroke secondary to large vessel occlusive disease.
The MERCI trial evaluated the safety and efficacy of the Merci clot retriever system in the treatment of ischemic stroke patients with a large vessel occlusion within 8 hours of symptom onset who were not eligible for intravenous rtPA (Smith et al 2005). Embolectomy using the Merci catheter was associated with a 7.8% rate of symptomatic intracerebral hemorrhage in the MERCI trial, defined as intracranial bleeding within 24 hours of treatment leading to a clinical worsening of greater than 4 points on the NIHSS or death. A second trial (Multi MERCI) reported a 9.8% rate of symptomatic intracerebral hemorrhage after embolectomy (Smith et al 2008). The Multi MERCI trial included patients that had persistent occlusions after standard dose intravenous rtPA and allowed adjuvant intra-arterial rtPA. Neither of these trials had a control arm; however, mechanical thrombectomy using the Merci Retriever was associated with significantly higher rates of recanalization (MERCI 46%, Multi MERCI 69.5%) than reported in the placebo arm of PROACT II (18%).
The Penumbra catheter was evaluated in a single-arm study of patients with acute ischemic stroke within 8 hours of symptom onset with a treatable intracranial large vessel occlusion (Penumbra Pivotal Stroke Trial Investigators 2009). Patients that were refractory to intravenous rtPA were included. Successful recanalization was reported in 81.6% of treated vessels, whereas sICH was reported in 11.2% of patients. MR Rescue was then designed with a goal to compare patients receiving Merci clot retriever or Penumbra system to standard treatment, with each group further divided in those with good MRI penumbral patterns (small infarct core and substantial salvageable brain tissue) and those without (large infarct core with little to no salvageable tissue). Despite an advanced imaging protocol with potential to improve selection of thrombolytic candidates, outcomes and sICH rates were similar in all groups (Kidwell et al 2013). Findings in both the IMS-3 and MR Rescue investigations correlate with current acute stroke management guidelines that strongly recommend use of intravenous rt-PA in eligible patients presenting within 4.5 hours of stroke symptom onset, only allowing consideration of endovascular therapies in cases where IV tPA was contraindicated or already administered (Jauch et al 2013).
Both the Solitaire™ FR Revascularization Device and Trevo Device retrievable stents show promise given the reportedly high recanalization rates with a low 6.7% incidence of symptomatic hemorrhage when used to treat acute ischemic stroke. However, only a limited number of case series are available to demonstrate this (Novakovic et al 2012). Although not heavily studied in randomized trials, these "stentrievers" did make their way on the scene in the later years of the IMS-3 investigation (Chimowitz 2013). Stent retrievers are thought by many experts to be underrepresented in IMS-3 and are deserving of further investigation in early post-stroke symptom onset windows.
Potential risk factors for post-thrombolysis symptomatic intracerebral hemorrhage.Following publication of a number of studies attempting to identify clinical predictors of post-thrombolysis symptomatic intracerebral hemorrhage, a systematic review of the literature identified a few risk factors that have repeatedly been associated with this dreaded complication (Lansberg et al 2007a). Lansberg and colleagues identified 12 studies that met their inclusion criteria, of which CT characteristics, elevated serum glucose or history of diabetes, and elevated NIHSS repeatedly were found to be independently associated with post-thrombolysis symptomatic intracerebral hemorrhage (NINDS t-PA Stroke Study Group 1997; Demchuk et al 1999; Jaillard et al 1999; Barber et al 2000; Dubey et al 2001; Kase et al 2001; Larrue et al 2001; Tanne et al 2002; Hill and Buchan 2005; Cocho et al 2006). Advanced age, increased time to treatment, high systolic blood pressure, low platelet count, history of congestive heart failure, low plasminogen activator inhibitor levels, prior antiplatelet use, non-smoking status, low density lipoprotein levels, MRI characteristics, and deviations from treatment protocols have also been associated with post-thrombolysis sICH in various publications, (Larrue et al 2001; Gilligan et al 2002; Selim et al 2002; Tanne et al 2002; Ribo et al 2004; Hill and Buchan 2005; Bang et al 2007; Marti-Fabregas et al 2007; Uyttenboogaart et al 2008; Wahlgren et al 2008b; Mokin et al 2012). However, not all risks were consistently replicated in follow up studies. The following are potential post-thrombolysis sICH risks selected for further review:
Elevated serum glucose and history of diabetes mellitus were identified to independently predict hemorrhage in stroke patients treated with thrombolytic therapy (NINDS t-PA Stroke Study Group 1997; Bruno et al 2002; Arnold et al 2014), as well as lead to worse outcomes 3 months post stroke (Putaala et al 2011). The exact pathophysiologic connection between glucose and post-thrombolysis hemorrhage is unclear. Current American Stroke Association guidelines recommend maintaining blood glucose within the 140 to 180 mg/dL range during hospitalization for acute stroke (Jauch et al 2013); however, no guidelines are available regarding glucose management during tPA administration (Hafez et al 2014).
Several studies have independently shown that stroke severity, as rated by high NIHSS scores, is associated with an increased risk of post-thrombolysis hemorrhage (NINDS t-PA Stroke Study Group 1997; Dubey et al 2001; Cocho et al 2006; Cucchiara et al 2009). Despite a higher risk of hemorrhage, patients with severe strokes are still more likely than not to benefit from thrombolytic therapies (NINDS t-PA Stroke Study Group 1997). Ischemic stroke patients 80 years of age and older treated with thrombolysis had almost 3 times the likelihood of sICH development in the NINDS trial (Longstreth et al 2010). Despite being chosen as an exclusion criterion in treatment within the 3 to 4.5 hour poststroke window in ECASS III, age alone has not been shown to offset the benefits of thrombolysis in stroke patients within 3 hours of onset.
Prior antiplatelet use may increase the rate of thrombolytic-associated intracerebral hemorrhage. Reports of acetylsalicylic acid (ASA) use preceding intravenous tPA-treated strokes have provided conflicting results (Anonymous 1997; Larrue et al 2001; Tanne et al 2002; Uyttenboogaart et al 2008). Patients receiving dual antiplatelet therapy with acetylsalicylic acid and clopidogrel may have particularly greater risk of thrombolysis-related sICH (Cucchiara et al 2009). In the SITS-MOST database, the rates of sICH were reported to be: 1.1% for antiplatelet naïve patients, 2.5% for any antiplatelet use, 2.5% for acetylsalicylic acid monotherapy, 1.7% for clopidogrel monotherapy, 2.3% for acetylsalicylic acid plus dipyridamole, and 4.1% for acetylsalicylic acid and clopidogrel (Diedler et al 2010). Although the rate of sICH is higher in the acetylsalicylic acid and clopidogrel cohort, this is still below the sICH rate reported in previous clinical trials and should not exclude otherwise appropriate patients from acute therapy.
