Biomedical subjects

P Menei

Publications and source records attributed to P Menei.

At least 37 records · Page 2Linked to original sources

PubMed2001

Therapeutic efficacy of 5-fluorouracil-loaded microspheres on rat glioma: a magnetic resonance imaging study.

The aim of this work was to assess the therapeutic efficacy of an intratumoral bolus injection of 5-fluorouracil (FU) compared to that of drug loaded in biodegradable microspheres, for the treatment of brain tumour. Experiments were carried out using a fast-growing C6-glioma rat model. The therapeutic protocols were performed 12 days after the injection of glioma cells. At this stage, the tumours were installed and the mean volume was 13 +/- 2 microl as measured by proton magnetic resonance (MR) imaging. This technique was used for the follow-up of the tumour volume with respect to time and therapy. In terms of rat survival, both therapies induced a significant 50% increase in animal life span (p < 0.05) compared to animals receiving no drug or unloaded microspheres. Whilst no cure was observed, analysis of the MR images showed that the local and sustained delivery of FU slowed the tumour development in the vicinity of the microspheres by a factor of 3, compared with the bolus intratumoral injection.

Animals↗

PubMed2001

Anatomical bases of the posterior approach to the brachial plexus for repairing avulsed spinal nerve roots.

Avulsion of nerve roots from the cervical spinal cord has always been considered as an untreatable injury, even by surgeons with expertise in this area. However, numerous experimental studies in animals, as well as a human case report, showed that if continuity is restored between the spinal cord and nerve roots, axons from spinal motor neurons can regrow into the peripheral nerve graft with a subsequent recovery of motor function. The posterior subscapular approach, based on the evolution of the posterolateral approach for removal of the first rib, is the only way to expose the entire brachial plexus from C5 to T1 from the ventral and dorsal roots to the distal nerve trunks. The purpose of this study is to investigate the topographic anatomy of the brachial plexus, with particular emphasis on the relationships important to the posterior approach and reimplantation of the ventral rootlets within the cord, either directly or using peripheral nerve grafts. The major advantage of the procedure is the proximal exposure of the plexus, with evaluation of the lesions being excellent (intradural, foraminal and proximal trunks). Reimplantation of ventral roots into the cord is relatively easy from C5 to C7, more difficult for C8 and problematic for T1, whereas reimplantation of dorsal roots into the cord is easy from C5 to T1. The disadvantages of this approach for exposure of the plexus and nerve root avulsion repair are significant: the surgical technical steps are difficult mainly because of the cervical paraspinal muscle mass, which cannot be easily "elevated and retracted" despite previous descriptions; bleeding from the venous plexus can be excessive as suggested by dissection and our own experience; the stability of the cervical spine may be compromised following extensive laminectomy with total unilateral facetectomy; exposure of the plexus distal to the division of the trunks is difficult; there may be injury to the long thoracic nerve and subsequent winging of the scapula; and pneumothorax. This approach is therefore only applicable in highly selected cases involving multiple avulsed roots with proximal lesions extending as far as the division of the trunks.

Aged↗

PubMed2001

Ideal intraspinal implantation site for the repair of ventral root avulsion after brachial plexus injury in humans. A preliminary anatomical study.

The advances made to date in root reimplantation for avulsion of the brachial plexus are modest considering that there are only reports from ten patients in the literature. However, the results are promising and should be applauded. The problem with reimplantation, in addition to the difficult surgical exposure, is to determine the ideal intraspinal implantation site for the graft. Given the non-permissive substrate properties of the CNS white matter, the outcome of grafts elsewhere in the spinal cord need to be evaluated. An inappropriate implantation site might explain the still modest recovery in this challenging group of patients. Consequently the microscopic anatomy of the cervical spinal cord segments C5 to T1 was studied. The aims were to 1--determine the relationships between the ventral gray horn and the ventrolateral sulcus of the spinal cord, and 2--analyse the location and course of the motoneuron fibres passing through the white matter to reach the ventral root. On the basis of the present findings it is proposed that reimplantation of nerve grafts or rootlets should be performed directly through the ventral root exit zone in contact with the ventromedial region of the ventral gray horn at a depth of 2 mm, rather than into the white matter of the lateral aspect of the cord. Initially we used a posterior approach with total facetectomies. An anterior approach is now evaluated for current use.

