Nursing care of acute stroke patients after receiving rt-PA therapy. The NINDS rt-PA Stroke Study Group

Treatment with tissue plasminogen activator (rt-PA) for acute stroke requires intensive care of the patient. The risk of thrombolytic therapy and the need for rapid interventions make it clear that the nursing role during this time is crucial. Nurses should be familiar with safe dosage and administration of rt-PA for stroke, which is clearly different than administration of rt-PA for myocardial infarction. Furthermore, thrombolytic stroke treatment must be accompanied by intensive neurological monitoring to observe for complications. Intracerebral hemorrhage is usually accompanied by an acute change in neurological status and vital sign instability. Intensive monitoring of neurologic condition, vital signs, cardiac status and other standard critical care practices must be initiated immediately to optimize patient outcome.     

Neuroradiologic evaluation of patients with acute stroke treated with recombinant tissue plasminogen activator. The rt-PA Acute Stroke Study Group

The breast is an organ of reproduction. The diagnosis and treatment of most benign breast conditions and a knowledge of the contemporary treatment of breast cancer are essential components of the current practice of obstetrics and gynecology.     

Using the NIH Stroke Scale to assess stroke patients. The NINDS rt-PA Stroke Study Group

The stroke patient is acutely ill within minutes of symptom onset. Typically, he or she is awake and thus requires a focal neurologic exam to evaluate vision, movement, sensation and language. With the advent of acute stroke treatments that need to be rapidly implemented, it is critical that the nurse be able to assess patients and relay the information accurately and efficiently to other members of the health care team. Performing and documenting the awake stroke exam in the most efficient and useful manner is key to the nursing care of the stroke patient. The National Institutes of Health Stroke Scale (NIHSS) is a systematic assessment tool designed to measure the neurologic deficits most often seen with acute stroke patients. Originally designed as a research tool, it is a nonlinear ordinal scale, with possible scores ranging form 0-42. Exam performance has been timed to take 5-8 minutes. Use of the NIHSS includes documentation of neurologic status and outcome, data collection for planning safe nursing care and standardization of information exchanges between nurse caregivers and other health care professionals.     

Use of tissue plasminogen activator factor for acute ischemic stroke

Recently, a new isoform of the type II transforming growth factor beta receptor (TGF-beta RII) was identified. This isoform (TGF-beta RII2) contains an insertion of 25 amino acids in the extracellular domain of the receptor. Using RT-PCR the authors demonstrated that both TGF-beta RII1 and TGF-beta RII2 are expressed by chondrocytes in murine and human articular cartilage. Bovine articular chondrocytes expressed TGF-beta RII1 mRNA but did not express detectable levels of TGF-beta RII2 mRNA, suggesting that the new isoform does not play an important role in normal bovine cartilage physiology. Because TGF-beta responses seem to be age related and differential TGF-beta responses have been described between normal cartilage and cartilage undergoing repair the authors studied if the relative mRNA expression between these isoforms is altered during cartilage repair and aging. No differences in the relative mRNA expression of the two isoforms of the type II TGF-beta receptor could be demonstrated in murine cartilage during aging or during the repair phase after mild PG depletion indicating that it is unlikely that age-related TGF-beta responses and differential TGF-beta responses between normal cartilage and cartilage undergoing repair are the result of differences in the relative expression of the two TGF-beta RII isoforms.     

Code Stroke: rapid transport, triage and treatment using rt-PA therapy. The NINDS rt-PA Stroke Study Group

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.     

Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS)

