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Biomedical subjects

L Pourcelot

Publications and source records attributed to L Pourcelot.

At least 19 recordsLinked to original sources

Influence of neonatal focal cerebral hypoxia-ischemia on cardiovascular and neurobehavioral functions in adult Wistar rats.

No experimental studies looked at the disturbances appearing after a neonatal focal cerebral hypoxia-ischemia (HI) when animals become adults. Using radiotelemetry, we examined the effects of neonatal focal cerebral HI on blood pressure (BP), heart rate (HR), locomotor activity (LA), body temperature (BT) levels and circadian rhythm parameters of unrestrained adult Wistar rats. At 15 weeks of age, we continuously recorded the cardiovascular and neurobehavioral parameters of HI (n = 6) and sham-operated (n = 6) rats. In adult rats, HI induced persistent hypertensive effects associated with alteration in BP circadian rhythms and pronounced decreases in mesor and percent rhythm of LA. HR and BT parameters were not significantly modified. Therefore, our results suggest that the rat cardiovascular and behavioural circadian control systems may involve several structures which present selective vulnerability to early cerebral HI.

Animals

Feto-maternal circulation: mathematical model and comparison with Doppler measurements.

OBJECTIVES: Clinicians are more and more frequently studying fetal blood flow velocity curves recorded by Doppler ultrasound in vital organs such as the placenta and fetal brain to evaluate fetal well-being. We have therefore developed a mathematical model of the utero-placental and fetal circulations which could be used for teaching and for a better understanding of regulatory mechanisms. METHODS: The model is based on two basic elements-an arterial segment and a bifurcation-and we have reproduced the major arteries of the feto-maternal circulation combining these basic elements. The mathematical model of the system is based on the Navier-Stokes equations. The peripheral areas such as the brain, kidneys and placenta are modeled by a simple Windkessel model and the model computes instantaneous flow and pressure at any point in the fetal arterial tree and the uterine arteries. RESULTS: We have compared the computed instantaneous flow curves and pressure with in vivo data and our results agree with the findings in physiological situations and in gravidic hypertension. CONCLUSIONS: Our model provides new interesting insights into fetal hemodynamics such as a better understanding of the mismatch impedance phenomena and is a promising model for the study of blood redistribution mechanisms in hypoxic situations.

Blood Vessels

Exploration of the dopamine transporter: in vitro and in vivo characterization of a high-affinity and high-specificity iodinated tropane derivative (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-m ethylph enyl)nortropane (PE2I).

For the diagnosis and follow-up of neurodegenerative diseases, many cocaine derivatives have been proposed as radioligands to explore the dopamine transporter. As none of them have all the criteria of specificity and kinetics for human use, we have developed a new derivative, (E)-N-(3-iodoprop-2-enyl)-2beta-carbomethoxy-3beta-(4'-methy lphenyl)nortropane (PE2I), which displays promising properties. We report the characterization of PE2I in vitro on rat striatal membranes and in vivo in rats and in monkeys. PE2I had a high affinity (Kd = 0.09 +/- 0.01 nM) and high specificity for the dopamine transporter. In rats we observed a high accumulation in the striatum; by contrast, a very low fixation was measured in the cortex. Moreover, a preinjection of a saturating dose of GBR 12909 prevented the striatal accumulation of PE2I by 74%. These results confirmed the specificity of PE2I for the dopamine transporter. In vivo in monkeys, SPECT studies showed a high accumulation in striatum. Moreover, an equilibrium state was obtained 1 h after injection. PE2I seemed to be the most promising ligand for the dopamine transporter exploration by SPECT using a single-day protocol.

Animals

Fetal heart modelling based on a pressure-volume relationship.

Study of the cardiovascular system of the human fetus is based on non-invasive measurement methods such as Doppler echography systems. The circulation conditions in fetal vessels are usually evaluated by resistance indices, giving limited physiological information on distal territories such as the placenta or the brain. To enhance the understanding of human fetal haemodynamics, a numerical model of the fetal heart has been developed, using the hydraulic-electric analogy. The model is based on a mechanical hypothesis of parallel functioning of the right and left ventricles, considered to have analogue elastance properties. Their behaviour is equivalent to that of a single ventricle ejecting an equivalent blood volume of 7 ml in the aorta. The characterisation of the equivalent ventricle is based on the determination of a set of four parameters (Emax, Vo, kv and Po) representing the maximum ventricle contractility, a reference volume, and volume and pressure constants, respectively. The model proposed is validated by studying the effects of preload and afterload variations on the fetal heart work, and by comparing the numerical results with literature and measured data. The model constitutes the first step towards a global model of the cardiovascular system of the human fetus.

