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Biomedical subjects

R Franco-Bourland

Publications and source records attributed to R Franco-Bourland.

18 recordsLinked to original sources
PubMed1996

Alteration of cyclosporin-A pharmacokinetics after experimental spinal cord injury.

The pharmacokinetics of the immunosuppressive agent cyclosporin-A (CsA) were studied in rats submitted to spinal cord (SC) injury. A single CsA 10 mg/kg dose was given either intraperitoneally (i.p.) or orally to rats submitted to experimental SC injury at the T8 level. Twenty four hours after lesion (acute stage of SC injury) i.p. CsA bioavailability was increased, while t1/2 was prolonged. However, oral bioavailability was reduced. Seven weeks after lesion (chronic stage of SC injury) CsA bioavailability, by either route, was not significantly different from control values. Results indicate that parenteral CsA bioavailability is increased during the acute stage of SC lesion, probably due to an impaired elimination. Oral bioavailability, however, is decreased, since there is also an important reduction in gastrointestinal CsA absorption that overrides the effect of impaired elimination. Alterations in CsA pharmacokinetics appear to revert during the chronic stage of SC injury. Changes in CsA bioavailability, depending on the route of administration and on time, must be considered to design an adequate immunosuppressive treatment in SC injury.

Administration, Oral↗
PubMed1996

Use of cyclosporin-A in experimental spinal cord injury: design of a dosing strategy to maintain therapeutic levels.

Cyclosporin-A (CsA) is frequently used as an immunosuppressive agent in experimental transplantations. CsA has been used in nervous tissue transplants in spinal cord injury (SCI). However, optimal results have not been obtained. This is likely due to the fact that SCI alters CsA pharmacokinetics and hence fixed dose regimens are not adequate. In this study, several CsA dosing regimens were evaluated in Long-Evans female rats subjected to a severe low thoracic (T8) SCI by the contusion method. Serum CsA concentrations were measured to determine which dosing regimen allowed CsA levels to be maintained within the therapeutic window. It was found that administration of 2.5 mg/kg/12 h intraperitoneally during the first 2 days after SCI (acute phase) followed by 5 mg/kg/12 h orally thereafter (subacute and chronic phases) yields CsA circulating levels within the therapeutic window, i.e., 0.120-0.275 microgram/mL. This dosing regimen represents a suitable alternative to fixed dosing to achieve an optimal CsA-induced immunosuppression in experimental models of SCI.

Animals↗
PubMed1994

Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo.

We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury.

Animals↗
PubMed1994

Development of post-traumatic cysts in the spinal cord of rats-subjected to severe spinal cord contusion.

To study the development of post-traumatic spinal cord (SC) cysts, and their fine anatomic characteristics, rats were subjected to severe SC contusion. Specimens were analyzed from day 1 to 1 year post-injury. Using conventional light, and transmission and scanning electron microscopy, three stages were typified, namely: necrosis, repair, and stability. The final cell composition and thickness of the cyst walls were not uniform. Astrocytes, fibroblasts, ependymal cells, and collagen fibers were the main constituents. Chronic inflammatory cells were also observed. The neuropathologic characterization of posttraumatic SC cysts could be useful in planning strategies for SC reconstruction at different times post-injury.

Animals↗
PubMed1991

Development of human neural transplantation.

The possibility of altering the course of Parkinson's disease by brain grafting is slowly becoming a reality through the efforts of many research groups worldwide. It has been shown that this procedure, as performed in high-level medical research centers, usually produces no permanent adverse effects and can effectively ameliorate parkinsonian signs in certain patients. This progress has served to reinforce our commitment to develop neural transplantation into an effective therapy to treat such a devastating neurodegenerative disease. We have summarized the most important events that have shaped the initial phase of this research. In the course of the last 4 years, considerable knowledge has been gained in the clinical neurosciences regarding the real potential of various brain grafting procedures in treating Parkinson's disease, their shortcomings, and their usefulness in carefully selected patients. There is still no consensus regarding the various fundamental aspects of human brain grafting in Parkinson's disease. Questions concerning surgical technique, candidate selection, the optimal brain regions for implantation, the optimal tissue for implantation, and the real usefulness of brain grafting must be addressed. The importance of the quality of adrenal medulla fragments for grafting, the requirement for immunosuppressors in fetal brain grafting, and the optimal fetal age and the amount of donor tissue for effective grafting are additional areas of concern. The potential of xenografting, preserved tissues, and genetically engineered cells for human brain grafting remain unanswered. The development of human neural transplantation is the responsibility and privilege of neurosurgery.

Animals↗
PubMed1991

Autologous adrenal medullary, fetal mesencephalic, and fetal adrenal brain transplantation in Parkinson's disease: a long-term postoperative follow-up.

We report on the clinical status of 5 patients with Parkinson's disease (PD) 3 years after autologous adrenal medullary (AM)-to-caudate nucleus (CN) implantation, and of 2 PD patients, 2 years after fetal ventral mesencephalon (VM)- and fetal adrenal (A)-to-CN homotransplantation. Current clinical evaluation of 4 of the AM grafted patients revealed sustained bilateral amelioration of their PD signs, most notably of rigidity, postural imbalance and gait disturbances, resulting in a substantial improvement in their quality of life. The disease-related dystonia of one of them disappeared only 2 years after surgery. The levodopa requirements of 2 of these patients and the anticholinergic therapy of another have been reduced. In agreement with the satisfactory clinical evaluation of these 4 patients, their neuropsychological and electrophysiological improvements, initially registered 3 months after surgery, have been maintained for 3 years. After 1 year of significant recovery, the 5th patient of this group has almost returned to her preoperative state. The 2 homotransplanted patients also showed sustained bilateral improvement of their PD signs. Two years after surgery, the most improved signs of the fetal VM case were rigidity, bradykinesia, postural imbalance, gait disturbances and facial expression. The fetal A case has only shown amelioration of rigidity and bradykinesia. Neither of them has shown significant neuropsychological changes. Their current levodopa requirements are less than before surgery. The improvements shown here by PD patients after brain tissue grafts go beyond those obtained using any other therapeutic approach, when levodopa fails. Although more studies and the development of these procedures are obviously required, these initial human trials appear to be resisting the test of time.