Brachial Plexus↗

PubMed2001

Pseudotumoral demyelination: a diagnosis pitfall (report of three cases).

Rare forms of demyelinating disease such as Balò's concentric sclerosis or Schilder's disease may simulate brain tumors, both clinically and on the computed tomography (CT) and magnetic resonance imaging (MRI). Even the histopathological diagnosis after a biopsy is not entirely reliable. We report three cases of pseudotumoral demyelinating disorders having required a stereotaxic biopsy, one of which was erroneously diagnosed as a malignant astrocytoma. We describe MRI especially the intense contrast enhancement with ill-defined margins, and the mild mass effect. We then detail the histopathological processes upon which differential diagnosis with a tumor can be based.

Adult↗

PubMed2001

PCV chemotherapy for oligodendroglioma: response analyzed on T2 weighted-MRI.

OBJECTIVE: Because oligodendroglioma are infiltrative tumors, the Mac Donald's response criteria, usually used for solid and contrast-enhanced tumors, seem not to be adapted. To precise more relevant radiological criteria, the radiological response of oligodendroglioma to PCV chemotherapy was evaluated on T2 weighted-MRI sequences only. METHODS: 25 patients with oligodendroglioma grade A or B were retrospectively analyzed. They were treated with up to six cycles of PCV standard regimen. Tumor size was calculated before and at the end of the treatment, on T2 weighted-MRI, by two methods: volumetric reconstruction (method 1) and maximal cross-sectional area (method 2). Responses were defined according to new criteria on T2 weighted-MRI. RESULTS: According to these criteria and with the method 1, 7 of 25 patients (28%) had a partial response to the PCV, 14 patients (56%) had stabilized disease, and 4 patients (16%) had progressive disease. With the method 2, 6 had partial response (24%), 18 had stabilized disease (72%) and 1 had progressive disease. CONCLUSION: Response rate to PCV chemotherapy in this study was lower than response observed in the literature. Because of the infiltrative feature of oligodendroglioma, we think that the radiological response of these tumors should be evaluated on T2 weighted-MRI. The two methods of tumor size estimation used in this study were almost equivalent. Then, the maximal cross-sectional area measurement, more practical, could be retained.

Adolescent↗

PubMed2001

Analysis of brain biocompatibility of drug-releasing biodegradable microspheres by scanning and transmission electron microscopy.

OBJECT: Stereotactically guided implantation of biodegradable microspheres is a promising strategy for delivery of neurotrophic factors in a precise and spatially defined brain area. The goal in this study was to show the biocompatibility of poly(D,L,lactide-co-glycolide) microspheres with brain tissue at the ultrastructural level and to analyze the three-dimensional (3D) ultrastructure after intrastriatal implantation of these microparticles. METHODS: Scanning and transmission electron microscopy were used to study the microspheres and their environment after implantation in an inert material (gelatin) and in the rat striatum. Observations were made at different time periods, ranging from 24 hours to 2 months postimplantation. CONCLUSIONS: The progressive degradation of the microspheres, with vacuolization, deformation, and shrinkage, was well visualized. This degradation was identical in microspheres implanted in the inert material and in the rat brain tissue, independent of the presence of macrophages. The studies preformed in the striatum permitted the authors to demonstrate the structural integrity of axons in contact with microspheres, confirming the biocompatibility of the polymer. Furthermore, scanning electron microscopy showed the preservation of the 3D ultrastructure of the striatum around the microparticles. These microparticles, which can be stereotactically implanted in functional areas of the brain and can release neurotrophic factors, could represent, for some indications, an alternative to gene therapy.

Animals↗

PubMed2001

Lateral interscalenic multilevel oblique corpectomies to repair ventral root avulsions after brachial plexus injury in humans: anatomical study and first clinical experience.

