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Biomedical subjects

M Molinari

Publications and source records attributed to M Molinari.

At least 91 records · Page 5Linked to original sources

Cerebro-cerebellar interactions in man: neurophysiological studies in patients with focal cerebellar lesions.

Recently Ugawa and co-workers reported that motor cortex excitability after magnetic stimulation in man can be reduced by coupling an electrical transcranial stimulus over the base of the skull. They hypothesised that the motor cortex inhibition observed was determined by activation of cerebellar structures. Nevertheless, the paradigm employed did not allow to exclude interference from extracerebellar structures due to spread of the electrical stimulus. In order to ascertain the role of the cerebellum in determining the modulation of the motor cortex excitability we examined, in 10 normal subjects and in 2 patients with unilateral cerebellar lesions, the effects of electrical stimuli over the base of the skull on the motor responses evoked by cortical magnetic stimulation. In both patients no inhibition of motor responses was present in the muscles ipsilateral to the lesion, whereas an inhibition, similar to that observed in controls, was evident on the opposite side. The present findings suggest the cerebellar origin of the motor effects seen after electrical stimulation of the base of the skull and further clarify the physiological cerebro-cerebellar interactions in man.

Action Potentials↗

Clinical and bacteriological efficacy and tolerability of FCE 22891 in patients with exacerbations of chronic obstructive pulmonary disease.

A beta-lactamase-stable antibiotic, the oral penem FCE 22891 (ritipenem acoxil), was investigated for use in exacerbations of chronic obstructive pulmonary disease (COPD). Thirteen of the 15 COPD patients had a proven lower respiratory tract infection. Symptom scores and forced expiratory volumes in 1 s significantly improved during therapy with FCE 22891 in combination with bronchodilators and intravenous corticosteroids. Conversion of representative sputum to nonrepresentative sputum or eradication of the original pathogen in representative sputum was effected in 12 patients. Resistance to FCE 22891 was observed in three cases with Haemophilus influenzae. Gastrointestinal disturbances, of which one was severe, were experienced by eight patients. Although FCE 22891 has some beneficial effect in exacerbations of COPD, there are reservations about its use because of adverse effects and potential inefficacy in the treatment of infection with H. influenzae.

Adult↗

Excitability of the motor cortex to magnetic stimulation in patients with cerebellar lesions.

The excitability of the motor cortex to magnetic stimulation was evaluated in seven patients with cerebellar lesions (six patients with a unilateral lesion) and in 20 control subjects. Magnetic motor threshold was defined at rest. In all but one of the patients with a hemicerebellar lesion the threshold was higher in the motor cortex contralateral to the impaired hemicerebellum and the right/left threshold asymmetry was clearly greater than normal. In the patient with a lesion involving both cerebellar hemispheres the magnetic threshold was above the normal limit on both sides. The latencies of motor responses were normal in all patients. This increase in the magnetic threshold of the motor cortex functionally related to the impaired hemicerebellum suggests the existence of a facilitating tonic action of the cerebellum on central motor circuits that might act at the cortical, or spinal level, or both.

Adult↗

Hemicerebellectomy and motor behaviour in rats. III. Kinematics of recovered spontaneous locomotion after lesions at different developmental stages.

The locomotion of rats with a right hemicerebellectomy (HCb) performed in adulthood was compared by means of kinematic analysis with the locomotion of rats with a similar lesion performed on the first postnatal day. The age at which the animals received cerebellar lesion made a significant difference with respect to the locomotor strategies utilized in adulthood. During stance, neonatal operate rats showed a clear hyperextension of both hindlimbs but not of the forelimbs. Their locomotor posture was characterized by spinal flexion with the head held lower than normal. During swing, they showed a tendency towards 'high stepping'. Their steps were regular and symmetrical but hypometric. Adult lesioned animals displayed a marked extensor hypotonia, ipsilateral to the lesion during stance and a relevant hyperflexion affecting both sides, during swing. Alteration of the interlimb coordination and modified sequence of steps were also observed. Thus, a highly asymmetrical, impaired and unstable locomotion was displayed by this group of animals. The present findings demonstrate the importance of the age-at-lesion factor in determining the motor strategies in the recovery of locomotor function after HCb in the rat. This evidence is discussed in the light of the widespread anatomical remodelling already demonstrated following neonatal, but not adult, HCb in rats.