A majority of stroke patients that are tPA candidates present with elevated blood pressure; however, high rates of sICH have been shown in those patients with high pre and post tPA treatment blood pressure recordings (Wahlgren et al 2008; Lansberg et al 2007). High risk of sICH has occurred in studies where elevated blood pressure was found during the initial 24 hours following thrombolysis (Derex et al 2005). Guidelines have thus evolved over the years to allow aggressive therapies in order to obtain blood pressure readings lower than 185/110 prior to treatment with tPA (Jauch et al 2013). National Get With the Guidelines-Stroke Registry (GWTG-Stroke) and Joint Commission Stroke requirements have guided participating hospitals to focus on reducing time between onset of stroke symptoms to thrombolytic treatment. As stroke centers continue to strive for rapid tPA treatment times, a national trend towards reduction of post thrombolysis sICH has transpired, supporting continued maintenance of efficient stroke protocols (Saver et al 2013).
Imaging characteristics. Several studies have demonstrated an increased risk of intracerebral hemorrhage following intravenous rtPA treatment in patients with evidence of early infarct signs on CT (NINDS t-PA Stroke Study Group 1997; Demchuk et al 1999; Jaillard et al 1999; Barber et al 2000; Dubey et al 2001; Larrue et al 2001; Tanne et al 2002; Cucchiara et al 2009). These early ischemic changes include hypoattenuation of the brain parenchyma, loss of cortical grey-white junction differentiation, and swelling with sulcal effacement. The risk of symptomatic intracerebral hemorrhage was increased in rtPA-treated patients with prominent signs of edema or mass effect on the baseline CT in the NINDS rtPA Stroke Trial (Patel et al 2001). The Alberta Stroke Programme Early CT Score (ASPECTS) is a quantitated CT score that helps predict functional outcome and intracerebral hemorrhage risk following thrombolytic therapy for acute ischemic stroke (Barber et al 2000). This score quantifies early ischemic CT changes in patients with anterior circulation strokes by subtracting points for each area of hypodensity. Several studies have correlated lower ASPECTS with higher rates of post-thrombolysis hemorrhage (Tanne et al 2002; Dzialowski et al 2006). Leukoaraiosis on CT of the brain is associated with an increased risk of symptomatic hemorrhagic transformation and worse clinical outcomes in tPA-treated stroke patients when compared to patients without leukoaraiosis (Aries et al 2010); however, rtPA should not be withheld in such cases. Despite increased risk of sICH in patients with subtle but common early infarct signs on CT, such imaging findings should not prevent an otherwise eligible patient from being treated with thrombolytic therapy where favorable outcome usually outweighs risk.
Similar to CT studies, investigators have been interested in specific MRI parameters that might identify patients who are at an increased risk for hemorrhagic transformation of an ischemic infarct in the setting of thrombolytic therapy. DWI lesion volumes predicted sICH in a retrospective analysis of patients treated with both intravenous and intra-arterial thrombolytics (Singer et al 2009). Larger infarct volumes, as measured by DWI, and reperfusion status have been shown to independently predict symptomatic intracerebral hemorrhage in patients enrolled in a study of rtPA between 3 and 6 hours identified to have a perfusion-diffusion mismatch on pretreatment MRI (Lansberg et al 2007b). In fact, thrombolysis and restoration of blood flow to ischemic brain with pretreatment regions of very low cerebral blood flow on perfusion weighted imaging was strongly associated with parenchymal hemorrhage (Campbell et al 2013). When ASPECTS is applied to DWI (DWI-ASPECTS), lower scores are associated with post tPA sICH as would be expected, whereas higher DWI-ASPECTS is not without risk (Nezu et al 2010). ASPECTS + W (DWI-ASPETS with DWI white matter scoring system) may be a better predictor of sICH risk following tPA (Kawano et al 2012).
Other potential MRI post-thrombolysis sICH predictors include use of T2* weighted MRI imaging and fluid-attenuated inversion recovery (FLAIR) sequences. Microbleeds on pretreatment T2* MRI sequence are associated with new post-treatment microbleeds and subsequent increased sICH (Kimura et al 2013). FLAIR hyperintensity on MRI seen within hours of stroke onset is thought to be associated with infarction that has evolved beyond the opportunity for thrombolysis; however, other studies have not validated sICH risk when FLAIR hyperintensities are seen in thrombolysed patients 3 to 6 hours after stroke onset (Campbell et al 2011).
A recent stroke within 3 months of an acute infarction is a contraindication to treatment with intravenous thrombolysis because of a perceived risk of increased hemorrhage risk into necrotic tissue. Up to 50% of patients who've experienced a transient ischemic attack have diffusion-weighted positive areas of subclinical infarction on MRI (Redgrave et al 2007). There may be an increased risk of hemorrhagic transformation with thrombolysis in stroke patients who report a recent transient ischemic attack; however, one study reported the rate of sICH in this group to be 8.3% (McKinney et al 2012), and another reported no influence of recent transient ischemic attack on post-thrombolysis outcomes (de Lecinana et al 2010).
Risk scores for predicting post-thrombolysis intracerebral hemorrhage. Several groups have proposed risk-scoring systems to better quantify the hemorrhagic risk associated with thrombolytic treatment of acute ischemic stroke. The Multicenter Stroke Survey Scale was developed using markers identified in the Multicenter rtPA Stroke Survey of post-thrombolysis risk factors (Tanne et al 2002; Cucchiara et al 2008). The risk factors used in this scale are age greater than 60 years, NIHSS greater than 10, admission serum glucose greater than 150 mg/dL, and platelet count less than 150,000. This scoring system was both developed and tested using the Multicenter rtPA Stroke Survey data set and has not been validated in an independent prospective cohort. The rate of symptomatic intracerebral hemorrhage using this tool was 0%, 5%, 4%, and 18% for 0, 1, 2, and 3 or more risk factors present, respectively (Cucchiara et al 2008). The Hemorrhage After Thrombolysis (HAT) Score was developed using a combination of previously published markers of increased post-thrombolysis hemorrhage risk that provided the highest predictive ability in their cohorts (Lou et al 2008). Using this method, the authors identified a history of diabetes or admission glucose above 200 mg/dL, pretreatment NIHSS, and early CT hypodensity as the most important risk factors. The rate of symptomatic intracerebral hemorrhage using this scale was 2%, 5%, 10%, 15%, and 44% for HAT Scores of 0, 1, 2, 3, and more than 3, respectively. This scale was largely derived and refined from the NINDS trial data set and has only independently been validated in a single small cohort of patients at the authors' institution. The GRASPS score assigns points for hemorrhagic risks, including glucose at presentation (G), race (Asian) (R), age (A), sex (male) (S), systolic blood pressure (P), and stroke severity (S) based on the NIHSS score. GRASPS is the first prediction tool validated in a large national data set that is available to assist clinicians in determination of symptomatic intracerebral hemorrhage risk following treatment with intravenous tPA (Menon et al 2012). Additional scores include SEDAN (sugar, early infarct signs, dense artery, age, NIHSS) (Strbian et al 2012a), THRIVE (with high scores correlating with older age, higher NISS, and whether or not patients have hypertension, diabetes, and/or atrial fibrillation) (Flint et al 2013), and DRAGON (dense artery, rankin score, age, glucose, onset to treatment time, and NIHSS) (Strbian et al 2012b).
