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H Yonas

Publications and source records attributed to H Yonas.

At least 37 records · Page 2Linked to original sources
PubMed2000

Xenon-enhanced computed tomography in the management of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

At the University of Pittsburgh, xenon-enhanced computed tomography (XeCT) serves numerous critical roles in the management of patients following aneurysmal subarachnoid hemorrhage (SAH). Routine baseline XeCT studies are obtained within 24 hours of surgery and are used for comparison to later studies. In the setting of a delayed neurological deficit, XeCT is used emergently to distinguish vasospasm from other possible causes and to triage patients to appropriate non-invasive or invasive therapies. In cases of a delayed neurologic deficit without CBF changes, regardless of transcranial doppler results which can be unreliable, XeCT can prevent unnecessary angiography and potentially harmful invasive treatments. For patients demonstrating territorial ischemia diagnostic of symptomatic vasospasm, XeCT is used to monitor the efficacy of both invasive and non-invasive interventions. This paper summarizes the results and significance of clinical studies of XeCT in the management of patients after SAH at our institution.

Humans↗
PubMed1999

Comprehensive transcript analysis in small quantities of mRNA by SAGE-lite.

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that SAGE does not require prior knowledge of the genes of interest and provides quantitative and qualitative data of potentially every transcribed sequence in a particular tissue or cell type. Furthermore, SAGE can quantify low-abundance transcripts and reliably detect relatively small differences in transcript abundance between cell populations. However, SAGE demands high input levels of mRNA which are often unavailable, particularly when studying human disease. To overcome this limitation, we have developed a modification of SAGE that allows detailed global analysis of gene expression in extremely small quantities of tissue or cultured cells. We have called this approach 'SAGE-Lite'. This technique was used for the global analysis of transcription in samples of normal and pathological human cerebrovasculature to study the molecular pathology of intracranial aneurysms. These samples, which are obtained during operative surgical repair, are typically no bigger than 1 or 2 mm and yield <100 ng of total RNA. In addition, we show that SAGE-Lite allows simple and rapid isolation of long cDNAs from short (15 bp) SAGE sequence tags.

Cell Line↗
PubMed1999

Intra-arterial papaverine for the treatment of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Intra-arterial papaverine (IAP) has been described as a treatment for cerebral vasospasm refractory to standard therapy. METHODS: We report a series of 15 consecutive patients with aneurysmal subarachnoid hemorrhage in which IAP was employed for the treatment of symptomatic vasospasm. All patients exhibited delayed ischemic neurologic deficits, focal cerebral hypoperfusion on stable xenon-enhanced computerized tomography cerebral blood flow studies, and angiographically defined arterial narrowing. Papaverine was infused into 32 arteries on 23 occasions. Six patients required multiple treatments between 1 and 8 days apart. In five instances, IAP was combined with angioplasty. RESULTS: Angiographically defined vasospasm was at least partially reversed immediately following treatment on 18 of 23 occasions. The associated clinical improvement was major on 6 occasions, and either minor or none on 17. Post-treatment cerebral blood flow was assessed on 13 occasions and showed improvement in previously ischemic areas on six occasions and no improvement on seven. Complications were encountered on four occasions. Systemic hypotension and transient brain-stem depression were seen with vertebral artery infusions; a generalized seizure and paradoxical aggravation of vasospasm resulting in hemispheric infarction occurred with internal carotid artery infusions. CONCLUSIONS: Intra-arterial papaverine resulted in reversal of arterial narrowing in the majority of cases (78%). However, this angiographic improvement was associated with cerebral blood flow augmentation in only 46% of cases analyzed, and major clinical improvement in 26%.

Adult↗
PubMed1999

Development of obstructive hydrocephalus with lumboperitoneal shunting following subarachnoid hemorrhage.

Hydrocephalus is a frequent complication of subarachnoid hemorrhage (SAH). The optimum method of treating hydrocephalus in this setting has not been determined. We review our experience with patients developing communicating hydrocephalus secondary to SAH and subsequently treated with lumboperitoneal (LP) shunts. Following hospitalization for the treatment of SAH, patients who developed clinical symptoms and radiologic signs of hydrocephalus were treated with (ventriculoperitoneal) VP or LP shunting. Eighteen patients received an LP shunt, of which seven (28%) developed a non-communicating or obstructive hydrocephalus. These seven patients underwent replacement with a VP shunt and have not had further complications. In the setting of post-SAH communicating hydrocephalus, obstructive hydrocephalus may develop after LP shunt placement. Patients who develop this complication and have their LP shunts converted to VP shunts have a favorable prognosis.