OBJECT: Because central nervous system white matter exerts a powerful inhibitory effect on axonal growth, implantation of nerve grafts or rootlets into the cervical spinal cord following ventral root avulsion injury should, ideally, be performed directly through the ventral root exit zone (VRExZ), which is located near the anteromedial aspect of the anterior horn; the grafts/rootlets should not be implanted into the white matter of the lateral cord. This is not possible when using a conservative posterior approach. Therefore, the authors have studied the anatomy encountered when using the anterolateral approach and evaluated the technique in the particular case of avulsed ventral nerve roots. They also present a case illustration of the procedure, which is used currently in their department. METHODS: Anterior access to the rootlets is obtained using a lateral interscalenic approach; the vertebral artery is exposed and mobilized, and oblique drilling of the vertebral bodies (VBs) is performed. Because the articular processes and half of the VBs are preserved, fusion is not required. The approach allows the surgeon to expose the anterior aspect of the cervical dura and the entire length of the emerging spinal nerves. The anterior aspect of the dura is opened at the desired levels for VRExZ exposure. and the position is ideal for implantation of the graft/rootlets. The interscalenic dissection is mandatory so that the lesions of the supraclavicular plexus can be evaluated and repaired. If necessary, the anterior approach allows for exploration of the infraclavicular plexus during the same procedure. CONCLUSIONS: The use of a true anterior approach to the ventral rootlets appears to be a valuable and appropriate approach that avoids extensive laminectomy/facetectomy while reimplantation is performed through the anterolateral sulcus itself. In this approach, however, reimplantation of dorsal roots into the spinal cord remains impossible.

Adult↗

PubMed2001

[Dermal sinus and dermoid cyst revealed by abscess formation in posterior fossa. Report of 2 pediatric cases and review of the litterature].

Cranial dermal sinus, usually associated with dermoid cyst, is the persistance of an abnormal embryonal communication between the skin and the central nervous system. It may be the source of intracranial infection, most often a meningitis and rarely an abscess formation. Two cases of little girls (18 months and 2 years) having dermal sinus with dermoid cyst revealed by cerebellar abscess formations are reported. In the first case there were multiple cerebellar abscesses with hydrocephalus leading to a raised intracranial pressure. In the second case there was an abscess formation adjacent to the dermoid cyst. CT scan showed cysts and abscesses but MRI, achieved in the second case, was useful in demonstrating the sinus tract as well as the associated cyst and abscess. The two patients underwent a posterior fossa surgery with antibiotic therapy. In the first case abscess drainage and ventricular external drainage were necessary before sinus and cyst excision. Two months after surgery the two patients were neurologically intact and developping well. Surgery with total excision of dermal sinus and dermoid cyst, even sometimes difficult, must be preferred to the simple abscess drainage and antibiotic therapy.

Abscess↗

PubMed2001

[A case of intramedullary primary melanocytic tumor: meningeal melanocytoma or malignant melanoma?].

We report a case of an intramedullary thoracic primary melanocytic tumor of the leptomeninges in a 38-year-old woman. According to the WHO classification, the lesion showed the histological features of a meningeal melanocytoma. Two local recurrences were successively operated on, two and three years after the first surgery respectively. The patient died of a subarachnoidian dissemination after a four year course. This case emphasized the therapeutic problems we have to deal with when facing an isolated black tumor of the central nervous system. The features and the differential diagnosis of the meningeal melanocytoma are detailed.

Adult↗

PubMed2000

Development of microspheres for neurological disorders: from basics to clinical applications.

