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Biomedical subjects

S Ferrari

Publications and source records attributed to S Ferrari.

At least 37 records · Page 2Linked to original sources
PubMed2005

Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators.

Occupational exposure to cytotoxic drugs of hospital personnel involved in their preparation and administration is a major issue: ever since the introduction of protective measures in recent decades, the handling of these drugs has always been referred to as an occupational health hazard. Isolator technology was one of the protective equipments aimed at providing safe handling, but it has not yet been studied regarding contamination. The present study evaluates surface contamination with four cytotoxic drugs [cyclophosphamide (CP), ifosfamide (IF), 5 fluorouracil (5FU) and methotrexate (MTX)] by wipe sampling in two hospital pharmacies. Wipe samples were taken from work surfaces both located inside and outside the isolators. In addition, working gloves, the surface of infusion bags filled with 5FU or CP, and gloves used in simulation of drug administration were analyzed. Contamination was routinely found inside the isolators but rarely outside the isolators, indicating that the isolator technology is offering good protection of the cytotoxic drug handlers as well as the environment during preparation. On the other hand, contamination was found on the surfaces of infusion bags and gloves in contact with infusion bags filled with cytotoxic drugs. Consequently, personal protective equipment is still recommended during the manipulation and administration of the drugs because of potentially contaminated drug vials and final products.

Antineoplastic Agents↗
PubMed2005

Correlation between differentiation plasticity and mRNA expression profiling of CD34+-derived CD14- and CD14+ human normal myeloid precursors.

In spite of their apparently restricted differentiation potentiality, hematopoietic precursors are plastic cells able to trans-differentiate from a maturation lineage to another. To better characterize this differentiation plasticity, we purified CD14- and CD14+ myeloid precursors generated by 'in vitro' culture of human CD34+ hematopoietic progenitors. Morphological analysis of the investigated cell populations indicated that, as expected, they consisted of granulocyte and monocyte precursors, respectively. Treatment with differentiation inducers revealed that CD14- cells were bipotent granulo-monocyte precursors, while CD14+ cells appeared univocally committed to a terminal macrophage maturation. Flow cytometry analysis demonstrated that the conversion of granulocyte precursors to the mono-macrophage maturation lineage occurs through a differentiation transition in which the granulocyte-related myeloperoxidase enzyme and the monocyte-specific CD14 antigen are co-expressed. Expression profiling evidenced that the observed trans-differentiation process was accompanied by a remarkable upregulation of the monocyte-related MafB transcription factor.

Antigens, CD34↗
PubMed2005

Phosphorylated 14-3-3zeta protein in the CSF of neuroleptic-treated patients.

The authors describe 12 neuroleptic-treated patients with dementia of various etiologies who showed CSF elevation of phosphorylated 14-3-3zeta and normal tau protein levels. This contrasted with elevated amounts of 14-3-3 gamma, epsilon, and unphosphorylated zeta coupled to high tau protein levels in Creutzfeldt-Jakob disease and negative 14-3-3 assay in drug-free patients with dementia. Characterization of CSF 14-3-3 isoforms and determination of tau protein level can help to distinguish different etiologies of dementia.

14-3-3 Proteins↗
PubMed2005

Skeletal site selectivity in the effects of calcium supplementation on areal bone mineral density gain: a randomized, double-blind, placebo-controlled trial in prepubertal boys.

BACKGROUND: Calcium supplementation during childhood and adolescence is considered an early means of preventing osteoporosis in adults. Prepuberty is an opportune time for detecting the benefits of calcium in girls. OBJECTIVE: The objective was to assess whether calcium supplementation increases bone mass gain in prepubertal boys in a skeletal site-specific manner. METHODS: In a 12-month double-blind, placebo-controlled trial with 1-yr follow-up, 235 healthy prepubertal boys aged 7.4 +/- 0.4 yr (mean +/- sd) were randomized to receive two food products providing 850 mg/d calcium (calcium supplement group, n = 116) or an isocaloric placebo (n = 119). Areal bone mineral density (aBMD) was determined by dual-energy x-ray absorptiometry at radius (two sites), hip (two sites), femoral diaphysis (FDia), and L2-L4 vertebrae. RESULTS: At 12 months, aBMD gain was greater at the FDia and at the mean of the five appendicular skeletal sites in the calcium supplement group in both intention-to-treat analysis [76 +/- 32 vs. 64 +/- 33 mg/cm(2).yr; difference, 12.0 (95% confidence interval, CI, 3.6-20.3), P = 0.006; and 33 +/- 16 vs. 28 +/- 16 mg/cm(2).yr; difference, 5.1 (95% CI, 0.9-9.2); P = 0.018, respectively] and active treatment analysis [81 +/- 32 vs. 64 +/- 31 mg/cm(2).yr; difference, 17.2 (95% CI, 7.9-26.5); n = 174, P < 0.001; and 35 +/- 16 vs. 28 +/- 14 mg/cm(2).yr; difference, 7.5 (95% CI, 2.9-12.2); P = 0.002]. There was no beneficial effect of calcium on lumbar spine. The calcium effect was still detectable by ANOVA repeated measures analysis at the FDia (P = 0.004) and at the mean of the five appendicular skeletal sites (P = 0.002) 1 yr after the end of intervention (active treatment analysis). There was no change in bone size. CONCLUSION: In prepubertal boys, calcium-enriched foods increased aBMD at several appendicular skeleton sites, but not at the lumbar spine, and this without any bone size change. This effect was maintained 1 yr after treatment discontinuation.

