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Biomedical subjects

S Baglioni

Publications and source records attributed to S Baglioni.

At least 19 recordsLinked to original sources

Antineoplastic effects of rosiglitazone and PPARgamma transactivation in neuroblastoma cells.

Neuroblastoma (NB) is the most common extracranial solid tumour in infants. Unfortunately, most children present with advanced disease and have a poor prognosis. In the present study, we evaluated the role of the peroxisome proliferator-activated receptor gamma (PPARgamma) agonist rosiglitazone (RGZ) in two NB cell lines (SK-N-AS and SH-SY5Y), which express PPARgamma. Rosiglitazone decreased cell proliferation and viability to a greater extent in SK-N-AS than in SH-SY5Y. Furthermore, 20 microM RGZ significantly inhibited cell adhesion, invasiveness and apoptosis in SK-N-AS, but not in SH-SY5Y. Because of the different response of SK-N-AS and SH-SY5Y cells to RGZ, the function of PPARgamma as a transcriptional activator was assessed. Noticeably, transient transcription experiments with a PPARgamma responsive element showed that RGZ induced a three-fold increase of the reporter activity in SK-N-AS, whereas no effect was observed in SH-SY5Y. The different PPARgamma activity may be likely due to the markedly lower amount of phopshorylated (i.e. inactive) protein observed in SK-N-AS. To our knowledge, this is the first demonstration that the differential response of NB cells to RGZ may be related to differences in PPARgamma transactivation. This finding indicates that PPARgamma activity may be useful to select those patients, for whom PPARgamma agonists may have a beneficial therapeutic effect.

Antineoplastic Agents↗

A novel microdeletion syndrome with loss of the MSH2 locus and hereditary non-polyposis colorectal cancer.

Constitutional chromosome deletions can predispose to the development of cancer with the phenotypic characteristics of inherited cancer syndromes, when the deleted region encompasses a tumour suppressor gene. Examples of such conditions are represented by the cytogenetic deletions associated with retinoblastoma, Wilms tumour and familial adenomatous polyposis. So far, no constitutional deletions involving the genes implicated in hereditary non-polyposis colorectal cancer (HNPCC) have been identified. This may be at least partially because of the lack of distinctive phenotypic manifestations in HNPCC. We describe the first case of a constitutional microdeletion associated with HNPCC. Suspicion of a microdeletion was prompted by the association of mental retardation, postnatal growth deficiency, minor congenital anomalies and early onset (37 years) sporadic colon cancer. The patient was found to harbour a microdeletion within chromosome 2p16-p21, including the MSH2 gene. Since there are very few reports of deletions of the 2p16-p21 region, our observation sets the grounds for the definition of a novel multiple congenital anomaly/mental retardation/cancer microdeletion syndrome.

Abnormalities, Multiple↗

Determination of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urine by high-performance liquid chromatography combined with mass spectrometry.

A simple, sensitive and specific method for the quantification of N-acetyl-S-(N-methylcarbamoyl)cysteine (AMCC) in urines of the general population and of exposed workers has been developed. Samples were first diluted with phosphate buffer followed by purification by solid-phase extraction (SPE) with SAX columns prior to analysis by liquid chromatography/mass spectrometry (LC/MS). An external standard was used for the quantification together with selected ion monitoring of m/z 219, [M-H]-. The linear calibration curve showed a good correlation (r2 = 0.98, p < 0.001) between 0.1-110 mg/L of AMCC, and the detection limit was calculated to be 2 microg/L. The within-day and between-day precision, calculated for exposed workers and general population AMCC levels in urine samples, were determined as 1.2 and 3.6%, respectively (as relative standard deviation (RSD)).

Acetylcysteine↗

Acylphosphatase overexpression triggers SH-SY5Y differentiation towards neuronal phenotype.

