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Biomedical subjects

E D'Angelo

Publications and source records attributed to E D'Angelo.

At least 19 recordsLinked to original sources
PubMed2006

Development of a disease-specific quality of life questionnaire for children & adolescents with idiopathic thrombocytopenic purpura (ITP-QoL).

Quality of life (QoL) assessment in children with coagulation disorders is a relatively unstudied area. While hemophilia-specific questionnaires (such as Haemo-QoL) are available, no instrument for children with idiopathic thrombocytopenic purpura (ITP) has been validated yet. A disease-specific questionnaire for children with ITP was therefore developed (ITP-QoL) in three phases: (a) a preparatory phase; (b) a developmental phase; (c) a pilot testing phase. Since dimensions of Haemo-QoL were considered important for children with ITP, items were adapted, reformulated and additional dimensions were included. Two age-group versions were designed for children (aged 3-7, 8-18 years) and parents in Italian, German, and Swedish languages and were pilot tested.

Adolescent↗
PubMed2005

Role of calcium binding proteins in the control of cerebellar granule cell neuronal excitability: experimental and modeling studies.

Calcium binding proteins, such as calretinin, are abundantly expressed in distinctive patterns in the central nervous system but their physiological function remains poorly understood. Calretinin is expressed in cerebellar granule cells which provide the major excitatory input to Purkinje cells through parallel fibers. Calretinin deficient mice exhibit dramatic alterations in motor coordination and in Purkinje cell firing recorded in vivo through unknown mechanisms. In the present paper, we review the results obtained with the patch clamp recording techniques in acute slice preparation. This data allow us to investigate the effect of a null mutation of the calretinin gene on the intrinsic electroresponsiveness of cerebellar granule cells at a mature developmental stage. Calretinin deficient granule cells exhibit faster action potentials and generate repetitive spike discharge showing an enhanced frequency increase with injected currents. These alterations disappear when 0.15 mM of the exogenous fast calcium buffer BAPTA is infused in the cytosol to restore the calcium buffering capacity. Furthermore, we propose a mathematical model demonstrating that the observed alterations of granule cell excitability can be explained by a decreased cytosolic calcium buffering capacity due to the absence of calretinin. We suggest that calcium binding proteins modulate intrinsic neuronal excitability and may therefore play a role in the information processing in the central nervous system.

Animals↗
PubMed2005

Synaptic plasticity at the cerebellum input stage: mechanisms and functional implications.

The mf-GrC relay provides the case of a synapse at which elementary neurotransmission mechanisms are particularly well understood allowing a precise investigation of synaptic plasticity. An interesting consequence is that a presynaptic mechanism of LTP could be precisely documented on the basis of quantal analysis. By being presynaptically expressed, LTP becomes instrumental to regulation of short-term synaptic dynamics thereby controlling time-dependent transformations of the incoming mossy fiber input. It is unknown to what extent these considerations could be generalized, but early observations were provided for comparable concepts and mechanisms in neocortical synapses (Tsodyks and Markram, 1997). Although several aspects remain to be investigated, mf-GrC LTP provides a wide substrate for information storage in the cerebellum. In the rat cerebellum, there are 10(11) GrCs and 4 times as many mf-GrC synapses. Mathematical models have suggested that mf-GrC LTP improves mutual information transfer, and that the combination of synaptic and non-synaptic changes improves sparse representation of the mf input (Schweighofer et al., 2000; Philipona et al., 2003). Moreover, mf-GrC LTP could play a key role in regulating neurotransmission dynamics, implementing adaptability in delay lines early envisioned by Breitenberg (1967) and then revisited by Medina and Mauk (2002). These observations challenge the simple view of spatial pattern separation proposed by Marr (1969). The potential consequences of mf-GrC LTP need to be further investigated and confronted with computational models of the cerebellar network.

Afferent Pathways↗
PubMed2001

Safety and immunogenicity of a conjugate vaccine against Haemophilus influenzae type b in splenectomized and nonsplenectomized patients with Cooley anemia.

Patients with thalassemia are at increased risk for infections, especially after undergoing splenectomy. Vaccinations and antimicrobial prophylaxis are recommended in these patients, but the optimal immunization schedule for Haemophilus influenzae type b (Hib) vaccine is unknown. The immunogenicity of a conjugate Hib vaccine was investigated in 57 patients with thalassemia, 32 of whom had undergone splenectomy. Anti-capsular antibodies to Hib (anti-polyribosylribitol phosphate) were measured before vaccination and 2, 6, 12, 24, and 36 months after vaccination. Immunization was well tolerated. All patients achieved protective (>1 microg/mL) antibody levels. Antibody titers declined after the initial postvaccination increase, becoming undetectable in 4 patients and decreasing to concentrations of 0.15-1 microg/mL in another 2 patients when tested 2-3 years after vaccination. Hib conjugate vaccine is safe and immunogenic in patients with thalassemia major; however, additional studies are needed to assess the need and timing of booster vaccination to maintain long-term immunity.

