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Biomedical subjects

F Donati

Publications and source records attributed to F Donati.

At least 91 records · Page 5Linked to original sources

Psychosocial aspects in the treatment of children with myelomeningocele: an assessment after a decade.

The aim of this study was to recognize the possible psychological advantages when children with a severe CNS disorder like myelomeningocele (MMC) are given very early rehabilitation treatment. One hundred and seven newborns with MMC seen between 1971-1992 were prospectively analysed with respect to two different therapeutic approaches. The children born during the period 1971-1980 did not receive very early therapeutic rehabilitation treatment, whereas those born during the period 1981-1992, received this treatment. In the latter group, special attention was paid to support an improvement in the difficult relationship between the parents and the child with MMC as well as between parents and caregivers. The following statistically significant differences between the two treatment programmes were found: (1) all children achieved independent locomotion at 5 years, in the very early intervention group, compared to only 35% (P < 0.001) in the group without this programme. Orthopaedic operations in the first-mentioned group were markedly reduced; (2) urological surgery decreased drastically in the group with very early urodynamic rehabilitation. Thus, there were 0.6 operations per patient in the older group, but only 0.06 operations per patient in the younger one (P < 0.001); (3) normal schooling was reached by 76% (22/29) and social continence by 80% (23/29) of the children with very early interventional therapy. In the older group only 54% reached normal schooling (P < 0.05) and 29% social continence (P < 0.001). The very early co-ordinated medical and physiotherapeutic rehabilitation treatment of children with MMC usually reduces the psychosocial stress and improves the quality of life of these children and of their families.

Female↗

Prolonged epileptic apneas in a newborn: a case report with ictal EEG recording.

We report a case of repetitive and prolonged apneas, correlating with EEG-focal epileptiform discharges over the right temporal region, in a full-term newborn. After administration of phenobarbital the apneas completely ceased. The neurological examination, the psychomotor development, and the EEG at the age of 12 months were normal. The prolonged duration of the epileptic apneas, the ictal rhythmic delta wave activity, and the favorable outcome distinguish our patient from the majority of previously reported cases.

Anticonvulsants↗

Onset of neuromuscular block after tourniquet inflation: comparison of suxamethonium with vecuronium.

To determine the influence of circulatory factors on onset of neuromuscular block, we have measured twitch height in an arm with a tourniquet inflated during onset and compared this with data from a control arm in 20 patients under fentanyl-thiopentone-nitrous oxide-isoflurane anaesthesia. Patients were allocated randomly to receive either vecuronium 0.1 mg kg-1 (n = 10) or suxamethonium 1 mg kg-1 (n = 10). The EMG response of the first dorsal interosseous to single twitch stimulation of the ulnar nerve every 10 s was recorded in both arms. When neuromuscular block was 20% (i.e. twitch height was 80% of control), the tourniquet was inflated to a pressure of 250 mm Hg. It was deflated 5 min later. In the vecuronium group, the rate of onset did not differ in both arms and mean maximum block was 95 (SD 4)% in the tourniquet arm, which was not different from 99 (2)% in the perfused arm. In the suxamethonium group, the presence of a tourniquet decreased the rate of onset by 66%. Maximum block was only 74 (20)% in the tourniquet arm compared with 97 (5)% in the perfused arm (P < 0.05). The difference in maximum neuromuscular block between arms was 4 (3)% in the vecuronium group and 22 (17)% in the suxamethonium group (P < 0.01). We conclude that during onset, neuromuscular block continued to increase in spite of interruption of blood flow, and this increase was greater with vecuronium than with suxamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Monitoring the onset of neuromuscular block at the orbicularis oculi can predict good intubating conditions during atracurium-induced neuromuscular block.

