Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To show relationship between degree of carotid arterial stenosis and cerebral blood flow reactivity (RES%) to induced hypercapnia, fluorine-18-fluoromethane and positron emission tomography (PET) was used to study 18 patients with carotid distribution transient ischaemic attacks (TIA), all free of stroke, who had angiographic-proven unilateral arterial disease. Non-involved carotid arteries were either normal or had non-stenotic plaque. Either normal arteries or nonstenotic ulcerations in the symptomatic carotid arteries were present in five of 18 (28%), ipsilateral carotid stenosis from 50-99% was present in eight of 18 (44%), and ipsilateral internal carotid occlusion was present in five of 18 (28%) patients. In comparison with 14 normal controls, all patients with symptomatic middle cerebral artery (MCA) flow territories had significantly lower mean (SEM) RES% [5.0' (0.2) vs 4.0 (0.9), p less than 0.04]. Symptomatic anterior borderzone (ABZ) RES% was also significantly lower [4.6 (0.4) vs 3.3 (0.9), p less than 0.04], than controls. In patient subgroup comparisons, the 50-99% stenosis subgroup clearly had the lowest MCA RES% [3.4 (0.2)] as well as the lowest ABZ RES% [2.8 (0.4)] on their symptomatic sides. Age, expired pCO2, mean arterial blood pressure, serum glucose, serum haematocrit and number, type and estimated duration of TIAs were not significantly different between subgroups. Linear regression showed a significant relationship between RES% and both measured percentage-stenosis (p = 0.04) and residual luminal diameter (p = 0.05) in symptomatic MCA territories. This approached significance in symptomatic ABZ regions. This preliminary data set suggests that unilateral carotid stenosis can and does result in impaired CO2 reactivity following hypercapnia. The relative normality of CO2 reactivity in those with carotid occlusion is discussed.
 ...
PMID:Blood flow reactivity to hypercapnia in strictly unilateral carotid disease: preliminary results. 190 47

Nineteen patients with strictly unilateral ischemic stroke as determined by clinical examination, computed tomography, magnetic resonance imaging, and standard angiography underwent cerebral blood flow (CBF) analysis using fluorine 18 fluoromethane and positron emission tomography. Mean flow values for averaged hemispheric, infarct, and homologous contralateral regions of interest (ROIs) were determined. All patient CBF values were significantly below comparable CBF ROIs in neurologically normal controls using Wilcoxon's two-sample rank testing. Multiple regression analysis disclosed a significant correlation between contralateral CBF are both localized CBF in the infarct ROI and patient age. Correlations between contralateral CBF and dependency score or severity of neurologic deficit at time of positron emission tomography, expired PCO2, mean arterial blood pressure, serum glucose or hematocrit, risk factor score, and number of days studied after stroke were not statistically significant. Although we did not identify the biologic mechanisms involved, we conclude that CBF reduction contralateral to a strictly unilateral ischemic infarction is due to a combination of aging and transhemispheric diaschisis.
 ...
PMID:Evidence for transhemispheric diaschisis in unilateral stroke. 234 86

We developed techniques to assess the utility of a nuclear magnetic resonance (NMR) indicator for cerebral blood flow studies in cats, using Freon-22 for the first candidate. A PIN-diode-switched NMR experiment allowed the acquisition of an arterial as well as a cerebral fluorine-19 signal proportional to concentration vs. time in a 1.89 T magnet. Mean +/- SD blood:brain partition coefficients for Freon-22 were estimated at 0.93 +/- 0.08 for gray matter and 0.77 +/- 0.12 for white matter. Using maximum-likelihood curve fitting, estimates of mean +/- SD resting cerebral blood flow were 50 +/- 19 ml/100 g-min for gray matter and 5.0 +/- 2.0 ml/100 g-min for white matter. Hypercapnia produced the expected increases in gray and white matter blood flow. The physiologic effects of Freon-22, including an increase in cerebral blood flow itself with administration of 40% by volume, may limit its use as an indicator. Nevertheless, the NMR techniques described demonstrate the feasibility of fluorine-19-labeled compounds as cerebral blood flow indicators and the promise for their use in humans.
Stroke 1989 Feb
PMID:Cerebral blood flow measured by NMR indicator dilution in cats. 264 93

