Biomedical subjects
Publications and source records attributed to M Molinari.
Despite improvement in knowledge of the etiopathogenesis of this syndrome, it is still difficult to formulate any prognosis. Our experience in long-term follow-up in order to avoid any possible complications is discussed.
Since 1987 we have treated 17 patients with bone sarcomas of the extremities (14 osteosarcomas, 3 malignant fibrous histiocytomas), with 2 cycles of neoadjuvant chemotherapy, consisting in iv high dose Methotrexate, Cis-Platin in 3 days in continuous infusion, and iv Adriamycin every 29th day. We obtained "good necrosis" (greater than 90%) in 13 patients (76.5%). We briefly report the possible correlations between angiographic findings after the first cycle and response to chemotherapy. All patients but one (94%), underwent conservative surgery. To date no patients have had local recurrence; 12 patients (70.5%) are disease free at a median follow up of 21.5 months; in 5 patients lung metastases appeared. To define overall survival and disease-free survival a longer follow up is required.
Immunocytochemistry of fetal and adult monkey thalamus reveals a dense concentration of tachykinin immunoreactive fibers and terminals in the dorsolateral part of the VPM nucleus in which the contralateral side of the head, face and mouth is represented. The immunoreactive fibers enter the VPM nucleus from the thalamic fasciculus and electron microscopy reveals that they form large terminals resembling those of lemniscal axons and terminating in VPM on dendrites of relay neurons and on presynaptic dendrites of interneurons. Double labeling strategies involving immunostaining for tachykinins after retrograde labeling of brainstem neurons projecting to the VPM failed to reveal the origin of the fibers. The brainstem trigeminal nuclei, however, are regarded as the most likely sources of the VPM-projecting, tachykinin positive fibers.
A method for the determination of aprotinin (bovine pancreatic trypsin inhibitor, BPTI) is described. The procedure involves the formation of the BPTI-trypsin complex in the presence of an excess of BPTI, quantitative separation of the residual BPTI from the mixture by affinity chromatography and identification and evaluation of the residual BPTI by reversed-phase high-performance liquid chromatography. The method is precise with a mean coefficient of variation of 4.0 and 4.3% for intra- and inter-assay runs, respectively, and has a limit of determination of 3.0 micrograms of aprotinin. The proposed method can be applied to commercial samples, even in very dilute solutions, for the standardisation of aprotinin.
In a group of ten hypertensive patients, the effects of methyldopa administration in two different formulations on serum prolactin (PRL) were studied. A single oral dose of normal release methyldopa significantly increased serum prolactin levels, peak concentrations occurring 3 to 6 h after drug administration. On the contrary, administration of sustained release methyldopa at the same dose was only followed by slight and not significant fluctuations in prolactin plasma levels. Both formulations produced a significant decrease of systolic and diastolic blood pressures, without significant differences between sustained and normal release methyldopa effects.
The distributions of fibers and terminals immunoreactive for somatostatin (SRIF), neuropeptide Y (NPY), substance P (SP) and cholecystokinin octapeptide (CCK), were studied in the diencephalon of cynomolgus monkeys. Immunoreactivity for all 4 peptides is found in extrinsic afferent fibers innervating the dorsal thalamus, ventral thalamus and epithalamus. The distributions of such fibers are more extensive than previously described and include many relay nuclei in their zones of terminations. SP fibers are particularly concentrated in the ventral posteromedial nucleus. All peptides are especially concentrated in fibers in the intralaminar and reticular nuclei. Afferent fibers immunoreactive for each of the 4 peptides approach the thalamus by two pathways. An anterior route is formed by the classical periventricular system ascending from the hypothalamus to the epithalamus. A posterior pathway ascends in the lateral midbrain tegmentum and provides innervation to posterior, intralaminar, and many relay nuclei, plus the ventral thalamus. A basal forebrain pathway, containing SRIF and NPY immunoreactive fibers, enters the thalamus in association with the ansa lenticularis and SP fibers also ascend from the substantia nigra.
