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Biomedical subjects

S Starkman

Publications and source records attributed to S Starkman.

At least 19 recordsLinked to original sources
PubMed2007

Intra-arterial thrombolysis for acute stroke in patients 80 and older: a comparison of results in patients younger than 80 years.

BACKGROUND AND PURPOSE: Intra-arterial fibrinolytic therapy is a promising treatment for acute ischemic stroke. Few data are available on its use in elderly patients. The purpose of this study was to compare the baseline characteristics, complications, and outcomes between intra-arterially treated ischemic stroke patients aged > or = 80 years and their younger counterparts. METHODS: Patients aged > or = 80 years (n = 33) were compared retrospectively with contemporaneous patients aged < 80 years (n = 81) from a registry of consecutive patients treated with intra-arterial thrombolysis over a 9-year period. RESULTS: The very elderly and younger cohorts were very similar in baseline characteristics, including pretreatment stroke severity (National Institutes of Health Stroke Scale [NIHSS] 17 versus 16), differing only in history of stroke/transient ischemic attack (42% versus 22%, P = .01) and weight (66.8 versus 75.8 kg; P = .02). Significant differences in recanalization (TIMI 2-3) rates could not be detected between the very elderly and younger patients (79% versus 68%, P = .10). Rates of major symptomatic hemorrhage (7% versus 8%) and any intracerebral hemorrhage (39% versus 37%) did not differ. Outcomes at 90 days showed lower rates of excellent functional outcome (mRS < or = 1, 26% versus 40%, P = .02) and survival (57% versus 80%, P = .01) among the very elderly. CONCLUSIONS: Intra-arterial fibrinolysis in the elderly can be accomplished with recanalization rates and hemorrhage rates equal to that in younger patients. Although mortality rates are higher and good functional outcomes are lower than in younger persons, nondisabling outcomes may be achieved in a quarter of patients. These findings suggest that the investigation and use of intra-arterial thrombolytic treatment in very elderly patients should not be avoided but pursued judiciously.

Adult↗
PubMed2006

Cholesterol level and symptomatic hemorrhagic transformation after ischemic stroke thrombolysis.

BACKGROUND: Prestroke statin use may improve ischemic stroke outcomes, yet there is also evidence that statins and extremely low cholesterol levels may increase the risk of intracranial hemorrhage. We evaluated the independent effect of statin use and admission cholesterol level on risk of symptomatic hemorrhagic transformation (sHT) after recanalization therapy for acute ischemic stroke. METHODS: We analyzed ischemic stroke patients recorded in a prospectively maintained registry that received recanalization therapies (IV or intra-arterial fibrinolysis or endovascular embolectomy) at a university medical center from September 2002 to May 2006. The independent effect of premorbid statin use on sHT post intervention was evaluated by logistic regression, adjusting for prognostic and treatment variables known to predict increased HT risk after ischemic stroke. RESULTS: Among 104 patients, mean age was 70 years, and 49% were men. Male sex, hypertension, statin use, low total cholesterol and low-density lipoprotein (LDL) cholesterol, current smoking, elevated glucose levels, and higher admission NIH Stroke Scale (NIHSS) score were all associated with a greater risk of sHT in univariate analysis. After adjusting for covariates, low LDL cholesterol (odds ratio [OR], 0.968 per 1-mg/dL increase; 95% CI, 0.941 to 0.995), current smoking (OR, 14.568; 95% CI, 1.590 to 133.493), and higher NIHSS score (OR, 1.265 per 1-point increase; 95% CI, 1.047 to 1.529) were independently associated with sHT risk. CONCLUSIONS: Lower admission low-density lipoprotein cholesterol level with or without statin use, current smoking, and greater stroke severity are associated with greater risk for symptomatic hemorrhagic transformation after recanalization therapy for ischemic stroke.

Aged↗
PubMed2006

Early MRI and outcomes of untreated patients with mild or improving ischemic stroke.

