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Biomedical subjects

M Fornaris

Publications and source records attributed to M Fornaris.

At least 19 recordsLinked to original sources
PubMed1993

Simultaneous determination of dextromoramide, propoxyphene and norpropoxyphene in necropsic whole blood by liquid chromatography.

Dextromoramide, propoxyphene and its main metabolite, norpropoxyphene, were determined in blood after solid-liquid extraction by means of an HPLC method using photodiode-array detection. Two cases of fatal overdose resulting from abuse of the two drugs are presented. In case 1 the necropsic whole blood contained dextromoramide at toxic level (194 ng ml-1) and propoxyphene (614 ng ml-1) and norpropoxyphene (1100 ng ml-1) within the therapeutic range; the death could be due to the combined effect of the two analgesics and, perhaps, other associated drugs. In case 2, the necropsic whole blood concentrations of propoxyphene and norpropoxyphene were 4330 and 3800 ng ml-1, respectively, and could be considered as lethal.

Adult↗
PubMed1988

[Intrarectal clonazepam in children. Plasma and CSF levels].

Eleven children with seizures were treated with clonazepam by rectal route. Thirty minutes after the administration, the plasma (8 to 28 ng/ml) and CSF (0.9 to 2.26 ng/ml) levels were satisfactory and correlated with a good clinical result. Since the tolerance of the drug was excellent, clonazepam appears to be as useful as diazepam in the management of childhood seizures.

Administration, Rectal↗
PubMed1986

Cold-induced bronchospasm in normal and sensitized rabbits.

In anesthetized, paralyzed and artificially ventilated rabbits, changes in lung resistance induced by cooling the inspired air were studied under dry air conditions. Airway response to cold was measured in normal animals and in rabbits sensitized to bovine serum albumin. The magnitude of cold-induced bronchospasm was significantly greater in sensitized than in normal rabbits but the time course for recovery of control lung resistance during rewarming was the same in both groups and lasted longer than 4 min. Inhalation of a nebulized aerosol of sodium cromoglycate (SCG) markedly reduced cold-induced bronchospasm and shortened the recovery period, which then lasted only 20 to 30 sec. Vagotomy abolished the airway response to cold air in all cases and this was observed whether the vagus nerves were cut before or after SCG inhalation. SCG or vagotomy exerted the same effect on the response to cold air in normal or sensitized rabbits. Sensitized animals showed an hyperresponsiveness to histamine as well as to cold air. These results suggest that cold-induced bronchospasm results from a vagally mediated reflex whose effects are only enhanced and prolonged by a local release of humoral factors, linked to the reflex path. The increased response to cold air in the sensitized rabbits seems to correspond to non-specific hyperresponsiveness of bronchial smooth muscle rather than to an increased local release of inflammatory mediators.

Aerosols↗
PubMed1986

Prevention of postischaemic ventricular fibrillation by long term beta adrenoceptor blockade with acebutolol in the anaesthetised dog.

Acute occlusions of the proximal left circumflex coronary arteriovenous pedicle were performed in open chest anaesthetised dogs. Twenty eight dogs were randomly allocated to receive acebutolol (3 mg X kg-1 twice daily) or placebo given blindly by mouth for five days; a control group of 14 dogs without any pretreatment underwent the same procedure. Coronary ligations in the randomised study were performed during seven consecutive days, and four dogs were operated on each day. This schedule was chosen in order to measure acebutolol plasma concentrations just before ligation from 60 to 540 min after the last dose of the drug. Long term oral treatment with acebutolol protected against postischaemic ventricular fibrillation and significantly reduced the incidence of both early phase (0-10 min postocclusion) ventricular arrhythmias and ventricular fibrillation. As a result the outcome was significantly improved after 60 min of ischaemia in acebutolol compared with placebo treated animals. The results in the control animals were similar to those in the placebo treated dogs. The protective effect of long term oral treatment with acebutolol lasted for nine hours and was apparently independent of the plasma concentrations of the drug. These data show that improved outcome in this canine model is due to the prevention of ischaemia induced ventricular fibrillation by long term beta adrenoceptor blockade, which is able to overcome the effect, if any, of partial agonist activity of acebutolol. A direct myocardial anti-ischaemic effect might explain the effectiveness of long term oral treatment, which is independent of plasma concentrations of the drug.

Acebutolol↗
PubMed1984

Spontaneous and provoked resistance to isoproterenol in isolated human bronchi.