The topographical relations among the terminal field of spinothalamic fibers and the cells projecting upon areas 4 and 5 were studied in the anterior intralaminar nuclei of the cat. Terminals anterogradely labeled from the spinal cord and cell populations retrogradely labeled from the lateral pericruciate and anterior suprasylvian cortex were simultaneously observed by means of a multiple fluorescent tracing strategy. The present findings confirm that spinal afferents in the central lateral and paracentral nuclei overlap with the cells projecting to area 4. Further, the present data demonstrate that spinal terminals are largely segregated from the intralaminar cell population projecting to area 5.
The organization of the cortical projections of the ventral medial thalamic nucleus (VM) was studied in the cat with retrograde tracers. The extent of the VM-cortical projections was first investigated with horseradish peroxidase injected in different cortical fields. The results obtained in the experiments indicated that the main target of VM efferents is represented by a large territory anterior to the cruciate sulcus involving area 6 and the gyrus proreus and extending into the anterior part of the medial cortical surface. The afferents to these precruciate fields arise from throughout the VM. In addition, the lateral third of VM projects upon the lateral precruciate cortex that is coextensive with the precruciate part of area 4, whereas VM efferents do not extend into the posterior sigmoid gyrus. A second major target of VM efferents is represented by the insular cortex in the anterior sylvian gyrus. VM projections also reach the prepyriform cortex and the cingulate gyrus. An anteroposterior decrease of density was found in the VM-cingulate projections. Sparse VM projections reach the temporal cortex, the adjacent posterior sylvian and ectosylvian fields, and the anterior ectosylvian gyrus. No VM projections were found either upon the visual areas 17 and 18 or upon the primary auditory cortex. The interrelations between some VM-cortical cell populations and their divergent collateralization were studied by using double retrograde labeling with fluorescent tracers. The results of these experiments demonstrated that a relatively high number (at least 20%) of VM cells projecting to the insula are also connected to the precruciate fields by means of axon collaterals. This finding indicates that VM is a highly collateralized structure of the cat's thalamus. Very few branched cells were found in the other combinations of cortical fields here examined (precruciate vs. posterior sylvian fields, lateral precruciate vs. proreal cortex, anterior vs. posterior cingulate fields). Altogether these data indicate that VM branched cells preferentially interconnect the two main cortical targets of the nucleus, i.e., precruciate and insular fields. The results of the present study are discussed in regard to the literature on the VM projections in the rat and the previously available data in the cat, to the afferent VM organization in the cat, to the relationships between VM and the nucleus submedius, and to the anatomical and functional role of VM in relation to the so-called "nonspecific" thalamocortical system.
The postlesional reorganization of the cerebellothalamic cells was here studied using a multiple retrograde tracing technique. To this purpose, the cerebellothalamic cell population was investigated in 3 groups of adult rats: (a) cases hemicerebellectomized at birth; (b) cases hemicerebellectomized in adulthood; and (c) control unlesioned ones. In all of the groups the fluorescent tracers Diamidino Yellow and Fast Blue were injected bilaterally in the thalamus and the retrograde labeling obtained in the cerebellar nuclei was analyzed quantitatively. In the adult unlesioned rats the cerebellar cells projecting to the ipsilateral thalamus represented 3-4% of the cell population projecting to the contralateral thalamus. Furthermore, in agreement with previous results, it was demonstrated that the ipsilateral component was almost totally formed by axon collaterals of the main contralateral cerebellothalamic pathway. The organization of the bilateral cerebellothalamic pathway was unaffected by a hemicerebellectomy performed in adulthood. However, when the hemicerebellectomy had been performed at birth, the number of cerebellar cells that project to the ipsilateral thalamus was 3 times higher than in the controls. In these lesioned cases, as in the other ones, the ipsilateral projecting cell population was mainly represented by branched cerebellar cells which project bilaterally upon the thalamus. These results indicate that the bilaterality of the cerebellothalamic pathway is enhanced after an early hemicerebellectomy, and that this phenomenon is responsible for the reinnervation of the deafferented thalamus. Further, the present study shows that the increase in the bilaterality of the system is sustained by cerebellar cells which bifurcate bilaterally upon the thalamus, and therefore that the reinnervation of the deafferented thalamus is performed by axon collaterals of the contralateral spared cerebellothalamic pathway.
