Low-molecular-weight heparins and heparinoids in acute ischemic stroke : a meta-analysis of randomized controlled trials

BACKGROUND AND PURPOSE: Low-molecular-weight heparins and heparinoids (LMWHs) are superior to unfractionated heparin in the prevention and treatment of venous thromboembolism and acute coronary syndromes. We performed a systematic review of randomized controlled trials (RCTs) to examine the safety and efficacy of LMWH in acute ischemic stroke. METHODS: Randomized, controlled, and nonconfounded trials of LMWH in acute ischemic stroke were identified from the Cochrane Library (version 2, 1999), previous systematic reviews, and a review of publication quality relating to acute stroke trials. The authors each independently extracted data by treatment group and assessed trial quality using Cochrane Collaboration criteria. RESULTS: Eleven completed RCTs involving 3048 patients were identified; data were available from 10 of these. Four trials explicitly excluded patients with presumed cardioembolic stroke. Treatment with LMWH was associated with significant reductions in prospectively identified deep vein thrombosis (OR 0.27, 95% CI 0.08 to 0.96) and symptomatic pulmonary embolism (OR 0.34, 95% CI 0.17 to 0.69) and with increased major extracranial hemorrhage (OR 2.17, 95% 1.10 to 4.28). Nonsignificant increases in end-of-treatment (OR 1.20, 95% CI 0.86 to 1.69) and end-of-trial (OR 1.05, 95% CI 0.83 to 1.32) case fatality and symptomatic intracranial hemorrhage (OR 1.77, 95% CI 0. 95 to 3.31) were observed. End-of-trial death and disability was nonsignificantly reduced (OR 0.87, 95% CI 0.72 to 1.06). CONCLUSIONS: ++LMWHs reduce venous thromboembolic events in patients with acute ischemic stroke and increase the risk of extracranial bleeding. A nonsignificant reduction in combined death and disability and nonsignificant increases in case fatality and symptomatic intracranial hemorrhage were also observed. On the basis of the current evidence, LMWH should not be used in the routine management of patients with ischemic stroke.     

The vestibulo-collic reflex

Until now there has no been no simple, reliable clinical test that assesses the function of the otolith organs. However, recent work has suggested the occurrence of an easily identifiable electromyographic (EMG) waveform in isometrically contracting sternomastoid muscles in response to loud clicks. This is thought to represent an otolith evoked disynaptic reflex. Equipment routinely used for evoked response audiometry (ERA) has been adapted to investigate this response. A short latency (8 ms) positive-negative EMG waveform has been recorded in 31 of 32 normal subjects. The latency of the positive peak (P1) is 11.7 ms ( sd = 0.89), and the negative peak (N1) is 20.5 ms ( sd = 1.89). It is predominantly ipsilateral, although a contralateral response was present in 35.5%. The response has also been recorded in three patients with a severe unilateral sensorineural hearing loss and normal caloric responses, and in a patient undergoing cochlear implantation for profound bilateral sensorineural hearing loss. Further work is required to delineate the value of this technique in investigating vestibular lesions.     

The selective serotonin-2A receptor antagonist M100907 reverses behavioral deficits in dopamine transporter knockout mice.

A hyperdopaminergic state in humans has been hypothesized to contribute to the pathology of a number of psychiatric illnesses, including schizophrenia, bipolar disorder, and attention deficit hyperactivity disorder. Mice that display elevated synaptic levels of dopamine due to a genetically engineered deletion of the dopamine transporter (DAT) model behavioral deficits that simulate the above conditions. As novel treatment strategies for these disorders have focused on the serotonin (5-HT) 2A receptor, we determined the capacity of the highly selective 5-HT(2A) receptor antagonist M100907 to reverse behavioral deficits in DAT knockout (KO) mice. Prior to drug treatment, DAT KO mice exhibited increased levels of locomotor activity and highly linearized movement in a novel environment, as well as reduced prepulse inhibition (PPI) of acoustic startle, compared to wild-type littermates. Treatment with M100907 (0.3-1.0 mg/kg, but not 0.1 mg/kg) reversed locomotor deficits in DAT KO mice. Similarly, treatment with 1.0 mg/kg M100907 reversed the PPI deficits in DAT KO mice. These data indicate that selective 5-HT(2A) receptor antagonists, such as M100907, may represent a class of drugs that can be used to treat conditions in which a chronic, elevated dopaminergic tone is present and contributes to abnormal behavior and sensorimotor gating deficits.     

Peripheral and local anaesthetic techniques for paediatric surgery

Peripheral nerve blocks (PNBs) in paediatric patients are usually used as an adjunct to general anaesthesia, providing intra- and postoperative analgesia. These blocks provide good-quality analgesia preventing morbidity related to pain and reducing adverse effects from systemic analgesics. PNBs aid early patient recovery and discharge, which is essential in day-case surgery. Like all invasive techniques, PNBs are associated with complications and adverse effects. They should therefore be performed only after careful analysis of the risk:benefit ratio for each child. This article discusses a general approach to PNBs in children. It covers a small selection of limb and trunk blocks, and discusses the benefit of ultrasound guidance.     

Bleeding time,stroke and myocardial infarction: the Caerphilly prospective study

The stressed bleeding time is a simple 'global' test of haemostasis, dependent upon platelet function, rheology, thrombosis and intimal function. It could be of considerable value in clinical practice if it were shown to be predictive of vascular disease events. A stressed bleeding time test was done on 1319 men aged 55-69 years in the Caerphilly Cohort Study of Heart Disease, Stroke and Cognitive Decline. The men were followed-up and during the following 7-10 years 155 men had a myocardial infarction (MI) and 72 an ischaemic stroke. The mean bleeding time was 323 (SD 113) s. This was shorter in men who smoked by an average of 45 s, and lengthened in men who took aspirin daily by 40 s. After making statistical adjustments for numerous possible confounding factors, the relative odds (ROs) of an MI within the third of men with the longest bleeding times, compared to the third with the shortest times, was 0.90 (0.40-2.03). For ischaemic stroke, the ROs in the third of men with the longest times were 1.42 (0.39-5.21). The stressed bleeding time does not predict either MI or ischaemic stroke. It has no place in health screening.