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Biomedical subjects

F Donati

Publications and source records attributed to F Donati.

At least 73 records · Page 4Linked to original sources

Developmental background and outcome in patients with nonepileptic versus epileptic seizures: a controlled study.

PURPOSE: This study was designed to evaluate the relevance of developmental emotional stress factors, which are considered to influence emotional functioning, as contributing factors in the development of psychogenic symptoms. METHODS: Ten patients with nonepileptic seizures (non-ESs) (frequently referred to as psychogenic seizures), in whom diagnosis had been confirmed by a placebo-infusion test (PT), and 10 control patients with complex partial seizures (ESs) were evaluated with regard to developmental background by using structured in-depth interviews performed by a single interviewer blinded to the diagnosis. In addition, outcome assessment in the non-ES group after PT was done. RESULTS: There were no significant differences between groups in developmental psychosocial stress or in any single developmental stress factor. Six months after PT, the outcome was favorable in patients with non-ES: six were seizure free, and two had a considerable reduction in frequency of seizures. CONCLUSIONS: Our research indicates the following: (a) a high incidence of developmental stress factors and functional disturbances may be found in patients with non-ESs and ESs; (b) assessment of developmental emotional stress and functional disturbances as a basis for validating the diagnosis of non-ES should be treated with caution; (c) use of PT followed by supportive information about the nonepileptic origin of the attacks may have a positive therapeutic effect or help to introduce psychotherapeutic treatment.

Adult↗

Concomitance of childhood absence and Rolandic epilepsy.

Five children (3 girls and 2 boys) who showed generalized synchronous 3/sec spike and wave complexes as well as centrotemporal spikes in the same EEG or in different EEGs are described. Among these five patients only 1 boy and 1 girl showed clinically both absence seizures and partial motor seizures with or without secondary generalization. One girl and 1 boy have only absences and the other girl only partial motor seizures. A concomitance of generalized synchronous 3/sec spike and wave discharges and centrotemporal spikes in the same patient is rarely found. The clinical manifestation of absences and partial motor seizures in the same patient is extremely rare.

Child↗

Tacrine does not alter the potency of succinylcholine in the rat.

PURPOSE: Tacrine is a cholinesterase inhibitor used to manage Alzheimer's dementia. Given iv, it prolongs succinylcholine blockade in humans but the effects of chronic oral tacrine are not known. METHODS: Groups of adult rats were given 2.5 mg.kg-1 tacrine (chronic groups) or l ml saline (control) twice daily by gavage for one, two, four or eight weeks. An additional (acute) group received 2.5 mg.kg-1 tacrine iv. Twelve to 18 hr after the last gavage of tacrine or saline, and -20 min after iv tacrine, cumulative dose-response curves of succinylcholine were determined in the tibialis and soleus muscles in anaesthetized, ventilated rats during monitoring of evoked twitch response to indirect (nerve) train-of-four stimulation. RESULTS: The ED50 and ED95 of succinylcholine in control rats were (mean +/- SD) 204 +/- 41 and 382 +/- 96 micrograms.kg-1, respectively in the tibialis muscle, and 280 +/- 52 and 629 +/- 168 micrograms.kg-1 in the soleus muscle (P < 0.05 between muscles). In the acute and chronic tacrine groups, the mean ED50 and ED95 ranged from 166-197 and 277-396 micrograms.kg-1., respectively, in the tibialis muscle, and 248-333 and 546-667 micrograms.kg-1, in the soleus muscle. Dose responses did not differ among acute and chronic tacrine groups and the control group. CONCLUSION: Chronic oral tacrine does not alter muscle response to succinylcholine in the rat. This may not apply to Alzheimer patients receiving chronic tacrine since the interaction between acute tacrine and succinylcholine in the rat differs from that in humans.

Administration, Oral↗

Rocuronium prevents succinylcholine-induced fasciculations.

