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Growth chamber experiments were conducted to evaluate the response of sesame to PRE and POST applications of soil residual herbicides. PRE applications of acetochlor andS-metolachlor at 1.26 and 1.43 kg ai·ha−1showed little or no sesame... more
Growth chamber experiments were conducted to evaluate the response of sesame to PRE and POST applications of soil residual herbicides. PRE applications of acetochlor andS-metolachlor at 1.26 and 1.43 kg ai·ha−1showed little or no sesame injury (0 to 1%) 4 wks after herbicide treatments (WAT). POST treatments of acetochlor and trifluralin made 3 wks after planting (WAP) resulted in greater sesame injury (40%) compared to applications at bloom (18%). Field studies were conducted in Texas and Oklahoma during the 2014 and 2015 growing seasons to determine sesame response to clethodim, diuron, fluometuron, ethalfluralin, quizalofop-P, pendimethalin, pyroxasulfone, trifluralin, and trifloxysulfuron-sodium applied 2, 3, or 4 weeks after planting (WAP). Late-season sesame injury with the dinitroaniline herbicides consisted of a proliferation of primary branching at the upper nodes of the sesame plant (in the shape/form of a broom). Ethalfluralin and trifluralin caused more “brooming” effect...
Research Interests: Agronomy, Biology, Chlorosis, Acetochlor, Trifluralin, and 4 morePendimethalin, Sowing, Growing Season, and Metolachlor
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Aims: Field studies were conducted to determine sesame response to the pre-emergence herbicides (acetochlor at 1.7 kg ai ha-1; S-metolachlor at 0.72, 1.43, and 2.86 kg ai ha-1; dimethenamid-P at 0.84 kg ai ha-1; pethoxamid at 0.22 kg ai... more
Aims: Field studies were conducted to determine sesame response to the pre-emergence herbicides (acetochlor at 1.7 kg ai ha-1; S-metolachlor at 0.72, 1.43, and 2.86 kg ai ha-1; dimethenamid-P at 0.84 kg ai ha-1; pethoxamid at 0.22 kg ai ha-1; pyroxasulfone at 0.09 kg ai ha-1and bicyclopyrone at 0.12 and 0.24 kg ai ha-1) applied 3 or 6 days after 50% emergence. Study Design: Randomized complete block design with 3-4 reps depending on location. Place and Duration of Study: Sesame growing areas of Alabama, Mississippi, and Texas during the 2016 through 2018 growing seasons. Methodology: Treatments consisted of a factorial arrangement of herbicide treatments at two early POST application timings. A non-treated control was included for comparison. Crop oil concentrate (Agridex®, Helena, Collierville, TN 38017) at 1.0% v/v was added to all herbicide treatments. Plot size was either five rows (76 cm apart) by 9.1 m or four rows (101 cm apart) by 7.3 m depending on location. Only the two m...
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Objective: To determine if IV rt-PA is safe in therapeutically anticoagulated or thrombocytopenic patients. Background: IV rt-PA guidelines generally exclude therapeutically anticoagulated or thrombocytopenic patients. However, these... more
Objective: To determine if IV rt-PA is safe in therapeutically anticoagulated or thrombocytopenic patients. Background: IV rt-PA guidelines generally exclude therapeutically anticoagulated or thrombocytopenic patients. However, these exclusion criteria may limit IV thrombolytic therapy to patients who might benefit. Design/Methods: Retrospective analysis of IV rt-PA treated patients receiving oral anticoagulation (warfarin (INR ≥1.7) or a novel oral anticoagulant (NOAC)), therapeutic heparin, low-molecular weight heparin (LMWH), or with thrombocytopenia (platelets Results: 67 patients were identified. 33 patients received therapeutic warfarin and one had a coagulopathy (unclear etiology). In these patients, mean INR was 2.2 (range 1.7–3). 5 patients received therapeutic IV heparin, 6 full dose (1 mg/kg BID) LMWH, and 10 therapeutic NOACs (3 dabigatran, 4 rivaroxoban, 3 apixiban). 12 patients had thrombocytopenia (mean platelet count 77K). 7 patients received adjunct intra-arterial (...
