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Biomedical subjects

D Lamotte

Publications and source records attributed to D Lamotte.

18 recordsLinked to original sources

[Efficacy of intrathecal baclofen in the treatment of spasticity in stroke].

OBJECTIVE: To determine whether intrathecal administration of baclofen reduced spastic hypertonia in a hemiplegic patient after hemorrhagic stroke. METHODS: A trial of intrathecal administration of baclofen was carried out with bolus injections of 50 and 75 microg baclofen and clinical and functional evaluation (Aschworth, articular amplitude) before and after injection in a patient with hemorrhagic stroke. After these trials, the placement of a pump was proposed to the patient. RESULTS: Aschworth score improved from 4 to 3 on triceps, quadriceps and adductus, with functional improvement of gait quality and perimeter and position in the wheelchair. Cephalgia, present before the treatment, increased after the implantation of the pump. The patient had some ejaculation trouble with the treatment, as well as some neurological pains after the pump implantation but experienced no effect on upper limbs. DISCUSSION: The intrathecal administration of baclofen has been used in some studies of hemiplegic patients, with reduced spasticity and improved the kinematic parameters of gait. The intrathecal baclofen administration could complement other treatment to control spasticity after stroke. CONCLUSION: Intrathecal baclofen administration could be an interesting complementary therapeutic among patients with important spasticity not controlled by the usual treatments.

Baclofen↗

[Strength, postural and gait changes following rehabilitation in multiple sclerosis: a preliminary study].

OBJECTIVE: To evaluate the impact of rehabilitation on balance, gait and strength in inpatients with multiple sclerosis (MS). METHODS: Twenty-one in patients with MS benefited from a program of rehabilitation with evaluation before and after rehabilitation. Balance was assessed by stabilometry, walking speed with use of a locometer device and maximal peak torque of knee extensor and flexor with use of an isokinetic dynamometer at 60 degrees /s speed. The functional independence measure (FIM) was also applied before and after rehabilitation. RESULTS: After rehabilitation, patients showed significant improvement in balance with opened and closed eyes, velocity gait, strength of the lower quadriceps and the higher hamstrings and FIM values. Absolute values of gait speed and strength parameters were related as were improvement in velocity speed and the higher hamstrings. CONCLUSION: The results are encouraging and confirm the interest and tolerance of a program of rehabilitation among patients with MS.

Adult↗

Motor determinants of gait in 100 ambulatory patients with multiple sclerosis.

A prospective analysis of gait and strength parameters was performed in 100 patients diagnosed with MS and pyramidal involvement admitted in a rehabilitation unit The patients were divided into two groups based on their ability to walk in daily life (nonassisted or cane-assisted gait) and into four clinical subgroups depending on associated involvements such as sensory loss or cerebellar ataxia. Twenty healthy subjects were studied as a control group. Gait parameters were evaluated with a Locometre and muscle strength with an isokinetic dynamometer. The results showed that the average velocity and strength of the hamstring and quadriceps were strongly correlated and reduced in the MS group in comparison with the control, and in the cane-assisted group compared with the nonassisted group. Gait velocity tended to be more correlated to hamstring strength in the nonassisted group with a determination coefficient (r2) reaching a value of 0.44 in the sensory subgroup. These findings provide evidence that a correlation between strength reduction and gait impairment is obvious whatever the clinical form in patients with MS. This correlation is higher with hamstrings but may change depending on the disability level and the clinical form. This could be taken into account in the individual assessment of further rehabilitation programmes.

Activities of Daily Living↗

[Relationship between gait speed and strength parameters in multiple sclerosis].

INTRODUCTION: Recent studies have focused on correlation between strength and gait parameters in hemiplegia, suggesting the interest for strength training in patients with central nervous system lesions. The aim of this study was to evaluate this correlation in multiple sclerosis (MS) patients with special regard to the different clinical forms including proprioceptive loss or cerebellar ataxia. PATIENTS AND METHOD: Gait speed and muscular function were performed in 27 patients with moderate affected gait (EDDS < 6). Gait speed was evaluated with Locometre and peak-torques of quadriceps and hamstrings were evaluated with isokinetic dynamometer. Patients were separated in three groups related to their deficiency: spastic group (8 patients), spastic with proprioceptive loss (12 patients) and spastic with cerebellar ataxia (7 patients). Gait parameters were evaluated in 10 healthy subjects as control group. RESULTS: Gait speeds (spontaneous and maximal) and peak torques of quadriceps and hamstring were similar in the three groups. In the whole patients group, gait speed was reduced and related to hamstring peak torque (r = 0.56 at spontaneous speed and 0.51 at high speed) but not with quadriceps peak torque. Patients with proprioceptive loss exhibited not only a higher correlation between gait speed and hamstring torque (r = 0.76 and 0.65 respectively) than other patients but also with quadriceps torque (r = 0.66 and 0.59 respectively) when patients in other groups did not. CONCLUSION: As it was previously pointed out in hemiplegic patients, MS patients exhibit some correlation between gait speed and muscle strength, mainly with hamstrings. These correlations can change in special sensory conditions suggesting that patients with sensory loss use different muscular strategies to maintain gait speed. Strength training may therefore be discussed in MS including specific modalities as a function of clinical parameters.