This study was designed to assess whether monitoring the orbicularis oculi (OO) can predict good tracheal intubating conditions. Fifty patients, ASA grade I or II were studied. Anesthesia was induced with thiopental (5 mg/kg) and fentanyl (3 micrograms/kg). The ulnar and facial nerves were simultaneously stimulated using train-of-four (TOF) stimulations every 10 s. The responses of the adductor pollicis (AP) and the OO were estimated visually. Patients were randomly allocated to receive either atracurium 0.5 mg/kg (n = 30) or 0.3 mg/kg (n = 20). In each group, endotracheal intubation was performed randomly when the OO or the AP was completely blocked. If complete block was not obtained, intubation was performed 300 s after administration of atracurium. Intubating conditions were scored on a 1 to 4 scale. All intubations were performed by the same physician unaware of the dose and the muscular responses. After 0.5 mg/kg, both muscles were completely blocked in all patients. The average onset time (time from the injection of atracurium to the disappearance of all muscular responses after TOF) was shorter at the OO (2.35 +/- 0.12 min) than at the AP (3.59 +/- 0.15 min) (P < 0.001) (mean +/- SD). Endotracheal intubating conditions were comparable in both groups: good or excellent after 0.5 mg/kg. After 0.3 mg/kg, complete block was achieved only 2/20 at the OO and 12/20 at the AP. Intubating conditions were comparable in both groups: poor or inadequate, except in the two patients with complete OO block, for whom conditions were good.(ABSTRACT TRUNCATED AT 250 WORDS)

Atracurium↗

In vitro plasma protein binding of neuromuscular blocking agents in different subpopulations of patients.

In vitro protein binding of several neuromuscular blocking agents (NMBAs) was measured by ultrafiltration in plasma from patients susceptible to demonstrate changes in their protein constituents. First, the relationship between the free fraction of atracurium and plasma lipoproteins levels in young volunteers (22-32 yr old, n = 6) and hyperlipidemic patients (44-68 yr old, n = 13) was studied, and second, the free fraction of atracurium, mivacurium, doxacurium, and vecuronium was determined in plasma of healthy young (27-47 yr old, n = 10), elderly (72-89 yr old, n = 11) and obese (21-57 yr old, n = 9, 200%-360% ideal body weight) patients scheduled for elective surgery. In hyperlipidemic patients, atracurium free fraction was significantly less than in young volunteers (40% +/- 5% vs 50% +/- 5%, mean +/- SD), and decreased as total cholesterol, low-density lipoprotein cholesterol and triglycerides increased (P < 0.05). In young individuals, NMBA free fraction was 25% +/- 5% for vecuronium, 58% +/- 8% for doxacurium, 52% +/- 6% for atracurium, and 72% +/- 3%, 70% +/- 3%, 70% +/- 4% for mivacurium trans-trans, cis-trans, and cis-cis isomers, respectively. Higher triglyceride concentrations in obese patients and lower high-density-lipoprotein cholesterol concentrations in both obese and elderly patients were observed when compared with young subjects. However, there was no significant difference in protein binding of NMBAs among these three groups. We conclude that, in otherwise healthy patients, age and weight are not likely to alter the free fraction of NMBAs.

Adult↗

Cardiac arrhythmias mimicking primary neurological disorders: a difficult diagnostic situation.

Cardiac arrhythmias can present with the signs and symptoms of a seizure disorder. This potentially life-threatening underlying cause of non-febrile seizures should be recognized early, since successful specific treatment is possible. The purpose of this retrospective study was to examine common features in such patients. Over a period of 25 years, eight patients were initially treated for up to 5 years at our institution for a seizure disorder until dysrhythmia as the underlying cause of the seizures was disclosed. The main symptom was drop attacks coinciding with physical activity or emotional stress. Convulsions were only rarely observed. In five of the eight patients the underlying disorder was the long-QT-syndrome (Romano-Ward syndrome). In one patient intermittent complete atrioventricular block was found, another patient showed ventricular tachydysrhythmia of unknown etiology and the last patient suffered from hypertrophic cardiomyopathy.

Adolescent↗

Considerations in the prophylactic treatment of transient ischemic attack or ischemic stroke in the carotid artery territory.

This non-randomized study surveys the prophylactic treatment of 154 patients after transient ischemic attack or ischemic stroke in the carotid artery territory. Clinical presentation and etiologies were compared on the basis of the proposed prophylactic treatment. A surgical intervention or a long-lasting anticoagulation was restricted to only 30 patients (20%) due especially to the gravity of the ischemic cerebral lesions, general deterioration, and the advanced age of most of the patients. The purpose is to emphasize the "down-to-earth" situation in current medical care of non-selected patients as distinguished from the strictly selected patients of randomized studies. More importance should be done to open studies which better reflect the daily medical reality.

