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Biomedical subjects

S Barbieri

Publications and source records attributed to S Barbieri.

At least 19 recordsLinked to original sources

Dyskerin expression influences the level of ribosomal RNA pseudo-uridylation and telomerase RNA component in human breast cancer.

Dyskerin is a nucleolar protein, altered in dyskeratosis congenita, which carries out two separate functions, both fundamental for proliferating cells. One function is the pseudo-uridylation of ribosomal RNA (rRNA) molecules, necessary for their processing, and the other is the stabilization of the telomerase RNA component, necessary for telomerase activity. A significant feature of dyskeratosis congenita is an increased susceptibility to cancer; so far, however, no data have been reported on dyskerin changes in human tumours. Therefore, in this study, the distribution of dyskerin in a large series of human tumours from the lung, breast, and colon, as well as from B-cell lymphomas, was analysed by immunohistochemistry. Dyskerin proved never to be lost or delocalized outside the nucleolus. A quantitative analysis of dyskerin mRNA expression was then performed in 70 breast carcinomas together with the evaluation of telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin mRNA levels were highly variable and directly associated with both telomerase RNA component levels and rRNA pseudo-uridylation. Dyskerin gene silencing in the MCF-7 human breast carcinoma cell line reduced telomerase activity and rRNA pseudo-uridylation. Significantly, patients with low dyskerin expression were characterized by a better clinical outcome than those with a high dyskerin level. These data indicate that dyskerin is not lost in human cancers and that the levels of its expression and function are associated with tumour progression.

Breast Neoplasms↗

Cerebral blood flow in fulminant hepatitis.

Fulminant hepatic failure (FHF) is often complicated with cerebral edema, intracranial hypertension, and coma. Cytotoxic and vasogenic factors have been recognized in the etiology of cerebral edema. One of the main causes seems to be the accumulation of glutamine in astrocytes, which is produced from ammonia and the excitatory neurotransmitter glutamate. Ammonia is detoxified within the brain in astrocytes, where it increases the osmotic pressure for water. Ammonia-induced astrocytic water accumulation seems to act as an integrative trigger for the development of intracranial hypertension. While cerebral blood flow is sometimes reduced in the first stage of FHF, as compensatory cerebral vasoconstriction to reduce mean arterial pressure, it later increases as hyperammonemia decreases cerebral arteriolar tone. Despite vasodilation in the systemic and splanchnic beds at early stages of the disease, cerebral vessel resistance may increase, so that cerebral perfusion pressure may be preserved. When cerebral vascular tone is no longer effective in the course of illness, vasodilation gradually develops and rapidly becomes poorly responsive to carbon dioxide stimulation, which signifies loss of autoregulatory tone and cerebral hyperemia develops. Prolonged excessive flow may lead to brain swelling, vasogenic edema, and intracerebral hemorrhage. Brain edema further aggravates the critically reduced cerebral perfusion and is responsible for the high mortality.

Blood Flow Velocity↗

Gender-related differences in the human subthalamic area: a local field potential study.

The objective of this study was to investigate the possible existence of gender-related neurophysiological differences in the oscillatory activity of the human subthalamic area. To this end, we recorded local field potentials (LFPs) after neurosurgical procedures for deep brain stimulation (DBS) in 24 patients (12 males and 12 females) with Parkinson's disease. LFP recordings at rest before levodopa medication (19 nuclei from 11 female patients and 16 nuclei from ten male patients) showed significantly higher power in the alpha/low-beta band (8-12 Hz, P<0.01; 13-20 Hz, P=0.03) in females than in males. After levodopa medication (ten nuclei from six female patients and 11 nuclei from seven male patients), the power in the high-gamma band (60-90 Hz) and of the 300 Hz rhythm was significantly higher in females than in males (high-gamma, P=0.007; 300 Hz, P=0.002). These findings show that functional gender-related differences in the central nervous system involve the human subthalamic area (STN) and its response to levodopa in Parkinson's disease. Gender-related neurophysiological differences may be important for understanding gender-specific features of neurodegenerative disorders and should be considered when interpreting LFP data from the human basal ganglia.