Adolescent↗
PubMed2001

Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow k+-dependent mechanism.

Neurons process information in a highly nonlinear manner, generating oscillations, bursting, and resonance, enhancing responsiveness at preferential frequencies. It has been proposed that slow repolarizing currents could be responsible for both oscillation/burst termination and for high-pass filtering that causes resonance (Hutcheon and Yarom, 2000). However, different mechanisms, including electrotonic effects (Mainen and Sejinowski, 1996), the expression of resurgent currents (Raman and Bean, 1997), and network feedback, may also be important. In this study we report theta-frequency (3-12 Hz) bursting and resonance in rat cerebellar granule cells and show that these neurons express a previously unidentified slow repolarizing K(+) current (I(K-slow)). Our experimental and modeling results indicate that I(K-slow) was necessary for both bursting and resonance. A persistent (and potentially a resurgent) Na(+) current exerted complex amplifying actions on bursting and resonance, whereas electrotonic effects were excluded by the compact structure of the granule cell. Theta-frequency bursting and resonance in granule cells may play an important role in determining synchronization, rhythmicity, and learning in the cerebellum.

4-Aminopyridine↗
PubMed2001

Factors influencing the shape of the inspiratory flow.

An index (IS), quantitating the departure of the inspiratory flow profile (IFP) from the rectangular one, i.e. the optimal profile (IS=0), was computed from pneumotachograms recorded in 26 normal, anesthetized subjects breathing spontaneously through the endotracheal tube (ETT) or face mask (FM) with or without added resistances (R) and in 27 awake subjects breathing through the mouth and FM in the supine and seated posture at rest and during exercise (40 W) on a cycloergometer, through the nose and FM, and through the mouthpiece (MP). During anesthesia, IS decreased with R both while breathing through the ETT (DeltaIS=-0.037+/-0.006 (SE); P<0.001) and FM (DeltaIS=-0.054+/-0.008; P<0.001). This indicates that (a) the change of IFP towards the optimal shape is reflex in nature and related to the dynamic inspiratory load, and (b) tracheobronchial mechanoreceptors and inspiratory muscles are involved in this response. The reflex is also operative in awake subjects, since IS decreased whenever the inspiratory dynamic load was increased, as on turning from seated to supine posture (DeltaIS=-0.024+/-0.003; P<0.001), shifting from mouth to nose breathing (DeltaIS=-0.034+/-0.003; P<0.05), from rest to mild exercise (DeltaIS=-0.066+/-0.005; P<0.001). The different IS value between FM and MP breathing (DeltaIS=0.036+/-0.004; P<0.001) indicates, however, that other factors, likely behavioral, also affect the IFP.

Adult↗
PubMed2001

Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum.

In recent years, it has become clear that motor learning, as revealed by associative eyelid conditioning and adaptation of the vestibulo-ocular reflex, contributes to the well-established cerebellar functions of sensorimotor integration and control. Long-term depression of the parallel fiber-Purkinje cell synapse (which is often called 'cerebellar LTD') is a cellular phenomenon that has been suggested to underlie these forms of learning. However, it is clear that parallel fiber LTD, by itself, cannot account for all the properties of cerebellar motor learning. Here we review recent electrophysiological experiments that have described a rich variety of use-dependent plasticity in cerebellum, including long-term potentiation (LTP) and LTD of excitatory and inhibitory synapses, and persistent modulation of intrinsic neuronal excitability. Finally, using associative eyelid conditioning as an example, we propose some ideas about how these cellular phenomena might function and interact to endow the cerebellar circuit with particular computational and mnemonic properties.

Animals↗
PubMed2001

The effects of CO2 on respiratory mechanics in anesthetized paralyzed humans.

