Biomedical subjects

A Baruzzi

Publications and source records attributed to A Baruzzi.

At least 55 records · Page 3Linked to original sources

PubMed1992

A within-subject analysis of carbamazepine disposition related to development in children with epilepsy.

The effect of aging on carbamazepine (CBZ) plasma level/dose ratio was evaluated retrospectively in 15 children who were receiving CBZ monotherapy and who were followed up for at least 3 years. Subjects of the study were selected from a population of roughly 4,500 patients attending our therapeutic drug monitoring service during a 12-year period. Results showed that the CBZ plasma level/dose ratio increases within subject during childhood, in agreement with data obtained in between-patient studies. However, the increase is not linear with age, the greatest modifications being observed between 9 and 13 years of age. Weight gain alone does not seem to explain this finding, implicating the involvement of complex physiological changes occurring during puberty.

Adolescent↗

PubMed1992

Fatal familial insomnia: clinical and pathologic study of five new cases.

In 1986, we reported two anatomoclinical observations of a familial condition that we called "fatal familial insomnia" (FFI). We now present the pedigree as well as the clinical and neuropathologic findings in five new subjects. The pedigree includes 288 members from six generations. Men and women are affected in a pattern consistent with an autosomal dominant inheritance. The age of onset of the disease varies between 37 and 61 years; the course averages 13 months with a range of 7 to 25 months. Progressive insomnia (polygraphically proven in two cases); autonomic disturbances including hyperhidrosis, hyperthermia, tachycardia, and hypertension; and motor abnormalities including ataxia, myoclonus, and pyramidal dysfunction, were present in every case, but with variable severity and time of presentation. Sleep and autonomic disorders were the earliest signs in two subjects, motor abnormalities were dominant in one, and others had intermediate clinical patterns. Pathologically, all the cases had severe atrophy of the anterior ventral and mediodorsal thalamic nuclei. Other thalamic nuclei were less severely and inconsistently affected. In addition, most of the cases had gliosis of the cerebral cortex, a moderate degree of cerebellar atrophy with "torpedoes," and severe atrophy of the inferior olivary nuclei. One case also showed spongy degeneration of the cerebral cortex. We conclude that all the lesions were primary, and that FFI is a multisystem disease in which the different structures are primarily affected with different severity. The insomnia appears to correlate best with the major thalamic pathology. The possibility that FFI belongs to the group identified as prion diseases or diseases transmitted by unconventional agents is examined.

Adult↗

PubMed1992

Cognitive effects of antiepileptic drug discontinuation.

We studied the cognitive effects of antiepileptic drugs (AEDs), by investigating epileptic patients who were seizure-free for a long time and who were undergoing fixed monotherapy. Ninety patients [27 with phenobarbital (PB), 18 with carbamazepine (CBZ), 16 with phenytoin (PHT), and 29 with valproate (VPA)] were examined by a neuropsychological battery exploring intelligence, vigilance, attention, memory, and visuomotor performances at full AED dose (T1) and compared to 28 normal volunteers. We also evaluated the effects of AED discontinuation by retesting patients 3 months after reduction at half drug dose (T2) and 3 months (T3) and 1 year (T4) after complete discontinuation. Our findings showed that patients receiving CBZ did not differ from controls at any time of examination. Patients receiving PB had significant differences only at T1 (visuomotor performance and immediate spatial memory). Patients receiving VPA showed differences in attention, visuomotor performance, verbal span and sensory discrimination tasks at T1, in visuomotor performance at T2 and in spatial span at T3, whereas no differences were detected at T4. Patients receiving PHT had a difference in intelligence and visuomotor performance at T1, in intelligence at T2, and no differences at T3 or T4. This study model is useful for investigating the cognitive effects of AED because it allows selection of a uniform sample, eliminating variables such as type, frequency, and gravity of seizures that complicate this kind of study.

Adolescent↗

PubMed1992

Therapeutic monitoring of antiepileptic drugs. I--Clinical aspects.

