Showing papers by "University of Milan published in 1988"

Evaluation of the baroreceptor-heart rate reflex by 24-hour intra-arterial blood pressure monitoring in humans.

Abstract: The baroreceptor control of the sinus node was evaluated in 10 normotensive and 10 age-matched essential hypertensive subjects in whom ambulatory blood pressure was recorded intra-arterially for 24 hours and scanned by a computer to identify the sequences of three or more consecutive beats in which systolic blood pressure (SBP) and pulse interval (PI) progressively rose (+PI/+SBP) or fell (-PI/-SBP) in a linear fashion, according to a method validated in cats. In normotensive subjects, several hundred +PI/+SBP and -PI/-SBP sequences of 3 beats were found whereas the number of sequences of 4, 5, and more than 5 beats showed a progressive drastic reduction. The mean slopes of +PI/+SBP (7.6 +/- 2.0 msec/mm Hg) and -PI/-SBP (6.4 +/- 1.5 msec/mm Hg) sequences were similar, but in both instances there was a large scattering of the values around the mean (variation coefficients: 64.2 +/- 4.7 and 62.6 +/- 2.4%). The slopes decreased as a function of the sequence length and baseline heart rate and increased to a marked extent during the night as compared with daytime values. All sequences were more rare (-33.2% for +PI/+SBP and -31.7% for -PI/-SBP) and less steep in hypertensive subjects (-40.3 and -36.2%, respectively), who failed to show the marked nighttime increase in slope observed in normotensive subjects. To our knowledge, these observations provide the first description in humans of the baroreceptor-heart rate reflex in daily life. This reflex is characterized by marked within-subject variations in sensitivity due in part to hemodynamic, temporal, and behavioral factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationships Between Lung Computed Tomographic Density, Gas Exchange, and PEEP in Acute Respiratory Failure

Abstract: Twenty-two patients with acute respiratory failure underwent lung computed tomography (CT) and physiological measurements at 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) to investigate the relationship between morphology and function. Lung densities were primarily concentrated in the dependent regions. From the frequency distribution of CT numbers (difference in x-ray attenuation between water and lung) and lung gas volume measurements the authors obtained a quantitative estimate of normally inflated, poorly inflated, and non-inflated lung tissue weight. This estimated average lung weight was increased twofold above normal and excess lung weight correlated with the mean pulmonary artery pressure (P less than 0.01). Venous admixture correlated with the non-inflated tissue mass (P less than 0.01). Increasing PEEP caused progressive clearing of radiographic densities and increased the mass of normally inflated tissue (anatomic recruitment), while reducing venous admixture. The cardiac index decreased after increasing PEEP while oxygen delivery was unchanged. The authors conclude that CT scan lung density and oxygen exchange efficiency are correlated; the main effect of augmenting PEEP is to recruit perfused alveolar units that were previously collapsed.

Autoantibodies to Glutamic Acid Decarboxylase in a Patient with Stiff-Man Syndrome, Epilepsy, and Type I Diabetes Mellitus

Abstract: Stiff-man syndrome is a rare disorder of the central nervous system consisting of progressive, fluctuating muscle rigidity with painful spasms. It is occasionally associated with endocrine disorders, including insulin-dependent diabetes, and with epilepsy. We investigated the possible existence of autoimmunity against the nervous system in a patient with stiff-man syndrome associated with epilepsy and Type I diabetes mellitus. Levels of IgG, which had an oligoclonal pattern, were elevated in the cerebrospinal fluid. The serum and the cerebrospinal fluid produced an identical, intense staining of all gray-matter regions when used to stain brain sections according to an indirect light-microscopical immunocytochemical procedure. The staining patterns were identical to those produced by antibodies to glutamic acid decarboxylase (the enzyme responsible for the synthesis of gamma-aminobutyric acid). A band comigrating with glutamic acid decarboxylase in sodium dodecyl sulfate-polyacrylamide gels appeared to be the only nervous-tissue antigen recognized by cerebrospinal fluid antibodies, and the predominant antigen recognized by serum antibodies. These findings support the idea that an impairment of neuronal pathways that operate through gamma-aminobutyric acid is involved in the pathogenesis of stiff-man syndrome, and they raise the possibility of an autoimmune pathogenesis.

