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Biomedical subjects

G Nicoletti

Publications and source records attributed to G Nicoletti.

At least 127 records · Page 7Linked to original sources

Comparative effects of amitriptyline and amineptine in patients affected by anxious depression.

In a double-blind, placebo-controlled study, the therapeutic efficacy of two antidepressants with different neurochemical mechanisms of action, amitriptyline and amineptine, was investigated in patients affected by anxious depression. Sixty-six patients with the primary diagnosis of major depression or bipolar affective disorder (DSM-III-R) and meeting additional operational clinical criteria such as anxiety, trepidation, restlessness, early and/or late insomnia, impulsivity, hostility, dysphoria, compulsivity, hyperperspiration, palpitation, pollakiuria and phobias were included. They were randomly assigned to three groups (n = 22) and treated either with placebo, amitriptyline (up to 100 mg/day) or amineptine (up to 200 mg/day) for 6 weeks. Patients showed better response to amitriptyline, a preferential inhibitor of serotonin reuptake, than to amineptine, a selective inhibitor of dopamine reuptake. The present results suggest that alterations in serotonergic rather than dopaminergic transmission contribute to the pathophysiology of anxious depression.

Adolescent↗

The in vitro activity of trospectomycin against anaerobic bacteria.

The authors evaluated the activity of trospectomycin, a new aminocyclitol which is characterized by good antibacterial and broad spectrum activity, in comparison with clindamycin and ampicillin on a sample of recent isolates: Bacteroides fragilis (15 strains), Bacteroides urealyticus (5 strains), Bacteroides vulgatus (5 strains), Bacteroides spp. (15 strains), Prevotella melaninogenica (6 strains), Porphyromonas asaccharolytica (7 strains), Mobiluncus spp. (3 strains), Peptococcus niger (3 strains), Peptococcus variabilis (9 strains), Peptococcus spp (30 strains), Peptostreptococcus anaerobius (5 strains), Peptostreptococcus asaccharolyticus (3 strains), Peptostreptococcus spp. (25 strains) and Propionibacterium spp. (7 strains). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined for all strains by microtiter serial dilutions in Wilkins-Chalgren broth in an anaerobic chamber in an atmosphere of 10% H2, 10% CO2, 80% N2. All the drugs tested exert their activity against Gram-positive and Gram-negative anaerobic isolates. In particular, trospectomycin is quite active against Gram-positive cocci (MIC 90 = 4 - 8 mg/l), Gram-negative rods (MIC 90 = 8 - 16 mg/l), Gram-positive rods (MIC 90 = 4 mg/l) and Mobiluncus spp. (MIC 90 = 0.5 mg/l).

Ampicillin↗

Enterococci: susceptibility patterns and therapeutic options.

Enterococcal isolates are increasingly responsible for nosocomial infections in the last decade and they are recently cited as being the second most common pathogen isolated from hospitalized patients. Enterococcal infections can be localized at different sites: endocarditis, CNS, intrabdominal, pelvic. The epidemiological trend may be a consequence of predisposing risk factors due to hospitalization such as instrumentation, immunosuppression, long-term hospitalization. Nevertheless the most alarming aspect of the problem is the increasing detection of antibiotic resistance Enterococcal strains, especially the high level resistance (HLR) to aminoglycosides, penicillin and glycopeptides must not be underestimated. Optimal antibiotic regimes for the treatment of multiple resistant strains in severe enterococcal infections are not been defined yet and antibiotic association such as aminoglycosides + glycopeptides or glycopeptides + fluoroquinolones could be suggested.

Journal Article↗

Enterococci: susceptibility patterns and therapeutic options.

Enterococci do not possess the common virulence factors found in many other bacteria, but they have a number of other characteristics which make them particularly pathogenic. These organisms are intrinsically resistant to a number of antimicrobial agents, including beta-lactams (penicillins and cephalosporins), polymyxins and the lincosamides. They are also tolerant to the bactericidal activity of penicillins and glycopeptides, and some of the group have acquired resistance to a number of other clinically important antimicrobial agents including ampicillin, aminoglycosides, chloramphenicol and erythromycin. Numerous national and international studies have demonstrated the changes in the antibiotic resistance of enterococci. Many strains now exhibit multiple drug resistance, the most important being high-level resistance to streptomycin and gentamicin. Organisms exhibiting this high-level resistance are usually resistant to all synergistic combinations of beta-lactam antibiotics and aminoglycosides. Ampicillin-resistant strains are now emerging, some of which are beta-lactamase producers. While resistance to glycopeptides remains rare, it is increasing dramatically in many areas of the world. As nosocomial isolates of enterococci have displayed resistance to essentially every useful antimicrobial agent, it is likely to become increasingly difficult to treat and control enterococcal infections. The glycopeptide antibiotics vancomycin and, particularly, teicoplanin are the only alternatives currently available. Although a bactericidal combination of antibiotics appears necessary only in endocarditis and meningitis and although knowledge of the prevalence of resistant strains can be used to guide the selection of appropriate therapy, optimal regimens for the treatment of infections caused by multiresistant strains have yet to be determined.(ABSTRACT TRUNCATED AT 250 WORDS)