Biomechanical Phenomena↗

[Multiple sclerosis and botulinum toxin].

INTRODUCTION: The aim of this work was to collect litterature datas to have an indication of botulinum toxin in multiple sclerosis disease. METHOD: The international literature relating the years 1982-2002 was carried out with the Medline data bank. The article presenting of the controlled studies were mainly retained. RESULTS: Thirty-seven articles were indexed, 6 were retained according to our criteria. The selected articles show mainly a use of botulinum toxin in the spasticity. The principal criteria of evaluation were the muscular tone, the spasms, the pain, the or passive amplitude of joint. Two articles report the effectiveness of toxin injection in acquired nystagmus and the paralysis of a vocal fold. DISCUSSION: This review shows that the principal indication of toxin in multiple sclerosis is spasticity with a good effectiveness of the treatment. However controlled-placebo studies among these patients are still very few. The side effects are rare but sometimes appearance of muscular weakness always making discuss the existence of a push. It is necessary to take account of these effects and their consequences before proposing the treatment. CONCLUSION: Botulinum toxin has an indication in the treatment of spasticity of patients with multiple sclerosis. However more studies are necessary with more sits of injection to fix the good indications.

Anti-Dyskinesia Agents↗

Protein delivery by Pseudomonas type III secretion system: Ex vivo complementation of p67(phox)-deficient chronic granulomatous disease.

Bacterial type III secretion system drives the translocation of virulence factors into the cystosol of host target cells. In phagocytes and in Epstein-Barr virus immortalized B lymphocytes, NADPH oxidase generates O(-2) through an electron transfer chain the activity of which depends on the assembly of three, p67(phox), p47(phox) and p40(phox) cytosolic activating factors with Rac 1/2 and a membrane redox component, cytochrome b(558). In p67(phox) deficient chronic granulomatous disease (CGD) patients, p67-phox is missing and NADPH oxidase activity is abolished. ExoS is a virulence factor of Pseudomonas aeruginosa which is secreted via the type III secretion system: it was fused with p67(phox). Pseudomonas aeruginosa synthesized and translocated the hybrid ExoS-p67(phox) fusion protein into the cytosol of B lymphocytes via the type III secretion system. Purified ExoS-p67(phox) hybrid protein was as efficient as normal recombinant p67(phox) in cell-free reconstitution of NADPH oxidase activity. Therefore, ExoS-p67(phox) was transferred via the type III secretion system of Pseudomonas aeruginosa into the cytosol of B lymphocytes from a p67(phox)-deficient CGD patient and functionally reconstituted NADPH oxidase activity. In the complementation process, ExoS acted as a molecular courier for protein delivery: the reconstitution of an active NADPH oxidase complex suggests type III secretion system to be a new approach for cellular therapy.

B-Lymphocytes↗

A new Chinese hamster ovary cell line expressing alpha2,6-sialyltransferase used as universal host for the production of human-like sialylated recombinant glycoproteins.

Chinese hamster ovary (CHO) cells are widely employed to produce glycosylated recombinant proteins. Our group as well as others have demonstrated that the sialylation defect of CHO cells can be corrected by transfecting the alpha2,6-sialyltransferase (alpha2,6-ST) cDNA. Glycoproteins produced by such CHO cells display both alpha2,6- and alpha2,3-linked terminal sialic acid residues, similar to human glycoproteins. Here, we have established a CHO cell line stably expressing alpha2,6-ST, providing a universal host for further transfections of human genes. Several relevant parameters of the universal host cell line were studied, demonstrating that the alpha2,6-ST transgene was stably integrated into the CHO cell genome, that transgene expression was stable in the absence of selective pressure, that the recombinant sialyltransferase was correctly localized in the Golgi and, finally, that the bioreactor growth parameters of the universal host were comparable to those of the parental cell line. A second step consisted in the stable transfection into the universal host of cDNAs for human glycoproteins of therapeutic interest, i.e. interferon-gamma and the tissue inhibitor of metalloproteinases-1. Interferon-gamma purified from the universal host carried 40.4% alpha2,6- and 59.6% alpha2,3-sialic acid residues and showed improved pharmacokinetics in clearance studies when compared to interferon-gamma produced by normal CHO cells.