BACKGROUND: There is little information concerning the carbon dioxide-related effects on respiratory mechanics in anesthetized, paralyzed subjects; however, hypocapnia or hypercapnia is often permitted in patients with severe brain injury or acute respiratory distress syndrome. Therefore, the carbon dioxide dependence of respiratory mechanics in healthy anesthetized, paralyzed subjects was investigated. METHODS: Interrupter resistance (Rint), additional tissue viscoelastic resistance (deltaR), and quasi-static elastance (Est) of lung (L) and chest wall were assessed by means of the rapid end-inspiratory occlusion method in two groups of seven healthy paralyzed subjects anesthetized with diazepam or isoflurane. They underwent ventilation with a fixed pattern and hyperoxic gas mixtures with different fractions of inspired carbon dioxide (FICO2) to produce a partial pressures of arterial carbon dioxide (PaCO2) of 24.4 +/- 3.4, 39.6 +/- 3.2, and 62 +/- 4.1 (SD) mmHg. RESULTS: Chest wall mechanics and Est,L were unaffected by PaCO2 changes. With diazepam anesthesia, Rint,L decreased linearly, with increasing PaCO2, from 2.3 to 1.4 cm H2O.s.l(-1), whereas deltaR,L decreased from 2 to 1.7 cm H2O.s.l(-1), though not significantly. With isoflurane anesthesia, the decrease of Rint,L (0.2 +/- 0.5 cm H2O.s.l(-1)) was not significant, and deltaRL remained unchanged. With diazepam, Rint,L was 45 (hypercapnia) to 110% (hypocapnia) greater than with isoflurane. CONCLUSIONS: Changes of PaCO2 from 20-65 mmHg cause increasing bronchodilation in anesthetized, paralyzed subjects, this effect being attenuated or abolished by drugs (e.g., halogenated anesthetics) that depress smooth muscle tone substantially. The carbon dioxide bronchodilating effects are probably direct for peripheral structures and are paralleled by a tendency of lung tissue resistance to decrease. Because local PaCO2-related changes in bronchomotor tone promote VA/Q matching, this mechanism should be impaired by anesthetics that cause bronchodilation.

Adult↗
PubMed2000

Long-term potentiation of intrinsic excitability at the mossy fiber-granule cell synapse of rat cerebellum.

Synaptic activity can induce persistent modifications in the way a neuron reacts to subsequent inputs by changing either synaptic efficacy or intrinsic excitability. After high-frequency synaptic stimulation, long-term potentiation (LTP) of synaptic efficacy is commonly observed at hippocampal synapses (Bliss and Collingridge, 1993), and potentiation of intrinsic excitability has recently been reported in cerebellar deep nuclear neurons (Aizenmann and Linden, 2000). However, the potential coexistence of these two aspects of plasticity remained unclear. In this paper we have investigated the effect of high-frequency stimulation on synaptic transmission and intrinsic excitability at the mossy fiber-granule cell relay of the cerebellum. High-frequency stimulation, in addition to increasing synaptic conductance (D'Angelo et al., 1999), increased granule cell input resistance and decreased spike threshold. These changes depended on postsynaptic depolarization and NMDA receptor activation and were prevented by inhibitory synaptic activity. Potentiation of intrinsic excitability was induced by relatively weaker inputs than potentiation of synaptic efficacy, whereas with stronger inputs the two aspect of potentiation combined to enhance EPSPs and spike generation. Potentiation of intrinsic excitability may extend the computational capability of the cerebellar mossy fiber-granule cell relay.

Action Potentials↗
PubMed2000

Volume and time dependence of respiratory system mechanics in normal anaesthetized paralysed humans.

The purpose of the present investigation was to assess the effect of large tidal volumes and mean lung volumes on the viscoelastic properties of the respiratory system in normal humans; and to verify if in this case the results could be satisfactorily described by a simple linear viscoelastic model of the respiratory system. Twenty-eight subjects (7 females), aged 14-28 yrs, were studied before orthopaedic surgery on the lower limbs. None were obese, or had clinical evidence of cardiopulmonary disease. The interrupter conductance and the viscoelastic constants of the respiratory system were assessed using the rapid end-inspiratory airway occlusion method during mechanical ventilation with tidal volumes up to 3 L and applied end-expiratory pressures up to 23 cmH2O. It was found that the interrupter conductance increased linearly with lung volume over a larger range than used previously; and the viscoelastic resistance and time constant did not change over the entire range of tidal volumes and end-expiratory pressures studied. In conclusion, in normal anaesthetized, paralysed subjects a simple linear viscoelastic model satisfactorily described the viscoelastic behaviour of the respiratory system over the whole range of volume studied.

Adolescent↗
PubMed2000

Performance of forced expiratory manoeuvre in children.

