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Biomedical subjects

B Bergamasco

Publications and source records attributed to B Bergamasco.

At least 73 records · Page 4Linked to original sources

Pain threshold and tolerance in Alzheimer's disease.

We tested both pain thresholds and pain tolerance in patients with Alzheimer's disease (AD) by means of phasic and tonic noxious stimuli. In the first case, electrical stimulation was used, whereas in the second case arm ischemia was studied. By comparing AD patients with normal subjects of the same age, we found no differences in stimulus detection and pain thresholds, whereas a clearcut increase in pain tolerance was present in AD patients. The severity of AD was assessed by means of the Mini Mental State Examination test (MMSE) and the spectral analysis of the electroencephalogram (EEG). There was a straightforward correlation between MMSE scores and pain tolerance such that the more severe the cognitive impairment the higher the tolerance to pain. In addition, analysis of the EEG power spectra indicated that patients with low alpha and high delta peaks showed an increase in pain tolerance to both electrical stimulation and ischemia. These findings show that, whereas the sensory-discriminative component of pain is maintained in AD patients, pain tolerance is altered and depends on cognitive and affective factors. Thus, pain tolerance is tightly related to the severity of the disease according to the rule, 'the more severe the MMSE and EEG changes, the higher the tolerance to pain'.

Aged↗

Neurophysiologic assessment of nerve impairment in posterolateral and muscle-sparing thoracotomy.

OBJECTIVE: This study was aimed at analyzing the degree of intercostal nerve impairment in posterolateral and muscle-sparing thoracotomy and at correlating the nerve damage to the severity of long-lasting postthoracotomy pain. METHODS: Neurophysiologic recordings were performed 1 month after either posterolateral or muscle-sparing thoracotomy to assess the presence of the superficial abdominal reflexes (mediated in part by the intercostal nerves), the somatosensory-evoked responses after electrical stimulation of the surgical scar, and the electrical thresholds for tactile and pain sensations of the surgical incision. RESULTS: The patients who underwent a posterolateral thoracotomy showed a higher degree of intercostal nerve impairment than the muscle-sparing thoracotomy patients as revealed by the disappearance of the abdominal reflexes, a larger reduction in amplitude of the somatosensory-evoked potentials, and a larger increase of the sensory thresholds to electrical stimulation for both tactile perception and pain. In addition, these neurophysiologic parameters were highly correlated to the postthoracotomy pain experienced by the patients 1 month after surgery, indicating a causal role for nerve impairment in the long-lasting postoperative pain. CONCLUSIONS: This study shows for the first time the pathophysiologic differences between posterolateral and muscle-sparing thoracotomy and suggests that the minor long-lasting postthoracotomy pain in muscle-sparing thoracotomy patients is partly due to a minor nerve damage. In addition, because nerve impairment is responsible for the long-lasting neuropathic component of postoperative pain, it is necessary to match specific treatments to the neuropathic pain-generating mechanisms.

Case-Control Studies↗

Dose-response relationship of opioids in nociceptive and neuropathic postoperative pain.

The treatment of neuropathic pain with opioid analgesics is a matter of controversy among clinicians and clinician scientists. Although neuropathic pain is usually believed to be only slightly responsive to opioids, several studies show that satisfactory analgesia can be obtained if adequate doses are administered. In the present study, we tested the effectiveness of buprenorphine in 21 patients soon after thoracic surgery (nociceptive postoperative pain) and 1 month after surgery in the same 21 patients who developed postthoracotomy neuropathic pain with a burning, electrical and shooting quality. According to a double-blind randomized study, the analgesic dose (AD) of buprenorphine needed to reduce the long-term neuropathic pain by 50% (AD50) was calculated and compared to the AD50 in the immediate postoperative period. We found that long-term neuropathic pain could be adequately reduced by buprenorphine. However, the AD50 in neuropathic pain was significantly higher relative to the AD50 in the short-term postoperative pain, indicating a lower responsiveness of neuropathic pain to opioids. We also found a strict relationship between the short-term and long-term AD50, characterized by a saturating effect. In fact, if the AD50 soon after surgery was low, the AD50 increase in the long-term neuropathic pain was threefold. By contrast, if the AD50 soon after surgery was high, the AD50 in neuropathic pain was only slightly increased. This suggests that, though neuropathic pain is indeed less sensitive to opioids, in some neuropathic patients a large amount of opioid resistance is already present in other painful conditions.