The management of epilepsy has been markedly improved during the last twenty years, although no new drug has been developed. These therapeutic advantages have been made possible by applying the concept of "therapeutic range" of antiepileptic drugs. This range was the result of some pioneer studies showing a good relationship between clinical effects and drug concentrations. Today, the approach to the drug therapy of epilepsy is heavily dependent on the application of this concept. Infact, important factors as patient compliance, variability in drug bioavailability and drug metabolism, drug interactions, disease interactions, etc, that may influence the clinical effect of a given dose, may be controlled by regular monitoring of antiepileptic drugs. However, the concept of "therapeutic range" should not be applied mechanically to patient treatment. The best results are obtained when the analytical results, the therapeutic situation and the clinical status of the patient are considered together. In this case, an important improvement of the quality of life of the epileptic patients can be reached.

Anticonvulsants↗

PubMed1992

Therapeutic monitoring of antiepileptic drugs. II--Analytical techniques.

Recent development of analytical techniques for therapeutic drug monitoring of antiepileptic drugs are reviewed. The most commonly used procedures are high performance liquid chromatography (HPLC) and immunochemical techniques. Innovations in HPLC include commercialization of instrumentations for automatic extraction and injection of biological samples and development of restricted access media columns for direct injection of plasma without prior extraction. For immunochemical techniques, principles of "classical" major procedures are described together with the new immunoenzymatic and immunochromatographic methods in solid phase, specifically developed with the aim of making drug monitoring possible outside the traditional laboratory.

Anticonvulsants↗

PubMed1991

Effect of age on the pharmacokinetics of oral levodopa in patients with Parkinson's disease.

The influence of age on the kinetics of a standard oral dose of levodopa administered with an inhibitor of peripheral dopa decarboxylase enzymes (benserazide) has been evaluated in 40 patients with Parkinson's disease (age 34-78 y) on chronic therapy. They were divided into 2 groups, on the basis of age below (21 patients, Group A) or above (19 patients, Group B) 65 y. The area under the plasma concentration-time curve (AUC) of levodopa was significantly greater in the older group (547 versus 428 mumol.l-1.min in Group B), coupled with a reduced apparent oral clearance (8.1 versus 10.7 ml.min-1.kg-1) and a longer plasma elimination half-life (67.6 versus 54.6 min). The age of the patients was positively correlated with the AUC of levodopa (r = 0.474) and its plasma elimination half-life (r = 0.391), and was negatively correlated with clearance (r = -0.489). The findings confirm previous data on volunteers that showed a reduction in the systemic clearance of levodopa due to age, which would probably account for the finding of a greater AUC of levodopa in older patients. The observed, age-mediated differences in levodopa pharmacokinetics, albeit statistically significant, were moderate and were likely to be of only minor importance for the dosing schedule.

Administration, Oral↗

PubMed1991

Cardiovascular dysautonomia in fatal familial insomnia.

Autonomic control of the cardiovascular system was assessed in two patients with Fatal Familial Insomnia. The diagnosis was confirmed at autopsy in patient 1. In the resting state blood pressure and heart rate were higher than controls in patient 1; plasma noradrenaline levels were elevated in both patients. Evaluation of cardiovascular reflexes indicated intact baroreflex pathways but with exaggerated blood pressure and biochemical responses to certain stimuli (postural change, Valsalva manoeuvre, isometric handgrip). There was no pressor response to intravenously infused noradrenaline, an increased response to atropine and diminished depressor and sedative effects to clonidine. Overall these results are indicative of an unbalanced autonomic control with preserved parasympathetic and higher background and stimulated sympathetic activity. These physiological, biochemical and pharmacological data, together with known neuro-pathological findings in this disorder, emphasize the possible role played by the thalamus in regulating autonomic control of cardiovascular function in man.

Adult↗

PubMed1991

Effects of acute valproic acid administration on carnitine plasma concentrations in epileptic patients.

Serial plasma samples collected after an acute administration of valproic acid, (VPA, 15 mg/kg as oral solution) in epileptic patients were selected for this study. The plasma samples were selected from three different groups of patients; patients on phenobarbital and phenytoin with clinical VPA intolerance (group A); patients on phenobarbital and phenytoin without clinical VPA toxicity (group B); and patients without phenobarbital and phenytoin and without clinical VPA toxicity (group C). Plasma samples from 6 patients per group were analyzed for carnitines and ammonia. Ammonia levels during acute study increased significantly (P less than 0.05) in patients who experienced VPA intolerance, while no changes were found in the other patients. After acute VPA administration, total carnitine was unchanged but free carnitine was decreased (P less than 0.05) and carnitine esters were increased (P less than 0.05) in all groups of patients studied. No difference in carnitine profiles was seen between patients with or without evidence of VPA administration has an important effect on carnitine metabolism. However, unlike the acute effect on ammonia metabolism, this acute effect does not seem to be correlated with any associated antiepileptic therapy, nor does it predict clinical VPA intolerance.