An acylphosphatase (AcPase) overexpression study was carried out on SH-SY5Y neuroblastoma cells, using a green fluorescent fusion protein (AcP-GFP), with GFP acting as a reporter protein. The cellular proliferation rate was significantly reduced by overexpression of AcPase by a factor of ten. In contrast, clones transfected with two inactive AcPase mutants showed a growth rate comparable to control cells. This suggests that AcPase catalyzes the proliferative down-regulation. AcPase-overexpressing clones showed a physiological mortality rate as assessed by an MTT reduction test and by evaluation of necrotic markers. DNA fragmentation analysis and assays of caspase-3 and poly (ADP-ribose) polymerase (PARP)-active fragments showed no evidence of any apoptotic pattern. AcPase overexpression led to a marked increase in PARP activity as well as Bcl-2 content; these are commonly up-regulated during differentiative processes in neuronal cells. In fact, the typical differentiation marker, growth-associated-protein 43, was significantly up-regulated. Microscopic observations also showed a clear increase in the differentiative phenotype in AcPase-overexpressing cells. Our results clearly show that AcPase plays a primary causative role in neuronal differentiation.

Acid Anhydride Hydrolases↗

An open, comparative pilot study of thiamphenicol glycinate hydrochloride vs clarithromycin in the treatment of acute lower respiratory tract infections due to Chlamydia pneumoniae.

The aim of this study was to evaluate the efficacy and tolerability of thiamphenicol glycinate hydrochloride (TGH) i.m. versus clarithromycin in acute lower respiratory infections due to Chlamydia pneumonia. 113 patients with suspected pneumonia were screened. 40 patients with IgM and/or IgA titers > or = 1:16 and/or IgG titers > or = 1:512 were assigned to 10 days of treatment with TGH 1500 mg daily or clarithromycin 1000 mg daily. 34 patients were considered a clinical success. 33 patients were a radiological success. 22 patients showed a decrease in IgG values. 3 patients had an increase in IgG values. Blood/urine values presented no clinically significant variations. Clinical efficacy was similar in both treatment groups. These are the first results confirming in vivo the recent in vitro evidence that TGH is effective against acute lower respiratory tract infections due to C. pneumoniae, thus representing an alternative therapy to clarithromycin.

Administration, Oral↗

Basis for nebulized antibiotics: droplet characterization and in vitro antimicrobial activity versus Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa.

The aims of this study were to (1) quantify the particle size characteristics of several antibiotics considered suitable for aerosol therapy after aerosolization with the PARI IS/2 nebulizer (Pari GmbH, Sarnberg, Germany) and (2) determine the degree to which in vitro antimicrobial activity of these antibiotics is maintained after nebulization. The aerosolized drugs were tobramycin sulfate, streptomycin, and imipenem, with saline solution as the control. Mean mass aerodynamic diameter of the nebulized drugs was 3.25 microns for tobramycin, 2.26 microns for imipenem, and 2.38 microns for streptomycin. In vitro tests showed that tobramycin and imipenem were unaltered in their bacteriostatic activity against strains of Escherichia coli (American Type Culture Collection [ATCC] 25922) and Staphylococcus aureus (ATCC 29213) as well as against Pseudomonas aeruginosa (ATCC 27853) with minimal inhibitory concentration (MIC) values less than 0.3 microgram/mL. Nebulized streptomycin showed significantly higher MIC values against P. aeruginosa (ATCC 27853). These results suggest that tobramycin and imipenem may be prescribed as an aerosol generated by jet nebulization (PARI IS/2) to treat S. aureus, E. coli, and P. aeruginosa infections without any risk of altering the drugs minimum bacteriostatic activity by the nebulization process. Aerosolization of streptomycin with this nebulizer may not be as effective against P. aeruginosa because it seems to alter the bacteriostatic activity.

Aerosols↗

Myasthenic inspiratory vocal cord dysfunction: efficacy of nasal continuous positive airway pressure treatment.

Myasthenic vocal cord dysfunction (VCD), presenting with severe inspiratory stridor, was successfully treated with nasal continuous positive airway pressure (nCPAP), thus giving the medical staff time to make the diagnosis and avoiding intubation or tracheostomy. An important sign leading to diagnosis was the very high MEF(50)/MIF(50) ratio calculated from the flow-volume loop. nCPAP treatment induced prompt remission of stridor and a sharp reduction in the MEF(50)/MIF(50) ratio from 9.90 to 1.36. A review of the literature has shown that VCD with inspiratory stridor is an unusual onset symptom of myasthenia gravis and that nCPAP treatment may avoid emergency oral/tracheal intubation and tracheostomy. After diagnosis, the patient underwent thymectomy, and today, 3 years later, he is well without any further therapy.

Adult↗

Prognostic significance of microsatellite instability in sporadic mucinous colorectal cancers.

