Biomedical subjects
Publications and source records attributed to C Cocuzza.
Spigelian hernia is a rare condition of the abdominal wall; 13 cases occurred in the last five years are here reported. These patients were treated surgically, using direct reconstruction of the abdominal wall in eight cases, while a tension-free hernioplasty was utilized in five cases.
Pulsed-field gel electrophoresis (PFGE) has become the gold standard of molecular methods in epidemiological investigations. In spite of its high resolving power, use of the method has been hampered by inadequate laboratory-to-laboratory reproducibility. In the project described here we have addressed this problem by organizing a multilaboratory effort in which the same bacterial strains (subtype variants of the Iberian and Brazilian methicillin-resistant Staphylococcus aureus--MRSA--clones) were analyzed by twenty investigators in thirteen different laboratories according to an indentical protocol, which is reproduced here in detail. PFGE patterns obtained were analyzed at a central laboratory in order to identify specific technical problems that produced substandard macrorestriction patterns. The results including the specific technical problems and their most likely causes are described in this communication. Also listed are seven major epidemic clones of MRSA which have been characterized by molecular fingerprinting techniques and the prototypes of which have been deposited at the American Type Culture Collection, from where they will be available for interested investigators for the purpose of typing MRSA isolates. It is hoped that this communication will contribute to the improvement of the reproducibility and technical/aesthetic quality of PFGE analysis.
Resistance to macrolides has increasingly been reported for Group A streptococci. In this study, the in vitro antibiotic susceptibility pattern of 305 clinical isolates of S. pyogenes was determined. Strains were isolated during 1996 from pharyngeal swabs of children with uncomplicated pharyngitis living in 2 Italian cities: Milano and Catania, situated in the North and South of Italy, respectively. All isolates were found to be fully susceptible to penicillin and other beta-lactam agents tested. Susceptibility to macrolides differed markedly between the two centers with relatively high resistance rates to erythromycin being observed in Milano (30%) as compared to Catania (3%). Resistance to erythromycin was always crossed with that of the other 14- and 15-membered macrolides tested. However, resistance to josamycin and clindamycin was generally found in approximately 25% of the erythromycin-resistant (ER) strains. The erythromycin-resistant isolates from Milano and Catania (58 strains) were further subdivided into the three previously described resistance phenotypes: constitutive, inducible, and novel resistance phenotypes. The novel resistance phenotype accounted for 58% of all resistant strains, while 17% and 26% were found to be of the inducible and constitutive resistance phenotypes. Strains of the novel resistance phenotype were characterized by lower MIC values (MIC90 = 16 mg/L) to 14 and 15 carbon atom macrolides as compared to the other two phenotypes (MIC90 > 128 mg/L), and retained susceptibility to clindamycin and to josamycin, a 16 carbon atom macrolide. Resistance to tetracyclines was found in 25% to 36% of the ER isolates as compared to 2% to 10% of the susceptible strains. In particular, resistance to this agent was more commonly associated to isolates belonging to the novel and constitutive resistance phenotypes. MIC values for chloramphenicol in all isolates were within the susceptible or intermediate range; decreased susceptibility to this agent did not appear to be associated with erythromycin resistance.
The serum levels of the heterodimeric cytokine IL-12 were measured by solid-phase ELISA in a group of healthy subjects, multiple sclerosis (MS) patients with secondary chronic progressive course of the disease and patients suffering from other neurological diseases (OND). Serum levels of IL-12 higher than 5 pg/ml (limit of sensitivity of the assay) were only found in 2/30 (6.7%) of the healthy subjects and none of the 8 subjects with OND. In contrast, IL-12 was found in the majority of CPMS patients' sera (10/15, 66.7%) with values ranging between 5.5 and 18.6 pg/ml. These results are suggestive for an up-regulated production of IL-12 in CPMS.
The efficacy and tolerability of brodimoprim OD versus norfloxacin BID were studied in patients affected by bacterial urinary tract infections. The study was performed in 203 patients divided into two parallel randomized groups orally given either brodimoprim 400 mg OD on the first day followed by 200 mg OD for 2 days, or norfloxacin 400 mg BID respectively. The efficacy of treatment was evaluated by the bacterial cultures, tolerability, analysis of signs and symptoms, a complete physical examination and from laboratory data. The results showed that brodimoprim and norfloxacin in the majority of patients resulted in a reduction of fever and symptoms caused by the infective process. Of the 103 patients enrolled in the brodimoprim OD group, 99 had a complete course of therapy with a positive outcome. There was only one case of failed treatment and 3 cases which could not be evaluated because of voluntary interruption of treatment. Of the 100 patients treated with norfloxacin BID, 94 completed therapy with a positive clinical outcome and there were 4 cases of treatment failure. Thus the efficacy of brodimoprim OD appears comparable to that of norfloxacin BID in the treatment of urinary tract infections.
