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Biomedical subjects

F Di Stefano

Publications and source records attributed to F Di Stefano.

At least 19 recordsLinked to original sources

Clinical approach to the patient with blood eosinophilia.

Increased blood eosinophil count may be caused by a range of diseases, from allergic disorders to malignant tumors. The allergist is often consulted to evaluate patients with this finding and he should not only rule out the presence of allergy, but through a detailed history taking and physical examination, he should provide a list of likely causes of the patient blood eosinophilia. Importantly used drugs capable of inducing blood eosinophilia and common parasitic infections that might be the culprit.

Autoimmune Diseases↗

Characterisation of molecular events following cisplatin treatment of two curable ovarian cancer models: contrasting role for p53 induction and apoptosis in vivo.

The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.

Adenocarcinoma↗

Diffusion-weighted MR imaging in the evaluation of renal tumours.

The aim of this study was to evaluate the capability and the reliability of diffusion-weighted MR imaging to differentiate benign from malignant renal lesions. Twenty healthy volunteers and 48 patients with known renal lesions underwent MR of the kidneys by using a 1.5 T superconductive magnet. Diffusion-weighted images (DWI) were obtained on the axial plane during breathhold (17 s) with a SE EPI single shot sequence using a b value of 500 s/mm2. One region of interest (ROI) (lesions < than 3 cm) or 3 ROI (lesions > than 3 cm) were placed within the lesion for the measurement of apparent diffusion coefficient (ADC). ADC map was obtained at each slice position. Mean ADC value in normal renal parenchyma was 2.2 +/- 0.20 x 10(-3) mm2/s, while ADC values in simple cysts (n = 20) were higher (mean ADC values 3.65 +/- 0.09 x 10(-3) mm2/s). Solid benign and malignant renal tumors (n = 19) showed a mean ADC value of 1.7 +/- 0.48 x 10(-3) mm2/sec. The comparison between ADC values in normal parenchyma group and tumour group were found to be statistically significant (p < 0.0001). ADC values of cystic renal cell carcinomas were higher than those of clear cell carcinomas (p < 0.001). In conclusion, DW MRI of the kidney seems to be a reliable means for differentiating normal renal parenchyma from different renal tumors.

Adenocarcinoma, Clear Cell↗

Effects of low frequency electromagnetic fields on expression of lymphocyte subsets and production of cytokines of men and women employed in a museum.

The objective of this study was to analyse the immune response to electromagnetic fields (ELMFs) in seven men and eight women employed in a museum. The workers were exposed in a room to an ELMFs (range 0.2-3.6 microT and 40-120 V/m) induced by 50 Hz electricity for 20 h a week. Control groups consisted of 47 women and 39 men with a similar percentage of atopic subjects, age (range 30-51 years) and smoking habits of the workers included in the study. Levels of blood lead (Pb) and urinary trans-trans muconic acid, a metabolite of benzene (markers of exposure to traffic and smoking) of the control and exposed groups were similar. Lymphocyte subsets were determined in men and women using conjugated antibodies. Serum interleukin (IL) 4 and interferon gamma and their 'in vitro' production by peripheral mononuclear blood cells (PMBCs) stimulated by phytohemoglutinin (PHA), as well as blastogenesis of PMBCs induced by PHA, were determined in women only. ELMF-exposed women showed a significant reduction in the percentage of B and NK CD3(-)-CD25+ lymphocytes and a slight reduction of CD16(+)-56+ NK lymphocytes. They also showed significantly lower levels of interferon gamma in serum, or produced in the supernatants by PMBCs both spontaneously and stimulated by PHA, while they did not show significant changes in serum and 'in vitro' produced IL-4, or in blastogenesis of PMBCs. Men working in the museum showed, in relation to the controls, a statistically significant reduction in both number and percentage of CD16(+)- CD56+ and CD3(-)-CD25+ lymphocyte subsets. On the whole, this investigation demonstrates a reduction of blood NK lymphocytes and of the production of interferon gamma in workers exposed to low frequency ELMFs. Recent studies have shown that stress and poor lifestyle induce the reduction of blood cytotoxic activities possibly acting on nervous functions. This may suggest that ELMFs reduces blood NK lymphocytes by combined effects on the immune and nervous systems.

Adult↗

Effect of natural allergen exposure on non-specific bronchial reactivity in asthmatic farmers.

The aim of the study was to assess the seasonal variability of non-specific bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. 'Graminae' and 'Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Paretaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.

Agriculture↗

Increase in CD45RO+ cells and activated eosinophils in chronic allergic conjunctivitis.

