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Biomedical subjects

G Fadda

Publications and source records attributed to G Fadda.

At least 19 recordsLinked to original sources

In vitro activity of Citrus bergamia (bergamot) oil against clinical isolates of dermatophytes.

OBJECTIVES: Recently, bergamot oil was shown to be a potent antifungal agent in vitro against clinically important Candida species. In this study, the activities of bergamot natural essence and its furocoumarin-free and distilled extracts on dermatophytes such as Trichophyton, Microsporum and Epidermophyton species were investigated. METHODS: In vitro susceptibility testing assays on 92 clinical isolates of dermatophytes (Trichophyton mentagrophytes n = 20, Trichophyton rubrum n = 18, Trichophyton interdigitale n = 15, Trichophyton tonsurans n = 2, Microsporum canis n = 24, Microsporum gypseum n = 1 and Epidermophyton floccosum n = 12) were performed using the CLSI M38-A broth microdilution method, except for employing an inoculum of 1-3 x 10(3) cfu/mL. MICs were determined at a visual endpoint reading of 80% inhibition compared with the growth control. RESULTS: MICs (v/v) of all fungi ranged from 0.156% to 2.5% for the natural essence, from 0.02% to 2.5% for the distilled extract, and from 0.08% to 1.25% for the furocoumarin-free extract. The three isolates of T. tonsurans and M. gypseum exhibited the highest MIC values. CONCLUSIONS: Data from this study indicate that bergamot oil is active in vitro against several common species of dermatophytes, suggesting its potential use for topical treatment of dermatophytoses.

Antifungal Agents↗

Recurrent upper airway infections and bacterial biofilms.

BACKGROUND: Bacterial biofilms identified in various medical devices used in otorhinolaryngology, including tympanostomy tubes, voice prostheses, and cochlear implants, can directly colonise mucosal tissues. The upper airways seem to be at high risk for this type of colonisation. Chronic and/or recurrent upper airway infections may be related to the complex structural and biochemical (quorum sensing) organisation of the biofilm which interferes with the activity of antibiotics (including those with proven in vitro efficacy), thus promoting the establishment of a chronic infection eradicable only by surgical treatment. Biofilm formation plays a role in upper respiratory infections: it not only explains the resistance of these infections to antibiotic therapy but it also represents an important element that contributes to the maintenance of a chronic inflammatory reaction. OBJECTIVES: To document the presence of biofilms in surgical tissue specimens from patients with recurrent infection diseases, and identify their possible role in the chronicity of these infectious processes. METHOD: We examined 32 surgical specimens from the upper respiratory tract (tonsils, adenoids, mucosa from the ethmoid and maxillary sinuses) of 28 patients (20 adults, eight children) with upper airway infections that had persisted despite repeated treatment with anti-inflammatory agents and antibiotics with demonstrated in vitro efficacy. Tissues were cultured using conventional methods and subjected to scanning electron microscopy for detection of biofilm formation. RESULTS: Over 80 per cent (26/32; 81.3 per cent) of the tissue specimens were culture-positive. Bacterial biofilms (associated in most cases with coccoid bacteria) were observed in 65.6 per cent of the tissue samples.

Adult↗

Prospective 3-year surveillance for nosocomial and environmental Legionella pneumophila: implications for infection control.

OBJECTIVES: To perform a 3-year, prospective surveillance program for legionnaires disease (LD) in a large university hospital in Rome, and to assess the usefulness of the hospital water monitoring program in predicting the risk of nosocomial LD. METHODS: Samples from patients with new cases of nosocomial pneumonia were sent for legionella laboratory investigations. Meanwhile, water samples for bacteriological analysis were collected every 6 months from high- and medium-risk hospital wards (10 in total). Legionella pneumophila isolates collected were serotyped and analyzed by pulsed-field gel electrophoresis. RESULTS: From June 2001 through May 2004, the pneumonia surveillance identified one case of nosocomial LD among 43 cases of nosocomial pneumonia (2.3%). Environmental investigations detected L. pneumophila in 12 (18.7%) of the 64 water samples, of which 50% belonged to serogroup 1. The L. pneumophila count and the percentage of positive locations never exceeded 10(2) colony-forming units/L and 20%, respectively, except when the LD nosocomial case occurred (positive water samples, 40%; L. pneumophila count, <10(2) colony-forming units/L). Genotyping showed 3 prevalent clones of L. pneumophila in the water distribution network, of which one persisted over the 3 years. One clone contained 3 different L. pneumophila serogroups (2, 4, and 6). CONCLUSIONS: The low incidence of nosocomial cases of LD appears to be associated with a low percentage (<20%) of positive water samples per semester and with a low contamination level (<10(2) colony-forming units/L). An infection control system for nosocomial LD should, therefore, be based on both environmental and clinical surveillance, together with the appropriate maintenance of the hospital water distribution system.

