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Biomedical subjects

David C Tong

Publications and source records attributed to David C Tong.

14 recordsLinked to original sources
PubMed2006

99mTc-HYNIC-annexin V SPECT imaging of acute stroke and its response to neuroprotective therapy with anti-Fas ligand antibody.

PURPOSE: The first aim of the study was to determine whether (99m)Tc-HYNIC-annexin V, a marker of cellular stress and apoptosis, can detect ischemic injury in patients with acute stroke. Secondly, we wished to test radiolabeled annexin's ability to monitor therapy in a rodent model of focal ischemic injury. METHODS: SPECT imaging of patients was performed between 1 and 2 h after intravenous injection of 30 mCi (1,110 MBq) of tracer. Eight MFL4 (anti-FasL) antibody-treated (400 microg i.p. days 0 and 3) and 21 control adult male Sprague-Dawley rats underwent small animal SPECT imaging with 5-10 mCi (185-370 MBq) of tracer, 1 and 6 days after a 2-h intraluminal thread occlusion of the left middle cerebral artery. RESULTS: Two patients with acute stroke had regions of multifocal annexin uptake that correlated with sites of restricted diffusion on MRI. Anti-FasL antibody treatment significantly reduced annexin uptake by 92% with a 60% decrease in the number of caspase-8 staining (apoptotic) neurons on day 1. On day 6, treated animals had an 80% reduction in tracer uptake with a 75% decrease in infarct size as compared with controls. Annexin uptake in controls and treated animals (day 6) linearly correlated with infarct size (r (2)=0.603, p=0.0036) and the number of TUNEL-positive (apoptotic) nuclei (r (2)=0.728, p=0.00084). CONCLUSION: Annexin imaging shows foci of increased uptake at sites of ischemic injury in patients with acute stroke. Annexin imaging can assess the effects of therapy for ischemic cerebral injury in rats, suggesting its potential as a non-invasive indicator of drug efficacy in future clinical trials.

Acute Disease↗
PubMed2005

Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America.

BACKGROUND: Despite advances in medical, surgical, and critical care interventions, infective endocarditis remains a disease that is associated with considerable morbidity and mortality. The continuing evolution of antimicrobial resistance among common pathogens that cause infective endocarditis creates additional therapeutic issues for physicians to manage in this potentially life-threatening illness. METHODS AND RESULTS: This work represents the third iteration of an infective endocarditis "treatment" document developed by the American Heart Association under the auspices of the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease of the Young. It updates recommendations for diagnosis, treatment, and management of complications of infective endocarditis. A multidisciplinary committee of experts drafted this document to assist physicians in the evolving care of patients with infective endocarditis in the new millennium. This extensive document is accompanied by an executive summary that covers the key points of the diagnosis, antimicrobial therapy, and management of infective endocarditis. For the first time, an evidence-based scoring system that is used by the American College of Cardiology and the American Heart Association was applied to treatment recommendations. Tables also have been included that provide input on the use of echocardiography during diagnosis and treatment of infective endocarditis, evaluation and treatment of culture-negative endocarditis, and short-term and long-term management of patients during and after completion of antimicrobial treatment. To assist physicians who care for children, pediatric dosing was added to each treatment regimen. CONCLUSIONS: The recommendations outlined in this update should assist physicians in all aspects of patient care in the diagnosis, medical and surgical treatment, and follow-up of infective endocarditis, as well as management of associated complications. Clinical variability and complexity in infective endocarditis, however, dictate that these guidelines be used to support and not supplant physician-directed decisions in individual patient management.

Ambulatory Care↗
PubMed2005

Intracranial angioplasty without stenting for symptomatic atherosclerotic stenosis: long-term follow-up.