Drug Resistance, Microbial↗

Third generation oral cephalosporins: comparative in vitro kinetics.

In order to provide additional data on the in vitro antibacterial activity of cefetamet-pivoxil against respiratory pathogens, we determined the bactericidal kinetics of this antibiotic in comparison to cefixime and ceftibuten against H. influenzae, M. catarrhalis, K. pneumoniae, E. coli, S. pneumoniae and S. pyogenes. time-kill studies were performed by using concentrations equal to a x MIC, and 4 x MIC of the antibiotics tested and different inocula (10(5), 10(7) and 10(9) CFU/ml). The strains were incubated in a shaking incubator at 37 degrees C and 1 ml samples were removed at regular intervals for viable count determination. The antibiotics were eliminated by serial ten-fold dilutions in physiological saline before plating. At 4 x MIC of cefetamet and at 10(5) CFU/ml inoculum the results were 99.9% killing or more of H. influenzae and M. catarrhalis at 4 h, and of E. coli and K. pneumoniae within 4 to 6 h, and of E. coli and K. pneumoniae within 4 to 6 h. At the same concentration of MIC and with the same inoculum a 99.9% reduction was achieved against S. pneumoniae within 4 h and against S. pyogenes within 2 h with no regrowth at 24 h in both cases. Similar results were obtained using 10(7) and 10(9) CFU/ml inocula. Cefetamet had efficient killing activity even at lower concentrations. Bactericidal kinetics of cefetamet favorably compare with those of cefixime and ceftibuten. The efficient bactericidal activity of cefetamet-pivoxil indicates a clinical role for this new oral cephalosporin in the treatment of respiratory tract infections.

Administration, Oral↗

Thallium-201-SPECT and 99Tc-HM-PAO SPECT imaging to study functionally cerebral supratentorial neoplasms: the biological basis of the functional imaging interpretation.

Nineteen patients with histologically diagnosed supratentorial cerebral neoplasms carried out CT and/or MRI, 201T1 SPECT and 99mTc-HM-PAO studies preoperatively. 99mTc-HM-PAO SPECT images revealed information about both tumoral perfusion and intracellular concentration of mediators converting 99mTc-HM-PAO to hydrophilic derivates (glutathione and other yet unknown factors) within viable tumoral cells while 201T1 SPECT images about permeability, extension of tumoral capillary network and viable tumoral cells presence. Basing on the different mechanisms of the tracer uptake, cerebral supratentorial tumors could be distinguished in three groups: 1) cerebral tumors presenting 201T1 very high uptake (201T1 index > 1.5) and homogeneous and high retention of 99mTc-HM-PAO (CBI > or = 1.05) (meningiomas, PRL adenoma); histologically these neoplasms presented very rich neoformed capillary network; 2) cerebral neoplasms with 201T1 high uptake (201T1 index > 1.5) and with inhomogeneous retention of 99Tc-HM-PAO (high grade gliomas amd metastasis); microscopically these tumors presented vascular proliferation, necrosis and high cellularity; 3) cerebral neoplasms characterized by 201T1 low uptake (201T1 index < 1.5) and lower retention of 99Tc-HM-PAO than cerebellum (low grade gliomas); at microscopic examination these neoplasms were characterized by absence of vascular proliferation and necrosis. These results suggest coupled 201T1/99Tc-HM-PAO SPECT is necessary to discriminate intra-axial from extra-axial tumor localization (lacking CT or MRI) and to detect the grade of malignancy of gliomas and tumor cell presence within necrotic areas.

Adult↗

Biologic characterization of pleural metastases from lung adenocarcinoma: description of the new DV90 cell line.

