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  1. Article ; Online: Pharmacogenetics as a predictor chemotherapy induced peripheral neuropathy in gynecologic cancer patients treated with Taxane-based chemotherapy.

    Mysona, David / Dorr, Katherine / Ward, Alex / Shaver, Ellen / Rungruang, Bunja / Ghamande, Sharad

    Gynecologic oncology

    2022  Volume 168, Page(s) 114–118

    Abstract: Background: This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.: Methods: Patients were enrolled from August 2020 to November 2020 ...

    Abstract Background: This study investigated whether there are pharmacogenomic markers predictive of chemotherapy induced peripheral neuropathy (CIPN) as a result of taxane-based chemotherapy.
    Methods: Patients were enrolled from August 2020 to November 2020 in a prospective, case-control trial evaluating pharmacogenetic predictors of CIPN. All women were treated with at least 3 cycles of taxane-based chemotherapy for histologically confirmed gynecologic malignancies. Buccal saliva samples were used to test for 32 drug metabolism variations. All testing was performed by ⍺LPHA-GENOMIX laboratories. Fisher's Exact test was used to assess for event differences of categorical variables.
    Results: Of 102 enrolled patients, 58%, 28%, and 14% had ovarian, endometrial, or cervical cancers, respectively. The median age was 67, 72% were Caucasian and 25% were African American. 16% of patients were treated with 3-4 cycles, 57% received 5-7 cycles, and 27% received 8 or more cycles of chemotherapy that included paclitaxel. Grade 2 CIPN was experienced by 51 patients. There was no difference in age, race, disease site, or number of chemotherapy cycles (p > 0.05) between those who did or did not develop CIPN. CYP2D6 genotype (p = 0.009) and CYP3A5 genotype (p = 0.023) had different frequencies among those with and without CIPN. Patients classified as having poor or intermediate function of CYP2D6 had increased risk of CIPN (OR 1.63, 95% CI 1.04-2.57, p = 0.026). There was no difference in CYP2D6 phenotype by race (p = 0.29). No patients with normal function of CYP3A5 developed CIPN. There were no Caucasians with normal function of CYP3A5, but 28% of African Americans had normal CYP3A5 function (p < 0.001).
    Conclusions: Pharmacogenomics appear associated with the development of CIPN and may be able to help personalize treatment decision making.
    MeSH term(s) Female ; Humans ; Antineoplastic Agents/adverse effects ; Breast Neoplasms ; Cytochrome P-450 CYP2D6/genetics ; Cytochrome P-450 CYP3A/genetics ; Genital Neoplasms, Female/drug therapy ; Genital Neoplasms, Female/genetics ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/genetics ; Pharmacogenetics ; Prospective Studies ; Taxoids/adverse effects ; Case-Control Studies ; Aged
    Chemical Substances Antineoplastic Agents ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1) ; Cytochrome P-450 CYP3A (EC 1.14.14.1) ; taxane (1605-68-1) ; Taxoids
    Language English
    Publishing date 2022-11-23
    Publishing country United States
    Document type Clinical Trial ; Journal Article
    ZDB-ID 801461-9
    ISSN 1095-6859 ; 0090-8258
    ISSN (online) 1095-6859
    ISSN 0090-8258
    DOI 10.1016/j.ygyno.2022.10.021
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  2. Article ; Online: Treatment with transducible phosphopeptide analogues of the small heat shock-related protein, HSP20, after experimental subarachnoid hemorrhage: prevention and reversal of delayed decreases in cerebral perfusion.

    Furnish, Elizabeth J / Brophy, Colleen M / Harris, Valerie A / Macomson, Samuel / Winger, Julia / Head, Geoffrey A / Shaver, Ellen G

    Journal of neurosurgery

    2010  Volume 112, Issue 3, Page(s) 631–639

    Abstract: Object: Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent ... ...

