Is clopidogrel superior to aspirin in secondary prevention of vascular disease?

The cornerstone in clinical evidence of the relative efficacy of thienopyridines (clopidogrel, ticlopidine) versus aspirin in the secondary prevention of vascular disease is the Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events trial. This trial showed a modest benefit in the reduction of vascular events by clopidogrel. The results differed according to qualifying disorder: myocardial infarction, -3.7%; ischaemic stroke, +7.3%; and peripheral arterial disease, +23.8% (P = 0.042). Similar results were found for ticlopidine after brain ischaemia. The safety of clopidogrel appears to be similar to that of aspirin and better than that of ticlopidine. However, the recent report of thrombotic thrombocytopenic purpura in association with clopidogrel causes concern

Sir John Charnley en de totale heuparthroplastiek

John Charnley, grondlegger van de moderne totale heuparthroplastiek, wordt in 1911 geboren in Bury (Lancashire). Zijn vader, Arthur, is chemicus in het nabijgelegen Manchester en zijn moeder, Lily, verpleegkundige in het Crumpsall Hospital. In 1929 start Charnley de opleiding geneeskunde aan de Victoria Universiteit in Manchester. Op vijfentwintigjarige leeftijd wordt hij de jongste Fellow ooit van het Royal College of Surgeons..

The plantar reflex : a historical, clinical and electromyographic study

The plantar reflex is one of the most important physical signs in medicine. Few patients undergoing a full medical examination can avoid having their soles stroked, because an upgoing great toe is regarded as a reliable sign of dysfunction of corticospinal nerve fibres. So far, there is little to justify a new study. One problem is, however, that it can be difficult to determine the direction of the reflex response: the movements of the great toe may be slight, wavering, inconstant, or masked by voluntary activity. Soon after the introduction of the reflex the comment had already been made that ' the average ward clerk's notes are quite worthless on the subject of the plantar reflex, though he may make fair notes on the knee jerk and the pupil reflex to light' (Harris, 1903 ). Anyone who is a regular participant in medical ward rounds knows that controversies about plantar reflexes still abound today. Decisions in such cases are ususally guided by a mixture of seniority and ill-defined intuition. This is because the toe response is widely regarded as an oracle which often speaks in riddles, rather than as a definite reflex phenomenon, subject to the rules of physiology. But to give the plantar reflex its proper value, the neurologist must be aware of what is happening in the spinal cord. Therefore the first leading theme of this study was to ascertain the connections between the roe responses and other spinal reflexes, and to apply these physiological relationships to the interpretation of equivocal plantar responses. A review of previous clinical studies about the plantar reflex precedes the actual experiments. Since Babinski discovered the toe response in 1896, he has been awarded a prominent place on the neurological Olympus, and his papers on the subject have been canonized (Wilkins and Brody, 1967). However, to get full insight into the meaning of Babinski's words, we must connect these with pre-existing concepts, with the subsequent development of Babinski's own ideas, and with additional clinical and physiological observations of others

Secondary prevention after cerebral ischaemia of presumed arterial origin: is aspirin still the touchstone?

Patients who have had a transient ischaemic attack or nondisabling ischaemic stroke of presumed arterial origin have an annual risk of death from all vascular causes, non-fatal stroke, or non-fatal myocardial infarction that ranges between 4% and 11% without treatment. In the secondary prevention of these vascular complications the use of aspirin has been the standard treatment for the past two decades. Discussions about the dose of aspirin have dominated the issue for some time, although there is no convincing evidence for any difference in effectiveness in the dose range of 30-1300 mg/day. A far greater problem is the limited degree of protection offered by aspirin: the accumulative evidence from trials with aspirin alone and only for cerebrovascular disease of presumed arterial origin as qualifying event indicates that a dose of aspirin of at least 30 mg/day prevents only 13% of serious vascular complications

Holter monitoring in patients with transient and focal ischemic attacks of the brain

The results of Holter monitoring in 100 patients with transient and focal cerebral ischemia were studied retrospectively. Atrial fibrillation (AF) was found in five patients compared with two from a group of 100 age and sex-matched control patients. Four of these had a previous history of AF or showed AF on the standard electrocardiogram. Episodic forms of sick sinus syndrome, which have also been related to cerebral embolism, were found in 32 of the TIA patients against 13 of the controls (p less than 0.0025). Sick sinus syndrome was of the bradyarrhythmia-tachyarrhythmia type in 14 of the TIA patients and in three of the controls (p less than 0.01). The relationship between TIAs and transient sinus node dysfunction could not be explained by concomitant heart disease. It is not yet clear whether the relationship is causal or indirect

Are white matter lesions directly associated with cognitive impairment in patients with lacunar infarcts?

Forty-four patients (mean age 66, SD 8 years) with either clinical evidence of a focal lacunar syndrome (n = 36) or with disorders of memory or gait (n = 8) in the presence of a lacunar infarct on CT were studied for cognitive functioning and for the presence of white matter lesions on MRI. MR images were assessed by a neurologist and a neuroradiologist blinded to the clinical data. Thirty-six patients had one or more lacunar infarcts on CT or MRI (in the thalamus in 5, in the caudate nucleus in 3 and in the internal capsule or corona radiata in the remaining patients). Twelve patients had multiple infarcts. Severe lesions of the white matted were found in 13 patients, mild to moderate lesions in 20 patients. Scores on Digit Span, Digit Symbol and delayed recall of the 15-Words test were significantly lower in the group with severe lesions, whilst there was a trend in the same direction for the Cognitive part of the Cambridge Examination of Mental Disorders in the Elderly, the Trailmaking B, Stroop colour interference test and the delayed visual reproduction of the Wechsler Memory Scale. These findings suggest that diffuse lesions of the white matter are an independent factor in the pathogenesis of intellectual dysfunction, also in patients with lacunar infarcts, but a truly independent analysis is difficult because the most severe involvement of the white matter tended to be associated with the largest number of lacunar infarcts

Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly

BACKGROUND AND PURPOSE: MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. METHODS: We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531

Correction: PAIS: paracetamol (acetaminophen) in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480]

BACKGROUND: The Paracetamol (Acetaminophen) In Stroke (PAIS) study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever.The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS) may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. METHODS: Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. CONCLUSION: The protocol change was initiated becau