We assessed the infiltration of CD45RO+ cells in conjunctival biopsies of fifteen subjects affected by seasonal allergic conjunctivitis by means of immunohistochemistry. Correlations between infiltration of CD45RO+ cells and serum and mucosal indices of eosinophilic activation were investigated. The study was performed in autumn and all selected patients showed < > also in absence of sensitising pollens. Fifteen healthy subjects were used as controls. The semi-quantitative count of CD45RO+ cells in biopsy specimens demonstrated that positive cells were higher in allergic patients than in controls (p < 0.001) and EG2+ eosinophils were present only in biopsies of allergic patients. Furthermore, a statistically significant positive correlation (r = 0.73; p < 0.001) between CD45RO+ lymphocytes and EG2 positive eosinophils, was observed in the biopsies of allergic patients. Total serum IgE significantly correlated with CD45RO+ cells (r = 0.61; p < 0.02) and EG2+ eosinophils (r = 0.67; p < 0.01) in the conjunctiva. On the other hand serum ECP did not correlate with any histological and immunohistochemical parameters in the conjunctival biopsies. The present study shows that mild symptoms in SCA patients out of pollen season are associated with inflammation of the conjunctiva as shown by an increased number of CD45RO and EG2 positive cells.

Adolescent↗

Influence of total IgE and seasonal increase of eosinophil cationic protein on bronchial hyperreactivity in asthmatic grass-sensitized farmers.

BACKGROUND: This study correlates biomarkers of atopy (serum total and specific IgE) and inflammation (serum eosinophil cationic protein) with bronchial hyperreactivity assessed after the complete end of pollination, in a group of farmers suffering from grass-allergic asthma. METHODS: A total of 28 asthmatic farmers, with allergy to grass pollen, reporting persistent asthma symptoms after grass pollination, were enrolled. An accurate allergologic screening excluded other sensitizations. Analysis of total and grass-specific IgE and eosinophil cationic protein was carried out before (March) and during (May) the following spring. After the complete end of pollination, bronchial hyperreactivity was assessed. RESULTS: Symptoms (cough, wheezing) persisted during the autumn for a mean period of 41 days (range 13-69). Total IgE was moderately high and grass-specific IgE ranged from 9.25 to 41.12 kU/l without significant differences before and during spring. On the contrary, serum ECP levels significantly increased during the pollination period. PD20 methacholine evaluated after the end of grass pollination was negatively significantly correlated with levels of total IgE (r=-0.73; P<0.01) and the increase (from March to May) of serum ECP (r=-0.75; P<0.01). However, PD20 methacholine did not correlate with grass-specific IgE and serum ECP absolute values of both March and May. A positive correlation was found between number of postseasonal days with symptoms and both spring increase of serum ECP (r=0.75; P=0.04) and levels of total IgE (r=0.76; P<0.01). The number of postseasonal days with symptoms inversely correlated with postseason PD20 methacholine (r=-0.76; P<0.01). CONCLUSIONS: The study demonstrates that in grass-sensitized farmers with asthmatic symptoms persisting for several weeks after grass pollination has ceased, the degree of airways hyperreactivity and the duration of postseasonal symptoms are directly related to the spring increase of ECP levels, as well as to the level of total IgE in serum. This allows us to identify two candidate biomarkers for the risk of developing prolonged asthma symptoms, and for the effective monitoring of anti-inflammatory treatment and allergen-specific immunotherapy.

Adult↗

Lymphocyte subset changes in blood and gastrointestinal mucosa after oral nickel challenge in nickel-sensitized women.

This study investigates lymphocyte subsets in both the gastrointestinal mucosa and blood, in patients with nickel allergic contact dermatitis, after 10 mg oral nickel challenge (double-blind, placebo-controlled). 6 such patients with cutaneous symptoms induced only by skin contact with nickel (group A), 6 with a flare-up of cutaneous symptoms after food nickel ingestion (group B) and 6 healthy controls (group C) were enrolled. Blood lymphocyte subsets (CD4, CD45RO, CD8) were analyzed before and after 4 and 24 h from the challenge (test 1, 2, and 3), and intestinal biopsies were performed 2 days later. Challenges were positive in group B and negative in group A and controls. Serum and urine nickel levels significantly increased after nickel ingestion, with no differences between the 3 groups. At test 3, a significant decrease of the all CDs studied was found in group B. Biopsies of this group showed higher levels of CD45RO+ cells in the lamina propria and in the epithelium and lower levels of epithelial CD8+ lymphocytes. This study confirms that ingested nickel may induce flare-up of cutaneous reactions in some nickel-allergic patients, independently of the degree of sensitization and the intake of metal. In these patients, oral nickel stimulates the immune system, inducing maturation of T lymphocytes from virgin into memory cells; these latter cells seem to accumulate in the intestinal mucosa. The immunoreaction also involves CD8+ cells, whose role is not yet clear.

Administration, Oral↗

Reduced intensity thiotepa-cyclophosphamide conditioning for allogeneic haemopoietic stem cell transplants (HSCT) in patients up to 60 years of age.