Adult↗
PubMed1999

Factors affecting survival rates for acute vertebrobasilar artery occlusions treated with intra-arterial thrombolytic therapy: a meta-analytical approach.

OBJECTIVE: To determine whether recanalization, coma at presentation, or clot location in the basilar artery influences the relative mortality risk after intra-arterial thrombolytic therapy for acute vertebrobasilar artery occlusions. METHODS: Studies were identified using the MEDLINE database for January 1987 to November 1997. Series were included if they involved 10 or more patients with basilar or vertebrobasilar artery occlusions, used urokinase and/or recombinant tissue plasminogen activator, and were written in English. A fixed-effect meta-analysis approach was used to estimate the risk of death with the aforementioned risk factors. Each study was weighted according to sample size. Relative risks were calculated with 95% confidence intervals. RESULTS: As calculated from peer-reviewed published data, the relative mortality risk for patients for whom recanalization was attempted but not achieved was 2.34 (95% confidence interval, 1.48-3.71; n = 126). Coma at presentation was associated with a relative mortality risk of 1.95 (95% confidence interval, 1.26-2.99; n = 145). Clot locations in the distal one-third of the basilar artery were shown to favor survival, compared with clots located in the proximal and/or middle portions of the basilar artery (relative risk, 0.52; 95% confidence interval, 0.31-0.86; n = 126). CONCLUSION: The combined data suggest that coma at presentation has an independent and adverse effect on survival rates. Complete recanalization, distal clot location, and responsiveness at the time of presentation are statistically significant factors for increased patient survival rates.

Adolescent↗
PubMed1999

Noninvasive continuous monitoring of cerebral oxygenation periictally using near-infrared spectroscopy: a preliminary report.

PURPOSE: To report on the use of near-infrared spectroscopy (NIRS) to examine the changes in cerebral oxygenation in the periictal period in patients with seizures. METHODS: Cerebral hemoglobin oxygen availability was monitored continuously and noninvasively with NIRS in three patients (one in the pediatric intensive care unit (ICU) and two in epilepsy-monitoring units) in conjunction with continuous EEG monitoring. Ictal events were recorded and compared with the pre-, intra-, and postictal periods for cerebral oxygen availability, as defined by oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and the redox state of cytochrome oxidase (cytox). RESULTS: Several important preliminary observations were made by using this technology. First, a preictal increase in cerebral oxygenation began between 1 and 2 h and >10 h before the ictal event. Second, despite adequate perfusion, based on an observed increased HbO2, reduction in cytox indicates a perfusion-metabolism mismatch during seizure activity. Third, continued seizure activity and even isolated ictal events were associated with decreased cerebral oxygen availability. Fourth, differences in cerebral oxygen availability were noted between different types of seizures (e.g., electrographic seizures were accompanied by rapid reductions in HbO2 and cerebral blood volume without reduction of cytox, whereas electroclinical seizures were characterized by marked increases in HbO2 with or without reduction of cytox). CONCLUSIONS: In this preliminary report on the use of NIRS for patients with seizures, we believe that NIRS allows continuous and noninvasive monitoring of changes in cerebral oxygenation periictally, thereby permitting investigations into the pathophysiology of seizures and the exploration of the potential of cerebral oximetry as a tool for seizure localization.

Brain↗
PubMed1999

Ischemic core and penumbra in human stroke.