Action Potentials↗

Non-synaptic mechanisms underlie the after-effects of cathodal transcutaneous direct current stimulation of the human brain.

Although cathodal transcranial direct current stimulation (tDCS) decreases cortical excitability, the mechanisms underlying DC-induced changes remain largely unclear. In this study we investigated the effect of cathodal DC stimulation on spontaneous neural activity and on motor responses evoked by stimulation of the central and peripheral nervous system. We studied 17 healthy volunteers. Transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES) of the motor area were used to study the effects of cathodal tDCS (1.5 mA, 10 min) on resting motor threshold and motor evoked potentials (MEPs) recorded from the contralateral first dorsal interosseous muscle (FDI). The electroencephalographic (EEG) activity in response to cathodal tDCS was analysed by power spectral density (PSD). Motor axonal excitability changes in response to transcutaneous DC stimulation of the ulnar nerve (0.3 mA, 10 min) were assessed by testing changes in the size of the compound muscle action potential (CMAP) elicited by submaximal nerve stimulation. Cathodal tDCS over the motor area for 10 min increased the motor threshold and decreased the size of MEPs evoked by TMS for at least 60 min after current offset (t(0) 71.7 +/- 5%, t(20) 50.8 +/- 11%, t(40) 47.7 +/- 7.7%, and t(60) 39.7 +/- 6.4%, P < 0.01). The tDCS also significantly decreased the size of MEPs elicited by TES (t(0) 64 +/- 16.4%, P = 0.09; t(20) 67.6 +/- 10.8%, P = 0.06; and t(40) 58.3 +/- 9.9%, P < 0.05). At the same time in the EEG the power of delta (2-4 Hz) and theta (4-7 Hz) rhythms increased (delta 181.1 +/- 40.2, P < 0.05; and theta 138.7 +/- 27.6, P = 0.07). At the peripheral level cathodal DC stimulation increased the size of the ulnar nerve CMAP (175 +/- 34.3%, P < 0.05). Our findings demonstrate that the after-effects of tDCS have a non-synaptic mechanism of action based upon changes in neural membrane function. These changes apart from reflecting local changes in ionic concentrations, could arise from alterations in transmembrane proteins and from electrolysis-related changes in [H(+)] induced by exposure to constant electric field.

Adult↗

Physiological recordings from electrodes implanted in the basal ganglia for deep brain stimulation in Parkinson's disease. the relevance of fast subthalamic rhythms.

Deep brain stimulation electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease allow electrophysiological recordings from the human basal ganglia. Subthalamic local field potential recordings revealed the presence of multiple rhythms, from the classical EEG frequency range (<50 Hz), to surprisingly high frequencies (70 Hz and 300 Hz). Fast rhythms are particularly attractive because of their likely interaction with the excitatory mechanisms of action of deep brain stimulation. Here we investigated whether the two rhythms at 70 Hz and at 300 Hz represent distinct modes of operation, and therefore different targets, within the subthalamic nucleus. We retrospectively analyzed the dataset we used to describe the 300 Hz rhythm (Foffani, Priori et al., Brain 126: 2153-2163, 2003) searching for significant 70 Hz oscillations after levodopa administration. Whereas (as previously reported) 300 Hz activity was a consistent feature in the dataset, significant 70 Hz activity was observed in only 2 of 11 nuclei. Therefore, 70 Hz oscillations are not a necessary condition for the presence of 300 Hz oscillations. The two rhythms probably arise from different mechanisms, reflecting different functional and/or spatial aspects of subthalamic pathophysiology. Fast subthalamic oscillations could be exploited for intra-operative electrophysiological monitoring of the subthalamic nucleus, post-operative confirmation of electrode placement and patient-specific 'reglage' of the electrical parameters for chronic deep brain stimulation.