Sympathetic predominance in essential hypertension: a study employing spectral analysis of heart rate variability

Abstract: In this study on 91 subjects we tested the hypothesis of an enhanced sympathetic activity in uncomplicated essential hypertension employing spectral analysis of heart rate variability. With this technique the tonic sympathetic and vagal activities and their changes are respectively assessed by the power of approximately 0.1 Hz (low frequency, LF) and approximately 0.25 Hz (respiratory linked, high frequency, HF) components of the spectrum of the beat by beat variability of RR interval. When comparing the 40 subjects with diastolic blood pressure consistently greater than 95 mmHg (hypertensives, Ht), with 35 age-matched controls (diastolic arterial pressure less than 90 mmHg, Nt), we observed that LF was greater and HF smaller in Ht as compared to Nt, thus suggesting an enhanced sympathetic activity and a reduce vagal activity in Ht. Additionally, passive tilt, which in Nt enhances LF [delta = 26 +/- 2 normalized units (nu)] and reduces HF (delta = -22 +/- 2, nu), produced smaller (P less than 0.05) changes in Ht (delta LF = 6.3 +/- 2.7 and delta HF = -7.5 +/- 2.3 nu). Furthermore, the values of LF at rest and the altered effects of tilt on LF and HF were significantly correlated with the degree of the hypertensive state. Chronic beta-adrenergic blockade (atenolol 100 mg once daily for 2 weeks, n = 13) reduced heart rate and blood pressure (from 162/103 to 136/88 mmHg) together with a significant diminution of LF and an increase of HF. Thus, spectral analysis of RR variability appears to be a convenient non-invasive technique to follow the progressive alterations in sympatho-vagal balance present in essential hypertension.

Evaluation of baroreceptor reflex by blood pressure monitoring in unanesthetized cats

Abstract: The arterial baroreceptor control of the sinus node operating in unanesthetized conditions was evaluated in 10 cats in which blood pressure was recorded intra-arterially and scanned by a computer t...

Spectral analysis of heart rate variability in the assessment of autonomic diabetic neuropathy.

Abstract: We studied heart rate variability in 49 uncomplicated diabetics (27 with insulin therapy; 22 with oral hypoglycemic agents) and in 40 age-matched controls. An automatic autoregressive algorithm was used to compute the power spectral density (PSD) of beat by beat RR variability derived from the surface ECG. The PSD contains two major components (a low frequency approximately 0.1 Hz (LF) and a high frequency, respiratory linked, approximately 0.25 Hz (HF] that provide, respectively, quantitative markers of sympathetic and vagal modulatory activities and of their balance. As compared to controls, in diabetics, besides a reduced RR variance at rest (2722 +/- 300 and 1436 +/- 241 ms2, respectively), we observed during passive tilt an altered response of spectral indices of sympathetic activation and vagal withdrawal, suggestive of a complex modification in the neural control activities. In addition, we compared this approach to the commonly used clinical tests score, and observed that the latter provides overall results similar to those obtained with spectral changes induced by tilt (r = 0.42; P less than 0.01). Of potential clinical importance is that the data obtained with spectral analysis appear more thoroughly quantifiable and do not require the active collaboration of the patients.

Stochastic Petri nets: an elementary introduction

Abstract: Petri nets in which random firing delays are associated with transitions whose firing is an atomic operation are known under the name “stochastic Petri nets” These models are discussed, with the purpose of explaining why they were proposed in the performance evaluation field, why random delays with negative exponential probability density functions are mainly used, and what are their strong and weak points An effort is made to summarize the lines of research that are currently being pursued, and to explain what new results would be regarded as breakthroughs and have the most impact on the use of this modeling technique in the application field

Water as a Free Electric Dipole Laser

Abstract: We show that the usually neglected interaction between the electric dipole of the water molecule and the quantized electromagnetic radiation field can be treated in the context of a recent quantum field theoretical formulation of collective dynamics. We find the emergence of collective modes and the appearance of permanent electric polarization around any electrically polarized impurity.