Pre- and postoperative positron emission tomography (PET) was performed in six patients undergoing extracranial to intracranial bypass procedures for the treatment of symptomatic extracranial carotid occlusion. The six patients were all men, aged 52 to 68 years. Their symptoms included transient ischemic attacks (five cases), amaurosis fugax (two cases), and completed stroke with good recovery (one case). Positron emission tomography was performed within 4 weeks prior to surgery and between 3 to 6 months postoperatively, using oxygen-15-labeled CO, O2, and CO2 and fluorine-18-labeled fluorodeoxyglucose. Cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rates for oxygen and glucose (CMRO2 and CMRGlu), and the oxygen extraction fraction (OEF) were measured in both hemispheres. Preoperatively, compared to five elderly control subjects, patients had increased CBV, a decreased CBF/CBV ratio, and decreased CMRO2, indicating reduced cerebral perfusion pressure and depressed oxygen metabolism. The CBF was decreased in only one patient who had bilateral carotid occlusions; the OEF, CMRGlu, and CMRO2/CMRGlu and CMRGlu/CBF ratios were not significantly different from control measurements. All bypasses were patent and all patients were asymptomatic following surgery. Postoperative PET revealed decreased CBV and an increased CBF/CBV ratio, indicating improved hemodynamic function and oxygen hypometabolism. This was associated with increased CMRO2 in two patients in whom the postoperative OEF was also increased. The CMRGlu and CMRGlu/CBF ratio were increased in five patients. Changes in CBF and the CMRO2/CMRGlu ratio were variable. One patient with preoperative progressive mental deterioration, documented by serial neuropsychological testing and decreasing CBF and CMRO2, had improved postoperative CBF and CMRO2 concomitant with improved neuropsychological functioning. It is concluded that symptomatic carotid occlusion is associated with altered hemodynamic function and oxygen hypometabolism. Cerebral revascularization results in decreased CBV, indicating improved hemodynamic reserve, but does not consistently improve oxygen metabolism.
 ...
PMID:Hemodynamic and metabolic effects of cerebral revascularization. 349 9

Using clinical presentation, angiography, computed tomography, and nuclear magnetic resonance imaging, 7 patients were identified who had strictly unilateral hemispheric infarction and unilateral cerebrovascular disease. In 6, cerebral blood flow measured by fluorine-18-fluoromethane inhalation and positron emission tomography was reduced in the contralateral hemisphere (p less than 0.05). Multiple regression analysis demonstrated a high correlation between contralateral flow reduction and the degree of flow impairment in the infarcted area (r = 0.941, p = 0.0014) but not with age, risk factor profile, blood pressure, PCO2, hematocrit, or duration of stroke. We conclude that transhemispheric diaschisis best explains the contralateral flow reduction seen in supratentorial ischemic stroke.
Stroke
PMID:Contralateral flow reduction in unilateral stroke: evidence for transhemispheric diaschisis. 349 40

We studied cerebellar metabolism in 118 subjects including young and elderly controls and patients suffering from stroke, supratentorial brain tumor and Alzheimer's disease using fluorine-18 fluorodeoxyglucose ([18F]FDG) and position emission tomography (PET). Alzheimer's disease and normal aging did not alter mean cerebellar metabolism. In stroke and tumor mean cerebellar metabolism was lower in the hemisphere contralateral to the supratentorial lesion. In tumor bilaterally significant reductions in absolute cerebellar metabolism also were noted, unlike stroke. Primary sensory stimulation did not alter absolute or relative cerebellar metabolism. These results show that absolute and relative values for cerebellar metabolism vary depending on the process under study. Thus analysis schemes employing normalization of regional metabolic data to cerebellar values may be subject to error.
 ...
PMID:Cerebellar glucose consumption in normal and pathologic states using fluorine-FDG and PET. 349 90

Hypoxic, non-functional, but viable, tissue may exist in heart and brain following an arterial occlusion. Identification of such tissue in vivo is crucial to the development of effective treatment strategies. It has been suggested that certain compounds capable of sensitizing hypoxic tumor cells to killing by x-rays (i.e., misonidazole) might serve as in vivo markers of hypoxic tissue in ischemic myocardium or brain if properly radiolabeled. To this end we have radiolabeled two fluorinated analogs of nitroimidazole based hypoxic cell sensitizers with the 110 minute half-lived positron-emitting fluorine-18. The ability of these tracers to quantitate the presence of hypoxic tissue has been studied in a gerbil stroke model. The in vivo uptake of one of these tracers [F-18]-fluoronormethyoxymisonidazole is dependent on the extent of tissue hypoxia, and thus, appears to have potential as a diagnostic indicator of non-functional but viable tissue when the tracer is used in conjunction with positron emission tomography.
 ...
PMID:Radiolabeled hypoxic cell sensitizers: tracers for assessment of ischemia. 360 Jan 79

