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Biomedical subjects

S Esposito

Publications and source records attributed to S Esposito.

At least 37 records · Page 2Linked to original sources

What is the role of glycopeptides in intensive care?

Bacterial infections are the major cause of illness and death in the intensive care unit (ICU). In general, each unit is in itself a high risk environment for infections, simultaneously containing many diverse factors that favor the spread of clinically evident and generally serious infections: the constant presence of serious concomitant diseases, the frequent use of invasive diagnostic methods and procedures, the elevated selective pressure caused by multiple and prolonged antibiotic treatment on endogenous and environmental microbial flora. Notwithstanding the fact that the bacterial epidemiology of the ICU varies slightly in different countries and in different ICUs, in the last 15 years a general and progressive increase in the etiology of Gram-positive aerobic bacteria has been observed. Currently, Staphylococcus aureus is the etiologic agent most frequently responsible for infections in the ICU; S. aureus + coagulase-negative Staphylococcus (CoNS) + Enterococcus are responsible for more than 60% of infections. More recent data confirm that next to modifications in bacterial etiology in the ICU, the most alarming phenomenon is the methicillin-resistance of S. aureus (MRSA). The high percentage of multi-resistance compels us to reconsider therapy relative to the choice of antibiotics to use and, in particular, raises the question of possibly selecting the class of glycopeptides, alone or in combination, as the choice of treatment every time that an infection is caused by a Gram-positive microorganism. The use of glycopeptides, as with all antibiotics, must be evaluated in a suitable manner with the objective of limiting the selective pressure on resistant bacterial flora caused by their use. It is widely understood that inappropriate use of antibiotics, such as selecting an antibacterial agent with an inadequate spectrum that is thus ineffective, determines an increase in the mortality rate compared to using an agent with an appropriate spectrum of activity.

Anti-Bacterial Agents↗

Recurrent respiratory tract infections in pediatric age: a population-based survey of the therapeutic role of macrolides.

In order to evaluate the efficacy of macrolides in pediatric patients with recurrent respiratory tract infections (RRTIs), we enrolled 1,706 children (783 females) aged between 6 months and 14 years (median: 4 years) with an acute respiratory infection and a history of RRTIs (> or = 8 episodes per year if aged < 3 years; > or = 6 episodes per year if aged > or = 3 years). The therapies were chosen by the primary care pediatricians and their effects on respiratory relapses were blindly analyzed. Regardless of age and clinical diagnosis, the children treated with macrolides showed a significantly higher rate of short- and long-term clinical success than those receiving beta-lactams (p<0.0001) or symptomatics alone (p<0.0001). These data show that macrolide therapy of acute respiratory infections influences the natural history of RRTIs, probably because of their elective activity on atypical bacteria. They also suggest the possible importance of these pathogens in causing recurrences of respiratory infections in children and show that the infections they cause may have a more complicated course unless treated with adequate antibacterial drugs.

Acute Disease↗

Modification of patients' endogenous bacterial flora during hospitalization in a large teaching hospital in Naples.

The increasing attention addressed to methicillin-resistant staphylococci, vancomycin-resistant enterococci (VRE) and Extended Spectrum beta-Lactamases (ESbetaL)-producing enterobacteria is due to their etiologic role especially in nosocomial infections. In March 2001 we started an 8-month microbiological prospective surveillance of patients in the General Surgery, Orthopedic and Obstetric & Gynecology wards of the Azienda Universitaria Policlinico, 2nd University of Naples, Italy, to monitor the possible changes in endogenous flora during patients' hospital stay and the possible emergence of bacterial resistance. Data concerning antibiotic surgical prophylaxis (antimicrobial agent and duration) and length of hospitalization (pre- and post-surgery) were also collected. All patients underwent a microbiological screening by culturing nasal, pharyngeal and rectal swabs performed at admission and during hospitalization. Overall, 526 nasal swabs, 506 pharyngeal swabs and 482 rectal swabs were performed. Methicillin-resistant staphylococci were isolated from nasal swabs at admission in 2.1% of patients and in 7.5% of patients during hospitalization (day-14). VRE and ESbetaL-producing strains were isolated from rectal swabs in 1.9 and 4.7% of patients, respectively, with no change during hospital stay. Nasal and pharyngeal flora significantly changed after 7-14 days of hospitalization, Gram-negative microorganisms being isolated more frequently following hospitalization. The authors conclude that excessive hospital stay duration, along with the inappropriate duration of surgical antibiotic prophylaxis could be important causes of bacterial flora modification.

Adult↗

Emerging role of Mycoplasma pneumoniae in children with acute pharyngitis.