Initially, it was thought that clinical risk-scoring schemes could provide clinicians with an additional tool to better estimate the risks associated with thrombolytic treatment in an individual patient. A recently published analysis of the Third International Stroke Trial looked at scoring potential of the above mentioned scores as well as several others, as they pertain to prediction of sICH and overall outcome. Patients were found to have more benefit than risk when treated with tPA regardless of concerning sICH prediction scores, and clinical prediction scores may not play nearly as much of a role in patient selection for tpa treatment as initially thought (Whiteley et al 2014).


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American Experience 1988 | TV Show Watchlist
Season 8, Episode 6 The Battle Over Citizen Kane
First Aired: January 29, 1996
"The Battle over `Citizen Kane' " chronicles how the fates of director Orson Welles and William Randolph Hearst collided after Welles painted a thinly disguised portrait of the publishing magnate in the film "Citizen Kane." Included: Welles' rise in theater and radio; the far-reaching power of Hearst's empire. Richard Ben Cramer narrates.
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- Premiered: October 4, 1988
- Rating: TV-PG
- Premise: This much-honored PBS documentary series explores American history, one topic or person at a time. Its Peabody Award winners include profiles of FDR and Malcolm X, and such diverse topics as Nixon's 1972 trip to China, the controversy surrounding `Citizen… (more)
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RELEASE: Administration Can Take Five Actions to Protect Us from Pollution Now
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Washington, D.C. — In the wake of this week's historic presidential victory, the Center for American Progress released "Administration Can Take Five Actions to Protect Us from Pollution Now," an analysis that outlines the five major actions President Barack Obama's administration can take before the start of his second term to protect our nation's public health from the ravages of pollution.
The proposed Environmental Protection Agency air pollution rules can produce net economic benefits of $70 billion to $187 billion dollars a year through the reduction of mercury and air toxins in power plants, industrial boilers, incinerators, and cement kilns. These economic benefits include lower healthcare costs due to the 12,540 hospitalizations and 199,000 asthma aggravation cases that would be avoided annually. Children and seniors are most vulnerable to respiratory infections due to ozone, and long-term exposure to soot can cause premature death, heart attacks, strokes, cancer, infant mortality, and low birth weight.
The CAP analysis lists five major and essential EPA rules to protect public health that the administration should finalize immediately:
- Reduce carbon pollution from new power plants, a measure which was supported by nearly 3 million comments sent to the Department of Energy in favor of the rule for both new and existing power plants
- Reduce hazardous pollution from industrial boilers—a rule which has been delayed since 2003. EPA estimates that Americans would receive $12 to $30 in health benefits for every dollar spent to reduce these pollutants
- Reduce smog pollution from cars, light trucks, and gasoline. The National Association of Clean Air Agencies estimates that anticipated reductions of sulfur in gasoline would be the equivalent of removing 33 million light cars and trucks off the road
- Modernize protection from soot. This new rule would improve public health and visibility by swiftly limiting short-term soot exposure
- Improve clean air quality standards for cement manufacturing—one of the largest industrial sources of mercury pollution in our nation. The EPA estimates that the rule would eliminate 92 percent of the mercury and fine-particulate soot emissions from cement kilns.
While many of these vital proposed health safeguards have been put in administrative limbo, finalizing these rules would clear the regulatory slate and enable the administration to focus on a climate-change and pollution-reduction agenda beginning in January. Reducing carbon pollution from existing power plants and strengthening ozone smog health standards to provide protection for children and seniors can be a major legacy of President Obama's second term.
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Carradice, Daniel MD (Hons), MBChB, MRCS; Wallace, Tom MBChB, MRCS; Gohil, Risha MBChB, MRCS, MSc; Chetter, Ian MD, MBChB, FRCS
Objective: To test the hypothesis that patients with soft tissue changes related to superficial venous insufficiency (SVI) have greater benefits from treatment than those with only symptomatic varicose veins.
Background: A commonly held view is that SVI is only a minor ailment, yet randomized clinical trials (RCTs) show that treatment improves quality of life (QoL) and is cost-effective. In an effort to curb the treatment costs of this common disorder, rationing is applied in many health care systems, often limiting the reimbursement of treatment to those with soft tissue changes.
Methods: This cohort study draws its data from an interventional RCT. After informed consent, consecutive patients with symptomatic unilateral SVI were randomized to receive surgical ligation and stripping or endovenous laser ablation. This analysis differentially studies the outcomes of patients with simple varicose veins (C2: n = 191) and soft tissue complications (C3–4: n = 76). Effectiveness outcomes measured up to 1 year included the following: Qol [short form 36 (SF36), EuroQol, and the Aberdeen Varicose Veins Questionnaire], clinical recurrence, and the need for secondary procedures. Multivariable regression analysis was used to control for potential confounding factors.
Results: Both groups saw significant improvements in QoL. All improvements were equal between groups apart from the SF36 domain of Bodily Pain, where C2 saw an improvement of 12.8 [95% confidence interval (CI): 4.8–20.8] points over C3–4 participants (P = 0.002), who also suffered more recurrence [odds ratio (OR) = 2.7, 95% CI: 1.2–6.1, P = 0.022] and required more secondary procedures (OR = 4.4, 95% CI: 1.2–16.3, P = 0.028).
Conclusions: This study suggests that rationing by clinical severity contradicts the evidence. Delaying treatment until the development of skin damage leads to a degree of irreversible morbidity and greater recurrence.
Trial registration: NCT00759434 Clinicaltrials.gov
© 2014 by Lippincott Williams & Wilkins.
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Upstate News
Darryl Geddes 315 464-4828
SUNY Upstate psychiatrist examines defiance in the family in new book
Defiance in children or adolescents is likely to occur when they lose faith in the adult world to care for them, suggests psychiatrist David Keith, M.D., in his new book, "Defiance in the Family: Finding Hope in Therapy" (Brunner-Routledge, 2001).
Keith will discuss his book Thursday, May 3 at 7:30 p.m. at Barnes and Noble Booksellers, 3454 Erie Boulevard East, Dewitt.
"Defiance is often an expression of a child or adolescent's distress about their family," said Keith, director of child and adolescent psychiatry and professor of psychiatry, family medicine and pediatrics at SUNY Upstate Medical University. "Parents may know intuitively that the child isn't the only problem, but they may be too anxious to articulate what else is wrong. The child's defiance is a successful way to divert attention away from other family problems. Punishment as a response has limits: it breeds only bitterness and brings more intense defiance."
What can change the defiance, Keith suggests, are therapy sessions involving all family members. These sessions should pay attention not only to the defiance, but to other stresses in and around the family, he said.
"The tendency for many therapists is to see the individual who is in the most distress, or the individual who is most available," he said. "My belief is that when the need for therapy is urgent, it is essential to include more family members at the therapy session."