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Follicular lymphoma (FL) is the most frequently occurring indolent B-cell non-Hodgkin lymphoma. Treatment typically involves rituximab in combination with bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or... more
Follicular lymphoma (FL) is the most frequently occurring indolent B-cell non-Hodgkin lymphoma. Treatment typically involves rituximab in combination with bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), or CVP (cyclophosphamide, vincristine, and prednisone). Disease relapse is high, and current treatment options for these patients are limited. BTK inhibition has limited clinical activity in FL patients, and while the PI3Kδ inhibitor idelalisib was recently approved, tolerability has been an issue. Limited clinical activity was observed with the Bcl-2 inhibitor venetoclax, due to a compensatory upregulation of Mcl-1 by the tumor cell. Consequently, novel treatment strategies are required for patients with relapsed/refractory FL. Cerdulatinib is a dual SYK/JAK inhibitor that targets the BCR and cytokine signaling pathways. We previously demonstrated in chronic lymphocytic leukemia (CLL) cells that cerdulatinib inhibited signaling via the BCR and IL-4 s...
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Hogarth Flyover is one of west London’s most notorious flyovers, carrying 10 500 vehicles over Hogarth Roundabout every day. The 250 m long, single-lane structure was built in 1971 as a temporary measure to reduce traffic congestion at... more
Hogarth Flyover is one of west London’s most notorious flyovers, carrying 10 500 vehicles over Hogarth Roundabout every day. The 250 m long, single-lane structure was built in 1971 as a temporary measure to reduce traffic congestion at the roundabout, with an estimated design life of around 5 years – and is still in use today after nearly 50 years. Following a detailed review and structural assessment by Conway Aecom, the structure was deemed to be in a seriously poor condition. A substandard bridge management system was instigated, followed by an accelerated scheme to demolish and reconstruct the flyover’s concrete deck. To meet the 6-week closure window imposed by Transport for London, repairs were made by clamping new concrete deck panels to the existing steel work supports, which were also repaired. The restorations also coincided with the summer school holidays, minimising the disruption to traffic. Hogarth Flyover was reopened to the public on 31 August 2014, 10 h ahead of sch...
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Endovascular coil embolization and craniotomy with clip ligation are the two most commonly used treatments for ruptured cerebral aneurysm. While coiling maintains the advantages of brevity and complete avoidance of brain retraction and... more
Endovascular coil embolization and craniotomy with clip ligation are the two most commonly used treatments for ruptured cerebral aneurysm. While coiling maintains the advantages of brevity and complete avoidance of brain retraction and manipulation, clipping offers the benefits of decompression of the injured brain and lower aneurysm recurrence rates. A combined, immediately sequential treatment strategy for acutely ruptured cerebral aneurysm that simultaneously maximizes the advantages of both techniques, while minimizing their respective disadvantages, may be a useful paradigm. To demonstrate the complementarity of clipping and coiling in acutely ruptured cerebral aneurysm. Patients with ruptured anterior circulation cerebral aneurysm standing to benefit from brain decompression were treated by a combination of coiling and microneurosurgery in rapid succession, under the same general anesthetic. Surgery consisted of clipping of the aneurysm via either craniotomy or craniectomy wit...
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Publisher Summary This chapter provides an overview of a graph-theoretic study of the numerical solution of sparse positive definite systems of linear equations. By following the formulation of elimination as a combinatorial process a... more
Publisher Summary This chapter provides an overview of a graph-theoretic study of the numerical solution of sparse positive definite systems of linear equations. By following the formulation of elimination as a combinatorial process a considerable insight into the elimination process by studying the evolution of the cycle structure and the vertex-separator, or cut-set, structure of a graph under elimination can be gained. Furthermore, by counting the arithmetic operations necessary to effect the decompositions, these criteria for optimization is related to the computational complexity of calculations involving the elimination process. A graph-theoretic approach for dealing with sparse systems in regard to Gaussian elimination is to attempt to find permutation matrices P, Q such that A = PMQ, which is block lower triangular, as in this case it is necessary only to decompose the diagonal blocks of PMQ. Naturally, such a transformation does not preserve symmetry. However, results of these are not applicable when M is symmetric positive definite and irreducible, because the algorithm would then produce only one diagonal block, M.
