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Biomedical subjects

H C Diener

Publications and source records attributed to H C Diener.

At least 19 recordsLinked to original sources
PubMed2001

Compensatory visual field training for patients with hemianopia after stroke.

Twenty-one patients with hemianopia received 4 weeks of compensatory visual field training. Detection of and reaction time to visual stimuli were measured with eyes fixating (condition A) and with use of exploratory eye movements (condition B) before and after training. Twenty-three healthy individuals served as control subjects for measurements of parameters during both conditions. Patients with hemianopia to either side showed a marked improvement of detection and reaction time during condition B, but minimum or no change during condition A. Improvements were maintained 8 months after training. Activity of daily living skills also improved in all patients. The size of scotoma on computerized perimetry, in contrast, remained unchanged. Training improved detection of and reaction to visual stimuli without restitution of the visual field defect.

Activities of Daily Living↗
PubMed2001

Arm training induced brain plasticity in stroke studied with serial positron emission tomography.

We used serial positron emission tomography (PET) to study training-induced brain plasticity after severe hemiparetic stroke. Ten patients were randomized to either task-oriented arm training or to a control group and scanned before and after 22.6 +/- 1.6 days of treatment using passive movements as an activation paradigm. Increases of regional cerebral blood flow (rCBF) were assessed using statistical parametric mapping (SPM99). Before treatment, all stroke patients revealed bilateral activation of the inferior parietal cortex (IPC). After task-oriented arm training, activation was found bilaterally in IPC and premotor cortex, but also in the contralateral sensorimotor cortex (SMC). The control group only showed weak activation of the ipsilateral IPC. After treatment, the training group revealed relatively more activation bilaterally in IPC, premotor areas, and in the contralateral SMC. Five normal subjects showed no statistical significant differences between two separate PET studies. In this group of patients, task-oriented arm training induced functional brain reorganization in bilateral sensory and motor systems.

Aged↗
PubMed2001

[Does early high dosage dipyridamole in prevention of secondary stroke induce cardiac events?].

In a post hoc analysis of the European Stroke Prevention Study 2 (ESPS2), we investigated whether dipyridamole given as antiplatelet drug in patients with TIA or stroke increases the risk of cardiac events. ESPS2 was a secondary prevention trial including 6602 patients with TIA or stroke. Patients were randomized into one of four treatment arms: 2 x 25 mg acetylsalicylic acid (ASA), 2 x 200 mg slow release dipyridamole (DP), the combination of DP and ASA and placebo. DP did not result in a higher number of cardiac events, e.g., angina pectoris, myocardial infarction or death. The combination of ASA plus DP was superior to either drug alone in the prevention of strokes.

Administration, Oral↗
PubMed2001

An in vivo rat model to study calcitonin gene related peptide release following activation of the trigeminal vascular system.

Calcitonin gene related peptide (CGRP) released from the C-fibers projecting from the trigeminal ganglion to the meninges has been suggested to play a crucial role in the pathophysiology of headache, particularly migraine. In humans it has been shown that CGRP is released during migraine-attacks, and this is attenuated by the administration of typical anti-migraine drugs such as dihydroergotamine or sumatriptan. We describe a new rat model which allows the study of CGRP release from the meninges into venous blood following activation of the trigeminal vascular system. The effects of classical and new anti-migraine drugs such as acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D agonist donitriptan (4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile) were evaluated in comparison with the established model of neurogenic inflammation in the meninges. Sumatriptan and donitriptan inhibited CGRP release as well as neurogenic inflammation. ASA, however, attenuated neurogenic inflammation, but not CGRP release, confirming the concept of prejunctional inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the further study of prejunctional pharmacology and mechanisms of neuropeptide release in the trigeminal vascular system, which might be crucial for the further development of potent, more effective anti-migraine drugs.

Animals↗
PubMed2001

Cyclandelate in the prophylaxis of migraine: a placebo-controlled study.