But some families balk at the idea of sitting down with the therapist. "A parent who requests to have an adolescent seen alone may be concerned for the child's well being, while protecting an upsetting relationship," Keith said. "Other times, a parent may not want to expose nonproblem children to the situation. However, most children are relieved to come to a setting which will provide help for the situation. We can only underestimate how much children worry about their family and its members."
Keith maintains that therapy will likely fail if not all family members are included. "Clearly, there are so many more issues that cannot be addressed properly if only one parent is available," he said. "That parent's absence from the session might be indicative of the tension in the family."
Keith's book, co-written with Gary M. and Linda C. Connell, is a 224-page overview and analysis of what defiance is, how it arises in the family setting and what sort of therapeutic interventions are needed to resolve the problem. "Defiance in the Family" is written most specifically for practitioners who do therapy with families. However, it is a very readable book that would be of interest to anyone who deals with defiant children and adolescents, such as teachers, guidance counselors, and primary care practitioners. "Defiance in the Family" might also be helpful for parents as a consumer's guide on what to expect in a therapy session.
Keith notes that therapy sessions begin with the first phone call, in which the therapist sets the ground rules, such as requesting that all family members be in attendance. "This power diminishes as empathy for the family develops," he said.
The father, usually the family member who combines high rank and emotional distance, is interviewed first. The mother, who almost always is the expert on emotion and relationships in the family, is interviewed last. "Family members are less influenced by her views if they are kept until the end," he noted.
The middle stages of therapy, according to Keith, may bring into focus issues simmering under the surface, such as parental depression or marital dysfunction. The therapist's role is crucial in this stage to avoid the families desire, in some cases, to sabotage the therapist's effort to help.
Terminating therapy is most often up to the patient and family. In all cases, Keith suggests that the issue of ending therapy be discussed early. "It's usually the last question of the first session," he said. "A therapist will ask: 'Do you want to come back?'"
What should not be done, he said, is for the therapist to offer the false promise of greater progress should the sessions continue. "Families get what they need from therapy: When they are ready to take responsibility for their living it is time to end."
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Copyright ©2004 by the American College of Physicians
Purpose: To review reported inflammatory reactions occurring after initiation of highly active antiretroviral therapy (HAART) in persons infected with HIV-1 and to explore the mechanisms leading to these reactions.
Data Sources: MEDLINE search of biomedical literature reporting inflammatory reactions after HAART. Bibliographies of retrieved reports were also reviewed.
Study Selection: Articles describing patients infected with HIV-1 who had immunologic and virologic responses to HAART and subsequently developed inflammatory reactions.
Data Extraction: Data on the immune status, clinical characteristics, and therapeutic management of patients who were seropositive for HIV-1 and had inflammatory reactions after HAART.
Data Synthesis: Inflammatory reactions involving opportunistic infections, AIDS-associated malignant conditions, and other noninfectious diseases have recently been described in patients infected with HIV-1. These conditions often appeared shortly after the introduction of HAART and were associated with pronounced reductions in plasma HIV-1 viral load and increases in CD4+ T-lymphocyte counts. Clinical presentation was often atypical of that in patients with untreated HIV-1 infection, probably because of restored immunity. Most cases improved despite continuation of HAART, although some patients required anti-inflammatory drugs or specific antimicrobial agents.
Conclusions: Clinicians caring for patients who are infected with HIV-1 and receiving HAART must be aware of this new and diverse clinical syndrome. As more HAART recipients are studied, new presentations will probably be observed.
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AstrologyNotes Astrological Knowledge Base
Validity of astrology
The validity of astrology is a controversial subject. The case for and the case against astrology's objective validity are presented here. Astrologers argue that astrology works by a mechanism or mechanisms that are unknown to science, or perhaps outside of the scientific paradigm. They believe it is validated by their personal experience when applied in real life cases. Many argue that it does not make the hard predictions science requires, but informs the user of subtleties to decisions that would otherwise be missed. Skeptics see astrology as repeatedly failing to demonstrate its effectiveness in controlled studies.
- 1 How astrologers view astrology
- 2 How skeptics view astrology
- 3 Astrology hypotheses
- 4 The case against astrology
- 5 Sources
- 6 External links
How astrologers view astrology
Most astrologers, whether they believe astrology has objective validity or not, consider astrology to be a useful tool by which people may come to better understand themselves, others, and the world in general. Some argue that astrology's objective validity is a non-issue, and that astrology's primary value lies in the introspection and self-examination it may provoke. Others are quite insistent that astrology has objective validity.
Part of astrology's continued appeal may rest on its ability to link an individual's life to the wider cosmos, and so give a feeling of uniqueness, meaning, and connection to the totality of things. Many argue that astrology contains archetypal symbolism, which, according to some schools of thought (such as Jungian psychology), can be found universally throughout humanity.
Most astrologers make no claim to be practicing a science and see their skill as an art or spiritual discipline conferring a structure to a dialogue with their client. Rather than the mechanical prediction of events, an astrologer's success would need to be measured in terms of the happiness and well-being of his or her subjects.
How skeptics view astrology
Skeptics think that astrology should be considered a form of pseudoscience, attempting to lay claim to the prestige of science without submitting itself to the discipline of scientific method. Skeptics consider astrology to lack falsifiability.
Newspapers and mass-market magazines often publish horoscope columns with the title "Astrological Forecast," perhaps implying that they should be considered on the same footing with weather forecasts. However, astrology has so far failed carefully designed empirical tests of its predictive claims [1], unlike meteorology, which—although not always correct—has been proved to be significantly more accurate than what some astrologers have been able to produce so far.
As is often the case with pseudoscience, skeptics argue that the proponents of astrology respond to such disproof either by changing their claims, or by refusing to accept the scientific method as a valid test of their claims.
On the other hand, if scientific method is to be rejected entirely, many skeptics assert that the difficulty of disproving astrology lies in the disagreement between astrologers on an alternative method of verification.
Astrology hypotheses
A number of hypotheses have been put forward concerning the mechanism behind astrology:-
Synchronicity - The vast majority of western astrologers in the world today believe that astrology is a purely correlative study which reflects the underlying patterns in various systems, without any mechanism for a causal planetary influence needed at all. Proponents of this theory usually point to the work of the German psychiatrist Carl Jung, and his theory of synchronicity.
Fractals - Some astrologers suspect fractal associations between the geometry of events in the sky and those on Earth.
Chaos theory - It could be argued that the mechanism behind astrology might operate less in terms of Newtonian laws, and more in terms of chaos (e.g. a butterfly flapping its wings in Brazil leads to a tornado in Texas).
Gravitational influence - The argument that since the gravitational forces of the Moon cause the movements of the tides, then by extension they must also have an effect on human life, was one first put fourth by Claudius Ptolemy in his 2nd century work known as the Tetrabiblos. While today few believe that gravitational or tidal forces are the mechanism behind astrology, the idea that tidal forces affect biological organisms has some scientific support.