In order to define the role, the risk factors, and the clinical and laboratory characteristics of Mycoplasma pneumoniae infection in children with pharyngitis, 184 patients with acute non-streptococcal pharyngitis (102 males; median age, 5.33 years) were studied. Acute Mycoplasma pneumoniae infection was demonstrated in 44 (23.9%) patients. A history of recurrent episodes of pharyngitis (defined as at least 3 acute episodes of pharyngitis in the 6 months preceding enrollment) appeared to be the more useful parameter for differentiating Mycoplasma pneumoniae pharyngitis from non-streptococcal non- Mycoplasma pneumoniae pharyngitis ( P<0.05 in multivariate analysis). These data, which highlight the emerging role of Mycoplasma pneumoniae in acute pharyngitis, must be taken into account in the diagnosis and treatment of this clinical manifestation in children.

Acute Disease↗

Medial degeneration does not involve uniformly the whole ascending aorta: morphological, biochemical and clinical correlations.

OBJECTIVE: To investigate whether and how the severity of medial degeneration (MD) lesions varies along the circumference of the dilated intrapericardial aorta. METHODS: Two groups of aortic wall specimens, respectively harvested 1cm distal to the non-coronary (NC) sinus (right postero-lateral wall) and to the right coronary sinus (anterior wall) in 22 patients undergoing surgery for dilatation of the intrapericardial aorta associated with aortic valve disease, were separately sent for pathology, morphometry and ultrastructural examination. MD lesions found at histology were classified into three degrees of severity. MD mean degree and morphometric findings in postero-lateral ('NC') and anterior ('coronary') specimens were compared by paired t-test. Correlation between degree of aortic dilatation at echocardiography and severity of MD was assessed separately for each of the two groups of specimens. After the preliminary results of the morphological study, we decided to send the specimens for biochemical investigation of protein electrophoretic patterns. This was performed in the last seven patients of this series. RESULTS: At histology, MD was found in all cases. A higher mean MD degree was found in the NC group (2.59+/-0.50 versus 1.59+/-0.67 in the coronary group; P<0.001). At morphometry, normal smooth muscle cells in the NC specimens were significantly reduced (P=0.012) and the length (P=0.011) and number (P=0.015) of elastic fibres reduced and increased, respectively. Correlation between aortic ratio and MD degree was significant in the NC specimens (P<0.001), not in the coronary ones (P=0.227). Quantitative differences between coronary and NC proteins from the same patient and between coronary proteins from different patients were found at electrophoresis. However, at this stage of the study, the sample was too small to allow for the identification of proteins involved in those differences. CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the right postero-lateral wall area, likely due to haemodynamic stress asymmetry.

Adult↗

[Treatment of Helicobacter pylori in children].

BACKGROUND: There are very few studies that compare therapeutic protocols against H. pylori infection in children and the few available data derive from studies that usually evaluate the remission of symptoms or the accuracy of diagnostic procedures before and after treatment. Furthermore, no randomised, controlled clinical trials using placebo have been carried out in children. METHODS: We systematically collected data from the pediatric literature on the treatment of H. pylori to assess the efficacy of various treatments. This review included all articles and letters published since 1987 and all abstracts presented at the three main international meetings from 1997 to 1999. The results of studies published in English and French journals were collected and analysed. RESULTS: We only found 30 articles and 17 abstracts containing results on the treatment of H. pylori, carried out respectively in a total of 870 and 1552 children. All the data collected seemed to indicate that single-therapy or dual therapy with an antisecretory drug combined with an antibiotic showed a low level of efficacy. Dual therapy proved effective, in the form of bismuth and one antibiotic (amoxycillin or a nitroimidazole) or two antibiotics when administered for two or more weeks. The same was true of triple therapy based on bismuth or a proton pump inhibitor associated with two antibiotics. Triple therapies were less effective in children than in adults, and although triple therapies based on bismuth were more effective when administered for at least two weeks, the triple therapies based on a proton pump inhibitor showed a comparable level of efficacy irrespective of duration. CONCLUSIONS: Dual therapies in children using two antibiotics appear to have a similar efficacy as triple therapies, and if the latter contain a proton pump inhibitor, they show a similar efficacy irrespective of duration. For this reason, it does not seem necessary to administer them for more than one week.

English Abstract↗

Universal photonic tunneling time.

We consider photonic tunneling through evanescent regions and obtain general analytic expressions for the transit (phase) time tau (in the opaque barrier limit) in order to study the recently proposed "universality" property according to which tau is given by the reciprocal of the photon frequency. We consider different physical phenomena (corresponding to performed experiments) and show that such a property is only an approximation. In particular, we find that the "correction" factor is a constant term for total internal reflection and quarter-wave photonic band gap, while it is frequency dependent in the case of an undersized waveguide and distributed Bragg reflector. The comparison of our predictions with the experimental results shows quite good agreement with observations and reveals the range of applicability of the approximate "universality" property.

Journal Article↗

Role of Mycoplasma pneumoniae and Chlamydia pneumoniae in children with community-acquired lower respiratory tract infections.

