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Search Results: 1 - 10 of 308660 matches for " William J Mack "
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Invasive and Noninvasive Multimodal Bedside Monitoring in Subarachnoid Hemorrhage: A Review of Techniques and Available Data
Baback Arshi,William J. Mack,Benjamin Emanuel
Neurology Research International , 2013, DOI: 10.1155/2013/987934
Invasive and Noninvasive Multimodal Bedside Monitoring in Subarachnoid Hemorrhage: A Review of Techniques and Available Data
Baback Arshi,William J. Mack,Benjamin Emanuel
Neurology Research International , 2013, DOI: 10.1155/2013/987934
Abstract: Delayed-cerebral ischemia is a major cause of morbidity and mortality in the setting of aneurysmal subarachnoid hemorrhage. Despite extensive research efforts and a breadth of collective clinical experience, accurate diagnosis of vasospasm remains difficult, and effective treatment options are limited. Classically, diagnosis has focused on imaging assessment of the cerebral vasculature. Recently, invasive and noninvasive bedside techniques designed to characterize relevant hemodynamic and metabolic alterations have gained substantial attention. Such modalities include microdialysis, brain tissue oxygenation, jugular bulb oximetry, thermal diffusion cerebral blood flow, and near-infrared spectroscopy. This paper reviews these modalities and examines data pertinent to the diagnosis and management of cerebral vasospasm. 1. Introduction Delayed-cerebral ischemia (DCI) is a major cause of morbidity and mortality in the setting of aneurysmal subarachnoid hemorrhage (aSAH) [1]. Early diagnosis and effective treatment of cerebral vasospasm remain considerable challenges. Neurologists, neurosurgeons, and intensivists utilize multiple advanced diagnostic imaging techniques and examine a broad spectrum of physiologic parameters in attempts to identify reversible cerebral ischemia following aSAH. These modalities provide important data that guide treatment decisions and influence management protocols. Nonetheless, vasospasm related morbidity and mortality remain exceedingly high. Over the past twenty years, efforts have centered on identifying metabolic substrates relevant to the pathogenesis of cerebral vasospasm. As a result, intracerebral monitoring has given rise to a new, multimodal discipline providing specialists, a wide a variety of novel biomarkers potentially relevant to the diagnosis and management of delayed cerebral ischemia. This paper reviews both invasive and noninvasive multimodal bedside monitoring strategies and examines data pertinent to the diagnosis and management of cerebral vasospasm. 2. Methods An extensive literature search through PubMed medical database through July 2012 was conducted using combinations of the keywords “aneurysmal subarachnoid hemorrhage,” “vasospasm,” “microdialysis,” “brain tissue oxygenation (Licox, Integra Neurosciences),” “jugular bulb oximetry,” “thermal diffusion cerebral blood flow (Hemedex, Hemedex Inc.),” and “near-infrared spectroscopy.” All titles and abstracts identified were reviewed. Additional articles were identified from the reference lists of the selected manuscripts. Articles in all languages were
Medical Management of Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage: A Review of Current and Emerging Therapeutic Interventions
Peter Adamczyk,Shuhan He,Arun Paul Amar,William J. Mack
Neurology Research International , 2013, DOI: 10.1155/2013/462491
Abstract: Cerebral vasospasm is a major source of morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). Evidence suggests a multifactorial etiology and this concept remains supported by the assortment of therapeutic modalities under investigation. The authors provide an updated review of the literature for previous and recent clinical trials evaluating medical treatments in patients with cerebral vasospasm secondary to aSAH. Currently, the strongest evidence supports use of prophylactic oral nimodipine and initiation of triple-H therapy for patients in cerebral vasospasm. Other agents presented in this report include magnesium, statins, endothelin receptor antagonists, nitric oxide promoters, free radical scavengers, thromboxane inhibitors, thrombolysis, anti-inflammatory agents and neuroprotectants. Although promising data is beginning to emerge for several treatments, few prospective randomized clinical trials are presently available. Additionally, future investigational efforts will need to resolve discrepant definitions and outcome measures for cerebral vasospasm in order to permit adequate study comparisons. Until then, definitive recommendations cannot be made regarding the safety and efficacy for each of these therapeutic strategies and medical management practices will continue to be implemented in a wide-ranging manner. 