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P Vert

Publications and source records attributed to P Vert.

At least 19 recordsLinked to original sources

An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. I. Behavioral characterization and determination of lumped constant.

An experimental model of status epilepticus has been developed in the immature rat by administration of pentylenetetrazol (PTZ) using repetitive, timed intraperitoneal injections of subconvulsive doses. The pattern of behavioral signs has been well characterized in each age group, i.e. 10 (P10), 14 (P14), 17 (P17) and 21 postnatal days (P21). In this model, the dose of convulsant could be adjusted as a function of interindividual sensitivity and status epilepticus lated for quite a long duration to allow the measurement of local cerebral metabolic rates for glucose (LCMRglc) by means of the [14C]2-deoxyglucose method [J. Neurochem., 28 (1977) 897-916]. To estimate LCMRglc during status epilepticus, the lumped constant (LC) was re-calculated in controls and PTZ-treated rats. The control LC was 0.54 at P10 and 0.50-0.51 at the three older ages studied (P14, P17 and P21). During status epilepticus, it increased to 0.64 in P10 rats and decreased to 0.42 and 0.40, respectively, in P17 and P21 animals. At P14, LC was not affected by seizures. The measurements of brain lactate levels showed a large 4.5-10-fold increase in PTZ-treated rats as compared to controls at all ages. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its postnatal age. Moreover, our results underscore the necessity of re-calculation of LC to the quantification of LCMRglc in such pathological states, particularly in immature animals.

Aging

An experimental model of generalized seizures for the measurement of local cerebral glucose utilization in the immature rat. II. Mapping of brain metabolism using the quantitative [14C]2-deoxyglucose technique.

The quantitative autoradiographic [14C]2-deoxyglucose technique (2DG) was applied to measure the effects of pentylenetetrazol (PTZ)-induced status epilepticus (SE) on local cerebral metabolic rates for glucose (LCMRglc) in 10 (P10)-, 14 (P14)-, 17 (P17)- and 21 (P21)-day-old rats. To produce long-lasting SE (55 min), the animals received repetitive, timed intraperitoneal injections of subconvulsive doses of PTZ until SE was reached. At P10 and P14, SE induced a marked increase in LCMRglc which affected 66 of the 76 structures studied. Increases were especially high (200-400%) in limbic and motor cortices at P10 and in some brainstem areas at these 2 ages. At P17 and P21, average brain glucose utilization was similar in seizing and control rats, but in PTZ-treated rats reflected a redistribution in local metabolic rates with increases in brainstem, midbrain, hypothalamus and septum, decreases in cortex, hippocampus, some sensory areas and white matter and no change in many motor and limbic structures. In a few cerebral regions, such as hippocampus, dentate gyrus and mammillary body, LCMRglc did not increase at P10 and P14 and decreased at P17 and P21 in PTZ- vs. saline-treated rats. The results of the present study show that the immature brain responds to sustained seizure activity in a specific way according to its maturational state. Moreover, these data allow the mapping of the vulnerability of cerebral structures to seizures, according to their metabolic response to convulsions.

Aging

Acute hypoxia induces specific changes in local cerebral glucose utilization at different postnatal ages in the rat.

The quantitative autoradiographic 2-[14C]-deoxyglucose technique (2-DG) was applied to measure the effects of an acute hypoxic exposure on local cerebral metabolic rates for glucose (LCMRglcs) in the 10 (P10)-, 14 (P14)-, and 21 (P21)-day-old rat. The animals were exposed to hypoxic (7% O2/93% N2) or control gas mixture (21% O2/79% N2) for 20 min before the initiation and for the duration of the 2-DG procedure. Lumped constants were not affected by hypoxia at any age. At P10, the exposure to the hypoxic gas mixture induced a generalized increase in LCMRglc which affected 41 structures of the 45 studied. At P14, average cerebral glucose utilization was similar in hypoxic and control rats. LCMRglc increased in 5 areas and decreased in 11 regions, mainly brainstem and respiratory areas in hypoxic rats. Finally, at P21, LCMRglc decreased in 11 structures of hypoxic rats. The increase in LCMRglc in the hypoxic 10-day-old rat likely reflects stimulation of anaerobic glycolysis. Conversely, at P14 and P21, when the brain has become more dependent upon oxygen supply for its energy metabolism, levels of LCMRglc are similar in both groups of animals or decreased in a few structures of hypoxic compared to normoxic rats. The results of the present study show that the immature brain responds to an acute hypoxic insult in a specific way according to its maturational state. They are also in good accordance with the higher resistance of the immature animal to oxygen deprivation.

