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P Menei

Publications and source records attributed to P Menei.

At least 19 recordsLinked to original sources
PubMed2006

Development and characterization of interleukin-18-loaded biodegradable microspheres.

Immunostimulation represents a promising approach designed to specifically eradicate malignant cells. Since glioma tumour cells hole up in the central nervous system (CNS) in a particularly inauspicious milieu to antitumour immune reactions we here propose a new strategy to revert the properties of this microenvironment by administering an antitumour cytokine into the CNS tumour itself. Thus, biodegradable poly(D,L-lactide-co-glycolide) (PLGA) sustained-release microspheres for stereotaxic implantation loaded with interleukin-18 (IL-18), that is known to exert antitumour activity and trigger immune cell-mediated cytotoxicity, were developed. Different tests for assessing IL-18 bioactivity were set-up and evaluated. A specific bioassay was considered as the most reliable test. The stability and integrity of IL-18 was then verified during the encapsulation process. Consequently, two procedures of IL-18 encapsulation in PLGA microparticles (W/O/W and S/O/W) were investigated. As determined by radiolabelling studies using 125I-IL-18 and a continuous flow system, the in vitro release profile of IL-18 was optimum with S/O/W method with a moderate burst effect and a subsequent progressive discharge of 16.5+/-8.4 ng/day during the next 21 days against 6.1+/-4.2 ng/day with the W/O/W method. Considering analytical testing of IL-18 together with its preserved biological activity after release from microspheres, amounts of the active cytokine obtained with S/O/W method were relevant to plan in vivo evaluation to validate the therapeutic strategy.

Absorbable Implants↗
PubMed2006

In vitro investigation of lipid implants as a controlled release system for interleukin-18.

Operating on the inductive and effective phases of an anti-tumor immune response and uncovering pivotal functions that may reduce cancer cell growth, interleukin-18 (IL-18) appears to be an attractive candidate for the sustained local adjuvant immunotherapeutic treatment of brain gliomas. The objective of this work was to develop IL-18 loaded lipid implants as a controlled delivery system. For the preparation of protein loaded triglyceride matrix material, a solid-in-oil (s/o) dispersion technique was chosen for which protein particles in the micrometer range were first prepared by co-lyophilization with polyethylene glycol (PEG). Implants of 1 mm diameter, 1.8 mm height and 1.8 mg weight were manufactured by compression of the powder mixture in a specially designed powder compacting tool. The in vitro release behavior of 125I-Bolton-Hunter-radiolabeled IL-18 was assessed in a continuous-flow system. A cell culture assay was established for the determination of bioactivity of released IL-18. Implants showed a continuous release of 10-100 ng IL-18 per day for 12 days. A progressive integrity loss was observed with ongoing release, which would be related to protein degradation during incubation. The initially released fraction proved complete retention of bioactivity, indicating that the manufacturing procedure had no detrimental effects on protein stability.

Animals↗
PubMed2006

Sleep-disordered breathing in patients with Chiari malformation: improvement after surgery.

Sixteen consecutive patients with Arnold-Chiari malformation type I and syringomyelia underwent full-night polysomnography (PSG). Sleep apnea syndrome (apnea-hypopnea index > 10) was diagnosed in 12 of 16 patients with 48% of central apneas. In six patients with sleep apnea syndrome, PSG was repeated an average of 203 days after decompression surgery. Postoperative PSG showed a decrease in the central apnea index from 14.9 +/- 5.5 to 1.3 +/- 0.6 (p = 0.03).

Adolescent↗
PubMed2005

Development of new polymer-based particulate systems for anti-glioma vaccination.

Biodegradable and biocompatible microspheres represent a promising alternative to conventional adjuvants for anti-tumour vaccination. Focusing on glioma, we developed two poly(D,L-lactide-co-glycolide) (PLGA)-based particulate systems presenting tumour antigens associated with plasma membranes or with cell lysates. Glioma cell fractions were prepared for adsorption onto poly-D-lysine (PDL)-coated PLGA microspheres formulated using a double-emulsion procedure. Adsorption was followed by (125)I-radiolabelling, Western blot and confocal laser scanning microscopy. Only a panel (34%) of the proteins isolated from both cell fractions adsorbed onto PDL-coated PLGA microspheres. The integrity of the epitopes after loading was preserved, as shown by identification of plasma membrane and cytoplasmic markers. Finally, one of the major potential advantages of those particulate systems resides in the fact they not only serve as injectable adjuvant matrices presenting tumour antigens to antigen presenting cells, but also as potential reservoirs for controlled delivery of active immunostimulant molecules.

