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Warren R Selman

Publications and source records attributed to Warren R Selman.

At least 19 recordsLinked to original sources

Regional metabolic status of the E-18 rat fetal brain following transient hypoxia/ischemia.

Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine several end-points to determine if the metabolic stress affects the developing brain. The uterine artery and uterine branch of the ovarian artery were occluded with aneurysm clamps for a period of 45 min, the clips removed and the metabolites in five regions of the perinatal brain were measured at 0, 2 and 6 h of reflow. Regional P-creatine, ATP and glucose levels were significantly depleted at the end of the 45 min occlusion. The levels of glycogen and glutamate at the end of the occlusion indicated a decreasing trend which was not significant. The concentration of citrate remained essentially unchanged at the end of the occlusion. To ensure that the insult was not lethal to the tissue, the recovery of the metabolites was examined at 2 and 6 h of reflow and generally the concentrations of the high-energy phosphates and glucose were normal or near-normal by 6 h of reperfusion in the five regions of the brain examined. The changes in the metabolites indicate that 45 min of hypoxia/ischemia is an appropriate model for studying neonatal development after fetal metabolic stress.

Adenosine Triphosphate↗

Molecular genetics of familial cerebral cavernous malformations.

Cerebral cavernous malformations (CMs) are angiographically occult neurovascular lesions that consist of enlarged vascular channels without intervening normal parenchyma. Cavernous malformations can occur as sporadic or autosomal- dominant inherited conditions. Approximately 50% of Hispanic patients with cerebral CMs have the familial form, compared with 10 to 20% of Caucasian patients. There is no difference in the pathological findings or presentation in the sporadic and familial forms. To date, familial CMs have been attributed to mutations at three different loci: CCM1 on 7q21.2, CCM2 on 7p15-p13, or CCM3 on 3q25.2-q27. The authors summarize the current understanding of the molecular events underlying familial CMs.

Animals↗

Recommendations for comprehensive stroke centers: a consensus statement from the Brain Attack Coalition.

BACKGROUND AND PURPOSE: To develop recommendations for the establishment of comprehensive stroke centers capable of delivering the full spectrum of care to seriously ill patients with stroke and cerebrovascular disease. Recommendations were developed by members of the Brain Attack Coalition (BAC), which is a multidisciplinary group of members from major professional organizations involved with the care of patients with stroke and cerebrovascular disease. SUMMARY OF REVIEW: A comprehensive literature search was conducted from 1966 through December 2004 using Medline and Pub Med. Articles with information about clinical trials, meta-analyses, care guidelines, scientific guidelines, and other relevant clinical and research reports were examined and graded using established evidence-based medicine approaches for therapeutic and diagnostic modalities. Evidence was also obtained from a questionnaire survey sent to leaders in cerebrovascular disease. Members of BAC reviewed literature related to their field and graded the scientific evidence on the various diagnostic and treatment modalities for stroke. Input was obtained from the organizations represented by BAC. BAC met on several occasions to review each specific recommendation and reach a consensus about its importance in light of other medical, logistical, and financial factors. CONCLUSIONS: There are a number of key areas supported by evidence-based medicine that are important for a comprehensive stroke center and its ability to deliver the wide variety of specialized care needed by patients with serious cerebrovascular disease. These areas include: (1) health care personnel with specific expertise in a number of disciplines, including neurosurgery and vascular neurology; (2) advanced neuroimaging capabilities such as MRI and various types of cerebral angiography; (3) surgical and endovascular techniques, including clipping and coiling of intracranial aneurysms, carotid endarterectomy, and intra-arterial thrombolytic therapy; and (4) other specific infrastructure and programmatic elements such as an intensive care unit and a stroke registry. Integration of these elements into a coordinated hospital-based program or system is likely to improve outcomes of patients with strokes and complex cerebrovascular disease who require the services of a comprehensive stroke center.

Academic Medical Centers↗

Neuronal migration is transiently delayed by prenatal exposure to intermittent hypoxia.