Cross Infection↗

Gene expression profiling of adrenal cortical tumors by cDNA macroarray analysis. Results of a preliminary study.

Adrenocortical carcinoma (ACC) are highly malignant tumors with poor prognosis. To verify if it is possible to assess their differential gene expression by a cDNA macroarray analysis using RNA extracted from paraffin sections, we analyzed two different cohorts of adrenal cortical adenoma (ACA) and ACC. Paraffin sections of seven ACC and seven ACA were analyzed. Transcriptional profiles were generated by commercially available c-DNA arrays testing 82 genes. Hybridization signals were quantified by densitometry and the intensity signal was compared for each gene between ACA and ACC cohorts. RNA was successfully extracted in only four out of 14 cases. Four genes displayed a significantly different expression (ACC/ACA ratio>1.5 or<0.6). Heat shock protein 60 (HSP-60) (ratio>2), Ciclin D1 and topoisomerase I (ratio>1.5) were overexpressed in the ACC cohort, while jun proto-oncogene was down-regulated. cDNA macroarray analysis from paraffin sections of adrenal tumors is feasible, despite with a low success rate. The different expression of HSP-60, Ciclin D1, jun proto-oncogene and topoisomerase I indicates that these genes may play a role in ACC pathogenesis and could represent potential diagnostic/prognostic/therapeutic target markers. Larger series of patients are necessary to confirm the biologic, diagnostic, prognostic and therapeutic implications of these findings.

Adrenal Cortex Neoplasms↗

Value of routine measurement of serum calcitonin concentrations in patients with nodular thyroid disease: A multicenter study.

BACKGROUND: The routine measurement of serum calcitonin (CT) has been proposed for patients with nodular thyroid disease (NTD), to detect unsuspected medullary thyroid carcinoma (MTC) before surgery. OBJECTIVE: To assess the prevalence of hypercalcitoninemia and MTC in NTD patients; to compare the ability of CT measurement and fine needle aspiration cytology (FNAC) to predict MTC; to identify age groups of NTD patients who should be better candidates than others to undergo routine measurement of CT. PATIENTS AND METHODS: 1425 consecutive patients, referred from April 1, 2003, through March 31, 2004, to four Italian endocrine centers due to NTD, were grouped depending on age, and underwent basal and, in some cases, pentagastrin (Pg)-stimulated CT measurement, FNAC and, when indicated, surgery. Serum CT concentrations were measured by an immunoluminometric assay (ILMA). RESULTS: Hypercalcitoninemia was found in 23 out of 1425 patients. MTC was discovered in 9 patients, all >40 yr old and showing high CT levels. Sensitivity of basal and Pg-stimulated CT to predict MTC before surgery was 100% for both tests, whereas specificity was 95 and 93%, respectively. CT specificity reached 100% when a cutoff value of 20 pg/ml was taken. FNAC showed an overall 86% sensitivity. When >10 mm MTC nodules were considered, FNAC sensitivity approached 100%. On the contrary, a correct cytological diagnosis was obtained in only one out of five patients with <10 mm MTC nodules (microMTC); in one patient with histologically proved microMTC, FNAC even demonstrated a benign lesion. Hypercalcitoninemia or MTC were associated with chronic thyroiditis in 30 or 33% of cases, respectively. C-cell hyperplasia was found in 57% of hypercalcitoninemic patients without MTC. CONCLUSIONS: Basal CT measurement detects elevated CT values in 1.6% of NTD patients. Although CT is not a specific marker of MTC, its routine measurement represents a useful tool in the pre-operative evaluation of NTD patients, particularly those >40 yr old presenting with nodules <10 mm, even when FNAC does not show malignant features. To our knowledge, this is the first trial using ILMA to assess the ability of pre-operative CT measurement to predict MTC in a large series of NTD patients.

Adolescent↗

Simultaneous immunohistochemical expression of HBME-1 and galectin-3 differentiates papillary carcinomas from hyperfunctioning lesions of the thyroid.