PURPOSE: The aim of this study was to assess the effect of rocuronium pretreatment at 3 and 1.5 min before succinylcholine administration on fasciculations, neuromuscular blockade and intubating conditions. METHODS: Sixty ASA I or II adults scheduled for elective surgery were anaesthetised with midazolam, fentanyl, propofol, N2O and isoflurane. They were randomised in a double blind manner into three groups: group ROC-3 min (n = 22) received 0.05 mg.kg-1 rocuronium, 3 min before 2 mg.kg-1 succinylcholine; group ROC-1.5 min (n = 20) received 0.05 mg.kg-1 rocuronium 1.5 min before 2 mg.kg-1 succinylcholine; and group NO ROC (n = 18) had no rocuronium before injection of 2 mg.kg-1 succinylcholine. Fasciculations and intubating conditions were evaluated by the same physician who was unaware of the randomisation. Neuromuscular block was measured at the adductor pollicis with an accelerometer. RESULTS: The incidence of fasciculations was lower in the ROC-3 min (9%) and ROC-1.5 min (30%) groups than in the NO ROC group (83%; P < 0.001). The intensity of fasciculations was also less in both pretreatment groups. No statistical difference was noted between pretreatment at 3 and 1.5 min. Intubating conditions, onset time and duration of succinylcholine blockade were comparable in all three groups. CONCLUSION: The incidence and severity of succinylcholine fasciculations can be reduced by giving 0.05 mg.kg-1 rocuronium either 1.5 min or 3 min before succinylcholine. The effects of 2 mg.kg-1 succinylcholine with rocuronium pretreatment, and 1 mg.kg-1 succinylcholine, without pretreatment, are similar with respect to intubating conditions, onset of paralysis and duration of blockade.

Adolescent↗

Comparison of rocuronium and d-tubocurarine for prevention of succinylcholine-induced fasciculations and myalgia.

PURPOSE: We compared d-tubocurarine and rocuronium for the prevention of succinylcholine-induced fasciculations and postoperative myalgia (POM) and evaluated the influence of both drugs on the speed of onset and recovery of succinylcholine. METHODS: Seventy-five women undergoing surgery of short duration were studied. They were randomized to one of three groups: group SAL received normal saline followed three minutes later by 1.0 mg.kg-1 succinylcholine; group ROC received 0.05 mg.kg-1 rocuronium + 1.5 mg.kg-1 succinylcholine; group DTC received 0.05 mg.kg-1 d-tubocurarine + 1.5 mg.kg-1 succinylcholine. Single-twitch stimulation was applied to the ulnar nerve every 10 sec and the EMG response of the adductor pollicis was recorded. Fasciculations were assessed by a blinded observer on a scale of 0-3. Patients were asked 24 and 48 hr later to rate POM using a scale of 0-10. RESULTS: The interval needed for twitch height to decrease to 10% of initial value after succinylcholine was longer in group ROC (58 +/- 20 sec) (mean +/- SD) compared with group SAL (44 +/- 13 sec) (P < 0.05). Recovery to 20% occurred faster in group ROC (324 +/- 83 sec) than in groups SAL (456 +/- 103 sec) and DTC (450 +/-132 sec) (P < 0.05). Fasciculations were more intense in groups SAL than in groups ROC and DTC (P < 0.001). Patients rated POM as less intense 24hr postoperatively only in group ROC (1.2 +/- 2.4) compared with group SAL (3.3 +/- 3.5) (P < 0.05). CONCLUSION: Rocuronium prevents succinylcholine-induced fasciculations and POM. Rocuronium also delays the onset of succinylcholine and shortens its duration compared with d-tubocurarine.

Adolescent↗

Pharmacokinetic-pharmacodynamic modeling of doxacurium: effect of input rate.

