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Biomedical subjects

A Lazzaro

Publications and source records attributed to A Lazzaro.

At least 19 recordsLinked to original sources

[Usefulness of atrial vulnerability in predicting atrial fibrillation in patients with sick sinus syndrome treated with DDD pacemaker].

BACKGROUND: Atrial fibrillation (AF) is common in patients with sick sinus syndrome (SSS) treated with dual-chamber pacing and it may complicate their management. This study was undertaken to establish the usefulness of atrial vulnerability (AV), determined by means of transesophageal electrophysiological study (TES), in predicting the risk of developing AF and in deciding the type and program of pacemaker (PM) to be implanted in patients with SSS. METHOD: AV was assessed preoperatively using TES in 81 consecutive patients with SSS. AV (AF > 1 min) was divided into "low threshold" (induction with burst < or = 300/min) and "high threshold" (induction with burst > or = 350 min or with incremental ramp). The PM was programmed to ensure constant atrial capture in all patients. Follow-up lasted three years. No patients received antiarrhythmic drugs. RESULT: AV was positive in 52% of patients (Group A) and negative in 48% of patients (Group B). A history of paroxysmal AF was present in 52% of patients in Group A and in 12% of patients in Group B. At follow-up, 38% of Group A and 2% of Group B patients had chronic AF. AV had sensitivity, specificity, positive predictive value (ppv) and negative predictive value (npv) of 94, 59, 38 and 97%, respectively. Thirty-eight percent of patients showed low threshold vulnerability, with sensitivity, specificity, ppv and npv of 87, 92, 87 and 93%, respectively. Sensitivity, specificity, ppv and pnv for history of AF were 93, 100, 98 and 84%, respectively. When the vulnerability threshold and the history of paroxysmal AF were considered together, the sensitivity, specificity, ppv and npv was 94, 100, 100 and 83%, respectively. Multivariate analysis was shown to be an independent predictive value only for history of AF (p = 0.0002). CONCLUSION: AV determined by means of TES, especially with a low induction threshold, shows excellent sensitivity and specificity in evaluating the risk of chronic AF. It could be useful in patients with SSS undergoing cardiac pacing who have never had AF, thus allowing a more accurate choice of the type and program of PM to be implanted. Case histories of paroxysmal AF could represent useful criteria for selecting patients at a high risk of developing chronic AF.

Aged

Primary human mesothelioma cells express class II MHC, ICAM-1 and B7-2 and can present recall antigens to autologous blood lymphocytes.

Mesothelioma cells (MMc) are considered to be weakly immunogenic and the experimental approaches attempting to induce an immune response against these cells have been disappointing. Our aim was to investigate whether MMc possess the surface accessory molecules involved in antigen presentation and whether these cells are capable of presenting recall antigens to autologous blood lymphocytes. Four primary MMc cultures were generated from malignant effusions and examined to assess whether the accessory molecules required for antigen presentation were present on their surfaces. Intercellular adhesion molecule-I (ICAM-I; CD54); class I and class II major histocompatibility complex-DR (MHCI and MHCII-DR); B7-1 (CD80.3); and B7-2 (CD86) expression by MMc was studied by immunocytochemical and/or FACScan analysis. MMc were pulsed with purified protein derivative (PPD), Tetanus toxoid (TT) and Candida albicans (CA) bodies, and incubated with autologous lymphocytes. Lymphocyte proliferation was estimated by radionucleotide incorporation. Phenotypic analysis showed the presence of MHCII-DR, ICAM-I and B7-2 on primary MMc cultures, whereas the phenotypic evaluation of 2 established MMc lines did not show the presence of the B7-1 and B7-2 molecules. In addition, MHCII-DR was detectable only after interferon gamma (IFN-gamma) stimulation. Primary MMc cultures acquired the capability to induce lymphocyte proliferation after pulse with the recall antigens. To achieve characterization of these lymphocytes, we generated a PPD-specific CD4+ T-cell clone. PPD-pulsed MMc were shown to specifically induce T-cell clone proliferation through a MHCII-DR-mediated process. We conclude that primary MMc possess the surface molecules required for antigen presentation and can present recall antigens to CD4+ lymphocytes.

Aged

GM1 reduces infarct volume after focal cerebral ischemia.