BACKGROUND AND PURPOSE: Angioplasty and stent placement have been reported for the treatment of intracranial stenosis. This study was undertaken to assess the efficacy and long-term clinical outcome of angioplasty without stent placement for patients with symptomatic intracranial stenosis. METHODS: A retrospective study was done to evaluate 36 patients with 37 symptomatic atherosclerotic intracranial stenosis who underwent primary balloon angioplasty. All patients had symptoms despite medical therapy. Thirty-four patients were available for follow-up ranging from 6 to 128 months. Mean follow-up was 52.9 months. RESULTS: Mean pretreatment stenosis was 84.2% before angioplasty and 43.3% after angioplasty. The periprocedural death and stroke rate was 8.3% (two deaths and one minor stroke). Two patients had strokes in the territory of angioplasty at 2 and 37 months after angioplasty. The annual stroke rate in the territory appropriate to the site of angioplasty was 3.36%, and for those patients with a residual stenosis of > or =50% it was 4.5%. Patients with iatrogenic dissection (n=11) did not have transient ischemic attacks or strokes after treatment. CONCLUSION: Results of long-term follow-up suggest that intracranial angioplasty without stent placement reduces the risk of further stroke in symptomatic patients.

Adult↗
PubMed2005

Mechanical thrombectomy for acute stroke.

BACKGROUND AND PURPOSE: We evaluated a mechanical thrombectomy protocol to treat acute stroke and report the angiographic results and clinical outcomes. METHODS: Patients with anterior circulation strokes <8 hours and posterior circulation strokes <12 hours were treated at a single center over 10 months. Patients were excluded if they were candidates for intravenous tissue plasminogen activator (tPA). Treatment involved one of two mechanical thrombectomy devices. Retrieval was augmented by low-dose intra-arterial tPA if needed. Outcome was measured by using the Modified Rankin score. RESULTS: Ten patients were treated: five with anterior circulation strokes, four with posterior circulation strokes, and one with embolic strokes involving both circulations. Mean National Institutes of Health Stroke Scale score at presentation was 24.6 +/- 10.9. In eight patients (80%), revascularization was successful (Thrombolysis in Acute Myocardial Infarction score, 3). Mean time from symptom onset to initiation of the procedure was 6 hours (5.3 hours for anterior circulation and 7.0 hours for posterior circulation). Mean time for recanalization from the start of the procedure was 1.17 +/- 0.58 hours for the six anterior circulation strokes and 2.75 +/- 1.34 hours in the two posterior circulation strokes. Five patients died within 48 hours; all had posterior circulation strokes. Mean Modified Rankin score at 90 days was 1.4. CONCLUSION: In this small series, mechanical thrombectomy of acute stroke appeared to improve recanalization rates compared with intra-arterial thrombolysis. No hemorrhagic complications occurred. Further study is required to determine the role of these techniques.

Aged↗
PubMed2004

Calcineurin phosphatase activity: activation by glucocorticoids and role of intracellular calcium.

BACKGROUND: Glucocorticoids stimulate release of intracellular calcium in peripheral lymphocytes, but their effects on calcineurin phosphatase activity are unknown. METHODS: Calcineurin phosphatase activity was measured in permeabilized Jurkat T cells using a specific orthophosphate substrate. Changes in intracellular calcium were measured by FURA-2 fluorescence. Inositol triphosphate levels were measured by radioimmunoassay. Transfection with luciferase reporter plasmids linked to glucocorticoid response elements were used to evaluate glucocorticoid receptor function in Jurkat T cells. RESULTS: Dexamethasone significantly (P<0.004) increased calcineurin activity within 15 sec, peaking at 10 min (P<0.001) and returning to basal levels by 180 min. Inhibition of DNA transcription with actinomycin D failed to block calcineurin activation, but co-incubation with RU-486 completely blocked enzyme stimulation. To determine whether Jurkat T cells express active glucocorticoid receptors, cells were transfected with a luciferase reporter plasmid linked to a glucocorticoid response element (GRE). Jurkat T cells incubated with dexamethasone (10 microM) for 24 hr failed to stimulate luciferase activity, whereas cells co-transfected with a transcriptionally active glucocorticoid receptor resulted in a doubling of luciferase activity. Dexamethasone rapidly increases intracellular inositol triphosphate (IP3) and intracellular calcium within 15 sec. Cells incubated with U-73122 (a nonspecific phospholipase C [PLC] antagonist) completely blocked dexamethasone-induced activation of calcineurin, whereas U-73343 failed to block enzyme activation. Dexamethasone-induced activation of calcineurin activity stimulates dephosphorylation of the proapoptotic protein BAD and augments apoptosis through a calcineurin-dependent pathway. CONCLUSION: Dexamethasone rapidly increases calcineurin activity through a transcription-independent mechanism involving activation of phospholipase C and the release of IP3-dependent calcium stores.