Aged↗

EPR investigations of the iron domain in neuromelanin.

The interactions between iron and neuromelanin (NM) have been studied by means of EPR spectroscopy. The variable temperature EPR spectral features of a specimen of NM extracted from normal human midbrains clearly indicate that iron is present as polynuclear oxy-hydroxy ferric aggregates as well as isolated Fe(III) centres. Ferric oxy-hydroxy phases are typical of the iron storage proteins ferritin and hemosiderin, but the comparison of the variable temperature EPR spectra of ferritin and NM highlights significant differences between the two iron(III)oxy-hydroxy domains. Moreover, further investigations on melanin models synthesised in the presence of either ferritin or a ferric salt as iron sources suggest that the same pathway of formation and inclusion of the polynuclear iron oxide is operating in NM and in the model systems, whatever is the source of iron.

Brain Chemistry↗

Modified and improved anti-acetylcholine receptor (AchR) antibody assay: comparison of analytical and clinical performance with conventional anti-AChR antibody assay.

We developed a modified anti-acetylcholine receptor (AChR) antibody (Ab) assay based on a radioreceptor assay and a calibration curve. We compared the analytical and clinical performances of this modified assay with those of the conventional anti-AChR Ab radioreceptor assay. Serum specimens were from patients with myasthenia gravis (MG) (n = 156) and from control subjects (n = 106). The modified assay demonstrated lower within-assay (4.0-6.6%) and between-assay (5.3-7.8%) CVs, greater linearity, lower cost, and shorter assay time than the conventional method. ROC curve analysis indicated almost identical specificity and sensitivity (> 0.92) for these two anti-AChR Ab assays. The modified and conventional assays were also equivalent for blocking anti-AChR Ab assay. Moreover, the modified anti-AChR Ab assay, differently from the conventional assay, allowed us to reveal anti-AChR Ab concentration differences among different clinical grades of MG.

Adolescent↗

Systemic high-dose recombinant-alpha-2a-interferon therapy modulates lymphokine production in multiple sclerosis.

Chronic systemic high-dose recombinant alpha 2a-interferon (rIFNA) therapy reduces exacerbation rate and MRI signs of disease activity in relapsing/remitting multiple sclerosis (RR MS) patients. In order to clarify the possible mechanisms underlying the clinical efficacy of rIFNA in MS, several immunologic studies were performed as a part of a pilot clinical trial. Twenty RR MS patients were treated with 9 x 10(6) IU of rIFNA (n = 12) or placebo (n = 8) intramuscularly every other day for 6 months. Cytokine production by cultured lymphocytes, major histocompatibility complex class II (MHC-II) antigen expression on cultured macrophages, peripheral blood (PB) and cerebrospinal fluid (CSF) lymphocyte phenotype, and IgG and beta 2 microglobulin levels were studied before therapy, after 6 months of therapy, and 6 months after stopping therapy. rIFNA therapy was associated with reduction of interferon-gamma and tumor necrosis factor-alpha production by PB lymphocytes (p < 0.04), and with slight, not significant, increase of transforming growth factor-beta 2 or interleukin (IL)-10 production. IL-4 was undetectable in the culture supernatants both before and after therapy. rIFNA therapy had no effect on macrophage MHC-II molecule expression. An increased percentage of CD8+, CD8+ high CD11b+ low, and CD3- CD16+ CD56+ cells, and of CD4+ absolute cell number was observed in CSF after rIFNA therapy. After rIFNA administration, IgG level significantly increased both systemically (p < 0.02) and intrathecally (p < 0.001). Serum beta 2 microglobulin level increased (p < 0.01), as well. Only 1 out of the 12 rIFNA treated patients developed neutralizing antibodies against rIFNA during therapy. Six months after stopping therapy all the immunologic changes returned to baseline. These data suggest that the beneficial effect of rIFNA therapy on MS disease activity is probably mediated by a downregulation of proinflammatory cytokine synthesis by PB lymphocytes rather than by macrophage MHC-II antigen expression. The immunologic effects of high-dose systemic rIFNA therapy are temporary and restricted to the period of drug administration.