Basal Ganglia↗

Heterodyne mixing of two far-infrared quantum cascade lasers by use of a point-contact Schottky diode.

We demonstrate heterodyne mixing of two free-running, multimode, 3.3-THz quantum cascade lasers by use of a point-contact Schottky diode. By temperature tuning the emission wavelength of one laser, a difference frequency signal spanning the 2-4-GHz range is obtained, with a signal-to-noise ratio of 30 dB. The frequency of the heterodyne signal is subject to random fluctuations of a few megahertz, principally from instabilities in the temperatures of the devices. From single-shot measurements we derive an instantaneous linewidth for a single Fabry-Perot mode of 20 kHz, corresponding to an integration time of 3.6 ms.

Journal Article↗

How long is IVIg effective in multifocal motor neuropathy?

The authors treated 10 patients with multifocal motor neuropathy (MMN) responding to an initial course of IV immunoglobulin (IVIg) with periodic infusion for 5 to 12 years (mean 8.2 years). At last follow-up, only two patients had maintained the maximal improvement achieved during therapy while eight worsened despite increasing Ig dosage. This decline started after 3 to 7 years (mean 4.8 years) of therapy and correlated with a reduction of distal compound muscle action potential amplitudes (p < 0.019). The effectiveness of IVIg in MMN often declines after several years possibly associated with the development of axonal degeneration.

Adult↗

The subthalamic nucleus in Parkinson's disease: power spectral density analysis of neural intraoperative signals.

To test a new tool for the neurophysiological identification of the human subthalamic nucleus (STN) during stereotactic surgery for the implantation of deep-brain-stimulation (DBS) electrodes, we analysed off-line the intraoperative signals recorded from patients with Parkinson's disease. We estimated the power spectral density (PSD) along each penetration track (8 patients, 13 sides) and determined the spatial correlation of the PSD with the target location estimated from neuroimaging procedures ("anatomical target"), and with the final target location derived from standard intraoperative neurophysiological procedures for STN localization ("clinical target"). At each step we recorded the 'on-line' signal for 120 seconds; because the PSD was estimated by calculating the periodogram for 6-second epochs of neural signal, we had 20 epochs at each step. When the electrode track crossed the STN, the PSD in the 0.25-2.5 kHz band increased, peaking on average <0.5 mm cranial to the clinical target and 1.00+/-1.51 mm caudal to the anatomical target. When the track was outside the nucleus, the PSD remained unchanged. Even on recordings with low signal-to-noise ratio, off-line PSD analysis of neural signals showed a good correspondence with the target indicated by the surgical team. On-line intraoperative estimation of the PSD may be a simple, reliable, rapid and complementary approach to electrophysiological monitoring during STN surgery for Parkinson's disease.

Aged↗

300-Hz subthalamic oscillations in Parkinson's disease.

Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.

Adult↗

Do intraoperative microrecordings improve subthalamic nucleus targeting in stereotactic neurosurgery for Parkinson's disease?

AIM: The clinical importance of intraoperative microrecordings for subthalamic nucleus (STN) localization in neurosurgical practice remains a matter of debate in the various groups. METHODS: To investigate their usefulness in localizing the STN, we retrospectively evaluated how intraoperative microelectrode recordings changed the targeting of the STN estimated only on intraoperative stimulation and neuroanatomic targeting procedures. For neuroradiologic targeting of the nucleus we used a TC-MRI fusion algorithm and direct visualization of the STN. Besides standard microrecordings we also analyzed the power spectral density (PSD) pattern of physiological signals along the track and its neuroanatomic and clinical correlations. RESULTS: In our series of 12 patients with Parkinson's disease undergoing surgery for implantation of deep-brain stimulation (DBS) electrodes in the STN we found that in 25% (1/4) of patients, microrecordings determined the choice of the optimal track. In all the tracks analyzed the PSD peak coincided with the point selected for the final electrode implantation on the basis of the standard procedure for intraoperative monitoring based on both microstimulation and recordings. CONCLUSION: Intraoperative microrecordings are of determinant importance for accurate STN localization and are essential for optimal results in neurosurgical practice. PSD analysis is a simple and quick quantitative signal descriptor that will probably provide even more precise, simple and rapid tool for intraoperative neurophysiological localization of the STN.