Frank Brown's Experiment
In 1954, a biologist named Frank Brown transported a shipment of oysters from New Haven, Connecticut several hundred miles away to Evanston, Illinois. Oysters open and close their shells in synchronization with the tide, and up until this time the accepted explanation for this phenomenon was simple—the physical force of the water gave the oysters some cue as to when to open and close their shells.
Dr. Brown placed his oysters in a controlled environment, and at first they responded as expected, opening and closing their shells in accord with the tide in New Haven. However, within a week, they began to get out of sync. Within two weeks, they had once again settled on a unanimous rhythm, opening and closing in correlation with the tidal forces of Evanston, despite the fact that there was no physical motion of water to prompt their action. Clearly, some mechanism in the oyster was "detecting" the tidal force.
One explanation advanced by biologists is that the Earth's magnetic fields are affected by tidal forces, and nearly all biological organisms (including humans) are affected by the Earth's magnetic field. While this has little bearing on the practice of astrology, it is strong evidence that tidal forces do indeed have an effect (albeit indirect) on living organisms.
The Mars effect
The Mars effect is based on some of the statistical analyses of French psychologist and statistician Michel Gauquelin published in the late 1960s. It claims that Mars occupies certain positions in the sky slightly more often (21%) at the birth of sports champions than at the birth of ordinary people (18%). Specifically, the claim is that sports champions are more likely to be born when Mars is rising in the eastern horizon or culminating in the upper meridian, known to astrologers as the ascendant and midheaven. Among hundreds of possible correlations Gauquelin tested, this was one of the most striking results that were found to statistically significant, but it was not the only one.
However, there is a problem with ambiguity (who qualifies as a "sports champion"?) known as the eminence factor, where the Mars effect only shows up in the most prominent athletes in their fields of prowess. Also, significant correlation does not prove that two variables are related or connected through some sort of causal mechanism per se. This is a common logical fallacy known as correlation implying causation.
The thirteenth zodiacal constellation explained
Many people cite the fact that there are 13 constellations of unequal size along the astronomical ecliptic, and not twelve equally-sized constellations, to try to discredit or otherwise disprove astrology. To astrologers, the size of the actual astronomical constellations is not an issue because most Western astrologers use the tropical zodiac, where the ecliptic is divided into 12 equal portions exactly 30 degrees each to get the 12 astrological signs. (12 signs x 30 degrees each sign = the 360 degrees of the ecliptic). The tropical zodiac is therefore aligned more with the seasons and the length of daylight in a given portion of the year during the course of the Sun's annual cycle.
Of the 13 modern signs of the zodiac (constellations of the ecliptic), Ophiuchus is the only one not counted as an astrological sign. Some astrologers argue that this is because the area of Ophiuchus intersected by the ecliptic previously belonged to more than one constellation. The constellations were redefined by the International Astronomical Union in 1930 and include a portion of Ophiuchus(Serpent-Bearer) on the ecliptic, to get 88 constellations. Prior to 1930 some areas of the sky did not belong to a constellation, forcing astronomers to refer to "the area between constellation X and constellation Y". Some areas, like the foot of Ophiuchus, belonged to more than one constellation. The modern constellation boundaries were defined to resolve this problem, so that every part of the sky belongs to one clearly defined constellation. However, Ptolemy recognised in ancient times that the sun passes through Opiuchus. Therefore some argue that, even by the ancient defintion, Opiuchus is a sign of the zodiac, and the arguments about the IAU 20th century redefinition of the constellations is specious: according to this view, the use by modern astrologers of only 12 signs is erroneous. This argument would only have bearing on the sidereal zodiac of the constellations, and not the tropical zodiac which is based on the seasons.
The case against astrology
Given that some astrologers claim to make predictions about future events, it should be possible to construct an experiment that measures its accuracy. No such experiment has ever demonstrated the objective validity of astrology. In addition, scientific double blind tests (example) have shown that many astrologers fare no better than random chance when matching astrological charts to personalities.
Here are some common arguments used by astrology skeptics.
Gravitational forces
There are various claims by astrologers that distant planets affect us through either gravitation, electromagnetism, or some other undetected force. However, scientifically we know of no force attributed to distant stars and planets capable or affecting our lives and personalities here on earth.
- It is pointed out that the moon causes tides on earth, and it is reasoned that the gravitational pull of other heavenly bodies affect us. This is invalid for the following reasons:
- The gravitational pull from e.g. Saturn, when calculated for its effect over an area the size of the human body, is equal to the gravitational pull from a car 1.7 meters away. Yet astrologers are uninterested in the positions of cars at the time of birth. In fact, the gravitational pull of Earth itself varies more from place to place than the gravitational pull of even the largest planets.
- If direction and strength of the gravitational field is important, then surely nearby massive objects (cars, mountains, houses) and the birthing position would play a greater role than distant planets.
- Astrology does not offer any explanation of how the gravitational pull from other planets, regardless of intensity, affects personality, nor why we are susceptible to gravitational influence during birth, nor how the gravitational influences at one point in the past affect our outlook for the future.
Magnetic influence
Another attempt at scientific explanation is that heavenly bodies affect the Earth's magnetic field, and that the magnetic field at the time of birth affects the person. To what extent this is true is largely irrelevant: The Earth's magnetic field is quite weak, and varies from 0.3 to 0.6 Gauss according to location. One would get a considerably stronger exposure to a magnetic field from an ordinary refrigerator magnet.
The question of distance
Astrology does not address how distance to a stellar object affects its astrological impact. If distance is relevant, astrological charts do not take it into account.
Extra heavenly bodies
Astrological charts do not consider all stellar objects, including planets, moons, and distant stars, although some fixed stars are included in most astrological systems.
Inconsistency of effect
Astrology shows an inconsistency on its terms. Assuming a theoretical force emanated by any celestial body, it is unclear how such a force could influence so differently two people located on Earth only hundreds of miles apart. Only the angle of incidence is left as a parameter. If this force exists, it shows a very singular behavior, unique in the physical laws, yet to be observed.
Astrological and astronomical zodiac differences
- The zodiac system used by astrologers has never fully aligned with the constellations. The tropical zodiac and the sidereal zodiac both divide the ecliptic into 12 equal portions of 30 degrees, but the constellations of the zodiac all vary in size, from 44 degrees across for Virgo to 20 degrees across for Cancer.
- The tropical zodiac used by most western astrologers begins at the vernal point, which gradually changes its position due to the precession of Earth's axis, known as the precession of the equinoxes. Over the course of 2000 years, the tropical zodiac has shifted about 24 degrees, so any celestial object said to be in one sign in the tropical zodiac will, upon observation of the present night sky, usually be found occupying the next zodiacal constellation.
- The sidereal zodiac, used by many eastern astrologers, currently deducts about 24 degrees to account for the precession of the equinoxes, but it still does not align perfectly with the constellations because the constellations are of unequal sizes, rather than each being 30 degrees across, as the sidereal zodiac requires.