Antibodies↗

Long term recombinant interferon alpha treatment in MS with special emphasis to side effects.

Twenty relapsing-remitting (RR) clinically definite MS patients were treated with 9 MIU intramuscular recombinant interferon alpha-2a (rIFNA) (Roferon-A, Roche) (n = 12) or placebo (n = 8) every other day for 6 months and followed up for a further 6 months after stopping treatment. Numbers of active lesions at MRI and of patients with clinical-MRI signs of disease activity and lymphocyte interferon gamma production, which were decreased during treatment, returned to values similar to baseline and placebos after stopping treatment. rIFNA chronic therapy seems therefore needed in order to maintain drug efficacy. Side effect profile was monitored, too, for over 1 year in the same 20 patients plus 25 additional RR MS patients. Besides the typical side effects of type I interferon therapy (fever, fatigue, depression, lymphopenia, hepatic enzyme elevation), occurrence of serum autoAbs was noted in 30% patients (in 60% antinuclear and in 80% antithyroid autoAbs). In two patients rIFNA treatment was stopped, in one case for antithyroid autoAbs and hypothyroidism, in the other for antinuclear autoAbs and a five-fold increase of ALT. A careful monitoring of serum autoAbs and of signs of thyroid or liver damage must always precede and accompany longterm type I IFN therapy.

Autoantibodies↗

Interferon alpha-2a treatment of relapsing-remitting multiple sclerosis: disease activity resumes after stopping treatment.

We evaluated the long-lasting effects of systemic high-dose recombinant interferon alpha-2a (rIFNA) in relapsing-remitting (RR) MS after discontinuing treatment in a single-blind randomized placebo-controlled trial with 20 RR clinically definite MS patients using either nine million IU intramuscular rIFNA (n = 12) or placebo (n = 8) every other day for 6 months. Follow-up continued for a further 6 months without IFN treatment. In rIFNA-treated patients, main outcome measures, significantly different from placebo during treatment, returned, after discontinuing treatment, to values similar to placebo or baseline. Active MRI lesions per patient increased from 0.08 +/- 0.08 to 1.2 +/- 0.4 (p < 0.02), number of patients with clinical MRI signs of disease activity from 2 of 12 to 8 to 12 (P < 0.04), lymphocyte IFN gamma production from 3.0 +/- 0.7 to 12.4 +/- 2.2 IU/mL (p < 0.01), lymphocyte tumor necrosis factor alpha production from 5.8 +/- 0.9 to 18.9 +/- 6.3 pg/mL (p < 0.05). All side effects of rIFNA treatment disappeared after discontinuing the drug. The reduction of clinical MRI signs of disease activity and the immunologic effects were temporary and restricted to the period of rIFNA administration. The depression of many immunologic and clinical MRI responses during drug administration and their simultaneous return to baseline after discontinuing the drug strongly argue all observed changes were related to drug administration.

Adult↗

Apomorphine SC treatment in parkinsonian patients with long-term L-dopa syndrome during L-dopa drug holiday.

The Long-Term Dopa Syndrome (LTDS) is one of the main problems in the management of advanced parkinsonian patients. A transient L-Dopa withdrawal (Drug Holiday, DH) can be useful to improve the drug response after DH, even if this approach presents risks due to patient akinesia. We tried to verify if Apomorphine sc administration during DH (DH with Apomorphine, DHA) can: a) reduce the risks connected with DH: b) maintain the benefits of DH: c) standardize the duration of DH. Twenty-five parkinsonian patients with LTDS were treated with Apomorphine sc during DH (14 days). No patient had any severe side effects. The follow-up at 180 days, conducted using the Unified Parkinson's Disease Rating Scale, demonstrated a significant improvement in the clinical conditions of about 70% of the patients, allowing a 27.1% reduction in daily L-dopa dosage. DHA can represent a valid therapeutical approach for parkinsonian patients with LTDS.

