C. Morocutti

Indobufen Versus Warfarin in the Secondary Prevention of Major Vascular Events in Nonrheumatic Atrial Fibrillation

BACKGROUND AND PURPOSE The results of a large prospective randomized trial have shown the efficacy of oral anticoagulation in the secondary prevention of major vascular events in patients with nonrheumatic atrial fibrillation (NRAF); less well established is the role of antiplatelet agents. The present study compared the effects of indobufen, a reversible inhibitor of platelet cyclooxygenase, with those of warfarin in this setting. METHODS A total of 916 patients with NRAF and a recent (< or = 15 days) cerebral ischemic episode were admitted to this multicenter, randomized study, during which they were treated with either indobufen (100 or 200 mg BID) or warfarin (to obtain an international normalized ratio of 2.0 to 3.5) for 12 months. The two groups (462 on indobufen and 454 on warfarin) were well balanced in terms of their main baseline characteristics. The primary outcome of the study was the combined incidence of nonfatal stroke (including intracerebral bleeding), pulmonary or systemic embolism, nonfatal myocardial infarction, and vascular death. RESULTS At the end of follow-up, the incidence of primary outcome events was 10.6% in the indobufen group (95% confidence interval, 7.7% to 13.5%) and 9.0% in the warfarin group (95% confidence interval, 6.3% to 11.8%), with no statistically significant difference between treatments. The frequency of noncerebral major bleeding complications was low: only four cases (0.9%) of gastrointestinal bleeding were observed, all of them in the warfarin group. CONCLUSIONS We conclude that, within the limitations of its design, this study may help the medical community in devising appropriate antithrombotic strategies for NRAF patients for whom oral anticoagulants are contraindicated or do not represent a feasible approach to treatment.

Early Detection of Neurological Involvement in IDDM and NIDDM: Multimodal Evoked Potentials Versus Metabolic Control

Clarification of the extent and mechanisms of damage to the central nervous system in diabetes is a frontier of current neurological research. Our aim was to obtain ample electrophysiological documentation of possible neurological abnormalities in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetic patients with a short duration of disease and without overt complications, taking into account metabolic control. Group 1 comprised 11 IDDM patients, and group 2 included 14 NIDDM patients treated with diet alone; the duration of disease was <4 yr, and no concomitant clinicalcomplications were present. Age and sex-matched normal subjects formed groups 3 and 4. Pattern visual evoked potentials (VEP), brain stem auditory evoked potentials (BAEP), and somatosensory evoked potentials (SEP; after the stimulation of both median and tibial nerves) were recorded in all subjects, and metabolic control was evaluated in terms of glycemia and glycosylated hemoglobin. In group 1, significant abnormalities were found in the latency values ofVEP, median SEP, and tibial SEP compared with control subjects. Similar latency abnormalities were shown in group 2 for VEP, median SEP, and tibial SEP values and for wave I latency of BAEP. Glycosylated hemoglobin values were correlated with BAEP and SEP abnormalities in many patients in both groups. Furthermore, in group 2, glycemic values correlated with SEP abnormalities. We therefore conclude that neurophysiological abnormalities are present at different levels in IDDM and NIDDM patients only a few years after clinical diagnosis and before the appearance of overt complications, and these abnormalities seem to be correlated with metabolic-control status.

Antiepileptic effects of a calcium antagonist (nimodipine) on cefazolin-induced epileptogenic foci in rabbits.

Summary: The epileptogenic properties of cefazolin (CFZ) were utilized to induce an electrophysiological pattern of epilepsy in the rabbit. CFZ, cortically applied in different concentrations (2 or 4%), produced epileptic activity in a degree proportional to the concentration of the substance. In this experimental epilepsy model, we evaluated the effects of increasing doses (0.025, 0.05, and 0.1 mg/kg i.v.) of the calcium antagonist nimodipine (Bay e 9736). In the evaluation of nimodipine effects, the spike‐and‐wave burst frequency per minute was taken into account. These data were compared with those of placebo‐treated (Bay e 9736 control test) control groups and statistically evaluated by two‐tailed t test. In 2% CFZ‐induced epilepsy, nimodipine at the 0.025‐ and 0.05‐mg/kg doses did not produce significant changes in the EEG pattern. A statistically significant reduction (p < 0.001) in epileptic activity was observed at the 0.1‐mg/kg nimodipine dose. This reduction was seen first in the contralateral focus leads and persisted for the entire time of observation. In the more intense epileptic form (4% CFZ), nimodipine at the doses employed did not induce noteworthy EEG modifications. These data indicate that nimodipine exerts an antiepileptic effect. The possible mechanisms involved in this activity of a calcium antagonist are discussed.

Parkinson disease: Electrophysiological (CNV) analysis related to pharmacological treatment

The contingent negative variation (CNV) was studied in a group of patients with Parkinsons disease. Testing was carried out 3 times: after a pharmacological wash-out period and at 15 and 30 days after the start of treatment with L-DOPA and bromocriptine. Peak and area CNV increased significantly after each treatment. The post-imperative negative variation (PINV) was observed in 6 out of 10 patients. The correlation found between electrophysiological functioning (CNV) measures and pharmacological treatment supports the view that dopaminergic brain activity mediates the generation of the slow negative event-related brain potentials.