Adult↗

Determination of midazolam and two of its metabolites in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic assay coupled with UV detection (254 nm) has been developed for the determination of midazolam and two of its hydroxylated metabolites, 1-hydroxymidazolam (1-OH) and 4-hydroxymidazolam (4-OH), in human plasma. Following a novel solid-phase extraction procedure, midazolam and its metabolites are well recovered from plasma. The analytes were extracted with C1 cartridges and the extracts were evaporated to dryness. The dry residues were dissolved in 200 microliters of mobile phase [0.02 M ammonium phosphate monobasic buffer-methanol-acetonitrile (60:35:5, v/v) (300 ml), 600 microliters of 0.2 M tetrabutylammonium bromide solution, adjusted to a pH* (apparent pH) of 4.10]. The separation of the analytes was performed on a Spherisorb C8 column (10 cm x 4.6 mm I.D.) maintained at 30 degrees C. The mobile phase was pumped at a flow-rate of 1.5 ml/min. The method has a lower limit of quantitation of 15 ng/ml of plasma for midazolam and proved to be reproducible (inter-assay precision 5.4%) and accurate (94 +/- 5%) over the therapeutic range of concentrations.

Chromatography, High Pressure Liquid↗

Neuromuscular effects of vecuronium and neostigmine in Montreal and Paris.

The potency of vecuronium was reported to be greater in Montréal than in Paris. This study was designed to determine whether there were differences in onset, duration, and reversibility with neostigmine between both centres. Twenty ASA I or II adults (ten men, ten women), aged 18-65 yr were studied in each of the two cities, during a standard thiopentone-fentanyl-nitrous oxide (60-70%) - isoflurane 0.5% end-tidal anaesthetic. Train-of-four stimulation was applied every 20 sec to the ulnar nerve at the wrist and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 0.1 mg.kg-1, was given as a bolus, and neostigmine, 0.04 mg.kg-1, was administered, with atropine 0.02 mg.kg-1, at 25% first twitch height recovery. Onset time to maximum blockade was (mean +/- SD) 3.9 +/- 1.3 min in Paris vs 4.5 +/- 1.3 min in Montréal (NS). Duration from injection to 25% first twitch recovery was shorter (28.5 +/- 6.8 min) in Paris than in Montréal (39.1 +/- 7.3 min) (P < 0.0001). Time from injection of neostigmine to a train-of-four ratio of 70% was not different in Paris (6.3 +/- 2.2 min) from Montréal (5.6 +/- 1.9 min). It is concluded that the duration of an "intubating" dose of vecuronium is longer in Montréal, but, when given at 25% first twitch recovery, neostigmine has the same efficacy in Montréal as in Paris.

Adolescent↗

Safety and potency of ANQ 9040 in male volunteers.

BACKGROUND: ANQ 9040 is an experimental nondepolarizing neuromuscular relaxant. Initial investigations in animals had indicated a rapid onset of action comparable to that of succinylcholine. The purpose of this study was to assess the safety and potency of ANQ 9040 in humans. METHODS: ANQ 9040 was assessed in 41 male volunteers. Anesthesia was induced with propofol and maintained with a propofol infusion and 60% N2O/40% O2. Neuromuscular function was measured by mechanomyography using train-of-four stimulation of the ulnar nerve every 12 s. After an initial pilot study, 23 volunteers received a single dose of ANQ 9040 of between 0.5 and 1.1 mg/kg to determine the dose-response relationship. The final 10 volunteers were given twice the estimated ED95 of ANQ 9040 as a single bolus dose. RESULTS: The estimated ED50 and ED95 of ANQ 9040 were 0.6 and 1.3 mg/kg, respectively. Apart from an increase in heart rate, no important adverse effects were noted after ANQ 9040 administration in the dose range 0.5-1.1 mg/kg. In the volunteers who received 2.6 mg/kg ANQ 9040, a substantial increase in plasma histamine was observed. This was associated with a 12% decrease in mean arterial pressure and a 49% increase in heart rate. In this group, the mean onset time to neuromuscular block was 51.3 s. CONCLUSIONS: ANQ 9040 is a rapid-onset neuromuscular blocking agent. However, twice the ED95 dose is associated with significant histamine release and tachycardia. This finding suggests that this drug will not be useful in clinical practice.