1. Introduction Aneurysmal subarachnoid hemorrhage (aSAH) occurs in approximately 30,000 patients in the United States each year [1]. Cerebral vasospasm is estimated to occur in up to 70% of all aSAH patients and remains a major cause of morbidity and mortality [2]. The complex cascade of factors and events that result in arterial narrowing has been subject to extensive research, leading to a vast array of proposed treatment methods. A large number of these experimental therapies have been evaluated at the basic and translational levels with fewer reported prospective randomized clinical trials. Despite these efforts, no single treatment modality has proven efficacious and trial results have been frequently mixed or conflicting. Therefore medical management practices are often wide-ranging with an assortment of strategies implemented in various permutations. In this report, we review the literature and provide a concise, updated summary of recent clinical trials and current medical treatments evaluated in patients with cerebral vasospasm secondary to aSAH. 2. Triple-H Therapy The current mainstay for medical management of vasospasm secondary to aSAH remains triple-H therapy. The protocol is defined by
Treatment of mechanically-induced vasospasm of the carotid artery in a primate using intra-arterial verapamil: a technical case report
Alexander L Coon, Geoffrey P Colby, William J Mack, Lei Feng, Philip Meyers, E Sander Connolly
BMC Cardiovascular Disorders , 2004, DOI: 10.1186/1471-2261-4-11
Abstract: As part of a study assessing the placement feasibility and safety of a catheter capable of delivering intra-arterial cerebroprotective therapy, a female 16 kg baboon prophylaxed with intravenous nitroglycerin underwent transfemoral CCA catheterization with a metallic 6-Fr catheter without signs of acute spasm. The protocol dictated that the catheter remain in the CCA for 12 hours. Upon completion of the protocol, arteriography revealed a marked decrease in CCA size (mean cross-sectional area reduction = 31.6 ± 1.9%) localized along the catheter length. Intra-arterial verapamil (2 mg/2cc) was injected and arteriography was performed 10 minutes later. Image analysis at 6 points along the CCA revealed a 21.0 ± 1.7% mean increase in vessel diameter along the length of the catheter corresponding to a 46.7 ± 4.0% mean increase in cross-sectional area. Mean systemic blood pressure did not deviate more than 10 mm Hg during the procedure.Intraluminal CCBs like verapamil may constitute an effective endovascular treatment for mechanically-induced vasospasm in medium to large-sized vessels such as the CCA.Rapid advancements in endovascular technology and techniques allow for treatment of an ever-increasing range of neurovascular diseases. Despite improvements in the safety and efficacy of these procedures, complications such as vasospasm, stroke, and perforation still occur [1]. Vasospasm, or contraction of smooth muscle fibers in the wall of a vessel, is a commonly recognized adverse event that may complicate an endovascular procedure by limiting distal blood flow.Vasospasm complicates many disease states, particularly those affecting small vessels. Recently, treatment of small-vessel vasospasm has proven amenable to pharmacological intervention. For example, in the treatment of cerebral artery spasm, intravenous nitrates [2], intravenous calcium channel blockers (CCBs) [3], and intra-arterial papaverine [4] and CCBs [5] have been shown to prevent or mitigate this small artery
White Matter Injury Due to Experimental Chronic Cerebral Hypoperfusion Is Associated with C5 Deposition
Qinghai Liu, Shuhan He, Leonid Groysman, David Shaked, Jonathan Russin, Steven Cen, William J. Mack
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0084802
Abstract: The C5 complement protein is a potent inflammatory mediator that has been implicated in the pathogenesis of both stroke and neurodegenerative disease. Microvascular failure is proposed as a potential mechanism of injury. Along these lines, this investigation examines the role of C5 in the setting of chronic cerebral hypoperfusion. Following experimental bilateral carotid artery stenosis, C5 protein deposition increases in the corpus callosum over thirty days (p<0.05). The time course is temporally consistent with the appearance of white matter injury. Concurrently, systemic serum C5 levels do not appear to differ between bilateral carotid artery stenosis and sham-operated mice, implicating a local cerebral process. Following bilateral carotid artery stenosis, C5 deficient mice demonstrate decreased white matter ischemia in the corpus callosum when compared to C5 sufficient controls (p<0.05). Further, the C5 deficient mice exhibit fewer reactive astrocytes and microglia (p<0.01). This study reveals that the C5 complement protein may play a critical role in mediating white matter injury through inflammation in the setting of chronic cerebral hypoperfusion.