    Abstract Object: Delayed vasospasm is a significant cause of morbidity and mortality after subarachnoid hemorrhage (SAH). Proteomic therapeutics offers a new modality in which biologically active proteins or peptides are transduced into cells via covalent linkage to cell permeant peptides (CPPs). The hypothesis of this study was that either intrathecal or intravenous delivery of a phosphopeptide mimetic of the small heat shock-related protein, HSP20, linked to a CPP, would inhibit delayed decreases in cerebral perfusion after experimental SAH in a rat model.
    Methods: This study was conducted in 3 parts: 1) prevention and 2) reversal of delayed decreases in cerebral perfusion via either intrathecal or intravenous administration of a CPP linked to phosphopeptide mimetics of HSP20 (AZX100) and 3) determining the effect of intravenous administration of AZX100 on blood pressure and heart rate. Subarachnoid hemorrhage was induced in rats by endovascular perforation. Subsequently, AZX100 was administered intrathecally via a cisternal catheter or intravenously. Cerebral perfusion was determined by laser Doppler monitoring. Blood pressure was monitored by telemetry in a separate group of naïve animals treated with AZX100 for 24 hours.
    Results: The maximal decrease in cerebral perfusion occurred 3 days after SAH. Cisternal administration of AZX100 (0.14-0.57 mg/kg) 24 hours after hemorrhage prevented decreases in cerebral perfusion after SAH. Animals receiving lower doses of AZX100 (0.068 mg/kg) or a scrambled sequence of the active HSP20 peptide linked to CPP developed decreases in cerebral perfusion similar to those seen in control animals. Intravenous administration of AZX100 (1.22 mg/kg) 24 hours after hemorrhage prevented the decreases in cerebral perfusion seen in the controls. Intravenous administration (0.175 mg/kg and 1.22 mg/kg) of AZX100 on Days 2 and 3 after SAH reversed decreases in cerebral perfusion as early as Day 3. There was no impact of AZX100 on blood pressure or heart rate at doses up to 2.73 mg/kg.
    Conclusions: Cisternal administration of AZX100 24 hours after hemorrhage prevented decreases in cerebral perfusion. Intravenous administration of AZX100 also prevented and reversed decreases in cerebral perfusion at doses that did not induce hypotension. Transduction of biologically active motifs of downstream regulators like HSP20 represents a potential novel treatment for SAH.
    MeSH term(s) Animals ; Biomimetics ; Blood Pressure/drug effects ; Cerebrovascular Circulation/drug effects ; Disease Models, Animal ; HSP20 Heat-Shock Proteins ; Heart Rate/drug effects ; Heat-Shock Proteins, Small/administration & dosage ; Heat-Shock Proteins, Small/therapeutic use ; Male ; Neuroprotective Agents/administration & dosage ; Neuroprotective Agents/therapeutic use ; Phosphoproteins/administration & dosage ; Phosphoproteins/therapeutic use ; Rats ; Rats, Wistar ; Subarachnoid Hemorrhage/drug therapy ; Subarachnoid Hemorrhage/mortality ; Time Factors
    Chemical Substances AZX 100 ; HSP20 Heat-Shock Proteins ; Heat-Shock Proteins, Small ; Neuroprotective Agents ; Phosphoproteins
    Language English
    Publishing date 2010-03
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 3089-2
    ISSN 1933-0693 ; 0022-3085
    ISSN (online) 1933-0693
    ISSN 0022-3085
    DOI 10.3171/2009.7.JNS09730
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  3. Article: Distal anterior inferior cerebellar artery aneurysms. Report of four cases.

    Zager, Eric L / Shaver, Ellen G / Hurst, Robert W / Flamm, Eugene S

    Journal of neurosurgery

    2002  Volume 97, Issue 3, Page(s) 692–696

    Abstract: Aneurysms of the distal anterior inferior cerebellar artery (AICA) are rare; fewer than 100 cases have been reported. The authors detail their experience with four cases and present endovascular as well as microsurgical management options. The medical ... ...

