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Biomedical subjects

R Fontana

Publications and source records attributed to R Fontana.

At least 73 records · Page 4Linked to original sources
PubMed1997

Disease history in 382 Italian patients with Crohn's disease.

AIMS: This large-scale study was aimed at evaluating the long-term history of Crohn's disease in a cohort of consecutive patients referred to the Careggi Hospital in Florence from January 1973 to June 1996. PATIENTS: A total of 382 patients (187 females, 195 males; mean age of 47 years) were included in our study. The median follow-up was more than 11 years and only 46 patients (12%) had a follow-up of less than 1 year. The main endpoints evaluated in these patients included mortality for any cause, disease-specific mortality, recurrences, and need for surgery. Furthermore, in a subgroup of 130 patients observed during the last 6 months of our study, a more detailed assessment of the disease was carried out in which the distribution of inflammatory, fibrostenosing and fistulizing forms was determined. RESULTS: Our results showed that the disease-specific mortality rate was extremely low (around 3% at 10 years and 5% at 20 years), but the rate of recurrence was approximately 50% at 3 years and more than 60% at 6 years. Surgery was needed in more than 50% of the patients over the 10 years following diagnosis, and the risk of a second operation was of a further 30% within 4 years of the first operation. CONCLUSIONS: These epidemiological data emerging from our study are interesting since a large patient population was evaluated and the duration of the follow-up is extremely long.

Adolescent↗
PubMed1996

Intrinsic penicillin resistance in enterococci.

Penicillin resistance development in enterococci has been associated with overproduction of a low-affinity penicillin-binding protein (PBP) that is a normal component of the PBP pattern of these bacteria and is apparently able to substitute the functions of the other PBPs. In resistant mutants of Enterococcus hirae ATCC 9790 the low-affinity PBP (PBP5) overproduction was associated with a deletion in a genetic element, located 1 kb upstream of the pbp5 gene, which negatively controlled PBP5 synthesis. Hypersusceptibility to penicillin was associated with a point mutation in the pbp5 gene, which causes premature termination of translation. Structural homologies between low-affinity PBPs of the different enterococcal species have been suggested by cross-reactivity of antibodies raised against E. hirae PBP5 with PBP5 of Enterococcus faecium and Enterococcus faecalis. Acquisition of a high-level ampicillin resistance in E. faecium was associated with overproduction of PBP5, which, compared with PBP5 of moderately resistant strains, appeared to be modified in its penicillin-binding capability. The modified phenotype of PBP5 was found to be associated to some amino acid substitutions in the region between the SDN and KTG motifs. In particular, the substitution converting a polar residue (T) in a nonpolar one (A or I) could play an important role in remodeling the penicillin-binding domain and determining the decrease in penicillin affinity.

Amino Acid Sequence↗
PubMed1996

Diffusion of carbapenems through the outer membrane of enterobacteriaceae and correlation of their activities with their periplasmic concentrations.

Scarce information is available on the real mechanism by which carbapenemes penetrate in Enterobacteriaceae, although a considerable amount of evidence suggests that in many species of this family the lack of certain outer membrane proteins is associated with the acquisition of resistance to these antibiotics. The existance of specific pathways for the carbapenems has never been demonstrated, although at times it has been postulated in both wild and mutant strains, on the basis of evident discordances between permeability patterns and suceptibility data. By using the Zimmerman and Rosselet technique, which requires the strain under investigation to harbor a suitable beta-lactamase, the permeability of intact Escherichia coli and Enterobacter cloacae cells to meropenem and imipenem was investigated by transferring a constructed vector carrying the carbapenem hydrolyzing CphA metallo-beta-lactamase gene into the parental strains and their porin-deficient mutants. Reduced amounts of nonspecific porins significantly reduced the penetration of both carbapenems. The virtual absence of porins caused the MICs of meropenem to increase, mostly in Enterobacter cloacae, while it did not affected the MICs of imipenem. No evidence of specific porin pathways of the type described in Pseudomonas aeruginosa was found.

Bacterial Outer Membrane Proteins↗
PubMed1996

Modification of penicillin-binding protein 5 associated with high-level ampicillin resistance in Enterococcus faecium.

