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Biomedical subjects

L de Medinaceli

Publications and source records attributed to L de Medinaceli.

At least 19 recordsLinked to original sources

Interpreting nerve morphometry data after experimental traumatic lesions.

Morphometric data were obtained in 2 experimental conditions: crush lesions of the sciatic nerve of rats, and transection of this nerve followed by repair. Ratios were used in order to facilitate comprehension of data. Results were compared to those obtained using a method of functional assessment. The study indicated that morphometric data provided a reliable picture of the trophic condition of regenerated nerves but did not correlate with the level of function.

Animals

Large amounts of polylactic acid in contact with divided nerve sheaths have no adverse effects on regeneration.

The stumps of divided rat sciatic nerves were coapted by suturing the epineurium to a small rectangular device made of a sheet of polylactic acid. One month later, significant degradation of the implanted material was observed. At that time, the local condition of the nerve was excellent, and the precise location of the initial injury could not be determined by examination under the operating microscope. Histology confirmed that there was no visible reaction to the biodegradable substance or its metabolites, and that neurotization of the distal stump was satisfactory. These findings were in agreement with those of other studies, and indicated that polylactic-acid devices affixed to divided nerves have no adverse effect on regeneration.

Animals

Applying "cell surgery" to nerve repair: a preliminary report on the first ten human cases.

We have applied a new technique of nerve repair, based on the principles of "cell surgery", to ten nerve lesions of the upper limb. Eight lesions were recent, five to 36 hours; they were divisions of the ulnar nerve (1), median nerve (2), sensory radial nerve (1), palmar and digital nerves (4). One lesion was 15 days old (median nerve). One eight-month-old loss of 4.5 cm. of the median nerve was grafted. In nine out of the ten cases, the short-term results were encouraging. Poor local conditions (fibrosis of the nerve bed) or poor general health (chronic alcoholism) had no adverse influence on the results. In the remaining case, the protocol was not followed in its entirety: it was not possible to crystallise properly the nerve, and trimming was done with scissors in the conventional way instead of smoothly trimming the solidified tips. The functional result in this case is a failure. These preliminary results seem to indicate that correctly applying the technique in its entirety may be more important than local conditions. We think that this technique can be applied to the majority of nerve lesions. The appropriate equipment is absolutely necessary in order to apply the method.

Adolescent

Experimental nerve reconnection: importance of initial repair.

We believe that the randomness of sprout regrowth is the cause of most poor experimental and clinical functional results after nerve repair. We have elaborated a technique of repair, called "nerve reconnection," aiming to minimize randomness of regrowth. This technique enhances the precision of repair by minimizing physical and chemical damage to the stumps and by ensuring stress-free stump abutment. In this study, the reconnection technique was compared to the conventional microsuture method. First, both techniques were tested as the primary method of repair. A method of behavioral evaluation, the sciatic functional index, was used to assess the results. The reconnection groups consistently showed satisfactory functional results, even after two successive procedures. In contrast, only one-third of the animals in the suture groups reached satisfactory functional levels. In the second part of the study, animals with unsatisfactory results after primary suture were reoperated in an attempt to improve the poor results of initial surgery. The secondary procedures used were either the reconnection technique or conventional microsuture. All secondary procedures failed to improve poor preexisting functional conditions. These findings stress the importance of the original "blueprint" of the nerve and the necessity of maintaining this unique pattern during initial repair.

Anastomosis, Surgical

Functional consequences of experimental nerve lesions: effects of time, location, and extent of damage.

The purpose of this experiment was to investigate the part played by each of the four fundamental components of a nerve in functional recovery from injury. In order to single out the role of cellular elements (the neurites), tissular elements (the Schwann cells), structural elements (the basal lamina tubes), and the blood-nerve barrier, various crush lesions were made on sciatic nerves of rats and functional recovery was studied. I examined the effects of the location and number of damaged sites and of the time elapsed between successive injuries. Results were assessed for a post-operative period of 2.5 months by studying tracks obtained from walking rats. This study suggested that (a) as far as neurites were concerned, the location of injury influenced the recovery pattern but the extent of damage did not; (b) the extent of damage to the Schwann cells had no measurable influence; (c) long-lasting deficits could be attributed to disruption of the basal lamina tubes, and (d) damage of the blood-nerve barrier could be responsible for slight and temporary disruption of the recovery pattern. I did not observe any of the possible beneficial effects of conditioning lesions described by some authors. This study emphasized the role of the basal lamina tubes in nerve injury and regeneration.

Animals

Functional consequences of experimental nerve lesions: effects of reinnervation blend.

In spite of a constant and irrepressible growth of sprouts from the proximal stump of peripheral nerves that have been injured, functional recovery varies greatly from one case to another. To try and understand the reasons for this variability, I have proposed a novel view of the events occurring in a regenerating nerve; based on this view, a probability model was designed that could represent all situations observed after nerve injury. This model, described elsewhere, is based on the assumptions that the guidance role of basal lamina tubes is fundamentally important and that when this guidance fails, regrowth is random. In the present study, this model was tested; behavioral results were measured after various procedures on rat sciatic nerve, and these data were compared with results predicted for similar injuries through the probability model. A good correlation was observed between theoretical and experimental results, indicating that the probability model was reliable. Using this model as the basis for my conclusions, the inconsistent results of current surgical techniques of nerve repair were tentatively explained.

Animals

Local autoimmune reaction and behavioral abnormalities after repeated nerve injury: an experimental study.

