Human parvovirus infection and transient erythroblastopenia of childhood.
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Erythroblasts↗
Biomedical subjects
K W Muir
Publications and source records attributed to K W Muir.
Safety and tolerability of 619C89 after acute stroke.
BACKGROUND: 619C89 is a use-dependent sodium channel blocker which reduces hemispheric infarction volume by up to 60% after permanent middle cerebral artery occlusion in rats. Intravenous doses of up to 1 mg/kg have been well tolerated by healthy young and elderly volunteers. This study sought to assess safety and tolerability of 619C89 in the treatment of acute stroke. METHODS: Patients were randomised within 12 h of onset of stroke to receive 619C89 or placebo as an intravenous loading dose, followed by maintenance doses given 8 hourly for 64 h in a double-blind, ascending-dose tolerance study. Dosing commenced at 0.5 mg/kg loading plus 0.25 mg/kg/8 h maintenance for the first group and increased in increments of 0.5 mg/kg loading +0.25 mg/kg/8 h maintenance thereafter. Safety evaluation was continued for 3 months. RESULTS: 48 patients were recruited. 12 received placebo and 36 received 619C89 in doses up to 2.5 mg/kg loading plus 1.25 mg/kg/8 h. Dose escalation was stopped after the occurrence of hallucinations in 5 of 18 patients who received 2 mg/kg/8 h or more. Gastro-intestinal upset and confusion were also possibly drug related. No drug-related effects on cardiovascular function were found. CONCLUSIONS: 619C89 was associated with significant central nervous system side-effects at doses of 2 mg/kg + 1 mg/kg/8 h or greater as discrete intravenous infusions within 12 h of stroke onset. It may also cause gastro-intestinal side-effects. Doses below this are well tolerated in patients. No adverse cardiovascular effects were seen.
Acute Disease↗
What constitutes a true hyperdense middle cerebral artery sign?
OBJECTIVES: The 'hyperdense MCA sign' refers to an appearance of increased attenuation of the proximal middle cerebral artery (MCA) that is often associated with thrombosis of the M1 MCA segment and may be the only diagnostic feature on computed tomography early after ischaemic stroke. False positives are recognized, and correct recognition of this sign has, therefore, assumed greater importance with the advent of thrombolytic therapy for stroke. We sought to define objective criteria for hyperdensity of the MCA. METHODS: Brain computed tomographs obtained by a standard protocol in a neuroradiology department were analyzed by a single observer. All consecutive scans reported as exhibiting a hyperdense MCA were compared to controls reported as having normal scans. Ovoid regions of interest were placed over the vessels and cerebral cortices, and the attenuation in Hounsfield units (HU) measured. Absolute attenuation and ratios of one side to the other were compared. RESULTS: MCA attenuation was unrelated to age in cases (n = 18) and controls (n = 80). The mean MCA attenuation was greater in the affected MCA of cases as compared with controls [54.0 HU (99% confidence interval CI 46.7-61.2) vs. 41.3 HU (99% CI 39.7-43.0); p < 0.00001]. Cases were subdivided into true and false positives by the ratio of denser:less dense MCA (within or without the 95% prediction interval for controls). In all true positives, the MCA ratio was > 1.2. 9 of 10 true positives had acute ischaemic stroke; 1 patient had herpes simplex encephalitis, but had MCA attenuation within the 95% CI for controls. False positives had mature cerebral infarction or non-ischaemic pathologies. The ratio of MCA attenuation to adjacent cerebral cortex was significantly higher in both true and false positives than in controls. CONCLUSIONS: Hyperdense MCAs associated with acute ischaemic stroke can be distinguished from normal vessels and false positives by measurement of absolute attenuation of affected and normal vessels: an absolute density of >43 HU and a MCA ratio of >1.2 defined hyperdensity and excluded all other pathologies. Confirmation in other centres is required.
Adolescent↗
Phase II clinical trial of sipatrigine (619C89) by continuous infusion in acute stroke.
BACKGROUND: The sodium channel blocker sipatrigine (619C89) prevents ischemia-induced glutamate release and is neuroprotective in animal models of stroke. Previous clinical experience found neuropsychiatric effects attributed to sipatrigine that may have been related to peak plasma concentrations of the drug. METHODS: Patients within 12 h of clinically diagnosed stroke were randomized to placebo or sipatrigine at total doses of 10, 18, 27, or 36 mg/kg by continuous intravenous infusion over 65 h. Pharmacokinetic and routine laboratory analyses were undertaken. The outcome at 30 days or 3 months was assessed by Barthel and Rankin scores. RESULTS: Twenty-seven patients were recruited: 7 of 21 patients stopped the sipatrigine infusion early due to adverse events as compared with none of 6 placebo patients. Neuropsychiatric effects (reduced consciousness, agitation, confusion, visual perceptual disturbance, or frank hallucinations) occurred in 16 of 21 patients receiving sipatrigine and in no placebo patients. Nausea, vomiting, infusion site reactions, and hyponatremia were also commoner in sipatrigine patients. Pharmacokinetic parameters were similar to those observed previously. No effects on outcome measures were demonstrated. CONCLUSIONS: Continuous infusion of sipatrigine is associated with neuropsychiatric effects. No difference in the nature of these events was evident between this regimen and repeated short infusions, but it was possible to administer higher doses.
Acute Disease↗