Adrenal Glands↗
PubMed1990

Fetal homotransplants (ventral mesencephalon and adrenal tissue) to the striatum of parkinsonian subjects.

Fetal ventral mesencephalon and fetal adrenal tissue grafted to the caudate nucleus of four and three parkinsonian patients, respectively, have been shown to be an alternative treatment for the amelioration of the signs of the disease. The ventral mesencephalon patients had a significant amelioration of rigidity, bradykinesia, postural imbalance, gait disturbance, and facial expression. Three of these four patients have returned to work. The fatal adrenal group only showed amelioration of rigidity and bradykinesia. Though these patients are now able to perform their basic daily living activities, and one of them has renewed her household tasks, the other two have not yet been able to return to work. The differences observed between the ventral mesencephalon- and the fetal adrenal-transplanted patients may be related to the heterogeneity of their disease and/or the type of graft implanted. However encouraging our results may be, this experimental procedure obviously requires further studies, and should not be practiced outside of highly qualified clinical research centers.

Adrenal Glands↗
PubMed1988

Neuropsychological effects of brain autograft of adrenal medullary tissue for the treatment of Parkinson's disease.

We describe the pre- and postoperative neuropsychological profiles of seven patients who received an autograft of adrenal medullary tissue to the caudate nucleus for the treatment of Parkinson's Disease (PD). The preoperative neuropsychological evaluations revealed specific cognitive deficits of varying degree. The patients showed frontal lobe-type deficits with alterations in behavioral programming leading to difficulties in the organization of motor sequences and alternating programs. They also showed memory disorders and visuospatial and visuoperceptual deficiences such as a loss of figure-ground perspective and fragmentation. Postoperative evaluations, carried out 3 months after neurosurgery, revealed a significant amelioration of the frontal lobe-type symptoms and visuospatial deficits, as well as an improvement in memory tasks that require an active organization of the response. Immediate and delayed memory difficulties remained unchanged. These observations were compared to neuropsychological data obtained from neurologically intact subjects and from unoperated PD patients. The improvements of the operated PD patients resulted in performance levels close to normal values and clearly distinguishable from those of unoperated PD patients, and were unrelated to improved mood, increased alertness, or sustained attention. Autotransplantation of adrenal medullary tissue to the caudate nucleus of PD patients showing a decreased effective response to L-dopa therapy can partially restore motor functions and frontal-type cognitive symptoms.

Adrenal Medulla↗
PubMedDate not supplied

[Human fetal homograft to the nigrostriatal system for the treatment of Parkinson's disease].

Four cases of transplant to the brain (striatum) of the ventral mesencephalic area (VMA) and three adrenal glands (A) to patients with Parkinson's disease are described as a new alternative for the improvement of this disease. The patients who received VMA showed a very significant improvement in the rigidity, bradykinesia, alterations in walking and posture, as well as the facial expression. Three of the four patients have returned to work. The group that received A tissue, showed a discreet improvement in the rigidity and bradykinesia, but none in the other signs of the disease. These patients are able to accomplish their daily needs, but two are unable to return to work. The differences which we observed between patients receiving VMA and A transplants, might be related to the heterogeneity of the disease, although we believe that the type of graft was responsible of these differences. Our results with the use of VMA, as well as that of other groups, are encouraging, although it is important to clearly establish that it is a procedure which is still in an experimental phase, requiring caution, and should only be practiced in highly qualified centers of clinical research.

Adrenal Glands↗
PubMedDate not supplied

[Autograft of the adrenal medulla to caudate nucleus as Parkinson disease treatment: long-term clinical evaluation].

This work presents the long-term evolution (12-27 months) of the patients with adrenomedullary autotransplants to the caudate nucleus for the treatment of Parkinson's disease. Sixteen men and 6 women, mean age of 49.9 years, received brain implants of their own adrenal medulla using the procedure of Madrazo et al. (1). Nineteen of the transplanted patients suffered idiopathic Parkinson's disease and 3 of them parkinsonism. Before surgery 20 patients were on L-dopa and suffered collateral signs due to the drug. The degree of severity of their disease was evaluated pre and postoperatively, with and without medication, in their "on" and "off" periods, using the international scales of Schwab and England, Hoehn and Yahr, Madrazo, and the UPRS, and was documented by videotape. Biochemical analyses were made of lumbar and ventricular cerebrospinal fluid, and neuropsychological and neurophysiological evaluations were performed before and after surgery. In some patients, the location and viability of the adrenal medullary implants were demonstrated by brain scintigraphy using 131-I-metaiodobenzylguanidine, a chromaffin specific radiopharmaceutical. The clinical evaluations of 18 autotransplanted patients (4 died) showed their significant functional recovery both in their "on" and "off" periods, that for the first patients operated has remained stable for 27 months. Also, their response to L-dopa improved allowing the reduction of their postoperative doses of medication to 30% of their preoperative requirements, with the disappearance of the collateral effects of the drug.

Acetylcholinesterase↗