    Abstract Aneurysms of the distal anterior inferior cerebellar artery (AICA) are rare; fewer than 100 cases have been reported. The authors detail their experience with four cases and present endovascular as well as microsurgical management options. The medical records and neuroimaging studies obtained in four patients who were treated at a single institution were reviewed. Clinical presentations, neuroimaging and intraoperative findings, and clinical outcomes were analyzed. There were three men and one woman; their mean age was 43 years. Two patients presented with acute subarachnoid hemorrhage (SAH), and two presented with ataxia and vertigo (one with tinnitus, the other with hearing loss). Angiographic studies demonstrated aneurysms of the distal segment of the AICA. In one patient with von Hippel-Lindau syndrome and multiple cerebellar hemangioblastomas, a feeding artery aneurysm was found on a distal branch of the AICA. Three of the patients underwent successful surgical obliteration of their aneurysms, one by clipping, one by trapping, and one by resection along with the tumor. The fourth patient underwent coil embolization of the distal AICA and the aneurysm. All patients made an excellent neurological recovery. Patients with aneurysms in this location may present with typical features of an acute SAH or with symptoms referable to the cerebellopontine angle. Evaluation with computerized tomography, magnetic resonance (MR) imaging, MR angiography, and digital subtraction angiography should be performed. For lesions distal to branches coursing to the brainstem, trapping and aneurysm resection are viable options that do not require bypass. Endovascular obliteration is also a reasonable option, although the possibility of retrograde thrombosis of the AICA is a concern.
    MeSH term(s) Adult ; Cerebellum/blood supply ; Cerebral Angiography ; Embolization, Therapeutic ; Female ; Humans ; Intracranial Aneurysm/pathology ; Intracranial Aneurysm/therapy ; Male ; Middle Aged ; Subarachnoid Hemorrhage/pathology ; Subarachnoid Hemorrhage/therapy
    Language English
    Publishing date 2002-09
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 3089-2
    ISSN 1933-0693 ; 0022-3085
    ISSN (online) 1933-0693
    ISSN 0022-3085
    DOI 10.3171/jns.2002.97.3.0692
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  4. Article: Heat shock protein expression in cerebral vessels after subarachnoid hemorrhage.

    Macomson, Samuel D / Brophy, Colleen M / Miller, W / Harris, Valerie A / Shaver, Ellen G

    Neurosurgery

    2002  Volume 51, Issue 1, Page(s) 204–10; discussion 210–1

    Abstract: Objective: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the ... ...

    Abstract Objective: The mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) remain controversial. Recent data have implicated two small heat shock proteins (HSPs), namely HSP20 and HSP27, in the regulation of vascular tone. Increases in the phosphorylation of HSP20 are associated with vasorelaxation, and increases in the phosphorylation of HSP27 are associated with impaired vasorelaxation. Therefore, we hypothesized that alterations in the expression and/or phosphorylation of these two small HSPs might play a role in cerebral vasospasm after SAH.
    Methods: A rat model of endovascular perforation was used to induce SAH. Middle cerebral arteries were harvested from control animals, sham-treated animals, and animals with SAH, 48 hours after SAH induction. Dose-response curves for endothelium-independent (sodium nitroprusside, 10(-8) to 10(-4) mol/L) and endothelium-dependent (bradykinin, 10(-10) to 10(-5) mol/L) relaxing agents were recorded ex vivo. Physiological responses were correlated with the expression and phosphorylation of HSP20 and HSP27 by using one- and two-dimensional immunoblots.
    Results: There was impaired endothelium-independent and endothelium-dependent relaxation in cerebral vessels after SAH. These changes were associated with decreased expression of both total and phosphorylated HSP20 and increases in the amount of phosphorylated HSP27.
    Conclusion: In this model, impaired relaxation of cerebral vessels after SAH was associated with increases in the amount of phosphorylated HSP27 and decreases in the expression and phosphorylation of HSP20. These data are consistent with alterations in the expression and phosphorylation of these small HSPs in other models of vasospasm.
    MeSH term(s) Animals ; Cerebral Arteries/pathology ; Cerebral Arteries/physiopathology ; Disease Models, Animal ; Endothelium, Vascular/pathology ; Endothelium, Vascular/physiopathology ; HSP20 Heat-Shock Proteins ; Heat-Shock Proteins/physiology ; Male ; Phosphopeptides/physiology ; Phosphoproteins/physiology ; Phosphorylation ; Rats ; Rats, Wistar ; Subarachnoid Hemorrhage/pathology ; Subarachnoid Hemorrhage/physiopathology ; Vasospasm, Intracranial/pathology ; Vasospasm, Intracranial/physiopathology
    Chemical Substances HSP20 Heat-Shock Proteins ; Heat-Shock Proteins ; Phosphopeptides ; Phosphoproteins
    Language English
    Publishing date 2002-07
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 135446-2
    ISSN 1524-4040 ; 0148-396X
    ISSN (online) 1524-4040
    ISSN 0148-396X
    DOI 10.1097/00006123-200207000-00029
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  5. Article: Golf-associated head injury in the pediatric population: a common sports injury.

