Rendu–Osler–Weber syndrome presenting with pulmonary arteriovenous fistula

A pulmonary arteriovenous fistula is an abnormal connection between pulmonary arteries and veins. Patients with Rendu–Osler–Weber syndrome may present with this vascular malformation, which is a typical finding of the disease. Approximately 5–15% of Rendu–Osler–Weber syndrome patients have pulmonary arteriovenous malformations (AVM) and there is usually a family history of AVM in these patients. The malformations are usually located in the lower lobes. In this paper, I describe a 49‐year‐old male patient with dyspnoea, cough, haemoptysis and epistaxis. Physical examination showed nasal telangiectasias, cyanosis of the lips and nails, and a systolic bruit over the left lung. Chest X‐ray revealed a 5‐cm mass in the left lower lobe and after magnetic resonance examination, together with 3‐D magnetic resonance angiography, it was demonstrated to be a pulmonary arteriovenous fistula. The history of a niece with a similiar history of suspected pulmonary arteriovenous fistula led me to consider the possibility of Rendu–Osler–Weber syndrome presenting with a pulmonary arteriovenous fistula.     

CoQ10 fails to protect brain against focal and global ischemia in rats

OBJECTIVE: Release of oxygen free radicals occurs following cerebral ischemia. Studies show that oxygen free radicals mediate ischemic brain injury. CoQ10 is a potent free radical scavenger and may offset brain injury associated with reperfusion. We tested exogeneous CoQ10 as a neuroprotectant in rats following both global and focal ischemic insults. METHODS: Rats were subjected to either 4-vessel occlusion ischemia (4-VO, 10 min occlusion, 7-day survival) or middle cerebral artery occlusion (MCAO, 120 min-occlusion, 22.5 h survival). Regional cerebral blood flows (rCBF) and physiological variables such as blood pressure, pO2, pCO2, plasma glucose and hematocrit were monitored and measured in focal ischemia. The animals were randomized to receive treatments of either phosphate buffered saline (PBS) vehicle or CoQ10 following global or focal ischemia. Injection times were at the end of ischemia and 3 h later for both models of ischemia. Histological outcomes are expressed as a percentage of hippocampal CA(1) cell injury in global ischemia or percentage of cortical infarct over that of non-ischemic hemisphere in focal ischemia. RESULTS: In global ischemia, animals treated with PBS vehicle and CoQ10 had 86+/-5% (n=8) and 83+/-10% (n=8), respectively, of hippocampal CA(1) cell injury (P>0.05). The percentage of infarct volumes in animals following focal ischemia were 23+/-9% (control, n=10) and 25+/-9% (CoQ10, n=10). There were no temperature or physiological differences between the two treatment groups. CONCLUSION: Acute treatment with CoQ10 via intraperitoneal injection does not prevent neuronal injuries following global and focal ischemia.     

Predictors of stroke outcome

Recent literature has identified many of the important factors helpful in predicting outcome even at the very acute stage of stroke. Demographic factors, risk factors, clinical exam findings, clinical scales laboratory tests, and neuroimaging all provide important information that can assist the clinician in predicting outcome. Specific factors seem to influence the effect of stroke treatments such as thrombolysis. Consideration of these factors is important when treatment decisions such as thrombolysis are being contemplated. New techniques such as eco-planar MR Imaging are now being developed that seem extremely accurate in predicting outcome. These techniques represent the "crystal ball" of predicting stroke outcome.     

Neuroprotection achieved with a novel proteasome inhibitor which blocks NF-kappaB activation

Activated NF-kappaB contributes to cerebral infarction by triggering a neuro-inflammatory response. Rats subjected to 90min middle cerebral artery occlusion developed a cortical infarct of 20+/-4% of hemispheric volume (n = 8). Treatment with the proteasome inhibitor CVT-634 resulted in a significantly smaller infarct of 13+/-2% (n = 7, p<0.01) and 12+/-2% (n = 8, p<0.001) of hemispheric volume at 1 day and 7 days, respectively. Since regional cerebral blood flows for the core and penumbral regions were not affected, we concluded that all animals received the same ischemic insult The reduction in infarction persisted for 7 days. This is the first indication that a proteasome inhibitor can reduce infarct volume in a focal model of cerebral ischemia.     

Caspase inhibitors reduce neuronal injury after focal but not global cerebral ischemia in rats

BACKGROUND AND PURPOSE: Studies show that blocking the activation of caspases by the caspase inhibitors z-VAD.FMK and z-DEVD.FMK can reduce ischemic neuronal injury after cerebral ischemia. Because the severity of ischemia was mild in some studies, we tested the efficacy of these caspase inhibitors on moderately severe but transient forebrain and focal ischemic insults in the rat. METHODS: Various regimens of z-VAD, z-DEVD, and control DMSO were given to rats subjected to either 4-vessel occlusion ischemia (4-VO, 10-minute occlusion, 7-day survival) or distal middle cerebral artery occlusion (MCAo, 90-minute occlusion, 22.5-hour survival). In global ischemia, treatments were given immediately after ischemia (experiment 1) or as preischemic and postischemic treatments (experiment 2). Three focal ischemia experiments were done. Injection times were 60 minutes into ischemia (experiment 1) and 60 minutes into ischemia plus 30 and 120 minutes after ischemia (experiment 2). Experiment 3 was identical to experiment 2 except that a 30-minute preischemia treatment was instituted. Core normothermia was maintained in all experiments during ischemia. However, in the last focal and global experiments, core and brain temperatures, respectively, were also measured after ischemia with telemetry probes. Because hyperthermia accompanied z-DEVD treatment, an extra z-DEVD-treated group (MCAo) was included with temperature clamped at normothermia. RESULTS: Neither z-VAD nor z-DEVD significantly reduced CA1 injury after global ischemia. In focal ischemia, both drugs significantly reduced infarction, but only in the third experiment, and the prevention of hyperthermia that accompanied z-DEVD treatment did not alter this. CONCLUSIONS: These results suggest a detrimental role of caspases in moderately severe focal but not global cerebral ischemia.     

Doubts, fears and misconceptions. What is the future of thrombolysis in acute stroke?

Alteplase for acute ischemic stroke may be the first stroke intervention to have a significant public health impact. In February 1999, this therapy was conditionally licensed in Canada for acute ischemic stroke within three hours of symptom onset. However, considerable controversy exists regarding its safety, its wider applicability outside clinical trials, and its ultimate availability. In this article we review the thrombolytic literature, attempt to answer many of the concerns, provide new guidelines for its use, and cite the need for more information about whom we should and should not be treating with this therapy.