BACKGROUND: Neonatal neurodevelopment is influenced by a variety of external factors, although the mechanisms responsible are poorly understood. Prenatal hypoxia, from physiological or chemical sources, can have no discernible effect, or can result in a broad spectrum of abnormalities. METHODS: To mimic some of the maternal effects of smoking, we developed a model that investigates the effects of intermittent hypoxia (IH), with or without concurrent nicotine in timed pregnant Sprague-Dawley rats. RESULTS: We found no significant differences between litter sizes or birthweight of pups from any treatment group, but animals exposed to IH (with or without nicotine) showed long term diminished body weights. Animals subjected to IH consistently showed a transient delay in neuronal migration early in the postpartum period, which was amplified by concurrent nicotine administration. We observed increased c-Abl protein levels in animals from the IH treatment groups. Multiple proteins involved in the intricate control of neuronal migration were also altered in response to this treatment, primarily the downstream targets of c-Abl: Cdk5, p25, and the cytoskeletal elements neurofilament H and F-actin and catalase. Catalase activity and protein levels, already elevated in response to IH, were further amplified by simultaneous nicotine exposure. CONCLUSIONS: This new model provides a novel system for investigating the effects of low grade IH in the developing brain and suggests that concurrent nicotine further aggravates many of the deleterious effects of IH.

Actins↗

Thrombolytic therapy of acute ischemic stroke: correlation of angiographic recanalization with clinical outcome.

BACKGROUND AND PURPOSE: The effect of vessel patency, following recombinant tissue plasminogen activator (rtPA) administration, on clinical outcome in acute ischemic stroke (AIS) has been controversial. We studied the effect of recanalization following intraarterial (IA) and intravenous/IA (IV/IA) rtPA on clinical outcome in AIS. METHODS: Recanalization was classified angiographically as complete (as compared with unoccluded vessel, thrombolysis in myocardial infarction classification [TIMI] 3), none (with no change from prethrombolysis, TIMI 0), and partial (when a change in the flow from baseline was noted, TIMI 1-2). Outcomes were symptomatic intracranial hemorrhage (sICH), 90-day modified Rankin scale (< or = 2 as a good outcome), and 3-month mortality. RESULTS: Ninety-six patients had either combined IV/IA (41) or IA (55) rtPA for AIS during a 7-year period. Any recanalization occurred in 69%; 55% of those had a good outcome versus 23% in the rest (Odds ratio = 3.9; 95% confidence interval [CI] = 1.4-11.2; P = .007). Only 24% had complete recanalization; 74% had a good outcome versus 36% in the nonrecanalization group (OR = 5.1; 95% CI = 1.6-16.8; P = .002). When adjusted to time to therapy and vessel occluded, these results lessened but remained significant. The sICH rate with any recanalization was 7.6% versus 13.3% in patients with persistent clot (relative risk (RR) = 0.6; 95% CI = 0.2-2.0; P = .45). Death occurred in 19.7% of those whose vessels recanalized versus 33.3% in the rest (RR = 0.56; 95% = 0.26-1.19; P = .2). CONCLUSION: A total of 24% and 69% of patients had complete and any recanalization, respectively, following endovascular rtPA therapy of AIS. The degree of recanalization was directly related to time to therapy and associated with good clinical outcome without an increase in the rate of adverse effect.

Aged↗

Management of normal pressure hydrocephalus.

Gait instability, urinary incontinence, and dementia are the signs and symptoms typically found in patients who have normal pressure hydrocephalus. Estimated to cause no more than 5 percent of cases of dementia, normal pressure hydrocephalus often is treatable, and accurate recognition of the clinical triad coupled with radiographic evidence most commonly identifies likely responders. Magnetic resonance imaging or computed tomography typically demonstrates ventricular dilation with preservation of the surrounding brain tissue. The abnormality in normal pressure hydrocephalus occurs secondary to an abnormality in fluid removal, leading to an increase in ventricular size and encroachment of enlarged ventricles on adjacent brain tissue. The pressure exerted on the cerebral parenchyma by immense fluid-filled cavities deforms white matter tracts, instigating gait abnormalities and incomplete control of the bladder, as well as difficulties in processing incoming stimulation and in producing expeditious responses. Signs and symptoms often occur as sequelae to an imbalance between the expected ongoing production of cerebrospinal fluid and continuous efflux. Ventriculoperitoneal shunting is used to relieve excess ventricular fluid not absorbed by normal physiologic channels. Multiple studies have explored various techniques to identify patients with normal pressure hydrocephalus in an effort to predict likely benefit from shunting. However, the effectiveness of cerebrospinal fluid diversion has never been proven in a randomized controlled trial comparing use of a shunt versus no shunt.