Acute Disease

Carotid chemoreceptor response to natural stimuli in the newborn kitten.

The activities of carotid chemoreceptors at three levels of inspired PO2 (55, 145 and 690 Torr) and at two levels of inspired PCO2 (35 and 70 Torr in O2) were studied in 28 anesthetized, mechanically ventilated kittens aged 0-17 days. A biphasic response to hypoxia was found in 46% of them: the chemosensory activity increased to a peak within 30 sec after the initial response to hypoxia and thereafter declined slowly to a stable value. The steady-state single-fiber chemosensory activity at an inspired PO2 of 55 Torr was significantly lower in kittens less than 10 days old (mean +/- SE: 5.8 +/- 0.6 impulses.sec-1) than in the older ones (8.8 +/- 1.3 impulses.sec-1, P less than 0.03). The response curves to arterial PO2 were hyperbolic in both groups but the curve for the younger kittens was displaced to the left of the curve for the older ones. The response to hypercapnia was a progressive increase in chemosensory activity with little evidence of rapid or slow adaptation. The response to hypercapnia was significantly stronger in the older kittens than in the young ones. It is concluded that, in the kitten, the carotid chemoreceptor response to hypoxia may be biphasic. The responses to hypoxia and hypercapnia are already developed but are weak at birth and continue to develop further during the first weeks of postnatal life.

Animals

Dual responses of carotid chemosensory afferents to dopamine in the newborn kitten.

The effects of dopamine and of dopamine D2 receptor blocker haloperidol on the activity of carotid chemoreceptors were studied in 24 anesthetized, paralyzed and artificially ventilated newborn kittens aged 0-17 days. Single or few fiber preparations of chemoreceptors were made from one carotid sinus nerve. The responses of the chemosensory afferents to intravenous injections of dopamine (5-50 micrograms.kg-1) were studied in kittens breathing air and 8% O2 in N2. The effects of haloperidol on the chemosensory activity in air or 100% O2 and on the chemosensory response to hypoxia were studied. Dopamine inhibited the chemosensory discharge in 25/44 studies in normoxia. Of the 9 studies performed in hypoxia, dopamine was excitatory in 5 or had no effect in 4 (P < 0.05 vs normoxia). Inhibition of the chemosensory discharge was observed in 24/37 studies performed in kittens aged more than 3 days and was predominantly excitatory in 6/7 studies in kittens aged 0-3 days (P < 0.01). One minute after haloperidol, the chemosensory discharge had increased significantly in all experiments. The biphasic pattern of chemosensory response to hypoxia (Marchal et al., Respir. Physiol. 87: 183-193, 1992) was not changed by haloperidol. The steady-state chemosensory activity was significantly increased after haloperidol, respectively from 3.9 +/- 0.7 impulses.sec-1 to 9.8 +/- 1.2 impulses.sec-1 in air, and from 13.1 +/- 1.4 impulses.sec-1 to 17.8 +/- 2.4 impulses.sec-1 in hypoxia (mean +/- SEM, P < 0.03). It is concluded that the dopaminergic mechanisms are active in the carotid body of the kitten, and the observed responses to dopamine and haloperidol are qualitatively similar to those reported in the adult cat.

Action Potentials

Doxapram for the initial treatment of idiopathic apnea of prematurity.