AIMS AND BACKGROUND: The characterization of pleural metastases from lung adenocarcinoma is often limited to single biologic features. METHODS: The present paper describes the cellular kinetic parameters, as well as immunocytochemical, ultrastructural and genetic characteristics of the new DV90 cell line, established from the pleural effusion of a stage IV lung adenocarcinoma. RESULTS: The cell line has a diploid DNA content, a doubling time of 24 h and 7% cloning efficiency, it is tumorigenic in nude mice. Ultrastructural investigation revealed the typical features of lung adenocarcinoma; the diagnosis was confirmed by its immunohistochemical reactivity with a panel of monoclonal antibodies specifically capable of identifying adenocarcinoma cells. Genetic analysis revealed a 46 X, -Y, +8, der (6)t(6?)(q27;?) karyotype and hyperexpression of the protein codified by genes Her2/Neu and p53. CONCLUSION: The importance of multidisciplinary biologic characterization in identifying the origin and biological behavior of pleural metastases deriving from lung adenocarcinoma is discussed.

Adenocarcinoma↗

H-2Kb and H-2Db gene transfections in B16 melanoma differently affect non-immunological properties relevant to the metastatic process. Involvement of integrin molecules.

Modification of non-immunological cell adhesion properties plays a major role in the decrease in metastatic ability observed after transfection of the H-2Kb gene in H-2-negative B16-derived melanoma clone cells. To investigate the role played by different class-I major histocompatibility complex (MHC) genes on non-immunological properties relevant for metastasis, transfection with the H-2Db gene alone or in conjunction with the H-2Kb gene was performed. H-2Db gene transfection did not modify either metastatic potential or non-immunological cell adhesion properties. Double KbDb transfectants showed a decreased metastatic ability when compared to control clones and to Db transfectants; a decrease in homotypic adhesive ability was also observed, even though not in all clones studied: therefore expression of the Db gene is also relevant. The mechanisms of homotypic cell adhesion were studied and found to be dependent upon temperature and divalent cations. Adhesion was partially inhibited by an antiserum directed against the beta 1 integrin subunit, whereas anti-alpha IIb beta 3 was ineffective. Cell pre-treatment with anti-beta 1 serum reduced metastatic ability. A decreased expression of alpha 4 and alpha 6 integrin subunits was observed in Kb clones, whereas no difference in the levels of some homophilic cell adhesion molecules, such as N-CAM and alpha IIb beta 3, was found. Adhesion required the activity of tyrosine kinases, as suggested by the decreased adhesive properties and impaired metastatic ability of cells pre-treated with the tyrosine-kinase-inhibitor genistein. These results are compatible with involvement of integrin molecules of the beta 1 family in the adhesive ability of these cells. Our data show that: (a) immunological and non-immunological effects of MHC transfection are correlated and depend on the class-I gene used, suggesting that MHC gene therapy can be highly successful only if appropriate MHC genes are transfected; (b) non-immunological cell-adhesion properties modified after MHC transfection could be related to an impairment of integrin-mediated adhesive interactions.

Animals↗

Laparoscopy diagnosis of chlamydial salpingitis using a tubal cytobrush.

This is a report of our nontraumatic technique using a tubal cytobrush for epithelial tubal cell recovery during laparoscopy diagnosis of C. trachomatis salpingitis. We performed a three-way laparoscopy in 95 women and inserted a long flexible fallopian tube brush through one of the trocars. This technique showed that it is possible to reach the infection site avoiding vaginal contamination and that sufficient tubal cells can be obtained for isolation of intracellular pathogens. The technique also allowed rapid antigen detection directly on tubal cells by IFA and C. trachomatis isolation on cell culture. Tubal scraping did not cause bleeding or adhesions as later observed in a matched group of women who underwent further laparoscopy during GIFT.

Biopsy↗

Survey on antibiotic resistance in gram-negative non-fermentative bacteria other than pseudomonas in Italy.

A survey was conducted to investigate the incidence and antibiotic resistance of clinical isolates of Gram-negative non-fermentative bacteria, isolated during a one-year period in Italy. Overall, these microorganisms account respectively for 11.47% and 20.5% of all Gram-negative bacteria. The most representative species isolated during the study were: Acinetobacter, Flavobacterium, Alcaligenes, Achromobacter and Xanthomonas species. As regards their antimicrobial pattern of resistance, this survey demonstrated the wide differences existing within each group. The antimicrobial agents usually active against Pseudomonas aeruginosa do not seem to be useful against these microorganisms.

Ciprofloxacin↗

Susceptibility of respiratory and urinary pathogens to ceftibuten and other comparative drugs: results of an Italian multicenter survey. The Italian Ceftibuten Study Group.