OBJECTIVE: To determine the frequency of early neurologic deterioration with infarct expansion (ENDIE) and poor outcomes among ischemic stroke patients not treated with reperfusion therapies because of rapidly improving or mild symptoms (RIMS) and to study the predictive value of hyperacute MRI in these patients. METHODS: We identified consecutive patients with symptoms of acute stroke undergoing multimodal MRI within 6 hours of onset without evidence of hemorrhage on imaging. Medical records were reviewed for evidence of early neurologic deterioration within 48 hours. All deteriorating patients had repeat MRI to ascertain causes of worsening. Poor outcome was defined as a discharge modified Rankin Scale (mRS) score of > or = 3. RESULTS: We identified 74 patients with stroke symptoms < or = 6 hours from onset. Forty had RIMS, and 39 did not receive reperfusion therapies because of RIMS. Among these 39, 4 experienced ENDIE, and 8 were discharged with mRS score of > or = 3. Eight of the 39 patients had large-vessel occlusions on MR angiography. Three of 8 patients with large-vessel occlusion as against only one of 31 patients without occlusion had ENDIE (odds ratio [OR] 18, 95% CI 1.6 to 209, p = 0.02). Four of 8 patients with large-vessel occlusion as against 4 of 31 patients without occlusion had a discharge mRS score of > or = 3 (OR 7, 95% CI 1.2 to 38, p = 0.04). CONCLUSIONS: About 10% of patients eligible for acute reperfusion therapy excluded on the basis of mild or rapidly improving symptoms show early neurologic deterioration with infarct expansion within 48 hours, and about 20% show poor outcome at discharge. Persisting large-vessel occlusion substantially increases the risk of early worsening and poor functional outcome.

Confidence Intervals↗
PubMed2006

Are elevated admission calcium levels associated with better outcomes after ischemic stroke?

Calcium (Ca(2+)) and magnesium (Mg(2+)) influence the molecular pathways of ischemic neuronal death. The authors evaluated the impact of admission serum Ca(2+) and Mg(2+) levels, on incident stroke severity and discharge functional outcome. After adjusting for covariates, higher admission Ca(2+) was significantly associated with lesser stroke severity and better discharge functional outcome. Admission Mg(2+) was not an independent clinical outcome prognosticator.

Adolescent↗
PubMed2006

Influence of gender on outcomes after intra-arterial thrombolysis for acute ischemic stroke.

Recent data suggest that women obtain greater benefit than men from IV fibrinolysis for acute ischemic stroke. It is unknown whether this gender-thrombolysis advantage extends to those treated with intra-arterial (IA) thrombolysis. The authors evaluated the independent effect of gender among ischemic stroke patients treated with IA fibrinolysis and found no differences in short-term clinical and angiographic outcomes between men and women who received IA thrombolysis for acute ischemic stroke.

Aged↗
PubMed2006

Thrombolytic therapy of acute ischemic stroke during pregnancy.

The authors report eight pregnant women with acute ischemic stroke treated with thrombolysis (rt-PA [recombinant human tissue plasminogen activator] or urokinase). Seven women recovered. Two extracranial and two asymptomatic intracranial hemorrhages complicated treatment; one woman died of arterial dissection complicating angiography. Three patients had therapeutic abortions, two fetuses were miscarried, and two babies were delivered healthy. Although pregnant women may be treated safely with thrombolytics, risks and benefits to mother and fetus must be carefully weighed.

Adult↗
PubMed2006

Magnesium sulfate neither potentiates nor inhibits tissue plasminogen activator-induced thrombolysis.

BACKGROUND: Increasing circulating magnesium concentrations to 2-fold over normal baseline may afford a neuroprotective effect in patients with acute cerebral ischemia. OBJECTIVES: As patients receiving magnesium sulfate (MgSO(4)) in human clinical trials may also be candidates for subsequent thrombolytic therapy with tissue plasminogen activator (t-PA), preclinical assessment of possible inhibition or potentiation of fibrinolytic activity by MgSO(4) has important clinical relevance. METHODS: We utilized an in vitro system, in which D-dimer release served as a reflection of t-PA-induced clot lysis, to measure the effect of magnesium at the target concentration being tested in human stroke clinical trials, and at 2- and 3-fold higher levels. Clots from normal volunteers were exposed to t-PA at concentrations that correspond to therapeutic or endogenous plasma t-PA levels. RESULTS: MgSO(4) had no effect on t-PA-induced clot lysis at up to 3-fold target magnesium concentration (6x normal serum concentration). CONCLUSIONS: MgSO(4) concentrations well above the targeted level in therapeutic stroke trials does not affect t-PA-induced fibrinolytic activity, and therefore is a suitable agent for trials of combined neuroprotective and thrombolytic therapy in patients with acute ischemic stroke.

Dose-Response Relationship, Drug↗
PubMed2005

Angiotensin 2 type 2 receptor activity and ischemic stroke severity.