OBJECTIVE: To evaluate the efficacy and safety of intravenous thrombolysis using recombinant tissue plasminogen activator (rt-PA) in patients with acute ischemic stroke. DESIGN: Randomized, prospective, multicenter, double-blind, placebo-controlled clinical trial. SETTING: A total of 75 hospitals in 14 European countries. PATIENTS: A total of 620 patients with acute ischemic hemispheric stroke and moderate to severe neurologic deficit and without major early infarct signs on initial computed tomography (CT). INTERVENTION: Patients were randomized to treatment with 1.1 mg per kilogram of body weight of rt-PA (alteplase) or placebo within 6 hours from the onset of symptoms. OUTCOME MEASURES: Primary end points included Barthel Index (BI) and modified Rankin Scale (RS) at 90 days. Secondary end points included combined BI and RS, Scandinavian Stroke Scale (SSS) at 90 days, and 30-day mortality. Tertiary end points included early neurologic recovery (SSS) and duration of in-hospital stay. Safety parameters included mortality and incidence of intracranial or extracranial hemorrhage. RESULTS: The distribution of demographic variables was similar among patients in the rt-PA and placebo treatment arms in both the intention-to-treat (ITT) analysis and the explanatory analysis for the target population (TP). A total of 109 patients (17.4%) were included in the trial despite major protocol violations but excluded from the TP. There was no difference in the primary end points in the ITT analysis, while the TP analysis revealed a significant difference in the RS in favor of rt-PA-treated patients (P = .035). Of the secondary end points, the combined BI and RS showed a difference in favor of rt-PA-treated patients in both analyses (P < .001). Neurologic recovery at 90 days was significantly better for rt-PA-treated patients in the TP (P = .03). The speed of neurologic recovery assessed by the SSS was significantly better up to 7 days in the ITT analysis and up to 30 days for the TP in the rt-PA treatment arm. In-hospital stay was significantly shorter in the rt-PA treatment arm in both analyses. There were no statistically significant differences in the mortality rate at 30 days or in the overall incidence of intracerebral hemorrhages among the rt-PA and placebo treatment arms in either analysis. However, the occurrence of large parenchymal hemorrhages was significantly more frequent in the rt-PA-treated patients. CONCLUSIONS: Intravenous thrombolysis in acute ischemic stroke is effective in improving some functional measures and neurologic outcome in a defined subgroup of stroke patients with moderate to severe neurologic deficit and without extended infarct signs on the initial CT scan. However, the identification of this subgroup is difficult and depends on recognition of early major CT signs of early infarction. Therefore, since treating ineligible patients is associated with an unacceptable increase of hemorrhagic complications and death, intravenous thrombolysis cannot currently be recommended for use in an unselected population of acute ischemic stroke patients.     

Lubeluzole treatment of acute ischemic stroke. The US and Canadian Lubeluzole Ischemic Stroke Study Group

BACKGROUND AND PURPOSE: Lubeluzole is a novel benzothiazole compound that has shown neuroprotective activity in preclinical models of ischemic stroke. The present multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of lubeluzole in the treatment of ischemic stroke. METHODS: Seven hundred twenty-one patients with clinical symptoms of acute ischemic stroke were randomized to receive either lubeluzole (7.5 mg over 1 hour, followed by a continuous daily infusion of 10 mg for up to 5 days) or placebo. Treatment was initiated within 6 hours of symptom onset. Mortality at 12 weeks was the primary efficacy end point. Secondary efficacy end points included neurological recovery (based on the National Institutes of Health Stroke Scale [NIHSS]), functional status (based on the Barthel Index), and level of disability (based on the Rankin Scale). Safety assessments included standard and continuous electrocardiographic monitoring, physical examination, measurements of vital signs, clinical laboratory evaluation, and adverse events reports. RESULTS: The overall mortality rate at 12 weeks for lubeluzole-treated patients was 20.7% compared to 25.2% for placebo-treated patients (NS). Controlling for relevant covariates, the degree of neurological recovery (NIHSS) at week 12 significantly favored lubeluzole over placebo (P = .033). Lubeluzole treatment similarly resulted in significantly greater improvements in functional status (Barthel Index) (P = .038) and overall disability (Rankin Scale) (P = .034) after 12 weeks. A global test statistic confirmed that lubeluzole-treated patients had a more favorable clinical outcome at 12 weeks (P = .041). The safety profile of lubeluzole resembled that of placebo. CONCLUSIONS: Treatment with lubeluzole within 6 hours of the onset of ischemic stroke had a nonsignificant effect on mortality and resulted in improved clinical outcome compared with placebo, with no safety concerns.     

Acute band-shaped keratopathy after intraocular fibrinolysis with recombinant tissue plasminogen activator (rt-PA)

The study was planned to determine the proportion of parents that wish to know the sex of their fetus at the 20-week anomaly scan, and to investigate our ability to diagnose correctly the sex of the fetus when undertaken as part of a routine scan. A total of 472 patients gave their informed consent. An attempt was made to identify the genitalia as part of the routine scan. No extra time was allowed to determine the sex of the fetus. Altogether 353 (74.7%) women wanted to know the sex, of which four (0.9%) wanted to know but did not want their partners to know. In 50 (10.6%) cases, it was not possible to determine the fetal sex in the time allowed. When the sex was identified, it was correct in 408 (96.7%) cases, and incorrect in 14 (3.3%) cases. Where the parents wanted to know the sex of the fetus, 24 (6.8%) scans were inconclusive, 319 (97%) were correctly identified, and ten (3%) were incorrectly identified (six male, four female). There were no terminations of pregnancy. The majority of prospective parents wish to know the sex of their child, and, in most cases, it is possible to determine the fetal sex at the time of the routine anomaly scan. During the time allowed, the fetal sex was undetermined in one in ten cases, and 3% were sexed incorrectly. If parents wish to know the gender of their fetus, it would appear reasonable to provide this information, provided that the parents are aware of the failure and error rates of sex identification using ultrasound.     

