Biomedical subjects

G Nicoletti

Publications and source records attributed to G Nicoletti.

At least 163 records · Page 9Linked to original sources

PubMed1991

Dopaminergic hypothesis for retarded depression: a symptom profile for predicting therapeutical responses.

We assessed the therapeutical efficacy of various antidepressants (amineptine, minaprine and clomipramine) in patients affected by retarded depression. All patients exhibited symptoms of retardation, including hypokinesia, anergia, reduction of speech, increased salivation, hypersomnia, Parinaud's syndrome, reduced sexual activity, slowness, hypomimia, orthostatic hypotension, dysphagia and drowsiness. Antidepressant drugs were administered for a 6-week period in a randomized double-blind vs placebo design. The rank order of clinical effectiveness (amineptine much greater than minaprine greater than clomipramine greater than placebo) paralleled the specificity of antidepressants as dopaminomimetic agents. These results support the view that a reduced dopaminergic transmission contributes to the pathophysiology of retarded depression.

Adult↗

PubMed1991

Direct and indirect pathogenicity of beta-lactamase-producing bacteria in respiratory tract infection in children. Role of cephalosporins resistant to enzymatic hydrolysis.

A recent increase in the incidence of beta-lactamase-producing aerobic and anaerobic bacteria in upper respiratory tract infection has been associated with an increase in the failure rate of penicillin treatment of these infections. Experimental evidence for this correlation has been reported by many investigators, who have described the sheltering of susceptible pathogens by beta-lactamase-producing organisms as 'indirect pathogenicity'. The organisms implicated in mixed infections that cooperate are Staphylococcus aureus, Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and Bacteroides spp., which are pathogenic and also normal oropharyngeal inhabitants. Since these bacteria exhibit both direct and indirect pathogenicity, effective treatment requires administration of antimicrobial therapy active against all microorganisms present in mixed infection. Oral third generation cephalosporins, which are resistant to enzymatic hydrolysis, seem to be suitable initial therapy.

Bacteria↗

PubMed1991

Macrolides: present and future. An appraisal of in-vitro activity and pharmacokinetic behavior.

Macrolides belong to a large family of drugs called macrocyclic antibiotics, that can be divided into four groups: macrolactamas or ansamycins, polyene macrolides, macrolide-like compounds and macrolide antibiotics. Macrolide antibiotics comprise a large group of drugs, which are very much alike, characterized by large lactonic cycle with 12, 14, 15 or 16 atoms, to which are bound sugar and/or aminosugar. Although there are very large structural differences, macrolides represent a homogeneous group of drugs for which both a spectrum and a mode of action are similar. Macrolide antibiotics bind to the large subunit of prokaryotic ribosomes and perturb protein synthesis. The antimicrobial activity of macrolides is broad spectrum, being exhibited against gram-positive and gram-negative bacteria, including actinomyces and mycobacteria, as well as against treponemes, mycoplasmas, chlamydiae, rickettsias and also against some protozoa. Depending on the drug concentrations, bacterial species and phase of growth, macrolides may be bacteriostatic or bactericidal. Macrolides show high tissue/serum rations and greater concentrations of antibiotics are though to be achieved at the presumed site of infection. Such findings are in agreement with the apparent volumes of distribution for all the macrolide drugs, which are generally large. The worldwide resurgence of interest in macrolide antibiotics has yielded several semisynthetic derivatives of 14- and 16-membered macrolides which have progressed to clinical trials.

Anti-Bacterial Agents↗

PubMed1991

In vitro activity of flurithromycin against some genital pathogens.

The in vitro antibacterial activity of a new macrolide drug, flurithromycin, was evaluated in comparison with the activity of erythromycin A against some genital pathogens. The strains tested, C. trachomatis, U. urealyticum. M. hominis, N. gonorrhoeae, S. agalactiae and M. genitalium, were both clinically isolates and ATCC standards. The evidenced activity of flurithromycin is similar to that of erythromycin A. Resistances with both macrolides were found in all M. hominis strains and in one strain of U. urealyticum. No particular differences are exhibited between clinical and standard microorganisms.