Electrodes, Implanted↗

Ultrafast coherent electron transport in semiconductor quantum cascade structures.

Coherent electron transport is studied in an electrically driven quantum cascade structure. Ultrafast quantum transport from the injector into the upper laser state is investigated by midinfrared pump-probe experiments directly monitoring the femtosecond saturation and subsequent recovery of electrically induced optical gain. We demonstrate for the first time pronounced gain oscillations giving evidence for a coherent electron motion. The coexistence of a long dephasing time of quantum coherence and high Coulomb scattering rates in the injector points to the occurrence of scattering-induced coherence in electron transport.

Journal Article↗

Movement-related modulation of neural activity in human basal ganglia and its L-DOPA dependency: recordings from deep brain stimulation electrodes in patients with Parkinson's disease.

Through electrodes implanted for deep brain stimulation in three patients (5 sides) with Parkinson's disease, we recorded the electrical activity from the human basal ganglia before, during and after voluntary contralateral finger movements, before and after L-DOPA. We analysed the movement-related spectral changes in the electroencephalographic signal from the subthalamic nucleus (STN) and from the internal globus pallidus (GPi). Before, during and after voluntary movements, signals arising from the human basal ganglia contained two main frequencies: a high beta (around 26 Hz), and a low beta (around 18 Hz). The high beta (around 26 Hz) power decreased in the STN and GPi, whereas the low beta (around 18 Hz) power decrease was consistently found only in the GPi. Both frequencies changed their power with a specific temporal modulation related to the different movement phases. L-DOPA specifically and selectively influenced the spectral power changes in these two signal bands.

Antiparkinson Agents↗

Distinctive abnormalities of motor axonal strength-duration properties in multifocal motor neuropathy and in motor neurone disease.

The strength-duration function is a classic measure of neural excitability. When studied on peripheral motor axons it reflects the intrinsic nodal membrane properties, and its time-constant (tau(SD) or chronaxie) predominantly depends on non-voltage-gated, rest Na(+) inward conductances. We assessed the strength-duration curve of ulnar motor axons in 22 nerves of healthy controls, in 18 nerves of patients with multifocal motor neuropathy with conduction blocks (MMN), and in 19 nerves of patients with motor neurone disease (MND). The compound muscle action potential (CMAP) was smaller in nerves of both groups of patients than in controls (P < 0.05). The rheobasic current (rh(50%)) [mean +/- standard deviation (SD)] was higher in patients with MMN than in controls (13.3 +/- 16.3 mA; controls 4.7 +/- 1.7 mA, P < 0.05). The tau(SD) was differentially abnormal in the nerves of the two groups of patients: it was prolonged in the nerves of patients with MND for >or=40 years (227.2 +/- 34.5 micro s; controls 190.9 +/- 51.0 micro s, P < 0.05), but it was shortened in the nerves of patients with MMN (146.5 +/- 55.4 micro s; controls 208.6 +/- 51.2 micro s, P < 0.05) who had not been treated recently with high-dose intravenous immunoglobulin (IVIg). Nerves of patients with recently treated MMN (<6 weeks) who were under the therapeutic effect of IVIg had a normal tau(SD)(.) Our results suggest that, probably due to an immuno-mediated rest Na(+) channel dysfunction, Na(+) conductances are reduced in MMN. This abnormality is a function of the time after the last IVIg treatment and involves also the axonal membrane outside the conduction block. Conversely, in MND, possibly owing to the ionic leakage of degenerating membrane, rest Na(+) conductances are increased. Measuring the strength-duration curve of the ulnar motor axons might be useful in the differential diagnosis between de novo MMN and MND.