Illicit drug-associated ischemic stroke in the Baltimore-Washington Young Stroke Study

BACKGROUND: Limited information exists on the frequency, trends in occurrence, risk factors, mechanisms, and outcome of ischemic stroke associated with illicit drug use among young adults in a geographically defined population. METHODS: We reviewed ischemic stroke in young adults (aged 15 to 44 years) in 46 regional hospitals for 1988 and 1991. We examined stroke mechanisms and outcome in patients with recent drug use. RESULTS: Recent illicit drug use was noted in 51/422 (12.1%) stroke patients. Patients with drug use were more likely than other stroke patients to be black (p=0.01), aged 25 to 39 years (p=0.004), and smokers (p=0.006), and were less likely to have hypertension (p=0.004) or diabetes mellitus (p=0.004). Drug use was the probable cause of stroke in 20 (4.7%) patients. Among 31 (7.3%) patients with drug use as a possible stroke mechanism, more likely diagnoses included cardioembolic stroke in 18, hematologic/collagen vascular in 6, nonatherosclerotic vasculopathy in 5, and atherosclerosis in 3. There was no difference in outcome between drug-associated and non-drug associated stroke. CONCLUSIONS: Recent illicit drug use occurs in 12.1% of young adult stroke patients. Drug-associated young adult stroke seems to relate to vascular mechanisms other than those related to hypertension or diabetes. Case-control studies are needed.     

Neurocritical care for acute ischemic stroke

Treatment strategies for acute ischemic stroke include general and specific measures. The rationale for these strategies is discussed, and the current practice in the acute phase of ischemic stroke is presented. Special attention is given to the patient requiring intensive care.     

Gene polymorphisms for plasminogen activator inhibitor-1/tissue plasminogen activator and development of allograft coronary artery disease

BACKGROUND: Impaired fibrinolytic activity has been linked to the presence and severity of allograft vasculopathy (Tx CAD). This impairment may be associated with the presence of certain fibrinolytic protein gene polymorphisms. METHODS AND RESULTS: To investigate the relation between donor-specific fibrinolytic protein genotypes and Tx CAD, we identified donor plasminogen activator inhibitor-1 (PAI-1) HindIII and tissue plasminogen activator (TPA) EcoRI restriction fragment length polymorphisms-based genotypes by Southern blot analysis in 48 recipients of cardiac allografts and correlated these genotypes with the development of CAD. No association was found between donor TPA genotypes and the presence of Tx CAD. Among the 48 patients, 17% were homozygous for the 1/1 PAI-1 genotype, 51% for the 2/2 PAI-1 genotype, and 32% for the 1/2 PAI-1 genotype. The actuarial freedom from any CAD for the recipients with each respective donor PAI-1 genotype at 12 and 24 months was 100% and 100% for the 1/1 PAI-1 genotype, 92% and 92% for the 1/2 PAI-1 genotype, and 75% and 45% for the 2/2 PAI-1 genotype (P=0.03). Recipients with a diseased 2/2 PAI-1 genotyped allograft had longer ischemic times (P=0.02) than those recipients with a Tx CAD-free allograft. CONCLUSIONS: These data suggest that recipients with a 2/2 PAI-1 genotype are at a significant risk of developing Tx CAD. This genotype may serve as a useful screening tool for predicting the future development of Tx CAD.     

Multinational randomised controlled trial of lubeluzole in acute ischaemic stroke. European and Australian Lubeluzole Ischaemic Stroke Study Group

The purpose of this investigation was to examine whether inhaled nitric oxide (NO) may alter oxidative stress parameters and induce lung inflammation in moderate hyaline membrane disease (HMD). Eighteen moderately premature lambs (130 days gestation, term = 147 days) were randomly assigned to treatment with 20 ppm inhaled NO (n = 8) from the onset of ventilation or used as control (n = 10). Except inhaled NO, treatments were intentionally similar to those applied in clinical situations. The main studied parameters were oxidative stress index measurements on lung parenchyma and in circulating blood, lung parenchyma microscopic examination and bronchoalveolar lavage cell count. We found that 20 ppm of inhaled NO for 5 h did not change significantly either malondialdehyde and total antioxidant status levels in circulating blood, or malondialdehyde, reduced glutathione, glutathione peroxidase and glutathione reductase in lung parenchyma. Amino-imino-propene bond generation, which are lipoperoxidation markers, was similar in both groups. Furthermore, no significant changes in the number of inflammatory cells in lung lavage products and in lung parenchyma microscopic examination could be found. Therefore, these data do not support the hypothesis that short-term NO inhalation increases oxidative stress and lung inflammation in an experimental model of moderate HMD.     

