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Biomedical subjects

G Stampacchia

Publications and source records attributed to G Stampacchia.

At least 19 recordsLinked to original sources

Functional and isokinetic assessment of muscle strength in patients with idiopathic inflammatory myopathies.

OBJECTIVE: To assess muscle strength in patients with idiopathic inflammatory myopathies (IIM) using neuromuscular scales and isokinetic testing. METHODS: Muscle function was evaluated in 27 IIM patients being followed at the Rheumatology Unit of the University of Pisa using: (i) a modified version of the grading system used to assess Duchenne dystrophy, (ii) the four-stage grading system of Henriksson and Sandstedt, (iii) an isokinetic muscle strength test (Kin Com, Chatanooga) and (iv) the Health Assessment Questionnaire (HAQ). RESULTS: The neuromuscular scales showed normal or only mildly impaired muscle strength in 60% (Duchenne scale) and 80% (Henriksson and Sandstedt scale) of the patients, respectively, whereas isokinetic testing detected moderate to severe reductions in muscle strength in almost 70% of the patients. No correlations were observed between muscle strength and disease activity, therapy, age at evaluation and disease duration. There was a correlation between the results of the HAQ and neuromuscular testing, but not the isokinetic test. CONCLUSIONS: Although less easy and more expensive to administer, isokinetic testing appears to be a more sensitive instrument than the standard neuromuscular tests for assessing muscle function in IIM patients. In particular, it can detect small reductions in muscle strength.

Adrenal Cortex Hormones↗

Plasma exchange for polyradiculoneuropathy following kidney transplantation: a case report.

We describe a case of polyradiculoneuropathy (PRN) following living donor kidney transplantation, without clinical evidence of preexisting infection. In this study plasma exchange treatment resulted 6 days later in improvement in extremity weakness and paresthesias in the upper and lower extremities. Total neurological recovery was obtained 3 months after the onset of symptoms.

Humans↗

Skeletal muscle and nutritional assessment in chronic renal failure patients on a protein-restricted diet.

BACKGROUND: The close relationship between protein-energy malnutrition and quality of life, morbidity and mortality, makes mandatory a careful evaluation of the nutritional status and muscle mass in chronic renal failure (CRF) patients. METHODS: Nutritional and skeletal muscle data were obtained from 28 nondiabetic patients with severe CRF (glomerular filtration rate, GFR < 15 mL min-1) on conservative treatment. Of them, 14 (8 males, 4 females) were on a conventional low-protein (0.6 g kg-1 body weight) diet (LPD) and 14 (8 males, 4 females) were on a very low-protein (0.3 g kg-1 body weight) diet supplemented with essential amino acids and ketoacids (Ketodiet); 28 healthy sex- and age-matched subjects served as controls. We evaluated biochemistry, anthropometry, bioelectrical impedance vector analysis, and three noninvasive tests investigating some skeletal muscle features: (a) myoelectrical fatigue phenomenon was studied using a surface electromyography technique that provides data on conduction velocity (CV), median frequency of power spectrum (MDF) and average rectified value (ARV) of myofibre action potential, at 15 and 35 Hz stimulation frequency; (b) muscle oxidative metabolism was studied by serum lactate following aerobic exercise; and (c) muscle strength of the legs was studied using an isokinetic exercise test at two different angular velocities (60 degrees and 180 degrees s-1). RESULTS: No difference between patients and controls was detected regarding CV, MDF and ARV, at 35 and 15 Hz testing. Serum lactate was higher in patients than in controls at 1, 5, 10 and 30 min recovery. A decreased knee extension and flexion strength was detected in CRF patients both at low (60 degrees s-1) and at high (180 degrees s-1) angular velocity; muscle strength deficit negatively correlated to serum albumin (r = -0.52, P < 0.01), but no relationship was found with protein intake or residual renal function. No difference was found between LPD and Ketodiet patients regarding the studied muscular tests as well as the anthropometry and bio-impedance data. CONCLUSIONS: Implementation of a proper dietary regimen, including severe restriction of protein intake can preserve lean body mass and nutritional status of advanced CRF patients. Skeletal muscle shows unchanged sarcolemma excitability but abnormal oxidative metabolism and reduced segmental strength. Regular physical activity and a close clinical and dietary monitoring should be recommended for the predialysis patient care.

Diet, Protein-Restricted↗

Change of stretch reflex threshold in spasticity: effect of botulinum toxin injections.