Thymopentin (TP-5) is a synthetic pentapeptide that corresponds to the active 32-36 amino acid sequence of the thymic hormone thymopoietin, of which it retains all the immunomodulatory properties. In this study, we have evaluated the effects of long term prophylactic treatment with TP-5 on the clinical, immunological and histological parameters of the SLE-like syndrome that spontaneously occurs in MRL/lpr-lpr (MRL-lpr) mice. TP-5, administered (s.c.) to these mice at the doses of 1, 10 and 100 mg/kg, was given daily, five times a week, from the 9th to the 26th weeks of life. The prophylactic treatment with TP-5 prolonged in a clear dose-dependent fashion the lifespan of MRL-lpr mice as compared with PBS-treated control mice, and the effect reached statistical significance at the doses of 10 and 100 mg/kg. In parallel ex vivo studies, this clinical effect was associated with multiple profound modifications of the immune system including: (i) the reduction of the spontaneous and Con A-induced release of interleukin-4 (IL-4); (ii) the increased secretion of interferon-gamma (IFN-gamma) and IL-6 upon polyclonal mitogenic stimulation, and (iii) the amelioration of the defective Con A-induced lymphoproliferative response. In contrast, although the drug diminished the severity of proteinuria in MRL-lpr mice, it neither reduced histological signs of lupus nephritis nor diminished the serum titres of anti-native DNA and anti-histone autoantibodies. These results indicate that TP-5 displayed powerful immunodulatory activities in a well known model of human SLE.
CD-1 mice were treated with methylprednisolone (mPDN) 2-5 mg/kg s.c., for 11 or 6 days, in order to achieve an immunosuppressed state. For the same length of time a group of mice also received pidotimod ((R)-3-[(S)-(5-oxo-2-pyrrolidinyl) carbonyl]-thiazolidine-4-carboxylic acid. PGT/1A, CAS 121808-62-6) i.p. at 100 or 10 mg/kg. At the end of treatment, peritoneal macrophages (MO) were recovered, purified by adherence to plastic and activated in vitro with different stimuli. After 24 h of incubation, the supernatants were collected and assayed for the presence of tumor necrosis factor-alpha (TNF-alpha) and nitrite (NO2-), which is the stable derivative of nitric oxide (NO) in acqueous solution. It is well known that TNF-alpha and NO represent two out of many molecules secreted by activated MO which are essential for killing microorganisms and for natural response to infections. It was observed that MO from mPDN-treated mice were unable to produce sufficient levels of both TNF-alpha and NO when stimulated in vitro with lipopolysaccharide, IFN-gamma or conidia from an opportunistic fungus, Aspergillus fumigatus, confirming that corticosteroids are able to inhibit the antimicrobial activity of MO. However, MO from mice received mPDN plus pidotimod fully recovered the capacity to produce TNF-alpha and NO in response to the same stimuli. Optimal dose of pidotimod was 100 mg/kg. In addition, pidotimod was also able to reconstitute the cellularity of the peritoneum and of the spleens of mice immunodepressed by mPDN.(ABSTRACT TRUNCATED AT 250 WORDS)
The possible interference of the novel antibiotic cefepime (CPE) with some functions of the immune system was investigated in vitro. Peripheral blood mononuclear cells (PBMC) cultured in the presence of drug concentrations ranging from 25 to 100 micrograms/ml normally maintained their responsiveness to polyclonal (PHA, Con A, PWM) mitogenic stimulation in regard to proliferative response, IgM and IgG synthesis and IFN-gamma and IL-2 secretory capacity. Moreover, PHA-induced expression of IL-2 receptors was comparable in PBMCs cultured in the presence or absence of CPE. Taken together, these data suggest that CPE does not interfere, at this specific level, with T- and B-cell mediated functions in vitro.
The antimicrobial profile of a new nitroimidazole derivative (5-nitro-1-methyl-imidazolyl-2-hydroxy-3 terbutylphenyl carbinol) has been studied. The in vitro activity of the new molecule has been evaluated against both aerobic and anaerobic bacteria, Trichomonas vaginalis, and mycetes, under suitable experimental conditions. The new compound was compared with ampicillin against aerobic bacteria; with metronidazole against anaerobic bacteria, lactobacilli and T. vaginalis; with nistatin and econazole against candida and with econazole and bifonazole against filamentous fungi. The new nitroimidazole derivative has been shown to be moderately active against some anaerobic bacteria belonging to both the Gram-positive and Gram-negative groups. Its inhibitory activity against T. vaginalis was similar to that of metronidazole.
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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.
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