BACKGROUND AND PURPOSE: The ischemic core and penumbra have not been thoroughly characterized after acute cerebral thromboembolic occlusion in humans. Differentiation between areas of potentially viable and irreversibly injured ischemic tissue may facilitate assessment and treatment of stroke patients. METHODS: Cerebral blood flow (CBF) was measured in 20 patients with acute middle cerebral artery (MCA) occlusion between 60 and 360 minutes after stroke onset, with the stable xenon computerized tomography (CT) technique. Threshold displays were generated at a single level, and the percentages of hemisphere with CBF </=6, </=10, 11 to 20, 21 to 30, and >30 cm3. 100 g-1. min-1 were measured. The corresponding images on 12 available follow-up CT scans were similarly assessed to determine the area of final infarct. Comparisons were analyzed with a paired Student's t test and Pearson's correlation coefficient. RESULTS: Discrete and confluent areas of CBF </=20 cm3. 100 g-1. min-1 were identified in all patients, ipsilateral to the symptomatic MCA territory. The average area of CBF </=20 cm3. 100 g-1. min-1 within the ipsilateral hemisphere was 66+/-17% compared with 36+/-12% contralaterally (P<0.001). A difference in the extent of low CBF was due primarily to areas with CBF </=10 cm3. 100 g-1. min-1 (48+/-18% versus 16+/-7%, P<0.001). The area of most severe ipsilateral ischemia (</=6 cm3. 100 g-1. min-1) best corresponded to the final area of infarction (37+/-18% versus 40+/-24%; correlation coefficient, 0.866; P<0.01). The acute ischemic core destined to infarction was not surrounded by a widened rim of moderate ischemia because the area with CBF 11 to 20 cm3. 100 g-1. min-1 was similar bilaterally (19+/-4% versus 20+/-7%, P=0.792, thus not significant). CONCLUSIONS: Our study in acute human stroke involving MCA occlusion indicates that a severely ischemic core (CBF </=6 cm3. 100 g-1. min-1), observed between 1 to 6 hours after stroke onset, corresponds to the cerebral tissue destined to infarction. The ischemic penumbra with flow values between 7 and 20 cm3. 100 g-1. min-1 surrounding the ischemic core is very narrow. Therefore, strategies to improve the outcome of many patients with acute MCA occlusion must either include interventions to reverse the ischemic process within a few minutes of onset or increase the cerebral tolerance of ischemia and thereby prolong the potential therapeutic window.

Acute Disease↗
PubMed1999

Functional polymorphism in the matrix metalloproteinase-9 promoter as a potential risk factor for intracranial aneurysm.

BACKGROUND AND PURPOSE: There is convincing evidence that susceptibility to intracranial aneurysms (ICAs) has a genetic component. However, few studies have sought to identify functional variation in specific candidate genes that may predispose individuals to develop an ICA. METHODS: ICA cases and controls were genotyped for a simple length polymorphism in the promoter of matrix metalloproteinase-9 (MMP-9) to test for association between variation in the promoter and the occurrence of ICA. Alternative alleles were cloned into an in vitro reporter vector, transfected into human HT1080 fibroblasts, and assayed for promoter activity by beta-gal and luciferase assays. Electrophoretic gel shift assays were used to assess nuclear factor binding. RESULTS: A length polymorphism in the promoter of MMP-9 was nonrandomly associated with the occurrence of ICA in a case-control study. This polymorphism was shown, by direct sequencing of 36 individuals, to be the only sequence variation within a 736-base pair region proximal to the transcriptional start site of the gene. Variation in the length of this repetitive element was shown to modulate promoter activity in an in vitro reporter assay, with the highest promoter activity being observed in constructs bearing the longest [(CA)23] element. Electrophoretic mobility shift assays were used to show that the (CA) element is bound by a sequence-specific DNA-binding protein. CONCLUSIONS: Genetic variation in the promoter of the MMP-9 gene results in variation in its expression at the level of transcription. This may result in subtle differences in MMP-9 activity within the circle of Willis, leading to increased susceptibility to ICA formation.

Alleles↗
PubMed1999

Advanced CT imaging (functional CT).

Computed tomography can provide anatomic and functional information about the brain. The conventional CT of the brain can be coupled with a cerebral blood flow examination using the stable xenon CT technique and with a CT angiography. Distinct subgroups of patients based on variations in cerebral blood flow and vascular pathology have been demonstrated. The addition of the functional information has become extremely important in triaging and determining the appropriate intervention in the patient with an acute neurological deficit.

Brain↗
PubMed1999

Saccular aneurysm formation in curved and bifurcating arteries.

BACKGROUND AND PURPOSE: Distinguishing whether forces resulting from the impingement of central blood flow streams at a curved arterial segment or at the apex of an intracranial bifurcation could be important for the understanding of aneurysm formation. Using finite element models, our purpose was to investigate the hemodynamics related to intracranial saccular aneurysm formation through computer simulations. METHODS: We present two-dimensional finite element models describing several distinct stages of aneurysm formation in both curved and bifurcating arteries. For each model, a description of the numeric solutions and results are presented. RESULTS: Our results suggest that the pressures and shear stresses that develop along the outer (lateral) wall of a curved artery and at the apex of an arterial bifurcation create a hemodynamic state that promotes saccular aneurysm formation. The impingement of the central stream results in greatly increased velocity/pressure gradients and high shear stresses at the apex compared with those in the proximal parent or distal daughter branches. The results also indicate that the maximal pressure generated at the apex of the arterial bifurcation ranges from two to three times the peak luminal pressure in the proximal parent artery. CONCLUSION: These data suggest that, in the absence of any underlying disease process, aneurysm development is a mechanically mediated event. These models offer a plausible hypothesis regarding the initiation, growth, and subsequent rupture of saccular intracranial aneurysms as they relate to the hemodynamics of intracranial arterial blood flow.