The prophylactic action of cyclandelate was investigated in a multicentre, randomized, placebo-controlled, parallel group study. A 4-week baseline period was followed by a 4-week placebo phase and a 16-week treatment period with either 1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine attacks/month were randomized. Neither the primary study endpoint (reduction of migraine days from baseline to the last 28 days) nor most of the secondary endpoints (reduction in the number of migraine attacks, severity or duration of attacks, frequency of autonomic disturbances, medication for treatment of attacks) showed a difference between cyclandelate and placebo. Cyclandelate, however, was superior to placebo in a global impression of efficacy rated by the patients and the treating physicians. Both treatments were well tolerated. In conclusion, cyclandelate was not superior to placebo in the prophylaxis of migraine with regard to parameters usually used in migraine prophylaxis trials.

Adolescent↗
PubMed2001

A comparative study of oral acetylsalicyclic acid and metoprolol for the prophylactic treatment of migraine. A randomized, controlled, double-blind, parallel group phase III study.

This study was a multinational, multicentre, double-blind, active controlled phase III trial designed to investigate efficacy and safety of 300 mg acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged 18-65 years, suffering between two and six migraine attacks per month were recruited. The main objective was to show equivalence with respect to efficacy, defined as a 50% reduction in the rate of migraine attacks. A run-in phase was carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both treatment groups the median frequency of migraine attacks improved during the study period, from three to two in the ASA group and from three to one in the metoprolol group; 45.2% of all metoprolol patients were responders compared with 29.6% with ASA. Medication-related adverse events were less frequent in the ASA group (37) than in the metoprolol group (73). The findings from this trial show that metoprolol is superior to ASA for migraine prophylaxis but has more side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a strict responder criterion ASA showed a responder rate comparable with the placebo rate in the literature.

Adolescent↗
PubMed2001

Treatment of migraine attacks with intranasal alniditan: an open study.

In this open phase-II clinical tolerability trial 17 neurologists enrolled a total of 112 patients and instructed them to administer a maximum of two doses of intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three consecutive migraine attacks of moderate to severe intensity. A second dose of the trial medication was allowed within 1-24 h after the first administration. At 1 h after intranasal administration, 70/103 (68%) patients had responded to treatment (reduction from severe or moderate headache before treatment to mild or no headache) after their first migraine attack, 65/94 (69%) after their second and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were considered responders at 1 h. The median time to onset of effect was 30 min. The migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3) after 4-5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the intranasal route, was effective in relieving migraine headaches in over two-thirds of the patients at 1 h.

Administration, Intranasal↗
PubMed2001

Imaging in cerebrovascular disease.

Various functional imaging modalities can be applied in acute ischaemic stroke to identify functionally impaired, but morphologically preserved tissue (i.e. the penumbra), and to distinguish it from irreversibly damaged tissue. Flow thresholds for irreversible tissue destruction resulting in functional impairment, as determined by positron emission tomography, perfusion and diffusion-weighted magnetic resonance imaging, single-photon computed tomography and xenon computed tomography, were comparable and ranged between 5 and 12 ml/100 g per min for the lower and 14 and 22 ml/100 g per min for the upper limit of penumbra. These imaging modalities help to select patients for thrombolytic therapy and provide evidence for the effect of this treatment on critically perfused tissue. They can also serve as surrogate markers in the evaluation of therapeutic efficacy. Further progress in interventional neuroradiology has been achieved with intra-arterial thrombolysis, which has become a treatment option beyond the 3-h therapeutic window in acute ischaemic stroke. Angioplasty and stenting of stenosis of arteries that supply the brain with blood have reached a point in their development at which a randomized trial to compare these treatments with vascular surgery is warranted.

Angiography, Digital Subtraction↗
PubMed2001

Glycine antagonist (GV150526) in acute stroke: a multicentre, double-blind placebo-controlled phase II trial.

