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J C Sol

Publications and source records attributed to J C Sol.

17 recordsLinked to original sources

Cell therapy of pain: Characterization of human fetal chromaffin cells at early adrenal medulla development.

Adult adrenal chromaffin cells are being utilized for therapeutic transplantation. With the prospect of using fetal chromaffin cells in pain therapy, we studied their phenotype, proliferative power, function, and growth in vitro and in situ in order to determine the optimal time for implantation. Between 7 and 10 gestational weeks (GW), we isolated, in vitro, two types of chromaffin cells with a noradrenergic phenotype akin to that observed, in situ. Among the adherent chromaffin cells first observed in vitro, only a few samples expressed met-enkephalin, whereas almost all the neurosphere-like colonies, which appeared later, expressed it. However, neither of the two types of populations expressed an adrenergic phenotype in line with that observed in situ. At the upper limits of the voluntary abortion period authorized in France, this phenotype (12 GW) and met-enkephalin expression (13 GW) were evidenced in situ. For the first time in man, we demonstrate the secretion of noradrenaline in vitro by the two populations of cells. Consistent with this result, we also noted dopamine beta hydroxylase (DbetaH) mRNA expression in vitro and in situ within this period. These observations on the expression of these biological factors indicate that 9-10 GW would be the best stage for sampling these cells for preclinical transplantation experiments.

Adrenal Medulla↗

Viability and functionality of bovine chromaffin cells encapsulated into alginate-PLL microcapsules with a liquefied inner core.

Implantation of adrenal medullary bovine chromaffin cells (BCC), which synthesize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides, has been proposed for the treatment of intractable cancer pain. Macro- or microencapsulation of such cells within semipermeable membranes is expected to protect the transplant from the host's immune system. In the present study, we report the viability and functionality of BCC encapsulated into microcapsules of alginate-poly-L-lysine (PLL) with a liquefied inner core. The experiment was carried out during 44 days. Empty microcapsules were characterized in terms of morphology, permeability, and mechanical resistance. At the same time, the viability and functionality of both encapsulated and nonencapsulated BCC were evaluated in vitro. We obtained viable BCC with excellent functionality: immunocytochemical analysis revealed robust survival of chromaffin cells 30 days after isolation and microencapsulation. HPLC assay showed that encapsulated BCC released catecholamines basally during the time course study. Taken together, these results demonstrate that viable BCC can be successfully encapsulated into alginate-PLL microcapsules with a liquefied inner core.

Alginates↗

Intrathecal grafting of porcine chromaffin cells reduces formalin-evoked c-Fos expression in the rat spinal cord.

Chromaffin cells from the adrenal gland secrete a combination of neuroactive compounds including catecholamines, opioid peptides, and growth factors that have strong analgesic effects, especially when administered intrathecally. Preclinical studies of intrathecal implantation with xenogeneic bovine chromaffin cells in rats have provided conflicting data with regard to analgesic effects, and recent concern over risk of prion transmission has precluded their use in human clinical trials. We previously developed a new, safer source of adult adrenal chromaffin cells of porcine origin and demonstrated an in vivo antinociceptive effect in the formalin test, a rodent model of tonic pain. The goal of the present study was to confirm porcine chromaffin cell analgesic effects at the molecular level by evaluating neural activity as reflected by spinal cord c-Fos protein expression. To this end, the expression of c-Fos in response to intraplantar formalin injection was evaluated in animals following intrathecal grafting of 10(6) porcine or bovine chromaffin cells. For the two species, adrenal chromaffin cells significantly reduced the tonic phases of the formalin response. Similarly, c-Fos-like immunoreactive neurons were markedly reduced in the dorsal horns of animals that had received injections of xenogeneic chromaffin cells. This reduction was observed in both the superficial (I-II) and deep (V-VI) lamina of the dorsal horn. The present study demonstrates that both xenogeneic porcine and bovine chromaffin cells transplanted into the spinal subarachnoid space of the rat can suppress formalin-evoked c-Fos expression equally, in parallel with suppression of nociceptive behaviors in the tonic phase of the test. These findings confirm previous reports that adrenal chromaffin cells may produce antinociception by inhibiting activation of nociceptive neurons in the spinal dorsal horn. Taken together these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

Animals↗

Intrathecal xenogeneic chromaffin cell grafts reduce nociceptive behavior in a rodent tonic pain model.