Acceleration of plasminogen activation by tissue plasminogen activator on surface-bound histidine-proline-rich glycoprotein

Histidine-proline-rich glycoprotein (HPRG), also known as histidine-rich glycoprotein, is a major plasminogen-binding protein. In this work we characterized extensively the circumstances under which HPRG accelerates plasminogen activation and the specificity of this effect. Soluble HPRG did not significantly influence plasminogen activation. In contrast, native HPRG bound to hydrazide or nickel chelate surfaces strongly stimulated the activation of plasminogen by tissue plasminogen activator, but not by urokinase or streptokinase. The efficiency of activation on surface-bound HPRG was increased for Glu-plasminogen (41-fold), Lys-plasminogen (17-fold), and cross-linked Glu-plasminogen (11-fold) but not for mini-plasminogen, and was mainly due to a decrease in the apparent Km. A reduced susceptibility to inhibition by chloride ions contributed to the higher activation rate of Glu-plasminogen on an HPRG surface. The immobilized N- and C-terminal domains, but not the histidine-proline-rich domain of HPRG, also bound plasminogen and stimulated its activation. HPRG-enhanced plasminogen activation was proportional to the quantity of HPRG immobilized and was abolished by anti-HPRG antiserum, by low concentrations of epsilon-aminocaproic acid, by methylation of lysine residues in HPRG, and by treatment of HPRG with carboxypeptidase B. Soluble HPRG and a plasminogen fragment, kringle 1-2-3, acted as competitive inhibitors by binding to plasminogen and immobilized HPRG, respectively. The interaction of the conserved C-terminal lysine of HPRG with the high affinity lysine binding site of plasminogen is necessary and sufficient to accelerate plasminogen activation. Unlike other stimulators of plasminogen activation, the effect of HPRG on fibrinolysis is modulated by factors that influence the equilibrium between solution and surface-bound HPRG.     

Pneumatic displacement of subretinal hemorrhage without tissue plasminogen activator

PURPOSE: To analyze the results of excimer laser phototherapeutic keratectomy (PTK) combined with simple excision in recurrent pterygium to minimize the recurrence rate and obtain a smooth corneal surface. SETTING: Veni Vidi Eye Health Centre, Istanbul, Turkey. METHODS: Combined pterygium excision and excimer laser PTK was performed in 22 eyes with recurrent pterygium (22 patients). Both spot and scan modes of the Meditec MEL 60 excimer laser were used to produce a wide ablation layer (depth 40 to 80 microns). RESULTS: During the mean follow-up of 16.5 months (range 6 to 27 months), visual acuity, refraction, slitlamp, and corneal topography examinations were recorded. Pterygium recurred in only 1 eye (4.5%). Postoperative visual acuity improved in 15 eyes (68.2%). Keratometric readings were not accurately measured preoperatively because of corneal surface irregularities but could be easily taken after the surgery. Corneal astigmatism ranged from 0 to 2.00 diopters (D) (mean 1.23 D). Three months after surgery, no haze persisted in any eye. No significant intraoperative or postoperative complication was detected. CONCLUSIONS: Excimer laser PTK appears to simplify pterygium surgery because a superficial keratectomy is sufficient to remove pterygium. The excimer laser can be used to ablate the visible residual tissues and smooth the corneal surface, resulting in good postoperative refraction and visual acuity. Consequently, this procedure seems to be effective and safe.     