Body Mass Index↗
PubMed2005

Psychiatric disorders and depression in multiple sclerosis outpatients: impact of disability and interferon beta therapy.

Associations between psychopathology and gender, duration of MS, disability and therapy with beta-interferons were studied in multiple sclerosis (MS) outpatients. A controlled descriptive epidemiological study was carried out in two Italian outpatient MS centres on 50 outpatients with clinically definite relapsing-remitting MS presenting for regular follow-up and 50 healthy controls matched for sex, age and educational level. Subjects were assessed with the Structured Clinical Interview for DSM-IV (SCID I), the Beck Depression Inventory (BDI) and the State Trait Anxiety Inventory (STAI). MS patients reported a higher prevalence of psychiatric disorders (odds ratio 3.17), with 46% (n=23) suffering from major depressive disorder. The risk of suffering from any non-mood psychiatric disorder was also higher in MS patients than in controls (odds ratio 2.67). Risk factors for depression were female sex and severity of disability, but not therapy with interferon beta or longer duration of illness. Disability level, but not therapy with beta-interferons, is a risk factor for depression in MS outpatients. Regular screening for depression in this population is appropriate.

Anxiety↗
PubMed2005

Thymidylate synthase structure, function and implication in drug discovery.

Recent methodologies applied to the drug discovery process, such as genomics and proteomics, have greatly implemented our basic understanding of drug action and are giving more input to medicinal chemists, in finding genuinely new targets and opportunities for the development of drugs with original mechanisms of action. In this paper, an example of the successful application of some new techniques to the target enzymes with the Thymidylate Synthase (TS) function is given. The improved knowledge of the complex mechanism of the biological pathways in which thymidylate synthase is involved represents a unique chance to find new mechanism-based inhibitors, aimed to treat not only cancerous diseases, but also infectious pathologies. Thymidylate synthase (TS or ThyA) has long been considered as one of the best-known drug targets in the anti-cancer area, after which old and new drugs, such as 5-fluoro uracil and the anti-folate ZD1694, have been introduced into chemotherapy to treat solid tumours. Only a few attempts have been made to find non-classical anti-folate inhibitors that are dissimilar to the folate co-factor, with the aim of finding unshared protein target domains on the enzyme structure, in order to specifically inhibit TS enzymes from pathogens. Only recently from omic studies, a new Thymidylate Synthase Complementing Protein (TSCP or ThyX) has been identified in a number of pathogens, showing a different structure with respect to human TS, thus opening new avenues to specific inhibitions. A depiction of the most recent progress in the study of Thymidylate Synthase enzymes is presented in the following sections.

Antineoplastic Agents↗
PubMed2004

Determination of polychlorobiphenyl congeners (PCBs) in the surface water of the Venice lagoon.

The purpose of this study is to evaluate the degree of PCB contamination of Venice lagoon water. The PCB determination was made on the filtrate ("dissolved PCBs") and on the particulate collected on the filters ("particulate PCBs") by continuous liquid-liquid extraction and sonication, respectively, and by HRGC-LRMS analysis. An estimation of the procedural and "working" blanks was also made. Water samples were collected at six sites, selected to represent all the pollution situations present in the lagoon, and at a site in the Adriatic Sea. The range of the total sum ("dissolved plus particulate") of 49 congener concentrations falls between 355 and 1868 pgl(-1); the "dissolved" fraction concentrations (250-792 pgl(-1)) are greater at six sites than that of the "particulate" fraction (105-1273 pgl(-1)). Chemometric analyses suggest that the PCB congener pattern in the Venice Lagoon is different from that in the Adriatic Sea.