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Abstract : A review is reported of the cost estimating techniques and capabilities that currently exist in the military departments. A major portion of this review consisted of visits to several subordinate commands of the Services'... more
Abstract : A review is reported of the cost estimating techniques and capabilities that currently exist in the military departments. A major portion of this review consisted of visits to several subordinate commands of the Services' materiel commands to observe how cost estimating and pricing is being performed on major weapon system programs. Estimates are discussed for three major purposes: planning, budget preparation, and contract pricing. These estimates were usually separate and distinct and little effort was made to compare them.
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Research Interests: Traumatic Brain Injury, Microcirculation, Medicine, Critical Care, Brain, and 11 moreHumans, INTENSIVE CARE, Subarachnoid hemorrhage, Intracerebral Hemorrhage, Intensive Care Medicine, Cerebral Blood Flow, Oxygen Consumption, Intracranial Pressure, Brain injuries, Cerebral perfusion pressure, and Neurointensive Care
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INTRODUCTIONFluorescence microscopy is used to visualize specific cellular components in as native a state and organization as possible. This article describes some of the main issues that must be considered when cells and tissues are... more
INTRODUCTIONFluorescence microscopy is used to visualize specific cellular components in as native a state and organization as possible. This article describes some of the main issues that must be considered when cells and tissues are fixed and permeabilized. To preserve cellular structure, the specimen is fixed chemically to retain the cells or tissue in a state as near to life as possible by rapidly terminating all enzymatic and other metabolic activities to minimize post-fixation changes. Sample fixation is one of the most crucial steps in assuring the accuracy of detection protocols and is therefore decisive in determining the subsequent success or failure of a given experiment. Underfixation of the sample leads to poor morphological preservation and/or loss of signal, whereas overfixation may lead to fixation artifacts, loss of signal, and/or increased nonspecific background signals (“noise”). An ideal fixative should preserve a given antigen in a fashion that reflects the in v...
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INTRODUCTIONThis protocol describes a method for embedding tissues in paraffin blocks for sectioning. Paraffin sections require extensive fixation and processing steps, but provide superior morphology compared with other sectioning methods.
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On rereading our paper, we find that nowhere in it did we mention the name ASTRAL (Analog Schematic Translator to Algebraic Language), which was finally given to the compiler. The designation serves to describe the compiler, as well as to... more
On rereading our paper, we find that nowhere in it did we mention the name ASTRAL (Analog Schematic Translator to Algebraic Language), which was finally given to the compiler. The designation serves to describe the compiler, as well as to give recognition to Convair-Astronautics (now General Dynamics Astronautics), the organization which supported the development of ASTRAL. In 1957, when the authors first began the work which eventually led to the ASTRAL compiler, the relationship between digital and analog computation was rather cool and distant. While analog and digital installations were often physically adjacent, the interaction of the groups using each type of equipment was almost nil. The idea that a problem was either of analog type or of digital type predominated; the assignment to one class or the other depended more on the background of the programmer than the na-
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Objective: To evaluate the outcome of ischemic stroke (IS) patients, including sub acute IS and IV rt-PA patients transferred to a large Comprehensive Stroke Center (CSC), as compared to patients directly admitted through the CSC9s ED.... more
Objective: To evaluate the outcome of ischemic stroke (IS) patients, including sub acute IS and IV rt-PA patients transferred to a large Comprehensive Stroke Center (CSC), as compared to patients directly admitted through the CSC9s ED. Background Although many IS patients are transferred to Stroke Centers, particularly CSCs, it is unclear whether this is beneficial. Given the substantial resources required for transfer, an analysis of outcomes of these patients is important. Also, if transferred patients are significantly different from direct ED admits, this could influence performance metrics, which are increasingly being used by regulatory authorities 1 . Design/Methods: Retrospective study of all consecutively treated IS patients between 7/2006-12/2010 either through the CSC9s ED or transferred. Outcomes measures included admit and discharge NIHSS, mortality and length of stay (LOS). Results: From 7/2006-12/2010, 1305 IS patients were evaluated. 77% were ED admits and 23% transferred patients. Transferred patients were 51% female, younger (mean 67yr vs. 75yr for ED patients), and had more severe strokes with a mean admission NIHSS of 10 vs. 6 for direct admits (p=0.0001). Transferred patients showed greater functional improvement between admission and discharge NIHSS (difference between pre- and post-NIHSS 3.2 vs. 1.3 for direct admits, p=0.0001), but had longer LOS (6.9d vs. 4.5d for ED patients). Mortality risk was greater among transfers (OR 2.5 95% CI 1.6 – 3.9, p=0.0001). Conclusions: Despite having more severe strokes, transferred patients had greater improvement during hospitalization than directly admitted patients. However, transfers had substantially longer LOS and higher mortality despite being significantly younger. These data suggest important differences between transferred and non-transferred IS patients, which may have important implications for stroke center performance metrics. Nevertheless, these data support the transfer of stroke patients to tertiary centers or CSCs, given the overall improved outcomes. Supported by: References: 1. Leifer, D, et al. Stroke 2011; 42: 849-877. Disclosure: Dr. Barazangi has received personal compensation for activities with Genentech Inc. Dr. Grosvenor has nothing to disclose. Dr. Bedenk has nothing to disclose. Dr. Rose has received personal compensation for activities with Boehringer Ingelheim as a speaker. Dr. Tong has received personal compensation for activities with Genentech, Inc. as a speaker.
