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Biomedical subjects

S Stefani

Publications and source records attributed to S Stefani.

At least 73 records · Page 4Linked to original sources

Intensive alternating combination chemotherapy and high dose chest radiotherapy in small cell lung cancer.

Sixty-nine patients, 32 with limited and 37 with extensive small cell lung cancer (SCLC), were admitted to the present study. Patients with limited disease underwent alternating combination chemotherapy consisting of CAV (cyclophosphamide, adriamycin, vincristine) and PE (cisplatin and etoposide) regimens and concurrent high dose thoracic radiotherapy (6,000 cGy); prophylactic brain irradiation (3,000 cGy) was administered to complete responders. Patients with extensive disease received the same alternating chemotherapy but not radiotherapy. In the 25 evaluable patients with limited disease we obtained an objective response (OR) in 80% with a complete response (CR) in 54% and partial response (PR) in 24%, stable disease (SD) in 4% and progressive disease (PD) in 16%. Median duration of response was 9.5 months for CR and 8.5 months for PR. Median survival was 14 months for all patients with 12% long-term survivors. Toxicity was acceptable. In the 32 evaluable patients with extensive disease we observed 65.6% OR with 18.7% CR and 46.8% PR, 9.3% minimal response and 25% PD. Median duration of response was 7 months for CR and 8 months for PR. Median survival was 10 months for all patients. The treatment was well tolerated. Our study did not show a therapeutic advantage for alternating combination chemotherapy in SCLC and failed to show the use of high dose chest radiotherapy in combined modality for limited disease.

Adult↗

FK-506 prevents diabetes in diabetes-prone BB/Wor rats.

The effect of the immunosuppressant FK-506 on the development of diabetes in BB/Wor rats was investigated. Using a treatment schedule (25 micrograms i.m. from day 27 to 120), not associated with detectable general ill effects, this drug was found to completely inhibit the appearance hyperglycemia and to reduce the histological signs of pancreatic insulitis. The treatment was also able to reduce the percentages of Ia+ T-lymphocytes and to block the appearance of detectable serum levels of gamma interferon (IFN).

Animals↗

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↗

Significance of Haemophilus spp. and Branhamella catarrhalis in upper respiratory tract infections.

Haemophilus influenzae and Branhamella catarrhalis can be considered inhabitants of the upper respiratory tract in humans. Although the pathogenetic role of H. influenzae cannot be discussed, the Authors report the mechanisms of pathogenicity of this microorganism; furthermore, they discuss the direct or indirect pathogenicity of B. catarrhalis in respiratory tract diseases and the ability of both microorganisms to produce beta-lactamases. H. influenzae and B. catarrhalis, together with S. pneumoniae, are the most common bacteria responsible for upper respiratory tract infections, namely otitis and sinusitis. The activity of these bacteria in the onset of otitis and sinusitis is reported.

Haemophilus Infections↗

[Fractures of the orbital floor. Apropos of a homogeneous series of 70 patients].

The authors report their experience based on a homogeneous series of 70 fractures of the orbital floor. Different anatomo-clinical forms were defined in particular fractures of the orbital floor, accompanying an "internal pivoting" of the cheek bone, which by their incarceration mechanism resemble the trap-door fractures. The blow-out fracture associated with the lower orbital margin also raises therapeutic problems. After a clinical and CT study, the authors recommend treatment via the lower orbital approach using silastic implants. The different sequelae are described clinically and are appraised medically and legally.

Adult↗

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↗

Establishment from an adult leukemic patient of two novel precursor B cell lines with different growth modality.

Two novel cell lines, PC-53 and PC-53A were established from an adult ALL patient, at third relapse and in the terminal accelerated phase respectively. Both lines displayed the phenotype of B-cell precursors (CD19+, CD38+, CD20-, cytoplasmic-mu-, immunoglobulin gene rearrangement), identical to the freshly isolated blast cells. Chromosomal analysis showed a prominent 45-XX karyotype, including three marker chromosomes. No chromosome 8 abnormalities were detectable, consistently with a non-rearranged c-myc locus. Both cell lines were EBV-negative. Growth stimulation by autologous supernatant was observed for PC-53 cells during the first 4 months in culture, whereas it was much less evident for PC-53A cells. Thus, PC-53 and PC-53A cells represent a useful tool to investigate the mechanisms involved in the clonal expansion of B-cell precursors.

Adult↗

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↗

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↗

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↗

Microbiological characterization of dactimicin: antibacterial activity towards gram-positive and gram-negative bacteria.

Dactimicin is the first aminoglycoside antibiotic of Dactylosporangium origin, consisting of a pseudo-disaccharide and an amino acid. It has also a formimidoyl moiety instead of the deoxystreptamine found in other aminoglycosides. The authors considered the antibacterial activity of dactimicin compared with amikacin, gentamicin and the fortimicins against Gram-positive and Gram-negative bacteria. Dactimicin showed remarkable antibacterial activity against all strains tested: in particular the MIC90 values ranged from 2 mg/l for Citrobacter sp. to 32 mg/l for Proteus sp. Methicillin-resistant staphylococci were poorly susceptible to all aminoglycosides tested, while dactimicin showed good activity against the methicillin-susceptible strains. MBCs and killing curves indicated that this drug is rapidly bactericidal against all strains tested.

Aminoglycosides↗

In vitro bactericidal activity and post-antibiotic effect of dactimicin, a new aminoglycoside, alone and in combination with other antibiotics.

The bactericidal activity of dactimicin, a novel aminoglycoside, has been tested in vitro in combination with piperacillin, mezlocillin and ceftazidime against freshly isolated Gram-negative and Gram-positive aerobes and compared with that of amikacin. Using the checkerboard test, the combination of dactimicin and amikacin with the other drugs resulted in a synergistic interaction with the Enterobacteriaceae strains analysed in 36 out of 39 and 37 out of 39 cases, respectively. Antagonism was never encountered. With the Pseudomonas isolates, indifference prevailed with dactimicin, whereas synergism was observed with amikacin in combination with the other drugs. No case of antagonism was encountered. When the time-kill system was employed, synergism prevailed, indifference was a rare case, and antagonism was not observed. In experiments carried out with dactimicin-susceptible staphylococcal and enterococcal isolates, a synergistic outcome was obtained employing both methods. Dactimicin induced a post-antibiotic effect (PAE) which ranged from about 1 h with Enterobacter cloacae to 3 h with Escherichia coli after exposure of the bacteria for 1 h to 4 x MIC. The PAE was also evaluated employing several drug associations. An average of 0.6 h PAE was apparent when dactimicin was combined with piperacillin, mezlocillin and ceftazidime, and the bacteria were exposed for 1 h to drug concentrations corresponding to one-half their MICs.

Aminoglycosides↗