Adult↗

Peripheral-type benzodiazepine receptors on human blood mononuclear cells are not regulated by ovarian steroids.

Peripheral-type benzodiazepine receptors (pBZr) have been shown to be sensitive to hormonal perturbations, including changes in ovarian steroids. This study examines whether estradiol and progesterone modulate pBZr binding in membranes of human blood mononuclear cells, as measured by binding of both 3H-PK 11195 and 3H-Ro 5-4864. Our findings were negative. There was no steroidal modulation of pBZr binding to these membrane preparations in vivo in normal women studied at different sex-steroid phases of the menstrual cycle, or during 8-30 weeks of pregnancy. There was also no effect of hormones on the binding sites in cultures of mononuclear cells treated with estradiol or progesterone (up to 10(-5) M) over a period between 2 and 72 h. Further, we performed in vitro competition experiments, which showed that both steroids are not active at the pBZr. Our data suggest that pBZr located in human blood mononuclear cells are insensitive to the physiological variations of circulating female hormones.

Benzodiazepinones↗

Evidence for a glycidic-lipidic matrix in human neuromelanin, potentially responsible for the enhanced iron sequestering ability of substantia nigra.

The high-resolution solid-state 13C-NMR spectrum of a neuromelanin specimen (from patients dying from nonneurological diseases) is compared with that obtained from enzymatically prepared dopamine-melanin. The main differences between the two spectra suggest the occurrence in neuromelanin of a glycidic/lipidic matrix tightly associated with the melanin macromolecule. Atomic emission spectroscopy revealed high iron content (1.5%) in the neuromelanin specimen, in full agreement with previous reports. These observations support the view that neuromelanin acts as a strong chelating (and insolubilizing) system for iron ions and further suggest that the attack to this compact composite substrate may be an important step to allow the release of iron ions responsible for the increased lipid peroxidation reported in the pathogenesis of Parkinson's disease.

Carbon Isotopes↗

Early modification of stretch reflex in Parkinson's disease.

We stretched quadriceps femoris in healthy subjects and in patients with a recent diagnosis of PD in order to assess whether modifications of the long-latency component of the stretch reflex is an early event in the course of Parkinson's disease (PD). We found a modified mechanical and electromyographic (EMG) behavior in stretching relaxed muscles of patients while voluntary activation greatly reduced differences between normal and Parkinsonian subjects, suggesting that a lower threshold of the response is an early sign in PD.

Adult↗

Associated polyneuropathy and demyelinating disease. Case report.

We report a case in which an acute Guillain-Barré-like syndrome was quickly followed by a central demyelinating disease, documented by the clinical findings as well as by magnetic resonance imaging (MRI), electrophysiological and cerebrospinal fluid examinations. The close follow-on of the clinical signs seems to exclude a simple coincidence of two separate diseases and it may constitute further evidence for a possible etiological link between central and peripheral myelin damage. We discuss the possibility of a common pathogenic factor underlying central and peripheral demyelination.

Acoustic Stimulation↗

An analysis of peripheral type benzodiazepine receptors on blood mononuclear cells during high dose steroid treatment of multiple sclerosis.

We report here a study of peripheral type benzodiazepine receptors (pBZr) in mononuclear cells (MNC) from blood of patients with multiple sclerosis (MS) during periods of stable and active disease and from normal controls. Most active MS patients were retested in a longitudinal study, both during a treatment with high dose steroids and while medication free. Active MS produces a significant decrease of receptor density compared with the controls whereas remission of the disease shows no effect. Four weeks of steroid treatment restore binding density to normal levels, and two weeks of drug withdrawal result in a small, but significant increase in number of the binding sites compared with the control value. We suggest that the number of pBZr in blood MNC might change during the clinical course and steroid therapy of MS.

Adult↗