Aging↗

Precision and accuracy of subjective time estimation in different memory disorders.

The aim of this study was to evaluate how different memory disorders affect subjective time durations. For this purpose we studied prospective time estimations in 4 amnesic (A) and in 15 Alzheimer's disease (AD) patients, and compared their performance with that of 5 matched young normal controls (YC) and 15 elderly subjects (EC). For the short-time durations we asked the subject to repeatedly reproduce a standard interval of 1 s. To test how subjects evaluated longer time durations, we choose a verbal estimation procedure. The subjects' task was to read either 5, 10, 20, or 40 digits appearing one at a time, while concurrently keeping the rhythm of 1 key press per second. At the end of each sequence, subjects had to judge the elapsed time from the beginning of the trial. Results showed that amnesics can correctly reproduce 1-s intervals. However, their accuracy of verbal estimates of longer durations was severely impaired. AD patients showed increased variability on repeated reproduction of 1-s intervals and were both inaccurate and imprecise in their verbal estimate of longer durations. Using the framework of the Scalar Timing Model, we conclude that amnesic patients exhibit a deficit in encoding and storing the current time for intervals that exceed their short-term memory range, while AD patients show a pattern of deficit that is explained by a more widespread involvement of both the clock, the memory, and the decisional mechanisms.

Adult↗

Time course of nigrostriatal system changes after tract hemisection and effects of ganglioside treatment: a multiple retrograde fluorescent tracing study.

The postlesion phenomena of nigrostriatal neurons following partial tract hemisection have been studied with retrograde axonal transport of dyes in rats treated with saline or GM1 ganglioside (30 mg/kg, i.p., daily for varying times). The time course of the plastic changes in both experimental animal groups was determined by a double retrograde fluorescent tracing technique, utilizing Fast blue (FB) as prelesion tracer, and Diamidino yellow (DY) as postlesion tracer. The data show that the number of nigral cells retrogradely labeled by the prelesion intrastriatal injection of FB declined progressively to 50% of their initial number over 3 weeks. The ganglioside treatment did not significantly influence this temporal pattern of labeled cell loss. By DY-labeling, an almost complete block of the retrograde axonal transport was observed up to 1 week postlesion and only after 3 weeks a partial recovery was evident, positively influenced by the GM1 treatment. Therefore, together with the findings on nigrostriatal cell loss, these data indicate that ganglioside treatment favors and/or accelerates the recovery of axonal transport of surviving nigral neurons but does not significantly affect their degenerative rate in the first 3 weeks after the lesion.

Amidines↗

Role of bioelectrical impedance analysis in acutely dehydrated subjects.

15 young healthy volunteers were studied to assess the reliability of bioelectrical impedance analysis (BIA) to determine body composition during acute dehydration. Body weight (BW), resistance and reactance measurements were performed before and 4h after a 40 mg intravenous administration of furosemide. BW decreased on average from 69.09 +/- 9.83 kg to 67.43 +/- 9.72 kg (p < 0.001), while resistance, reactance, and phase angle showed significant increases. The individual variations in bioelectrical parameters were not related to the BW loss. Formulae to derive body composition predicted poorly the true water loss (mean individual error: 40% of real loss). The errors in body composition prediction were unrelated to basal percentage of fat free mass, to body mass index, or to BW loss after furosemide administration. In conclusion, BIA proved unreliable in calculating the body composition of acutely dehydrated subjects.

Journal Article↗

[The usefulness of dietetic supplementation in feeding after gastric and pancreatic surgeries].