Adrenal medullary chromaffin cells synthetize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides. Previous reports have shown that implantation of chromaffin cells into the spinal subarachnoid space can reduce both acute and chronic pain in several animal models. We recently demonstrated that human chromaffin cell grafts in the cerebrospinal fluid (CSF) could alleviate intractable cancer pain after failure of systemic opiates. However, wider application of this approach was limited by the limited availability of allogeneic donor material. Alternatively, chromaffin cells from xenogeneic sources such as bovine adrenal medulla were successful in the experimental treatment of pain, but recent concern over risk of prion transmission precluded use of bovine grafts in human clinical trials. The objective of the present study was to investigate the possibility of developing a new xenogeneic porcine source of therapeutic chromaffin cells because this strategy is currently considered the safest for transplantation in man. In the present study, we report the isolation and the characterization of primary porcine chromaffin cells (PCC) compared to bovine cells. We show, for the first time, that these cells grafted in the rat subarachnoid space can attenuate pain-related behaviors as assessed by the formalin test, a model of tonic pain. Moreover, in addition to behavioral studies, immunohistochemical analysis revealed robust survival of chromaffin cells 35 days after transplantation. Taken together, these results support the concept that porcine chromaffin cells may offer an alternative xenogeneic cell source for transplants delivering pain-reducing neuroactive substances.

Adrenal Medulla↗

Deep brain stimulation for parkinson's disease: correlation between intraoperative subthalamic nucleus neurophysiology and most effective contacts.

Though intraoperative neurophysiology is essential to precisely define the definitive target, little is known regarding its predictive value in defining the most effective contact for chronic deep brain stimulation. In this retrospective study, we reviewed the correlation between intraoperative neurophysiology and contacts selected for chronic stimulation. Twenty consecutive patients implanted for subthalamic nucleus (STN) stimulation were reviewed. There was no significant correlation between the electrophysiologically defined STN and the most effective contact for chronic stimulation at 3 months or at 6 months. Furthermore, there was a discrepancy between the most effective contact for rigidity versus akinesia or tremor at 3 months. Interestingly, at 3 months, the same electrode contact was maximally efficient for rigidity, akinesia and tremor in only 13 of the 39 cases. This lack of correlation did not affect the global improvement.

Adult↗

Vertebral pedicle anatomy in relation to pedicle screw fixation: a cadaver study.

New techniques to stabilize and correct the thoracic and lumbar spine have been developed in recent years. In view of the wide variety and complexity of fixation devices, the optimum configuration of spinal instrumentation systems needs to be defined. Linear and angular measurements of both vertebral pedicles were made in ten complete thoracic and lumbar cadaveric spines using callipers and a goniometer. The vertical interpedicular distance gradually increased along the spine up to L5. The transverse interpedicular distance was larger at both ends of the spine. Pedicular height gradually increased from T1 to L5, plateauing between T3 and T9, being widest at the thoracolumbar junction. Pedicular width was greatest at the three junctional regions of the spine. The sagittal pedicular angle decreased along the length of the spine to zero at L5. The transverse pedicular angle decreased from T1 to T12 and then increased to L5. Of the pedicular measurements only width limits the diameter of fixation screws. The vertical interpedicular distance determines the distance between the holes of plates, while the length of the transfixator is related to the transverse interpedicular distance. The pedicular angles enable triangulation of screws and determine the stability of the fixation.

Aged↗

Methodological and technical issues for integrating functional magnetic resonance imaging data in a neuronavigational system.