Drug delivery to the central nervous system remains a challenging area of investigation for both basic and clinical neuroscientists. Numerous drugs are generally excluded from blood to brain transfer due to the negligible permeability of the brain capillary endothelial wall, which makes up the blood brain barrier in vivo. For several years, we have explored the potential applications of the microencapsulation of therapeutic agents to provide local controlled drug release in the central nervous system. Due to their size, these microparticles can be easily implanted by stereotaxy in discreet, precise and functional areas of the brain without damaging the surrounding tissue. This type of implantation avoids the inconvenient insertion of large implants by open surgery and can be repeated if necessary. We have established the compatibility of poly(lactide-co-glycolide) microspheres with brain tissues. Presently, the most developed applications concern Neurology and Neuro-oncology, with local delivery of neurotrophic factors and antimitotic drugs into neurodegenerative lesions and brain tumours, respectively. The drugs that had been encapsulated by our group included nerve growth factor (NGF), 5-fluorouracil (5-FU), idoxuridine and BCNU. Preclinical studies have been performed with each drug. Studies with NGF are reported as an example. A phase I/II clinical trial has been carried out in patients with newly diagnosed glioblastomas to assess the potentialities of 5-FU-loaded microspheres when intracranially implanted.

Animals↗

PubMed2000

Intracerebral implantation of NGF-releasing biodegradable microspheres protects striatum against excitotoxic damage.

Intrastriatal implantation of genetically modified cells synthesizing nerve growth factor (NGF) constitutes one way to obtain a long-term supply of this neurotrophic factor and a neuronal protection against an excitotoxic lesion. We have investigated if NGF-loaded poly(d,l-lactide-co-glycolide) microspheres could represent an alternative to cell transplantations. These microspheres can be implanted stereotaxically and locally release the protein in a controlled and sustained way. In order to test this paradigm, the NGF release kinetics were characterized in vitro using radiolabeled NGF, immunoenzymatic assay, and PC-12 cells bioassay and then in vivo after implantation in the intact rat striatum. These microspheres were thus implanted into the rat striatum 7 days prior to infusing quinolinic acid. Control animals were either not treated or implanted with blank microspheres. The extent of the lesion and the survival of ChAT-, NADPH-d-, and DARPP-32-containing neurons were analyzed. In vitro studies showed that microspheres allowed a sustained release of bioactive NGF for at least 1 month. Microspheres implanted in the intact striatum still contained NGF after 2.5 months and they were totally degraded after 3 months. After quinolinic acid infusion, the lesion size in the group treated with NGF-releasing microspheres was reduced by 40% when compared with the control groups. A marked neuronal sparing was noted, principally concerning the cholinergic interneurons, but also neuropeptide Y/somatostatin interneurons and GABAergic striatofuge neurons. These results indicate that implantation of biodegradable NGF-releasing microspheres can be used to protect neurons from a local excitotoxic lesion and that this strategy may ultimately prove to be relevant for the treatment of various neurological diseases.

Animals↗

PubMed2000

Intraseptal implantation of NGF-releasing microspheres promote the survival of axotomized cholinergic neurons.

Neurotrophic factors therapy requires their precise delivery to the targeted neuronal population. For this purpose, a wide range of strategies have been developed, and among them the stereotaxic implantation of biodegradable microparticles. To assess the in vivo activity of NGF-releasing PLGA microspheres, unloaded and NGF-loaded microparticles were implanted in the rat brain, near the septal cholinergic neurons, axotomized by an unilateral transection of the fornix-fimbria. Histological analysis at two and six weeks after implantation revealed a non-specific astro- and micro-glial reaction around the microspheres, identical for both unloaded and NGF-loaded microspheres. No neuronal toxicity was noticed, and healthy looking neurons were observed in contact with the microspheres. In the non-treated animals, the percentage of axotomized surviving neurons, when compared to the contralateral intact side, was 31 +/- 2 and 27 +/- 1% at two and six weeks, respectively. Unloaded microspheres caused no protective nor neurotoxic effects (40 +/- 9 and 39 +/- 6% of surviving cholinergic neurons at two and six weeks, respectively). In contrast, NGF-loaded microspheres showed a significant effect on the survival of axotomized cholinergic neurons at two and six weeks after implantation (66 +/- 9 and 61 +/- 5% when compared to the contralateral intact side, respectively). These results show that PLGA microparticles present no neurotoxicity and release sufficient amounts of bioactive NGF to significantly limit the lesion-induced disappearance of cholinergic neurons in the septum during at least six weeks. PLGA microparticles can be used in the future to administer neurotrophic factors in central nervous system disorders.