We investigated the prognostic significance of microsatellite instability (MI) in 50 consecutive patients with sporadic mucinous colorectal cancer who had undergone only surgery. We evaluated MI and the pathological features with a possible prognostic value for each tumor, and the effect of the examined parameters on patients' outcome was statistically analyzed (univariate and multivariate analysis). All patients were followed-up for a minimum of 72 months or until death; in evaluating survival, only deaths of colorectal cancer were considered. DNA extracted from tumor sections and the corresponding normal tissue was analyzed by polymerase chain reaction at six microsatellite loci: D2S123, D3S1611, D3S49, D5S107, BAT26, BAT40. Alterations at two or more loci were detected in 36% of cases (MI+ tumors). MI+ and MI- cancers differed significantly in the pattern of growth, and most MI+ tumors showed an expanding type of growth (72.2%, P = .005). At univariate analysis, improved survival rate was significantly associated with MI, as well as with the following parameters: expanding cancer growth, Dukes stage, and absence of venous invasion. Nevertheless, at multivariate analysis, only the pattern of cancer growth and Dukes stage were independent prognostic factors, whereas the effect on survival of MI and venous invasion was found to be negligible. In our study, MI+ and MI- cancers differ only on the pattern of growth; therefore, our data suggest that the better survival rate in mucinous cancers with genomic instability is strictly related to their less aggressive type of growth.

Adenocarcinoma, Mucinous↗

Nasal-continuous positive airway pressure in the treatment of near-drowning in freshwater.

In patients who have experienced near-drowning, hypoxemia is the major clinical consequence. We report two cases of patients who have experienced near-drowning in freshwater who were successfully treated with nasal-continuous positive airway pressure (N-CPAP) plus oxygen therapy. Both patients presented a radiographic appearance of bilateral pulmonary edema. We suggest the use of N-CPAP as an easier and less costly alternative to tracheal intubation for treating near-drowning in patients who are breathing spontaneously and who have not experienced loss of consciousness.

Adolescent↗

Effect of bamiphylline on tracheobronchial mucus clearance in subjects with smokers' simple chronic bronchitis.

A double-blind study versus placebo was performed to assess the effect of bamiphylline, a new xanthylic derivative, on tracheobronchial mucus clearance (TBMC) in smokers with simple chronic bronchitis and impaired mucus clearance as compared to normal controls. Twenty patients were enrolled and divided into two randomized groups. The first group was treated with bamiphylline (600 mg b.d.) for 15 days, while the second group received placebo with the same oral dosage regimen. Complete clinical-functional examinations were made before and after the test period to establish the effects of treatment. At the end of the study, only the group treated with bamiphylline showed a net increase in mucus clearance (mean radioaerosol elimination 28 +/- 7% before treatment and 38 +/- 11% after treatment; p < 0.01) and an improvement in the clinical score and pulmonary function parameters, in particular the residual volume (RV = 3.41 +/- 0.75 liters before treatment and 2.7 +/- 0.6 after treatment; p < 0.01) and the forced expiratory volume at 1 s (FEV1 = 2.37 +/- 0.7 liters before treatment and 2.88 +/- 0.5 after treatment; p < 0.05). No side effects or adverse reactions that could be attributed to the study drug were observed.

Aged↗

Mild prematurity and respiratory functions.

Pulmonary function tests and bronchial reactivity to methacholine (MCH) were measured in 34 randomly selected prematures (21 males, 13 females; mean age 11.6 years; mean gestational age 34.9 weeks; mean birth weight 1980 g) and in 34 siblings (22 males, 12 females; mean age 12.5 years, mean gestational age 39.5 weeks; mean birth weight 3030 g). None had suffered neonatal respiratory distress syndrome or had been artificially ventilated. Prematurely born children had a residual volume (RV) and residual volume/total lung capacity (RV/TLC) significantly (P < 0.01) increased compared to controls, although the mean values of both groups were still within the upper limits of normal. Furthermore, an increase of closing volume/vital capacity and closing capacity/total lung capacity (CC/TLC) was observed in most patients with increased RV and RV/TLC. No significant difference was observed for bronchial responsiveness to MCH between prematurely born and control children (11.8% and 5.9% of hyperreactive subjects, respectively). Maternal smoking during pregnancy was prevalent in prematures with impaired respiratory functions. In conclusion clinically normal children of smoking mothers who have survived prematurity but present some respiratory function impairment compared to their born-at-term siblings, should be fully informed and protected from risk factors for chronic obstructive pulmonary disease (COPD) in adult life.