OBJECTIVE: The aim of this article was to analyze the technical and methodological issues resulting from the use of functional magnetic resonance image (fMRI) data in a frameless stereotactic device for brain tumor or pain surgery (chronic motor cortex stimulation). METHODS: A total of 32 candidates, 26 for brain tumor surgery and six chronic motor cortex stimulation, were studied by fMRI scanning (61 procedures) and intraoperative cortical brain mapping under general anesthesia. The fMRI data obtained were analyzed with the Statistical Parametric Mapping 99 software, with an initial analysis threshold corresponding to P < 0.001. Subsequently, the fMRI data were registered in a frameless stereotactic neuronavigational device and correlated to brain mapping. RESULTS: Correspondence between fMRI-activated areas and cortical mapping in primary motor areas was good in 28 patients (87%), although fMRI-activated areas were highly dependent on the choice of paradigms and analysis thresholds. Primary sensory- and secondary motor-activated areas were not correlated to cortical brain mapping. Functional mislocalization as a result of insufficient correction of the echo-planar distortion was identified in four patients (13%). Analysis thresholds (from P < 0.0001 to P < 10(-12)) more restrictive than the initial threshold (P < 0.001) had to be used in 25 of the 28 patients studied, so that fMRI motor data could be matched to cortical mapping spatial data. These analysis thresholds were not predictable preoperatively. Maximal tumor resection was accomplished in all patients with brain tumors. Chronic motor cortex electrode placement was successful in each patient (significant pain relief >50% on the visual analog pain scale). CONCLUSION: In brain tumor surgery, fMRI data are helpful in surgical planning and guiding intraoperative brain mapping. The registration of fMRI data in anatomic slices or in the frameless stereotactic neuronavigational device, however, remained a potential source of functional mislocalization. Electrode placement for chronic motor cortex stimulation is a good indication to use fMRI data registered in a neuronavigational system and could replace somatosensory evoked potentials in detection of the central sulcus.

Adolescent↗

Chronic motor cortex stimulation for phantom limb pain: correlations between pain relief and functional imaging studies.

Chronic motor cortex stimulation (CMCS) has provided satisfactory control of pain in patients with central or trigeminal neuropathic pain. We used this technique in 3 patients with intractable phantom limb pain after upper limb amputation. Functional magnetic resonance imaging (fMRI) correlated to anatomical MRI permitted frameless image guidance for electrode placement. Pain control was obtained for all the patients initially and the relief was stable in 2 of the 3 patients at 2 year follow-up. CMCS can be used to relieve phantom limb pain. fMRI data are useful in assisting the neurosurgeon in electrode placement for this indication.

Adult↗

Chiari I malformation: a rare cause of noncommunicating hydrocephalus treated by third ventriculostomy.

OBJECT: Hydrocephalus associated with Chiari I malformation is a rare entity related to an obstruction in the flow of cerebrospinal fluid (CSF) in the foramen of Magendie. Like all forms of noncommunicating hydrocephalus. it can be treated by endoscopic third ventriculostomy (ETV). The object of this study is to report a series of five cases of hydrocephalus associated with Chiari I malformation and to evaluate the use of ETV in the treatment of this anomaly. METHODS: Five patients (four women and one man with a mean age of 29.6 years) underwent ETV for hydrocephalus associated with Chiari I malformation between April 1991 and February 1997. All patients had presented with paroxysmal headaches, which in two cases were associated with visual disorders. All patients had also presented with hydrocephalus (mean transverse diameter of the third ventricle 12.79 mm; mean sagittal diameter of the fourth ventricle 18.27 mm) with a mean herniation of the cerebellar tonsils at 13.75 mm below the basion-opisthion line. Surgery was performed in all patients by using a rigid endoscope. No complications occurred either during or after the procedure, except in one patient who experienced a wound infection that was treated by antibiotic medications. The mean duration of follow up in this study was 50.39 months. Four patients became completely asymptomatic and remained stable throughout the follow-up period. One patient required an additional third ventriculostomy after I year, due to secondary closure, and has remained stable since that time. Postoperative magnetic resonance images demonstrated a significant reduction in the extent of hydrocephalus in all patients (mean transverse diameter of the third ventricle 6.9 mm [p = 0.0035]; mean sagittal diameter of the fourth ventricle 10.32 mm [p = 0.007]), with a mean ascent of the cerebellar tonsils from 13.75 mm below the basion-opisthion line to 7.76 mm below it (p = 0.01). In addition, CSF flow was identified on either side of the orifice of the third ventriculostomy in all patients postoperatively. CONCLUSIONS: Results in this series confirm the efficacy of ETV in the treatment of hydrocephalus associated with Chiari I malformation. It is a reliable, minimally invasive technique that also provides a better understanding of the pathophysiology of this malformation.