The negative expiratory pressure (NEP) method has been previously used to assess the performance of forced vital capacity (FVC) manoeuvre in normal adults. The aim of the present study is to assess whether flow limitation is achieved during FVC manoeuvres in children aged 6-14 yrs. NEP (-10 cmH2O) was successfully applied in 177 normal children, the portion of FVC over which expiratory flow did or did not change with NEP being taken as effort-dependent and effort-independent, respectively. In all children peak expiratory flow (PEF) and forced expiratory volume in one second (FEV1) increased with NEP, indicating that PEF was in the effort-dependent portion of FVC. This portion decreased significantly with age (50-20% of FVC from 6-14 yrs). It is suggested that this mainly reflects the poorer coordination of specialized motor acts in younger children because of incomplete morphological and functional maturation of the relevant central nervous system (CNS) mechanisms. The results indicate that most unexperienced children aged 6-14 yrs can perform acceptable forced vital capacity manoeuvres, eventually achieving flow limitation over a portion of the forced vital capacity that increases with age. The negative expiratory pressure method can be used for online assessment of the performance of forced vital capacity manoeuvres and evaluation of treatment-related effects.

Adolescent↗
PubMed1999

Neuroprotective effects of riluzole: an electrophysiological and histological analysis in an in vitro model of ischemia.

The protective effects of riluzole against the neuronal damage caused by O2 and glucose deprivation (ischemia) was investigated in rat cortical slices by recording electrophysiologically the cortico-cortical field potential and by evaluating histologically the severity of neuronal death. Five minutes of ischemia determined an irreversible depression of the amplitude of the field potential. In addition, this insult caused a clear enhancement of the number of death cells that were specifically colored with trypan blue (a vital colorant which stains altered cells). We found that riluzole, which by itself depressed the synaptic transmission, neuroprotected when perfused 15-20 min before and during ischemia. In fact, due to the treatment with riluzole, the ischemia-induced irreversible depression of the field potential recovered and less cells were stained with trypan blue. These findings demonstrate that riluzole prevents neuronal death in an in vitro model of ischemia and suggest a therapeutic use of this drug in order to reduce the pathophysiological outcomes of stroke.

Animals↗
PubMed1999

Influence of abdomen on respiratory mechanics in supine rabbits.

Previous studies showed that abdominal evisceration has no effect on respiratory system compliance. We hypothesized that this could be related to lung distortion in eviscerated animals. Methods were developed for continuous recording of pleural pressure (Ppl) at various sites over the costal (co) and diaphragmatic lung surface (di) in acutely and chronically instrumented rabbits. We compared deltaPpl,co and deltaPpl,di recorded at mid-lung height during inflations in anesthetized, paralyzed supine rabbits before and after evisceration. Cranial and caudal deltaPpl.co were the same under all conditions. In intact animals, deltaPpl.co and deltaPpl,di were equal at all inflation volumes, whilst in eviscerated animals, deltaPpl,di were smaller than deltaPpl,co, the difference increasing with lung inflation. At any given volume, rib cage circumference (Crc) was smaller after evisceration, but the Crc deltaPpl,co relationship remained unchanged. These results are indicative of non-uniform lung expansion after evisceration and are consistent with model predictions based on cylindrical deformation and lung stress-strain relationship. This deformation should mimic the effect of a reduced lung compliance, keeping respiratory system compliance of eviscerated animals nearly normal. Similar deformation should have occurred also in intact rabbits during strong inspiratory efforts and in the erect posture, because lower Ppl,di than Ppl,co values were observed at the same lung height under these conditions.

Abdomen↗
PubMed1999

Effect of inspiratory flow waveform on work on endotracheal tubes: a model analysis.

OBJECTIVE: This model analysis aimed to predict the impact of different inspiratory flow wave-forms, i. e., constant, sinusoidal, and two linearly decreasing flows, on the resistive work (Wres) performed on endotracheal tubes. DESIGN: Model analysis. RESULTS: Model analysis predicts that: (i) minimal Wres is obtained with the constant flow; (ii) for any given tidal volume/inspiratory duration (V(T)/T(I), mean inspiratory flow), Wres increases with decreasing tube size; (iii) for any given inspiratory flow waveform, Wres increases with increasing V(T)/T(I), being lowest with constant flow. CONCLUSIONS: These findings have major clinical implications: at any given ventilator setting, not only the size of the endotracheal tube but also the inspiratory flow waveform must be taken into account to interpret the values of Wres and hence of the total work of breathing.

Airway Resistance↗
PubMed1999

Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fiber-granule cell transmission in rat cerebellum.

