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Biomedical subjects

H L Lutsep

Publications and source records attributed to H L Lutsep.

14 recordsLinked to original sources
PubMed2001

Current status of neuroprotective agents in the treatment of acute ischemic stroke.

To keep ischemic brain cells alive, neuroprotective agents target events in the ischemic cascade that might be injurious to the cells. They can be divided broadly into groups that restore ion balance, block receptors, prevent reperfusion injury, or promote neuronal healing. To date, neuroprotective agents have either shown a lack of efficacy in clinical stroke trials or been limited by side effects. Ongoing clinical trials with novel agents are trying to enroll a more homogeneous population of stroke patients in an effort to demonstrate treatment benefit.

Acute Disease↗
PubMed2001

Does reversal of ischemia on diffusion-weighted imaging reflect higher apparent diffusion coefficient values?

This study investigated whether ischemia on diffusion-weighted imaging (DWI) that reverses has higher apparent diffusion coefficients (ADCs). A patient treated with thrombolytics was evaluated with serial magnetic resonance imaging studies before treatment, at 3 and 14 days and at 4 weeks. A 100.01-cm3 left frontoparietal stroke on baseline DWI was only 18.11 cm3 (18%) on 4-week fluid attenuated inversion recovery. The mean ADC was 7.43 x 10(-3) mm2/s in the 6 regions that reversed and 7.31 x 10(-3) mm2/s in the 6 regions that persisted (P < .036). With thrombolytic treatment, large ischemic lesions on DWI may reverse, and these areas display higher mean ADCs.

Brain Ischemia↗
PubMed2001

Potential of anticytokine therapies in central nervous system ischaemia.

Central nervous system (CNS) ischaemia is associated with an acute inflammatory response which appears to potentiate CNS injury, especially following reperfusion. This response includes the release of inflammatory mediators called cytokines including IL-1 and TNF-alpha, which triggers the production of additional cytokines including IL-6 and activates leukocytes which infiltrate into the CNS. Increased expression of cytokines has been demonstrated to occur in the first few hours after CNS ischaemia. Preliminary clinical studies suggest that plasma levels of IL-6 are correlated with functional recovery while brain levels of cytokines have been demonstrated to increase following experimental ischaemia. Although there are no current clinical 'anti-cytokine' treatment studies for stroke, experimental studies modulating IL-1 and TNF-alpha have shown neuroprotection.

Animals↗
PubMed2000

Association of intracranial stenosis with cortical symptoms or signs.

The association of the presence of cortical symptoms or signs and anterior circulation intracranial stenosis in patients with anterior circulation ischemia and no known extracranial carotid or cardiac etiology was studied. Fifteen percent (5/33) of patients with cortical symptoms or signs had symptomatic intracranial stenosis of 50% or more by MR angiography or angiography, compared with 0% (0/15) of those without such findings (p < 0.005).

Aged↗
PubMed1999

Neuroprotection in acute ischaemic stroke. Current status and future potential.

Acute ischaemic strokes can potentially be treated by 2 different mechanisms: lysing the thrombus to enhance brain perfusion or salvaging brain tissue directly. Neuroprotective agents are designed to try to salvage brain tissue. They work either during acute ischaemia or during reperfusion, when additional brain injury may occur. Despite the completion of a number of clinical trials investigating neuroprotective agents that have various mechanisms of action, as yet no effective agent has been identified. Some drugs, such as N-methyl-D-aspartate (NMDA) receptor antagonists and anti-leucocyte adhesion agents, have been limited by adverse effects and drug reactions. However, the development of other agents in these classes that have better risk to benefit ratios may lead to an effective neuroprotective drug. Other drugs, including citicoline, clomethiazole and nalmefene, have more efficacy in certain patient subgroups than in the stroke population as a whole. Therefore, targeting these agents toward the groups in which they are most likely to work, such as patients with a certain size of stroke, may uncover efficacy. Encouragingly, a number of drugs that are in the early stages of development, such as YM 872, Bay X 3702 and BMS 204352, appear to offer new hope for neuroprotection.

Acute Disease↗
PubMed1999

Clinical acute stroke evaluation.

This article outlines the evaluation and management of acute stroke patients in the emergency room and during the acute stroke period. Although a few neurologic and metabolic processes can mimic stroke, a stroke can often be diagnosed and localized from the history and examination. The availability of a treatment that must be given within 3 hours of symptom onset, tissue plasminogen activator (tPA), necessitates that the initial evaluation be streamlined. The assessment of the potential tPA candidate requires specific attention to bleeding risks. All stroke patients benefit from interventions to limit complications in the acute period although in the thrombolytic-treated patient, blood pressures are managed more aggressively to prevent intracranial hemorrhage.

Diagnostic Imaging↗
PubMed1998

Modular organization of cognitive systems masked by interhemispheric integration.

After resection of the corpus callosum, V.J., a left-handed woman with left-hemisphere dominance for spoken language, demonstrated a dissociation between spoken and written language. In the key experiment, words flashed to V.J.'s dominant left hemisphere were easily spoken out loud, but could not be written. However, when the words were flashed to her right hemisphere, she could not speak them out loud, but could write them with her left hand. This marked dissociation supports the view that spoken and written language output can be controlled by independent hemispheres, even though before her hemispheric disconnection, they appeared as inseparable cognitive entities.