The Role of Epigenetic Modification in Tumorigenesis and Progression of Pituitary Adenomas: A Systematic Review of the Literature
Matthew Pease, Chao Ling, William J. Mack, Kai Wang, Gabriel Zada
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082619
Abstract: Background Pituitary adenomas (PAs) are commonly occurring neoplasms with diverse endocrine and neurological effects. Although somatic gene mutations are uncommon in sporadic PAs, recent studies lend support to epigenetic modification as a potential cause of tumorigenesis and tumor progression. Methods A systematic literature review of the PubMed and Google Scholar databases was conducted to identify abstracts (n=1,082) pertaining to key targets and mechanisms implicated in epigenetic dysregulation of PAs published between 1993-2013. Data regarding histopathological subtype, target genes, mode of epigenetic modification, and clinical correlation were recorded and analyzed. Results Of the 47 that studies met inclusion criteria and focused on epigenomic assessment of PAs, only 2 were genome-scale analyses. Current evidence supports epigenetic alteration in at least 24 PA genes, which were categorized into four groups based on function and epigenetic alteration: 1) Sixteen tumor suppressor genes silenced via DNA methylation; 2) Two oncogenes overexpressed via histone acetylation and hypomethylation; 3) Three imprinted genes with selective allelic silencing; and 4) One epigenome writer inducing abnormal genome-scale activity and 5) Two transcription regulators indirectly modifying the genome. Of these, 5 genes (CDKN2A, GADD45y, FGFR2, caspase-8, and PTAG) showed particular susceptibility to epigenetic modification, with abnormal DNA methylation in >50% of PA samples. Several genes displayed correlations between epigenetic modification and clinically relevant parameters, including invasiveness (CDKN2A; DAPK; Rb1), sex (MAGE-A3), tumor size (GNAS1), and histopathological subtype (CDKN2A; MEG3; p27; RASSF1A; Rb1). Conclusions Epigenetic modification of selected PA genes may play a key role in tumorigenesis and progression, which may translate into important diagnostic and therapeutic applications.
Characterizing Immunoglobulin Repertoire from Whole Blood by a Personal Genome Sequencer
Fan Gao, Edwin Lin, Yaping Feng, William J. Mack, Yufeng Shen, Kai Wang
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075294
Abstract: In human immune system, V(D)J recombination produces an enormously large repertoire of immunoglobulins (Ig) so that they can tackle different antigens from bacteria, viruses and tumor cells. Several studies have demonstrated the utility of next-generation sequencers such as Roche 454 and Illumina Genome Analyzer to characterize the repertoire of immunoglobulins. However, these techniques typically require separation of B cell population from whole blood and require a few weeks for running the sequencers, so it may not be practical to implement them in clinical settings. Recently, the Ion Torrent personal genome sequencer has emerged as a tabletop personal genome sequencer that can be operated in a time-efficient and cost-effective manner. In this study, we explored the technical feasibility to use multiplex PCR for amplifying V(D)J recombination for IgH, directly from whole blood, then sequence the amplicons by the Ion Torrent sequencer. The whole process including data generation and analysis can be completed in one day. We tested the method in a pilot study on patients with benign, atypical and malignant meningiomas. Despite the noisy data, we were able to compare the samples by their usage frequencies of the V segment, as well as their somatic hypermutation rates. In summary, our study suggested that it is technically feasible to perform clinical monitoring of V(D)J recombination within a day by personal genome sequencers.