Animals↗
PubMed2005

[Botulinum toxin injections and hypertonic upper limbs. Which functional results?].

OBJECTIVES: To assess the efficacy of botulinum toxin injections for hypertonic upper limbs in patients with residual motricity that allows a functional use of the hand. METHODS: Patients were seen between February 2000 and November 2002, before and after botulinum toxin injections for hypertonic upper limbs due to upper motor neuron syndrome. All patients had voluntary motricity in fingers and wrist extensors. Impairment (range of motion, spasticity [Ashworth's scale]), pain (10 centimeters visual analog scale) prehension (400-point measure) and patients' satisfaction were recorded. Two or three functional goals were predefined. Patients were injected after locating the target area with neurostimulation. The aim of the injections was functional improvement. RESULTS: Eight patients were included. After injections, mean pain score decreased by 3.4 points; mean spasticity decreased by 1.0; and prehension improved, especially for bimanual functions. Three-quarters of the functional goals were reached. Optimal efficacy required repeated injections, with modification of muscle targets and doses. CONCLUSION: Botulinum toxin injection is efficient for impairment, pain and prehension in hypertonic upper limbs, even if the hypertonic hand is still the "nondominant" hand. Motricity in antagonist muscles is essential for functional improvement, and the assessment must include bimanual tasks. Intrinsic as well as extrinsic muscles must be injected and a neurostimulator used for forearm muscles. Comparative studies are required to define more clearly the place of this treatment among medical and surgical treatments of spasticity.

Adolescent↗
PubMed2005

Pharmacologically active microcarriers: a tool for cell therapy.

To overcome certain problems encountered in cell therapy, particularly cell survival, lack of cell differentiation and integration in the host tissue, we developed pharmacologically active microcarriers (PAM). These biodegradable particles made with poly(D,L-lactic-co-glycolic acid) (PLGA) and coated with adhesion molecules may serve as a support for cell culture and may be used as cell carriers presenting a controlled delivery of active protein. They can thus support the survival and differentiation of the transported cells as well as their microenvironment. To develop this tool, nerve growth factor (NGF)-releasing PAM, conveying PC12 cells, were produced and characterized. Indeed, these cells have the ability to differentiate into sympathetic-like neurons after adhering to a substrate, in the presence of NGF, and can then release large amounts of dopamine. Certain parameters such as the size of the microcarriers, the conditions enabling the coating of the microparticles and the subsequent adhesion of cells were thus studied to produce optimized PAM.

Animals↗
PubMed2005

Combining polymeric devices and stem cells for the treatment of neurological disorders: a promising therapeutic approach.

Cell therapy will probably become a major therapeutic strategy for neuronal disorders in the coming years. Nevertheless, due to poor survival of grafted cells and limited differentiation and integration in the host tissue, certain ameliorations must be envisaged. To address these difficulties, several strategies have been developed and among them, two methods seem particularly promising : in situ controlled drug delivery and implantation of cells adhered on biomaterial-based scaffolds. Indeed, the ability of drugs, such as growth factors, to regulate neuronal survival and/or plasticity infers the use of these molecules to treat neurodegeneration associated with human diseases. Moreover, the synthesis of cell scaffolds which mimic the extra-cellular matrix can help guide morphogenesis and tissue repair. Furthermore, cells can be cultivated on these matrices that may eventually make graft therapy a more practical approach for the treatment of neurological diseases. Nevertheless, for those two encouraging approaches multiple parameters have to be considered, such as the drug targeting strategy, but also the physical and morphological characteristics of the scaffold and the type of cells to be conveyed. This review thus focuses on those two promising strategies and also on their possible association to improve stem cell therapy of neurodegenerative disorders. Indeed, tissue replacement by grafting cells within or adhered onto drug delivering biomaterial-based devices, has recently been reported and seems to be very promising.

Animals↗
PubMed2004

Characterization and detection of experimental rat gliomas using magnetic resonance imaging.

Two different experimental rat brain tumours (F98 glioma and 9L glioma) were characterized using T1 and T2, apparent diffusion coefficient (ADC) and magnetization transfer ratio (MTR). Even though both tumours appeared homogenous at the early stage of growth, significant differences were measured for all parametric images between tumours and normal brain tissue. Irrespective of the sequence used, tumour lesion/normal parenchyma contrast for the non-infiltrative 9L was twice that of the infiltrative F98 glioma. The use of spin preparation via an inversion pulse in a fast spin echo sequence increases contrast by a factor of 20-30.

Animals↗
PubMed2004

Pitfalls in the detection of lipid vectors in neural cell culture and in brain tissue.