HLA-LINKED SPINOCEREBELLAR ATAXIA - A CLINICAL AND GENETIC-STUDY OF LARGE ITALIAN KINDREDS

Five families with late onset autosomal dominant spinocerebellar ataxia, were studied. Linkage between the disease and HLA loci on the short arm of chromosome 6 was shown in the two largest pedigrees. Clinical study of 26 patients and neuropathological study in one are reported. The disease was characterized by cerebellar and pyramidal involvement variably associated with cranial nerve and peripheral nervous system disorders. A remarkable concordance of the main clinical features was observed in patients with similar disease duration. Comparison with previous reports of HLA‐linked spinocerebellar ataxia kindreds showed differences in clinical phenotypes. Although these might be due to genetic variation, the hypothesis is suggested that the phenotype might appear more homogeneous if disease duration is taken into account.

AZT-induced mitochondrial myopathy

Histochemical, electron microscopy and biochemical studies were performed on muscle biopsy specimens from 11 AIDS patients treated with zidovudine. A peculiar association of structural abnormalities and mitochondrial dysfunction was found. Focal cytochrome c oxidase (COX) deficiency was evident in muscle sections from 9 patients, 8 of whom had received long-term treatment while one had been treated for 1 month only. Electron microscopy showed changes in number, size and structure of mitochondria. Biochemical studies proved partial COX and succinate cytochrome c reductase (SCR) deficiency in 4 patients; one patient had only reduced SCR activity. Our data confirm that AZT therapy can cause toxic myopathy with mitochondrial dysfunction.SommarioSono state esaminate le biipsie muscolari di 11 pazienti affetti da AIDS in trattamento con Zidovudina. Si è riscontrato una caratteristica associazione di anormalità strutturali delle fibre e di disfunzione mitocondriale.Un deficit focale di citocromo c ossidasi (COX) era presente nelle sezioni muscolari di nove pazienti, otto dei quali avevano subito un trattamento di lunga durata, mentre uno era stato trattato solo per un mese.La microscopia elettronica mostrava modificazioni della struttura, del numero e volume dei mitocrondri. Le indagini biochimiche hanno evidenziato un deficit parziale di COX e di succinato citocromo c reduttasi (SCR) di quattro pazienti, mentre in un paziente riduzione di attività della sola SCR. I nostri dati confermano che la terapia con AZT può causare una miopatia tossica con disfunzione dei mitocondri.

A CNV study in a group of patients with traumatic head injuries

CNVs were studied in a group of 27 subjects with traumatic head injuries followed by protracted coma. Before CNV recording, all patients were subjected to Wechsler-Bellevue Intelligence Scale and to Bentons visual retention test. The findings were compared with those obtained from 80 normal subjects. A statistically significant decrease was observed in the CNV area in the group with traumatic lesions. No correlation could be found between CNV parameters and the results of the mental tests. In 7 of the subjects who presented the highest percentage of errors in Bentons test, a large post-imperative negative variation was observed.

Autonomic involvement in multiple sclerosis: a pupillometric study

To study pupillary autonomic function in multiple sclerosis (MS), we examined 36 subjects with low disability, preserved visual acuity and no recent history (2 years) of optic neuritis or actual visual complaints. Compared to controls, MS patients showed a greater dilatator reaction with darkness and, for the light reflex, a lower amplitude and contraction rate and a greater recovery of pupillary diameter 5 s after the stimulus. Within the MS group, no difference was found comparing patients with or without the following characteristics: nuclear magnetic resonance imaging evidence of midbrain lesions; increased visual evoked potential P100 latency; and a previous history of optic neuritis. No correlation was found between P100 latency, duration of disease and pupillometric parameters. Our results indicate that in MS patients there is autonomic dysfunction with a reduction of parasympathetic tone and a relative increase in sympathetic dilatator tone to the pupils. We suggest that pupillary abnormalities could be due to non-specific impairment of the central pathways subserving pupil functions.

Pre-perceptual pain sensory responses (N1 component) in type 1 diabetes mellitus.

We investigated the integrity of the ascending pathways for pain sensitivity in the early stage of type 1 diabetes mellitus, by measuring the N1 component and the conventional N2/P2 vertex potentials of laser evoked potentials (LEPs). Brain responses to laser stimuli were obtained in 21 healthy volunteers and 21 type 1 diabetic patients, without either clinical neuropathy or electrophysiological evidence of large-fiber damage. In diabetic patients N1 and P2 latencies were prolonged and the N1 and N2/P2 amplitudes were decreased after foot stimulation. A significant reduction of the conduction velocity of A&dgr; fibers in the lower limbs was also observed. LEPs reveal an early, subclinical and selective damage of pain sensation in diabetic patients. N1 and P2 potentials are delayed and decreased in parallel giving evidence that LEP abnormalities are not secondary to a cognitive dysfunction and mostly reflect a small-fiber dysfunction.

Low contrast stimuli enhance PERG sensitivity to the visual dysfunction in Parkinson's disease

The pattern electroretinogram (PERG) was recorded at different contrast levels (96%, 71%, 47%) in 10 Parkinsons disease patients before and during dopaminergic monotherapy. The data were compared to a control group of 8 normal subjects recorded with the same procedure. PERG P50 latency progressively increased as contrast was decreased both in normal subjects and patients; however, this trend was much more pronounced in PD patients without therapy; consequently in this group the difference between P50 latency obtained with 96% and 47% contrast was statistically significant (P = 0.01, analysis of variance corrected by post-hoc Tukey test). By contrast this was not seen in the control group. Statistical analysis (Bonferronis t test) showed at the 47% contrast level a significant P50 latency increase (P less than 0.01) in PD patients without therapy if compared with the control group. Dopaminergic monotherapy induced a P50 latency recovery in PD patients. We conclude that low contrast stimuli enhance PERG sensitivity to the visual dysfunction of PD patients. Moreover, the effects observed after therapy confirm that abnormal contrast response functions in PD patients are linked to dopaminergic deficiency.