Blood Pressure

Non-invasive quantification of diaphragm kinetics using m-mode sonography.

PURPOSE: The standard conditions of spirometry (i.e., wearing a noseclip and breathing through a mouthpiece and a pneumotachograph) are likely to alter the ventilatory pattern. We used "time motion" mode (M-mode) sonography to assess the changes in diaphragm kinetics induced by spirometry during quiet breathing. METHODS: An M-mode sonographic study of the right diaphragm was performed before and during standard spirometry in eight patients without respiratory disease (age 34 to 68 yr). RESULTS: During spirometry, the diaphragm inspiratory amplitude (DIA) increased from 1.34 +/- 0.18 cm to 1.80 +/- 0.18 cm (P = 0.007), whereas the diaphragmatic inspiratory (T1 diaph) increased from 1.27 +/- 0.15 to 1.53 +/- 0.23 sec, (P = 0.015, without change in diaphragmatic total time interval (Ttot diaph). Therefore, the diaphragm duty cycle (T1 diaph/Ttot diaph) increased from 38% +/- 1% to 44% +/- 4% (P = 0.023). The diaphragm inspiratory (DIV) and expiratory (DEV) motion velocity (P = 0.007). CONCLUSION: M-mode sonography enabled us to demonstrate that the wearing of a nose clip and breathing through a mouthpiece and a pneumotachograph induce measurable changes in diaphragm kinetics.

Adult

[Cerebral HITS: diagnosis, clinical relevance, outlook].

After 6 years of experience, Spencer and colleagues described the detection of embolus signals as height intensity transient signals (HITS) within Doppler flow spectrum from intracranial vessels. These signals (gaseous or materials) are recorded in many situations such as cardiac prosthetic valves, atrial fibrillation, carotid stenosis, carotid surgery or angioplasty. The clinical value is not well known: neurological impairment associated with brain lesions is described in case of cardiac prosthetic valves. The observation of HITS in carotid stenosis is associated with an increased risk of stroke. The detection of HITS offers a new orientation in studying stroke but some technical and/or clinical difficulties have to be solved.

Carotid Stenosis

Ultrasound contrast agents. Examples of blood pool agents.

PURPOSE: The concept of contrast agents has been extended to ultrasonography (US) almost 30 years ago. Due to technical limitations, the development of US contrast agents (USCA) was slow until the last decade. The ideal USCA should be nontoxic, i.v. injectable, capable to cross the pulmonary capillary bed after a peripheral injection, and be stable enough to achieve enhancement for the total duration of the examination. It should provide not only Doppler but also B-mode enhancement, at a reasonable cost. The efficacy of the most advanced USCA has been reviewed. RESULTS AND CONCLUSION: Doppler examinations improved in cases of deep or small vessels, vessels with low or slow flow, or vessels studied with a bad insonation angle. USCA also enhanced detection of flow within normal and abnormal vessels, including tumor and stenotic vessels. Ischemic areas were better delineated. Specific settings and software developed by US equipment manufacturers and US sequences (such as second harmonic imaging or transient imaging) prefigured the necessary adaptation of US units to the new potentials of USCA. Second harmonic properties will improve detection of smaller vessels including neovascularization associated with tumors. Targeting possibilities will increase the efficacy of USCA, and allow specific delivery of active drugs such as anticoagulants or cytotoxic compounds. New generations of USCA appear very promising, and are becoming part of the US future.

Contrast Media

[Circulation and cerebral metabolism in neonatal hypoxia-ischemia].