We evaluated the efficacy of an oral artificial supplementation in 22 patients who underwent surgery for gastric or pancreatic cancer. From 8th to 14th postoperative day, 11 patients (cases) received a diet consistent in their REE, and an oral integrator (40% of REE); controls received only the diet. On 7th and 15th day, nutritional and anthropometric parameters were evaluated, and bioelectrical impedance analysis (BIA) was performed to assess body composition. The dietary caloric input was similar in cases (1154 kcal, 86.0% of REE) and controls (1393 kcal, 92.3% of REE). Due to the integrator, cases reached 121.4% of REE (p less than 0.001). The nutritional and anthropometric parameters studied did not show significant variations in the two groups, but BIA showed a decrease of fat mass in controls with respect to cases (p less than 0.02). Our results demonstrate that the oral artificial supplementation was well tolerated, and did not reduce food intake, but induced a significant increase of total caloric input.

Adult↗

[Need for control and anxiety of losing it--reflections on the treatment of anorexia nervosa].

In connection with the symptoms of anorexia nervosa, which are usually based on a fear of losing control over food intake, we describe a therapeutic approach with the following important aims: To reduce patient's fear of loss of control, to free parents from controlling the food intake of their daughter and to establish a framework that provides a good climate for effective family-oriented or individual psychotherapy or both. In patients with anorexia that began early, we recommend starting with family therapy. This can be followed by individual psychotherapy, which is in fact often requested by the patients themselves.

Adolescent↗

Neonatal anoxia induces transitory hyperactivity, permanent spatial memory deficits and CA1 cell density reduction in developing rats.

Physical and reflex development, spontaneous behavior in open field and spatial memory abilities have been studied in rats after neonatal anoxia. Histological analysis of the hippocampal fields have been carried out in selected animals at the end of the testing period. No differences between control and anoxic rats were recorded in the physical and reflex development. Hyperactivity in open field was present in anoxic animals only transiently between P20 and P45. Spatial memory abilities, tested at two developmental stages by means of a maze and a water maze, appeared to be defectual not only during the hyperactivity period but also in adulthood. The histological analysis of the different hippocampal fields demonstrated a significant difference between anoxic and control rats in the cell density of the CA1 field. The present data demonstrate that neonatal anoxia, besides determining only transitory defects in open field behavior, profoundly affects cognitive abilities and cell density in CA1 hippocampal field. These results might be of relevance in the interpretation of the substrate of the cognitive impairment seen in hyperactive children that are exposed to hypoxia at birth.

Animals↗

Parvalbumin- and calbindin-containing neurons in the monkey medial geniculate complex: differential distribution and cortical layer specific projections.

Neuronal immunoreactivity for the calcium binding proteins, parvalbumin and calbindin, has been examined immunohistochemically in the monkey medial geniculate complex. Neurons containing one or other of these proteins were present in most (but not all) regions of the complex and were differentially distributed; parvalbumin immunoreactive neurons tended to form densely packed clusters in the ventral nucleus and rather loose arrangements in the anterodorsal and posterodorsal nuclei, whereas most calbindin neurons were scattered, with concentrations in the caudal end of the posterodorsal and in the magnocellular nuclei. In fluorescent tracer experiments combined with immunohistochemistry, it was found that parvalbumin and calbindin neurons project to layer IV and to layer I, respectively, of the primary auditory cortex. These results suggest the presence of parallel and chemically differentiated geniculocortical pathways which make different contributions to the neuronal circuitry of the auditory cortex.

Animals↗

Hemicerebellectomy and motor behaviour in rats. I. Development of motor function after neonatal lesion.

This study was undertaken to determine the effect of a neonatal hemicerebellectomy (HCb) on the motor development of rats and to determine whether various aspects of motor behaviour were affected to a similar degree. Postnatal development of postural reflexes, locomotion and dynamic postural adjustments was examined during the first four months of life in normal and in neonatal HCbed rats. The results indicate that classes of motor responses are controlled by cerebellar networks to clearly different extents. Emergence of quadruped stance, placing reactions and swimming development were unaffected by neonatal cerebellar lesion. Righting reflexes, cliff avoidance and geotaxic reactions, pivoting and crawling all showed a delayed development although the subsequent recovery was almost complete. The complex postural adjustments required in crossing a narrow path or in suspending on a wire remained permanently impaired. Finally, some behaviours developed normally and only subsequently became defective. This "growing into a deficit" was displayed by the progressively reduced hindlimb grasping and the development of a vestibular drop response with a directional bias. An impressive finding was the shifting of postural asymmetries from the lesion side to the contralateral one occurring around the third postnatal week. These data providing a description of the effect of HCb on motor development are interpreted as indicating a progressive involvement of the archi- and neo-cerebellar structures in the motor function of the rat.