- Many astrologers ignore this, while some consider (see [2]) the discrepancy between the tropical signs and the sidereal constellations is irrelevant because the astrological signs and constellations are considered by astrologers to be two distinctly different, non-equivalent things. The actual constellations are seldom used by western astrologers, except for those who use the sidereal zodiac or the fixed stars.
The thirteenth constellation: Ophiuchus
The constellation Ophiuchus, the serpent holder, was recognized by the ancient Greeks (although not as a specific sign), and is partially in the path of the ecliptic. It contains the sun once a year (in early December), and the planets at various other times. Even Ptolemy—one of the great astrologers of antiquity—recognized it as a constellation, but not as a tropical sign in it of itself.
Knowing about things which can not be changed. A paradox?
Many say that astrology does not necessarily claim complete immutability. Nonetheless a thought-provoking question can be raised: Future prediction necessarily implies a degree of immutability: it is the very reason which makes any prediction possible. But if the future is immutable, then what is the point of knowing what can not be changed?
- Gauquelin, Michel , The Cosmic Clocks, San Diego, CA: ACS Publications, (1967). Paperback version: Grafton Books, (1998) ISBN 0586081585
- Seymour, Percy The Scientific Basis of Astrology, W. Foulsham, Slough, U.K.: Quantum, (November 1997). ISBN 0-572-02181-X
- Wikipedia's article on the Validity of astrology - retrieved 12/25/2005 under the GNU Free Documentation License
External links
Non-skeptic sites
- Planetos is an online journal that contains many resources and papers that discuss Gauquelin's work as well as the Mars Effect controversy http://www.planetos.info/
- The full text of The Cosmic Clocks is available online at: http://www.astrologer.ru/rarebooks.html.en (in DjVU format - requires plug-in from http://www.djvu.com )
Skeptic sites
- Astrology and Science - A series of articles in which believers and skeptics debate the merits of astrology.
- The Magus of Magnetism BBC TV interview transcript in which scientist Dr. Percy Seymour defends his suport of astrology]
- The Astrotest - An account of a test of the predictive power of astrology, with references to other experiments.
- The True Disbelievers by Richard Kamann and Marcello Truzzi is a report of alleged internal events at CSICOP regarding their own claimed confirmation of M. Gauquelin's 'Mars Effect'
- The Skeptic's Dictionary on astrology
- The Skeptic's Dictionary on the Mars effect
- An Astrophysicist's Sympathetic and Critical View of Astrology - by Victor Mansfield.
- Proof of Astrology? - A critical look at Percy Seymour's books.
- Bad Astronomy: Misconceptions: Astrology - an "attempt to show that astrology has no basis in reality whatsoever", by Philip Plait
- RGCSA Research Group for the Critical Study of Astrology (UK). Has an extensive citation list of astrology validity research.
- The real romance in the stars - A critical view of astrology by Oxford scientist Richard Dawkins.
- Astrology theory and tests
- The Time Twin Study Refutation of astrology's claims.


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Pittsburgh Penguins (29-11-1) @ New Jersey Devils (16-16-8)
Root Sports, MSG Plus, NHLN-CA – 1:00 pm/et
Prudential Center – Newark, New Jersey
The Penguins officially enter the second half of the NHL season with a game in New Jersey.
Edit: Jaromir Jagr can tie Mario Lemieux in all-time points with a point today.
Say goodbye to 2013 everyone.
Leading Scorers:
Penguins: Sidney Crosby (22G, 36A: 58P)
Devils: Jaromir Jagr (13G, 21A: 34P)
Starting Goaltenders:
Penguins: Marc-Andre Fleury (22-9-1, 2.16 GAA, .920 Sv%)
Devils: Martin Brodeur (11-8-3, 2.31 GAA, .906 Sv%)
Official Previews from Team Websites: [Penguins] [Devils]
Last Games:
Penguins: Defeated Columbus Blue Jackets 5-3.
Devils: Defeated New York Islanders 2-1.
Opposition Blog: [In Lou We Trust]
What They're Saying: "Game Preview #41"
Sidney Crosby is the most dangerous player in the world and arguably the best in the world right now. The only thing he isn't top of the league in is in possession and even that has gone quite well for him. He leads the NHL in scoring with 22 goals and 36 assists in 41 games. Patrick Kane is five points back of Crosby and third place sits at 44 points. Short of a cold streak or an injury, Crosby has the inside track to lead the entire league in scoring again. But #87 is so dangerous because of his linemates. He usually rolls with Chris Kunitz, who's got 21 goals and 21 assists, and Pascal Dupuis. But Dupuis is injured. The answer? James Neal, one of the best shooters in the league. He's missed time due to injury and suspension but he's got 14 goals and 16 assists in 21 games. On Sunday, he was absolutely amazing alongside Kunitz and Crosby and was involved in all five of Pittsburgh's goals. The Devils may have the last change but it's really a case of hope to try and limit a dynamite trio like those three.
What Happened Last Time: December 13, 2013 – Pens won 3-2. [Our Recap]
The current top six is Crosby, Malkin, Kunitz, Megna, Jokinen and the remains of Pascal Dupuis. The defense is riddled with injuries. And yet they just keep winning games. A rather interesting trend developing is the Penguins surging out to large leads and then basically just playing with their food and hoping they don't choke. In this one, much like the San Jose game, they jumped out to a lead and hung on.
One thing that can't be disputed is the goaltending they are getting from Marc-Andre Fleury. He very well may be playing the best hockey of his career. It's something no one could have predicted except maybe that sports psychologist. In previous years, maybethe Penguins lose this game. But Fleury stole the third. Every time it seems the Pens are going to collapse, he's been steadying them.
Penguins Player(s) to Watch: Sidney Crosby, because he's Sidney Crosby.
Devils Player(s) to Watch: Jaromir Jagr, because he's Jaromir Jagr.
Gif that Seems Appropriate for Today's Game:
Pittsburgh Penguins lines from Daily Faceoff:
Chris Kunitz – Sidney Crosby – Joe Vitale
Chris Conner – Jussi Jokinen – James Neal
Chuck Kobasew – Brandon Sutter – Brian Gibbons
Tanner Glass – Zach Sill – Craig Adams
Brooks Orpik – Deryk Engelland
Matt Niskanen – Rob Scuderi
Robert Bortuzzo – Simon Despres
Marc-Andre Fleury
New Jersey Devils lines from Daily Faceoff:
Dainius Zubrus – Travis Zajac – Jaromir Jagr
Ryane Clowe – Adam Henrique – Michael Ryder
Patrik Elias – Stephen Gionta – Steve Bernier
Reid Boucher – Andrei Loktionov – Cam Janssen
Andy Greene – Mark Fayne
Bryce Salvador – Marek Zidlicky
Eric Gelinas – Jon Merrill
Martin Brodeur


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To the Editor.