Adult↗

PubMed1991

Atrial natriuretic peptide and catecholamines in obstructive sleep apnea syndrome.

Nocturnal polyuria with repeated micturitions during the night is a clinically evident feature of obstructive sleep apnea syndrome (OSAS). These effects are reversed by continuous positive airway pressure (CPAP). There is some evidence that atrial natriuretic peptide (ANP) and catecholaminergic activity may be implicated in the pathogenesis of these symptoms. We studied these biochemical parameters in six patients with severe OSAS during two nights: the first (basal) in their normal conditions and the second during CPAP treatment. CPAP treatment reversed apnea episodes in all our patients. A significant (p less than 0.035) reduction of nocturnal urine volume (from 902 +/- 297 to 447 +/- 130 ml; mean +/- SD), sodium excretion (from 150 +/- 33 to 89 +/- 35 mEq/12 h), noradrenaline excretion (from 95 +/- 101 to 52 +/- 16 micrograms/g creatinine), noradrenaline plasma concentrations (from 325 +/- 96 to 259 +/- 75 pg/ml), ANP plasma concentrations (from 35 +/- 20 to 19 +/- 5 pg/ml) was observed during the night under CPAP application. These data suggest that in OSAS patients the high ANP plasma concentration is responsible for the observed elevated diuresis and sodium excretion. These effects are rapidly reversible, as they are reversed during the first CPAP treated night.

Adult↗

PubMed1991

Combined levodopa-anticholinergic therapy in the treatment of Parkinson's disease. Effect on levodopa bioavailability.

The effect of chronic intake of the anticholinergic drug orphenadrine on the bioavailability of levodopa was studied in six patients with Parkinson's disease. Plasma levodopa profiles and corresponding motor response to a standard dose of levodopa plus an inhibitor of peripheral L-aromatic aminoacid decarboxylase (benserazide) were followed, over a 5-h period, on two different sessions, with and without anticholinergic cotherapy. Six control patients were also included in the study for assessment of intrasubject variability in levodopa absorption under identical conditions. A considerable delay in levodopa absorption was found in one patient, and decreased absorption in an additional two patients while on anticholinergic. Patients' clinical performance corresponded well to plasma levodopa profiles. A significant impairment of basal clinical state was observed in two cases on anticholinergic withdrawal, probably as a result of pharmacodynamic interactions. Our observations suggest that chronic anticholinergic intake may contribute to a less predictable pattern of levodopa absorption and related therapeutic response in some subjects.

Adult↗

PubMed1991

Autonomic nervous system function in migraine without aura.

Autonomic nervous system functions were studied in 13 females with migraine without aura during headache-free intervals, using physiological, pharmacological and biochemical methods. Heart-rate in the resting condition and blood pressure rises in the cold-face and isometric handgrip tests were higher than in controls. Normal cardiovascular responses to the Valsalva manoeuvre and to noradrenaline infusion suggest that the baroreflex arc is intact. Normal heart rate responses to the Valsalva manoeuvre, to the cold-face test and to deep breathing confirmed a normal cardiac parasympathetic function. Clonidine infusion showed a sedative and depressor effect and an inhibition of plasma NA similar to those occurring in controls, suggesting a normal central sympathetic tone. As a whole, the physiological, pharmacological and biochemical tests were consistent with a non-specific sympathetic hyperactivity, but do not confirm any impairment of the autonomic control of the cardiovascular system in migraine patients in headache-free intervals.

Adolescent↗

PubMed1991

Familial hypomelanosis of Ito.

Two siblings presented the typical skin changes of hypomelanosis of Ito (HI) associated with mental and cerebellar signs. Their mother showed only the skin changes of HI but no neurological disturbances. HI is a hereditary disorder, in which familiarity may go unnoticed because of the different expressions of neural and cutaneous features.

Adult↗

PubMed1990

Severe dysautonomic onset of Guillain-Barré syndrome with good recovery. A clinical and autonomic follow-up study.