Annexin A5↗
PubMed2003

Detection of diffusion-weighted MRI abnormalities in patients with transient ischemic attack: correlation with clinical characteristics.

BACKGROUND AND PURPOSE: Although diffusion-weighted MRI (DWI) has demonstrated clear superiority over other conventional imaging modalities in the detection of hyperacute cerebral ischemia, its value in the evaluation of patients with transient symptoms has received only limited attention. We assessed the utility of DWI in patients with transient ischemic attack (TIA) to further evaluate the usefulness of this technique in these individuals. METHODS: A retrospective analysis was performed on all patients entered in the Stanford Stroke Center database during 1997-2001 who were clinically diagnosed with a TIA and who had also undergone a DWI scan or=1 hour, 16 times more likely to have had motor deficits, and 25 times more likely to have had aphasia than patients with negative DWI scans. The combination of all 3 symptoms was 100% specific for an abnormality on DWI. In 7 of 16 cases (44%), a DWI abnormality was present on both DWI and conventional imaging (T2-weighted imaging or fluid-attenuated inversion recovery [FLAIR]). In all of these cases the DWI clarified the extent or acuity of the lesion (n=7) or identified additional lesions not detected by conventional imaging (n=9). CONCLUSIONS: In TIA patients, symptom duration >or=1 hour, motor deficits, and aphasia were each independently correlated with detecting an abnormality with DWI. DWI was also helpful in differentiating between chronic versus acute lesions. These data may be of value in identifying those TIA patients for whom MRI evaluation with DWI is of greatest clinical utility.

Diffusion Magnetic Resonance Imaging↗
PubMed2003

New magnetic resonance imaging and computed tomography techniques for imaging of acute stroke.

With continued advances in acute stroke therapy, the ability to accurately assess the physiologic status of ischemic brain tissue and related vascular lesions has become increasingly important. In this review, evidence regarding the use of new magnetic resonance imaging and computed tomography techniques to guide thrombolytic therapy, diagnose stroke subtype, and detect acute hemorrhage are discussed in order to provide a clearer picture of the status of these neuroimaging techniques in the assessment of acute ischemic stroke patients.

Animals↗
PubMed2002

Use of diffusion weighted MRI to predict the occurrence and severity of hemorrhagic transformation in a rabbit model of embolic stroke.

Severe hemorrhagic transformation (HT) is an important complication of thrombolytic therapy. A method to identify stroke victims destined to severe HT could improve the patient selection and thus the safety of such treatment. In this study, we investigated whether very early serial diffusion weighted magnetic resonance imaging (DWI) could predict the occurrence of HT in an embolic model of experimental stroke. We tested the hypothesis that the ischemic brains with very low initial apparent diffusion coefficients (ADC) are destined to severe early (<or=5.5 h) HT. We retrospectively analyzed DWI scans of 45 New Zealand white rabbits subjected to thromboembolic stroke and treated with thrombolysis. DWI was obtained 0.5, 2, 3 and 5 h after embolization. Various thrombolytics were administered 1 h post embolization. The percentage of pixels within the ischemic hemisphere with ADC values below 550 x 10(-6) mm(2)/s was calculated and then compared to the severity of HT observed on gross brain sections at 5.5 h. As early as 30 min after embolization, ischemic brains destined to severe HT exhibited a significantly greater percentage of pixels below the cut-off value compared to those without HT: severe HT: 25%, 18.75-37.25% vs. no HT: 12%, 5.00-16.00% (median, 25th-75th %, P<0.001). Petechial HT when percentages were in the intermediate range. Quantitative analysis of initial ADC value might identify individual stroke patients at risk of severe HT.

Animals↗
PubMed2002

Intravenous rt-PA for stroke.