Adolescent↗

Comparison of twitch depression of the adductor pollicis and the respiratory muscles. Pharmacodynamic modeling without plasma concentrations.

BACKGROUND: Although the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings. METHODS: The pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (C(effect)) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (k(eo)); and (2) effect is a function of C(effect), the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/k(eo)) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40-70 micrograms/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia. RESULTS: For IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1. CONCLUSIONS: Vecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.

Humans↗

[The dedication of the "inaugural lecture" (1766) of Samuel-Auguste Tissot].

Samuel-Auguste Tissot (1728-1797) has been appointed professor of medicine at the Academy of Lausanne. He gave his inaugural lecture on "De Morbis Litteratorum" on April the 9th 1766 and published it 15 days later under the title "Sermo inauguralis de valetudine litteratorum". The affirmations, made by some of his recognized biographers, that this publication was dedicated to the King of Poland (Stanisław August Poniatowski) are erroneous. In reality, this dedication starts with the inscription: "Inclytae Reipublicae Bernensis Consulibus (...)". The dedication itself and the following "Epistola" are both entirely consecrated to the excellencies and senators of the Republic of Berne.

Faculty, Medical↗

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery.

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T4/T1 > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-of-four (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg.kg-1, during thiopentone-N2O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg.kg-1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg.kg-1, was given. Two minutes later, edrophonium, 0.1 mg.kg-1, was given if T4/T1 did not reach 0.7. After another two minutes, edrophonium, 0.2 mg.kg-1, was given if T4/T1 did not reach 0.7 or more. Finally, if T4/T1 was still < 0.7, a dose of 0.4 mg.kg-1 was given. Seventeen patients (42.5%) required 0.1 mg.kg-1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg.kg-1 and six patients (15%) required 0.4 mg.kg-1. Only one patient received 0.8 mg.kg-1. There was a good correlation between T4/T1 two minutes after the first dose of edrophonium and pre-reversal T4/T1 (r = 0.6; P = 0.00014). All patients with pre-reversal T4/T1 > 0.23 required at most 0.2 mg.kg-1 of edrophonium for successful reversal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Potentiation of pancuronium and vecuronium neuromuscular blockade by intravenous salbutamol.

Three doses of salbutamol 125 micrograms iv were given, over 3.5 hr, to a 28-yr-old healthy, previously non-asthmatic man during thiopentone-O2/N2O-isoflurane anaesthesia for treatment and prophylaxis of bronchospasm. Force of contraction of the adductor pollicis was measured before and after the last two injections. Initially, the patient was given pancuronium, 5 mg. Salbutamol, 125 micrograms iv, was given when T1 blockade was 45%. Blockade increased to 66% over five minutes and returned to 45% after 18 min. Vecuronium was subsequently used to maintain relaxation. At the end of surgery, salbutamol was followed by an increase in T1 blockade, from 66% to 86%, over five minutes which returned to 66% after ten minutes. It is concluded that intravenous salbutamol potentiates the neuromuscular blocking effect of nondepolarizing muscle relaxants.

Adult↗

Pharmacodynamic behaviour of rocuronium in the elderly.