Cumulative concentration-response curves to isoproterenol were constructed in 74 preparations of human airways (group A) contracted with acetylcholine (80% of maximal contraction). In 52 bronchi (group A1), the maximal relaxation to isoproterenol represented at least 70% of the acetylcholine contraction (average 98% +/- 3) and the mean concentration (+/- SD) causing 50% of the relaxation (EC50) was 6.0 X 10(-8)M +/- 0.8. Resistance to isoproterenol (significant decrease of the maximal relaxation and right shift of the concentration-response curve) was provoked in 25 preparations by incubating them with isoproterenol (concentration 100 times higher than the individual EC50) for 30 min. The response to isoproterenol remained stable over the same time interval in eight control preparations. Incubation with isoproterenol did not modify the relaxing response to theophylline (n = 8). Indomethacin had no effect on the resistance provoked by isoproterenol incubation (n = 11). Incomplete relaxation to isoproterenol (maximal relaxation averaging 47% +/- 2 of the acetylcholine contraction) was observed in 22 preparations (group A2; mean EC50 = 1 X 10(-6)M +/- 0.2, significantly different [p less than 0.001] from group A1). Such preparations could be completely relaxed by theophylline (n = 7). For the whole group A, a significant negative correlation was found between isoproterenol EC50 and the magnitude of the maximal relaxation to isoproterenol (expressed as percent of acetylcholine contraction). There was no significant correlation between acetylcholine EC50 and isoproterenol maximum relaxation. Spontaneous resistance to isoproterenol was neither related to the technique of isoproterenol administration (cumulative versus noncumulative; n = 11) nor the magnitude of acetylcholine contraction (70% and 95% of maximal contraction; 14 bronchi, group B).

Airway Resistance↗
PubMed1982

Simultaneous plasma levels determination of mexiletine and one of its metabolites by electron capture gas-liquid chromatography.

A sensitive and specific electron capture gas-liquid chromatographic method is developed for the determination in human plasma both of mexiletine and of one of its hydroxymethyl metabolites appearing progressively during the kinetics and the presence of which is characterized by mass spectrometry. This method involves the use of two internal standards and the extraction of the drug and of its metabolite from alkaline plasma with diethyl ether followed by back extraction into sulfuric acid (0.2 N) for clean-up procedure and re-extraction by diethyl ether. The limits of detection of the heptafluorobutyryl derivatives of mexiletine and of its metabolite are 20 and 7 ng/ml of plasma, respectively. The preliminary results of the pharmacokinetic study performed in a cardiological unit after single oral administration and during long-term oral maintenance therapy are described in this paper. The method makes it possible to get a better knowledge of the kinetic behaviour of mexiletine and of its metabolite and contributes to the understanding of the origins of the variable pharmacokinetics of mexiletine in patients.

Arrhythmias, Cardiac↗
PubMed1980

Pulmonary mechanics during hypoxia in spontaneously breathing anesthetized rabbits.

Changes in lung mechanics were measured during hypoxia (FIO2 = 0.10 during 5 min) in spontaneously breathing anesthetized rabbits. In intact animals, hypoxia induced scattered variations in total lung resistance (RL) (decrease, increase or no alteration) and dynamic lung compliance (CL), whereas in carotid body denervated animals it was accompanied by an almost constant decrease in RL (-12%); but if a subsequent vagotomy was performed, there was no significant variation in RL. In animals which had been only vagotomized, CL decreased significantly during hypoxia (-23%) without any associated change in RL. So, the arterial chemoreceptor mediated bronchoconstrictor effects due to hypoxia could be normally masked by the dilator effects (metabolic and/or sympathetic) on the airways.

Airway Resistance↗
PubMed1980

Assessment of the central chemosensitivity in man under transient or progressive hypercapnia.

