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Biomedical subjects

L Silvestri

Publications and source records attributed to L Silvestri.

At least 19 recordsLinked to original sources
PubMed2005

Ultrafast all optical switching via tunable Fano interference.

Tunneling induced quantum interference experienced by an incident probe in asymmetric double quantum wells can easily be modulated by means of an external control light beam. This phenomenon, which is here examined within the dressed-state picture, can be exploited to devise a novel all-optical ultrafast switch. For a suitably designed semiconductor heterostructure, the switch is found to exhibit frequency bandwidths of the order of 0.1 THz and response and recovery times of about 1 ps.

Journal Article↗
PubMed2005

Handwashing in the intensive care unit: a big measure with modest effects.

Handwashing is widely accepted as the cornerstone of infection control in the intensive care unit. Nosocomial infections are frequently viewed as an indicator of poor compliance of handwashing. The aim of this review is to evaluate the effectiveness of handwashing on infection rates in the intensive care unit, and to analyse the failure of handwashing. A literature search identified nine studies that evaluated the impact of handwashing or hand hygiene on infection rates, and demonstrated a low level of evidence for the efforts to control infection with handwashing. Poor compliance cannot be blamed as the only reason for the failure of handwashing to control infection. Handwashing on its own does not abolish, but only reduces transmission, as it is dependent on the bacterial load on the hand of healthcare workers. Finally, recent studies, using surveillance cultures of throat and rectum, have shown that, under ideal circumstances, handwashing can only influence 40% of all intensive care unit infections. A randomised clinical trial with the intensive care as randomisation unit is required to support handwashing as the cornerstone of infection control.

Clinical Trials as Topic↗
PubMed2005

Control of imported and acquired methicillin-resistant Staphylococcus aureus (MRSA) in mechanically ventilated patients: a dose-response study of enteral vancomycin to reduce absolute carriage and infection.

This study aimed to quantify the animate source provided by the patients using the concept of "absolute carriage" by multiplying the carrier rate by the level of carriage; and to compare the impact of a low and high dose of an oropharyngeal vancomycin gel on the absolute MRSA carriage and infection. In all, 265 patients were included, 126 were MRSA positive. Fifty-five patients received 2% vancomycin gel during the first year whilst 4% vancomycin gel was given to 50 patients during the second year. Surveillance swabs of throat and rectum were obtained from all eligible patients on admission and then twice weekly. The vancomycin protocol was started as soon as the surveillance cultures were positive for MRSA. Those patients received one gram of enteral vancomycin daily, divided into four doses. During the first year 2% vancomycin gel 4 ml (80 mg) was applied in the oropharynx in four doses in addition to the enteral solution (Group A). During the second year 4% vancomycin gel 4 ml (160 mg) was used (Group B). The absolute carriage was high during both periods: 3.6 for Group A, and 3.2 for Group B. The 4% vancomycin protocol significantly reduced the absolute carriage, compared to the 2% vancomycin protocol: 2.6 versus 1.5 (P < 0.01). Significant reduction in secondary endogenous infections was found in the second year: seven versus 15 patients (P < 0.05). A total of 3,588 microbiological samples were processed. Neither Staphylococcus aureus with intermediate sensitivity to vancomycin (VISA) nor vancomycin-resistant enterococci (VRE) were detected.

Administration, Rectal↗
PubMed2004

Prevention of MRSA pneumonia by oral vancomycin decontamination: a randomised trial.