Action Potentials↗

Multifocal motor neuropathy: clinical and immunological features and response to IVIg in relation to the presence and degree of motor conduction block.

OBJECTIVE: To determine whether patients with clinically typical multifocal motor neuropathy (MMN) with or without definite or probable conduction block (CB) differ in terms of clinical presentation, immunological findings, or response to treatment with intravenous immunoglobulin (IVIg). METHODS: 23 consecutive patients were studied with the typical clinical features of MMN, consisting of a progressive multineuropathic motor impairment with minimal or no sensory loss. In 14 patients, electrophysiological studies disclosed the presence of a definite or probable CB according to the criteria proposed by the American Association of Electrodiagnostic Medicine (AAEM) in at least one motor nerve. Six patients had possible CB, defined as a degree of CB 10% less than that required by the AAEM for probable CB, while no CB was detected in three patients. RESULTS: Patients with possible CB did not differ from those with a definite or probable CB in terms of age at disease onset (mean 38.8 v 38.2 years, respectively), distribution and severity of limb weakness, clinical impairment (mean Rankin score 2.2 in both), and frequency of antiganglioside antibodies (33% v 29%). Patients with possible CB had a longer mean disease duration (9 v 5.9 years, p < 0.05) and a less frequent consistent response to IVIg (67% v 86%) than those with a definite or probable CB. Patients without a detectable CB had a similar frequency of antiganglioside antibodies (33%) but had a longer disease duration (20.3 years), greater impairment (Rankin score 2.7), and more frequent signs of axonal degeneration (41% of examined motor nerves) than patients with CB (13-15%, p < 0.005). Only one patient without detectable CB (33%) consistently improved with IVIg. CONCLUSIONS: Patients with possible CB were clinically and immunologically indistinguishable from those with definite or probable CB, albeit with a slightly less frequent response to IVIg. This finding suggests that failure to fulfil AAEM criteria for CB in patients with otherwise clinically typical MMN should not preclude this diagnosis and consequently a treatment trial with IVIg. Whether the longer duration and greater severity of the disease and more frequent axonal impairment in patients without detectable CB than in those with CB explain their lower response to IVIg remains to be established.

Adult↗

Clinical relevance of hemochromatosis-related HFE C282Y/H63D gene mutations in patients on chronic dialysis.

BACKGROUND: The actual prevalence and the clinical relevance of gene mutations of HFE (which are linked to hemochromatosis) have not yet been established in patients on chronic dialysis. On the basis of theoretical premises, it could be hypothesized that these genetic determinants might influence the response to iron intake and the susceptibility for iron overload in patients in parenteral iron therapy. Furthermore, carriers for these mutations might be prone to develop sporadic porphyria cutanea tarda and cardiovascular events. METHODS: C282Y/H63D mutations of HFE gene were evaluated in 132 patients (34 in peritoneal dialysis, 98 in HD) and correlated with biochemical parameters of iron status (ferritin (FER) concentration and transferrin saturation (TSAT)), red cell parameters (red cell size and hemoglobin content), erythropoietin (EPO) dosage, major cardiovascular events and C-reactive protein as marker of chronic inflammation, in patients without iron therapy and after i.v. iron supplementation (< or = 60 mg/week) and with the presence of biopsy-proven porphyria. RESULTS: C282Y heterozygous mutation was found in 8/132 (6.6%); H63D homozygous and heterozygous mutations were found in 3/132 (2.3%) and 22/132 (16%) patients, respectively. Two patients (1.5%) showed double heterozygosis. No differences in baseline serum FER and TSAT and the other biochemical and clinical parameters were found in patients bearing mutations alleles nor after continuous iron therapy at low dosages. However, the prevalence of patients capable of maintaining normal hemoglobin (Hb) level without EPO therapy is increased in the C282Y-mutated patients. Only 1 patient out of the 4 with biopsy-proven porphyria cutanea tarda was bearing gene mutations (H63D heterozygosis). CONCLUSION: C282Y/H63D HFE gene mutations do not seem to be related to major abnormalities in biochemical parameters of iron status in dialysis patients without iron therapy or after i.v. iron supplementation, granted that low dosages are employed. Obviously, as our patients were exposed to a relatively uniform iron regimen in our clinical center (< or = 60 mg/week), it is unclear if other dosing regimens will unmask clinically significant differences between the heterozygotes and normals. The fact that the C282Y-mutated patients more frequently maintain high Hb values without EPO is interesting as could suggest a better use of available iron for erythopoiesis, but needs to be confirmed in larger samples. No clear association is demonstrated with porphyria cutanea tarda and major cardiovascular events.