Spasticity is a disorder of hypertonus associated with neurological diseases, characterized by a decrease in stretch reflex threshold. Stretch reflex threshold of wrist flexors has been recorded in subjects affected by forearm spasticity due to acute neurological lesions, occurred from one to sixty-one months before. In all the subjects a decreased stretch reflex threshold was recorded and a negative correlation between stretch reflex threshold and time of the disease resulted. In five subjects affected by mild spasticity the velocity stretch reflex threshold was tested one-three months after stroke and then six months later. In three cases a further decrease in stretch reflex threshold was recorded. Sixteen subjects affected by heavy forearm spasticity (quantified by Ashworth scale), were treated with Botulinum toxin injections to reduce spasticity. Fourteen of 16 subjects were responsive to the antispastic therapy: a decrease of at least 1 point in the Ashworth scale was detected after the treatment. In all the responsive cases an increase of stretch reflex threshold was recorded. The results confirm that the stretch reflex threshold is decreased in spastic muscles; it decreases progressively in time after the acute lesion. In addition, these results demonstrate that the decreased stretch reflex threshold can be reversed with Botulinum toxin injections. It is known that Botulinum toxin reduce the presynaptic release of Acetylcholine of neuromuscular synapses, but there are experimental evidences that it acts even on spindle's fibres, decreasing the sensitivity of intrafusal muscle fibres. This effect explains how Botulinum toxin increases the stretch reflex threshold in spastic muscles.

Action Potentials↗

Modulation of vestibulospinal reflexes through microinjection of an alpha 1-adrenergic antagonist in the dorsal pontine tegmentum of decerebrate cats.

1. The possibility that the norepinephrine (NE)-containing locus coeruleus (LC) neurons produce changes in posture as well as in gain of the vestibulospinal (VS) reflexes by acting on the dorsolateral pontine tegmentum (DPT) and the related medullary inhibitory reticulospinal (RS) system through alpha 1-adrenoceptors has been investigated in decerebrate cats. 2. Injection of the alpha 1-adrenergic antagonist prazosin PRZ (0.25 microliter at 0.1-1 microgram/microliter solvent) into the DPT, namely in the dorsal pontine reticular formation (pRF), as well as in the peribrachial nucleus of one side, decreased the postural activity in the ipsilateral limbs while increasing that of the contralateral limbs. In addition, the amplitude of modulation and thus the gain of the multiunit EMG responses of the ipsilateral and to a lesser extent of the contralateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees, increased. These effects appeared 5-10 min after the injection, reached the highest values in about 40-60 min and persisted for additional 1.5-2 h before disappearing. 3. The effects were site-specific and to some extent dose-dependent. However, neither changes in posture nor in gain of the VS reflexes were obtained after injection in the effective area of an equal volume of solvent. 4. In order to account for these findings it was postulated that the alpha 1-antagonist blocks the tonic inhibitory influence that the NE-containing LC neurons exert on ipsilateral DPT either by exciting through alpha 1-receptors interposed inhibitory interneurons, or by inhibiting presynaptically excitatory afferents to the same pontine tegmental structures. The increased discharge of these neurons and the related medullary inhibitory RS neurons would reduce the postural activity in the ipsilateral limbs. However, since the inhibitory RS neurons show a response pattern to tilt opposite in sign to that elicited by the excitatory VS neurons, we could expect that for a given labyrinth signal, the increased discharge of the RS neurons in the animal at rest would lead to a greater disinhibition of limb extensor motoneurons during ipsilateral tilt. These motoneurons would then respond more efficiently to the same excitatory volleys elicited by given parameters of stimulation, thus leading to an increased gain of the EMG responses of forelimb extensors to labyrinth stimulation. The possibility that the DPT of one side activates inhibitory RS neurons of both sides explains why PRZ increases the gain of the VS reflexes not only ipsilaterally but also contralaterally to the side of the injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic alpha-1 Receptor Antagonists↗

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal stimulation of labyrinth receptors.