Biomechanical Phenomena↗
PubMed1998

Effect of xenon-induced flow activation on xenon-enhanced computed tomography cerebral blood flow calculations.

Computer simulations of stable xenon ((S)Xe) uptake curves were used to evaluate the effect of xenon-induced flow activation on CBF calculations by xenon-enhanced computed tomography. Estimates of flow activation were based on repeated transcranial Doppler measurements of blood velocity during 4.5 minutes of (S)Xe inhalation. The synthetic curves were generated from a generalized Kety equation that included time-varying blood flow activation. In contrast to the peak 35% increase in blood flow velocity during (S)Xe inhalation, a standard analysis of the flow-varying synthetic curves revealed only minor 3% to 5% increases in calculated CBF. It is concluded that brief xenon inhalations can provide blood flow estimates that contain minimal bias from activation.

Administration, Inhalation↗
PubMed1998

Qualitative versus quantitative assessment of cerebrovascular reserves.

OBJECTIVE: Quantitative studies of cerebral blood flow (CBF) combined with a vasodilatory challenge have defined a subgroup of patients with symptomatic carotid occlusion who have an increased risk for stroke. These are patients whose CBF paradoxically decreases in response to a vasodilatory challenge. Recent reports suggest that qualitative CBF techniques, such as single photon emission tomography with 99m-hexamethylpropyleneamine oxime, can also define the same high-risk subgroup. To determine whether qualitative measures of CBF are sufficient for predicting the risk of stroke, we converted our quantitative CBF data, obtained with xenon-enhanced computed tomography (Xe/CT), to qualitative ratios in a manner similar to that used with single photon emission tomography data. METHODS: We analyzed CBF values within the territory of the middle cerebral artery for 94 patients with symptomatic carotid occlusion. Values obtained using Xe/CT before and after the intravenous administration of 1 g of acetazolamide were used to derive an asymmetry index: (Coccl - Cnon)/Cavg x 100. The difference between the postacetazolamide asymmetry index and the baseline asymmetry index was used to classify the patients into groups according to CBF values. The threshold for abnormal qualitative CBF reactivity was defined as a percent change in the asymmetry index of less than -10%. Quantitative (Xe/CT) CBF was considered abnormal ("steal" response) when the response to acetazolamide (percent change) on the occluded side was a decrease of 5% or greater. RESULTS: Of 34 patients whose cerebrovascular reserves were considered compromised based on qualitative criteria, 17 (50%) did not have a steal response as defined by quantitative Xe/CT CBF (i.e., false positive). Eleven of 62 (18%) who were not considered compromised by qualitative criteria had a steal response (i.e., false negative). Our data indicate that a qualitative approach has a 61% sensitivity and a 75% specificity for detecting patients with compromised reserves. Further, the positive predictive value of this method is only 50%. Therefore, the two methodologies do not predict the same patients as having compromised reserves. CONCLUSION: Previous studies have shown that patients at high risk for stroke can be identified with quantitative CBF methods. This study shows that the important subgroup cannot be accurately defined with qualitative methodology. The implications of using the more reliable methodology are important for individual patient management and for designing clinical trials.

Acetazolamide↗
PubMed1998

Staged volume radiosurgery followed by microsurgical resection: a novel treatment for giant cerebral arteriovenous malformations: technical case report.

OBJECTIVE AND IMPORTANCE: We describe the successful treatment of symptomatic giant arteriovenous malformations (AVMs) using staged volume radiosurgery followed by microsurgical resection. CLINICAL PRESENTATION: A 57-year-old man presented with Spetzler-Martin Grade 5 AVMs, with persistent headaches and seizures. He had previously undergone eight attempts at AVM embolization and a craniotomy for attempted AVM resection; he had suffered four episodes of brain hemorrhaging but had made a good neurological recovery. INTERVENTION: Because of the persistent symptoms of the patient and his history of hemorrhaging, a treatment plan based on staged radiosurgical treatments of different portions of the AVMs (three sessions, spaced 6 mo apart), followed by delayed microsurgical removal of the much-reduced residual AVMs (3 years later), was undertaken. The patient did not suffer any additional hemorrhaging episodes, his AVMs were completely removed, and he has made a good recovery. CONCLUSION: Staged volume radiosurgery followed by microsurgical resection of the residual AVMs represents a novel treatment strategy for the management of Grade 5 AVMs that might be untreatable by any single treatment method used alone.

Cerebral Angiography↗