The divergent collateralization of the ipsilateral descending limb of the brachium conjunctivum was here studied in the rat by means of fluorescent retrograde double-labeling. Tracer injections in the lateral part of the medulla oblongata were combined with injections of another tracer in the contralateral thalamus. Retrogradely single-labeled cells, as well as a relatively high number of double-labeled ones, were found in the lateral part of the interpositus and in the dorsolateral hump in the cerebellar nuclei ipsilateral to the medullary injections. The present results demonstrate that the same cerebellar cells interconnect by means of axon collaterals the ipsilateral medulla oblongata and the contralateral thalamus.
Connections ascending to the thalamus. Contrary to classical opinion, all thalamic nuclei receive extrathalamic afferents. Segregation or convergence within a topographically defined nucleus represent two modalities of thalamic afferents. In addition, certain topographically organized thalamic afferents possess "privileged" or primary "targets" in the thalamic nucleus while others possess supplementary "targets" in other thalamic nuclei (see cerebellar, pallidal and spinothalamic projections). Ascending connections from several brain stem structures can converge on the same nucleus or diverge to several thalamic nuclei. Thalamic connections with the telencephalon. Methods for determining axonal transport have demonstrated that all thalamic nuclei, with the exception of the reticular nucleus and the ventral part of the lateral geniculate body, project towards the cerebral cortex. Four nuclear complexes can be recognized in the cat as a function of the different modalities of localization, concentration and lamination of the projections towards the cortex and the central grey nuclei. In general, the thalamocortical connections have reciprocal ipsilateral corticothalamic projections originating in the infragranular layers of the cerebral cortex. The reticular nucleus and the ventral part of the lateral geniculate body, which is not projected to the cerebral cortex, are exceptions. Each cortical area receives a "privileged" connection from a thalamic nucleus and a supplementary connection- from one or several other thalamic nuclei. The "privileged" connections usually pass to the fourth and third layers of the neocortex, and sometimes also to the first layer. In contrast, the supplementary connections pass to different superficial or deep cortical layers. Each nucleus is formed of subunits which possess different hodologic and topographic characteristics as a function of the nucleus considered. Convergence or divergence of thalamocortical and corticothalamic projections on the different thalamic nuclei, as well as the laminar distribution of efferents in the cerebral cortex, are related strictly to the hodologic organization of different cellular subunits constituting the nuclei. Concentration or diffusion of thalamic projections on cerebral cortex is related more to the single or multiple projection of cell populations belonging to a thalamic nucleus than to widespread collateralization of thalamocortical axons.
Numerous recent experimental studies have evidenced that considerable remodelling takes place in the central nervous system following an injury. The postlesional reorganization is particularly active in the central circuits when the injury occurs during development. The basic structural postlesional mechanisms, such as axonal sprouting and synaptic rearrangement, are here briefly outlined. Experimental evidence of postlesional structural reorganization of central neurons is provided, with special reference to the remodelling that follows cerebellar lesions.