Animals↗

PubMed1999

Local and sustained delivery of 5-fluorouracil from biodegradable microspheres for the radiosensitization of glioblastoma: a pilot study.

BACKGROUND: The authors have developed a new method of drug delivery into the brain using implantable biodegradable microspheres. In this study, this method was used to provide localized and sustained delivery of 5-fluorouracil (5-FU) after the surgical resection of glioblastoma. This antimetabolite and radiosensitizing drug was selected in an attempt to decrease the rate of local recurrence of the tumor. METHODS: Eight patients with newly diagnosed glioblastoma were included in the study and 2 increasing amounts of 5-FU were studied (70 mg and 132 mg). After surgical resection of the tumor, poly(D-L lactide-co-glycolide) 5-FU-loaded microspheres with an average dimension of 45 microm were implanted in the wall of the surgical bed. External beam radiation (59.4 grays) was initiated before the seventh postsurgical day. Patients were followed by clinical examination, magnetic resonance imaging, and 5-FU assays in the blood and cerebrospinal fluid (CSF). RESULTS: 5-FU assays confirmed sustained concentrations in the CSF for at least 1 month. Concentrations of 5-FU in the blood were lower and transitory. Systemic tolerance to the treatment was good; one case of recurrent brain swelling was observed at the higher dose studied. At the time of last follow-up the overall median survival time was 98 weeks from the time of implantation and 2 patients had achieved disease remission at 139 and 153 weeks, respectively. CONCLUSIONS: This study demonstrates that biodegradable microspheres are efficient systems for drug delivery into the brain and may have future application in the treatment of brain tumors. Further studies are needed to confirm the potential of 5-FU-loaded microspheres for the radiosensitization of glioblastoma. [Please see editorial on pages 197-9, this issue].

Adolescent↗

PubMed1999

Ventral transdural herniation of the thoracic spinal cord: surgical treatment in four cases and review of literature.

BACKGROUND: A specific cause of progressive Brown-Sequard syndrome has been identified: a ventral herniation of the thoracic spinal cord through the dural sleeve on one side. METHOD: Four female patients who were affected by a progressive Brown Sequard syndrome related to a transdural spinal cord herniation have been investigated and were submitted to surgery and postoperative evaluation. FINDINGS: The MRI scan showed atrophy and forward displacement of the spinal cord on one side and adhesion of the spinal cord to the dura mater. CT myelography demonstrated the disappearance of the premedullar rim at the level of the herniation and the shadow of the extradural herniation. Surgical treatment consisted in the excision of the arachnoid cyst when there was one, section of the dentate ligament, release of the adhesions, detachment of the spinal cord from the hernial orifice, and lastly suture of the dural tear or placement by a patch. Follow-up examination showed motor improvement with persistent sensory deficit in two cases and stabilisation in two cases. INTERPRETATION: The cause of the dural tear, either traumatic or congenital could not be confirmed in the four cases. Symptoms probably occur when herniation fills the orifice and strangulation happens which explains the late appearance and progressive evolution of this myelopathy. Mobilisation of the herniated spinal cord back into the intradural space can be achieved by surgery and may stop the evolution of the symptoms and signs.

Adult↗

PubMed1999

Why does PEG 400 co-encapsulation improve NGF stability and release from PLGA biodegradable microspheres?

PURPOSE: The aim of this work was to understand the mechanism by which co-encapsulated PEG 400 improved the stability of NGF and allowed a continuous release from PLGA 37.5/25 microspheres. METHODS: Microparticles were prepared according to the double emulsion method. PEG 400 was added with NGF in the internal aqueous phase (PEG/PLGA ratio 1/1 and 1.8/1). Its effect was investigated through interfacial tension studies. Protein stability was assessed by ELISA. RESULTS: A novel application of PEG in protein stabilization during encapsulation was evidenced by adsorption kinetics studies. PEG 400 limited the penetration of NGF in the interfacial film of the primary emulsion. Consequently, it stabilized the NGF by reducing the contact with the organic phase. In addition, it avoided the NGF release profile to level off by limiting the irreversible NGF anchorage in the polymer layers. On the other hand, the amount of active NGF released in the early stages was increased. During microparticle preparation, NaCl could be added in the external aqueous phase to modify the structure of microparticles. This allowed to reduce the initial release rate without affecting the protein stability always encountered in the absence of PEG. CONCLUSIONS: PEG 400 appeared of major interest to achieve a continuous delivery of NGF over seven weeks from biodegradable microparticles prepared by the double emulsion technique.