Thrombolytic therapy remains the most potent known treatment for acute ischaemic stroke. Treatment can significantly improve neurological outcome with only a mild increase in haemorrhage risk. Previous concerns over the importance of subtle CT detect early infarct signs appears unwarranted. Most patients with a significant neurological deficit and without evidence of haemorrhage on initial head imaging in the < 3 h window should be considered for treatment. Subgroup analysis suggests that even patients with severe strokes and early signs of cerebral ischaemia on CT may benefit from treatment, albeit to a lesser degree. Community based studies indicate that a similar degree of efficacy can be achieved in routine clinical practice, especially at centres experienced at thrombolytic administration. Treatment beyond 3 h may also be efficacious in selected cases, but further clinical trials are necessary before routine use in this time period can be advocated.

Clinical Trials as Topic↗
PubMedDate not supplied

Association of early CT abnormalities, infarct size, and apparent diffusion coefficient reduction in acute ischemic stroke.

BACKGROUND AND PURPOSE: Diffusion-weighted (DW) imaging is more sensitive for early ischemia than CT, and apparent diffusion coefficient (ADC) mapping permits quantification of the severity of cytotoxic edema. We examined the relationship between early CT findings, ischemic lesion volume on DW images, and edema subtype. METHODS: Patients in whom early signs of ischemia were detected on baseline CT scans were scored CT positive. Baseline DW lesion volumes were compared between the CT-positive and CT-negative patients. In CT-positive patients, we outlined the CT-positive part of the DW lesion and transferred these regions of interest to the corresponding DW sections. The ADC values of the outlined CT-positive areas were then compared with the ADC values of the CT-negative areas within patients. Lesions with significantly increased T2 hyperintensity were excluded to correct for the effect of early vasogenic edema on ADC measurements. RESULTS: Twenty-four patients with cerebral ischemia in whom both CT and DW imaging were performed within 8 hours of symptom onset were entered into the study. Patients with early CT signs of infarction (n = 12) had significantly larger DW lesion volumes than did patients without early CT abnormalities (mean volume, 62.8 versus 14.6 mL; P =. 002). In patients displaying early CT abnormalities, CT-positive regions of the DW lesion had lower relative ADC (rADC) values than did the CT-negative regions, when lesions with significant T2 hyperintensity were excluded (mean rADC, 0.65 versus 0.75; P =.037). CONCLUSION: These findings support the hypothesis that early CT signs of infarction indicate more extensive and severe cerebral ischemia, as reflected by lower ADC.

Acute Disease↗
PubMedDate not supplied

Automated method for generating the arterial input function on perfusion-weighted MR imaging: validation in patients with stroke.

BACKGROUND AND PURPOSE: The choice of arterial input function (AIF) can have a profound effect on the blood flow maps generated on perfusion-weighted MR imaging (PWI). Automation of this process could substantially reduce operator dependency, increase consistency, and accelerate PWI analysis. We created an automated AIF identification program (auto-AIF) and validated its performance against conventional manual methods. METHODS: We compared the auto-AIF against manually derived AIFs from multisection PWIs of 22 patients with stroke. Time to peak, curve width, curve height, and voxel location determined with both techniques were compared. The time to maximum of the tissue residue function (Tmax) and cerebral blood flow (CBF) were computed on a per-pixel basis for each AIF. Spatial patterns of 528 map pairs were compared by computing Pearson correlation coefficients between maps generated with each method. RESULTS: All auto-AIF-derived PWI map parameters, including bolus peak, width, and height, were consistently superior to manually derived ones. Reproducibility of the auto-AIF-based Tmax maps was excellent (r = 1.0). Paired Tmax maps and CBF maps from both techniques were well correlated (r = 0.82). Time to identify the AIF was significantly shorter with the auto-AIF method than with the manual technique (mean difference, 72 seconds; 95% confidence interval: 54, 89 seconds). CONCLUSION: An automated program that identifies the AIF is feasible and can create reliably reproducible and accurate Tmax and CBF maps. Automation of this process could reduce PWI analysis time and increase consistency and may allow for more effective use of PWI in the evaluation of acute stroke.

Adult↗