UNLABELLED: Transplant-related mortality (TRM) remains a major problem in older patients undergoing allogeneic haemopoietic stem cell transplants (HSCTs). We have therefore explored a less intensive conditioning in 33 patients with a median age of 52 years (range 43-60) transplanted from human leucocyte antigen (HLA)-identical siblings. The underlying disease was chronic myeloid leukaemia (n = 15), acute myeloid leukaemia (n = 6), myelodysplasia (n = 7) or a chronic lymphoproliferative disorder (n = 5); 15 patients (45%) had advanced disease. The regimen consisted of thiotepa (THIO; 10 mg/kg) on day -5 and cyclophosphamide (CY; 50 mg/kg) on days -3 and -2 (total dose 100 mg/kg). The source was bone marrow (BM) (n = 17) or granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood (PB) (n = 16), which were infused without manipulation. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporin A (CyA) and a short course of methotrexate. Mean time to achieve a neutrophil count of 0.5 x 109/l was 17 d (range 11-23) and full donor chimaerism was detected in 79% of patients by day 100. Acute GVHD grade III or IV occurred in 3% of patients. Chronic GVHD was seen in 45% of patients, with a significant difference for PB (69%) compared with BM transplants (23%) (P = 0.009). For BM grafts, the actuarial 2-year TRM was 6%, the relapse 56% and survival 87%; for PB grafts, these figures were, respectively, 27%, 33% and 68%. Twenty-five patients are alive at a median follow-up of 762 d (range 216-1615) and 20 patients (60%) remain free of disease. Thirteen patients (39%) received donor lymphocyte infusion (DLI) either for persisting or relapsing disease and six patients had complete remission. IN CONCLUSION: (i) patients up to the age of 60 years can be allografted with reduced intensity conditioning; (ii) the procedure was associated with a low transplant-related mortality, particularly for bone marrow grafts, because of a lower risk of chronic GVHD; and (iii) DLI were required after transplant in half the patients for persisting disease or relapse.

Adult↗

Glutaraldehyde: an occupational hazard in the hospital setting.

BACKGROUND: We report a series of 24 health-care workers with respiratory symptoms suggestive of occupational asthma due to glutaraldehyde exposure. METHODS: The history of asthmatic symptoms was investigated with peak expiratory flow rate (PEFR) monitoring, and in eight of the subjects, the specific bronchial provocation test (SBPT) was applied as reference standard for diagnosis of occupational asthma. Levels of glutaraldehyde were monitored in the challenge chamber during the SBPT. Work environmental levels of glutaraldehyde were measured from air samples collected at least once during the PEFR monitoring of endoscopy and theatre nurses. Specific IgE antibodies to glutaraldehyde were measured with a series of glutaraldehyde modified proteins. RESULTS: In the eight workers who underwent SBPT, the diagnosis of occupational asthma was confirmed by a positive reaction (late and dual reaction in five and in three subjects, respectively). The mean level of glutaraldehyde observed during the challenge tests was 0.075 mg/m3 (range 0.065-0.084 mg/m3). In 13 out of the 16 remaining workers, the serial PEFR monitoring showed a work-related effect. In three workers, there was no physiological confirmation of occupational asthma. Levels of glutaraldehyde from the air samples collected in the workplace were as follows: personal short-term samples (mean 0.208 mg/m3; median 0.14 mg/m3; range 0.06-0.84 mg/m3), personal long-term samples (mean 0.071 mg/m3; median 0.07 mg/m3; range 0.003-0.28 mg/m3). Measurements of specific IgE antibodies to glutaraldehyde-modified proteins were positive in seven patients (29.1%) according to a cutoff value of 0.88% RAST binding. The presence of atopy to common environmental allergens and smoking was not associated with specific IgE positivity (P>0.05; Fisher's exact test). CONCLUSIONS: Our report indicates the importance of glutaraldehyde as an occupational hazard among exposed health-care workers. Intervention in the workplace, training of personnel handling this chemical, and accurate health surveillance may reduce the risk of developing occupational asthma due to glutaraldehyde.

Adult↗

[The surgical therapy of renal carcinomas. The prognostic factors and long-term results].

BACKGROUND: Image diagnosis of kidney neoplasms allows good preoperative staging using the TNM system, but surgical management cannot be based on these data because a tumour apparently confined to the kidney may have produced metastasis in extraregional lymph nodes. METHODS: Thirty-three patients with renal carcinoma were observed over a seven-year period. Preoperative staging using the TNM system was performed and then compared with postoperative staging. Radical nephrectomy and regional lymphadenectomy were performed in all patients. Extensive lymphadenectomy was undertaken in 10 cases presenting neoplasms larger than 10 cm. At the preoperative assessment, 20 patients were stage T2, 13 stage T3, for factor N six were N1, two M1; postoperative staging confirmed T2 in 15 cases, whereas five T2 became T3. After postoperative staging, the N1 patients increased from 6 to 13. Fifteen patients were at Robson's stage II, four at stage IIA, twelve IIIB and two stage IV. RESULTS: The 5-year survival rate was 63.2%. CONCLUSIONS: The authors conclude that from an analysis of the correlation between tumour size and lymph node metastasis it can be seen that low T values do not represent grounds for conservative treatment.