GV150526 is a novel glycine antagonist at the NMDA receptor complex. It is a potent neuroprotective agent in animal models of acute stroke including permanent middle cerebral artery occlusion in the rat. GV150526 was very well tolerated in early human studies. The purpose of this randomised, double-blind, multicentre, placebo-controlled trial was to assess the safety and population pharmacokinetics of GV150526 in patients with a clinical diagnosis of acute stroke. Exploratory assessment of efficacy, quality of life and resource utilisation was also undertaken. Upon clinical diagnosis of acute stroke within 12 h of onset of symptoms, patients were treated with a loading dose of 800 mg GV150526 (or placebo), followed by 5 maintenance doses of 400 mg GV150526 (or placebo) given every 12 h over 3 days. Following observation of asymptomatic hyperbilirubinaemia, the maintenance dose was reduced mid-study to 200 mg. CT/MRI scanning was not mandatory prior to treatment. The study treated 128 patients (38 with GV 800 mg/400 mg, 48 with GV 800 mg/200 mg and 42 with placebo). Fewer patients with mild stroke (NIH scores < or =5) were enrolled in the GV150526-treated groups than in the placebo group (placebo 38%, GV 800 mg/400 mg 18%, GV 800 mg/200 mg 15%). There was also an imbalance in the proportion of patients with haemorrhagic strokes (placebo 5%, GV 800 mg/400 mg 3%, GV 800 mg/200 mg 15%). Mortality at 1 month was unbalanced between treatment groups, being 10, 18 and 17% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively (no significant difference). Similarly, adverse events, though consistent with an acute stroke population, appeared more often in the GV 800 mg/200 mg group. Functional outcomes at 1 month also showed imbalances, the percentage of patients with a Barthel Index score of > or =95 at 1 month being 52, 39 and 27% in the placebo, GV 800 mg/400 mg and GV 800 mg/200 mg groups, respectively. These results probably reflect a prognostically significant baseline difference between the groups rather than the effect of GV150526. GV150526 was generally well tolerated in patients with a clinical diagnosis of acute stroke and formal efficacy studies were considered justified.

Aged↗
PubMed2001

Drug-induced headache: long-term follow-up of withdrawal therapy and persistence of drug misuse.

Patients suffering from migraine, tension-type headache (TTH), or combined headache (CH) are at risk of developing drug-induced headache (DIH) due to regular use of analgesics, ergot alkaloids, and triptans. The aim of our study was to determine (1) the clinical features of DIH, (2) the outcome of withdrawal therapy using high methodological standards, and (3) predictors which could explain the high relapse rate (more than 40%) after a previously successful withdrawal therapy. We retrospectively reviewed 103 patients with migraine or TTH who underwent withdrawal therapy between 1994 and 1998. The long-term follow-up (2-4 years after therapy) was conducted by phone and by specially trained psychologists using a structured interview which enclosed characteristics of headache and medication behavior as well as patients global assessment of success. Complete sets of data were available from 83 patients (38 migraine, 26 TTH, 19 CH). The most frequently abused drugs were caffeine-combined analgesics (24%), followed by caffeine-combined ergotamines (19%), pure ergot alkaloids (17%), and monoanalgesics (17%). 48.5% of the patients suffered an abuse relapse within 4 years and developed the complete features of DIH again. Analgesic and ergot alkaloid combinations with caffeine lead significantly more often to a relapse. A long-term successful therapy is connected with a significant reduction of the frequency of headache attacks. Under relapse conditions, the patients reached their former headache frequency level. The data show a higher relapse rate than previously assumed and that certain substance groups bear a higher relapse risk.

Adult↗
PubMed2001

Treatment of acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the TOPAS trial. Therapy of Patients With Acute Stroke (TOPAS) Investigators.

BACKGROUND AND PURPOSE: To study the safety and efficacy of the low-molecular-weight heparin certoparin, we performed a randomized, double-blind, dose-finding multicenter trial in patients with acute ischemic stroke (Therapy of Patients With Acute Stroke [TOPAS]). METHODS: We randomized 404 patients to 4 treatment groups within 12 hours of stroke onset: 3000 U anti-factor Xa (aXa) certoparin once daily (treatment group 1); 3000 U aXa twice daily (group 2); 5000 U aXa twice daily (group 3); and 8000 U aXa twice daily (group 4). The primary efficacy variable was the proportion of patients reaching a favorable functional outcome (Barthel Index >/=90 points) at 3 months. CT was performed at trial entry, after 7 days, and on clinical deterioration. RESULTS: The proportion of patients with Barthel Index >/=90 was not different between treatment arms (61.5%, 60.8%, 63.3%, and 56.3% in the 4 groups, respectively; intent-to-treat population). European Stroke Scale scores improved in all treatment groups within the first 14 days to a similar extent. During the follow-up of 6 months, percentages of patients with recurrent stroke/transient ischemic attack were 11.0%, 5.9%, 9.7%, and 13.0% in the 4 groups, respectively. Overall mortality was only 7.4%. Two parenchymal cerebral hematomas and 1 extracranial bleeding episode occurred in treatment group 1 versus 1 and 0 in group 2, 2 and 0 in group 3, and 4 and 5 in group 4, respectively. During certoparin treatment, 1 deep vein thrombosis but no pulmonary embolism was observed. CONCLUSIONS: Dose increase of certoparin up to 8000 U aXa twice daily did not improve the functional outcome of patients with ischemic stroke. Severe bleeding tended to be more frequent in the highest dose group only.