Shift of activity from slow to fast muscle during voluntary lengthening contractions of the triceps surae muscles in humans

Abstract: 1. Raw or rectified and integrated electromyograms (integrated EMGs) of the leg muscles were recorded during (a) isotonic ramp shortening or lengthening contractions consisting of foot plantar flexions against a constant load, or dorsal flexions accomplished by braking the load and yielding to it, respectively, and (b) isometric increasing or decreasing plantar torques accomplished by graded contractions or relaxations of the triceps muscles. 2. During plantar flexions or increasing torques, the EMG of soleus, gastrocnemius lateralis, medialis, and peroneus increased in parallel. During decreasing torques, motor unit derecruitment took place gradually and simultaneously. The tibialis anterior was silent. During dorsal flexions, one of two characteristic patterns was observed in different subjects: (a) soleus was abruptly derecruited at the beginning of the task, while gastrocnemius lateralis (or medialis) exhibited a large recruitment lasting throughout the lengthening contraction; (b) soleus remained active during the task, showing large motor unit potentials, while the gastrocnemius lateralis recruitment was of a lesser extent than in (a). Peroneus derecruitment was gradual and tibialis anterior activity was absent in both cases. 3. The EMG patterns observed during plantar flexions or in increasing and decreasing torques, and the two patterns observed during shortening or lengthening contractions, were closely reproduced during sinusoidal oscillations of the foot or in isometric contractions and relaxations. 4. When recruitment of the gastrocnemius lateralis was present during dorsal flexion, the slope of its integrated EMG envelope was steeper, the higher the velocity of lengthening contraction. The most rapid and the slowest tasks, however, did not require its activation. Gastrocnemius lateralis integrated EMGs of an amplitude similar to those occurring during lengthening contractions were observed only during ballistic plantar flexions. 5. The two patterns of triceps activation occurring during lengthening contraction could be traced to different mechanical characteristics of the soleus muscles, the gastrocnemius lateralis being activated preferentially in subjects with long soleus half-relaxation times, and the soleus in subjects with short soleus half-relaxation times. 6. The soleus and gastrocnemius lateralis H reflexes were tested during shortening and lengthening contractions.(ABSTRACT TRUNCATED AT 400 WORDS)

The determinants of the step frequency in running, trotting and hopping in man and other vertebrates.

Abstract: 1. During each step of running, trotting or hopping part of the gravitational and kinetic energy of the body is absorbed and successively restored by the muscles as in an elastic rebound. In this study we analysed the vertical motion of the centre of gravity of the body during this rebound and defined the relationship between the apparent natural frequency of the bouncing system and the step frequency at the different speeds. 2. The step period and the vertical oscillation of the centre of gravity during the step were divided into two parts: a part taking place when the vertical force exerted on the ground is greater than body weight (lower part of the oscillation) and a part taking place when this force is smaller than body weight (upper part of the oscillation). This analysis was made on running humans and birds; trotting dogs, monkeys and rams; and hopping kangaroos and springhares. 3. During trotting and low-speed running the rebound is symmetric, i.e. the duration and the amplitude of the lower part of the vertical oscillation of the centre of gravity are about equal to those of the upper part. In this case, the step frequency equals the frequency of the bouncing system. 4. At high speeds of running and in hopping the rebound is asymmetric, i.e. the duration and the amplitude of the upper part of the oscillation are greater than those of the lower part, and the step frequency is lower than the frequency of the system. 5. The asymmetry is due to a relative increase in the vertical push. At a given speed, the asymmetric bounce requires a greater power to maintain the motion of the centre of gravity of the body, Wext, than the symmetric bounce. A reduction of the push would decrease Wext but the resulting greater step frequency would increase the power required to accelerate the limbs relative to the centre of gravity, Wint. It is concluded that the asymmetric rebound is adopted in order to minimize the total power, Wext + Wint.

Progressive language impairment without dementia: a case with isolated category specific semantic defect.

Abstract: A patient is described with a 5 year progressive defect of naming and auditory verbal comprehension, the pathological nature of which was presumably degenerative. The auditory comprehension defect unevenly affected different semantic categories, and was particularly severe for the names of animals, fruits and vegetables. The patients showed loss of the verbal knowledge of the physical attributes of the concepts corresponding to the words he was unable to understand, and sparing of the verbal knowledge of the functional attributes. His performance was defective also on the colour-figure and sound-picture matching test.