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The genome of Arabidopsis thaliana is known to contain numerous open reading frames apparently encoding transposases. In order to test the hypothesis that transposable elements have played a role in segmental duplication in this species,... more
The genome of Arabidopsis thaliana is known to contain numerous open reading frames apparently encoding transposases. In order to test the hypothesis that transposable elements have played a role in segmental duplication in this species, we compared the distribution of transposable elements with that of genomic windows that shared gene families to a greater extent than expected by chance. Phylogenetic analyses indicated that duplication of these segments occurred after the monocot-dicot divergence and probably after the eurosid I-eurosid II divergence. Known transposable elements were found to occur in putatively duplicated segments to a far greater extent than expected on the basis of their genome-wide distribution, suggesting that transposition may have played a role in segmental duplication in this species.
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Research Interests: Chemistry, Organic Chemistry, Medicinal Chemistry, Pharmacokinetics, Medicine, and 15 moreFibrinogen, In Vitro, Prodrugs, Humans, Platelet aggregation, Animals, Prodrug, Bioavailability, In Vivo, Rat, Medicinal, Chemical Synthesis, Molecular Structure, Platelet Aggregation Inhibitors, and Pharmacology and pharmaceutical sciences
Research Interests: Chemistry, Organic Chemistry, Medicinal Chemistry, Pharmacokinetics, Medicine, and 15 moreDogs, Humans, Mice, Animals, Medicinal, Beta Lactams, Macaca fascicularis, Biological activity, Bleeding Time, Biological Availability, Alkanes, Hydroxylamines, lactams, Pharmacology and pharmaceutical sciences, and In Vitro Techniques
We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of... more
We have previously found that the 4-[4-(N-substituted carbamoyl)-1-piperazinyl]-6,7-dimethoxyquinazolines can function as potent and selective inhibitors of platelet-derived growth factor receptor (PDGFR) phosphorylation. A series of highly potent, specific, orally active, small molecule kinase inhibitors directed against members of PDGFR receptor have been developed through modifications of the novel quinazoline template I. Systematic modifications in the A-bicyclic ring and D-rings of protype I were carried out to afford potent analogues, which display IC(50) values of <250 nM in cellular betaPDGFR phosphorylation assays. An optimized analogue in this series, 75 (CT53518), inhibits Flt-3, betaPDGFR, and c-Kit receptor phosphorylation with IC(50) values of 50-200 nM, whereas 15-20-fold less potent activity against CSF-1R was observed. This analogue also inhibits autophosphorylation of Flt-3 ligand-stimulated wild-type Flt-3 and a constitutively activated Flt-3/internal tandem duplication (ITD) with IC(50) values of 30-100 nM. Through this optimization process, 75 was found to be metabolically stable and has desirable pharmacokinetic properties in all animal species studied (F% > 50%, T(1/2) > 8 h). Oral administration of 75 promotes mice survival and significantly delayed disease progression in a Flt-3/ITD-mediated leukemia mouse model and shows efficacy in a nude mouse model of chronic myelomonocytic leukemia.