In order to evaluate the role of Mycoplasma pneumoniae and Chlamydia pneumoniae, we studied 613 children aged 2-14 years who were hospitalized for community-acquired lower respiratory tract infections (LRTIs). The patients were enrolled in the study by 21 centers in different regions of Italy from May 1998 through April 1999. Paired serum samples were obtained on admission and after 4-6 weeks to assay the titers of M. pneumoniae and C. pneumoniae antibodies. Nasopharyngeal aspirates for the detection of M. pneumoniae and C. pneumoniae were obtained on admission. Acute M. pneumoniae infections in 210 patients (34.3%) and acute C. pneumoniae infections in 87 (14.1%) were diagnosed. Fifteen of the 18 children with M. pneumoniae and/or C. pneumoniae infections whose treatments were considered clinical failures 4-6 weeks after enrollment had not been treated with macrolides. Our study confirms that M. pneumoniae and/or C. pneumoniae plays a significant role in community-acquired LRTIs in children of all ages and that such infections have a more complicated course when not treated with adequate antimicrobial agents.

Acute Disease↗

Heparan N-sulfatase: in vitro mutagenesis of potential N-glycosylation sites.

Heparan N-sulfatase cDNA contains five potential N-glycosylation sites at Asn positions 41, 142, 151, 264, and 413. We used site-directed mutagenesis, substituting the codon of asparagine for glutamine, to eliminate selected glycosylation sites and then performed expression studies in COS-7 cells to determine the influence on the catalytic activity, lysosomal targeting, and glycosylation-phosphorylation of the enzyme. Elimination of site 5 did not affect significantly enzyme activity; elimination of sites 2 and 4 gave a partial reduction, while elimination of sites 1 and 3 resulted in drastic reduction of catalytic activity (25 and 14%, respectively, of normal values), indicating that glycosylation of asparagine 41 and asparagine 151 is essential for catalysis and/or enzyme stability. Wild type enzyme produced in the presence of tunicamycin was also inactive, indicating that glycosylation is required for acquisition of enzyme activity and/or for enzyme stability. Metabolic labeling of each mutant cDNA, transiently transfected into COS cells, showed that enzyme from mutants N142Q, N264Q, and N413Q appeared to be properly folded, as judged by its ability to be proteolytically processed to a lower molecular weight form, while enzyme from mutants N41Q and N151Q did not reach lysosomes. These studies confirm that the five glycosylation sites of heparan N-sulfatase are all functional and show that Asn 41 and Asn 151 have a role in protein folding and/or stability.

Amino Acid Substitution↗

Glucose-6-phosphate dehydrogenase in barley roots: kinetic properties and localisation of the isoforms.

Two different isoforms of glucose-6-phosphate dehydrogenase (Glc6PDH; EC 1.1.1.49) have been partially purified from barley (Hordeum vulgare L., cv. Alfeo) roots. The procedure included an ammonium sulfate step, Q-Sepharose and Reactive Blue agarose chromatography, and led to 60-fold and 150-fold purification for the two enzymes, respectively. The Glc6PDH 1 isoform accounts for 17% of total activity of the enzyme in roots, and is very sensitive to the effects of NADP+/NADPH ratio and dithiothreitol; the Glc6PDH 2 isoform is less affected by reducing power and represents 83% of the total activity. The isoforms showed distinct pH optima, isoelectric points, Km for glucose-6-phosphate and a different electrophoretic mobility. The kinetic properties for the two enzymes were affected by ATP and metabolites. Both enzymes are inhibited to different extents by ATP when magnesium is omitted from the assay mixture, whereas the addition of ATP-Mg2+ had no effect on Glc6PDH activities. The Glc6PDH isoforms are usually present in the plastids and cytosol of plant cells. To verify the intracellular locations of the enzymes purified from barley roots, Glc6PDH was purified from isolated barley root plastids; this isoform showed kinetic parameters coincident with those found for Glc6PDH 1, suggesting a plastid location; the enzyme purified from the soluble fraction had kinetic parameters resembling those of Glc6PDH 2, confirming that this isoform is present in the cytosol of barley roots.

Blotting, Western↗

Use of antimicrobial agents for community-acquired lower respiratory tract infections in hospitalised children.

Data collected from 613 children aged 2-14 years who had been hospitalized for acute bronchitis, wheezing, or pneumonia were analysed to evaluate the prescribing practices of pediatricians treating community-acquired lower respiratory tract infection. Antibiotics were prescribed for 92.1% of the children: 85% had acute bronchitis, 72% had wheezing, and 97.9% had pneumonia. A high frequency of antibiotic overuse and inappropriate prescriptions was noted. In order to contain costs and limit the risk of resistant bacteria emerging, it is urgent that pediatricians and parents be educated in the proper use of antibiotics.