Adult↗
PubMed1997

Clinical utility of diffusion-weighted magnetic resonance imaging in the assessment of ischemic stroke.

Diffusion-weighted imaging (DWI) detects small changes in water diffusion that occur in ischemic brain. This study evaluated the clinical usefulness of a phase-navigated spin-echo DWI sequence compared with T2-weighted magnetic resonance imaging (T2W MRI) in patients with cerebral ischemia and assessed apparent diffusion coefficient (ADC) and T2-weighted imaging (T2WI) changes over time. ADC values and T2 ratios of image intensity were measured from the region of ischemia and from the corresponding contralateral brain region. The clinical histories of patients with DWI scans obtained over the course of 1 year were reviewed to ascertain whether DWI aided in clinical diagnosis or management. Of 103 scans obtained a mean of 10.4 days after symptom onset, DWI detected six lesions not seen on T2WI and discriminated two new infarcts from old lesions. DWI was most useful within 48 hours of the ictus. The evolution of ADC values and T2 ratios was evaluated in 26 cases with known symptom onset times. ADC values were low at less than 1 week after stroke onset and became elevated at chronic time points. T2 ratios were near normal acutely, increasing thereafter. DWI was superior to T2W MRI in detecting acute stroke, whereas both techniques assisted in determining lesion age.

Aged↗
PubMed1997

The therapeutic potential of anti-cytokine strategies in central nervous system ischaemia.

Central nervous system (CNS) ischaemia is associated with an acute inflammatory response which appears to potentiate CNS injury, especially following reperfusion. This response includes the release of inflammatory mediators, including the cytokines interleukin-1 (IL-1) and TNF-alpha. These trigger the production of additional cytokines, including IL-6, and activate leukocytes which infiltrate the CNS. IL-6 appears to play a central role in modulating this response, exhibiting both pro-inflammatory and anti-inflammatory activities. Preliminary clinical studies suggest that plasma levels of IL-6 are correlated with stroke size and functional recovery. Conversely, brain levels of cytokines have been demonstrated to increase following experimental ischaemia. Although there are at present no clinical ;anti-cytokine' treatment studies, experimental studies modulating cytokines have shown neuroprotection.

Journal Article↗
PubMed1995

Cerebral and callosal organisation in a right hemisphere dominant "split brain" patient.

Patients described in previous reports who have undergone corpus callostomy for control of seizures have been left hemisphere dominant for language. To determine the hemispheric localisation (and possible coexistence) of language and traditional right hemisphere skills in reversed dominance, the first right hemisphere dominant corpus callostomy patient was studied. Localisation of callosal functions was also investigated, as MRI showed 1.5 cm of spared callosal body. The patient, KO, a 15 year old girl with familial left handedness, underwent two stage callosotomy in 1988. Lateralised visually presented stimuli requiring same or different comparisons between visual fields showed chance performance. Oral naming and reading showed better performance by the right hemisphere than the left, whereas both hemispheres were proficient in auditory comprehension. Active voice syntax was above chance only in the right hemisphere. Face recognition was significantly better in the right hemisphere than in the left. Tasks requiring tactile comparisons between hands showed above chance performance except in the instance in which the non-dominant right hand was stimulated first in a point localisation task between hands. This case showed hemispheric coexistence of language and traditional right hemispheric skills in a corpus callosotomy patient with reversed language dominance. Tactile transfer was localised to the mid-posterior callosal body.

Adolescent↗
PubMed1989

Ultrastructural, morphometric, and immunocytochemical study of anterior horn cells in mice with "wasted" mutation.

Mice with the autosomal recessive gene "wasted" (wst/wst) manifest hindlimb paralysis and tremulousness, develop reduced secretory immune responses, and have abnormal DNA repair mechanisms. There is prominent vacuolar degeneration of neurons within anterior horns of the spinal cord and motor nuclei of the brainstem. A morphometric analysis of motor neurons in the spinal cord was performed on 2-hydroxyethyl methacrylate-embedded tissue from ten wst/wst mice, ten littermates (wst/+, +/+) without clinical deficits, and ten parental (+/+) control mice. Vacuolated neurons were present only in wst/wst mice (p = 0.0008). Fibrillary neurons were more numerous in the wst/wst mice than in littermates (p = 0.01) or controls (p = 0.007). The number of total or normal neurons did not differ significantly among the three groups. Volume measurements for normal, fibrillary, vacuolated, and total neurons were greater in wst/wst mice (p less than 0.008). Electron microscopic studies revealed vacuolar degeneration exclusively within neurons of wst/wst mice with the prominent accumulation of neurofilaments. Immunocytochemical staining of Araldite-embedded sections with monoclonal antibodies (MAb) to 68 kDa, 160 kDa, and 200 kDa neurofilament proteins showed prominent staining of vacuolated and fibrillary neurons in wst/wst mice exclusively with the MAb to 200 kDa neurofilaments. Dephosphorylation of tissue reduced the staining of 200 kDa neurofilaments in wst/wst mice. These studies suggest that phosphorylated neurofilaments may be important in events producing neuronal dysfunction. Therefore the "wasted" mutation may be an excellent model for the study of motor neuron disease.

Animals↗