—Though the article by Durkin and Durant in the March Archives (139:333-336,1979) may be a worthwhile contribution to the internal medicine literature, their observation concerning residual mass lesions following treatment for Hodgkin's disease is by no means an original realization. Most radiotherapists with substantial experience in the treatment of Hodgkin's disease have learned to anticipate that it is not unusual for a patient to have persistent fibrotic masses in a region of previous massive tumor involvement. As with the two cases reported by Durkin and Durant, this is most usually seen with the nodular sclerosing variety. In view of the relative frequency with which this phenomenon occurs, I would certainly be very skeptical of a recommendation of thoracotomy for a patient with a persistent mediastinal mass four months following mantle irradiation.For a concise and straightforward description of the phenomenon of persistent benign mass lesions following treatment
Thank you for submitting a comment on this article. It will be reviewed by JAMA Internal Medicine editors. You will be notified when your comment has been published. Comments should not exceed 500 words of text and 10 references.
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Firereel Film Festival May 1st-2nd
Hey guys check out Sands of Ikkera playing tomorrow at the Fire Reel Film Festival at the Cascade Theatre in Redding Ca. It will be in the local block starting... Read more
Sands of Ikkera BTS Trailer
Hello everyone we wanted to share our new teaser for Sands and the behind the scenes of the film that the DVD and Blu Rays will come... Read more
Tickets are online for purchase!
Follow the link below to get your ticket for the world premiere of Sands of Ikkera. Very limited seating so get yours soon!
Official Poster and more news!
We are hard at work with the final few weeks till our premiere night at the Valley 11 Cinemas in Anderson CA. With limited time and all our resources put into... Read more
Sands of Ikkera: Official Trailer
Well our official trailer is out and on to post work. We will be premiering our film in Redding CA in November and then off to film festivals.
The film... Read more
Teaming up with Speropictures!
Just wanted to let everyone know where we're at these days. The footage has been meticulously organized with notes from the director, the trailer is being tweaked and polished, and... Read more
Trailer coming soon!
We are currently in post production with Sands but wanted to say we will be releasing a trailer soon. Thank you everyone for your support and we will be releasing... Read more
"Sands of Ikkera" Filming Done!
We just got done with our two week shoot and could not of done it without our amazing cast and crew. Our next step post production and in the fall... Read more
110% Funded!!!
This morning we hit our fundraising goal! No more worries about not making it and the film not getting funded. Phew!
The extra 10%+ that has come in is going... Read more
97% Funded!!
Just wanted to post a little update here just to thank everyone who has been pledging and sharing. This has all happened because of you all. We really appreciate all... Read more
We've received this offer from a talented jewelry designer. If you add to your donation she will give you a gift double the amount your "added" pledge. We... Read more
Painting Armor!
We had a blast with the AMA yesterday, and since then we've been working painting our marauder armor! After working with the EVA foam and detailing it we put a... Read more
AMA Tuesday on Reddit
Tuesday the 10th at 12:00pm (PST) we will be posting an AMA (Ask Me Anything) on Reddit for anybody who wants to know about our film, what we do, anything! We... Read more
A Costume Beginning to Take Shape
We are blessed to have an amazing costume designer and seamstress on our team! She started what we are calling the "miner's cape" which is part of a disguise our... Read more
Cascade Theatre - A Marvelous Stretch Goal
We were privileged to have our short film "The Inbetween" screened at the Sundial Film Festival at the beautiful Cascade Theatre last night!
We not only hope to have a... Read more
The World of Ikkera
A land ravaged, a race nearly wiped out, the remnants struggle to survive, hoping to rebuild that which was lost.
The Name
The name "Ikkera" was discovered one day after... Read more
Marauder Mask 2 Progress
Busy busy all week!!! Here are some pics of our second marauder mask. Also we've been getting ready for the Sundial Film Festival this weekend at the Cascade Theater. Get tickets... Read more
Marauder Mask Progress!
We've been working hard and wanted to show some WIP pictures of one of our marauder masks.
Rifles and Pistols and Star Wars! Oh My!
So, this is Daniel fully decked out in his kit of Boba Fett inspired armor. He built it all himself (minus the helmet, although a custom helmet is an upgrade... Read more
Fabric for Costumes - Marauder Mask WIP
Our lovely costume designer came over today to present the fabrics we'll be using to create the original costumes.
We thought we'd share so you all can see it before... Read more
Snow Mobile = Hover Speeder
Hey everyone, we just wanted to make a quick update that we found a snowmobile to modify into our hover speeder! We will be gutting it, lifting it up and... Read more
Our Kickstarter Made the News!
Our campaign was featured as a story on our local Redding KRCR news channel! Needless to say, we are thrilled! It's a nice little story focusing on our love of... Read more


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Top Definition
A real sleazy dude who is always sneakin up and hittin on you.
Girrrrrrl, I just got creeped on by that creepdog over there at the bar. He came out of NOWHERE!
מאת Dina 15 בפברואר, 2005
Trending Now
Can you define these popular missing words?
Guy that has something "off" about him. He is weird, scary, perverted... just a huge creep.
That 50 year old that just hit on your little sister is a huge creep-dog
מאת 301 1 באוגוסט, 2006
someone who looks plain creepy and can't do anything about it
my bro shaved his head, so far he's been creep-doggin all summer
מאת creepdogexpert 28 ביולי, 2010


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If you need immediate assistance, call 877-SSRNHelp (877 777 6435) in the United States, or +1 585 442 8170 outside of the United States, 8:30AM to 6:00PM U.S. Eastern, Monday - Friday.
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State Reps. Andre Jacque and Chris Taylor discuss the political impact of the abortion issue for voters in 2014
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- Flat Rate Shipping. Any Size Order! -
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HOME Seattle Seahawks Gear Seattle Seahawks Collectibles Seattle Seahawks Collectibles Imagine that (60 items) Product ID: 1578388
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If there were any feelings of tension between Indonesian Foreign Minister Marty Natalegawa and Tony Abbott over boat policy, both were doing their best to hide it as they gripped hands and grinned at the Halim airforce base in Jakarta yesterday afternoon.
Mr Abbott lurched up to Mr Natalegawa for a two-handed shake, his Foreign Minister Julie Bishop also smiling behind him as she descended the steps.
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Abbott brings 'Labor spats' to Indonesia
Tony Abbott has openly criticised Labor policies during talks with Indonesian President Susilo Bambang Yudhoyono, who agrees more bilateral work needs to be done about asylum seekers. Michael Bachelard reports.
The Prime Minister began his first overseas trip as Prime Minister yesterday afternoon, and the stakes could barely be higher. Mr Natalegawa has been adamant since March 2010, when Mr Abbott first announced his boat tow-back policy, that it was unacceptable, and his opposition is only growing, on the basis that it offends Indonesian sovereignty.
With that in mind, Mr Abbott's first call on Indonesia could be interpreted as a sop to Indonesian sensitivities.
At the Heroes Cemetery in the Jakarta suburb of Kalibata, 7000 veterans of the Indonesian battle for independence from the Dutch are buried.