    Rahimi, Scott Y / Singh, Harshpal / Yeh, David J / Shaver, Ellen G / Flannery, Ann Marie / Lee, Mark R

    Journal of neurosurgery

    2005  Volume 102, Issue 2 Suppl, Page(s) 163–166

    Abstract: Object: Golf-related injuries constitute a common type of sports injury in the pediatric population. The increase in the frequency of these injuries is largely attributed to the increase in the popularity of golf and greater use of golf carts by ... ...

    Abstract Object: Golf-related injuries constitute a common type of sports injury in the pediatric population. The increase in the frequency of these injuries is largely attributed to the increase in the popularity of golf and greater use of golf carts by children.
    Methods: The purpose of this study was to investigate the mechanisms and complications associated with golf-related injuries in the pediatric population and, by doing so, assist in the prevention of such injuries. We reviewed the charts of 2546 pediatric patients evaluated by the neurosurgery service at the authors' institution over a 6-year period. There were 64 cases of sports-related injuries. Of these, 15 (23%) were golf-related, making these injuries the second-largest group of sports-related injuries. Depressed skull fracture was the most common injury observed. Neurosurgical intervention was required in 33% of the cases. With rare exceptions, patients made good recoveries during a mean follow-up period of 22.2 months. One death occurred due to uncontrollable cerebral edema following a golf cart accident. One child required shunt placement and several revisions following an injury sustained from a golf ball.
    Conclusions: Children should be advised on the proper use of golf equipment as a preventive measure to avoid these injuries. Precautionary guidelines and safety training guidelines should be established. The institution of a legal minimum age required to operate a golf cart should be considered.
    MeSH term(s) Adolescent ; Adult ; Athletic Injuries/epidemiology ; Athletic Injuries/prevention & control ; Brain Injuries/diagnostic imaging ; Brain Injuries/epidemiology ; Brain Injuries/surgery ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Golf/injuries ; Golf/statistics & numerical data ; Humans ; Male ; Neurosurgical Procedures/methods ; Skull Fracture, Depressed/epidemiology ; Skull Fracture, Depressed/surgery ; Tomography, X-Ray Computed
    Language English
    Publishing date 2005-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3089-2
    ISSN 1933-0693 ; 0022-3085
    ISSN (online) 1933-0693
    ISSN 0022-3085
    DOI 10.3171/jns.2005.102.2.0163
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  6. Article ; Online: Experimental Acute Subdural Hematoma in Infant Piglets

    Shaver, Ellen G. / Duhaime, Ann-Christine / Curtis, Mark / Gennarelli, Laura M. / Barrett, Ronald

    Pediatric Neurosurgery

    1996  Volume 25, Issue 3, Page(s) 123–129

    Abstract: Traumatic acute subdural hematoma is associated with high mortality in the pediatric population, yet the pathophysiology remains poorly understood. The objective of this study was to develop a pediatric model of acute subdural hematoma, and to evaluate ... ...