Cerebral Vasospasm in Traumatic Brain Injury
Daniel R. Kramer,Jesse L. Winer,B. A. Matthew Pease,Arun P. Amar,William J. Mack
Neurology Research International , 2013, DOI: 10.1155/2013/415813
Abstract: Vasospasm following traumatic brain injury (TBI) may dramatically affect the neurological and functional recovery of a vulnerable patient population. While the reported incidence of traumatic vasospasm ranges from 19%–68%, the true incidence remains unknown due to variability in protocols for its detection. Only 3.9%–16.6% of patients exhibit clinical deficits. Compared to vasospasm resulting from aneurysmal SAH (aSAH), the onset occurs earlier and the duration is shorter. Overall, the clinical course tends to be milder, although extreme cases may occur. Traumatic vasospasm can occur in the absence of subarachnoid hemorrhage. Surveillance transcranial Doppler ultrasonography (TCD) has been utilized to monitor for radiographic vasospasm following TBI. However, effective treatment modalities remain limited. Hypertension and hypervolemia, the mainstays of treatment of vasospasm associated with aSAH, must be used judiciously in TBI patients, and calcium-channel blockers have offered mixed clinical results. Currently, the paucity of large prospective cohort studies and level-one data limits the ability to form evidence-based recommendations regarding the diagnosis and management of vasospasm associated with TBI. 1. Introduction Traumatic brain injury (TBI) bears a heavy societal burden [1]. With an incidence rate of approximately 1.5 million new cases per year, TBI is the leading cause of death in the USA between the ages of one and forty-five [1]. Primary TBI management focuses on patient stabilization and treatment of elevated intracranial pressure (ICP). Surgical decompression and/or clot evacuation can decrease mass effect and cerebral edema, thus mitigating progressive neurological decline [2, 3]. The frequency of SAH following head trauma is estimated at 39%–65% [4–9], and its presence is an independent predictor of poor functional outcome [4, 7, 10, 11]. Severity of hemorrhage on CT scan has been shown to correlate with clinical status [12]. Although significant morbidity and mortality are attributable to the inciting trauma, deleterious sequelae of secondary injury are considerable and remain a critical focus of medical therapies. Vasospasm is a delayed, secondary consequence that can profoundly impact neurological recovery and functional outcome after TBI. Although vasospasm may result from traumatic subarachnoid hemorrhage (tSAH), other mechanisms such as blast-induced neurotrauma are increasingly recognized as causative factors [13–16]. This paper reviews the epidemiology, diagnosis, pathophysiology, prevention, and treatment of vasospasm
Matrix Metalloproteinases in Cerebral Vasospasm following Aneurysmal Subarachnoid Hemorrhage
Vivek Mehta,Jonathan Russin,Alexandra Spirtos,Shuhan He,Peter Adamczyk,Arun P. Amar,William J. Mack
Neurology Research International , 2013, DOI: 10.1155/2013/943761
Abstract: Delayed cerebral vasospasm is a significant cause of morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH). While the cellular mechanisms underlying vasospasm remain unclear, it is believed that inflammation may play a critical role in vasospasm. Matrix metalloproteinasees (MMPs) are a family of extracellular and membrane-bound proteases capable of degrading the blood-rain barrier (BBB). As such, MMP upregulation following SAH may result in a proinflammatory extravascular environment capable of inciting delayed cerebral vasospasm. This paper presents an overview of MMPs and describes existing data pertinent to delayed cerebral vasospasm. 