A survey aimed at assessing the ability of ceftibuten, a new oral third-generation cephalosporin, to eradicate in vitro selected bacterial pathogens was conducted in 1991 in 17 microbiology laboratories evenly distributed in Italy. Over 8700 organisms collected from in- and outpatients affected mainly by respiratory and urinary tract infections were analyzed. This collection of bacteria did not include staphylococci, enterococci, Pseudomonas and other oxidative species naturally refractory to the action of most antibiotics employed. Susceptibility to ceftibuten, cefaclor, cefuroxime, amoxicillin, amoxicillin-clavulanate, cotrimoxazole and erythromycin was assessed using a standardized agar-diffusion method. Production of beta-lactamases was confirmed by the nitrocefin test. Among the microorganisms studied E. coli (32.1%) prevailed, followed by P. mirabilis (17.1%), K. pneumoniae (10.9%), S. pyogenes (6.6%), E. cloacae (5.1%), Serratia spp. (4.5%), Enterobacter spp. (4.2%), H. influenzae (3.6%), S. pneumoniae (2.2%) and M. catarrhalis (2%). Within this group of pathogens amoxicillin resistance, often mediated by synthesis of beta-lactamases, was widely diffused (46.2%). The overall inhibitory activity of the drugs tested decreased as follows: ceftibuten (90.4%), cefuroxime (80.4%), amoxicillin-clavulanate (77.4%), cotrimoxazole (75.3%), cefaclor (72.6%), amoxicillin (53.8%) and erythromycin (32.8%). When the efficacy of the antibiotics was assessed against the collection of respiratory isolates producing beta-lactamases only ceftibuten maintained the same overall potency manifested against the general population while the comparative agents were far less effective. The results of this national survey indicate that, given the low incidence of resistance among the most prevalent causative agents of respiratory and urinary tract infections, ceftibuten can be safely used at present in the empiric therapy of these conditions especially when they occur in community settings.

Ceftibuten↗

In vitro antimycoplasmal activities of rufloxacin and its metabolite MF 922.

The in vitro activities of rufloxacin and its metabolite, MF 922, were compared with those of ofloxacin, ciprofloxacin, erythromycin, and minocycline against Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, and Ureaplasma urealyticum. Rufloxacin, MF 922, and ciprofloxacin shared similar activities against all mycoplasmas tested. (MICs for 90% of isolates tested [MIC90s], 0.5 to 4 micrograms/ml. Ofloxacin had the lowest MIC90s for U. urealyticum, M. fermentans, and M. hominis (MIC90s, 0.25 to 1 micrograms/ml) and erythromycin had the lowest MIC90 for M. pneumoniae (MIC90, 0.004 micrograms/ml).

Anti-Infective Agents↗

[Microbiological aspects of antibiotics with immunomodulating action].

Through the introduction of a 7-mercapto-1,3-thiazole chain at position 3' of the dihydrothiazine ring, cefodizime, which is structurally similar to cefotaxime, has acquired a number of remarkable immunomodulatory properties while retaining a potent antimicrobial spectrum of activity. Cefodizime penetrates in fact readily through the bacterial cell wall and interacts with its molecular targets in such a way that at high concentrations cell death and lysis are rapidly induced. Its spectrum of action encompasses the Enterobacteria, Neisseriae, Haemophilus, Moraxella catarrhalis, methicillin-susceptible staphylococci and streptococci, with pneumococci included. Cefodizime is devoid of useful potency against Pseudomonas, Acinetobacter and enterococci. Given the wide occurrence of strains synthesizing beta-lactamases in several primary pathogens of community-acquired and nosocomial infections, the complete stability of cefodizime towards the most prevalent of these hydrolytic enzymes (TEM-1, TEM-2, SHV-1, BRO-1 and the staphylococcal penicillinases) seems reassuring. Only a few chromosomally-coded and extended spectrum beta-lactamases produced by gram-negative microorganisms inactivate the new cephalosporin. Since the distribution of pathogens carrying these enzymes depends on the local trends of antibacterial consumption and cannot be easily predicted, a large multicenter study in Italy has recently assessed the antibacterial potency of cefodizime, in comparison with suitable drugs, on 1985 selected nosocomial strains. In this survey cefodizime was more effective in vitro than amoxicillin-clavulanate, gentamicin and piperacillin while being substantially similar in the rates of eradication of gram-negative and gram-positive organisms to other third generation cephalosporins like ceftazidime and ceftriaxone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Inhibition of tumor growth and enhancement of metastasis after transfection of the gamma-interferon gene.