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The anterograde transport of lectin-conjugated horseradish peroxidase (WGA-HRP) was here employed in order to visualize crossed corticothalamic efferents of the motor cortex in rats and cats. After WGA-HRP cortical injections in the rat retrogradely labeled cells were observed in the ipsilateral thalamus, and heavy anterograde labeling was observed both in the ipsi- and contralateral thalamus. The contralateral anterograde labeling was less intense than the ipsilateral one and it was distributed in the anterior intralaminar structures, in the parafascicular nucleus, in the ventromedial, ventrolateral and ventrobasal nuclei and in the posterior complex, symmetrically to the labeling observed on the ipsilateral side. Further experiments were made in the rat in order to ascertain that the bilateral anterograde labeling in the thalamus derived unilaterally from the cortex. To this purpose, kainic acid was injected unilaterally either into the frontal cortex or into the thalamus, and WGA-HRP was later injected on the same side in the frontal cortex. Moreover, WGA-HRP was injected into the frontal cortex after splitting of the corpus callosum. The results obtained in these experiments confirmed that cortical neurons projected bilaterally upon the thalamus. Further, these experiments indicated that at least the majority of the contralateral fronto-thalamic fibers crossed the midline in the thalamic massa intermedia. WGA-HRP injections into the pericruciate cortex in the cat confirmed the presence of anterogradely labeled terminals in the contralateral anterior and posterior intralaminar, ventral anterior, ventromedial and ventrolateral nuclei. The labeling was in all cases heavier in the intralaminar nuclei than in the other structures, but it was less intense than that observed in the rat.(ABSTRACT TRUNCATED AT 250 WORDS)
The organization of the claustrocortical system was investigated in rat by means of cortical injections of either lectin-conjugated horseradish peroxidase or retrograde fluorescent tracers. The latter were also employed in cat. Evans Blue, Fast Blue, True Blue, Nuclear Yellow and Diamidino Yellow were used in different combinations and were injected, uni- or bilaterally, in different cortical fields. Cells retrogradely labeled from each cortical injection were observed in the ipsi- and contralateral claustrum. Anterogradely labeled terminals were also seen in the claustra of both sides in the horseradish peroxidase experiments. The topographic and quantitative study of the distribution of labeled neurons showed a topographic organization of the rat's claustrocortical system, although a certain degree of overlap of the cell populations projecting to frontal and occipital fields was also evident. Four types of branched claustrocortical neurons were observed in the double labeling experiments: neurons branching ipsilaterally (A) or contralaterally (B) to anterior and posterior cortical fields; neurons branching bilaterally to homotopic (C) or heterotopic (D) cortical fields. Each population of branched neurons was equivalent to a different percent value of the total labeled cell populations; the percent value decreased from type A to type D. Type C branched neurons were also identified in the claustrofrontal system of the cat. The intricate organization of the claustral-ascending projections suggests that the nucleus is involved in different cortical activities and that its efferents may also provide the substrate of a powerful subcortical mechanism of interhemispheric communication.
The present study was aimed at the anatomical identification in the rat of neurons of the lower brainstem reticular formation which give off axonal branches ascending bilaterally to more rostral structures and descending unilaterally to the spinal cord. Three fluorescent tracers were injected in one and the same animal. Fast Blue was injected in the midbrain tegmentum, in the termination areas and fiber bundles of the ascending reticular efferents; Evans blue was injected in the midbrain tegmentum on the other side; either Nuclear Yellow or Diamidino Yellow was injected in the white and gray matter of the upper cervical cord. All three populations of single-labeled cells, as well as double labeled either from the midbrain injections or from the ipsilateral injections in the mesencephalon and spinal cord, were intermingled in the medial reticular formation. Very few cells double labeled from the contralateral mesencephalon and ipsilateral spinal cord were also seen. However, the main finding of the present study was the visualization of triple-labeled cells. The latter were mainly located ipsilaterally to the injections in the spinal cord. The present results indicate that reticular cells give off divergent multiple branches descending to the ipsilateral spinal cord and ascending bilaterally to rostral centers.
In order to investigate the topographical relationships between the caudal diencephalic cells of origin of ascending and descending projections in the rat, one fluorescent retrograde tracer was injected into the striatum and another into the medulla oblongata. The medullary injections were mainly centered in the inferior olive. Cells labeled from the striatal injections densely filled the thalamic parafascicular nucleus. Cells labeled from the medullary injections were seen ventrally to the fasciculus retroflexus in the subparafascicular nucleus. The two populations were mixed in a small area at the ventromedial border of the fasciculus retroflexus. No double labeled cells were observed. The present results indicate that caudal diencephalic cells which ascend to the striatum are different from those descending to the medulla oblongata and that they partially overlap.