BACKGROUND: Drugs that increase angiotensin 2 formation, including thiazides, calcium channel blockers, and angiotensin 2 type 1 (AT1) receptor blockers, may be more effective in stroke prevention than angiotensin 2 suppressive drugs such as angiotensin-converting enzyme inhibitors and beta-blockers. OBJECTIVE: To assess whether angiotensin 2 formation increasing drugs reduce incident stroke severity compared with angiotensin 2 formation suppressive drugs. METHODS: Consecutive patients presenting within 24 hours of first-ever ischemic stroke over an 18-month period were studied. Subjects were only included if they were on only angiotensin 2 formation increasers, only angiotensin 2 formation suppressors, or no antihypertensive agents. NIH Stroke Scale (NIHSS) score at presentation was used as the index of stroke severity. Demographic data, risk factors, admission blood pressures, other medications, and stroke mechanisms were controlled for across the three groups using least absolute deviation linear regression. RESULTS: One hundred seventy-five individuals met study criteria. Mean age was 67.4 years; 45% were women. Forty-nine patients were on angiotensin 2 formation suppressors and 16 on angiotensin 2 formation increasers. Age at admission, atrial fibrillation, previous antithrombotic use, cardioembolic and large-vessel atherosclerotic mechanisms, and mean systolic and diastolic blood pressure were significant univariate predictors of presenting median NIHSS score. On multivariate analysis, the adjusted median NIHSS score was lower in the angiotensin 2 increasers (median = 2.2; p = 0.005) and trended lower for angiotensin 2 suppressors (median = 4.4; p = 0.054) compared with the no-antihypertensive group (median = 6.0). There was no difference in stroke severity between angiotensin 2 increasers compared with angiotensin 2 suppressors (p = 0.123). CONCLUSIONS: Angiotensin 2 formation increasing agents did not reduce ischemic stroke severity more than angiotensin 2 formation suppressing agents. However, the prestroke use of antihypertensives was associated with reduced severity of incident ischemic strokes.

Adrenergic beta-Antagonists↗
PubMed2005

Frequent infection of Hylobates pileatus (pileated gibbon) with species-associated variants of hepatitis B virus in Cambodia.

As well as being distributed widely in human populations, hepatitis B virus (HBV) infections occur frequently in chimpanzee, gibbon and other ape populations in sub-Saharan Africa and South-East Asia. To investigate the frequency and genetic relationships of HBV infecting gibbons in Cambodia, pileated gibbons (Hylobates pileatus) that were originally wild-caught were screened for surface antigen. Twelve of 26 (46 %) were positive, of which 11 were positive for HBV DNA. Phylogenetic analysis of complete genome sequences revealed two distinct genetic groups in the gibbon/orangutan clade. Three were similar to previously described variants infecting H. pileatus in Thailand and eight formed a distinct clade, potentially representing distinct strains of HBV circulating in geographically separated populations in South-East Asia. Because of the ability of HBV to cross species barriers, large reservoirs of infection in gibbons may hamper ongoing attempts at permanent eradication of HBV infection from human populations in South-East Asia through immunization.

Animals↗
PubMed2003

Acute seizures after intracerebral hemorrhage: a factor in progressive midline shift and outcome.

OBJECTIVE: To determine whether early seizures that occur frequently after intracerebral hemorrhage (ICH) lead to increased brain edema as manifested by increased midline shift. METHODS: A total of 109 patients with ischemic stroke (n = 46) and intraparenchymal hemorrhage (n = 63) prospectively underwent continuous EEG monitoring after admission. The incidence, timing, and factors associated with seizures were defined. Serial CT brain imaging was conducted at admission, 24 hours, and 48 to 72 hours after hemorrhage and assessed for hemorrhage volume and midline shift. Outcome at time of discharge was assessed using the Glasgow Outcome Scale score. RESULTS: Electrographic seizures occurred in 18 of 63 (28%) patients with ICH, compared with 3 of 46 (6%) patients with ischemic stroke (OR = 5.7, 95% CI 1.4 to 26.5, p < 0.004) during the initial 72 hours after admission. Seizures were most often focal with secondary generalization. Seizures were more common in lobar hemorrhages but occurred in 21% of subcortical hemorrhages. Posthemorrhagic seizures were associated with neurologic worsening on the NIH Stroke Scale (14.8 vs 18.6, p < 0.05) and with an increase in midline shift (+ 2.7 mm vs -2.4 mm, p < 0.03). There was a trend toward increased poor outcome (p < 0.06) in patients with posthemorrhagic seizures. On multivariate analysis, age and initial NIH Stroke Scale score were independent predictors of outcome. CONCLUSION: Seizures occur commonly after ICH and may be nonconvulsive. Seizures are independently associated with increased midline shift after intraparenchymal hemorrhage.

Adult↗
PubMed2001

Diffusion-perfusion MRI characterization of post-recanalization hyperperfusion in humans.