Bacteria↗

PubMed1991

Reduced metastatic ability of in vitro differentiated human rhabdomyosarcoma cells.

We studied the human embryonal rhabdomyosarcoma cell line RD and 8 derivatives obtained in our laboratory either by cell cloning or by culturing in vitro cells from tumors or secondaries grown in nude mice. The expression of desmin and of the embryonic isoform of myosin and the formation of multinuclear myotube-like structures were studied as specific markers of myogenic differentiation. During continuous growth, each derivative contained a proportion (ranging from 5 to 80% among derivatives) of desmin-positive cells and a small number of myosin-positive or multinuclear elements. Cells from continuous cultures were injected intravenously in nude mice, producing lung and kidney/adrenal nodules. No correlation was found between the proportion of cells expressing desmin and metastatic capacity. When cultures were grown in differentiation medium (Dulbecco's minimal essential medium + 2% horse serum) some derivatives (designated type A) showed a strong increase in the proportion of myosin-positive cells, while others (type B) showed no increase. In vitro differentiation significantly reduced the metastatic ability of type A cells, while no modification was observed in type B after growth in differentiation medium. The proliferative ability of type A and type B cells grown in differentiation medium did not correlate with the proportion of myosin-positive cells, and extensive formation of multinuclear myotubes was never observed. It was concluded that reduction of experimental metastatic ability was mediated by events related to late, though not necessarily terminal, differentiation of rhabdomyosarcoma cells.

Animals↗

PubMed1991

Sulbactam/ampicillin in the treatment of otitis and sinusitis.

The importance of beta-lactamase-producing strains in acute otitis media and acute/chronic sinusitis, and the effectiveness of sulbactam/ampicillin were ascertained in vitro and in vivo. Of the strains isolated from 19 patients with otitis media, 40% are beta-lactamase producers whereas 44% of strains isolated from 22 patients with sinusitis produced beta-lactamase. When the most commonly isolated strains were treated with a range of antibiotics in vitro, they all showed 100% sensitivity to sulbactam/ampicillin. The clinical results for otitis media showed 63% recovery and 26% improvement, with only one (5%) failure (one patient did not complete treatment). For sinusitis the results were 55% recovery and 45% improvement, and no failures. For sinusitis, the end-of-treatment microbiological results showed complete eradication of the pathogens responsible for infection. The results indicate that sulbactam/ampicillin is an effective treatment for infections of the ear, nose and throat.

Adolescent↗

PubMed1990

Sequential and synchronous chemo-radiotherapy in the management of locally advanced carcinoma of the head and neck.

Thirty-nine consecutive patients with stage III-IV squamous cell carcinoma of the head and neck entered a pilot study of sequential and synchronous chemo-radiotherapy. The study was planned as follows: two cycles of induction chemotherapy (MTX, BLM, DDP) followed by radical radiotherapy (66 Gy) with synchronous weekly administration of DDP (20 mg/m2) as a radiosensitizer. Out of the 39 patients evaluable for induction chemotherapy 25 (64%) achieved partial or complete response. Two patients underwent radical surgery after induction chemotherapy and 3 patients died of treatment. Out of the remaining 34 patients, 25 were untreated and 9 presented recurrence after primary surgery. Grade 4 mucositis was the major side effect of concurrent chemo-radiotherapy. Local control after synchronous therapy was obtained in 11 (44%) previously untreated patients and only in 1 (11%) patient of the surgically pre-treated group. At the time of the analysis 11 patients were alive, 8 of them free from disease (4 after salvage surgery). Actuarial 2-year survival for previously untreated patients was 33% and 24% for all the patients. This survival is not significantly different (log rank test) from that of a similar group of 24 patients treated at the same institution with radiotherapy alone. The important toxicity of the induction chemotherapy regimen and the poor 2-year survival do not show any benefit from such a combined approach in locally advanced head and neck carcinoma. Nevertheless, despite our disappointing results many data in the literature suggest a role for chemotherapy-based treatments of locally advanced head and neck cancer. Further controlled randomized studies are required to better define the place of chemotherapy in the multi-modality management of stage III-IV head and neck cancer.