Lipid particles (liposomes and lipid-coated microbubbles) are currently studied as vectors for drug delivery to the central nervous system. The visualization of these particles is usually based on their labeling with a lipophilic fluorescent dye (3,3'-dioctadecycloxacarbocyanine perchlorate) or staining with Oil Red O. The purpose of this article was to highlight the difficulties and pitfalls encountered with the use of these techniques in the detection of lipid particles in neural cell cultures and in brain tissue. In vitro and in vivo studies were conducted on different neural cell cultures (rat and human tumors, microglial cells) and animal models of brain lesion (lipopolysaccharide and quinolinic acid-induced lesion, induced brain tumor). The cells or brain slices were observed with optical microscopy after staining with Oil Red O, fluorescent microscopy, or scanning electron microscopy. Intra and extracytoplasmic lipid particles (stained with Oil Red O or autofluorescent or visualized by scanning electron microscopy) were naturally found in the cells and tissues studied. Intracytoplasmic lipid microparticles were present in tumoral and microglial cells. These lipid microparticles were also observed with some extracytoplasmic lipid droplets in the induced brain lesions. These images could be misinterpreted as lipid vectors if the cells or animals would have been treated with such a vector.

Animals↗
PubMed2004

Mutations within the MGC4607 gene cause cerebral cavernous malformations.

Cerebral cavernous malformations (CCM) are hamartomatous vascular malformations characterized by abnormally enlarged capillary cavities without intervening brain parenchyma. They cause seizures and focal neurological deficits due to cerebral hemorrhages. CCM loci have already been assigned to chromosomes 7q (CCM1), 7p (CCM2), and 3q (CCM3) and have been identified in 40%, 20%, and 40%, respectively, of families with CCM. Loss-of-function mutations have been identified in CCM1/KRIT1, the sole CCM gene identified to date. We report here the identification of MGC4607 as the CCM2 gene. We first reduced the size of the CCM2 interval from 22 cM to 7.5 cM by genetic linkage analysis. We then hypothesized that large deletions might be involved in the disorder, as already reported in other hamartomatous conditions, such as tuberous sclerosis or neurofibromatosis. We performed a high-density microsatellite genotyping of this 7.5-cM interval to search for putative null alleles in 30 unrelated families, and we identified, in 2 unrelated families, null alleles that were the result of deletions within a 350-kb interval flanked by markers D7S478 and D7S621. Additional microsatellite and single-nucleotide polymorphism genotyping showed that these two distinct deletions overlapped and that both of the two deleted the first exon of MGC4607, a known gene of unknown function. In both families, one of the two MGC4607 transcripts was not detected. We then identified eight additional point mutations within MGC4607 in eight of the remaining families. One of them led to the alteration of the initiation codon and five of them to a premature termination codon, including one nonsense, one frameshift, and three splice-site mutations. All these mutations cosegregated with the disease in the families and were not observed in 192 control chromosomes. MGC4607 is so far unrelated to any known gene family. Its implication in CCMs strongly suggests that it is a new player in vascular morphogenesis.

Female↗
PubMed2004

[French neurosurgical practice in Neuro-Oncology (national survey--part I)].

OBJECTIVE: The aim of this work is to summarize the elements of the "Cancer Plan" applicable to neurosurgical practice, and to give the results of a national inquiry concerning the daily practice of Neuro-Oncology from the neurosurgical point of view. METHOD: The Neuro-Oncology Group of the French Society of Neurosurgery has submitted a questionnaire to every department of Neurosurgery in France. RESULTS: The response rate of the public centers was 96.5%. Moreover, responses were available from 7 private centers. The results are detailed in the text. CONCLUSION: This national survey highlights the interest and implication of French neurosurgeons in the field of Neuro-Oncology. But also, to be in accordance with the guidelines for good clinical practice, the importance of developing official neuro-oncological networks in order to offer the best access to clinical and fundamental data and hence optimise patient's care. The publication of the "Cancer Plan", the creation of a National Neuro-Oncology Group, and the results of this survey (actual multidisciplinary approach, better information and transparency, individualized care of the patients), are in the line with updating our daily practice, even though discrepancies remain among centers. French neurosurgeons must continue along the same path, but at the same time there is a need for additional help to definitely reach a truly, and homogeneous, optimized care of neuro-oncological patients.

France↗
PubMed2004

Treatment of spasticity with intrathecal Baclofen administration: long-term follow-up, review of 40 patients.