Environmental Monitoring↗
PubMed2004

[Prevention of cortisone-induced osteoporosis].

Osteoporosis and fractures are the frequent consequences of glucocorticoid therapy. Cancellous bone is primarily affected with a decrease of bone formation and an increase of bone resorption. Prevention of corticosteroid-induced osteoporosis is based upon general measures such as calcium and vitamine D supplementation, adequate protein intake, regular physical exercise, and upon specific therapies like those used in primary osteoporosis. Bisphosphonates which are potent bone resorption inhibitors have been shown to reduce bone mineral density and to decrease vertebral fracture rate. Therefore, they appear to be a first choice in the prevention of corticosteroid-induced osteoporosis.

Adrenal Cortex Hormones↗
PubMed2004

Long-term outcome for patients with non-metastatic Ewing's sarcoma treated with adjuvant and neoadjuvant chemotherapies. 402 patients treated at Rizzoli between 1972 and 1992.

We evaluated the long-term results obtained in 402 patients with non-metastatic Ewing's sarcoma (ES) of the bone treated in a single institution with adjuvant and neoadjuvant chemotherapies between 1972 and 1992. Multivariate analyses showed male gender, age older than 14 years, high serum lactate dehydrogenase (LDH) level, axial location of the tumour, use of radiotherapy alone as a local treatment, and poor histological response to chemotherapy, to be independent, adverse prognostic factors for event-free survival (EFS). At a mean follow-up of about 18 years (10-30 years), 177 patients (44.0%) remained continuously free of disease, 2 died of doxorubicin-induced cardiotoxicity and 8 developed a second neoplasm (5 died, and 3 are alive and free of disease). 215 patients relapsed with metastases and/or local recurrence: 14 are alive and free of disease, 1 is alive with uncontrolled disease, and 200 died. The overall survival (OS) at real follow-ups of 5-, 10-, 15- and 20-years was 57.2, 49.3, 44.9 and 38.4%, respectively. We conclude that since local or systemic relapses, treatment-complications and second malignancies are more common after 5 years or more from the beginning of treatment; a long-term follow-up is mandatory for patients with ES.

Adolescent↗
PubMed2004

Surgery for lung metastases in Ewing's sarcoma of bone.

The addition of chemotherapy and radiotherapy to local treatment for Ewing's sarcoma of bone (ES) significantly bettered its prognosis. Nonetheless, although with no signs of local recurrence some patients still relapse with lung metastases. These patients are generally treated with non-surgical procedures. The few reports in literature on surgical resection of metachronous pulmonary metastases do not allow any conclusions. This study aims to report the results achieved in 24 Ewing's sarcoma patients who relapsed only with lung metastases, and no local recurrence, treated with surgery at the authors' institution.

Adolescent↗
PubMed2004

Osteosarcoma of the pelvis.

AIMS: To describe the outcomes of a large number of patients with pelvic osteosarcoma, and to define the guidelines for appropriate treatment. METHODS: We reviewed 60 consecutive patients with primary pelvic high-grade osteosarcoma. The tumour involved the whole hemipelvis in 15 cases, while the most common location was the iliac wing in 29 cases (48.3%): 25 of these adjacent to or passing the sacroiliac joint. RESULTS: Thirty patients underwent surgery; there were 16 hindquarter amputations and 14 internal hemipelvectomies. All the patients who presented with metastasis died of their disease. In 18 cases wide margins were achieved, however, eight patients experienced local recurrence. Of the series, only eight patients are still alive. CONCLUSION: The use of intense chemotherapy and surgical wide margin, hardly seems to achieve local control, however, tumour necrosis was correlated with positive prognosis. When internal hemipelvectomy it is not safe enough, amputation must be considered, particularly for cases with sacrifice of the sciatic nerve roots or for older patients where a shorter surgical procedure can be less risky.

Adolescent↗
PubMed2004

A study about remedial measures to reduce 222Rn concentration in an experimental building.