A 39 year old man with acute panautonomic and mild somatic neuropathy had severe postural hypotension 1 week after onset. Porphyric neuropathy was excluded. The final diagnosis was Guillain-Barré syndrome (GBS). After 2 months he began to recover progressively and after 9 months he presented asymptomatic postural hypotension. We consider the hypothesis of a spectrum of clinico-pathological entities at one end of which lies GBS with autonomic signs and at the other acute pure dysautonomia. The site of the autonomic lesion, might have been in post-ganglionic sympathetic fibers and vagus nerve.

Adult↗

PubMed1990

Cognitive effects of valproate.

The effects of valproate on cognition are usually considered to be minimal, but few formal neuropsychological studies are available. We studied the psychomotor performances of 20 seizure-free epileptics during fixed valproate monotherapy and after its withdrawal. Our findings suggest some adverse effects of valproate which appear to be completely reversible after withdrawal.

Adult↗

PubMed1990

Response to a standard oral levodopa test in parkinsonian patients with and without motor fluctuations.

The acute dose-response profile of a standard oral levodopa dose was followed, over a maximum 8-h period, in 13 patients with and 10 patients without motor fluctuations using a battery of motor quantitative tests (tapping and walking speed, and multiple choice reaction and movement times). Thirteen age-matched normal controls performed tapping and psychomotor tests, at the same time intervals, over a 4-h period. Tapping test and movement times proved significantly impaired in all patients and were the best indicator of levodopa effect, while walking speed and reaction times were apparently of less value, except in severely affected patients. The duration of the levodopa antiparkinsonian effect differed markedly between the two groups, since fluctuating patients returned to prelevodopa dose values within 4 h (mean +/- SEM: 203 +/- 16 min), while in the stable group motor scores remained significantly higher than baseline values up to at least 7 h postdose. The magnitude of the effect was similar in the two groups, but response was complicated by mild to severe dyskinesias in 9 of 13 fluctuating subjects. The pharmacokinetic parameters of levodopa were almost identical in the two groups. Our data add further weight to the hypothesis that cerebral pharmacokinetic or pharmacodynamic factors are responsible for motor fluctuations. Oral levodopa doses coupled with objective tests of motor performance may prove a practical clinical tool to assess and optimize the relationship between drug dose and therapeutic effect.

Adult↗

PubMed1990

Flunarizine plasma concentrations and side effects in migraine patients.

Flunarizine plasma concentrations and side effects were evaluated in migraine patients during a 3 month course of prophylactic treatment. Plasma concentrations did not correlate with daily dose (in mg/kg). Mean flunarizine levels were higher in patients showing sleepiness or sedation. Weight gain was independent of plasma concentrations. Future clinical trials of flunarizine should be supported by drug monitoring in order to clarify the relationship between plasma levels and drug effects.

Adolescent↗

PubMed1989

Computer analysis of saccadic eye movements: assessment of two different carbamazepine formulations.

The central effects of two different formulations of Carbamazepine (CBZ) have been examined by analysis of saccadic eye movements (SEM) in 6 healthy volunteers, who took part in a double-blind, latin-square, placebo controlled study. Both a conventional- and a controlled-release formulation of CBZ produced a significant effect on peak saccadic velocity and saccade accuracy, but only the former affected saccade latency. Computer analysis of SEM confirmed it to be a highly sensitive method for detection of subclinical drug effects on the CNS.

Adult↗

PubMed1989

The thalamus participates in the regulation of the sleep-waking cycle. A clinico-pathological study in fatal familial thalamic degeneration.

Loss of slow-wave sleep (SWS) and abnormal REM sleep behaviour were associated with a lack of vegetative and endocrine circadian rhythms in a patient with fatal familial thalamic degeneration. Physiological EEG patterns of SWS (spindles, K complexes, delta activity) were absent. EEG fast rhythms could not be induced by barbiturate or benzodiazepine administration. RO 15-1788, a benzodiazepine antagonist, induced arousal and awakened the patient from coma. Pathological findings were severe neuronal loss restricted to the anterior and dorso-medial thalamic nuclei. The clinical and electrophysiological data, together with the pathological correlates, emphasize the role played by the thalamus in the regulation of the sleep-waking and other circadian cycles.

Circadian Rhythm↗