Adult↗

Suprasellar seeding of a benign choroid plexus papilloma of the fourth ventricle with local recurrence.

A suprasellar location of a benign choroid plexus papilloma is reported. Local recurrence within the fourth ventricle was also present, 8 years after apparently complete removal. Imaging and histological findings were similar to those of the initial lesion. At surgery, the suprasellar lesion had no connection with the ventricular system. Seeding of choroid plexus papillomas is discussed, and the pertinent literature reviewed.

Female↗

[Endoscopic anatomy of the third ventricle].

According to the development of neurosurgical endoscopy (and especially for third ventriculostomy), the endoscopic anatomy in hydrocephalus should be well known and utilized for orientation. The endoscopic pictures are obtained with a 30; telescope, acquired by a digitalized camera and visualized on a video monitor. The pictures are then numerized on a DKR system. Endoscopic anatomy of the third ventricle is described with a particular focus on the anatomical landmarks and their variations around the foramen of Monro, the anterior and posterior walls of the third ventricle. The knowledge of this anatomy is essential for the safety and the reliability of intraventricular endoscopic procedures.

Endoscopy↗

[Clinical perspectives of xenografts: encapsulated chromaffin cells and pain].

Intrathecal allograft of chromaffin cells can be effectively used in replacement of more conventional therapies for treating intractable chronic pain, such as in cancer. The efficacy of this technique depends on the ability of those cells to produce analgesic opioids and on the immuno-privileged property of the central nervous system, in which rejection risks are limited. However, there are some limitations to the generalization of this new therapy, mainly due to the low number of available grafts. Thus other sources than humans have to be considered. Here we discuss the pros and cons of the xenogeneic chromaffin cells of bovine or porcine origin. Graft immuno-isolation, for example, by using cell encapsulation, seems to be unavoidable in spite of the graft site.

Animals↗

[Management of intractable cancer pain: from intrathecal morphine to cell allograft].

The durable effectiveness of intrathecal morphine administration is well established for the management of intractable cancer pain, after failure of systemic opioids, secondary to the persistence of non-reversible undesirable side effects. Many patients are referred to late in the disease course. This conservative method to control pain of malignant origin must not be reserved for last resort treatment for terminal patients. Intra-cerebro-ventricular morphine administration is a very effective and generally safe method for controlling intractable cancer pain. Because of the chronic implantation of an intra-ventricular catheter this method is somewhat invasive. Its indications remain a simple and effective alternative when the topography of nociceptive pain is diffuse or cephalic. In clinical practice, intrathecal and/or intra-cerebro-ventricular administration of opioids is limited by cost, the need for specialized maintenance and mechanical malfunctions if implantable drug delivery systems, or by the risk of bacterial contamination and ambulatory constraints when repeated daily injections via an intrathecal access port are used. To answer these limitations, cell therapy using intrathecal chromaffin cell allograft is a promising approach for the management of cancer pain refractory to traditional drug therapy and pain lesion surgery. The basic rationale and preclinical studies on experimental pain models have enabled starting prospective clinical trials. Prior to transplantation, handling and preparation of the chromaffin tissue is critical for allograft viability. The initial results of clinical trials with human chromaffin cell grafts from intractable cancer pain have reported long-lasting pain relief, in correlation with met-enkephalin release into the CSF. Convincing evidence will require controlled studies. The limitations of this innovative cell therapy and especially the lack of human adrenal gland availability point to the need for new sources of cells. Perspectives include xenogenic or engineered cell lines.