Adult↗

Treatment of obstetric and gynecologic infections with meropenem: comparison with imipenem/cilastatin.

The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections. This was a controlled, multicenter, randomized study with two parallel groups and a follow-up period of up to 4 weeks. A total of 105 hospital in-patients requiring antibacterial parenteral therapy were enrolled, 52 in the meropenem group and 53 in the imipenem/cilastatin group. Both drugs were administered at 0.5 g every 8 hours, by slow intravenous infusion over 20-30 minutes; for meropenem the administration by intravenous bolus injection (over approximately 5 minutes) was allowed. The mean duration of therapy was 5 days for both treatments. At the end of treatment, all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response, while in the imipenem/cilastatin group 5/49 patients were clinical failures. The difference between the treatment groups in clinical response was statistically significant (100% vs 89.8%; p=.026). A similar result was seen in the intention-to-treat analysis (98% vs 84.6%; p=0.017). Both treatments were well tolerated, but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin (11.5% vs 15.1%).

Adolescent↗

Occupational asthma due to glutaraldehyde.

In recent years glutaraldehyde has emerged as the main cause of occupational asthma among healthcare workers. Presently glutaraldehyde is the best biocide agent for high-level disinfection and cold sterilization and its use has become widespread in hospitals. Surveillance schemes in the UK, Finland and the USA have reported an increasing number of cases of occupational asthma due to glutaraldehyde. The real magnitude of the problem is not well known as epidemiological studies carried out on a large scale among healthcare workers are not yet available. In countries where surveillance schemes are implemented, reports of occupational asthma cases due to glutaraldehyde should be circumstantiated by more diagnostic details and the diagnosis confirmed by objective means, to avoid an overestimation of frequency of disease. The pathogenetic mechanisms of occupational asthma due to glutaraldehyde are debatable as with other low molecular weight chemicals. A recent study has documented the first evidence of immunological sensitization in healthcare workers exposed to this chemical. Occupational asthma caused by glutaraldehyde can develop at levels of exposure well below the standards accepted in most countries. In the UK the Occupational Exposure Standard (OES) of this agent will be lowered from 0.2 ppm (parts of vapour per million parts of air by volume) to 0.05 ppm. Substitution of glutaraldehyde with an alternative agent is not currently feasible. Intervention in the workplace and education of personnel handling this chemical remain irreplaceable parts of any prevention strategy. Early detection of disease and prompt removal of personnel from further exposure are the only ways of avoiding any deterioration of occupational asthma.

Air Pollutants, Occupational↗

Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study.

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.

Adult↗

Modified peptidoglycan chemical composition in shape-altered Escherichia coli.

Peptidoglycan synthesis and its fine chemical composition were studied in dividing cocci of Escherichia coli carrying the lov-1 mutation and in which the coccal shape was obtained either by mecillinam treatment or by transferring a pbpA mutation (penicillin-binding protein 2- phenotype), as compared to normal rods and non-dividing cocci. Synchronously dividing cocci showed peptidoglycan synthesis only in the cell cycle phase corresponding to cell septation. During the phase corresponding to lateral wall elongation, peptidoglycan synthesis was strongly reduced. This type of synthesis suggests that the dividing cocci consisted only of the two poles. Analysis of the muropeptide composition revealed a specific fourfold increase in the tetra-tetra-tetra trimer in dividing cocci as compared to non-dividing cocci or parental rods. We postulate that, in E. coli, the chemical composition of septal peptidoglycan differs from that of lateral wall peptidoglycan.

Amdinocillin↗

[Effect of some drugs on physiological icterus in the newborn].

The Authors have correlated neonatal jaundice with the administration of oxytocin and prifinium bromide to the mother either alone or in association during labour. The percentage of neonatal jaundice in women treated with ritodrine hydrochloride during the second and third trimester of pregnancy was also calculated. A total of 1.101 deliveries were taken into consideration between January 1984 and June 1986. Thirty-three patients were treated with oxytocin alone; 444 patients with oxytocin and prifinium bromide; 81 patients with ritodrine hydrochloride during the second and third trimesters of pregnancy, and 192 patients were untreated. This study indicates that all drugs may contribute to producing neonatal jaundice, as shown in the graphs, and drugs during labour should be used with extreme caution and be limited in quantity and period.

Female↗