Animals↗

[Immunotargeting of tumors: state of the art and prospects in 2000].

Following 15 years of experimental studies, tumor immunotargeting using monoclonal antibodies directed against tumor associated antigens shows now important monoclonal antibodies directed against tumor associated antigens shows now important clinical developments. This is mainly due to encouraging therapeutic results which have obtained using humanized antibodies such as the anti-CD20 rituximab in follicular B lymphomas and the anti-DrbB2 herceptin in breast carcinomas. Thanks to genetic engineering it is possible to graft variable or hypervariable regions from murine antibodies to human IgG, and even to obtain fully human antibodies by using either transgenic mice containing a large part of the human repertoire of human IgG, or selection of human antibody fragments expressed by phages. Radiolabeling of antibodies played a major role to demonstrate the tumor immunotargeting specificity and remains attractive for the diagnosis by immunoscintigraphy as well as for the treatment by radioimmunotherapy of some cancers. In this review, the current results and the prospects of diagnostic and therapeutic uses of anti-tumor antibodies and their fragments will be described. Concerning diagnosis, 123-iodine or 99m-technetium labeled Fab fragments allowed very demonstrative tumor images but this technique has a limited effect upon the therapeutic attitude. Immuno-PET (positron emission tomography) could enhance the sensitivity of this imaging method. Radio-immunoguided surgery and immunophotodetection are attractive techniques still under evaluation. Concerning therapy, 131-iodine labeled anti-CD20 antibodies gave spectacular results in non-Hodgkin's B lymphomas. In solid tumors which as less radiosensitive, radioimmunotherapy could concern small tumors and need the use of two-steps targeting and/or alpha emitters radioisotopes. Some other strategies will be described such as bispecific antibodies directed against tumors and immune effector cells, some antibody fragments expressed on T cells called T-bodies or some biological studies using intrabodies. Published data and works in progress demonstrate that immunotargeting of tumors will have a growing place in the treatments of cancer patients.

Animals↗

Effect of spinal cord stimulation on regional myocardial perfusion assessed by positron emission tomography.

Spinal cord stimulation (SCS) can relieve symptoms in patients with severe angina pectoris refractory to conventional medical or surgical therapy. This symptomatic improvement may result from decreased myocardial ischemia. To test this hypothesis, positron emission tomography (PET) and potassium-38 as a flow tracer were used in 8 patients for the quantitative evaluation of regional myocardial perfusion at rest and after exercise, before and during SCS. Potassium uptake was evaluated as myocardial clearance (flow times net extraction) in ml/min/100 g. Tomographic segments were categorized as nonaffected and affected on the basis of the absence or presence of arterial stenosis on coronary angiography and on the basis of thallium scintigraphic data. In nonaffected segments, before SCS, regional myocardial clearance significantly increased from rest (28 +/- 4) to exercise (47 +/- 13 clearance units; p less than 0.004). A similar increase occurred after SCS. In affected segments, before SCS, regional myocardial clearance barely increased (p = 0.065) from rest (26 +/- 6) to exercise (33 less than or equal to 12). In comparison, after SCS, the resting regional myocardial clearance was slightly elevated (29 +/- 8) reflecting an increased double product, but did not increase (p = 0.192) with exercise (34 +/- 12). However, the magnitude and duration of ST-segment depression decreased during treatment with SCS. Anginal pain occurred in all patients during control exercise, but was attenuated in all but one with SCS. These results indicate that SCS improves exercise-induced angina and electrocardiographic signs of ischemia but this influence does not appear to be mediated by changes in regional myocardial perfusion.

Aged↗

[Methods and clinical applications of positron emission tomography in endocrinology].

Positron emission tomography (PET) allows to detect in coincidence photons issued from annihilation between positrons and electrons nearby situated. Tomographic detection (plane by plane) and tomographic reconstruction will lead to the quantitation of radioactive distribution per voxel, in the organ of interest. Recent tomographs can acquire simultaneously several transaxial slices, with a high sensitivity and a spatial resolution of 3-5 mm. Commonly used positron emitters have a short half-life: 2, 10, 20 and 110 min for 150, 13N, 11C and 18F, respectively. The use of these isotopes requires on line production of radionuclides and synthesis of selected molecules. In endocrinology, PET allows among others to study noninvasively the receptor density of hormone-dependent neoplasms such as breast, uterus, prostate tumors and prolactinomas. These last tumors represent a particular entity because of several combined characteristics: high turnover rate of amino acids, high density of dopaminergic receptors and response to bromocriptine (analogue of dopamine inhibiting the secretion of prolactin) in relation to the level of receptors. Because PET permits to evaluate the density of dopaminergic receptors and the metabolism of amino acids, theoretical response of the prolactinoma to bromocriptine can be predicted, the achieved therapeutic efficacy can be estimated and the long-term follow up of tumor growth can be assessed. This example illustrates the clinical value of PET in endocrinology.