AIMS: The histological diagnosis is critical for the postsurgical management and follow-up of thyroid malignancies. The differential diagnosis between papillary carcinoma and hyperfunctioning lesions, either with papillary hyperplasia or with a follicular architecture, can create real diagnostic difficulty. The aim of this study was to evaluate the expression of several antibodies considered to be markers of malignancy in malignant and hyperfunctioning thyroid neoplasms and to include the most effective of them in a diagnostic panel. METHODS AND RESULTS: One hundred resected thyroid nodules--58 hyperfunctioning benign lesions and 42 papillary carcinomas (14 follicular variant, 14 macrofollicular variant and 14 classic type)--were immunohistochemically studied for HBME-1, galectin-3, cytokeratin (CK) 19 and RET-proto-oncogene. HBME-1 and galectin-3 showed 92.8% and 89% sensitivity, respectively, and their coexpression was present in 36 out of 42 papillary carcinomas (85.7%) and absent in non-malignant lesions. Their association increased sensitivity to 94.7% and the diagnostic accuracy to 97.9% and involved the highest number of cases (95%) in comparison with two other panels including, respectively, three (HBME-1, galectin-3, CK19) and all four antibodies. CONCLUSION: An immunohistochemical panel consisting of HBME-1 and galectin-3 can make a correct distinction between malignant and hyperfunctioning thyroid neoplasms with high diagnostic accuracy.

Biomarkers, Tumor↗

Efficacy of N-acetyl-cysteine in combination with thiamphenicol in sequential (intramuscular/aerosol) therapy of upper respiratory tract infections even when sustained by bacterial biofilms.

A total of 102 patients with recurrent upper respiratory tract infections underwent microbiological exploration with appropriate sampling and direct biopsies of the infected sites. Therapy was then started and on day 1 each patient received two intramuscular injections of thiamphenicol glycinate acetylcysteinate (TGA). From day 2 to 10 sequential therapy with the same drug was continued employing TGA administered by aerosol. All putative etiologic agents recovered were susceptible to thiamphenicol and only 24 demonstrated the ability to produce in vitro biofilms. The organisms comprised 10 Staphylococcus aureus, 6 Streptococcus pyogenes, 4 Streptococcus pneumoniae and 3 Haemophilus influenzae. Of the 24 subjects in whom biofilms were demonstrated to be present in vivo by Scanning Electron Microscopy, clinical and bacteriological cure was obtained in 21 cases (87.5%) following sequential therapy with TGA. Failures were considered to be persistent signs and symptoms at day 15 after initiation of treatment and lack of eradication of 3 S. aureus strains, despite their in vitro susceptibility to thiamphenicol. Very few adverse events attributable to TGA were reported in this cohort of patients. In no case was discontinuation of treatment deemed necessary by the attending physician.

Acetylcysteine↗

The Sentinel Project: an update on the prevalence of antimicrobial resistance in community-acquired respiratory Streptococcus pneumoniae and Haemophilus spp. in Italy.

A total of 460 Streptococcus pneumoniae and Haemophilus spp. collected from respiratory infections during 2000 was tested for their susceptibility to 15 selected antibiotics. Overall, penicillin resistance among pneumococci was 10.5%, while lack of susceptibility to macrolides, co-trimoxazole, tetracycline and chloramphenicol reached 35.2%, 26.2%, 22.6% and 6.0%, respectively. Amoxicillin/clavulanic acid and levofloxacin were the most potent compounds (100% and 99.9% susceptible strains, respectively). Among isolates of Haemophilus influenzae and Haemophilus parainfluenzae, beta-lactamase production (12.5% and 10%, respectively), and co-trimoxazole (19.9% and 40.0%) and clarithromycin (11.2% and 40.0%) resistance were the prevalent threats. This study confirms the trend observed in Italy since 1992: macrolide resistance among respiratory microorganisms is increasing, while several drugs including amoxicillin/clavulanic acid, third generation injectable cephalosporins and fluoroquinolones remain active on the great majority of these pathogens.

Community-Acquired Infections↗

Antimicrobial susceptibility patterns of contemporary pathogens from uncomplicated urinary tract infections isolated in a multicenter Italian survey: possible impact on guidelines.

During 2004 four Italian Laboratories assessed the prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female out-patients. A total of 600 urine samples from individuals aged 18-65 were studied. The overall prevalence of Escherichia coli was 85.3%. Klebsiella pneumoniae, Staphylococcus saprophyticus, Proteus mirabilis, Enterococcus faecalis and other rarer species were far less represented. Determination of the antibiotic susceptibility pattern of the entire collection of E. coli (512 organisms) revealed that among the drugs analyzed ampicillin was the least active molecule with only 62.5% of the strains being inhibited. Amoxicillin-clavulanate and cefuroxime displayed a higher potency (87.7% and 89.2% respectively). Cotrimoxazole inhibited only 70.1% of the uropathogens. The three fluoquinolones tested had comparable activity ranging from 83.0% for ciprofloxacin, to 83.6% for levofloxacin and 84.9% for prulifloxacin, indicating an identical spectrum of cross resistance. Nitrofurantoin (96.7%) and fosfomycin (98.6%) were the most potent drugs. Against the whole collection of uropathogens, only cefuroxime, nitrofurantoin and fosfomycin overcame the threshold of 90% activity, with the fluoroquinolones and amoxicillin-clavulanate suffering from about 15% resistance. The results of this survey strongly support the conclusions of recent Italian guidelines concerning the best empiric treatment of UTI in this country today.