Alzheimer Disease↗

Pituitary tumor apoplexy: characteristics, treatment, and outcomes.

Pituitary tumor apoplexy is an uncommon event heralded by abrupt onset of severe headache, restriction of visual fields, deterioration of visual acuity, and weakness of ocular motility frequently coupled with clinical indications of decreased endocrine function. Hemorrhage into or necrosis of a preexisting sellar mass, usually a pituitary macroadenoma, produces an expansion of sellar contents. Compression of adjacent structures elicits the variable expression of symptoms referable to displacement of the optic nerves and chiasm and impingement of the third, fourth, and sixth cranial nerves. Damage to or destruction of the anterior pituitary leads to multiple acute and/or chronic hormone deficiencies in many patients. Medical management may be used in rare cases in which the signs and symptoms are mild and restricted to meningismus or ophthalmoplegia deemed to be stable. In patients with visual or oculomotor lability or an altered level of consciousness, expeditious surgical decompression, accomplished most commonly through a transsphenoidal approach, should be performed to save life and vision and to optimize the chance of regaining or maintaining pituitary function.

Adenoma↗

Compromised metabolic recovery following spontaneous spreading depression in the penumbra.

Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra. SD was elicited in one group of rats by injecting KCl directly into a frontal craniectomy and the wave of depolarization was recorded in two craniectomies 3 and 6 mm posterior to the first one. In a second group, the middle cerebral artery was occluded using the monofilament technique and a recording electrode was placed 5 mm lateral to the midline and 0.2 mm posterior to bregma. To determine the metabolic response in the penumbral region of the cortex ipsilateral to the occlusion, brains from both groups were frozen in situ when the deflection of the SD was maximal. The spatial metabolic response of SD in the ischemic cortex was compared to that in the non-ischemic cortex. Coronal sections of the brains were lyophilized, pieces of the dorsolateral cortex were dissected and weighed, and analyzed for ATP, P-creatine, inorganic phosphate (Pi), glucose, glycogen and lactate at varying distances anterior and posterior to the recording electrode. ATP and P-creatine levels were significantly decreased at the wavefront in both groups and the levels recovered after passage of the wavefront in the normal brain, but not in the ischemic brain. Glucose and glycogen levels were significantly decreased and lactate levels significantly increased in the tissue after the passage of the wavefront. While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex. SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised. Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra.

Adenosine Triphosphate↗

Length of stay and mortality in neurocritically ill patients: impact of a specialized neurocritical care team.

OBJECTIVE: To determine predictors of in-hospital and long-term mortality and length of stay in patients admitted to the neurosciences critical care unit. DESIGN: Retrospective analysis of a prospectively collected database. SETTING: Neurosciences critical care unit of a large academic tertiary care hospital. PATIENTS: Adult patients (n = 2381) admitted to our neurosciences critical care unit from January 1997 to April 2000. INTERVENTIONS: Introduction of a specialized neurocritical care team. MEASUREMENTS AND MAIN RESULTS: Data obtained from the database included demographics, admission source, length of stay, neurosciences critical care unit and hospital disposition, admission Acute Physiology and Chronic Health Evaluation (APACHE) III score, and principal and secondary diagnoses. The introduction of a neurocritical care team in September 1998 was also collected, as was death at 1 yr after admission. Univariate analysis was carried out using Student's t-test, Mann-Whitney U test, or chi-square test (significance, p < .05). A logistic regression model was used to create a prediction model for in-hospital and long-term mortality. A general linear model was used to determine predictors of length of stay (after log transformation). Independent predictors of in-hospital mortality included APACHE III (odds ratio, 1.07 [1.06-1.08]) and admission from another intensive care unit (odds ratio, 2.9 [1.4-6.2]). The presence of a neurocritical care team was an independent predictor of decreased mortality (odds ratio, 0.7 [0.5-1.0], p = .044). Admission after the neurocritical care team was implemented was associated with reduced length of stay in both the neurosciences critical care unit (4.2 +/- 4.0 vs. 3.7 +/- 3.4, p < .001) and the hospital (9.9 +/- 8.0 vs. 8.4 +/- 6.9, p < .0001). There was no difference in readmission rates to the intensive care unit or discharge disposition to home before and after the neurocritical care team was established. The availability of the neurocritical care team was not associated with significant changes in long-term mortality. Factors independently associated with long-term mortality included female gender, admission from another intensive care unit, APACHE III score, and being moderately disabled before admission. CONCLUSION: Introduction of a neurocritical care team, including a full-time neurointensivist who coordinated care, was associated with significantly reduced in-hospital mortality and length of stay without changes in readmission rates or long-term mortality.