Biodegradation, Environmental↗

PubMed1999

Correlation between cerebral oxygen saturation measured by near-infrared spectroscopy and jugular oxygen saturation in patients with severe closed head injury.

UNLABELLED: Near-infrared spectroscopy has been used to monitor cerebral oxygen saturation during cerebral circulatory arrest and carotid clamping. However, its utility has not been demonstrated in more complex situations, such as in patients with head injuries. The authors tested this method during conditions that may alter the arteriovenous partition of cerebral blood in different ways. METHODS: The authors compared changes in measured cerebral oxygen saturation and other hemodynamic parameters, including jugular venous oxygen saturation, in nine patients with severe closed head injury during manipulation of arterial carbon dioxide partial pressure and after mean arterial pressure was altered by vasopressors. RESULTS: The Bland and Altman representation of cerebral oxygen saturation versus jugular oxygen saturation showed a uniform scatter. Values for changing arterial carbon dioxide partial pressure were: bias = 1.1%, 2 SD = +/-21%, absolute value; and those for alterations in mean arterial pressure: bias = 3.7%, 2 SD = +/-24%, absolute value. However, a Bland and Altman plot of changes in cerebral oxygen saturation versus changes in jugular oxygen saturation had a negative slope (alteration in arterial carbon dioxide partial pressure: bias = 2.4%, 2 SD = +/-17%, absolute value; alteration in mean arterial pressure: bias = -4.9%, 2 SD = +/-31%, absolute value). Regression analysis showed that changes in cerebral oxygen saturation were positively correlated with changes in jugular venous oxygen saturation during the carbon dioxide challenge, whereas correlation was negative during the arterial pressure challenge. CONCLUSIONS: Cerebral oxygen saturation assessed by near-infrared spectroscopy does not adequately reflect changes in jugular venous oxygen saturation in patients with severe head injury. Changes in arteriovenous partitioning, infrared-spectroscopy contamination by extracerebral signal, algorithm errors, and dissimilar tissue sampling may explain these findings.

Administration, Inhalation↗

PubMed1999

[Spontaneous spinal cord herniation: a little-known cause of Brown-Sequard syndrome. Report of two cases and review of the literature].

We report two cases of spinal cord herniation. The first one concerns a 28 year-old female who presented with an eighteen-month past history of spasticity of the right lower limb associated with somesthetic sensorial disturbances of the left side with a T4 level, related to a T3-T4 spinal cord herniation. The second case concerned a 58 year-old female with a past history of a left lower limb pyramidal syndrome associated with somesthetic and proprioceptive sensibilities disturbances of the right side with a T5 level related to a T4-T5 spinal cord herniation. Spinal cord herniation is an uncommon and underestimated cause of a progressive Brown-Sequard syndrome. The diagnosis is now easy on the MRI, showing a ventral attraction of the cord. The outcome is usually good, following the surgical reduction of the herniation.

Adult↗

PubMed1999

[Intracranial meningiomas revealed by hemorrhage. Report of three cases and literature review].

Three cases of meningioma revealed by hemorrage are reported. The first patient, 65 presented with a temporal hematoma associated with intraventricular contamination. The diagnosis of a tumoral origin of the hemorrhage was made only few weeks later when the total hematoma resorption was ended. The second patient, 49 presented with a sudden right hemiplegia. CTscan and MRI revealed a left frontal tumor surrounded by hematoma. The third patient, 46, presented with a transient aphasia and superior limb dysesthesia. CT scan showed a temporal hematoma; a carotid angiography revealed a typical meningioma blush. A review of the literature collected 54 additional cases of meningioma associated with hemorrage. Clinical findings and mechanisms are discussed.

Aged↗