Objective-To determine the benefit of midodrine, an agonist, on symptom frequency and haemodynamic responses during head up tilt in patients with neurocardiogenic syncope. Setting-Cardiovascular investigation unit (a secondary and tertiary referral centre for the investigation and management of syncope). Patients-16 outpatients (mean (SD) age 56 (18) years; five men) with frequent hypotensive symptoms (more than two syncopal episodes and fewer than 20 symptom free days per month), and reproducible syncope with glyceryl trinitrate (GTN) during head up tilt. Design and intervention-Randomised double blind placebo controlled study. Patients were randomised to receive either placebo or midodrine for one month. Symptom events were recorded during each study month. At the end of each study month patients completed a quality of life scoring scale (Short Form 36) and a global assessment of therapeutic response. They received GTN with head up tilt for measurement of heart rate (electrocardiography), phasic blood pressure (digital photoplethysmography), and thoracic fluid index (transthoracic impedance plethysmography) during symptom provocation. Results-Patients administered midodrine had an average of 7.3 more symptom free days than those who received placebo (95% confidence interval (CI) 4.6 to 9; p < 0.0001). Eleven patients reported a positive therapeutic response with midodrine (p = 0.002). All domains of quality of life showed improvement with midodrine, in particular physical function (8.1; 95% CI 3.7 to 12.2), energy and vitality (14.6; 95% CI 7.3 to 22.1), and change in health status (22.2; 95% CI 11 to 33.4 ). Fourteen patients who were given placebo had tilt induced syncope compared with six given midodrine (p = 0.01). Baseline supine systolic blood pressure was higher and heart rate lower in patients who received midodrine than in those who were given placebo ( p < 0.05). A lower thoracic fluid index in patients administered midodrine indicates increased venous return when supine and during head up tilt. There were no serious adverse eVects. Conclusions-Midodrine had a conspicuous beneficial eVect on symptom frequency, symptoms during head up tilt, and quality of life. Midodrine is recommended for the treatment of neurocardiogenic syncope in patients with frequent symptoms. (Heart 1998;79:45-49)

We describe three patients with mitochondrial myopathy, dementia, loss of vision and hearing, seizure disorder with myoclonus, intermittent headaches of a vascular type, visual hallucinations, cerebellar dysfunction, and lactic acidosis. Muscle biopsies in all patients and liver biopsy in one revealed abnormal mitochondria. The disorder may be due to a deficiency of mitochondrial NADH-CoQ dehydrogenase.

Patients with SS often suffer considerable distress due to sicca symptoms and the complications of mucosal dryness. Although there are many topical treatments available, the literature on their use is scant. This paper describes the treatments available and suggests a rationale for the choice of product.

W hile the physiology of the normal carotid baroreflex is reasonably well established, the pathophysiology of carotid sinus hypersensitivity (CSH) remains obscure. It has been proposed that central a 2 adrenoceptor upregulation provides the substrate for the changes in baroreflex gain which manifest as CSH. 1 This hypothesis suggests that carotid sinus stiffness resulting from age related cardiovascular disease causes relative diminution of afferent baroreceptor neural traffic, with compensatory brain stem post-synaptic a 2 adrenoceptor upregulation. This physiologic denervation hypersensitivity then causes the overshoot bradycardia and hypotension following carotid sinus stimulation that is clinical CSH. Though widely quoted, this hypothesis has no evidence base, and no attempts have been made to date to test it. If a 2 adrenoceptor hypersensitivity was the major pathophysiological defect in CSH, a centrally active a 2 adrenoceptor antagonist should abolish or attenuate the effects of carotid sinus massage (CSM) in such individuals.1 2 In order to test this hypothesis we studied the effects of the central a 2 adrenoceptor antagonist yohimbine 3 on the vasodepressor response to CSM in syncopal subjects with CSH, in a randomised, double blind, placebo controlled study, utilising a crossover design. METHODSEighteen consecutive patients with syncope caused by CSH, who had been referred for permanent pacemaker implantation through our syncope facility and had a minimum reproducible vasodepressor response of 20 mm Hg during CSM post-pacemaker, participated in this study. While a 50 mm Hg fall in systolic blood pressure (SBP) during CSM defines vasodepressor CSH, 4 a previous study has shown that during supine CSM in healthy subjects, mean vasodepression was 19 mm Hg on the right, and 14 mm Hg on the left. 5Subjects were studied post-pacemaker implantation so that the fixed cardiac pacing rate avoided the confounding effects of hypotension secondary to variable bradycardic or asystolic responses to CSM. The investigation had local ethical approval. Following informed, written consent, 10 ml solutions of intravenous yohimbine hydrochloride (0.063 mg/kg) and normal saline were infused over two minutes into each subject via antecubital cannulae, on separate days, in random, double blind fashion with a minimum 48 hours between injections to ensure adequate washout of the active drug (distribution half life 0.4-18 minutes, elimination halflife 15-150 minutes) (fig 1). 3Twelve lead ECG and non-invasive beat-to-beat blood pressure measurements (Finapres, Ohmeda, Wisconsin, USA) were then recorded at baseline and during supine, sequential, bilateral and longitudinal CSM (with a one minute interval between episodes) for five seconds before and after each injection. Continuous ECG and blood pressure monitoring occurred throughout the study periods. Time to SBP nadir with CSM was also recorded. The mean differences in vasodepressor response and time to SBP nadir following bilateral CSM before and after saline injection were comp...

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