One of the basic assumptions in pharmacokinetic-pharmacodynamic modeling (PK-PD) is that drug equilibration rate constant between plasma concentration and effect (Ke0) is not changed by input rate. To test this assumption in a clinical setting, a 25 micrograms/kg i.v. dose of doxacurium was administered either by bolus injection or 10-min infusion to 15 anesthetized patients. Neuro-muscular function was monitored using train-of-four stimulation of the ulnar nerve. For the short infusion dose, arterial concentrations were measured at I-min intervals during infusion and at frequent intervals thereafter. Following the iv bolus dose, the early PK profile of doxacurium was investigated by measuring doxacurium arterial concentrations every 10 sec during the first 2 min and at frequent intervals thereafter. PK-PD modeling was performed using nonparametric approach with and without including a finite receptor concentration (Rtot) in the effect compartment. Kinetic parameters were unchanged. For the bolus and the infusion, Ke0 values were 0.053 +/- 0.006 and 0.056 +/- 0.009 min-1, respectively. Using the Rtot model, corresponding Ke0 values were 0.148 +/- 0.016 and 0.150 +/- 0.024, respectively. The relatively faster Ke0 obtained with the Rtot model is compatible with the high potency of doxacurium. Our results show that PK-PD parameters derived with either a bolus or an infusion mode of administration are equally reliable.

Adult↗

The effects of chronic tacrine therapy on d-tubocurarine blockade in the soleus and tibialis muscles of the rat.

Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it is not clear how its chronic use might affect response to nondepolarizing muscle relaxants. We determined the magnitude and time course of the effects of chronic oral THA and of intravenous (IV) THA on d-tubocurarine (dTC) blockade at the soleus and tibialis muscles. Six groups of adult rats were given 10 mg/kg THA twice daily by gavage for 1, 2, 4, or 8 wk (chronic THA groups), or 1 mL of saline twice daily by gavage for 1-8 wk (control), or IV THA approximately 20 min before (acute), and the cumulative dose-response curves of dTC at the tibialis and soleus muscles were determined during indirect train-of-four stimulation in the anesthetized, mechanically ventilated rat. The 50% effective dose (ED50) and 95% effective dose (ED95) of dTC in control rats were (mean +/- SD) 30 +/- 10 and 61 +/- 18 microg/kg in the tibialis and 32 +/- 8 and 75 +/- 19 microg/kg in the soleus; respectively. IV THA increased the ED95 of dTC 2.5- to 3-fold (P < 0.05) but did not alter the ED50. Chronic THA increased both the ED50 and ED95 of dTC 1.5- to 2-fold (P > or = 0.05), and this effect tended to decrease with duration of THA therapy. We conclude that chronic THA therapy in rats causes resistance to dTC, with a tendency for the resistance to decrease with time, probably because of down-regulation of postsynaptic acetylcholine receptors. The same may apply to Alzheimer's patients taking THA chronically.

Administration, Oral↗

Pharmacokinetics of mivacurium isomers and their metabolites in healthy volunteers after intravenous bolus administration.

BACKGROUND: Previous studies report the pharmacokinetics of mivacurium isomers after an infusion using venous blood sampling. Although the extent of the mivacurium arterial-venous gradient is not known, the sampling site is likely to influence mivacurium pharmacokinetic parameters because the drug is rapidly metabolized as it traverses the circulation. The objectives of this study were (1) to determine the pharmacokinetics of mivacurium isomers in healthy persons after intravenous bolus administration using intensive arterial blood sampling, and (2) to characterize the formation and elimination of mivacurium metabolites in human plasma. METHODS: Eight persons classified as American Society of Anesthesiologists physical status 1 or 2 who were scheduled to undergo elective surgery under balanced anesthesia received 0.15 mg/kg mivacurium chloride as an intravenous bolus. Arterial blood samples were collected every 10 s during the first 2 min and at frequent intervals for 4 h thereafter. Plasma concentrations of mivacurium isomers and their metabolites were determined by two stereoselective high-performance liquid chromatographic methods coupled with fluorometric detection and noncompartmental pharmacokinetic parameters. RESULTS: Mean elimination half-lives of the trans-trans, cis-trans, and cis-cis isomers were 2.4, 2, and 28.5 min, respectively, with corresponding mean plasma clearances of 29.2, 45.7, and 6.7 ml.min 1.kg-1. The volumes of distribution at steady state of the trans-trans, cis-trans, and cis-cis isomers were 0.047, 0.054, and 0.189 l/kg, respectively. Plasma concentrations of monoester and alcohol metabolites peaked 25 s (median) after mivacurium injection, with half-lives in the range of 90 min, except for the cis alcohol metabolite, which was only negligibly and transiently formed. CONCLUSIONS: Substantial hydrolysis of mivacurium isomers by cholinesterases was confirmed by the rapid appearance of mivacurium metabolites in plasma. The intensive arterial sampling proved to be critical for the trans-trans and cis-trans isomers because the area under the curve between 0 and 2 min accounted for 75% and 86% of the total, respectively.

