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Biomedical subjects

Philippe Menei

Publications and source records attributed to Philippe Menei.

24 records · Page 2Linked to original sources
PubMed2004

Striatal implantation of GDNF releasing biodegradable microspheres promotes recovery of motor function in a partial model of Parkinson's disease.

The recent identification of neurotrophic factors, such as the glial cell line derived neurotrophic factor (GDNF), acting on mesencephalic dopaminergic neurons, offers the possibility to stimulate the axonal regeneration of these cells which are affected in Parkinson's disease. Nevertheless, a safe and efficient GDNF delivery system that may be used in clinical trials is still lacking. We have developed GDNF-releasing microspheres capable of releasing the neurotrophic factor for at least 2 months in vivo. In this study we demonstrate that these microspheres, when implanted in the brains of 'Parkinsonian' rats, were well tolerated, and were able to induce sprouting of the preserved dopaminergic fibers with synaptogenesis. Moreover, this neural regeneration was accompanied by functional improvement. The implantation of GDNF-releasing microspheres could be a promising strategy in the treatment of Parkinson's disease.

Absorbable Implants↗
PubMed2004

Influence of 5-fluorouracil-loaded microsphere formulation on efficient rat glioma radiosensitization.

PURPOSE: To determine (i) the efficiency of radiosensitizing 5-FU-loaded microspheres and (ii) the impact of microparticle formulation on response to treatment. METHODS: C6 tumor-bearing rats were stereotactically implanted with microspheres and/or allocated to: control groups (untreated) or treatment (only radiotherapy; fast-release 5-FU microspheres + radiotherapy; slow-release 5-FU microspheres + radiotherapy). The next day, fractionated radiotherapy, limited to the hemibrain, was initiated in all treated animals. The irradiation cycle included 36 Gy, given in 9 sessions for 3 consecutive weeks. Tumor development was assessed by T2-weighted MRI. RESULTS: 5-FU microspheres associated with radiotherapy caused a 47% complete remission rate (9/19) as opposed to the 8% rate (1/12) when radiotherapy alone or 0% in control animals. Drug delivery for 3 weeks produced better survival results (57%) compared to one-week sustained release (41%). MR images showed exponentially increasing tumor volumes during the first half of the radiotherapy cycle, followed by a decrease, and the disappearance of the tumor if survival exceeded 120 days. CONCLUSIONS: 5-FU controlled delivery is a promising strategy for radiosensitizing gliomas. Drug delivery system formulation is unambiguously implicated in both the response to treatment and the limitation of toxic side effects.

Animals↗
PubMed2004

Spastic equinus foot: multicenter study of the long-term results of tibial neurotomy.

OBJECTIVE: Tibial neurotomy is a surgical technique widely used for the treatment of spastic equinus foot, but it has rarely been evaluated. The primary objective of this prospective study was to provide an objective quantification of the long-term results of tibial neurotomy. METHODS: This multicenter prospective study was conducted from 1999 to 2003. Fifty-five patients with spastic equinus foot were treated in five neurosurgical centers. Preoperative and postoperative clinical evaluation comprised description of the foot deformity, study of stretch reflexes, evaluation of the repercussions of the deformity, and gait analysis. Selective neurotomy was performed in all patients. RESULTS: No postoperative complications were observed. The mean postoperative follow-up was 10 months. Tibial neurotomy improved the appearance of the foot (equinus and varus deformities, claw toes); the equinus score decreased from 1.54 to 0.273 after the operation. Stretch reflex scores were decreased significantly and for a long term after surgery; the mean triceps surae stretch reflex score decreased from 2.46 to 0.47. The angle of passive dorsiflexion of the ankle increased significantly (from -0.56 degrees to +6.85 degrees). Gait analysis demonstrated a statistically significant increase in the speed of the patient's gait after surgical treatment; the time taken by the patient to walk 10 m at a normal speed in shoes decreased from a mean of 55 seconds to 35.16 seconds. Postoperatively, 92.7% of preoperative objectives had been achieved. CONCLUSION: Tibial neurotomy ensures long-term functional improvement of patients with spastic equinus foot. It provides a lasting response for these patients compared with other, more transient treatments.

Adolescent↗
PubMed2003

Therapeutic effectiveness of novel 5-fluorouracil-loaded poly(methylidene malonate 2.1.2)-based microspheres on F98 glioma-bearing rats.

BACKGROUND: Drug delivery to the central nervous system (CNS) remains a real challenge for neurosurgeons and neurologists, because many molecules cannot cross the blood-brain barrier (BBB). In recent years, solid polymeric materials have been implanted into animal and human brains either by surgery or using stereotactic methods to assure the controlled release of a drug over a determined period, thus circumventing the difficulties posed by the BBB. Poly(methylidene malonate 2.1.2) (PMM 2.1.2) is a new polymer that was described a few years ago and that allows the fabrication of novel, 5-fluorouracil (5-FU)-loaded PMM 2.1.2 microspheres. The objective of the current study was to assess the therapeutic effectiveness of those particles in a rat brain tumor model, the F98 glioma. METHODS: Forty-three rats were used in this study. First, a histologic evaluation of the F98 tumor model was performed on Fischer female rats. Thereafter, different groups of rats were injected and were treated with 5-FU microspheres in 2 different suspension media: carboxymethylcellulose (CMC) aqueous solution with or without 5-FU. RESULTS: The tumor was confirmed as extremely aggressive and invasive, even in early development. The 5-FU-loaded microspheres improved rat median survival significantly compared with untreated animals, CMC-treated animals, and 5-FU solution-treated animals when injected in CMC without 5-FU, demonstrating the interest of a sustained release and the efficacy of intratumoral chemotherapy against an established tumor. CONCLUSIONS: PMM 2.1.2 microspheres appeared to be a promising system, because their degradation rate in vivo was longer compared with many polymers, and they may be capable of long-term delivery.

Animals↗