Breast Neoplasms↗

Plasmodium falciparum growth inhibition by human platelets in vitro.

Platelets take an active part in immunological processes as well as in haemostasis, especially in the host-parasite relationship. Our aim is to assess the growth of Plasmodium falciparum, cultured in human erythrocytes in the presence of fresh washed human platelets, since thrombocytopaenia is frequently observed during malarial infections. Our results show that platelets induce a dose-related growth inhibition of P. falciparum. Both proliferation and maturation of intraerythrocytic stages of the parasite are inhibited. This growth inhibition is triggered by the parasite itself as neither specific antibodies nor any other components are needed to activate platelets. Activated platelets are directly toxic since complement is not involved. Furthermore, inhibition is not mediated by erythrocyte lysis or by toxic oxygen metabolites. Platelets induce an inhibition of P. falciparum growth, at least in vitro, although the importance of their role played in vivo in malarial immunity has yet to be evaluated.

Animals↗

[Regional blood flow and oxygen consumption in the leg muscles of normal subjects and in those with arterial insufficiency. Study of the distribution of C15O2 and of 15O2 using positron emission tomography].

We first studied the distribution of radioactivity during continuous inhalation of C15O2 and 15O2 in traverse tomograms of the greatest diameter of legs, at rest and immediately after exercise (ankle flexions). C15O2 and 15O2 were distributed homogeneously and symmetrically in both legs of normal subjects at rest. The activity accumulated in the anterolateral region after exercise. In patients, this pattern of distribution was similar but asymmetrical, depending on the arterial pathology. No systematic distribution of either C15O2 or 15O2 was observed. In a second step, we studied quantitatively blood flow (F), oxygen uptake (R) and oxygen extraction (E) in 11 subjects: 5 normals (23 +/- 1 years) and 6 patients (60 +/- 11 years) suffering from unilateral intermittent claudication. We used the bolus inhalation technique of C15O2 and 15O2. In the normal leg at rest, ranges were 2.5 to 8.0 ml/min.hg for F, 0.9 to 21.3 mumol/min.hg for R and 3.6 to 33.4% for E. In the pathological leg at rest, ranges were 3.7 to 11.3 ml/min.hg for F, 3.8 to 10.6 mumol/min.hg for R and 7.1 to 24.5% for E. After exercise, ranges were 6.4 to 62.8 ml/min.hg for F, 66.0 to 386.3 mumol/min.hg for R and 29.2 to 89.5% for E in both legs. There was no straight difference between normal and pathological legs soon after exercise. This study allows us to expect that the demonstration of such a difference implies a longer delay of data acquisition following the slow post-ischemia recovery.

Adult↗

Myocardial blood flow and glucose uptake after myocardial infarction.

Position emission tomography can picture the distribution of flow tracers as well as of metabolic substrates or analogs. Studies of the distribution of these tracers allow to infer information about regional myocardial clearance (flow X extraction) and substrate utilization. In a study of 32 patients after myocardial infarction, we have contrasted flow and substrate utilization to demonstrate ischemic but viable myocardium in the arterial territory of the infarct in a number of patients also specially after fibrinolytic reperfusion. Restoration of blood flow to the ischemic but viable myocardium through coronary bypass or dilatation improves flow from 56.3% to 84.2% of control and restores substrate utilization. In another group of 32 patients studied with the Strontium-82/Rubidium-82 generator, we have demonstrated perfusion changes both in the myocardial infarct area and at a distance. These changes predominate in patients with multiple vessel disease. Combined PET studies of flow and substrate utilization are new tools to study early intervention after myocardial infarction and to document the benefits of revascularization.

Aged↗

[Study of cerebral metabolism and blood flow in partial complex epilepsy and status epilepticus in man using positron emission tomography].

Positron Emission Tomography (PET) with the oxygen-15 steady state inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen consumption (CMRO2) and oxygen extraction ratio (OER) in 25 patients with partial complex seizures during the interictal state, in 1 patient with recurrent temporal seizures and in 3 patients whose EEGs were characterized by periodic lateralized epileptiform discharges (PLEDs). Interictal scans showed temporal zone(s) of hypoperfusion and hypometabolism in 80% of patients with normal X-ray CT Scan. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the EEG abnormalities. Comparison of the different values of CBF, CMRO2 and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease in OER, the latter was always the most prominent in the region of the focus determined by serial EEG recordings. The observed imbalance between blood flow and oxidative glucose metabolism could suggest an impairment of O2 utilization by the mitochondria in the epilepticus focus during seizures or status epilepticus.