Research Interests: Chemistry, Organic Chemistry, Medicinal Chemistry, Enzyme Inhibitors, Medicine, and 15 moreDogs, Humans, Mutation, Mice, Female, Animals, Male, Plasma, Phosphorylation, Medicinal, Macaca fascicularis, Biological Availability, Autophosphorylation, Pharmacology and pharmaceutical sciences, and In Vitro Techniques
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The synthesis and biological activity of analogues containing spiro piperidinylpyridine and pyrrolidinylpyridine templates are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility... more
The synthesis and biological activity of analogues containing spiro piperidinylpyridine and pyrrolidinylpyridine templates are described. The potent activity of these compounds as platelet aggregation inhibitors demonstrates the utility of the spiro structures as central template for nonpeptide RGD mimics.
Research Interests: Chemistry, Organic Chemistry, Medicine, Humans, Platelet aggregation, and 14 moreAnimals, Stereochemistry, P-glycoprotein, Rats, Bioorganic and medicinal Chemistry, Biological activity, Structure activity Relationship, Biological Availability, Chemical Synthesis, Minimum inhibitory concentration, Blood platelets, Platelet Aggregation Inhibitors, Pharmacology and pharmaceutical sciences, and Minimum Inhibitory Concentration(Animals, Stereochemistry, P-glycoprotein, Rats, Bioorganic and medicinal Chemistry, Biological activity, Structure activity Relationship, Biological Availability, Chemical Synthesis, Minimum inhibitory concentration, Blood platelets, Platelet Aggregation Inhibitors, Pharmacology and pharmaceutical sciences, and Minimum Inhibitory Concentration)
(Animals, Stereochemistry, P-glycoprotein, Rats, Bioorganic and medicinal Chemistry, Biological activity, Structure activity Relationship, Biological Availability, Chemical Synthesis, Minimum inhibitory concentration, Blood platelets, Platelet Aggregation Inhibitors, Pharmacology and pharmaceutical sciences, and Minimum Inhibitory Concentration)
Page 1. Printed on recycled paper. COLLISION POTENTIAL OF EIDERS AND OTHER BIRDS NEAR A PROPOSED WINDFARM AT ST. LAWRENCE ISLAND, OCTOBERNOVEMBER 2002 Prepared for Ecological Services ...
INTRODUCTIONParaffin sections of bone usually require a decalcification step after fixation before sectioning. This protocol describes a method for decalcifying fixed tissue.
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Introduction: Thrombolysis rates remain low. One important factor is emergency physician (EP) participation. We routinely trained EPs to use SMART (Simplified Management of Acute Stroke Using Revised Treatment) criteria with real time... more
Introduction: Thrombolysis rates remain low. One important factor is emergency physician (EP) participation. We routinely trained EPs to use SMART (Simplified Management of Acute Stroke Using Revised Treatment) criteria with real time feedback, resulting in high thrombolysis rates. The goal of this study was to determine the sustainability of this approach. Methods: Retrospective analysis of all consecutively treated IV rt-PA treated patients from 1/2006-6/2017, presenting to the ED at a large tertiary/quaternary stroke referral center. All EPs are trained using SMART criteria, which greatly lessen the contraindications to thrombolytic treatment. In addition the protocol requires response by the stroke neurologist ≤10min, and continuous real time feedback to the EP to maximize physician training. Formal in-service training is de-emphasized. Data regarding thrombolysis rates, and patient characteristics were routinely collected, including outcomes, safety and mortality. Results: From...
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OBJECTIVE: To evaluate the safety of applying the SMART (Simplified Management of Acute Stroke using Revised Treatment) criteria to IV rt-PA patients from community hospitals transferring to a large Comprehensive Stroke Center (CSC).... more
OBJECTIVE: To evaluate the safety of applying the SMART (Simplified Management of Acute Stroke using Revised Treatment) criteria to IV rt-PA patients from community hospitals transferring to a large Comprehensive Stroke Center (CSC). BACKGROUND: Thrombolysis rates remain low nationally (1-3%)¹. The SMART criteria expand rt-PA use by reducing exclusion criteria. When applied to all acute ischemic stroke (AIS) patients at a large CSC, the thrombolysis rate increased to 25-30%, with low symptomatic intracranial hemorrhage (sICH) rates². This study investigates the safety of applying these criteria to AIS patients who transferred from outside community hospitals. DESIGN/METHODS: Retrospective study of all AIS patients treated with IV rt-PA from 10/1/2008-8/1/2012 at the local CSC ED or an outside hospital before transfer to the CSC. Baseline characteristics, admission status, and stroke severity were obtained. Primary outcomes included NIHSS and discharge disposition. Safety was determi...