Sciatic nerves of rats were submitted to single and repeated injuries. The animals' gait was used to study motor function; autophagia was used to study sensory effects. An association with local post-traumatic autoimmune reaction was sought, after histochemical studies of the nerves. Our results indicated that a preliminary nerve lesion had a slight but significant influence on the recovery observed after a subsequent injury: after secondary damage, motor recovery was slightly delayed and sensory abnormalities were suggested by significant increase in autophagia. A causal role of autoimmunization was suggested but not proven. An interpretation of autophagia is proposed.

Analysis of Variance

Is it possible to predict the outcome of peripheral nerve injuries? A probability model based on prospects for regenerating neurites.

The long term functional consequences of peripheral nerve injuries are notoriously unpredictable. We hypothesized that considering the individual regrowth of the elementary components of a nerve (the neurites) rather than the global regeneration of the organ could lead to a better understanding of the mechanisms of nerve repair. Our basic assumptions were that regrowth was random and regrowth of any individual neurite could be defined in terms of its influence on recovery; this influence could be either valid, neutral or invalid. We designed a probability model describing the prospects of regrowth for nerves composed of several types of fibers. Our goal was to propose a general explanation of nerve healing rather than to predict the outcome in individual situations. The results suggested that this model satisfactorily described the events taking place in a healing nerve.

Animals

Promoting functional plasticity in the damaged nervous system.

Damage to the central and peripheral nervous system often produces lasting functional deficits. A major focus of neuroscience research has been to enhance functional restitution of the damaged nervous system and thereby produce recovery of behavioral or physiological processes. Promising procedures include surgical, physical, and chemical manipulations to reduce scar formation and minimize the disruption of support elements, administration of growth-stimulating substances, tissue grafts to bridge gaps in fiber pathways, and embryonic brain tissue grafts to provide new cells with the potential to generate fiber systems. Two elements are required for functional nervous system repair: (i) neurons with the capacity to extend processes must be present, and (ii) the regenerating neurites must find a continuous, unbroken pathway to appropriate targets through a supportive milieu.

Age Factors

Posttraumatic autoimmune reaction in peripheral nerve: effect of a single injury.

This study was conducted to show that local autoimmune reactions could be observed in rat sciatic nerve after a single injury. Furthermore, we attempted to correlate the intensity of the immunological reaction with the severity of nerve damage, with the type of surgical treatment and with the degree of functional recovery. Through the use of direct immunofluorescence techniques, we found that the severity of the initial damage was associated with the intensity of the local immunological response assessed 2.5 months after surgery. There was an association between type of surgical treatment and intensity of the autoimmune reaction. A correlation between autoimmune reaction and degree of long-term functional impairment was not immediately clear. The probable factors that underlie these results are discussed.

Animals

Posttraumatic autoimmune reaction in peripheral nerve: effect of two successive injuries at the same site.

We studied local autoimmune reactions in rat sciatic nerve after two successive injuries at the same site. The behavioral consequences of these injuries were also examined. We found that repetitive injuries had a moderately adverse effect on function and were accompanied by local autoimmune reactions. A causal relation between the two phenomena was possible but not clearly established.

Animals

Posttraumatic autoimmune reaction in peripheral nerve: effect of two successive injuries at different locations.

We studied the influence of previous nerve damage on the evolution of recovery that follows a second nerve injury. Recovery from nerve injury was assessed by analyzing rats' foot prints during a 74-day period. In addition, at the end of this period, the surgically treated sciatic nerves were immunohistochemically stained for the presence of immunoglobulins, an indicator of an autoimmune reaction. We found there was a moderately adverse effect of previous nerve damage on the sciatic functional recovery, a fact that suggests some systemic response to the distantly placed initial damage. Immunohistochemical staining showed various degrees of immunoglobulin deposition depending on the type of the two injuries. An interpretation of our results is proposed.

Animals

Rat sciatic functional index data management system with digitized input.

Quantification of the functional condition of rat sciatic nerve is an important experimental procedure. In the present study, a system for management of the sciatic functional index ( SFI ) data is described. Results obtained with the Sciatic Index Management System (SIMS) were compared with results obtained with other measurement techniques. Validity and reliability of the SIMS were found to be excellent, and speed of data analysis was increased. It is concluded that the SIMS represents a significant advance in the quantification of nerve regeneration data.

Animals

Peripheral nerve reconnection: inhibition of early degenerative processes through the use of a novel fluid medium.

Two pharmacologic manipulations were applied to injured nerves in the rat to minimize the secondary damage that accompanies peripheral nerve transection. It is known that calcium influx into the nerve is responsible for some of the processes that have been termed Wallerian degeneration. These disruptive effects of high intracellular calcium were retarded by chlorpromazine, a potent inhibitor of calmodulin. Our results suggested a new method for reducing posttraumatic neural disruption and supported our hypothesis regarding the involvement of calmodulin or some other Ca2+ binding protein in Wallerian degeneration. The second part of this report describes changes observed at the tips of a severed nerve and their prevention through the use of polyvinyl alcohol. Finally, we showed that neither substance produced functional deficits when injected directly into the sciatic nerve of rats and could thus be used in animal experimentation.

Animals

Peripheral nerve reconnection: immediate histologic consequences of distributed mechanical support.

We tested the possibility of improving the quality of axonal repair after peripheral nerve transection by suppression of all mechanical stresses from the zone of repair. A method was developed involving mechanical support of the sciatic nerve from below in a grooved chamber with additional support provided by suturing the nerve to a rubber sleeve. Histological studies of silver-impregnated specimens from rabbit sciatic nerve using this technique revealed that the axons' tips were closely reconnected with minimal disruption in their direction or in the alignment of fibers and without extraneous material between the severed stumps. Comparison of these results with those of current microsurgical techniques showed the unequivocal superiority of this method in terms of immediate histologic aspects. The course of Wallerian degeneration was not modified.

Animals