Identifying hypoxic tissue after acute ischemic stroke using PET and 18F-fluoromisonidazole

OBJECTIVE: To show that PET with 18F-fluoromisonidazole (18F-FMISO) can detect peri-infarct hypoxic tissue in patients after ischemic stroke. BACKGROUND: PET with (15)O-labeled oxygen and water is the only established method for identifying the ischemic penumbra in humans. We used PET with 18F-FMISO in patients after ischemic stroke to identify hypoxic but viable peri-infarct tissue likely to represent the ischemic penumbra, and to determine how long hypoxic tissues persist after stroke. METHODS: Patients with acute hemispheric ischemic stroke were studied using PET with 18F-FMISO either within 48 hours or 6 to 11 days after stroke onset. The final infarct was defined by CT performed 6 to 11 days after stroke. Tracer uptake was assessed objectively by calculating the mean activity in the contralateral (normal) hemisphere, then identifying pixels with activity greater than 3 SDs above the mean in both hemispheres. Positive studies were those with high-activity pixels ipsilateral to the infarct. RESULTS: Fifteen patients were studied; 13 within 48 hours of stroke, 8 at 6 to 11 days, and 6 during both time periods. Hypoxic tissue was detected in 9 of the 13 patients studied within 48 hours of stroke, generally distributed in the peripheries of the infarct and adjacent peri-infarct tissues. None of the 8 patients studied 6 to 11 days after stroke exhibited increased 18F-FMISO activity. All 6 patients studied both early and late exhibited areas of increased activity during the early but not the late study. CONCLUSIONS: PET with 18F-FMISO can detect peri-infarct hypoxic tissue after acute ischemic stroke. The distribution of hypoxic tissue suggests that it may represent the ischemic penumbra. Hypoxic tissues do not persist to the subacute phase of stroke (6 to 11 days).     

Assignment of the binding site for tissue plasminogen activator on human fibronectin

The tissue-type plasminogen activator (t-PA) has been found to bind reversibly to human fibronectin (Fn). To locate the binding site on Fn for t-PA, the Fn was degraded with N-tosyl-L-phenylalanyl chloromethyl ketone-treated trypsin, and the resulting fragments were monitored by the enzyme-linked immunosorbent assay method for t-PA binding activities. A 20-kDa fragment with t-PA binding activity was identified, separated, and purified. It was subjected to further degradation with Staphylococcus aureus proteinase V8. An active 10-kDa fragment was finally purified by reverse-phase high pressure liquid chromatography on a C3 column. The dissociation constants of the binding of Fn and the 10-kDa fragment to t-PA were estimated by Scatchard plot to be 1.13 x 10(-8) and 2.08 x 10(-8) M, respectively. The 10-kDa fragment was sequenced and proved to be located at the 8-9th domains of type I homology of Fn. Based on the structural analysis of the 8-9th domains, a heptadecapeptide corresponding to the sequence Thr535-Glyl551 of Fn, which resided at the large disulfide loop of domain (I-9), was designed and synthesized. Both the 10-kDa fragment and the synthetic peptide could competitively inhibit the binding of Fn to t-PA. The synthetic peptide showed about one-tenth of the binding activity of Fn to t-PA with a dissociation constant of 1.35 x 10(-7) M and was proved to be the binding region of Fn for t-PA. In addition, like the intact Fn, both the 10-kDa fragment and the synthetic peptide could remarkably enhance the amidolytic activity of t-PA in a dose-dependent manner, as shown by using S-2288 as a chromogenic substrate.     

Recombinant tissue plasminogen activator for the treatment of spontaneous adult intraventricular hemorrhage

BACKGROUND: Intraventricular hemorrhage (IVH) has a poor prognosis with mortality rates of between 80 and 100% when all four ventricles are involved. Fibrinolytic therapy has been reported to improve overall outcome. METHODS: Patients with severe primary IVH were treated by direct intraventricular injection of recombinant tissue plasminogen activator (rt-PA) into the lateral ventricles, followed by cerebrospinal fluid (CSF) drainage if the intracranial pressure rose above 20 mm Hg. RESULTS: Over a 15-month period from 1995 through 1996, 10 patients were treated, (4 male and 6 female, mean age 35 years; range, 21-55 years). The mean Glasgow Coma Scale score on admission was 6 (range, 4-8) and the mean Graeb score for severity of IVH on the first CT scan was 10 (range, 8-12). Angiography was negative in five cases but identified arteriovenous malformations in three, a post-traumatic pseudoaneurysm in one, and Moya-moya disease in one. The mean total dose requirement of rt-PA was 8.25 mg (range, 6-12 mg) with a significant reduction in the mean Graeb score after 7 days to 3.9 (range, 2-7, p<0.0001). Outcome at 3 months was death in one case (mortality 10%), severe disability in two (20%), moderate disability in three (30%), and good result in four (40%). Four patients (40%) required subsequent CSF shunting. No complications of rehemorrhage, infection, or catheter obstruction were encountered. CONCLUSION: Intraventricular fibrinolysis with rt-PA seems to be safe and effective for the treatment of severe IVH.