APACHE↗

Extreme elevation of intrasellar pressure in patients with pituitary tumor apoplexy: relation to pituitary function.

The dominant mechanism for hypopituitarism and hyperprolactinemia commonly observed in patients with pituitary macroadenomas was postulated to be increased intrasellar pressure (ISP) caused by the slow and gradual expansion of adenomas within the sella turcica. Hemorrhagic infarction of adenomas (pituitary tumor apoplexy) is associated with a rapid, rather than gradual, increase in intrasellar contents. The impacts of the sudden increase in intrasellar contents on ISP and pituitary function are unknown. ISP and pituitary function were determined in 13 patients with pituitary tumor apoplexy who had surgical decompression within 1 wk of symptoms' onset. ISP measurements were remarkably high (median, 47 mm Hg), whereas serum prolactin (PRL) concentrations were generally low (median, 3.5 microg/liter). There was an inverse correlation (r = -0.76; P < 0.01) between ISP measurements and serum PRL concentrations. Postoperatively, partial recovery or maintenance of pituitary function was noted in seven of 13 patients. These seven patients had higher (P = 0.013) serum PRL levels (9.3 +/- 7.4 microg/liter) and lower (P < 0.001) ISP measurements (35.9 +/- 7.3 mm Hg) than the respective values in the remaining six with persistent postoperative hypopituitarism (1.6 +/- 0.6 microg/liter and 55.9 +/- 2.4 mm Hg, respectively). The low serum PRL levels in patients with tumor apoplexy suggested that ischemic necrosis of the anterior pituitary resulting from sudden and extreme elevation of ISP was commonly observed in this setting. A normal or elevated serum PRL level in patients with non-PRL-secreting macroadenomas indicates the presence of viable pituitary cells and the high likelihood of postoperative recovery of pituitary function.

Adult↗

Early carotid artery stenting and angioplasty in patients with acute ischemic stroke.

OBJECTIVE: To determine the safety of early percutaneous endovascular carotid angioplasty and stenting (CAS) after an ischemic stroke. METHODS: The neurointerventional database was reviewed for patients who underwent CAS after an acute ischemic stroke in two university hospitals. Clinical and radiological data were reviewed. Outcomes were worsening stroke, new stroke, or stroke-related death up to 30 days after the procedure. Procedure-related complications were also documented. RESULTS: A total of 38 patients with 39 procedures were identified. The mean age was 67 +/- 15 years; 31 of 38 patients were Caucasian and 24 were female. Hypertension was found in 21 patients, peripheral vascular disease in 12, diabetes in 13, and coronary artery disease in 18. The median initial National Institutes of Health Stroke Scale score was 8. The carotid artery showed severe to high-grade stenosis in 28 patients, dissection was present in 6, and the rest had an acute occlusion treated with thrombolysis followed by CAS. The mean time from stroke onset to CAS was 55 +/- 34 hours. The mean degree of stenosis at baseline was 86 +/- 11%. In 37 procedures, complete recanalization was achieved, defined as less than 10% residual narrowing; in 2 procedures, the residual stenosis was mild (10-20%). Neurological deterioration occurred after three procedures (7.7%), with minor nondisabling stroke in two and death from intracranial hemorrhage in one. CONCLUSION: If deemed necessary and in certain circumstances, early CAS seems to be safe after acute ischemic stroke if infarction volume is small and neurological deficit is mild.

Aged↗

Vasospasm.

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Cerebrospinal Fluid↗