1. Background Delayed cerebral vasospasm is a devastating complication of subarachnoid hemorrhage (SAH). It typically occurs within fourteen days of aneurysmal rupture, and it is associated with significant morbidity and mortality [1, 2]. While pathophysiology remains incompletely understood, the interplay between inflammation and the innate immune response is strongly implicated. Following SAH, increased blood-brain barrier (BBB) permeability engenders a proinflammatory milieu in the cerebral cisterns and extravascular space. Subarachnoid blood initiates leukocyte transmigration via cellular margination, adhesion, rolling, and diapedesis [3]. The process necessitates violation of the tight junctions between endothelial cells of the BBB and typically occurs in response to stimulatory chemoattractants or chemokines. Coupled with concurrent physiologic derangements, these molecular alterations can incite delayed cerebral vasospasm. Regulation of the extracellular matrix and basal lamina by matrix metalloproteinase (MMP) enzymes may play a critical role in vasospasm. MMPs have been studied extensively in the pathogenesis of ischemic stroke and the development of aortic and cerebral aneurysms [4]. Recently, investigations have examined the role of MMPs in the setting of SAH. In this paper, we specifically review the function of MMPs in cerebral vasospasm. Understanding the complex interactions between inflammation and degradation of the extracellular matrix may ultimately allow for better development of diagnostic markers and targeted therapies relevant to the management of delayed cerebral vasospasm. 2. MMP Review MMPs are a family of extracellular and membrane-bound proteases capable of degrading or proteolytically modifying the extracellular matrix (ECM) through interactions with collagenases, laminins, and proteoglycans [5]. They utilize zinc-dependent endopeptidases to regulate physiologic
Advanced Imaging Modalities in the Detection of Cerebral Vasospasm
Jena N. Mills,Vivek Mehta,Jonathan Russin,Arun P. Amar,Anandh Rajamohan,William J. Mack
Neurology Research International , 2013, DOI: 10.1155/2013/415960
Abstract: The pathophysiology of cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH) is complex and is not entirely understood. Mechanistic insights have been gained through advances in the capabilities of diagnostic imaging. Core techniques have focused on the assessment of vessel caliber, tissue metabolism, and/or regional perfusion parameters. Advances in imaging have provided clinicians with a multifaceted approach to assist in the detection of cerebral vasospasm and the diagnosis of delayed ischemic neurologic deficits (DIND). However, a single test or algorithm with broad efficacy remains elusive. This paper examines both anatomical and physiological imaging modalities applicable to post-SAH vasospasm and offers a historical background. We consider cerebral blood flow velocities measured by Transcranial Doppler Ultrasonography (TCD). Structural imaging techniques, including catheter-based Digital Subtraction Angiography (DSA), CT Angiography (CTA), and MR Angiography (MRA), are reviewed. We examine physiologic assessment by PET, HMPAO SPECT, 133Xe Clearance, Xenon-Enhanced CT (Xe/CT), Perfusion CT (PCT), and Diffusion-Weighted/MR Perfusion Imaging. Comparative advantages and limitations are discussed. 1. Introduction and Historical Perspective Cerebral vasospasm is a delayed complication of subarachnoid hemorrhage. It generally occurs 4–14 days after aneurysmal rupture and is associated with morbidity and mortality rates between 10 and 30% [1]. While changes are commonly observed in the large caliber conveyance arteries, effects on the smaller vessels of the microcirculation, including alterations in blood brain barrier permeability, may be equally important in determining clinical impact. Such factors may account for the higher incidence of vasospasm as defined by imaging criteria (“radiographic vasospasm”) than rates of neurological dysfunction (“clinical vasospasm”). Early diagnosis and treatment could potentially prevent and/or minimize delayed ischemic neurological deficits (DIND). Advances in clinical management of cerebral vasospasm have lagged far behind innovations in brain imaging. Given that radiographic vasospasm does not strongly associate with DIND, efforts have refocused on understanding pathophysiology through advanced correlative imaging. Technological developments have enabled accurate assessment of tissue oxygenation, metabolic uptake, and cerebral perfusion. This paper will review imaging modalities applied to the detection of cerebral vasospasm and the diagnosis of DIND. A historical background is presented, and
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