The ventilatory effects of doxapram in the initial pharmacotherapy for apnea in the newborn were evaluated in 8 premature infants with idiopathic apnea. All received doxapram for 48 h at 0.25 mg/kg/h on the first day and 1 mg/kg/h on the second day. The ventilatory effects and the airway occlusion pressure (p0.1) were measured by means of a face mask, and a pneumotachograph. Compared to the pretreatment period, the mean of the frequency of central apnea greater than or equal to 15 s decreased significantly (p less than 0.01) by 48 and 75% during the first and second day, respectively. Both doses significantly increased inspiratory drive measured by airway occlusion pressure by 20% (p less than 0.05) and 32% (p less than 0.01) on the first and second day of drug treatment, respectively. Minute ventilation, tidal volume and mean respiratory flow significantly increased only with 1 mg/kg/h of doxapram, accompanied by a significant decrease in transcutaneous PCO2. No side effects were noted. Data suggested that doxapram alone at a dose of 1 mg/kg/h is effective for the treatment of neonatal apnea.

Apnea

[Hemodynamic and renal adaptation of newborn infants of hypertensive mothers treated with acebutolol].

A prospective study of the hemodynamic and renal changes was undertaken in 11 neonates whose mothers were treated with acebutolol for hypertension during pregnancy, compared with a control group of 11 infants born to normotensive mothers. Monitoring of the cardio-respiratory system was performed for a period of 4 days. Renal function was studied during 2 periods (12-36, 60-84 hours of life). Hemodynamic failure was observed in 5 of 11 children from treated mothers. The data concerning the renal function of treated group showed: 1) a diuresis significantly lower during the first period (p less than 0.05); 2) the absence of significant rise in the glomerular filtration rates during the second period; 3) a lower sodium balance during the 1st and 2nd periods (p less than 0.02 and p less than 0.05), a lower calcium balance during the 1st period (p less than 0.01). No relationship was found between the renal changes and the hemodynamic disturbances. The direct effect of the drug on the glomerular and tubular functions and/or the renal arteriolar vasomotricity could explain these changes in the renal function in the newborns prenatally exposed to acebutolol.

Acebutolol

Clonazepam in neonatal seizures: dose regimens and therapeutic efficacy.

The attempt has been made to define the optimal dose regimen of clonazepam in newborns suffering from neonatal convulsions. Results obtained from 22 patients (GA 28-41 weeks; PNA 4 h to 23 days) indicated that a dose of 0.1 mg/kg every 24 h was satisfactory in the majority of the patients. It is recommended as a starting regimen.

Asphyxia Neonatorum

Postaxial acrofacial dysostosis (Miller) syndrome: a new case.

We describe a new case of postaxial acrofacial dysostosis (Miller) syndrome. This syndrome consists of mandibulofacial dysostosis, similar to that seen in Treacher Collins syndrome, and postaxial limb deficiency. The mode of inheritance remains uncertain.

Abnormalities, Multiple

Respiratory mechanics in spontaneously breathing term and preterm neonates.

The compliance (Crs), resistance (Rrs) and passive time constant (tau rs) of the respiratory system were determined by the single-breath method (sb) in 24 healthy term and preterm newborns. In 22 of them, Crssb was compared to the slope of the pressure-volume curve determined by the multiple occlusion technique (mo), which is not dependent on the assumption of a linear flow-volume relationship. Crssb and Rrs correlated significantly with body weight (kg): Crssb = 0.56 x kg + 1.22 (r = 0.67); Rrs = -20.1 x kg + 134.6 (r = -0.68). No difference in Crs and Rrs between prone and supine positions was found. tau rs was not significantly different between premature (0.21 +/- 0.06 s) and full-term infants (0.21 +/- 0.05 s). Crssb was significantly higher than Crsmo in premature babies (2.27 +/- 0.41 ml.cm H2O-1 vs. 1.98 +/- 0.47 ml.cm H2O-1. This difference may be explained by a continuous braking of expiratory airflow after release of the occlusion, or more likely, by a difference in the lung volume at which Crssb and Crsmo are measured. However, the difference between Crssb and Crsmo (approximately 15%) is in the same range as the intrasubject variability, and is meaningless compared to the alterations of respiratory mechanics observed during neonatal ventilatory disorders. Therefore, the single-breath method appears to be a suitable and noninvasive method to measure respiratory mechanics in nonintubated prematures.

Airway Resistance

Placental transfer and perinatal pharmacokinetics of betaxolol.