The efficacy of monosialoganglioside GM1 treatment was evaluated in a model of experimental stroke. Cerebral ischemia was induced by permanent occlusion of left middle cerebral artery. GM1 was administered intravenously soon after the occlusion of the artery and then intramuscularly daily for 7 days. Results indicate that GM1 can reduce the extent of infarct volume and neurochemical deficits associated with the ischemic event. The protection was more evident in the cortex than in the caudate-putamen. These observations confirm and extend the evidence of the GM1 efficacy in experimental models of stroke and further support the usefulness of gangliosides in the treatment of these pathologies.

3,4-Dihydroxyphenylacetic Acid

Effects of granulocyte-macrophage colony-stimulating factor and interleukin-3 on small cell lung cancer cells.

Nonhematopoietic malignant cells may express receptors for hematopoietic growth factors and respond to these peptides. The aim of the present study was to investigate whether small cell lung cancer (SCLC) cells may be stimulated to proliferate by hematopoietic growth factors such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3), which are currently used in clinical trials in combination with cytotoxic chemotherapy. We studied two SCLC cell lines, H69 and N417. The effects of GM-CSF and IL-3 were evaluated by studying clonal growth, 3H-thymidine incorporation, BUDR/DNA bivariate flow cytometry, c-myc and N-myc oncogene expression, and myeloid surface markers. Our experiments show that both GM-CSF and IL-3 can increase 3H-thymidine incorporation and cloning efficiency and reduce DNA synthesis time of H69 and, to a lesser extent, N417 cells, supporting the hypothesis that hematopoietic growth factors can stimulate the growth of some malignant nonhematopoietic cells in vitro. Further in vitro and in vivo studies are needed to determine whether clinical trials applying these factors for bone marrow recovery after chemotherapy of solid tumors may be hazardous by potentially stimulating growth of remaining tumor tissue.

Carcinoma, Small Cell

Orally administered glycolipid derivative LIGA20 reduces infarct volume and behavioral impairment after focal cerebral ischemia.

The efficacy of p.o. semisynthetic glycolipid LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-aceta mide-4-trans- octadecene) treatment in stroke was studied in a permanent left middle cerebral artery occlusion model in the rat. A dose-dependent increase of plasma LIGA20 and its presence in the brain were documented after p.o. drug application. Oral administration of 50 to 200 mg/kg of LIGA20, initiated 24 hr before middle cerebral artery occlusion and continued for 7 days, reduced the motor and cognitive impairment after the stroke, measured by the rotarod and the passive avoidance test, respectively. The 10-mg/kg dose was effective when given i.v. but not p.o. Oral treatment with 100 mg/kg of LIGA20 reduced the infarct size in the cortex but not in the ischemic core (the striatum). No biochemical or behavioral adverse effects of LIGA20 treatment were observed. Further studies are needed to evaluate the full therapeutic potential of this compound.

Administration, Oral

Central diabetes insipidus due to acute monocytic leukemia: case report and review of the literature.

We describe a 69-year-old man who presented with a four-month history of polyuria and polydipsia. Plasma vasopressin levels were undetectable, and a dehydration test was abnormal. Based on these findings, a diagnosis of central diabetes insipidus has been established. Hematologic studies showed acute monocytic leukemia. A relationship between the hematologic and endocrine disturbance has been hypothesized, and histological examination at autopsy showed leukemic infiltration of the pituitary stalk. This patient represents the third case in the world literature of central diabetes insipidus associated with acute monocytic leukemia.

Diabetes Insipidus

Ganglioside derivative LIGA20 reduces NMDA neurotoxicity in neonatal rat brain.

The semisynthetic ganglioside derivative LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-ac eta mide-4-trans-octadacene) was found to be about ten times more potent than the natural ganglioside GM1 in protecting neurones in culture against glutamate toxicity. Here we show that, in vivo, LIGA20 attenuated toxicity of the glutamate receptor agonist N-methyl-D-aspartate (NMDA). In seven-day-old rats NMDA was injected intracerebroventricularly, while LIGA20 or GM1 were administered subcutaneously. The loss in brain weight, five days following treatment, was used to estimate NMDA toxicity. Significant protection was observed with 2.5 mg kg-1 of LIGA20, while at least ten times this dose was needed for GM1, thus suggesting the superior in vivo pharmacological action of LIGA20.

Animals

Monosialoganglioside GM1 reduces NMDA neurotoxicity in neonatal rat brain.