Animals↗

Hemicerebellectomy and motor behaviour in rats. II. Effects of cerebellar lesion performed at different developmental stages.

Rats with a right hemicerebellectomy (HCb) performed in adulthood or at weaning were compared behaviourally to rats with a similar lesion performed on the first postnatal day. The age at which animals received cerebellar lesions made a significant difference with respect to the behavioural outcome in adulthood. Posture, locomotion and motor behaviour were analysed by a battery of sensorimotor tests. Behavioural measurements showed a clear relationship between age at surgery and behavioural effects; rats with neonatal cerebellar lesions showed a slight extensor hypotonia contralateral to the lesion side and efficient locomotor activity, while the adult operated group exhibited a severe extensor hypotonia ipsilateral to the lesion side and hampered locomotion characterized by a wide base and ataxia. Weanling operated rats displayed a symptomatology similar to that observed in adult operates, although less severe. In the postural dynamic adjustments which the sensorimotor tests required, the youngest operated animals obtained higher scores in comparison to the other two experimental groups, except for the lack of hindlimb usage in the suspension on a wire test. These results, which show the importance of the age-at-lesion factor for the recovery of motor function after HCb in the rat, are discussed in the light of the widespread anatomical reorganization already demonstrated following neonatal HCb in rats.

Aging↗

A microcolumnar structure of monkey cerebral cortex revealed by immunocytochemical studies of double bouquet cell axons.

Immunocytochemical methods were used to study 28,000 mol. wt calbindin and tachykinin immunoreactivity in the monkey cerebral cortex. Calbindin and tachykinin immunoreactivity give rise to a generally different pattern of staining of cell bodies and terminal-like puncta. However, the staining of long, vertically-oriented bundles of processes--identical to classical double bouquet cell axonal arborizations--is the most prominent feature of the pattern of both calbindin- and tachykinin-immunoreactive staining. These bundles form a widespread and regular columnar system descending from layer II to layers III-V. The bundles are most evident in layer III where, in tangential sections, they have a density of 7-15 bundles/10,000 microns 2 with a center-to-center spacing of 15-30 microns. The distribution of immunoreactive bundles through the cortex is not homogeneous; somatic sensory, auditory, and visual areas display a large number of calbindin-immunoreactive bundles while tachykinin-immunoreactive bundles are only numerous in the auditory areas and in area 18 of the visual cortex. In the motor cortex (area 4) few or no immunoreactive bundles are visualized with either antibody. Correlative light and electron microscope analysis of tachykinin immunoreactive bundles in the primary auditory cortex shows that the tachykinin-positive axons of the bundles form symmetrical synaptic contacts with dendritic shafts (57%) and spines (43%). Frequently, several immunoreactive boutons that arise from the same fiber are seen climbing along the surfaces of vertically-oriented, non-immunoreactive processes which include myelinated and unmyelinated axons and probably glial processes. The same ultrastructural features and a similar synaptic distribution were found in a previous study [DeFelipe et al. (1989) Brain Res. 503, 49-54] of calbindin-positive bundles in the somatic sensory cortex (areas 3a and 1). Despite the virtually identical morphological features of tachykinin- and calbindin-immunoreactive bundles, colocalization studies demonstrate little coexistence of the two antigens in somata and none in the axonal bundles of double bouquet cells. These data suggest that the double bouquet cell is a chemically heterogeneous, but ubiquitous morphological type of cortical interneuron, whose uniquely bundled axonal system, which is probably GABAergic, imposes a fundamental microcolumnar organization upon the cerebral cortex.

Animals↗