To show a relationship between age and cerebral blood flow as well as between age and cerebral vasocapacitance to induced hypercapnia or cerebral reserve percentage, positron emission tomography (PET) with fluorine-18-fluoromethane was used to study 36 normal subjects and 36 patients, all free of stroke, who presented with transient ischemic attacks in a unilateral carotid distribution. Symptomatic-side data have been published elsewhere. All asymptomatic carotid arteries were either normal or had nonstenotic plaque, and subjects were free of intracranial stenoses. Cerebral blood flow and cerebral reserve percentage were calculated for both middle cerebral artery flow territories. Serum hematocrit, expired carbon dioxide tension, and mean arterial blood pressure did not distinguish the two groups of patients or show an age effect. For the 72 normal nonstenotic sides in the volunteers, linear regression showed that while increasing age was significantly related to decreasing cerebral blood flow in the middle cerebral artery, there was no particular relationship between age and decreasing cerebral reserve percentage. In patients, while no overwhelming linear relationships were found between age and decreases in either cerebral blood flow or cerebral reserve percentage, the latter values approached significance as declining cerebral reserve percentage did relate to increasing age. Over a 60-year range in normal subjects, cerebral blood flow declined 37% with age; there was a 21% age-related decrease when normal subjects 50 years and younger were compared to those 50 years and older.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cerebral vasocapacitance in human aging. 806 81

A 2-[18F]-Fluoro-2-Deoxy-D-Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.
 ...
PMID:Left and right hemisphere contribution to recovery from neglect after right hemisphere damage--an [18F]FDG pet study of two cases. 845 81

Hypoxia occurs to a variable extent in a vast majority of rodent and human solid tumors. It results from an inadequate and disorganized tumor vasculature, and hence an impaired oxygen delivery. A probe for the non-invasive detection of tumor hypoxia could find important utility in the selection of patients for therapy with bioreductive agents, anti-angiogenic/anti-vascular therapies and hypoxia-targeted gene therapy. In addition, tumor hypoxia has been shown to predict for treatment outcome following radio- or chemotherapy in human cancers, the underlying mechanism for which may involve hypoxia driving genetic instability and resulting tumor progression. Beyond oncology, utility can also be envisaged in stroke, ischemic heart disease, peripheral vascular disease, arthritis and other disorders. Design, validation, preclinical development and current status of a fluorinated 2-nitroimidazole, N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-l-imidazolyl) acetamide (SR 4554, CRC 94/17), which has been rationally designed for the measurement of tumor hypoxia by magnetic resonance spectroscopy (MRS) and imaging (MRI), are reviewed. Application in positron emission tomography (PET) detection is also proposed. Design goals were: (i) a nitro group with appropriate redox potential for selective reduction and binding in hypoxic tumor cells; (ii) hydrophilic/hydrogen bonding character in the side chain to limit nervous tissue penetration and prevent neurotoxicity; and (iii) three equivalent fluorine atoms to enhance MRS/MRI detection, located in a metabolically stable position. Reduction of SR 4554 by mouse liver microsomes was dependent on oxygen content, with a half-maximal inhibition at 0.48 +/- 0.06%. SR 4554 underwent nitroreduction by hypoxic but not oxic tumor cells in vitro and electron energy loss spectroscopic analysis showed selective retention in the hypoxic regions of multicellular tumor spheroids. Pharmacokinetic design goals were met. In particular, low brain tissue concentrations were seen in contrast to excellent tumor levels, as measured by high performance liquid chromatography. The extent of this restricted entry to brain tumor was surprising given the overall octanol/water partition coefficient and was attributed to the hydrophilic/hydrogen bonding character of the side chain. Quantitative MRS was used to assess the retention of 19F signal in murine tumors and human tumor xenografts. The 19F retention index (FRI; ratio of 19F signal levels at 6 h relative to that at 45 min) ranged from 0.5 to 1.0 and 0.2 to 0.9 for murine tumors and human xenografts respectively. The correlation between SR 4554 retention and pO2 was not a linear one, but when FRI was > 0.5, the % pO2 < or = 5 mmHg was always > 60%, indicating that high FRI was associated with low levels of oxygenation. Finally, whole body 19F-MRI in mice demonstrated that SR 4554 and related metabolites localized mainly in tumor, liver and bladder regions. A selective MRS signal was readily detectable in tumors at doses at least 7-fold lower than those likely to cause toxicity in mice. We conclude that proof of principle is established for the use of SR 4554 as a non-invasive MRS/MRI probe for the detection of tumor hypoxia. Based on these promising studies, SR 4554 has been selected for clinical development.
 ...
PMID:Preclinical development and current status of the fluorinated 2-nitroimidazole hypoxia probe N-(2-hydroxy-3,3,3-trifluoropropyl)-2-(2-nitro-1-imidazolyl) acetamide (SR 4554, CRC 94/17): a non-invasive diagnostic probe for the measurement of tumor hypoxia by magnetic resonance spectroscopy and imaging, and by positron emission tomography. 975 26


1 2 3 4 5 6 7 8 9 10 Next >>