Aged↗

Limb immobilization for the treatment of focal occupational dystonia.

BACKGROUND: Occupational focal upper-limb dystonia is characterized by involuntary muscle contractions that selectively interfere with the execution of specific motor tasks such as writing or playing a musical instrument. Occupational dystonias have a severe social impact, especially in certain professions. The available medical treatments offer little benefit. METHODS: In eight patients with idiopathic occupational focal dystonia of the upper limb, the dystonic forearm and hand were immobilized with a plastic splint for mean (+/-SD) 4.5 +/- 0.75 weeks. Before splinting (base line) and at various intervals afterwards (4, 12, and 24 weeks), the authors assessed the severity of dystonia and the patients' motor performance objectively (Arm Dystonia Disability Scale and Tubiana and Chamagne Score) and subjectively (Self-Rating Score). RESULTS: Assessment 4 weeks after splint removal, when patients had regained normal voluntary movements, showed that the severity of dystonia and the patients' performance of the impaired motor task had improved; the benefit persisted unchanged at later follow-up visits (Arm Dystonia Disability Scale: base line 20.6 +/- 30.2%; after 4 weeks 83.9 +/- 23.8%, p = 0.007; after 12 weeks 83.9 +/- 23.8%, p = 0.007; after 24 weeks 79.7 +/- 29.5%, p = 0.015. Tubiana and Chamagne Score: base line 28.6 +/- 22.7%; after 4 weeks 80.0 +/- 23.1%, p = 0.015; after 12 weeks 80.0 +/- 23.1%, p = 0.015; after 24 weeks 74.3 +/- 32.1%, p = 0.031. Self-Rating Score: base line 20.6 +/- 19.3%; after 4 weeks 63.7 +/- 25.2%, p = 0.015; after 12 weeks 66.9 +/- 28.1%, p = 0.015; after 24 weeks 70.6 +/- 31.8%, p = 0.015). At the 24-week visit the improvement disappeared in one patient, was moderate in three, and marked in four. CONCLUSIONS: Limb immobilization can be a simple, effective, safe, and inexpensive treatment for focal occupational upper-limb dystonia.

Adult↗

Transient improvement induced by motor fatigue in focal occupational dystonia: the handgrip test.

Muscle fatigue induced by a previous sustained contraction temporarily decreases the motor output, transiently worsening motor performance. Whether muscle fatigue alters motor performance also in dystonia-a disorder whose main pathophysiological abnormality is motor overflow-remains unknown. To assess the effects of muscle fatigue in patients with focal occupational upper limb dystonia, we studied the effect of a previous maximum fatiguing voluntary contraction on motor performance in 10 musicians with focal occupational dystonia, in 3 musicians with hand motor impairment due to non-dystonic disorders, and in 5 normal musicians. The fatiguing task consisted of grasping a spring handgrip as long as possible until the task failed. In dystonic musicians, a fatiguing contraction significantly improved motor performance. The improvement lasted less than 5 minutes and appeared only after fatigue of the affected upper limb. In contrast, in musicians with non-dystonic motor impairment, motor performance remained unchanged or worsened, and normal musician performance consistently worsened.

Adult↗