Brain↗

Regional cerebral blood flow and metabolic rates in human focal epilepsy and status epilepticus.

Positron emission tomography with the oxygen-15 steady state or bolus inhalation technique was used to provide quantitative values of regional cerebral blood flow (CBF), oxygen extraction ratio (OER) and oxygen consumption (CMRO2) in 25 patients with partial complex seizures during the interictal state and in 5 patients during status epilepticus. Glucose utilization (CMRglu) was also studied in one case of status epilepticus with the 18F-fluorodeoxyglucose technique (18FDG). Interictal scans showed zone(s) of hypoperfusion and hypometabolism without significant variation of the OER in approximately 80% of patients. In 62%, there was a strong correlation between the overall EEG localization and the area(s) of hypoperfusion and hypometabolism. In all cases, ictal scans revealed a focal or multifocal increase in CBF and CMRO2. The localization of the most affected regions correlated well with the spatial distribution of the electroencephalograph (EEG) abnormalities. Comparison of the different values of CBF, CMRO2, and OER showed that the increase in perfusion always exceeded that of oxygen consumption and hence was accompanied by a significant decrease of OER; the latter was always the most prominent in the region of the epilepticus focus determined by serial EEG recordings. These results showed that the supply of oxygen by blood flow is large enough to meet metabolic demand. When comparing these values with CMRglu, it appeared that the relative changes in CMRglu and CBF were very similar, indicating that the increase in blood flow correlated with the enhancement in glucose utilization. The observed imbalance between blood flow, glucose utilization, and oxygen consumption could suggest that an impairment of oxygen utilization by the mitochondria could occur in the epileptic focus during prolonged status epilepticus.

Cerebrovascular Circulation↗

[Positron tomographic study of the behavior of 13N-labeled nitrous oxide in the human brain].

The synthesis of 13N-labelled nitrous oxide was made following NICKLES' method. After a partial denitrogenisation by breathing pure oxygen for 3 min, the subject inhaled a bolus of 13N-labelled nitrous oxide diluted in 2 l of oxygen (a mixture of 5% 13N2O and 95% O2). After an apnea of 30 sec the subject began to breathe in a closed respiratory system containing a mixture of 10% N2O and 90% O2. Eight images of the brain taken at level OM + 3 in 4 subjects showed an important uptake in the cerebellum and in the frontal and temporal cortex. Six min after inhalation of the bolus, the radioactivity in the cerebellum showed a clear decrease, whereas little decrease was observed in the frontal cortex and only a slight decrease in the temporal cortex. In order to suppress the activity due to the vascular comportment, an experiment was performed under the same conditions as the previous one, but using sodium pyrophosphate containing tin and 25 mCi of Tc-99m pertechnetate. The correction factors vary from 0.394 to 0.894 depending on the R.O.I. The activity curves after correction showed a predominance in the frontal cortex. It can therefore be concluded that some specific zones of the brain are receptive to N2O and in particular the frontal cortex. These results were compared with the data obtained from the electrophysiological recording of the frontal region of the brain (C.N.V.: Contingent Negative Variation).

Adult↗

Effect of exercise on the leg distribution of C15O2 and 15O2 in normals and in patients with peripheral ischemia: a study using positron tomography.

In order to evaluate regional muscle blood flow and oxygen utilization, we study with positron emission tomography (PET) the distribution of C15O2 and 15O2 in 17 subjects: 5 normals (24 +/- 3 years) and 12 patients (63 +/- 13.5 years). C15O2 and 15O2 are inhalated with a steady-state technique. Positron tomograms are recorded in supine position at the greatest diameter of the leg. Exercise consists in simultaneous ankle flexions. In all normals, C15O2 and 15O2 are distributed homogeneously and symmetrically in both legs. At rest, they concentrate in the region of vascular pedicle. After exercise, C15O2 and 15O2 are electively distributed in the anterolateral region of the leg. In patients, this pattern of distribution is similar but asymmetrical. Moreover, the regional uptake of C15O2 and 15O2 often dissociates. In conclusion, C15O2 and 15O2 allow to study repeatedly muscle blood flow and oxygen utilization in patients with peripheral ischemia, both at rest and after exercise. The broad spectrum of pathological changes observed in this study needs further metabolic investigations.

Adult↗