The basic physiological variable in hypoxic-ischaemic brain injury is cerebral oxygen delivery. When oxygen delivery becomes insufficient to meet the cellular demands for oxygen, a sequence of biochemical events will be triggered leading to cell death. High levels of CBF following severe birth asphyxia is now well documented by Doppler ultrasound which has been shown to be a useful prognostic indicator following birth asphyxia. Near infrared spectroscopy (NIRS) is of great potential value since it may be used at the bed-sid and allows to measure the cerebral blood volume and the concentrations of cytochrome aa3. Magnetic resonance spectroscopy (MRS) allows noninvasive assessment of cerebral metabolism in asphyxiated neonates. 31P MRS has demonstrated that birth asphyxia leads to delayed impairment of cerebral energy metabolism and is predictive of later neurodevelopmental outcome. 1H MRS has shown lactate accumulation and a later decline in N-acetyl aspartate concentration.

Asphyxia Neonatorum

[Diaphragm kinetics coupled with spirometry. M-mode ultrasonographic and fluoroscopic study; preliminary results].

Most techniques used so far for the evaluation of diaphragm kinetics are either invasive (electromyography, fluoroscopy), or indirect (respiratory pressures, impedance plethysmography). The aim of this study was to determine whether assessment with ultrasound or fluoroscopy differed, and which technique appeared more suitable in the investigation of quantitative hemidiaphragmatic displacement. Six patients (3 female, 3 male, aged 29 to 40) without respiratory disease were studied during systematic X-Ray chest examination, spirometry, and abdominal sonography. The amplitude of the right diaphragm motion could be measured in all patients with M-mode sonography as well as with fluoroscopy. The vertical ascending motion of the diaphragm measured by M-mode sonography, reached 60% of its maximum amplitude at 50% of inspiratory capacity. There was a significant correlation between the maximum amplitude of diaphragm motion as measured by M-mode sonography (5.8 +/- 0.4 cm; r = 0.89; p = 0.019) or fluoroscopy (5.6 +/- 0.7 cm; r = 0.84; p = 0.036) and the inspiratory capacity (2.73 +/- 0.39 l). M-mode sonography has technical, quantitative and qualitative advantages over fluoroscopy and should be the method of choice in the investigation of suspected diaphragmatic movement disorder. When coupled with other techniques like spirometry, this technique could represent a useful adjunct to functional respiratory studies.

Adult

An iodinated derivative of moclobemide as potential radioligand for brain MAO-A exploration.

In vivo evaluation of MAO-A would be of great value for the diagnosis and follow-up of therapy of depression. In order to perform this exploration by SPECT, we developed an iodinated derivative of the reversible MAO-A inhibitor, moclobemide. Ro 11-9900 was synthesized and analysed by IR, NMR and HPLC. Radioiodination was carried out by nucleophilic exchange of [125I] on the brominated precursor, and yielded [125I]-Ro 11-9900 with high specific activity. In vitro experiments on rat brain homogenates showed that Ro 11-9900 had poor inhibitory activity on MAO-A, as already described for moclobemide. By contrast, in vivo biodistribution in the rat brain showed that [125I]-Ro 11-990 accumulated in a region corresponding to the localization of locus coeruleus known for its high density of MAO-A. Moreover, preinjection of the irreversible MAO-A inhibitor clorgyline (10 mg.kg-1) prevented accumulation of radioactivity by 40 to 60% and we found that the radioactivity in the brain corresponded exclusively to [125I]-Ro 11-9900 and not to a metabolite. [125I]-Ro 11-9900 was highly accumulated in the pineal gland, both on MAO-A and on MAO-B sites. We concluded that the unmetabolized iodinated derivative of moclobemide, Ro 11-9900, preferentially labeled MAO-A in vivo in the rat brain. This compound would therefore be a potential tracer for evaluation of MAO-A by SPECT.

Animals

[Color Doppler ultrasonography of local recurrent breast cancer].

Local lesions occurring after conservative surgery for breast neoplasms require diagnostic means capable of detecting and assessing the recurrence of such cancers. In the present color-coded Doppler was used in 20 women who had under gone conservative surgery (mean 4 years before) to screen all suspect lesions. Among the 14 malignant lesions assessed histologically, one or more arterial vessels were detected inside or beside the lesion in 13. Among the 6 benign lesions, only of one arterial vessel was detected, in all cases far from the lesion (12.5 to 3.3 mm). No significant difference was observed for systolic velocities and resistance index. These results indicate high accuracy of color coded Doppler examination associated with echotomography and mammography for positive diagnosis of recurrent lesions in post-conservative follow-up of breast cancer.