High-level ampicillin resistance in Enterococcus faecium has been shown to be associated with the synthesis of a modified penicillin-binding protein 5 (PBP 5) which had apparently lost its penicillin-binding capability (R. Fontana, M. Aldegheri, M. Ligozzi, H. Lopez, A. Sucari, and G. Satta. Antimicrob. Agents Chemother. 38:1980-1983, 1994). The pbp5 gene of the highly resistant strain E. faecium 9439 was cloned and sequenced. The deduced amino acid sequence showed 77 and 54% homologies with the PBPs 5 of Enterococcus hirae and Enterococcus faecalis, respectively. A gene fragment coding for the C-terminal part of PBP 5 containing the penicillin-binding domain was also cloned from several E. faecium strains with different levels of ampicillin resistance. Sequence comparison revealed a few point mutations, some of which resulted in amino acid substitutions between SDN and KTG motifs in PBPs 5 of highly resistant strains. One of these converted a polar residue (the T residue at position 562 or 574) of PBP 5 produced by susceptible and moderately resistant strains into a nonpolar one (A or I). This alteration could be responsible for the altered phenotype of PBP 5 in highly resistant strains.

Amino Acid Sequence↗
PubMed1996

Modulatory effects of hen egg-white lysozyme on immune response in mice.

The effect of her egg-white lysozyme (HEWL) on immune response was evaluated by measuring antibody-producing cells and circulating antibodies in mice inoculated with the test antigen (SRBC or BSA) and HEWL at the same time but in a separate body area. HEWL caused a premature decline in SRBC-specific plaque forming cells (PFC) and a reduction in the total amount of these cells. HEWL inhibited antibody production against BSA in the primary response, but was devoid of any effect on the secondary response elicited in the same mice by a second inoculation of the test antigen. The inhibitory effect of HEWL was dose-dependent, being maximal with 300 micrograms, required an enzymatically active protein and was not shown by other basic proteins. HEWL also abolished the enhancing effect of LPS and CFA on anti-BSA antibody production. The inhibitory activity of HEWL was further increased by hydrolyzed peptidoglycan. These results suggest that HEWL modulates the immune response in mice and performs this function through activation of non-specific suppression mechanisms.

Adjuvants, Immunologic↗
PubMed1996

Lysozyme inhibitors enhance immune response in mice.

The effect of hen egg-white lysozyme (HEWL) inhibitors (such as heparin, histidine methylester, chitotriose, chitobiose) on immune response was evaluated by measuring antibody-producing cells and circulating antibodies in mice inoculated with these substances and the test antigen (SRBC or BSA). It was found that these compounds have an immuno-enhancing effect which is directly proportional to their inhibitory activity on HEWL. Conversely, HEWL inhibited the immunoenhancing effect of these compounds when injected together with these and the test antigen. The results suggest that one possible mechanism by which adjuvants stimulate immune response may be the inhibition of endogenous lysozyme.

Adjuvants, Immunologic↗
PubMed1996

Comparative affinities for penicillin-binding proteins of multipolar ionic amphoteric cephalosporins in gram-negative bacteria.

Chemical modification of the highly reactive 7-aminocephalosporanic acid has yielded many compounds with improved activities and expanded clinical spectra. Introduction of an alpha-oxyimino group in C-7 position has given rise to improved activity against Gram-negative bacteria as a consequence of the high affinity of compounds carrying this substituent for the essential penicillin-binding protein (PBP) 3. The spectrum of activity of oxyimino cephalosporins has been further expanded by introduction of substituents with a quaternary nitrogen in C-3 position. These compounds have maintained their high affinity for the essential PBP 3, typical of the third generation cephalosporins and have acquired an improved ability to cross the outer membranes of Gram-negative bacteria. Among these compounds cefepime also exhibits high affinity for PBP 2, a very unusual property among cephalosporins.

Bacterial Proteins↗
PubMed1996

A simple method to detect bacteriolytic enzymes produced by enterobacteriaceae.

The production of bacteriolytic enzymes by Enterobacteriaceae in various growth conditions was investigated. Peptone-based media containing killed Gram-negative cells facilitated detection of bacteriolytic enzyme production in the highest number of species. These belonged to the genera Serratia, Proteus, Morganella and Providencia. In contrast, Escherichia coli, Shigella, Salmonella, Klebsiella, Enterobacter and Citrobacter species did not produce bacteriolytic activities in any of the conditions tested.