Bronchial Hyperreactivity↗

99mTc-DTPA-surfactant inhalation in adult respiratory distress syndrome (ARDS): a new diagnostic-therapeutic tool.

ARDS is a life-threatening pulmonary disease with a rapidly progressive decline due mainly to multi-organ failure. Death occurs in 50-75% of ARDS cases. The diagnosis and therapy should start in the first six days of this fatal disease when mortality is at its lowest level. The 99mTc-DTPA-measured pulmonary alveolar epithelial permeability (PAEP) is strikingly increased in ARDS even in comparison to heavy smokers. Furthermore, surfactant inhalation has been shown to be of therapeutic value. In five ARDS patients with increased PAEP (T0.5 = 12% pred.) 20 mg/kg of aerosolized surfactant determined a dramatic improvement in blood gases and PAEP (51.8% pred.) No patient remained dependent on ventilatory treatment.

Administration, Inhalation↗

Prediction of pulmonary immunodeficiency in chronic bronchitis by cutaneous hypoergy to multitest.

Multitest (Pasteur Mérieux) is a plastic disposable device used to assess delayed cutaneous hypersensitivity (DCH) to seven antigens. Hypoergy to Multitest is believed to reflect a status of compromised cell-mediated immunity. Among the many possible pathogenic factors of chronic bronchitis, immunodepression has been little investigated. Indeed, whether lower immunodefence is the cause or the consequence of chronic bronchitis is still a subject of debate. The aim of the study was to evaluate DCH in a large group of patients with chronic obstructive pulmonary disease (COPD) and in a control group, in order to relate DCH (expressed as score, mm) to clinical and functional impairment. One hundred patients with COPD in stable conditions and not undergoing treatment with immunomodulating drugs (mean age, yr, M +/- SD: 66.1 +/- 6.5) and 40 normal controls in the same age range were admitted to the study. Evaluated parameters were: symptoms scores, physical examination, lung function tests and Multitest. Fifty-three percent of the COPD patients were hypoergic compared with 14% of controls. The Multitest score was 10 +/- 10 (mm M +/- SD) in COPD compared with 17 +/- 9 in controls. The Multitest score was significantly related to age (r = -0.45) in the control group, but not in COPD patients. DCH to only three of the seven antigens may predict a response to Multitest, with a sensitivity of 90%.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

[Quantitative analysis of the lung CT in normal subjects and in patients with noncardiac pulmonary edema].

A quantitative analysis was performed of the CT images relative to 7 normal human subjects and to 22 patients affected with ARF (Acute Respiratory Failure). The CT scanner image quality was investigated, and the unit was checked with quality control procedures, in order to assure reliability and reproducibility. In every patient the lung was scanned at 3 different levels--basis, hilum and apex. The frequency distribution of CT numbers was studied. The lung areas were calculated for the different conditions, and the data correlated with functional lung data. A method was then tested to evaluate lung weight; the data obtained did not differ from literature data. All the patients were treated with different positive and expiratory pressure (PEEP). For different PEEP values, the quantitative data from CT analysis were correlated with morphofunctional indices.

Adult↗

Relationships between lung computed tomographic density, gas exchange, and PEEP in acute respiratory failure.

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.

Acute Disease↗

Inflammatory pulmonary edema and positive end-expiratory pressure: correlations between imaging and physiologic studies.

The anatomic and physiologic response to positive end-expiratory pressure (PEEP) was investigated using computed tomography (CT) in patients with adult respiratory distress syndrome (ARDS). The lesions (densities) in ARDS are distributed inhomogeneously but tend to concentrate in the dependent regions. The estimated lung weight (by CT scan, quantitative analysis, and lung gas volume measured with helium dilution) is, on the average, 200% higher than expected. Changing the body position from supine to prone causes a change in the density distribution in response to gravitational forces. The main effect of PEEP is to clear the densities through alveolar anatomic recruitment. Anatomic recruitment changes the mechanical characteristics of the lung and parallels the improvement in gas exchange. The effects of PEEP on pulmonary arterial pressure appear to be related to anatomic recruitment.

Humans↗