In precollicular decerebrate cats the electrical activity of 141 individual neurons located in the locus coeruleus-complex, i.e. in the dorsal (n = 41) and ventral parts (n = 67) as well as in the locus subcoeruleus (n = 33), was recorded during sinusoidal tilt about the longitudinal axis of the whole animal, leading to stimulation of labyrinth receptors. Some of these neurons showed physiological characteristics attributed to the norepinephrine-containing locus coeruleus neurons, namely, (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore- and hindpaw compression consisting of short impulse bursts followed by a silent period, which has been attributed to recurrent and/or lateral inhibition of the norepinephrine-containing neurons. Furthermore, 16 out of the 141 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered coeruleospinal or subcoeruleospinal neurons. A large number of tested neurons (80 out of 141, i.e. 56.7%) responded to animal rotation at the standard frequency of 0.15 Hz and at the peak amplitude of 10 degrees. However, the proportion of responsive neurons was higher in the locus subcoeruleus (72.7%) and the dorsal locus coeruleus (61.0%) than in the ventral locus coeruleus (46.3%). A periodic modulation of firing rate of the units was observed during the sinusoidal stimulus. In particular, 45 out of the 80 units (i.e. 56.2%) were excited during side-up and depressed during side-down tilt (beta-responses), whereas 20 of 80 units (i.e. 25.0%) showed the opposite behavior (alpha-responses). In both instances, the response peak occurred with an average phase lead of about + 18 degrees, with respect to the extreme side-up or side-down position of the animal; however, the response gain (imp./s per deg) was, on average, more than two-fold higher in the former than in the latter group. The remaining 15 units (i.e. 18.7%) showed a prominent phase shift of this response peak with respect to animal position. Similar results were obtained from the subpopulation of locus coeruleus-complex neurons which fired at a low rate (less than 5.0 imp./s), as well as for the antidromically identified coeruleospinal neurons. The response gain of locus coeruleus-complex neurons, including the coeruleospinal neurons, did not change when the peak amplitude of tilt was increased from 5 degrees to 20 degrees at the fixed frequency of 0.15 Hz. This indicates that the system was relatively linear with respect to the amplitude of displacement.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Convergence and interaction of neck and macular vestibular inputs on locus coeruleus and subcoeruleus neurons.

Extracellular recordings were obtained in precollicular decerebrate cats from 90 neurons located in the noradrenergic area of the dorsal pontine tegmentum, namely in the dorsal (LCd, n = 24) and the ventral part (LC alpha, n = 40) of the locus coeruleus (LC) as well as in the locus subcoeruleus (SC, n = 26). Among these units of the LC complex, 13 were coerulospinal (CS) neurons antidromically identified following stimulation of the spinal cord at T12-L1. Some of these neurons showed the main physiological characteristics of the norepinephrine (NE)-containing LC neurons, i.e., a slow and regular resting discharge and a typical biphasic response to fore- and hindpaw compression consisting of a short burst of excitation followed by a period of quiescence, due, in part at least, to recurrent and/or lateral inhibition. Unit firing rate was analyzed under separate stimulation of macular vestibular, neck, or combined receptors by using sinusoidal rotation about the longitudinal axis at 0.15 Hz, +/- 10 degrees peak amplitude. Among the 90 LC-complex neurons, 60 (66.7%) responded with a periodic modulation of their firing rate to roll tilt of the animal and 67 (74.4%) responded to neck rotation. Convergence of macular and neck inputs was found in 52/90 (57.8%) LC-complex neurons; in these units, the gain and the sensitivity of the first harmonic of the response corresponded on the average to 0.34 +/- 0.45, SD, impulses.s-1.deg-1 and 3.55 +/- 2.82, SD, %/deg for the neck responses and to 0.23 +/- 0.29, SD, impulses.s-1.deg-1 and 3.13 +/- 3.04, SD, %/deg for the macular responses. In addition to these convergent units, 8/90 (8.9%) and 15/90 (16.7%) LC-complex units responded to selective stimulation either of macular or of neck receptors only. These units displayed a significantly lower response gain and sensitivity to animal tilt and neck rotation with respect to those obtained from convergent units. Most of the convergent LC-complex units were maximally excited by the direction of stimulus orientation, the first harmonic of responses showing an average phase lead of about +31.0 degrees with respect to neck position and +17.6 degrees with respect to animal position. Two populations of convergent neurons were observed. The first group of units (43/52, i.e., 82.7%) showed reciprocal ("out of phase") responses to the two inputs; moreover, most of these units were excited during side-down neck rotation, but inhibited during side-down animal tilt.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Responses of locus coeruleus and subcoeruleus neurons to sinusoidal neck rotation in decerebrate cat.