This study was undertaken to assess whether oropharyngeal vancomycin may control oropharyngeal carriage and lower airway infection due to methicillin-resistant Staphylococcus aureus (MRSA) acquired in the intensive care unit (ICU). Secondary endpoints were the emergence of vancomycin-resistant enterococci, vancomycin-intermediate S. aureus and vancomycin consumption. A total of 84 patients, admitted to a medical/surgical ICU and mechanically ventilated for >72 h, were randomly assigned to control (n=42) or test (n=42) group. Both groups received the protocol of selective decontamination of the digestive tract, including polymyxin E, tobramycin and amphotericin B. Patients in the test group received 0.5 g of a 4% vancomycin gel at 6-h intervals in the oropharynx. Lower airway infections due to MRSA acquired on the ICU were reduced in the test group, as was oropharyngeal carriage. Neither vancomycin-resistant enterococci nor vancomycin-intermediate S. aureus were isolated from either surveillance or diagnostic samples during the study period. The vancomycin costs were lower in the test group. This study demonstrates that oropharyngeal vancomycin, which controls intensive care unit-acquired lower airway infections and secondary carriage due to methicillin-resistant Staphylococcus aureus, is cost-effective and safe in terms of vancomycin-resistant enterococci and vancomycin-intermediate Staphylococcus aureus.

Administration, Oral↗
PubMed2002

Structure-function studies of analogues of parathyroid hormone (PTH)-1-34 containing beta-amino acid residues in positions 11-13.

The 1-34 N-terminal fragments of human parathyroid hormone (PTH) and PTH-related protein (PTHrP) elicit the full spectrum of bone-relevant activities characteristic of the intact hormones. The structural elements believed to be required for receptor binding and biological activity are two helical segments, one N-terminal and one C-terminal, connected by hinges or flexible points located around positions 12 and 19. To test this hypothesis, we synthesized and characterized the following analogues of PTH-(1-34), each containing single or double substitutions with beta-amino acid residues around the putative hinge located at position 12: I. [Nle(8,18),beta-Ala(11,12),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); II. [Nle(8,18),beta-Ala(12,13),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); III. [Nle(8,18),beta-Ala(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); IV. [Nle(8,18),beta-hLeu(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); V. [Nle(8,18),beta-Ala(12), Nal(23),Tyr(34)]bPTH-(1-34)NH(2); VI. [Nle(8,18),beta-Ala(13), Nal(23),Tyr(34)]bPTH-(1-34)NH(2) (beta-hLeu = beta-homo-leucine; beta-Ala = beta-alanine; Nal = L-2-naphthyl-alanine; Nle = norleucine). Analogues I and III exhibit very low binding affinity and are devoid of adenylyl cyclase activity. Analogue II, despite its very low binding capacity is an agonist. Biological activity and binding capacity are partially restored in analogue IV, and completely restored in analogues V and VI. The conformational properties of the analogues were investigated in aqueous solution containing dodecylphosphocholine (DPC) micelles as a membrane-mimetic environment using CD, 2D-NMR, and molecular dynamics calculations. All peptides fold partially into the alpha-helical conformation in the presence of DPC micelles, with a maximum helix content in the range of 30-35%. NMR analysis reveals the presence of two helical segments, one N-terminal and one C-terminal, as a common structural motif in all analogues. Incorporation of beta-Ala dyads at positions 11,12 and 12,13 in analogues I and II, respectively, enhances the conformational disorder in this portion of the sequence but also destabilizes the N-terminal helix. This could be one of the possible reasons for the lack of biological activity in these analogues. The partial recovery of binding affinity and biological activity in analogue IV, compared to the structurally similar analogue III, is clearly the consequence of the reintroduction of Leu side-chain of the native sequence. In the fully active analogues V and VI, the helix stability at the N-terminus is further increased. Taken together, these results stress the functional importance of the conformational stability of the helical activation domain in PTH-(1-34). Contrary to expectation, insertion of a single beta-amino acid residue in positions 11, 12, or 13 in analogues III-VI does not favor a disordered structure in this portion of the sequence.

Amino Acid Sequence↗
PubMed2002

Most nosocomial pneumonias are not due to nosocomial bacteria in ventilated patients. Evaluation of the accuracy of the 48 h time cut-off using carriage as the gold standard.