Adult

[In utero measurement of the umbilical cord in full term pregnancy].

OBJECTIVE: The length of the umbilical cord varies widely from one pregnancy to another. Although its average length is 50 cm, this measurement could vary from as little as 20 cm to more than one metre. The purpose of our study was to evaluate, in utero, the length of the umbilical cord during the third trimester of pregnancy knowing the propagation velocity of the pressure wave along the cord. MATERIAL AND METHODS: The computation of the apparent length requires two ultrasound transducers, one situated at the aortic fetal arch, the other at the placental extremity of the umbilical artery. Knowing the velocity of the pressure wave (v), as well as the time interval between the systolic peak of two waves (delta t), we can deduce the length of the umbilical cord (delta t x v). RESULTS: The comparison between the calculated length and the actual length measured shows a significant correlation with a probability of 1%. CONCLUSION: The knowledge of the length of the umbilical cord is quite useful in the physio-pathological interpretation of the placental resistance index. It is also of interest, before the delivery, to know the length of the cord in order to foresee dystocy and how it relates cord which is either too short or too long.

Blood Flow Velocity

[Nuclear magnetic resonance spectroscopy: methodology and applications to the study of asphyxia neonatorum].

Cerebral metabolism has been extensively studied by magnetic resonance spectroscopy (MRS). MRS allows the study of neonates brain maturation as well as the onset and the evolution of brain injury. The use of phosphorous spectroscopy allows the quantification of phosphorylated metabolites. Thus, the measurement of the relative concentrations of creatine-phosphate and inorganic-phosphate is a prognostic factor of the outcome of a neonate after birth asphyxia. Absolute concentrations have more recently been studied and seem to be more significant. Proton MRS gives access to brain metabolites such as choline, lactate, N-acetyl aspartate and taurine. Its use is more recent than the phosphorous spectroscopy but first results already show its potential in neonatology.

Asphyxia Neonatorum

[Cognitive evoked potentials in children: normal and abnormal development].

The first part of this review on event-related potentials (ERPs) in children summarizes the role of ERPs in the study of normal cognitive development. The ERPs vary both as a function of the age of the child and also as a function of the cognitive processes that are required by the tasks. Topographical studies allow one to identify cortical regions involved in specific cognitive processes, and monitor their age-related changes. The second part of this paper reviews two examples of abnormal cognitive development (attention deficit hyperactivity disorder and childhood autism) where the ERPs allow a better understanding of the dysfunction underlying the observed cognitive disorders.

Adolescent

Concurrent changes in intracranial pressure, cerebral blood flow velocity, and brain energy metabolism in rabbits with acute intracranial hypertension.

The relationship between intracranial pressure or cerebral perfusion pressure (CPP), cerebral blood flow, and brain energy failure is unpredictable throughout the development of acute intracranial hypertension. The purpose of the present study was to correlate intracranial pressure with cerebral blood flow velocities and brain energy metabolism in adult rabbits. The acute intracranial hypertension was achieved by pressure transmission. Transcranial Doppler wave-forms were obtained from the basilar artery for monitoring cerebral blood flow velocities. 31P-Magnetic resonance spectroscopy was used to assess brain energy metabolism. The diastolic blood flow velocity began to decrease significantly (34.5%) when the intracranial pressure was equal to half the diastolic arterial pressure for a CPP of 36 +/- 18 mmHg. Circulatory cerebral resistances increased significantly (55%) for the same value of CPP. Diastolic frequency was near zero when intracranial pressure approached diastolic arterial pressure (51 +/- 12 mmHg), corresponding to a CPP of 30 +/- 15 mmHg. At the same time, only a tendency for brain energy metabolism to decrease was observed. Consequently, transcranial Doppler sonography could be proposed for the follow-up of intracranial hypertension. Magnetic resonance spectroscopy could help to monitor these patients and could be especially proposed in case of high intracranial pressure (near diastolic arterial pressure). The joint use of these two methods would help in making appropriate therapeutic decision in humans.

Animals