Adolescent↗

[Syncope of unclear origin--role of 2 diagnostic tests with high specificity].

We report the diagnostic evaluation of an elderly woman admitted with recurrent syncopes induced by head rotation. A cardiac origin was exclude by Holter ECG, echocardiography and carotid sinus compression. Angiography showed unilateral vertebral artery hypoplasia, suggesting the possibility of hemodynamic vertebrobasilar insufficiency. This origin, however, could be ruled out by monitoring of blood flow velocities in both posterior cerebral arteries with transcranial Doppler, which showed no alteration during syncope induced by head rotation. Detailed analysis of the course of the syncope recorded on videotape suggested a psychogenic event. Furthermore, the syncopes could be prevented with a "protective" placebo despite head rotation, and induced by a "provocative" placebo without head rotation while EEG monitoring showed normal brain activity. This finding underscored the suggestion of a psychogenic cause.

Aged↗

Properties of fibres, endplates and acetylcholine receptors in the diaphragm, masseter, laryngeal, abdominal and limb muscles in the goat.

PURPOSE: Although differences in fibre composition, fibre size or acetylcholine receptor (AChR) density between muscles have often been proposed to explain the unequal sensitivities of muscles to muscle relaxant drugs, it is not clear whether or how these parameters differ among muscles or are related to one another, In this study, several muscles were examined to determine the composition and cross-sectional area (CSA) of types I and II fibres, the surface area of their motor endplates (ESA), and their AChR density. METHODS: Biopsies from the thyroarytenoideus, cricoarytenoideus dorsalis, masseter, diaphragm, transversus abdominis, rectus abdominis, gastrocnemius and soleus muscles of goats were processed by muscle histochemistry and morphometry and the ESA:CSA ratio was computed. The number and density of AChRs per endplate were estimated by 125I-alpha-bungarotoxin binding studies. RESULTS: The mean type I fibre composition (range: 0-100%), fibre diameter (28-50 microns) and the ESA:CSA ratio (0.27-1.01) differed among muscles (P = 0.0001), but there were no significant differences (P > 0.05) in the mean endplate size (577-725 microns 2) AChR number (6.6-14.5 x 10(6)) or AChR density (8,900-22,300 microns-2) probably because of marked individual variations. Fibre size increased and the ESA:CSA ratio decreased in the order laryngeal, diaphragm, jaw, limb and abdominal muscles. CONCLUSION: It is concluded that between muscles fibre size varies more than endplate size or AChR number.

Adenosine Triphosphatases↗

Duration of succinylcholine and vecuronium blockade but not potency correlates with the ratio of endplate size to fibre size in seven muscles in the goat.