Radon gas emanating from underground can spread to adjoining closed areas. It can concentrate and reach levels which represent a risk to people's health. It is well known that radon presence in most areas depends mainly on the area's geological features. Indoor radon concentrations further depend on the type of structure, construction materials and the technology used for the building. Therefore, indoor radon monitoring is of primary importance for deciding whether remedial measures are to be adopted for reducing harmful concentrations. This approach has been tried by measuring radon concentration in an experimental building situated in Milan (Italy). This building situated in a geological area that is considered at low radon risk. The results were obtained after analysing radon concentration in indoor rooms, crawl spaces, soil gas and in the atmosphere outside and by measuring before and after adoption of remedial measures. The study shows that improper building design can give rise to higher indoor radon accumulation even in an area of poor radon exhalation. Furthermore, the results enable quantification of the effectiveness of the remedial measures.

Air Pollution, Indoor↗
PubMed2004

Effects of intramyocardial pVEGF165 delivery on regional myocardial blood flow: evidence for a spatial 'delivery-efficacy' mismatch.

The aim of this study was to determine the effects of direct intramyocardial pVEGF165 gene transfer on regional myocardial blood flow in a porcine model of chronic myocardial ischaemia. Pigs underwent placement of an ameroid constrictor around the left circumflex coronary artery. After 3 weeks, animals received direct intramyocardial injections of pVEGF165 (20 x 50 microl at 1 microg/microl, n=11) or a plasmid vector encoding chloramphenicol acetyltransferase (20 x 50 microl at 1 microg/microl, n=11) into a specified target area (TA) of the left lateral wall. At 3 weeks after gene transfer, animals underwent final evaluation including a systematic assessment of regional myocardial blood flow (MBF) under resting and stress conditions. In all, 20 animals (10 per group) reached final studies. There was no change in mean arterial blood pressure or Rentrop collateral score from gene delivery to final studies in either group, nor were there differences between study groups. MBF was significantly higher in the areas adjacent to the TA in the VEGF group under resting (P<0.001) and stress conditions (P<0.05). In addition, pVEGF165 gene transfer abolished flow differences between the adjacent areas and the septum. MBF was not different between study groups in the TA, the anterior wall, or the septum. In conclusion, direct intramyocardial pVEGF165 gene transfer significantly improves myocardial blood flow. However, this effect is limited to the myocardial segments adjacent to the area of gene delivery. These data, therefore, demonstrate a spatial 'delivery-efficacy' mismatch with implications for myocardial gene delivery sites and detection of treatment effects in vivo.

Animals↗
PubMed2004

A defective nontransmissible recombinant Sendai virus mediates efficient gene transfer to airway epithelium in vivo.

Recombinant Sendai virus (SeV)-mediated gene transfer to differentiated airway epithelial cells has shown to be very efficient, because of its ability to overcome the intra- and extracellular barriers known to limit gene delivery. However, this virus is transmission competent and therefore unlikely to be suitable for use in clinical trials. A nontransmissible, replication-competent recombinant SeV has recently been developed by deleting the envelope Fusion (F) protein gene (SeV/DeltaF). Here we show that SeV/DeltaF is able to mediate beta-galactosidase reporter gene transfer to the respiratory tract of mice in vivo, as well as to human nasal epithelial cells in vitro. Further, in an ex vivo model of differentiated airway epithelium, SeV/DeltaF gene transfer was not importantly inhibited by native mucus. When compared to the transmission-competent SeV in vivo, no difference in gene expression was observed at the time of peak expression. The development of an F-defective nontransmissible SeV, which can still efficiently mediate gene transfer to the airway epithelium, represents the first important step towards the use of a cytoplasmic RNA viral vector in clinical trials of gene therapy.

Adult↗
PubMed2004

The aggregation-promoting factor of Lactobacillus crispatus M247 and its genetic locus.

AIMS: Characterization of the aggregation-promoting factor (APF) of the human intestinal isolate Lactobacillus crispatus M247 and its homologous nonaggregating mutant Mu5. METHODS AND RESULTS: Western blot analysis revealed that the supernatant of both M247 and Mu5 contains a 28-kDa protein which cross reacts with the antiserum produced against the APF of Lact. gasseri 4B2. The apf genes of M247 and Mu5 strains were identical and were shown to be 672 nucleotides in length and encoding a protein of 223 amino acids with a predicted molecular weight of 24.0 kDa. CONCLUSION: Our results shows that the lost of aggregation in Mu5 is not related to a defect in secretion of the APF protein or a mutation in the apf gene. SIGNIFICANCE AND IMPACT OF THE STUDY: These results suggest that the mutation in Mu5 may be contained in another molecule involved in aggregation such as a possible receptor for APF.

Amino Acid Sequence↗