Adolescent↗

In vitro activity of bergamot natural essence and furocoumarin-free and distilled extracts, and their associations with boric acid, against clinical yeast isolates.

OBJECTIVES: There is very little information, to date, on the antifungal activity of bergamot oil. In this study, we investigated the in vitro activity of three bergamot oils (natural essence, furocoumarin-free extract and distilled extract) against clinically relevant Candida species. We studied the two derivatives, components of Italian pharmaceutical products, that are supposed to be less toxic than the essential oil. METHODS: In vitro susceptibility of 40 clinical isolates of Candida spp. (Candida albicans, n=20; Candida glabrata, n=13; Candida krusei, n=4; Candida tropicalis, n=2; Candida parapsilosis, n=1), associated with symptomatic and asymptomatic vulvovaginal candidiasis, was determined using a modification of the NCCLS M27-A2 broth microdilution method. MICs were evaluated for each of the oils alone and combined with sub-inhibitory concentrations of the well-known antiseptic, boric acid. To boric acid, all isolates had MIC values ranging from 0.094% to 0.187% (w/v). RESULTS: At 24 h readings, the MIC(90 )s (for all isolates) were (v/v): 5% for natural essence of bergamot, 2.5% for the furocoumarin-free extract, and 1.25% for the distilled extract. At the 48 h reading, these values increased to >10%, 5% and 2.5%, respectively. At both readings, MIC(90 )s for all oil+boric acid combinations were significantly lower than corresponding values for the oils alone (P <0.05). CONCLUSIONS: These data indicate that bergamot oils are active in vitro against Candida spp., suggesting their potential role for the topical treatment of Candida infections.

Antifungal Agents↗

Solitary liver metastasis from Hürthle cell thyroid cancer: a case report and review of the literature.

Metastasis to the liver from thyroid cancer is a rare event with a reported frequency of 0.5%. Metastatic liver involvement from differentiated thyroid cancer (DTC) is nearly always multiple or diffuse and usually found along with other distant metastases (lung, bone and brain). The authors describe a patient with a solitary liver metastasis from Hürthle cell thyroid cancer, which appeared during long-term follow-up. The lesion was diagnosed by progressive increase of thyroglobulin in the serum and imaged with I-131 whole body scan, ultrasonography, magnetic resonance imaging (MRI) and F-18 fluoro-deoxyglucose positron emission tomography (FDG-PET) scan. For patients with a Tg level above some arbitrary limit, the administration of a large dose (3.7-5.5 GBq; 100-150 mCi) of I-131, in order to obtain a highly sensitive Tx whole body scan (WBS), remains the best diagnostic strategy. However, on very rare occasions, physiological enteric radioactivity can hide possible abdominal lesions and further indepth studies, such as FDG-PET scans, are sometimes necessary.

Adenoma, Oxyphilic↗

Antimicrobial susceptibility profiles of Pseudomonas aeruginosa and Staphylococcus aureus isolated in Italy from patients with hospital-acquired infections.

Here we report the results of the Sentinel Project 2000 and give the susceptibility to selected antibiotics of 108 Pseudomonas aeruginosa and 108 Staphylococcus aureus strains isolated from patients with hospital-acquired lower respiratory tract infections. In P. aeruginosa, susceptibility to aztreonam and ciprofloxacin was lower than 50%. The resistance rate to beta-lactams was up to 25% and to amikacin 15.7%. Blood isolates showed 80-90% susceptibility to all antibiotics tested except for aztreonam and tobramycin. Overall, oxacillin resistance in S. aureus was 45%, reaching 64.3% among the bronchoalveolar lavage isolates, and 42.9% among the blood isolates. These worrying results confirm the need for continuous monitoring of bacterial resistance trends in the hospitals, mainly in ICUs.

Anti-Bacterial Agents↗

Modifications in the head group and in the spacer of cholesterol-based cationic lipids promote transfection in melanoma B16-F10 cells and tumours.