Cells from the spontaneous metastatic TS/A mammary adenocarcinoma of a BALB/c mouse were transfected with the murine gamma-interferon (IFN-gamma) gene. Six clones (IFN-gamma clones) releasing between 2 and 6,000 international units (IU) of IFN-gamma/ml culture medium, were compared to TS/A parental cells (TS/A-pc) and to cells transfected with neomycin resistance gene only (NEO cells). Autocrine IFN-gamma up-regulated membrane expression of H-2 class-I and Ly-6 glycoproteins, but did not alter cellular proliferation in vitro. All IFN-gamma clones gave rise to progressive tumors with a growth rate significantly slower than that of tumors induced by TS/A-pc and NEO cells, and inversely correlated with the amount of IFN-gamma secreted. TS/A-pc and NEO tumors displayed a marginal reactive infiltrate, whereas those formed by IFN-gamma clones were massively infiltrated mostly by macrophages. In T- and NK-deficient mice the growth of tumors formed by IFN-gamma clones was not enhanced. In vitro tests showed that IFN-gamma clone cells were markedly more lysed by macrophages than TS/A-pc and NEO cells, while they remained poorly sensitive to NK and LAK cells. These data as a whole suggest that the development of solid tumors by IFN-gamma clones is primarily hampered by macrophages and not by T-lymphocytes or NK cells. When spontaneous metastatic ability was compared, 2 IFN-gamma clones releasing 2-4 IFN-gamma IU/ml were significantly more metastatic, while most IFN-gamma clones appeared to be as metastatic as NEO cells. By contrast, following intravenous challenge, all IFN-gamma clones produced 5-10 times more experimental metastases than NEO cells. The higher metastatic ability of IFN-gamma clones was attributed to increased resistance to NK cells since, in NK-depleted BALB/c mice, metastatic spread of IFN-gamma clones was not enhanced, whereas a 50-fold increase in the number of metastases was found upon injection of NEO cells.

Adenocarcinoma↗

Orbital "blow-in" fracture: MRI.

A case of traumatic orbital encephalocele following a "blow-in" fracture is presented. Computed tomography (CT) and magnetic resonance imaging (MRI) findings are shown. Although CT was useful for identifying the orbital roof fracture, bone fragments and soft tissue abnormalities, MRI was more sensitive to brain herniation and an intraorbital haematoma.

Adult↗

The antimicrobial activity in vitro of chlorhexidine, a mixture of isothiazolinones ('Kathon' CG) and cetyl trimethyl ammonium bromide (CTAB).

Chlorehexidine, two 4% chlorhexidine antiseptic handwashes ('Bioprep' and 'Hibiclens'), cetyl trimethyl ammonium bromide (CTAB) and isothiazolinones ('Kathon') were tested against Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Proteus vulgaris and Candida albicans. The activities measured were the minimum inhibitory concentration (MIC), minimum microbicidal concentration (MMC), rate of kill in water and broth, effect of organic soil, the development of microbial resistance on continuous exposure and agent bioavailability in media and formulation. 'Kathon' was the most active microbistatic agent showing maximal activity at low concentration, least inactivation by organic soil and media components and the lowest level of development of bacterial resistance. It was synergistic with chlorhexidine against S. marcescens and P. aeruginosa. Media, formulation components and organic soil affected the performance of chlorhexidine and CTAB. Chlorhexidine was more broadly active than CTAB but showed a greater reduction in activity in the presence of soil and engendered a greater level of bacterial resistance. It was more rapidly bactericidal to P. aeruginosa and S. marcescens than to S. aureus. Stable resistance to chlorhexidine and CTAB was developed by P. aeruginosa and S. marcescens, the latter showing the higher level of resistance. Chlorhexidine-resistant strains were also resistant to CTAB. The antiseptic formulations were more rapidly bactericidal than chlorhexidine alone but were otherwise of comparable activity. Mixtures of disinfectants, in particular a combination of chlorhexidine and a preservative level of 'Kathon', were more active than single disinfectants. The importance of standardization of media and test conditions and the use of chemically defined media for accurate and reproducible in-vitro testing of disinfectant activity is emphasized. Disinfection kinetics, expressed as time-kill curves, log reduction factors or decimal reduction times were shown to be valuable in differentiating microbistatic from microbicidal activity, showing the effects of dilution and soil on activity and indicating possible different mechanisms of action.

Anti-Infective Agents, Local↗