PURPOSE: Muscles differ in their response to neuromuscular relaxants. This study investigated whether (1) the relative responses of muscles is inverted between succinylcholine (SUX) and vecuronium (VEC), and (2) differences in dose-response or duration of action are related to the morphology of fibres, endplates and acetylcholine receptors (AChR) in muscles. METHODS: In goats during thiopentone anaesthesia, the evoked EMG response to indirect train-of-four stimulation was monitored and the cumulative dose-response curves and duration of action of SUX and VEC in the diaphragm, cricoary-tenoideus dorsalis, thyroarytenoideus, transversus abdominis, rectus abdominis, soleus and gastrocnemius muscles were determined and related to their fibre composition, fibre size, endplate size, endplate to fibre size ratio, AChR number or AChR density by regression analysis. RESULTS: There were no differences in the ED50S of SUX [range, 119 +/- 11 (SE) to 159 +/- 20 micrograms.kg-1] or VEC [range, 2.8 +/- 0.2 to 3.7 +/- 0.8 microgram.kg-1] among muscles. With either drug, duration to 25% or 50% T1 recovery was shortest at the laryngedl muscles and longest at abdominal muscles (P = 0.0001), and correlated directly with fibre size (r > or = 0.40; P < 0.004) and inversely with the endplate to fibre size ratio (r > or = 0.40; P < 0.008). CONCLUSION: The results show that (1) the relative responses of muscles do not differ between depolarizing and non-depolarizing relaxants; (2) the duration of blockade is shorter in muscles composed of small fibres with large endplates relative to fibre size; and (3) there is no relation between fibre type composition and sensitivity to muscle relaxants.

Animals↗

The onset of rocuronium, but not of vecuronium or mivacurium, is modified by tourniquet inflation.

A previous investigation showed that inflation of a tourniquet did not interrupt onset of vecuronium neuromuscular block. To test the hypothesis that this effect depended on potency, twitch tension was measured in an arm with a tourniquet inflated during onset and compared with a control arm in 30 patients under fentanyl-thiopental-nitrous oxide-isoflurane anesthesia. Patients were randomly allocated to receive either vecuronium 0.1 mg/kg (n = 10), rocuronium 0.6 mg/kg (n = 10), or mivacurium 0.2 mg/kg (n = 10). The electromyographic response of the first dorsal interosseus to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e., twitch tension was 80% of control), the tourniquet was inflated to a pressure of 300 mm Hg. It was deflated 5 min later. In the vecuronium and mivacurium groups, the tourniquet did not influence onset of block. In the rocuronium group, maximum neuromuscular block was (mean +/- SD) 79% +/- 10% in the tourniquet arm, compared with 96% +/- 4% in the perfused arm (P < 0.05). The maximum rate of onset was half that of the perfused arm. The difference in maximum neuromuscular block between arms was 17% +/- 7%, 5% +/- 5%, and 0% +/- 2% in the rocuronium, vecuronium, and mivacurium groups (P < 0.05). To explain that onset of block continues in spite of interruption of blood flow, drug molecules must gain access to the neuromuscular junction via routes other than the circulation. The results of this investigation are consistent with the hypothesis that there is redistribution of drug from extrajunctional to junctional areas during onset of action of muscle relaxants and this process is more important for the more potent drugs (vecuronium and mivacurium) than for rocuronium.

Adult↗

Mivacurium neuromuscular block at the adductor muscles of the larynx and adductor pollicis in humans.

BACKGROUND: Laryngeal muscles must be paralyzed for tracheal intubation. Time to peak effect (onset time) is shorter and intensity of blockade is less at laryngeal muscles compared with the adductor pollicis. The authors' aim in this study was to determine the neuromuscular effects of mivacurium at the laryngeal adductor muscles and the adductor pollicis. METHODS: In 22 adults, anesthesia was induced and maintained with propofol and alfentanil. The force of contraction of the adductor pollicis was recorded, and the laryngeal response was evaluated by measuring the pressure change in the cuff of a tracheal tube positioned between the vocal cords after train-of-four stimulation. Mivacurium (0.07 mg.kg-1 or 0.14 mg.kg-1) was given intravenously (10s). RESULTS: With 0.07 mg.kg-1 mivacurium, onset time was 151 +/- 40 s(mean +/- SD) at the larynx and 241 +/- 79 s at the adductor pollicis, respectively (P < 0.005). Maximum block was 78 +/- 18% and 95 +/- 8%, respectively (P < 0.002), and time to 90% recovery was 11.1 +/- 2.9 min and 23.3 +/- 7.6 min, respectively (P < 0.001). With 0.14 mg.kg-1 mivacurium, onset time also was more rapid at the vocal cords (137 +/- 20 s) than at the adductor pollicis (201 +/- 59 s, P < 0.01). Maximum block was 90 +/- 7% and 99 +/- 1% (P < 0.005), and time to 90% recovery was 16.4 +/- 4.9 min and 27.4 +/- 7.8 min, respectively (P < 0.01). CONCLUSIONS: With mivacurium, onset and recovery are faster at the laryngeal muscles, but block is less intense than at the adductor pollicis. A dose greater than 0.14 mg.kg-1 mivacurium is necessary to ensure complete relaxation at the vocal cords.