Platelets as a model for neurones

Abstract: The multiple biochemical and pharmacological similarities existing between blood platelets and 5-hydroxytryptamine (5-HT)-containing neurones of the CNS point to the platelets as a reliable model for the biochemical characterization of 5-HT releasers and uptake blockers which interfere with the storage and the active carrier mechanism of 5-HT in the neurones, respectively. In addition, the affinity displayed by dopamine and by dopaminergic neurotoxin MPP+ for the platelet 5-HT transport and storage indicates also some similarities between platelets and the dopaminergic system of the CNS. Since human platelets contain almost exclusively monoamine oxidase type B (MAO-B), they can be used as a source for the purification and characterization of this human enzyme. Human platelets thus offer an excellent peripheral model to indirectly assess the degree and duration of MAO-B inhibition occurring in the CNS. To date, knowledge of the many biochemical mechanisms underlying platelet physiology is still fragmentary. In fact, the functional role of binding sites located on the platelet cytoplasmic membrane, i.e. their coupling to a specific transmembrane signalling mechanism, is still in need of a precise biochemical and physiological characterization.

Differential effect of alpha-latrotoxin on exocytosis from small synaptic vesicles and from large dense-core vesicles containing calcitonin gene-related peptide at the frog neuromuscular junction

Abstract: The regulatory peptide called calcitonin gene-related peptide (CGRP) was detected by immunofluorescence in frog motor neurons and motor nerve terminals. In motor nerve terminals, CGRP-like immunoreactivity was found to be segregated within large dense-core vesicles. To determine whether exocytosis from acetylcholine-containing small synaptic vesicles and from CGRP-containing large dense-core vesicles can be independently stimulated, nerve-muscle preparations were exposed to alpha-latrotoxin. This toxin induced complete depletion of acetylcholine-containing small synaptic vesicles but did not induce a parallel depletion of CGRP-like immunoreactivity and of large dense-core vesicles. These effects were independent of the presence of extracellular Ca2+ and occurred both at room temperature and at low temperature (1-3 degrees C). These findings suggest that exocytosis from the two vesicle populations is mediated by distinct biochemical mechanisms, which might be differentially regulated by physiological stimuli.

Muscarinic control of the hyperpolarization-activated current (if) in rabbit sino-atrial node myocytes.

Abstract: 1. The mechanism by which acetylcholine (ACh), by stimulation of muscarinic receptors, acts to inhibit activation of the hyperpolarization-activated 'pacemaker' current, if was investigated in isolated rabbit sino-atrial (SA) node myocytes. 2. Intracellular loading with GTP gamma S, a non-hydrolysable analogue of GTP, did not impair the ACh action on if, but made it irreversible. On the other hand, the ACh action on if disappeared after a few minutes of cell loading with GDP beta S, a GDP analogue known to bind to G-proteins and prevent their receptor-stimulated action. Furthermore, incubation of cells in a solution containing pertussis toxin (PTX) led to abolition of the if response to ACh. These results indicate that the inhibitory effect of ACh on if is mediated by G-proteins activated by muscarinic receptors. 3. Intracellular loading with phosphodiesterase (PDE) increased the rate of if current run-down, but did not abolish the inhibitory action of ACh on if. 4. Extracellular perfusion with isobutylmethylxanthine (IBMX), a PDE inhibitor, increased if activation by shifting the current activation range to more positive voltages, as inferred by a three-pulse protocol analysis; in the presence of IBMX, the inhibition of if by ACh was not abolished. 5. The ACh-induced if depression persisted also in cells loaded with cyclic GMP. In these cells, as in those loaded with PDE, the if run-down was fast. 6. Oxotremorine, a muscarinic agonist coupled to adenylate cyclase but not to phosphoinositide turnover in cardiac cells, simulated ACh in its inhibitory action on if. The above results rule against the ACh action being mediated by PDE or by phosphoinositide turnover. 7. To investigate the possible involvement of cyclic AMP as a second messenger in the ACh action on if, we loaded cells with cyclic AMP and IBMX; under these conditions the action of ACh disappeared within a few minutes of whole-cell recording. 8. In cells where the slow inward Ca2+ current (isi) was measured together with if, ACh was seen to depress both currents. 9. In cells superfused with forskolin, the if amplitude on stepping to the half-activation voltage range was enhanced as a consequence of a depolarizing shift of the activation curve; ACh was not effective on if following stimulation by forskolin, but strongly depressed in the same cell the if current stimulated to a similar degree by isoprenaline.(ABSTRACT TRUNCATED AT 400 WORDS)

Inhibition of the hyperpolarization-activated current (if) induced by acetylcholine in rabbit sino-atrial node myocytes.