A prospective observational cohort study was undertaken with two endpoints: (1) to compare the time cut-off of 48h and the carrier state criterion for classifying lower airway infections in adult and paediatric long-term ventilated patients, and (2) to evaluate the potential of optimized time cut-offs for characterizing imported and ICU-acquired lower airway infections. All patients admitted to the general and paediatric intensive care units and expected to require mechanical ventilation for a period > or = 3 days were enrolled. Surveillance cultures of throat and rectum were obtained on admission and thereafter twice weekly to distinguish micro-organisms that were imported into the unit from those acquired during the stay on the unit. A total of 130 adults and 400 children were studied. In the adult population, 70% of lower airway infections were classified as ICU-acquired by the 48 h cut-off and 48% by the criterion of carriage; on the paediatric ICU the percentages were 65% and 20%, respectively. To separate imported from ICU-acquired infections, eight days was optimal in the adult population and 10 days in the paediatric population. Sensitivity, specificity, positive predictive value and negative predictive value for a time cut-off of eight days for adults were 86, 77, 80, 83%, respectively, and using 10 days for children were 87, 62, 90, 56%, respectively. The use of the 48 h cut-off rule classifies patients as having nosocomial pneumonia, when in fact the infections are commonly caused by microorganisms carried in by the patients. In contrast, using the carriage method, the proportion of lung infections due to nosocomial bacteria was relatively small and was a late phenomenon. Although in prolonging the time cut-off the difference between the two types of classification was shorter, time cut-offs were still found to be unreliable for distinguishing imported from unit-acquired lower airway infections.

Adult↗
PubMed2001

Mechanism of cyclosporin-induced inhibition of intracellular collagen degradation.

The immunosuppressant cyclosporin A (CsA) markedly inhibits collagen degradation by an intracellular phagocytic pathway in fibroblasts, an effect that can lead to massive gingival overgrowth. We used a collagen bead model of collagen phagocytosis to determine whether CsA inhibits internalization by blocking efflux of calcium from endoplasmic reticulum (ER) and mitochondrial calcium stores. CsA caused dose-dependent inhibition of phagocytosis of collagen-coated (but not bovine serum albumin-coated) beads. Chelation of intracellular Ca(2+) with BAPTA/AM or inhibition of Ca(2+)-ATPase of ER stores with thapsigargin reduced collagen bead phagocytosis. Measurement of intracellular calcium by ratio fluorometry showed increases in response to collagen-coated beads. Preincubation with CsA or thapsigargin caused a >3-fold decrease in intracellular calcium elevations in response to stimulation with collagen beads. Direct measurements of Ca(2+) in mitochondrial and ER stores showed that CsA only slightly inhibited collagen bead-induced discharge of calcium from mitochondria, but almost completely blocked discharge from ER stores. We reduced the numbers of mitochondria with chronic ethidium bromide treatment to test for the importance of ER/mitochondrial interactions. In these cells, CsA delayed collagen bead-induced calcium discharge from mitochondria. Collectively, these data indicate that CsA inhibits collagen phagocytosis by blocking calcium release from ER stores and may perturb functional interactions between the ER and mitochondria that regulate calcium stores.

Animals↗
PubMed2000

Conformational studies of parathyroid hormone (PTH)/PTH-related protein (PTHrp) chimeric peptides.

The N-terminal 1-34 segments of both parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) bind and activate the same membrane-embedded G protein-coupled receptor (PTH1 Rc) present on the surface of cells in target tissues such as bone and kidney. This binding occurs in spite of major differences between the two hormones in their amino acid sequence. Recently, it was shown that in (1-34) PTH/PTHrP hybrid peptides, the N-terminal 1-14 segment of PTHrP is incompatible with the C-terminal 15-34 region of PTH in terms of bioactivity. The sites of incompatibility were identified at positions 5 in PTHrP and 19 in PTH. In the present paper we describe the synthesis, biological evaluation, and conformational characterization of two segmental hybrids: PTHrP(1-27)-[Tyr(34)]bPTH(28-34)-NH(2) (hybrid I) and PTHrP(1-18)-[Nal(23), Tyr(34)]bPTH(19-34)-NH(2) (hybrid II). Hybrid I is as active as PTH(1-34)NH(2) and more than two orders of magnitude more active than hybrid II. The conformational properties of the hybrids were studied in water/trifluoroethanol (TFE) mixtures and in aqueous solutions containing dodecylphosphocholine (DPC) micelles by CD, two-dimensional nmr and computer simulations. Upon addition of TFE to the aqueous solution, both hybrids undergo a coil-helix transition. The helix content in 1:1 water/TFE obtained by CD data is about 75% for both hybrids. In the presence of DPC, helix formation is observed at detergent concentrations above critical micellar concentration and the maximum helix content is of approximately 35 and approximately 30% for hybrid I and II, respectively. Combined nmr analysis, distance geometry, and molecular dynamics calculations suggest that, in both solvent systems, the biologically active hybrid I exhibits two flexible sites, centered at residues 12 and 19, connecting helical segments. The flexibility point at position 19 is not present in the poorly active hybrid II. Our findings support the hypothesis, proposed in our previous work, that in bioactive PTH analogues the presence and location of flexibility points between helical segments are essential for enabling them to fold into the bioactive conformation upon interaction with the PTH1 receptor.