Bacteriolysis↗
PubMed1995

Activities of oral antibiotics on Providencia strains isolated from institutionalized elderly patients with urinary tract infections.

More than 250 Providencia strains isolated from the urine of institutionalized elderly patients were tested against cefaclor, cefuroxime, cefetamet, cefpodoxime, ciprofloxacin, and amoxicillin-clavulanic acid. Our results confirm the strong activities of expanded-spectrum oral cephalosporins against Providencia isolates, f1p4ell as the marked differences in susceptibilities among accurately identified Providencia species.

Administration, Oral↗
PubMed1995

Relative importances of outer membrane permeability and group 1 beta-lactamase as determinants of meropenem and imipenem activities against Enterobacter cloacae.

The roles of outer membrane permeability and Bush group 1 beta-lactamase activity in determining Enterobacter cloacae susceptibility to either meropenem or imipenem were investigated. A beta-lactamase-deficient strain was obtained by mutagenesis from a clinical isolate of E. cloacae, and a porin-deficient strain was selected from this mutant with cefoxitin. Both strains were transformed with the plasmid pAA20R, which contained the gene coding for the carbapenem-hydrolyzing CphA beta-lactamase, and the carbapenem permeability coefficients were measured by the Zimmermann and Rosselet technique (W. Zimmermann and A. Rosselet, Antimicrob. Agents Chemother. 12:368-372, 1977). The permeability coefficient of meropenem was roughly half that of imipenem in the normally permeable strain and almost seven times lower than that of imipenem in the porin-deficient strain. In the porin-deficient strain, the virtual absence of porins caused the MICs of meropenem to increase from 8 to 16 times, while it did not affect the MICs of imipenem. Conversely, the beta-lactamase affected imipenem but not meropenem activity: meropenem showed a similar activity in the parent strain and in the beta-lactamase-deficient mutant with both a low- and high-density inoculum, whereas imipenem was 16 times less active against the parent strain when the high-density inoculum was used. It is concluded that outer membrane permeability and stability to group 1 beta-lactamase have different impacts on the activities of meropenem and imipenem against E. cloacae.

Bacterial Proteins↗
PubMed1995

Target for bacteriostatic and bactericidal activities of beta-lactam antibiotics against Escherichia coli resides in different penicillin-binding proteins.

The relationship between cell-killing kinetics and penicillin-binding protein (PBP) saturation has been evaluated in the permeability mutant Escherichia coli DC2 in which the antimicrobial activity of beta-lactams has been described as being directly related to the extent of saturation of the PBP target(s). Saturation of a single PBP by cefsulodin (PBP 1s), mecillinam (PBP 2), and aztreonam (PBP 3) resulted in a slow rate of killing (2.5-, 1.5-, and 0.8-log-unit decreases in the number of CFU per milliliter, respectively, in 6 h). Saturation of two of the three essential PBPs resulted in a marked increase in the rate of killing, which reached the maximum value when PBPs 1s and 2 were simultaneously saturated by a combination of cefsulodin and mecillinam (4.7-log-unit decrease in the number of CFU per milliliter in 6 h). Inactivation of all three essential PBPs by the combination of cefsulodin, mecillinam, and aztreonam further increased the killing kinetics (5.5-log-unit decrease in the number of CFU per milliliter), and this was not significantly changed upon additional saturation of the nonessential PBPs 5 and 6 by cefoxitin. Similar relationships between PBP saturation and killing kinetics were obtained with imipenem and meropenem at concentrations which inhibited only one PBP (PBP 2), only two PBPs (PBP 1s and 2), or all three essential PBPs. Saturation of one or more PBPs also resulted in a different rate of bacteriolysis, the highest rate being obtained by the cefsulodin-mecillinam combination and by 5 micrograms of either imipenem or meropenem per ml. All of these conditions caused saturation of PBP 2 and saturation or extensive binding of PBP 1s. However, none of these conditions caused determined the fastest possible rate of killing, which occurred only when all three essential PBPs were saturated. It was concluded that the actual killing effect of beta-lactams is reflected by killing rates that approach the fastest possible rate for the given microorganism and that the targets for the bactericidal activity are precisely those PBPs whose saturation or binding occurs under conditions.