Adult↗

PubMed1990

Circulation in Italy of beta-lactamase-producing strains within the major groups of bacterial pathogens.

A multicenter study was undertaken in Italy to assess the circulation of beta-lactamase-producing organisms and their current incidence within the major groups of bacterial pathogens. Almost four thousand strains, all freshly isolated from clinical material, were examined at four centers serving different areas of Italy. Despite some significant center-to-center differences, this survey documented the occurrence of a large overall circulation of beta-lactamase-producing organisms among clinical bacterial isolates. In particular, ampicillin resistance was recorded in one third to one half of the isolates of some Enterobacteriaceae, including Escherichia coli, Proteus, and Citrobacter species, and 80-90% of these resistant strains proved to be beta-lactamase producers. Both ampicillin resistance and beta-lactamase production were almost the rule in other Enterobacteriaceae, including Klebsiella, Enterobacter, and Serratia species. beta-lactamase was also produced by about 80% of glucose-non-fermenting gram-negative bacteria and Aeromonas hydrophila strains, by all of the isolates of Branhamella catarrhalis manifesting ampicillin resistance (i.e. more than half the total number of isolates), and by about two thirds of the ampicillin-resistant Haemophilus strains (which accounted for 20-25% of all Haemophilus isolates examined). In contrast, no beta-lactamase producers were observed among Neisseria gonorrhoeae isolates.

Ampicillin Resistance↗

PubMed1990

Hygienic hand disinfection: a comparative study with chlorhexidine detergents and soap.

The efficacy of two chlorhexidine hand-wash detergents and liquid soap was compared in a laboratory trial using artificial contamination of fingers with Micrococcus and Serratia. Agents were assessed for both a rapid and sustained effect after a single contact, and for a cumulative persistent effect after multiple contact over four days. Disinfectant activities were compared by statistical analysis of log reduction factors and log count time gradients (decimal reduction times). The latter analysis attempted to accommodate significant subject variation in response to both agent and organism. All handwashing methods significantly reduced contamination levels. Both chlorhexidine formulations were significantly better than soap in their activity against Micrococcus, but were not more effective than soap in removing contamination with Serratia. Both chlorhexidine preparations showed significant skin persistence and were generally acceptable to subjects after prolonged use. Some effect of the formulation of the hand-wash on chlorhexidine activity was demonstrated.

Chlorhexidine↗

PubMed1990

In-vitro activity of ampicillin/sulbactam and other antibiotics against clinical isolates of Haemophilus sp. and Branhamella catarrhalis.

The ampicillin/sulbactam combination is one of several such drug combinations of a beta-lactam and suicide inhibitor having a wide spectrum of activity. These characteristics induced us to evaluate the in vitro activity of this combination towards 54 strains of Haemophilus sp. (38 beta-lactamase producers) and 20 strains of Branhamella catarrhalis (16 beta-lactamase producers). All strains were isolated from sputum, sinusal aspiration and tympanocentesis. In the case of Haemophilus sp beta-lactamase producers, minimal inhibitory concentrations of ampicillin were reduced 8 times by the use of the inhibitor; good results were also obtained for B. catarrhalis. Haemophilus influenzae, B. catarrhalis together with Streptococcus pneumoniae are recognized as the major pathogens involved in upper respiratory tract infections. The increasing frequency of beta-lactamase producing strains has impaired the use of aminopenicillins. The combination of an inhibitor and beta-lactam restore the activity of the latter, suggesting that this combination can serve as first choice in therapy.

Ampicillin↗

PubMed1990

Epidemiology of antibiotic resistance in human isolates of Enterobacteriaceae in Sicily.