The electrical activity of 99 neurons located in the locus coeruleus-complex, namely in the dorsal (n = 26) and the ventral part of the locus coeruleus (n = 46) as well as the locus subcoeruleus (n = 27), has been recorded in precollicular decerebrate cats during sinusoidal displacement of the neck. This was achieved by rotation of the body about the longitudinal axis of the animal, while maintaining the head stationary. A proportion of these neurons showed some of the main physiological characteristics attributed to the noradrenergic locus coeruleus neurons, i.e. (i) a slow and regular resting discharge, and (ii) a typical biphasic response to fore and hindpaw compression consisting of short bursts of impulses followed by a period of quiescence, due at least in part to recurrent or lateral inhibition of the corresponding neurons. Moreover, 14 out of the 99 neurons were activated antidromically by stimulation of the spinal cord at T12 and L1, thus being considered as coeruleo- or subcoeruleospinal neurons. Among these locus coeruleus-complex neurons tested, 73 out of 99 (i.e. 73.7%) responded to neck rotation at the standard frequency of 0.15 Hz and at the peak amplitude of displacement of 10 degrees. In particular 40 of 73 units (i.e. 54.8%) were excited during side-down neck rotation and depressed during side-up rotation, while 18 of 73 units (i.e. 24.7%) showed the opposite pattern. In both instances the peak of the responses occurred with an average phase lead of +34.2 degrees for the extreme side-down or side-up neck displacement; however, the response gain (impulses/s per deg) was on the average more than two-fold higher in the former than in the latter group of units. The remaining 15 units (i.e. 20.5%) showed phase angle values which were intermediate between those of the two main populations. As to the coeruleo or subcoeruleospinal neurons, 11 of 14 units (78.6%) responded to the neck input, the majority (nine of 11 units, i.e. 81.8%) being excited during side-down neck rotation. Within the explored region, the proportion of responsive units was higher in the locus subcoeruleus (85.2%) than in the locus coeruleus, both dorsal and ventral (69.4%). Moreover, units located in the former structure showed on the average a response gain higher than that found in the latter structures. Similar results were also obtained from the population of locus subcoeruleus-complex neurons which fired at a low rate (less than or equal to 5.0 impulses/s).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Responses of locus coeruleus neurons to convergent neck and vestibular inputs.

The locus coeruleus (LC) complex, located in the dorsolateral pontine tegmentum, is composed of noradrenergic and self-inhibitory adrenoceptive neurons, which project to broad regions of the brain, including the spinal cord. Experiments were performed in decerebrate cats to find out whether units which had the physiological characteristics of noradrenergic neurons (i.e., a slow and regular resting discharge and a typical response to a noxious stimulus consisting of a short burst of excitation followed by a silent period), received a convergent input from both labyrinth and neck receptors. Among 90 LC-complex units, 13 of which could be identified antidromically as coeruleospinal (CS) neurons following electrical stimulation of the spinal cord at T12-L1, 52 (57.8%) responded to roll tilt of the animal and neck rotation at 0.15 Hz, +/- 10 degrees. The responses were particularly related to the extreme animal and neck displacements. Most of these convergent neurons (43/52, i.e., 82.7%) showed reciprocal ('out of phase') responses to the two inputs, while only a few units (9/52, i.e., 17.3%) showed parallel ('in phase') responses. Moreover, the majority of the 'out of phase' units showed an increased discharge during side-up animal tilt and side-down neck rotation. These predominant response patterns were just opposite to those of the vestibulospinal (VS) neurons projecting to the same segments of the spinal cord. The response characteristics of the LC-complex neurons to combined neck and vestibular inputs elicited during head rotation usually corresponded to those predicted by a vectorial summation of the individual neck and labyrinth responses, as shown for the VS neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Injections of beta-adrenergic substances in the locus coeruleus affect the gain of vestibulospinal reflexes in decerebrate cats.

1. The tonic discharge of the noradrenergic locus coeruleus (LC) neurons is dampened by norepinephrine (NE) which acts not only on alpha2-adrenoceptors located on the somatodendritic membrane, through mechanisms of recurrent inhibition, but also on beta-receptors. Experiments were performed to find out whether inactivation of LC neurons by local injection of the beta-adrenergic agonist isoproterenol into the LC complex of one side produced changes in posture as well as in the gain of vestibulospinal reflexes acting on forelimb extensors. 2. In precollicular decerebrate cats the amplitude of modulation and thus the gain of the multiunit EMG responses of the forelimb extensor triceps brachii to animal tilt at 0.15 Hz, +/- 10 degrees, leading to sinusoidal stimulation of labyrinth receptors, were quite small. Microinjection of 0.25 microliter of a solution of the beta-adrenergic agonist isoproterenol at the concentration of 4.5-9.0 microgram/microliter of sterile saline into the LC complex of one side decreased the extensor rigidity in the ipsilateral limbs and to a lesser response gain of the ipsilateral triceps brachii to the same parameters of labyrinth stimulation greatly increased (t-test, P less than 0.001); moreover, a slight but significant increase in phase lead of the responses was observed. These findings appeared within 5-10 min after the injection of isoproterenol, fully developed within 20-30 min and persisted for about 2-3 hours after the injection. 3. The increased gain of the vestibulospinal reflexes acting on the triceps brachii did not depend on the decreased postural activity following injection of the beta-adrenergic agonist, since it was still observed if the reduced EMG activity of the extensor muscle following the injection was compensated for by an increased static stretch of the muscle. The positive correlation (t-test, P less than 0.001) between gain of the multiunit EMG response of the triceps brachii to animal tilt and base frequency observed in the control experiment disappeared and was substituted by a slight negative correlation (t-test, P less than 0.05) after injection of isoproterenol into the LC complex, probably due to a more prominent recruitment of motor units for low level of background discharge of the muscle. 4. In addition to the effects which involved the triceps brachii ipsilateral to the side of the injection, a smaller but significant increase in response gain affected the contralateral extensor muscle. This increase in gain was also associated with a slight increase in phase lead of the responses.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Injections of a beta-adrenergic antagonist in pontine reticular structures modify the gain of vestibulospinal reflexes in decerebrate cats.