Analgesics, Opioid↗

Enzymatic degradation of neuropeptide FF and SQA-neuropeptide FF in the mouse brain.

Degradation of neuropeptide FF (NPFF) and SQA-neuropeptide FF (SQA-NPFF) by mouse brain sections was investigated by using capillary electrophoresis with UV detection for the separation and the identification of the degradation products. The half disappearance time of SQA-NPFF was 2-fold greater than that of NPFF. NPFF was cleaved preferentially into an inactive metabolite, Gln-Arg-Phe-NH2, in the cerebrum slices. SQA-NPFF was hydrolyzed by an unidentified degrading activity to generate NPFF, and NPFF accounted for a larger part of SQA-NPFF degradation in the hindbrain and cervical spinal cord than in the cerebrum slices. These findings suggest that, depending on the brain regions, NPFF produced from SQA-NPFF could prolong the biologic effects of SQA-NPFF.

Animals↗

Imaging in neurenteric cysts of the posterior cranial fossa.

Neurenteric cysts are cystic masses lined by a columnar epithelium of endodermal origin. They are rare in the central nervous system. We report two neurenteric cysts in the posterior cranial fossa and describe their neuroradiological features. The lesions were of low density on CT and more accurately delineated on MRI. They gave the same signal as cerebrospinal fluid on all sequences. There was no contrast enhancement.

Adult↗

Recurrent intracranial neurenteric cysts.

Neurenteric cysts are cystic lesions lined by a columnar epithelium of endodermal derivation. They are rarely located in the central nervous system. We describe the case history of two recurrent neurenteric cysts located within the posterior fossa: one in the 4th ventricle and the second in the cerebellopontine angle. The literature is reviewed and the follow-up and recurrence of such cysts are discussed.

Adult↗

[Treatment of spasticity with the intrathecal administration of baclofen].

Direct intrathecal administration of baclofen in the treatment of severe spasticity was proposed in 1984 by Richard Penn with the objective to carry out a selective spinal distribution of the active principle thus avoiding supraspinal side effects. We presented our first results at the French Language Association of Neurosurgery in 1985 within the framework of a report on "Functional neurosurgery of cerebral palsy" (Neurochirurgie, 1985, 31 (suppl 1): 1-118). This study aims to specify the selection criteria and current indications of this method for the treatment of severe chronic diffused spasticity of spinal and cerebral origin in adults and in children. This report relates to our experience concerning 60 patients (10 children) that benefit from the use of a totally implantable system for chronic administration. The total follow-up of all patients was 48 months (from 3 to 140 months). The initial effective daily amount of baclofen was 156 micrograms/24 hours and progressed in time to reach in the long run 280 micrograms/24 hours, with a very broad interindividual variability from 36 to 1050 micrograms/24 hours. All the patients benefited from a reduction in muscular hypertonicity as well as painful muscular spasms. On the other hand, the functional improvement was very variable from one patient to another and depended primarily on the initial clinical state and the etiology of the spasticity. The results observed were more significant in post-traumatic paraplegia than those secondary to demyelination disease even if they were stabilized with regard to spasticity of spinal origin. This mode of administration currently plays a significant role in the treatment of spasticity of cerebral origin, in particular in children presenting a motor disorder of cerebral origin with spastic prevalence. The current limitations of this type of treatment are technical because of the frequent catheter malfunctions, but are due essentially to the importance and constraint of the multi-disciplinary organization needed for the out-patient follow-up.

Baclofen↗