The authors have studied the antimicrobial susceptibility of 1073 clinical isolates of various genera of Enterobacteriaceae (collected during the period July-December 1988) to ampicillin, piperacillin, cefotaxime, ceftazidime, ceftriaxone, aztreonam, imipenem, gentamicin, amikacin, netilmicin, norfloxacin, and ciprofloxacin. Antimicrobial susceptibility was determined by Bauer-Kirby disk diffusion method. Of 1073 tested bacteria, 704 (65.6%) produced beta-lactamase detectable by nitrocefin test. The highest percentage of resistant strains occurred with ampicillin (70%) followed by piperacillin (24%) and cefotaxime (19%). Lower percentages of resistant strains were found for gentamicin (10%), aztreonam (8%), netilmicin (7%), norfloxacin (5%) and amikacin (4%). Two percent of the strains were resistant to ciprofloxacin and 0.5% to imipenem. The incidence of resistance in Klebsiella sp., Enterobacter sp., E. coli and Proteus sp. was compared to that found among 872 strains isolated during July-Dec. 1984. In all the Enterobacteriaceae, mainly Enterobacter sp., the increase in the resistance was high for ampicillin, piperacillin and cefotaxime and lower for gentamicin.

Drug Resistance, Microbial↗

PubMed1990

Comparative in-vitro activity of piperacillin and piperacillin plus tazobactam towards beta-lactamase producing clinical isolates.

The authors evaluated the in-vitro antibacterial activity of piperacillin alone and of piperacillin combined with tazobactam, a new beta-lactamase inhibitor, on 398 clinical isolates, both Gram-positive and Gram-negative. The piperacillin/tazobactam combination was evaluated in the fixed ratio 8:1. The vast majority of the microorganisms tested had reduced susceptibility to piperacillin (minimum inhibitory concentration (MIC) range 0.12- greater than 256 mg/l) due to beta-lactamase production. The following results were obtained: against Haemophilus influenzae, tazobactam was effective in reducing the MICs of piperacillin by 512 fold. The activity of piperacillin/tazobactam was lower against Pseudomonas sp., while some activity was demonstrated against some strains of Klebsiella. Good activity was seen not only against methicillin-susceptible (MS) staphylococci but also against some methicillin-resistant (MR) strains. In the latter, the combination of piperacillin/tazobactam was active only if the strains showed beta-lactamase production. These findings are interesting above all in regard to the synergistic effect demonstrated against MR beta-lactamase producing staphylococci and the Klebsiella-Enterobacter-Serratia (KES) group.

Drug Synergism↗

PubMed1990

Peripheral neuroectodermal tumour (neuroepithelioma) of the thoracopulmonary region: light and electron microscopic cytology.

We describe a case of peripheral neuroectodermal tumour of the thoracopulmonary region diagnosed by fine needle aspiration cytology. Light microscope examination revealed numerous small tumour cells arranged in large irregular aggregates occasionally delimiting empty vascular-type spaces or forming rosette-like structures. Cytologically the tumour cells showed a marked degree of nuclear anaplasia, scanty cytoplasm and long thin cytoplasmic processes. Electron microscopy revealed cells with characteristics of neuroectodermal differentiation.

Humans↗

PubMed1990

In vitro activity of sulbactam/ampicillin against ampicillin-resistant, beta-lactamase-producing bacteria isolated in Italian hospitals.

A multicenter study aimed at assessing the in vitro activity of sulbactam/ampicillin against a wide range of bacterial pathogens was performed using 2,209 clinical strains, all recently collected from inpatients in seven Italian centers and preliminarily screened as being ampicillin-resistant and beta-lactamase producers. In comparative disk diffusion trials using 8 large-spectrum antimicrobials, the percentage of resistance to sulbactam/ampicillin in staphylococci was similar to the percentage of resistance to netilmicin and lower than to the other antibiotics; with gram-negative bacteria, only netilmicin, ofloxacin, and, less consistently, cefotetan showed lower incidences of resistance. The minimal inhibitory concentrations (MICs) of ampicillin alone and sulbactam/ampicillin together were determined using the agar dilution method. The Enterobacteriaceae strains which shifted to ampicillin susceptibility in the presence of sulbactam averaged 68%, but values significantly above or below average were observed in some genera of this family. The percentage of strains which the presence of sulbactam rendered ampicillin-susceptible in vitro reached 97% in Haemophilus strains and 100% in branhamellae and gonococci. High percentages were also recorded in staphylococci, with a peak of 100% in oxacillin-susceptible Staphylococcus aureus strains. In general, center-to-center differences were relatively limited.