This study compared the potency and time course of action of rocuronium (ORG 9426) in elderly and young patients during nitrous oxide-opioid anaesthesia. One hundred ASA physical status I-II patients (60, aged 65-80 yr, and 40, aged 20-45 yr) were studied by measuring the force of contraction of the adductor pollicis in response to train-of-four stimulation of the ulnar nerve. After induction of anaesthesia with thiopentone and maintenance with N2O/O2 and fentanyl, rocuronium 120, 160, 200, or 240 micrograms.kg-1 was administered to determine dose-response curves. When maximum block had been obtained, further rocuronium to a total of 300 micrograms.kg-1 was given. Additional doses of 100 micrograms.kg-1 were administered when the first twitch height (T1) had recovered to 25% control. At the end of surgery neuromuscular blockade was allowed, whenever possible, to recover spontaneously until T1 was 90% of control before administration of neostigmine. There was no difference in the potency of rocuronium in the elderly and the younger patients. The ED50 was 196 +/- 8 (SEE for the mean) in elderly, vs 215 +/- 17 micrograms.kg-1 in young patients (NS). When individual cumulative dose-response curves were constructed, the ED50 was 203 +/- 7 (SEM) and 201 +/- 10 micrograms.kg-1 in the elderly and the young respectively (NS). However, the onset of maximum neuromuscular block was slower in the elderly 3.7 +/- 1.1 (SD) vs 3.1 +/- 0.9 min, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Influence of aging on the pharmacokinetics and pharmacodynamics of doxacurium.

Doxacurium (30 micrograms/kg) pharmacokinetics and pharmacodynamics were evaluated in nine elderly (age range, 70 to 83 years) and nine young (age range, 19 to 39 years) patients under nitrous oxide-isoflurane anesthesia. The force of contraction of the adductor pollicis was monitored and plasma samples were collected for an 8-hour period. In the elderly group, doxacurium elimination half-life was prolonged (119.7 versus 75.9 minutes) and plasma clearance was significantly reduced (1.75 versus 2.54 ml/min/kg) without any change in volume of distribution. Onset (12.9 versus 8.9 minutes) and recovery times (113.4 versus 48.1 minutes) were longer in the elderly group. The equilibrium rate constant to the effect compartment (kco) was decreased in the elderly (0.039 versus 0.051 min-1), whereas the effect compartment concentration at 50% block was similar in both groups (44.7 versus 54.1 ng/ml). An age-related reduction in muscle blood flow may be responsible for the decrease in kco. The pharmacokinetic changes observed in the elderly are consistent with a decreased function in the organs of elimination.

Adult↗

Onset of maximum neuromuscular block following succinylcholine or vecuronium in four age groups.

BACKGROUND: Increasing age appears to be associated with a slower onset of neuromuscular blockade, but such an effect has not been studied with the same doses of the same drugs across pediatric and adult age groups. METHODS: The authors measured the evoked compound action potential of the adductor pollicis muscle in response to 0.1-Hz stimulation of the ulnar nerve, during fentanyl-thiopental-oxygen anesthesia, in 160 patients aged 1-3 yr, 3-10 yr, 20-40 yr, or 60-80 yr. Subparalyzing doses of vecuronium (0.03 mg/kg) or succinylcholine (0.3 mg/kg), or paralyzing doses of vecuronium (0.1 mg/kg) or succinylcholine (1.0 mg/kg), were administered to ten patients in each age group. RESULTS: Onset time, defined as the time from injection to maximum depression of response with a subparalyzing dose or the time from injection to ablation of visible response with a paralyzing dose, varied with age in all groups (P < 0.001). For 0.3 mg/kg succinylcholine, it increased from 49 +/- 6 s in 1-3-yr-old patients, to 104 +/- 9 s in 60-80-yr-old patients (P < 0.00001). For 0.03 mg/kg vecuronium, onset time was 3.6-5.9 times longer than for succinylcholine, increasing from 219 +/- 15 s in 3-10-yr-old patients to 473 +/- 30 s in 60-80-yr-old patients (P < 0.00001 by linear regression). For paralyzing doses, succinylcholine 1.0 mg/kg had an onset time of 58 +/- 7 s and 95 +/- 7 s, in 1-3-yr-old and 60-80-yr-old patients, respectively (P < 0.001). For 0.1 mg/kg vecuronium, onset time varied between 125 +/- 19 s in 1-3-yr-old patients to 295 +/- 31 s in 60-80-yr-old patients (P < 0.00001), and was 2.1-3.3 times longer than 1 mg/kg succinylcholine. CONCLUSIONS: Increasing age is associated with slower onset for both succinylcholine and vecuronium. When equipotent, subparalyzing doses of succinylcholine and vecuronium are compared, onset time is 4.5 times as long with vecuronium.

Adult↗