Abstract: 1. The action of acetylcholine (ACh) on the hyperpolarization-activated ('pacemaker') current if was studied in single myocytes from the sino-atrial (SA) node region of the rabbit heart, where low doses of ACh slow spontaneous activity by prolonging the diastolic depolarization phase. 2. Besides activating an outward component at voltages positive to the K+ equilibrium potential (iK,ACh), ACh depressed the current if activated on hyperpolarization at concentrations in the range 0.03-1 microM. 3. The ACh-dependent if depression was dissected from modifications of iK,ACh by blocking iK,ACh with barium and was studied under conditions that minimized the interference of other current changes caused by ACh. 4. The study of if modification by ACh with three-pulse protocols and the measurement of fully activated I-V relations of if with and without ACh revealed that ACh acted on if by shifting the current activation range to more negative voltages, with no obvious alteration of the fully activated current amplitude. 5. The action of ACh on if was opposite to that caused by catecholamines. The presence of isoprenaline (IP) did not prevent ACh inhibition of if, nor did the presence of ACh prevent the if stimulation caused by IP. The effects of IP and ACh on if were additive. 6. The ACh-induced inhibition of if was reversed by addition of atropine and could be mimicked by muscarine, indicating that muscarinic receptors mediate it. The implications of these findings on the regulation of pacemaker activity by ACh is discussed.

Postural adjustments associated with voluntary contraction of leg muscles in standing man.

Abstract: The postural adjustments associated with a voluntary contraction of the postural muscles themselves have been studied in the legs of normal standing men. We focussed on the following questions. Do postural adjustments precede the focal movement as in the case of movements of the upper limb? Which muscle(s) are involved in the task of stabilizing posture? Can the same postural muscle be activated in postural stabilization and in voluntary movement at the same time, in spite of the opposite changes in activity possibly required by these conditions? Six subjects standing on a dynamometric platform were asked to rise onto the tips their toes by contracting their soleus muscles, or to rock on their heels by contracting their tibialis anterior muscles. The tasks were made in a reaction time (RT) situation or in a self-paced mode, standing either freely or holding onto a stable structure. Surface EMGs of leg and thigh muscles, and the foot-floor reaction forces were recorded. The following results were obtained in the RT mode, standing freely. 1. Rising onto toe tips: a striking silent period in soleus preceded its voluntary activation; during this silent period, a tibialis anterior burst could be observed in three subjects; these anticipatory activities induced a forward sway, as monitored by a change in the force exerted along the x axis of the platform. 2. Rocking on heels: an enhancement in tonic EMG of soleus was observed before tibialis anterior voluntary burst, at a mean latency from the go-signal similar to that of the silent period; this anticipatory activity induced a backward body sway. 3. Choice RT conditions showed that the above anticipatory patterns in muscle activity were pre-programmed, specific for the intended tasks, and closely associated with the focal movement. When both tasks were performed in a self-paced mode, all the above EMG and mechanical features were more pronounced and unfolded in time. If the subjects held onto the frame, the early features in the soleus or tibialis anterior EMG were absent, and the corresponding changes in the foot-floor reaction forces were lacking. The anticipatory phenomena observed are considered postural adjustments because they appear only in the free-standing situation, and induce a body sway in the appropriate direction to counteract the destabilizing thrust due to the voluntary contraction of soleus or tibialis anterior. The central organization and descending control of posture and movements are briefly discussed in the light of the short latency of the anticipatory phenomena and of their close association with the focal movement.

Recovery from aphasia and neglect after subcortical stroke: neuropsychological and cerebral perfusion study.

Abstract: Cortical regional cerebral perfusion was assessed by N, N, N1-trimethyl-N1-(2)-hydroxy-3-methyl-5-(I-123) iodobenzyl-1, 3-propanediamine 2 HCl I-123 (HIPDM) and single photon emission computerised tomography (SPECT) in six aphasic and two neglect patients with unilateral subcortical vascular lesions. Assessments were carried out both in the acute phase and after a period ranging from 1 to 6 months after stroke onset. In all patients an almost complete spontaneous recovery occurred and was associated with a significant improvement of cortical perfusion. A relationship between severity of aphasia and degree of cortical hypoperfusion was found, in both the acute and the follow up assessments, in the aphasic subgroup.