Ampicillin↗

PubMed1990

Microbiological study of Enterococcus faecium SF68: post-antibiotic effect and growth curves.

We studied the microbiological characteristics of Enterococcus faecium SF 68 (an oral vaccine) assessing post-antibiotic effect of ampicillin and growth curves in different media. Results showed a good resistance of the microorganism tested which has important implications in clinical practice. The growth ability of Enterococcus faecium SF 68 was similar on all media tested.

Ampicillin↗

PubMed1990

High-level resistance to aminoglycosides in enterococci; incidence and alternative active antibiotic combinations in vitro.

Enterococci with high-level resistance to aminoglycosides have been frequently isolated from clinical specimens in the last few years. It is well known that this resistance is linked to a lack of synergism of the beta-lactam/aminoglycoside combination used in the treatment of severe infections. Many authors have reported an increasing incidence of isolation of enterococci highly resistant to gentamicin. In order to overcome the failure of the currently used antimicrobial combinations, in this work the degree of activity of ciprofloxacin plus, respectively, the glycopeptides vancomycin and teicoplanin, and also the combination teicoplanin/netilmicin, was evaluated. The results obtained with ciprofloxacin/teicoplanin and teicoplanin/netilmicin combinations show a good percentage of synergy (about 70-80%) with respect to the combination of ciprofloxacin plus vancomycin. The results are encouraging also in the highly resistant strains.

Aminoglycosides↗

PubMed1989

Modulation by IFN-gamma of the metastatic ability of murine, human, and H-2-transfected tumor cells.

Interferon-gamma (IFN-gamma) can enhance the experimental metastatic ability of B16 melanoma. The in vitro treatment with IFN-gamma of four clones derived from the murine mammary adenocarcinoma TS/A increased the number of lung colonies observed after intravenous injection in syngeneic mice. The spontaneous metastatic ability of these clones was not altered by the IFN-gamma pretreatment nor by daily intratumor injection of low-dose IFN-gamma. The experimental metastatic ability in nude mice of the human rhabdomyosarcoma cell line RD was decreased by in vitro pretreatment with IFN-gamma. To study the role played by major histocompatibility complex gene products in the IFN-gamma-mediated enhancement of B16 experimental metastasis, a mutant B16 clone, B78H1, was transfected with the H-2Kb gene. B78H1 cells are not capable of expressing H-2b even after treatment with IFN-gamma; IFN-gamma readily induced high levels of H-2Kb in a set of transfected clones, but did not enhance their experimental metastatic ability.

Animals↗

PubMed1989

Myogenic differentiation of human rhabdomyosarcoma cells induced in vitro by antineoplastic drugs.

The effect of various antineoplastic drugs (1-beta-D-arabinofuranosylcytosine, 5-azacytidine, cisplatin, dactinomycin, epirubicin, vincristine, and the activated metabolite of cyclophosphamide, mafosfamide) on cell differentiation in vitro was investigated using a human alveolar rhabdomyosarcoma cell clone, RMZ-RC2. These cells are able to differentiate spontaneously from small mononuclear proliferating elements to terminal, extremely elongated multinuclear structures resembling myotubes; morphological differentiation is accompanied by the expression of myosins, in particular the embryonic isoform, which was used in this study as a specific marker of myogenic differentiation. The proportion of differentiated myosin-positive cells, which was around 10-15% in control cultures 10-15 days after seeding, was increased by some drug treatments up to 30-40%; the proportion of multinuclear elements was also increased. 1-beta-D-arabinofuranosylcytosine and 5-azacytidine were the most effective drugs, while dactinomycin had no effect; other molecules ranked in between. Since significant increments were usually observed after treatment with drug doses inhibiting cell growth, the kinetic behavior of the absolute number of myosin-positive cells or nuclei was analyzed to assess whether some effects could be due to a negative selection of proliferating, undifferentiated cells. This appeared to be the case for vincristine and epirubicin, while 1-beta-D-arabinofuranosylcytosine, 5-azacytidine, and, to a lesser degree, mafosfamide and cisplatin actually seemed to increase differentiation ability.

Antineoplastic Agents↗