Adult↗

[Sleep disorders in childhood].

Sleep disorders in childhood are frequent and usually harmless. They rarely point to a serious disease. Difficulty in falling asleep and nightly awakenings are age-dependent and transitory. While the largely harmless somnambulism and pavor nocturnus occur in the deep sleep of the first third of the night, the anxiety dreams of REM sleep appear preferentially in the second half of the night. Other disorders such as nocturnal enuresis and talking in sleep may occur during the whole night. It is very important to inform the parents because this helps to counter fears and false expectations. Consistent sleep hygiene needs to be developed with avoidance of irregular sleep rhythm and an unrestful sleep environment. Sometimes it is necessary to learn new behaviour patterns with the child. Only exceptionally is drug therapy indicated. However, nocturnal breathing disorders and nocturnal epilepsy do have a pathological significance and need specific therapy. In order to clarify the reasons for sleep disorders, it is necessary to keep a sleep diary, to undertake specific examinations (e.g. psychological, pneumological, neurological, urological, otorhinolaryngological and possibly using diagnostic equipment such as video-polysomnography).

Cataplexy↗

High-performance liquid chromatographic assays with fluorometric detection for mivacurium isomers and their metabolites in human plasma.

Two high-performance liquid chromatographic assays coupled with fluorometric detection have been developed for the determination of mivacurium isomers (trans-trans, cis-trans and cis-cis) and their monoester and alcohol metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of the mivacurium isomers (mean 98%) and their monoester metabolites (mean 83%), whereas the alcohol metabolites were analyzed after direct precipitation of plasma proteins. For all analytes, these assays proved to be sensitive (LOQ 3.9-15.6 ng/ml), reproducible (C.V. < 15%) and accurate (> 94%) over the therapeutic range of concentrations of mivacurium and its metabolites. These two methods were applied successfully to a pharmacokinetic study of mivacurium after a bolus dose of 0.15 mg/kg in anesthetized patients.

Chromatography, High Pressure Liquid↗

Factors predicting the risk of relapse after antiepileptic drug discontinuation in children with partial seizures.

The purpose of this study is to identify possible factors which could influence the seizure recurrence after anti-epileptic drug (AED) withdrawal in children with partial epilepsy. AED was discontinued in 82 children who had been free of partial epileptic seizures for 2.0-11.0 years (mean 4.7 years). Twenty-four patients (29.3%) had a relapse from a few days to 6.1 years (mean 1.2 years) after AED discontinuation. Significantly more common in children who relapsed were: younger age at beginning of AED withdrawal, occurrence of complicated febrile convulsions (5/24 vs 1/58, P < 0.01), abnormal neurological examination (8/24 vs 8/58, P < 0.05), delayed psychomotor development (7/24 vs 7/58, P < 0.05), focal slowing (6/24 vs 3/58, P < 0.01) and focal epilepti-form discharges (7/24 vs 6/58, P < 0.05) in the last EEG before AED discontinuation. Between the two groups no statistical significant differences concerning the age at onset of seizures, the duration at AED therapy after the last seizure, the familial occurrence of epilepsy and background EEG abnormalities in the last EEG before AED discontinuation were found. On the basis of EEG, occurrence of febrile convulsions, and neurological and developmental examination it may be possible to predict which children have the best chance to remain free of recurrence after AED discontinuation.

Anticonvulsants↗