Circular Dichroism↗
PubMed2000

Selective decontamination of the digestive tract: a life saver.

Selective decontamination of the digestive tract (SDD), a strategy designed to prevent or minimize the impact of infection by potentially pathogenic micro-organisms in critically ill patients requiring long-term mechanical ventilation, comprises four component protocols, aiming to control the three types of infection occurring in such cases: (i) a parenteral antibiotic, cefotaxime, administered for a few days to prevent primary endogenous infections typically occurring 'early'; (ii) the topical antimicrobials polymyxin E, tobramycin and amphotericin B employed throughout the stay in the intensive care unit to prevent secondary endogenous infections tending to develop 'late'; (iii) a high standard of hygiene to prevent exogenous infections that may occur throughout the stay in the intensive care unit; (iv) surveillance samples of throat and rectum to distinguish between these three types of infection, to monitor the compliance and the efficacy of the treatment, and to detect the emergence of resistance at an early stage. A recent, rigorous, meta-analysis examining 33 randomized SDD trials involving 5727 patients demonstrated a significant reduction in overall mortality (20%) and in the incidence of respiratory tract infections (65%); conclusive evidence that SDD saves the lives of critically ill patients and confirmation that SDD is now an evidence based medicine manoeuvre. This same meta-analysis found no instance of the emergence of resistance or of associated superinfections and/or outbreaks in any of the 33 studies during a period extending upwards of 10 years. By the criterion of cost-per-survivor, four recent randomized trials showed that patient survival is improved more cheaply by employing SDD than by the traditional approaches.

Antibiotic Prophylaxis↗
PubMed2000

[Registry of genetic and malformative diseases in the province of Macerata].

OBJECTIVES: The aim of this epidemiological research is to evaluate the prevalence of genetic diseases and malformative syndromes in paediatric population living in the Macerata county. MATERIAL AND METHODS: All the data were collected through a careful analysis of a specific questionnaire sent to all the family paediatricians. RESULTS: 23,379 children living in Macerata county, aged 0 to 9 years, were evaluated (93.8% of all this paediatric population). Among those were found N 400 cases of genetic diseases and malformative syndromes: Malformations Tot.N. 255 cases (63.3% of the reported cases); Malformative Syndromes Tot. N. 55 cases (27.8% of the reported cases); Endocrinology and Metabolic Diseases Tot. N. 41 cases (10.3% of the reported cases); Osteochondrodysplasia Tot. N. 22 cases (5.7% of the reported cases); Other Tot. N. 28 cases (7.0% of the reported cases); Male population was found more affected than female: M/F ratio = 1.4. The analysis of the data showed an increasing trend in detecting these pathological conditions, consistent with the increase in geographic altitude (3 areas considered): 0-100 meter = 0.88%; 100-600 m.a.s. = 1.34%; over 600 m.a.s. = 1.88%. CONCLUSION: The knowledge of the number of children affected by genetic and malformative diseases in the Macerata county is relevant in order to establish a Genetic Service with the aim to better support the medical assistance of these patients and counselling service for the families.

Child↗