A series of four cationic lipids derived from cholesterol was synthesised and their efficiencies to vectorise nucleic acids were compared. The investigation concerns the effects of systematic chemical modifications in the polar head and in the spacer. The cationic lipid molecules used are in the same family of 3beta[N-(N',N',N'-trimethylaminoethane)-carbamoyl] cholesterol iodide (TMAEC-Chol), presenting a spacer of two or three carbons and a quaternary ammonium polar head ramified with methyl or ethyl groups. These lipids formed stable liposomes sizing from 100 to 200 nm when prepared with the colipid dioleoyl phosphatidylethanolamine (DOPE). The goal of this work was to investigate the effect of the chemical structure of these cationic lipids on lipofection. Their ability to form complexes with DNA, their cytotoxicity and their transfection efficiency in vitro and in vivo were studied. Results were compared with those obtained from the well known cholesterol-based cationic lipid DC-Chol. In a melanoma cell line (B16-F10), results showed that either the polar head or the spacer affected the cytotoxicity. Cationic lipids with three ethyl groups in the head are more toxic than those with three methyl groups while cationic lipids with three carbons in the spacer are less toxic than those with two carbons in the spacer. The best transfection level was obtained in vitro and in vivo with cationic lipids having 3C in the spacer. Data indicated that among these lipids, in vivo gene transfer is advantaged by the methylated polar head while in vitro the best level was obtained with the ethylated one. Finally, it was observed that the chemical structure influences the transfection in the presence of serum while the complex charge and the DOPE ratios in liposomes preferentially affect the interaction with erythrocytes. Argumentations are proposed to explain the discrepancies between in vitro and in vivo transfection results concerning the optimal charge ratio and the chemical nature of the cationic lipid head group.

Animals↗

Hospital-acquired candidemia in HIV-infected patients. Incidence, risk factors and predictors of outcome.

A retrospective case-control study was performed to analyze hospital-acquired candidemia in HIV-positive patients. To understand the impact of Highly Active Antiretroviral Therapy (HAART) on the incidence of nosocomial candidemia, two time periods were compared: A (1992-1996) and B (1997-2001). 32 out of 38 (84%) cases of candidemia were hospital-related. A significant reduction in the incidence of all cases of hospital-acquired candidemia has been observed in the post-HAART in respect to pre-HAART period (0.09 episodes vs. 1.1 per 100/py). Multivariate analysis showed that the presence of central venous catheter was the only variable independently associated with the development of nosocomial candidemia. The overall mortality rate was 59%. Univariate analysis indicated three prognostic indicators: presence of concomitant opportunistic infections, isolation of non-albicans Candida species; neutropenia. Multivariate analysis of prognostic indicators showed that isolation of non-albicans Candida species is the only independent variable. Despite the use of HAART, this disease still represents a severe complication of advanced stage of AIDS.

Adult↗

Mycobacterium avium sub. paratuberculosis in tissue samples of Crohn's disease patients.

Crohn's disease is a non-specific chronic transmural inflammatory disease. The disease was associated with a frameshit mutation in the NOD2 gene. Nevertheless, other researchers associated the presence of M. paratuberculosis within the intestinal tissues of patients with the disease. An adapted "in situ hybridization" technique was used to detect IS900 M. paratuberculosis DNA in paraffin embedded tissue from Crohns tissue disease samples. We were able to identify M. paratuberculosis DNA in around 69% of the paraffine embedded intestinal samples of Crohn's disease patients analysed. The presence of M. paratuberculosis DNA in the intestinal samples analysed does not necessarily mean that M. paratuberculosis is responsible for Crohn's disease. Our results support the hypothesis that infection may be caused by cell wall defective M. paratuberculosis since no bacteria were detected by Ziehl Neelsen stain.

Crohn Disease↗

Bacterial and viral DNA in periodontal disease: a study using multiplex PCR.

Recent studies have suggested an association between periodontal disease and the presence of Herpesviruses, in particular: Epstein-Barr virus (EBV) and Human Cytomegalovirus (CMV) (Contreras et al., 1999--Contreras et al., 2000--Slots et al., 2000--Ting et al., 2000). In the work reported in this paper, we use a multiplex Polymerase Chain Reaction (PCR) to compare the presence of Herpesviruses and putative bacterial pathogens in patients with periodontal disease and in healthy individuals. Direct detection of microorganisms with PCR is shown to offer significant advantages in terms of time, effort and cost. The study detected no statistically significant differences between the prevalence of EBV and CMV in patients and controls. The failure to replicate previous findings may be due to differences in the age composition and the geographical and social origins of the study groups. The study detected a significant excess of HSV-1 in periodontal patients. This suggests that the role of Herpesviruses in the pathogenesis of periodontal disease deserves further investigation. The bacterial assay confirmed the results of previous studies showing a strong association between periodontitis and the presence of A. actinomycetemcomitans, P. gingivalis and P. intermedia.

Actinobacillus Infections↗