Betaxolol levels in blood were monitored in the perinatal period in 28 pregnant hypertensive women and in their babies. In the mothers betaxolol concentrations at delivery ranged from less than 1 to 115 ng.ml-1 after doses of 10 to 40 mg.day-1. The apparent blood half-life was 15.6 to 22.1 h mean (19 h). Umbilical cord levels indicated a rapid equilibrium between fetal and maternal units (ratio 0.93) within few hours after dosing. Milk betaxolol concentrations, measured in few cases, exceeded those in blood by a factor of 3. Amniotic fluid concentrations were similar to those observed in maternal venous blood and umbilical cord blood. In neonates, the blood betaxolol half-life ranged from 14.8 to 38.5 h, with a definite trend towards a negative correlation with gestational age. A 11-61% rise in the betaxolol concentration was observed in 64% of the neonates during the first 12 h of extrauterine life. The data indicate that betaxolol kinetics is not altered in pregnant women and they stress the need for careful and prolonged (72-96 h) intensive monitoring of neonates born to hypertensive mothers treated with beta-blocking agents.

Adult

Effect of sympathetic nervous system on cerebral blood flow in the newborn piglet.

The role of the sympathetic nervous system on cerebral blood flow (CBF) autoregulation was evaluated in newborn piglets. Six animals were studied after ablation of the right superior sympathetic ganglion and compared to 6 control animals. Mean arterial blood pressure (MABP) was decreased by successive blood withdrawal and CBF was measured by radioactive microspheres. In denervated animals, MABP and CBF correlated positively according to a parabolic curve showing an absence of autoregulation when MABP is above 50 mm Hg (y = 0.079x2 - 5.9x + 154, p less than 0.01). In control animals, CBF remains stable throughout the experiment (y = 0.28x + 5). These data suggest a shift to the left of the upper limit of the autoregulation range in denervated animals and consequently a poor adaptation to increased MABP.

Animals

[Post-transfusion cytomegalovirus infection in premature infants weighing less than 1,500 g].

The incidence of cytomegalovirus (CMV) infection among 107 low birth weight transfused infants (birth weight less than or equal to 1,500 g) admitted to an intensive care nursery over an 18 month period was evaluated. The diagnosis of CMV infection was based on specific serologic tests (presence of IgM, increased IgG by ELISA technic) and identification of the virus in the urine. During the first 8 months, the infants received untested blood and CMV disease occurred in 8 infants out of 44 (18.2%). During the following 10 months, all transfusions performed in 63 infants were supposed to be CMV negative. However, 32 infants received untested blood due to emergency, and 5 of them developed a CMV infection (15.6%). Finally, only 31 infants received CMV negative blood without any case of CMV infection. These data clearly demonstrate that, considering the severity of the CMV disease in the premature infants, transfusions should be performed with CMV negative blood products.

Cytomegalovirus

Autoregulation of cerebral blood flow. Effect of phenobarbital and pancuronium in the newborn piglet.

The effect of phenobarbital and pancuronium on cerebral blood flow (CBF) and CBF autoregulation are studied in newborn piglets after chemically induced seizures with bicuculline. Given 3 or 15 min after the onset of seizures, phenobarbital significantly reduces CBF (59 +/- 11 and 56 +/- 17 vs. 84 +/- 24 ml/min/100 g - p less than 0.01). Moreover, during graded hypotension induced by graded haemorrhage, phenobarbital provides reestablishment of CBF autoregulation altered by seizures. In the same experimental model, pancuronium induces in control animals a rise of CBF (61 +/- 15 vs. 38 +/- 11 ml/min/100 g - p less than 0.001). During graded hypotension pancuronium is associated to a loss of CBF autoregulation (r = 0.76, p less than 0.001). Given as an adjunct treatment, in case of seizures, pancuronium has no significant effect on changes in cerebral haemodynamics. From these data, we conclude that pancuronium jeopardizes the haemodynamic adaptation to the induced hypovolemia and that phenobarbital may present a protective effect on cerebral haemodynamics and the subsequent risk for ischaemia or haemorrhage.

Animals