BACKGROUND: Animal and human studies have demonstrated that postischemic hyperperfusion may occur both early and late timepoints following acute cerebral ischemia. OBJECTIVE: To use diffusion-perfusion MRI to characterize hyperperfusion in humans following intra-arterial thrombolysis. METHODS: MRI were performed before treatment, several hours following vessel recanalization, and at day 7 in patients successfully recanalized with intra-arterial thrombolytics. RESULTS: Hyperperfusion was visualized in 5 of 12 patients within several hours after recanalization (mean volume, 18 mL; range, 7 to 40 mL), and in 6 of 11 patients at day 7 (mean volume, 28 mL; range, 4 to 45 mL). Within the core region of hyperperfusion, mean cerebral blood flow was 2.1 times greater than in the contralateral homologous region at the early time point, and 3.1 times greater at day 7. Seventy-nine percent of voxels with hyperperfusion at day 7 demonstrated infarction at day 7, whereas only 36% of voxels (within the initial hypoperfusion region) not showing hyperperfusion at day 7 demonstrated infarction at day 7. Mean pretreatment apparent diffusion coefficient (ADC) and perfusion values were more impaired in voxels that subsequently developed hyperperfusion compared with other at-risk voxels (all p values < 0.0001). There were no significant differences in the degree of clinical improvement in patients with regions of hyperperfusion versus those without, although sample size limited power to detect group differences. CONCLUSIONS: Postischemic hyperperfusion, visualized with perfusion MRI in humans following recanalization by intra-arterial thrombolytic therapy, occurred in about 40% of patients within hours and in about 50% of patients at day 7. Hyperperfusion developed mainly in regions that went on to infarction. Compared with other abnormal regions, tissues that developed postischemic hyperperfusion had greater bioenergetic compromise in pretreatment apparent diffusion coefficient values and greater impairment in pretreatment blood flow measures.

Adult↗
PubMed2001

Diffusion-perfusion MR evaluation of perihematomal injury in hyperacute intracerebral hemorrhage.

BACKGROUND: It has been suggested that a zone of perihematomal ischemia analogous to an ischemic penumbra exists in patients with primary intracerebral hemorrhage (ICH). Diffusion-perfusion MRI provides a novel means of assessing injury in perihematomal regions in patients with ICH. OBJECTIVE: To characterize diffusion-perfusion MRI changes in the perihematomal region in patients with hyperacute intracerebral hemorrhage. METHOD: Twelve patients presenting with hyperacute, primary ICH undergoing CT scanning and diffusion-perfusion MRI within 6 hours of symptom onset were reviewed. An automated thresholding technique was used to identify decreased apparent diffusion coefficient (ADC) values in the perihematomal regions. Perfusion maps were examined for regions of relative hypo- or hyperperfusion. RESULTS: Median baseline NIH Stroke Scale score was 17 (range, 6 to 28). Median hematoma volume was 13.3 mL (range, 3.0 to 74.8 mL). MRI detected the hematoma in all patients on echo-planar susceptibility-weighted imaging and in all seven patients imaged with gradient echo sequences. In six patients who underwent perfusion imaging, no focal defects were visualized on perfusion maps in tissues adjacent to the hematoma; however, five of six patients demonstrated diffuse ipsilateral hemispheric hypoperfusion. On diffusion imaging, perihematomal regions of decreased ADC values were identified in three of 12 patients. All three subsequently showed clinical and radiologic deterioration. CONCLUSIONS: A rim of perihematomal decreased ADC values was visualized in the hyperacute period in a subset of patients with ICH. The presence of a rim of decreased ADC outside the hematoma correlated with poor clinical outcome. Although perfusion maps did not demonstrate a focal zone of perihematomal decreased blood flow in any patient, most patients had ipsilateral hemispheric hypoperfusion.

Acute Disease↗
PubMed2001

Trends in acute ischemic stroke trials through the 20th century.