Adolescent↗

Asymmetric medial degeneration of the intrapericardial aorta in aortic valve disease.

BACKGROUND: A geometrical and functional asymmetry in the normal aortic root has been recently demonstrated. Whether the distribution of medial degeneration (MD) within the wall of the dilated ascending aorta in adult patients reflects such asymmetry, still has to be assessed. METHODS: Nineteen patients with fibrocalcific aortic valve disease and dilatation of the intrapericardial aorta, without clinical signs and familiar history of primary elastic connective tissue disorders, underwent surgery. Biopsies (57 specimens) were taken in each patient from three areas of the ascending aortic wall distal to the three sinuses of Valsalva. MD lesions found at histology in each specimen were classified in three degrees. Comparisons were made between the three sites as to distribution of the three degrees and between one site and the other two as to incidence of the highest degree. RESULTS: A mild degree of MD was found in 26 specimens (45.6%), moderate in 14 (24.6%), severe in 17 (29.8%). The distribution of the three degrees of MD changes was significantly different between one of the three studied wall areas and the other two (P<0.001): a significantly greater incidence of the highest degree of involvement in the aortic wall distal to the non-coronary sinus than in the wall areas corresponding to the coronary sinuses was found (P<0.001). CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the wall area distal to the non-coronary sinus, likely due to haemodynamic stress asymmetry.

Adult↗

Management of upper respiratory tract infections in primary care in Italy: a national survey.

This prospective study, carried out in Italy during the winter of 1998 by the means of questionnaires, was designed to investigate the diagnostic and therapeutic approach of the Italian general practitioners (GPs) to the management of acute upper respiratory tract infections (URTIs) in adult outpatients. A total of 354 GPs were questioned about ten adult patients each who had visited the surgery with an URTI requiring an antibiotic prescription. Our data showed there was a tendency to prescribe antibiotics only on the basis of clinical diagnosis, microbiological investigations being required very rarely. Orally administered antibiotics were preferred and compliance with the number of daily doses strongly influenced the antibiotic prescription. In patients affected by more severe infections, injectable antibiotics were frequently prescribed.

Administration, Oral↗

Short-course therapy with cefaclor for treatment of streptococcal pharyngotonsillitis.

Short-course treatments for streptococcal pharyngotonsillitis with oral cephalosporins or macrolides have resulted in a similar bacteriological and clinical cure rate and better compliance compared with the conventional 10-day course. One hundred and thirty eight of 420 recruited patients had a positive culture for Streptococcus pyogenes and were randomly assigned to receive cefaclor (25 mg/kg/bid) for a 5-day (70 patients) or 10-day (68 patients) course. Patients were assessed clinically and bacteriologically 2-3 days after completing the course and followed up after 20-30 days. All 420 recruited patients belonged to a population of 2800 children who had been previously screened for a streptococcal carrier state to exclude carriers from final evaluation. Clinical cure and bacterial eradication was recorded in 92.8 and 92.6% of patients in groups A and B, respectively. Therefore, short-course therapy with cefaclor may offer an effective alternative treatment to conventional regimens, with potential for better compliance.

Cefaclor↗

Emerging role of Mycoplasma pneumoniae and Chlamydia pneumoniae in paediatric respiratory-tract infections.

Increased use of specialised diagnostic techniques over the past 10 years has allowed considerable new information to be obtained concerning Mycoplasma pneumoniae and Chlamydia pneumoniae infections. In children, these pathogens seem to have a more important role in causing respiratory-tract infections than previously thought; they have been associated with wheezing, and they are also frequent in children aged under 5 years. Contrary to original belief, no clinical, laboratory, or radiological findings seem to be unique to M. pneumoniae or C. pneumoniae; furthermore, there is no rapid and cost-effective diagnostic test capable of identifying these pathogens. Appropriate antimicrobial treatment of the infections they cause is needed to reduce the recurrent episodes of wheezing and other respiratory symptoms, to decrease morbidity, and to avoid the spread of the pathogens. However, a number of therapeutic issues remain unsolved.

Adolescent↗

In vitro activity of LY333328 (oritavancin) against Gram-positive aerobic cocci and synergy with ciprofloxacin against enterococci.

Gram-positive cocci are a major cause of nosocomial bacteraemias and are often resistant to most antibiotics. The emergence of enterococci with reduced susceptibility to vancomycin has created an urgent need for novel antibiotics to combat infections associated with these bacteria. In this study the in vitro activity of LY333328 (oritavancin), a semi-synthetic glycopeptide, was evaluated. LY333328 was effective against all strains of staphylococci, streptococci and enterococci tested. A combination of LY333328 and ciprofloxacin was additive for 50% of Enterococcus faecium strains resistant to both vancomycin and ciprofloxacin, and for 100% of vancomycin-susceptible and either ciprofloxacin-susceptible or -resistant strains.

Anti-Bacterial Agents↗