Adolescent↗
PubMed2001

Cardiac safety in the European Stroke Prevention Study 2 (ESPS2).

The second European Stroke Prevention Study investigated the prevention of stroke and/or death in 6602 patients with transient ischaemic attack or stroke with aspirin (25 mg b.d.), dipyridamole (400 mg b.d.), the combination of aspirin and dipyridamole or placebo. This post hoc analysis investigated cardiac events in patients with coronary heart disease or myocardial infarction (MI) at entry. Dipyridamole did not result in a higher number of cardiac events, e.g. angina pectoris, MI, or death from all causes. The combination of aspirin plus dipyridamole was superior to either drug alone in the prevention of stroke.

Angina Pectoris↗
PubMed2000

Aura in some patients with familial hemiplegic migraine can be stopped by intranasal ketamine.

Migraine aura is probably caused by cortical-spreading depression. No treatment for acute and severe migraine aura has been described previously. The effect of ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling auras resulting from familial hemiplegic migraine. In five patients ketamine reproducibly reduced the severity and duration of the neurologic deficits, whereas in the remaining six patients no beneficial effect was seen. Ketamine offers, for the first time, a possible treatment option for severe and prolonged aura.

Administration, Intranasal↗
PubMed2000

Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. GAIN International Investigators.

BACKGROUND: Early treatment may improve acute ischaemic stroke outcome. Gavestinel is a selective antagonist at the glycine site of the N-methyl-D-aspartate (NMDA) receptor, and is neuroprotective in animal models of ischaemic stroke. METHODS: We did a randomised, double-blind, placebo-controlled trial to test whether gavestinel could improve functional outcome after acute stroke in human beings. Conscious patients with stroke involving limb weakness received either gavestinel at an intravenous loading dose of 800 mg followed by 200 mg every 12 h for five doses, or matching placebo, within 6 h of stroke onset. Stratification variables were age and stroke severity. A computed tomography brain scan within 18 h of stroke onset identified the primary efficacy population with ischaemic stroke. Outcome was assessed by an independent observer with the Barthel index at 3 months. Three outcome categories were applied: good (Barthel index 95-100), moderate (60-90), and poor (0-55 or dead). Analysis was by intention to treat. FINDINGS: Of 1804 patients randomised, 16 received no treatment, and 333 had primary intracranial haemorrhage. 891 patients received gavestinel and 897 received placebo. Outcome in 721 patients who received gavestinel and were analysed for the primary endpoint at 3 months was good in 246 (34.1%), moderate in 136 (18.8%), and poor in 339 (47.0%), compared with 256 (34.9%), 133 (18.1%), and 345 (47.0%), respectively, of 734 patients who received placebo (p=0.8). Mortality at 3 months was 147 (20.4%) in the gavestinel group and 138 (18.8%) in the placebo group. Outcomes within preplanned subgroup and secondary analyses were also neutral. There were no significant differences in serious side-effects between the groups. INTERPRETATION: Treatment with gavestinel within 6 h of acute ischaemic stroke did not improve outcome.

Acute Disease↗
PubMed2000

A possible role of the human cerebellum in conditioning of the jaw-opening reflex.

The role of the human cerebellum in classical conditioning of the jaw-opening reflex was investigated using positron emission tomography (PET) in healthy subjects. The jaw-opening reflex was elicited by electrical stimulation of the right corner of the mouth (unconditioned stimulus, US). The conditioned stimulus was a tone preceding the US and coterminating with the US. Changes of regional cerebral blood flow (rCBF) were correlated with the rate of conditioning per PET scan. Conditioning effects were present in one third of all subjects. In these subjects, a significant increase of rCBF in the ipsilateral, intermediate cerebellum was shown during ongoing conditioning. Thus, the intermediate cerebellum appears to be involved in classical conditioning of the jaw-opening reflex in humans.

Adult↗