Anti-Bacterial Agents↗
PubMed1995

Identification of a gene (arpU) controlling muramidase-2 export in Enterococcus hirae.

Muramidase-2 of Enterococcus hirae is a 74-kDa peptidoglycan hydrolase that plays a role in cell wall growth and division. To study its regulation, we isolated a mutant defective in muramidase-2 release under certain growth conditions. This mutant had cell walls which apparently lacked 74-kDa muramidase-2 but which accumulated two proteolytic fragments of 32 and 43 kDa, which exhibited muramidase-2 activity in the membrane fraction. By complementation cloning, we identified a 2.6-kb fragment of the E. hirae chromosome containing a gene cluster coding for proteins of 58 to 137 amino acids. One of these genes (arpU), which encoded a 15.9-kDa protein, was shown to complement the defect of the A9 mutant in trans. We propose that this gene may be involved in the regulation of muramidase-2 export.

Amino Acid Sequence↗
PubMed1995

Structure-activity relationship of new 2-substituted penem antibiotics.

The antibacterial activities of three new penems with 4-hydroxyprolinamide, 1-prolinamide and N-methyl-N-2-propionamide substituents, respectively, in position 2 and of their stereoisomers were examined against Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Escherichia coli and Pseudomonas aeruginosa. All substitutes conferred a broad antibacterial spectrum on the penem moiety. Changes in stereoisomerism selectively improved the activity against E. coli, S. aureus or enterococci. The structure-activity relationships of each compound were discussed in relation to minimum inhibitory concentrations, penicillin-binding protein (PBP) affinity and outer membrane permeability coefficient in E. coli. In this microorganism, PBP 2 was the target for all compounds. Changes in stereoisomerism influenced the affinity for PBPs 1A/B and 2. All antibiotics easily permeated the outer membrane of E. coli and, within each group of compounds, the penetration rate correlated with the antibacterial activity.

Anti-Bacterial Agents↗
PubMed1995

"High risk" anterior basal skull fractures. Surgical treatment of 64 consecutive cases.

Anterior Basal Skull Fractures (ABSFs) may be complicated by Cerebrospinal Fluid (CSF) fistulae and intracranial infections. An initially non-operative management is usually suggested since most fistulae spontaneously stop within a few days thus requiring no surgical repair. However, if the fistula fails to stop or recurs, surgical treatment is to be considered. Furthermore, if the fracture is complicated by meningitis, there is a relative risk of recurring infections and surgical repair may be also considered. Finally, surgical repair may be suggested in cases of compound, comminuted, depressed, largely extended cranio-facial fractures (the so-called "fracas craniofaciaux") where spontaneous healing is considered unlikely and risk of infection is high. Accordingly we termed "high risk" fractures those associated with active (persistent or recurring) cerebrospinal fluid fistula, those with meningitis and the so-called "fracas craniofaciaux". In this paper, we report our personal experience in surgical treatment of 64 consecutive "high risk" anterior basal skull fractures. Thirty-seven patients had persistent or recurring fistulae, ten had intracranial infections and seventeen had severe bone derangement of the anterior skull base. The osteodural repairs were performed through bilateral or unilateral subfrontal approach. In 59 cases the initial procedure was successful whereas 4 patient needed additional surgery but were ultimately successfully treated. One patient died. No major permanent neurologic or neuropsychologic impairments were reported. On the basis of our experience, we think that intracranial repair is a very suitable treatment modality in facing "high risk" anterior basal skull fractures.

Aged↗
PubMed1994

Leptomeningeal dissemination of juvenile pilocytic astrocytoma: case report.

The authors report a case of leptomeningeal spinal metastasis of chiasmatic juvenile pilocytic astrocytoma. A 7-year-old boy underwent surgery and radiation therapy for a chiasmatic pilocytic astrocytoma. Three years later he experienced a syndrome of medullary compression. A lumbosacral intradural extra-axial tumor was discovered and subtotally excised. Pathologic examination revealed a metastasis of the chiasmatic tumor without any evidence of malignant transformation. Only five cases of leptomeningeal spinal dissemination of pilocytic astrocytoma have been previously reported. The authors review and discuss the clinical and pathologic features of these cases.

Astrocytoma↗