Monosialoganglioside GM1 prevents excitatory amino acid (EAA)-related neuronal death in cultured central nervous system (CNS) neurons and reduces the severity of acute brain damage in different experimental models of cerebral ischemia. Using a model of brain damage induced by intracerebroventricular administration of N-methyl-D-aspartate (NMDA) in neonate rats, we evaluated whether GM1 is capable of exerting antiexcitotoxic effects following its systemic administration in vivo. Newborn rats subjected to brain damage by NMDA and contemporaneously treated subcutaneously with GM1 showed significantly reduced (i) loss in hemispheric weight, (ii) loss in tissue choline acetyltransferase activity, and (iii) morphological damage in various brain areas. These results indicate that systemic GM1 treatment is efficacious in reducing EAA-related neuronal damage in vivo and suggest that such a phenomenon may underlie its capability to ameliorate neurological outcome following cerebral ischemia.

Animals

Effects of monosialoganglioside GM1 in experimental models of ischemic brain damage.

Systemic administration of monosialoganglioside GM1 is efficacious in reducing excitatory amino acid (EAA)-related neurotoxicity in vivo following intracerebroventricular injection of N-methyl-D-aspartate (NMDA) in 7-day-old rats. Five days later, NMDA-treated animals showed extensive brain damage which was accompanied by significant decreases in brain weight, choline acetyltransferase activity and 3H-ouabain binding. All these neurotoxic effects were significantly reduced with ganglioside treatment. Since excessive activation of EAAS is implicated in hypoxic-ischemic brain damage, these results favor the hypothesis that a similar effect is involved in the ability of ganglioside to ameliorate outcome following cerebral ischemia.

Animals

Protective effects of a monosialoganglioside derivative following transitory forebrain ischemia in rats.

We evaluated the effects of treatment with the inner ester derivative of the monosialoganglioside GM1 on cortical electroencephalographic activity and hippocampal CA1 morphology after transitory, near-complete cerebral ischemia in rats. Ischemia was induced by the four-vessel occlusion method, and we studied only the 58 rats that showed flattening of the cortical electroencephalogram for the entire 30 minutes of occlusion. The ganglioside (n = 30) or saline (n = 28) was administered intravenously immediately after release of the carotid clips and then intramuscularly for 21 days of observation. Cortical electroencephalographic activity was monitored throughout the experiment. After 21 days of recirculation we assessed hippocampal CA1 damage by light microscopy. The results indicate that treatment with the ganglioside reduces postischemic secondary damage to the cortical circuitry (as indicated by significantly higher cortical electroencephalographic activity late after reperfusion) and limits neuronal loss in the CA1 region. Our results lend support to the possible therapeutic use of ganglioside in human pathologic conditions associated with cerebrovascular insufficiencies.

Animals

Monosialoganglioside effects following cerebral ischemia: relationship with anti-neuronotoxic and pro-neuronotrophic effects.

Increasing evidence is available indicating that systemically administered GM1 is able to provide for functional recovery in different experimental models of CNS injury, including cerebral ischemia. Current evidence indicates that the GM1 effects are associated, in the acute phase, with attenuation of secondary neuronal damage due to its capability to antagonize excitatory amino acid-related neurotoxicity in vivo as in vitro. Furthermore, the ganglioside is able to facilitate occurrence of long-term reparative processes, an effect most likely reflecting the potentiation of the action of neuronotrophic factors. This bifaceted action of GM1 makes the ganglioside ideally suited for clinical treatment of patients afflicted by cerebrovascular insufficiencies.

Animals

Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside.

In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation. Systemic administration of GM1 appears to be efficacious in reducing acute neuronal damage and in facilitating medium- and long-term functional recovery after brain injury. We propose that GM1 protective effects in the acute injury phase results from attenuation of excitotoxicity, whereas the functional recovery seen at longer term could reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in humans is suggested by clinical studies demonstrating improved neurologic outcome in stroke patients.

Amino Acids

[Prevention of recurrent respiratory infections in adults].

The authors compared the results obtained by using antibiotic therapy, vaccine, thymomodulin (a calf thymus acid lysate) and association of vaccine-thymomodulin in order to prevent acute infectious episodes in a group of 85 patients suffering with recurrent respiratory infections. The use of thymomodulin, alone and in association with vaccine, at the dose of 120 mg/die for 20 days/month during the period of observation (4 months), determined a higher reduction, (p less than 0.001) if compared with the other treatments, of the number and the duration of infectious episodes and moreover of the antibiotics' intake. Also the respiratory symptoms, and in particular the fits of coughing, showed an improvement. The pulmonary function indices and the laboratory parameters were unchanged in all groups studied.

Adult