STUDY DESIGN: Case series of a consecutive sample. Retrospective audit. OBJECTIVE: To analyze the long-term safety and efficacy of intrathecal baclofen (ITB), and technical incidents. SETTING: Neurosurgical and Physical Medicine Departments of two university hospitals in western France. METHODS: The medical records of 40 patients who underwent ITB pump placement for the treatment of severe chronic spasticity were reviewed. Patients were eligible independently of the origin of the spasticity (spinal cord origin 33, brain damage 8). They underwent a final assessment with clinical examination and questionnaire in 2001. Ashworth scale scores were assessed, patient satisfaction was rated on a visual analog scale (VAS), functional independence before and after treatment was classified as bed-ridden, wheelchair dependent or ambulant, and the frequency and nature of complications were noted. RESULTS: The average follow-up period was of 4 years. The average Ashworth score at the final assessment was 1.8+/-0.6. Average patients satisfaction was 7.4/10+/-2.21 on VAS. In all, 85% would have undergone the procedure again if they had to make the decision. In 85% of the cases the ambulation status was unchanged. Technical incidents occurred at least once in 37% of the patients (due to the catheter in 58% and to the pump in 42%). They included catheter disconnections (4), migration (4), kinks (3), obstruction (3), development of fibrosis (3), disconnection of pump reservoir (2), porosity of pump membrane (2), unexplained pump dysfunction (4) leakage, and subcutaneous collection (5). Severe pharmacological side effects requiring transfer to intensive care unit occurred in 12% of cases, 80% of which were directly related to pump refill procedures. CONCLUSION: ITB remained effective in the long term and patients were satisfied. Nevertheless, complications were frequent, involving mainly the catheters, which would require further technical improvements.

Adult↗
PubMed2004

In vivo evaluation of pharmacologically active microcarriers releasing nerve growth factor and conveying PC12 cells.

Cell therapy will probably become a major therapeutic strategy in the coming years. Nevertheless, few cells survive transplantation when employed as a treatment for neuronal disorders. To address this problem, we have developed a new tool, the pharmacologically active microcarriers (PAM). PAM are biocompatible and biodegradable microparticles coated with cell adhesion molecules, conveying cells on their surface and presenting a controlled delivery of growth factor. Thus, the combined effect of growth factor and coating influences the transported cells by promoting their survival and differentiation and favoring their integration in the host tissue after their complete degradation. Furthermore, the released factor may also influence the microenvironment. In this study, we evaluated their efficacy using nerve growth factor (NGF)-releasing PAM and PC12 cells, in a Parkinson's disease paradigm. After implantation of NGF-releasing or unloaded PAM conveying PC12 cells, or PC12 cells alone, we studied cell survival, differentiation, and apoptosis, as well as behavior of the treated rats. We observed that the NGF-releasing PAM coated with two synthetic peptides (poly-D-lysine and fibronectin-like) induced PC12 cell differentiation and reduced cell death and proliferation. Moreover, the animals receiving this implant presented an improved amphetamine-induced rotational behavior. These findings indicate that PAM could be a promising strategy for cell therapy of neurological diseases and could be employed in other situations with fetal cell transplants or with stem cells.

Amphetamines↗
PubMed2003

Therapeutic efficacy study of novel 5-FU-loaded PMM 2.1.2-based microspheres on C6 glioma.

The aim of this study was to evaluate the potential of poly(methylidene malonate 2.1.2) as a new drug delivery system to the central nervous system. 5-Fluorouracil microspheres were formulated by an emulsion-extraction method, and evaluated on a C6 glioma model. Twenty-seven Sprague-Dawley female rats underwent implantation of various C6 cell concentrations. Magnetic resonance imaging was performed at day 10 to control the setting of the tumor, by using a T2-weighted sequence. At day 12, 18 animals received blank or 5-FU-loaded microspheres, while 9 animals were not implanted and constituted the controls. Thereafter, MRI was performed twice a week to follow the tumor growth. In 12 animals, an alloimmune rejection of the tumor was observed, showing the limitations of the C6 glioma model. When tumor developed, no relationship was observed between the number of C6 cells injected and the tumor volume. 5-FU microsphere efficacy could statistically be demonstrated by significantly improving the median survival of C6 glioma-bearing animals and also by decreasing tumor burden.

Animals↗
PubMed2003

Implantable drug-releasing biodegradable microspheres for local treatment of brain glioma.

Our group have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this mini-review, we describe the development, preclinical studies and clinical trials involving 5-fluorouracil-releasing microspheres for interstitial radiosensitization of malignant glioma. Future developments concerning these microspheres for treatment of brain tumors are presented.

Adolescent↗
PubMed2003

[Update on cellular and molecular biology techniques].

Cellular and molecular biology techniques have invaded all fields of medicine and neurosurgery is not an exception as can be seen at congresses and in our journals. The purpose of the present review is to provide an update on current techniques.

Cytological Techniques↗