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OBJECTIVE: To determine the safety and efficacy of using CT perfusion (CTP) imaging in selection of patients for intra-arterial (IA) therapy post-IV thrombolysis while expanding eligibility by using SMART (Simplified Management of Acute... more
OBJECTIVE: To determine the safety and efficacy of using CT perfusion (CTP) imaging in selection of patients for intra-arterial (IA) therapy post-IV thrombolysis while expanding eligibility by using SMART (Simplified Management of Acute Stroke using Revised Treatment) criteria. BACKGROUND: Perfusion imaging may help select patients who would benefit from thrombolytic therapy. However few data are available demonstrating the routine use of CTP in patients receiving sequential full-dose IV and IA thrombolysis in combination with SMART criteria, which expand eligibility for IV rt-PA. DESIGN/METHODS: Retrospective chart review (1/2008-2/2012) of patients who had CTP and received IV and IA rt-PA, with eligibility determined by SMART criteria. In this protocol, patients receive CTP/CTA prior to IA therapy, and proceed only if significant mismatch and treatable large artery occlusion are identified. RESULTS: 38 patients were eligible; 35 had CTP mismatch. Median age was 65 (range 31-94). 9...
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Introduction: Common IV rt-PA exclusion criteria may limit its use. The SMART criteria expand eligibility by reducing exclusions and can increase thrombolysis rates. However, applicability of SMART criteria to non-specialized centers is... more
Introduction: Common IV rt-PA exclusion criteria may limit its use. The SMART criteria expand eligibility by reducing exclusions and can increase thrombolysis rates. However, applicability of SMART criteria to non-specialized centers is uncertain. We hypothesized that it is safe and efficacious to use SMART criteria in a wide range of hospital settings. Methods: Retrospective study of 539 consecutive acute ischemic stroke (AIS) patients receiving IV rt-PA using SMART criteria. Patients receiving IV rt-PA at a Comprehensive Stroke Center (CSC; n=267) versus Outlying Spoke Hospital (OSH; n=272) prior to transfer to the CSC were compared. There were 35 OSH (25-500+ beds) encompassing 120,000 sq miles in Northern California. The CSC neurologist was consulted by telephone (64%) or telemedicine (36%) in all cases. Primary outcomes were symptomatic intracranial hemorrhage (sICH) rate and favorable discharge outcome (mRS ≤ 1). Secondary measures were mortality and number of common rt-PA con...
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1. Introduction 2. From the Industrial Revolution to World War I 3. Wars and peace 4. The economics of property transactions 5. Post-war legislation 6. Conclusions
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Efforts to increase mink reproductive success (live births and litter sizes) can be partly assessed by measurement of blood progesterone levels. However, the stress of blood sampling increases the incidence of failed matings, aborted... more
Efforts to increase mink reproductive success (live births and litter sizes) can be partly assessed by measurement of blood progesterone levels. However, the stress of blood sampling increases the incidence of failed matings, aborted fetuses and death of the dam. We have therefore non-invasively measured fecal progesterone metabolite (progestin) concentrations during the reproductive cycle of mink. We tested the hypothesis that fecal progestin concentrations during the window of implantation (late March-early April) will, (1): be higher for whelping than non-whelping mink, and (2): be higher for mink mated multiple times, compared to single matings. Mink were mated once (March 3), twice (March 3 and 10) or three times (March 3, 10 and 11) and fecal progestin concentrations determined from March 1 to April 30. The percent mink in each group giving birth to live offspring was 42.8%, 80.8% and 92.3% for mink mated once, twice or three times, respectively (P<0.05). Litter sizes did n...