BACKGROUND AND PURPOSE: The advent of controlled clinical trials revolutionized clinical medicine over the course of the 20th century. The objective of this study was to quantitatively characterize developments in clinical trial methodology over time in the field of acute ischemic stroke. METHODS: All controlled trials targeting acute ischemic stroke with a final report in English were identified through MEDLINE and international trial registries. Data regarding trial design, implementation, and results were extracted. A formal 100-point scale was used to rate trial quality. RESULTS: A total of 178 controlled acute stroke trials were identified, encompassing 73 949 patients. Eighty-eight trials involved neuroprotective agents, 59 rheological/antithrombotic agents, 26 agents with both neuroprotective and rheological/antithrombotic effects, and 5 a nonpharmacological intervention. Only 3 trials met conventional criteria for a positive outcome. Between the 1950s and 1990s, the number of trials per decade increased from 3 to 99, and mean trial sample size increased from 38 (median, 26) to 661 (median, 113). During 1980-1999, median time window allowed for enrollment decreased per half decade from 48 to 12 hours. Reported pharmaceutical sponsorship increased substantially over time, from 38% before 1970 to 68% in the 1990s. Trial quality improved substantially from a median score of 12 in the 1950s to 72 in the 1990s. CONCLUSIONS: Accelerating trends in acute stroke controlled trials include growth in number, sample size, and quality, and reduction in entry time window. These changes reflect an increased understanding of the pathophysiology of acute stroke, the imperative for treatment initiation within a critical time window, and more sophisticated trial design.

Acute Disease↗
PubMed2001

Outcome of stroke patients without angiographically revealed arterial occlusion within four hours of symptom onset.

BACKGROUND AND PURPOSE: Follow-up imaging data from stroke patients without angiographically apparent arterial occlusions at symptom onset are lacking. We reviewed our Emergency Management of Stroke (EMS) trial experience to determine the clinical and imaging outcomes of patients with ischemic stroke who showed no arterial occlusion on angiograms obtained within 4 hours of symptom onset. METHODS: All patients in this report were participants in the EMS trial that was designed to address the safety and potential efficacy of combined IV and intraarterial thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. RESULTS: Thirty-five patients were randomized to receive either IV rt-PA (n = 17) or placebo (n = 18), followed by cerebral angiography. No symptomatic arterial occlusion was evident in 10 (29%) of the 34 patients. Eight (80%) of 10 patients without angiographically apparent clot within 4 hours of symptom onset had a new cerebral infarction confirmed on follow-up brain imaging. The median 72-hour infarction volume was 2.4 cc (range, 1-30 cc). Four of the 10 "no-clot" patients had a favorable 3-month outcome as assessed by Barthel Index (score, 95 or 100) and modified Rankin Scale (score, 0 or 1). The six remaining patients had 3-month Rankin Scale scores of 1 (Barthel of 90), 2, 3, 4, or 5. CONCLUSION: Acute ischemic stroke patients with a neurologic deficit but a negative angiogram during the first 4 hours after symptom onset usually develop image-documented cerebral infarction, and approximately half suffer from long-term functional disability. The two most likely explanations for negative angiograms are very early irreversible ischemic damage despite recanalization or ongoing ischemia secondary to clot in non-visible penetrating arterioles or in the microvasculature.

Aged↗
PubMed2000

Identifying stroke in the field. Prospective validation of the Los Angeles prehospital stroke screen (LAPSS).

BACKGROUND AND PURPOSE: Reliable identification of stroke patients in the field by prehospital personnel could expedite delivery of acute stroke therapy. The Los Angeles Prehospital Stroke Screen (LAPSS) is a 1-page instrument designed to allow prehospital personnel to rapidly identify acute stroke patients in the field. We performed a prospective, in-the-field validation study of the LAPSS. METHODS: Paramedics assigned to 3 University of California at Los Angeles-based advanced life support units were trained and certified in use of the LAPSS. Over 7 months, paramedics completed the LAPSS on noncomatose, nontrauma patients with complaints suggestive of neurological disease. LAPSS form stroke identification results were compared with emergency department and final hospital discharge diagnoses. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and likelihood ratios were calculated for LAPSS identification of ischemic stroke, currently symptomatic transient ischemic attack, and intracerebral hemorrhage. RESULTS: Of a total of 1298 runs, 34% were for nontraumatic, noncomatose neurologically relevant complaints. Thirty-six of these patients (3% of all transports) had a final diagnosis of acute symptomatic cerebrovascular disease (21 ischemic strokes, 7 transient ischemic attacks, and 8 intracerebral hemorrhages). LAPSS forms were completed on 206 patients. Paramedic performance when completing the LAPSS demonstrated sensitivity of 91% (95% CI, 76% to 98%), specificity of 97% (95% CI, 93% to 99%), positive predictive value of 86% (95% CI, 70% to 95%), and negative predictive value of 98% (95% CI, 95% to 99%). With correction for the 4 documentation errors, positive predictive value increased to 97% (95% CI, 84% to 99%). CONCLUSIONS: The LAPSS allows prehospital personnel to identify patients with acute cerebral ischemia and intracerebral hemorrhage with a high degree of sensitivity and specificity.

Aged↗