    Abstract Traumatic acute subdural hematoma is associated with high mortality in the pediatric population, yet the pathophysiology remains poorly understood. The objective of this study was to develop a pediatric model of acute subdural hematoma, and to evaluate the resultant histopathological changes in the brain. Ten 3-week-old piglets were studied. A 5-mm craniotomy was made in the right frontal skull. A small silastic tube was inserted through the underlying intact dura into the subdural space. A craniotomy was made posterior to the right coronal suture with underlying dura left intact (closed cranial window model). Injection of 5 ml autologous, nonheparinized blood was accomplished through the silastic tube. Animals were sacrificed after 72 h or 1 week. During the subdural injection, intracranial pressure rose to 62 ± 8 mm Hg, and returned to baseline within 1 h of surgery. Mean arterial blood pressure increased transiently. Cresyl violet and hematoxylin and eosin staining demonstrated extensive areas of white matter necrosis under the hematoma after 72 h survival (n = 7). Zones of necrosis were also noted in cortex, but were less extensive than those seen in white matter. These results differ from adult rodent models in which cortex is primarily affected. This is the first reported pediatric model of traumatic acute subdural hematoma. This model can be used in future studies to investigate pharmacological or other therapies which may improve outcome after this type of injury.
    Keywords Acute subdural hematoma ; Cranial window model ; Histopathology ; Piglet
    Language English
    Publisher S. Karger AG
    Publishing place Basel
    Publishing country Switzerland
    Document type Article ; Online
    ZDB-ID 1091757-3
    ISSN 1423-0305 ; 1016-2291 ; 1016-2291
    ISSN (online) 1423-0305
    ISSN 1016-2291
    DOI 10.1159/000121109
    Database Karger publisher's database

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  7. Article ; Online: Results and Complications after Reoperation for Failed Epilepsy Surgery in Children

    Shaver, Ellen G. / Harvey, Simon / Morrison, Glenn / Prats, Antonio / Jayakar, Prasanna / Dean, Patricia / Duchowny, Michael

    Pediatric Neurosurgery

    1997  Volume 27, Issue 4, Page(s) 194–202

    Abstract: The seizure outcome and neurological outcome in children who undergo reoperation for failed epilepsy surgery have not been well documented. This retrospective study evaluated 20 children who underwent a second resective surgery for recurrent seizures. ... ...

    Abstract The seizure outcome and neurological outcome in children who undergo reoperation for failed epilepsy surgery have not been well documented. This retrospective study evaluated 20 children who underwent a second resective surgery for recurrent seizures. Four categories of patients were identified: (1) extension of the initial resection was performed in 8 patients; (2) 5 patients underwent lobectomy or corticectomy in a region remote from the original surgical site; (3) multilobar resection which may have included further resection of the initial procedure was accomplished in 4 patients; (4) hemispherectomy was performed in 3 patients. Patients with reoperation in the same lobe as the first procedure (group 1) had a 62% seizure-free rate, while 44% of patients in groups 2 and 3 were free from seizures at follow-up evaluation. Patients undergoing hemispherectomy had a 67% seizure-free rate. Significant unexpected neurological deficits occurred in 3 patients who underwent multilobar resection at reoperation. Complications included motor and language deficits. Reoperation for intractable partial epilepsy is beneficial in selected children. Patients who require multilobar resections may have higher risk of postoperative neurological deficit than those patients with reoperation in one lobe. These factors may be useful in counseling parents of children considering reoperation for recurrent epilepsy.
    Keywords Reoperation ; Epilepsy surgery ; Children
    Language English
    Publisher S. Karger AG
    Publishing place Basel
    Publishing country Switzerland
    Document type Article ; Online
    ZDB-ID 1091757-3
    ISSN 1423-0305 ; 1016-2291 ; 1016-2291
    ISSN (online) 1423-0305
    ISSN 1016-2291
    DOI 10.1159/000121251
    Database Karger publisher's database

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