Long-term potentiation (LTP) is a form of synaptic plasticity that can be revealed at numerous hippocampal and neocortical synapses following high-frequency activation of N-methyl--aspartate (NMDA) receptors. However, it was not known whether LTP could be induced at the mossy fiber-granule cell relay of cerebellum. This is a particularly interesting issue because theories of the cerebellum do not consider or even explicitly negate the existence of mossy fiber-granule cell synaptic plasticity. Here we show that high-frequency mossy fiber stimulation paired with granule cell membrane depolarization (-40 mV) leads to LTP of granule cell excitatory postsynaptic currents (EPSCs). Pairing with a relatively hyperpolarized potential (-60 mV) or in the presence of NMDA receptor blockers [5-amino--phosphonovaleric acid (APV) and 7-chloro-kynurenic acid (7-Cl-Kyn)] prevented LTP, suggesting that the induction process involves a voltage-dependent NMDA receptor activation. Metabotropic glutamate receptors were also involved because blocking them with (+)-alpha-methyl-4-carboxyphenyl-glycine (MCPG) prevented potentiation. At the cytoplasmic level, EPSC potentiation required a Ca2+ increase and protein kinase C (PKC) activation. Potentiation was expressed through an increase in both the NMDA and non-NMDA receptor-mediated current and by an NMDA current slowdown, suggesting that complex mechanisms control synaptic efficacy during LTP. LTP at the mossy fiber-granule cell synapse provides the cerebellar network with a large reservoir for memory storage, which may be needed to optimize pattern recognition and, ultimately, cerebellar learning and computation.

Animals↗
PubMed1998

The weaver mutation causes a loss of inward rectifier current regulation in premigratory granule cells of the mouse cerebellum.

Considerable interest has recently focused on the weaver mutation, which causes inward rectifier channel alterations leading to profound impairment of neuronal differentiation and to severe motor dysfunction in mice (Hess, 1996). The principal targets of mutation are cerebellar granule cells, most of which fail to differentiate and degenerate in a premigratory position (Rakic and Sidman, 1973a,b). Two hypotheses have been put forward to explain the pathogenetic role of mutant inward rectifier channels: namely that inward rectifier channel activity is either lacking (Surmeier et al., 1996) or altered (Kofuji et al., 1996; Silverman et al., 1996; Slesinger et al., 1996). We have examined this question by recording inward rectifier currents from cerebellar granule cells in situ at different developmental stages in wild-type and weaver mutant mice. In wild-type mice, the inward rectifier current changed from a G-protein-dependent activation to a constitutive activation as granule cells developed from premigratory to postmigratory stages. In weaver mutant mice, G-protein-dependent inward rectifier currents were absent in premigratory granule cells. A population of putative granule cells in the postmigratory position expressed a constitutive inward rectifier current with properties compatible with mutated GIRK2 channels expressed in heterologous systems. Because granule cells degenerate at the premigratory stage (Smeyne and Goldowitz, 1989), the loss of inward rectifier current and its regulation of membrane potential are likely to play a key role in the pathogenesis of weaver neuronal degeneration.

Anesthetics, Local↗
PubMed1998

Assessment of respiratory system viscoelasticity in spontaneously breathing rabbits.

Airflow, volume (V), inspiratory time (TI), tracheal pressure (Ptr), abdomen (Dab) and rib cage diameters (Drc), peak diaphragm (Adi) and parasternal muscle activity (Aic) were measured in thirteen anaesthetized and vagotomized rabbits and in six vagotomized rabbits with cordotomy at T1 during unimpeded inspirations followed by rapid end-inspiratory airway occlusion, relaxation against closed airways, and inspiratory effort. To modify the inspiratory flow pattern, such sequences were performed at different volume, levels of chemical drive, and body temperatures (BT). Under all conditions, Adi, Aic, TI, Drc and Dab at iso-volume were the same for unimpeded and occluded inspirations; end-inspiratory Ptr was lower for occluded than for unimpeded inspirations, the difference (Pdiff) being larger the lower the volume at which occlusions were performed and the higher the chemical drive and BT. After paralysis, the viscoelastic constants of the respiratory system, modelled as a Kelvin body, were assessed according to the rapid airway occlusion method and used together with the inspiratory flow waveform to predict the end-inspiratory viscoelastic pressure (Pvisc) of unimpeded inspirations. Since the slope of the Pdiff vs. Pvisc relationship never differed from unity, Pdiff under the specified conditions should represent the effective Pvisc of unimpeded inspirations.

Animals↗