In healthy man, the central chemosensitivity to CO2 was studied after depression of the arterial chemoreflex drive by inhalation of pure oxygen. The effectiveness of the functional decrease of arterial chemoreceptor function was assessed by the delayed hyperventilation which followed transient inhalation of hypercapnic gas mixtures for 3 or 5 breaths in hyperoxic conditions. In such a case the first significant increase in tidal volume (VT) occurred 13.9 +/- 3.2 (SE) sec later than the early change in this variable measured in normoxic conditions. The stimulus strength was estimated by the change in CO2 partial pressure in end-tidal alveolar gas (delta PETCO2). The central chemosensitivity (SCO2), defined as the ratio between change in ventilation (delta V) and delta PETCO2, was assessed either by transient inhalation of gas mixtures containing 5 to 8% CO2 in pure O2 ("varying transients") or by progressive hypercapnia (rebreathing in pure O2). In both cases, the first significant change in ventilation was due to an increase in VT, but, for a given delta PETCO2, VT changes were higher during rebreathing than after transient hypercapnia; (2) The respiratory frequency (fR) was progressively enhanced during rebreathing (shortening of expiratory duration in all cases and of inspiratory time in some subjects) but the ventilatory rhythm diminished after transient stimulation as soon as delta PETCO2 reached one kPa, and this was due to an increase in inspiratory duration; (3) The associated changes in VT and fR during rebreathing could explain that SCO2 values given by this method were 5.2 times greater than after transient hypercapnia ("varying tests"). The differences are discussed in terms of, (1) isolated changes in arterial PCO2 or associated decrease in pH of the cerebrospinal fluid; (2) changes in brain blood flow, and (3) stimulation of lung stretch receptors by the important increase in VT during rebreathing.

Adolescent↗
PubMed1979

Transient hypoxia: ventilatory response after vagotomy and during artificial phasic inflation.

The early ventilatory response to transient hypoxia was examined in the anaesthetized rabbit. In intact spontaneously breathing animals, an increase in tidal volume (VT) with an accompanying slight increase in inspiratory duration (TI) and a decrease in the expiratory duration (TE) was observed. After vagotomy, the ventilatory response was distinguished by a greater increase in VT and a significant decrease in TI and TE. In another group of artificially ventilated rabbits, an increase in inspiratory volume with a simultaneous decrease in breathing frequency was found to involve a smaller reflex increase in phrenic inspiratory discharge after onset of transient hypoxia. These observations suggest that afferents from pulmonary vagal stretch receptors inhibit those from arterial chemoreceptors.

Animals↗
PubMed1979

Pattern of the ventilatory response to transient hypoxia in man: differences from transient hypercapnic test.

The pattern of change in ventilatory variables after inhalation of pure N2 for two breaths was studied in normal children and adults. In six subjects the trends of change were compared to the ventilatory response to transient hypercapnia. We observed differences in the patterns of increasing ventilation with an initial abrupt increase of tidal volume for transient hypoxia and a progressive change for hypercapnia. In both cases respiratory frequency was progressively but unsystematically enhanced. A highly significant positive correlation was demonstrated between individual sensitivities to CO2 and O2, with a greater response to hypercapnia (5.6 time) than to hypoxia. Finally, a very short-latency decrease in expiratory duration occurred in the first breath after inhalation of hypercapnic mixture, supporting the recent data of Cunningham et al. (1977).

Adult↗
PubMed1978

Interaction between vagal and chemoreceptors afferents in ventilatory response to transient hypercapnia (awake rabbits).

The ventilatory response to a transient hypercapnia was studied in four awake rabbits maintained in a volume displacement plethysmograph : the increase in inspiratory volume (VI) was associated or not with an increase in inspiratory and expiratory durations (TI and TE). These ventilatory variations were consistent with the activation of the peripheral chemoreceptors by carbon dioxide (short latency of the initial response). After vagal blockade by local anaesthesia, relative ventilatory variations were not significantly different from those previously measured. Central activity seems an important factor reducing inhibitory vagal input and favouring peripheral chemoreceptor afferents.

Afferent Pathways↗
PubMed1976

[The curve of the intraventricular pressure-volume relationships is not mono-exponential].

The graphic and statistic investigations have let us to assert that the right ventricular P/V relationship's curve is characterized by two successive segments: linear and exponential respectively. We have proposed an interpretation based on Roach's and Burton's works. Interest of information about this curve is double: 1) it is a function of the ventricular cavity volume; 2) it gives a general idea about the mode of ventricular filling.

Cardiac Volume↗
PubMed1975

[Pressure-volume relationship in the right ventricle].

The curve of the pressure-volume relationships of the right ventricular cavity is not a mono-exponential one. It can be characterized by the presence of two successive segments: linear and exponential. The points that constitute the first of them could not be subjected to Starling's law. This is material for the physiopathology of the tamponade.

Animals↗
PubMed1975

[Tension-volume relationship of the wall of the isolated right ventricle].

The variations of tension on the wall of the isolated right verticle have been observed on 18 dogs. The Tension/Volume curve we got can be superimposed to that obtained by pressures. The wall of the right ventricle itself (the radius of the curve in the cavity and the wall-thickness) seems to vary only with the changes in its tension in a rather small part of the curve.

Animals↗