1. The norepinephrine (NE)-containing locus coeruleus (LC) neurons control posture as well as the gain of the vestibulospinal reflexes either through direct coeruleospinal (CS) projections or by inhibiting the dorsal pontine reticular formation (pRF) and the related medullary inhibitory reticulospinal (RS) system. The question whether these inhibitory influences on the pRF are mediated through beta-adrenoceptors was investigated by injecting in precollicular decerebrate cats small doses of the non-selective beta-adrenergic antagonist propranolol in different pontine tegmental structures. 2. Injection of propranolol (usually 0.25 microliters at the concentration of 4.5 micrograms/microliters of saline) in dorsal pontine structures, which decreased the tonic contraction of limb extensors ipsilateral to the side of the injection, greatly increased the amplitude of the multiunit EMG responses of the ipsilateral triceps brachii to roll tilt of the animal at 0.15 Hz, +/- 10 degrees. Correspondingly, the response gain of the forelimb extensor to labyrinth stimulation increased. Moreover, a slight decrease in phase lead of the responses was observed. These responses were always characterized by an increased EMG activity during ipsilateral tilt and a decreased activity during contralateral tilt, as shown in the control records (alpha-responses). The same injection also produced in some instances an increase of the extensor tonus of the contralateral limbs, associated with an increased EMG activity of the contralateral triceps brachii; on the other hand, the amplitude of modulation and thus the response gain of this muscle to the same parameters of labyrinth stimulation decreased, while the response pattern reversed (beta-responses), thus being opposite to that displayed by the triceps brachii ipsilateral to the side of the injection. 3. The changes in posture and reflexes described above appeared 10-20 min after unilateral injection of propranolol in the pRF, reached in highest values in about 60-100 min and persisted for more that three hours before returning to the control level. These effects were not due to irritative phenomena following injection of the fluid, since neither changes in posture nor in the response gain of the triceps brachii to labyrinth stimulation were observed after injection of an equal volume of saline in the pRF of that side. Moreover, the magnitude of the effects increased to some extent in relation to the dose of the beta-adrenergic blocker. 4. Histological controls indicated that the structure responsible for these postural and reflex changes was located in the dorsal pontine tegmental region immediately ventral to the LC and included the peri-LC alpha and the surrounding dorsal pRF.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Cholinergic brainstem sites for gain control of vestibulospinal reflexes in cats.

Decerebrate cats were injected with carbachol into the locus coeruleus (LC) or with carbachol or bethanechol into the dorsal pontine reticular formation (pRF) of one side; recordings were made of the tonic contraction of forelimb extensor muscles of both sides and of their responses to sinusoidal roll tilt of the animal. Both drugs had similar effects when injected into the pRF: a decrease in the tonic contraction of limb extensors and a greatly enhanced amplitude and gain with slightly decreased phase lead in the responses to animal tilt of the forelimb extensor, triceps brachii, ipsilateral to the side of injection. Injected into the LC, carbachol produced a response opposite to the above: it increased the tonic contraction of limb extensors ipsilateral to the side of injection, but decreased the amplitude and gain of the EMG responses of limb extensor muscles to labyrinth stimulation induced by sinusoidal tilt. These findings did not depend on changes in posture since they were still observed when postural EMG activity was maintained constant by appropriate changes in static stretch of the muscle. Moreover, the magnitude of the effects increased in a dose-dependent manner. Results suggest that cholinergic activation of dorsal pRF neurons through muscarinic receptors increases the background discharge of medullary inhibitory reticulospinal (RS) system neurons, thus increasing their modulatory influence. Further, it is postulated that cholinergic activation of LC neurons would cause them to inhibit this tonic facilitatory drive by the pRF. Common to both sites of carbachol injection is the increase in phase lag of the EMG response of limb extensors to animal tilt.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