It's a proud and well-kept patch of ground, with helmets placed on every grave. It's also a well-trodden route for foreign leaders. Then Defence Minister Stephen Smith went there in April; British Prime Minister David Cameron in 2012.
Each came looking to use a symbol to deepen the relationship with Indonesia; but neither confronted the hurdles that Mr Abbott has erected between himself and goal.
As he mounted the marble steps to the Merdeka (Freedom) Palace for his meeting with Susilo Bambang Yudhoyono, Mr Abbott's fists were clenched.
He knows he'll need more than a two-handed shake and a grin to get what he wants in Jakarta.


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I am on a huge heater!!!
I usually only cashout 1k via western union... now i find my account at 45k - seems like bank wires are the only option for me with a 7k max... will my bank raise any questions when these bank wires hit my account? What do i tell them if they ask...
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Understanding the role that carbohydrates play in glucose control is critical to managing diabetes and insulin resistance. The goal of this session is to help you balance your daily carbohydrate intake with minimal medication.
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Need an insulin pump refresher? This session is for current pumpers who desire a re-fresher about the basics of insulin pumping such as basal/bolus theory, bolus calculator use, understanding pump settings, infusion site and high glucose trouble shooting.
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Group Sessions are often covered by insurance through medical nutrition therapy or other education benefit. Some individuals may attend these sessions as part of the purchase price of their insulin pump. If you do not have insurance or training benefits then classes are $25-$37.50.
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The belief that mental disorder is linked to violence drives much of mental health policy. Steadman et alArticle compare violence by people discharged from acute psychiatric facilities with violence by other residents of the same neighborhoods. No differences were found between the violence rate of patients without symptoms of substance abuse and that of their neighbors. Substance abuse raised violence rates in both groups and a higher portion of patients than residents reported such symptoms. These findings indicate that community violence by people discharged from psychiatric facilities varies considerably according to presence of co-occurring substance abuse.
A commentary by Link and Stueve appears in this issue.Article
It is difficult to interpret sex ratio differences in rates of depression because studies have used different methods of sample selection and case identification. Gater et alArticle report from the World Health Organization Study of Psychological Problems in General Health Care, which used a consistent method in 15 centers around the world. There was a consistent female preponderance for current depression and agoraphobia. In contrast, the sex ratio for generalized anxiety varied between centers, suggesting that local differences may contribute to the sex difference in rates for this disorder.
Obsessive-compulsive disorder (OCD), unipolar depression, and panic disorder are psychiatric conditions that share similar neuropsychological deficits. However, the specific nature of cognitive deficits for each of these disorders remains largely unknown. Purcell et alArticle report that patients with OCD are impaired for visual memory, executive functioning (higher-level processing), and motor speed, in contrast to patients with unipolar depression and panic disorder who perform normally on these tasks. These findings suggest that the selective deficits observed in patients with OCD are related to the specific illness processes that are associated with the disorder.
Binge eating disorder is a new diagnostic concept. The cardinal feature is binge eating but, in contrast to bulimia nervosa, the binge eating is not accompanied by inappropriate compensatory behavior such as self-induced vomiting and the misuse of laxatives. In a study of the causes of binge eating disorder, Fairburn et alArticle found that its antecedent risk factors consisted primarily of adverse childhood experiences, parental depression, negative self-evaluation, and childhood obesity. In contrast, perfectionism and pronounced vulnerability to obesity seemed to be especially characteristic of bulimia nervosa. These findings provide support for the validity of the distinction between binge eating disorder and bulimia nervosa.
Neuropathological studies in schizophrenia have implicated limbic structures paralleling the neuropsychological deficits reported in memory. However, quantitative magnetic resonance imaging studies have yielded mixed results. Nelson et alArticle used meta-analysis to evaluate 18 volumetric magnetic resonance imaging studies of the hippocampal formation in schizophrenia, which included 522 patients and 426 controls. Meta-analytic effects indicated bilateral hippocampal reduction in patients compared with controls. The hippocampal size for patients was, on average, 4% less than that of controls. Additional analyses indicated similar reduction in the amygdala and examined the role of scan variables, sample characteristics, and other study features that might explain the variability across volumetric studies. This meta-analytic report provides strong evidence of medial temporal volume reduction in schizophrenia.
Schizophrenia is associated with several polysomnographic abnormalities, notably variable reductions in delta sleep. Keshavan et alArticle applied both visually scored and automated analyses of sleep polysomnographic data in medication-free schizophrenic patients. Robust reductions in delta sleep were seen in these patients, as well as in the subset of patients who were neuroleptic naive. These findings suggest that the functional integrity of thalamocortical circuits, which mediate delta sleep, may be abnormal in schizophrenia.
There have been few outcome studies of psychotherapy for human immunodeficiency virus–positive patients. Markowitz et alArticle conducted a 4-cell, 16-week trial comparing interpersonal psychotherapy, cognitive behavioral therapy, supportive psychotherapy, and imipramine plus supportive psychotherapy as treatments for human immunodeficiency virus–positive patients with depressive symptoms. Symptoms diminished across cells, but pharmacotherapy and interpersonal psychotherapy were statistically superior to the other conditions.
Providing cost-effective community-based care for persons with severe mental illness is an important challenge. Rosenheck et alArticle tested a Veterans Affairs program of intensive community care, based on the Wisconsin Assertive Community Treatment (ACT) model, that emphasized frequent contacts, small caseloads, and high continuity. At neuropsychiatric (long-stay) facilities the model reduced total societal costs by $34,197 per patient for 2 years but did not improve clinical outcomes. At short-stay facilities the program was cost neutral when implemented as intended and improved 2-year outcomes. This study demonstrates the importance of considering institutional context and monitoring model adherence in the evaluation of intensive community treatment.
Depression is a common and serious disorder. Lyons et alArticle interviewed more than 3000 male twin pairs. More severe depression seemed to be influenced by genetic factors and the nonfamily environment, but not the family environment; less severe forms were influenced by the family and nonfamily environments, but not genetic factors. When major depression was divided into early-onset and later-onset cases, there was a stronger genetic influence on early-onset cases. Thus, environmental factors seem to play a more important role when depression is milder and starts later, while genetic influences play a relatively greater role when depression is more severe and starts earlier.
The link between adverse early experiences and adult psychopathology is widely recognized. In an earlier study by Coplan et alArticle infant primates were nursed by mothers randomly assigned to variable foraging demand (VFD) or nonvariable foraging conditions (non-VFD). The VFD group demonstrated elevations of cerebrospinal fluid corticotropin-releasing factor and decreased cortisol concentrations vs those in the non-VFD group. Follow-up cisternal taps revealed elevated concentrations of serotonin and dopamine metabolites and of somatostatin in the VFD vs non-VFD groups. Positive correlations between corticotropin-releasing factor and each elevated neurochemical were noted in the VFD group but not in the non-VFD group. The findings support the hypothesis that adverse early rearing has long-standing effects on primate neurochemicals relevant to emotional regulation.
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Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
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Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers' bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
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