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OBJECTIVE: To evaluate the frequency and effects of variability in CYP2C19 metabolism in cerebrovascular disease patients. BACKGROUND: Recently, concern has been raised over the possibility of reduced efficacy of clopidogrel due to... more
OBJECTIVE: To evaluate the frequency and effects of variability in CYP2C19 metabolism in cerebrovascular disease patients. BACKGROUND: Recently, concern has been raised over the possibility of reduced efficacy of clopidogrel due to genetic variations in CYP2C19 metabolism. An FDA black box warning recommends all patients be tested. It has been estimated that ∼ 3% (range 2-14%) of the population are poor metabolizers, with significant racial/ethnic variation, but little data is available for cerebrovascular patients. DESIGN/METHODS: A retrospective review of all stroke and TIA patients tested for the clopidogrel CYP2C19 genotype from 4/2010 to 2/2012 was performed, with collection of data including race/ethnicity, CYP2C19 status, and presence of recurrent vascular events. RESULTS: A total of 53 cerebrovascular patients were tested; consisting of 5.7% poor (n=3), 26.4% intermediate (n=14), 62.3% extensive (n=33), 3.8% indeterminate (n=2), and 1.9% “mixed ultra rapid and poor” (n=1) metabolizers. Only 10/38 Caucasians (26.3%) were intermediate or poor metabolizers, compared with 7/15 (46.7%) non-Caucasians. Of 43 patients treated with clopidogrel, 3/27 extensive metabolizers (11.1%) had recurrent cerebrovascular events or thrombosis compared with 33.3% of intermediate metabolizers (4/12), and 50% of poor metabolizers (1/2). CONCLUSIONS: These data suggest that the proportion of poor and intermediate clopidogrel metabolizers in cerebrovascular patients are comparable to cardiovascular studies, with a similarly higher prevalence of reduced metabolism, and potentially recurrent events, in non-Caucasian patients. Given the significant racial/ethnic differences, the large proportion of patients who are intermediate or poor metabolizers, and the need for long-term therapy with this medication, routine CYP2C19 testing of clopidogrel treated stroke/TIA patients, particularly in non-Caucasians, may be warranted. In addition, the emergence of generic clopidogrel could substantially increase usage, making this issue of even more importance. Disclosure: Dr. Spokoyny has nothing to disclose. Dr. Barazangi has received personal compensation for activities with Genentech, Inc. Dr. Jaramillo has nothing to disclose. Dr. Rose has received personal compensation for activities with Boehringer Ingelheim as a speaker. Dr. Chen has nothing to disclose. Dr. Wong has nothing to disclose. Dr. Tong has nothing to disclose.
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Abstract 1. In its 3rd trial of flexitime, Kentucky state government reports its findings from questionnaires given to line employees and division directors in 22 agencies. Responses were favorable in assessing flexitime's effects on... more
Abstract 1. In its 3rd trial of flexitime, Kentucky state government reports its findings from questionnaires given to line employees and division directors in 22 agencies. Responses were favorable in assessing flexitime's effects on the key factors of productivity, ...
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Uncontrolled hypertension is often encountered after brain injury. The mechanisms surrounding this physiopathological response are related to autoregulatory responses aimed at preserving the cerebral blood flow in injured areas. The... more
Uncontrolled hypertension is often encountered after brain injury. The mechanisms surrounding this physiopathological response are related to autoregulatory responses aimed at preserving the cerebral blood flow in injured areas. The initial hypertensive response may precipitate further injury. Conversely, aggressive blood pressure reduction may be associated with ischemia. Despite the clear role of blood pressure as a modulator of acute brain injury, there is considerable controversy and a lack of high-quality data regarding the demographics, outcomes, and optimal management of high blood pressure in acute brain-injured patients. Recognition of the autoregulatory abnormalities seen after brain injury and careful control of blood pressure are necessary for the optimal management of these patients.
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Research Interests: Endocrinology, Biology, Medicine, Internal Medicine, Adrenal Gland, and 2 moreMink and Adrenalectomy(Mink and Adrenalectomy)
(Mink and Adrenalectomy)
INTRODUCTIONAfter a specimen is labeled, coverslips containing cells or tissues are mounted onto microscope slides, or slides containing sections are overlaid with a coverslip. A number of recipes for commonly used mounting media are... more
INTRODUCTIONAfter a specimen is labeled, coverslips containing cells or tissues are mounted onto microscope slides, or slides containing sections are overlaid with a coverslip. A number of recipes for commonly used mounting media are presented in this article, each with particular recommendations.