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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The third most common stroke complication is infection. We studied the rates of aspiration pneumonia and urinary tract infection (UTI), their risk factors and their effect on outcome in the 1455 Glycine Antagonist (Gavestinel) in Neuroprotection (GAIN) International patients with ischaemic stroke. Forward stepwise logistic regression and Cox proportional hazards modelling identified baseline factors that predicted events and the independent effect of events up to day 7 on poor stroke outcome at 3 months in patients alive at day 7, after correcting for prognostic factors. Higher baseline National Institute of Health Stroke Scale (NIHSS) and age, male gender, history of diabetes and stroke subtype predicted pneumonia, which occurred in 13.6% of patients. Female gender and higher baseline NIHSS and age predicted UTI, which occurred in 17.2% of patients. Pneumonia was associated with poor outcome by mortality (hazard ratio, 2.2; 95% confidence interval, 1.5-3.3), Barthel index (<60) (odds ratio, 3.8; 2.2-6.7), NIHSS (4.9; 1.7-14) and Rankin scale (>/=2) (3.4; 1.4-8.3). UTI was associated with Barthel index (1.9; 1.2-2.9), NIHSS (2.2; 1.2-4.0) and Rankin scale (3.1; 1.6-4.9). Pneumonia and UTI are independently associated with stroke poor outcome. Patients with identified risk factors must be closely monitored for infection.
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PMID:Pneumonia and urinary tract infection after acute ischaemic stroke: a tertiary analysis of the GAIN International trial. 1469 88

It has long been accepted that high concentrations of glutamate can destroy neurons, and this is the basis of the theory of excitotoxicity during brain injury such as stroke. Glutamate N-methyl-D-aspartate (NMDA) receptor antagonists such as Selfotel, Aptiganel, Gavestinel and others failed to show neuroprotective efficacy in human clinical trials or produced intolerable central nervous system adverse effects. The failure of these agents has been attributed to poor studies in animal models and to poorly designed clinical trials. We also speculate that NMDA receptor antagonism may have hindered endogenous mechanisms for neuronal survival and neuroregeneration. It remains to be proven in human stroke whether NMDA receptor antagonism can be neuroprotective.
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PMID:The rise and fall of NMDA antagonists for ischemic stroke. 1503 9

During cerebral ischemia, there is excessive activity of excitatory amino acids, especially glutamate. Activation of glutamate receptors leads to a marked increase in intracellular calcium, which in turn leads to activation of intracellular enzymes and neuronal death--the so-called excitotoxic cascade. The calcium antagonist nimodipine, which acts at L-type calcium channels, was tested for a putative neuroprotectant effect in patients with acute ischemic stroke, but no beneficial effect was demonstrated. Glutamate receptors are attractive targets for neuroprotectant drugs because glutamate plays a central role in the excitotoxic cascade. Clinical trials of NMDA (N-methyl-D-aspartate) antagonists have been disappointing, however, and psychiatric side effects seem to be a general problem with this class of drug. Another strategy proposed for interfering with NMDA receptor function is the infusion of magnesium. The NMDA receptor is normally blocked by magnesium ions and will only respond to glutamate when this magnesium-induced block is removed on depolarization. A large clinical trial to investigate possible neuroprotection by magnesium is underway. The NMDA receptor also has a glycine-binding site and a polyamine-binding site, and the cation channel will only open in response to glutamate if glycine and polyamines are already bound to these obligatory modulatory sites. Gavestinel is selective for the glycine-binding site, and eliprodil for the polyamine site, but large international clinical trials have failed to find any beneficial effects in patients with acute ischemic stroke. Neurotoxic free radicals are also generated during cerebral ischemia. Laboratory stroke models suggest that free radical scavengers might be effective neuroprotectants. One of these, NXY-059, was effective in several animal studies, and preliminary studies in human subjects show that plasma concentrations that are neuroprotective in animal models can be achieved and are well tolerated. Lubeluzole interferes with the glutamate-induced neuronal damage mediated through the formation of nitric oxide. However, a meta-analysis of all clinical trials of lubeluzole was unable to detect a neuroprotectant effect of the drug. There is now some evidence that, in addition to necrosis, some neurons die as a result of apoptosis after cerebral ischemia. Several drugs that interfere with the apoptosis cascade, for example, caspase inhibitors, are under investigation. Clomethiazole ('ZENDRA'; a trademark, the property of the AstraZeneca group of companies) is also undergoing a second large clinical trial in patients with major ischemic strokes. This drug's mechanism of action is not completely clear, but it is known to activate a nonbenzodiazepine site on the GABA(A) (gamma-aminobutyric acid) receptor. This causes increased chloride conductance and hyperpolarization. In vitro clomethiazole inhibits ischemia-induced glutamate efflux from cerebral neurons. The first large controlled trial showed it to be well tolerated and suggested a clinically significant effect in patients with deficits of a major stroke.
J Stroke Cerebrovasc Dis 2000 Nov
PMID:Mechanisms of action of neuroprotectants in stroke. 1789 14