Biomedical subjects

A Gabrielli

Publications and source records attributed to A Gabrielli.

At least 19 recordsLinked to original sources

PubMed2002

Probabilistic approach to the Bak-Sneppen model.

We study here the Bak-Sneppen model, a prototype model for the study of self-organized criticality. In this model several species interact and undergo extinction with a power-law distribution of activity bursts. Species are defined through their "fitness" whose distribution in the system is uniform above a certain threshold. Run time statistics is introduced for the analysis of the dynamics in order to explain the peculiar properties of the model. This approach based on conditional probability theory, takes into account the correlations due to memory effects. In this way, we may compute analytically the value of the fitness threshold with the desired precision. This represents a substantial improvement with respect to the traditional mean field approach.

Journal Article↗

PubMed2001

Field theory of self-organized fractal etching.

We propose a phenomenological field theoretical approach to the chemical etching of a disordered solid. The theory is based on a recently proposed dynamical etching model. Through the introduction of a set of Langevin equations for the model evolution, we are able to map the problem into a field theory related to isotropic percolation. To the best of the author's knowledge, this constitutes the first application of field theory to a problem of chemical dynamics. By using this mapping, many of the etching process critical properties are seen to be describable in terms of the percolation renormalization group fixed point. The emerging field theory has the peculiarity of being self-organized in the sense that without any parameter fine tuning the system develops fractal properties up to a certain scale controlled solely by the volume V of the etching solution. In the limit V-->infinity the upper cutoff goes to infinity and the system becomes scale invariant. We present also a finite size scaling analysis and discuss the relation of this particular etching mechanism to gradient percolation. Finally, the possibility of considering this mechanism as a generic path to self-organized criticality is analyzed, with the characteristics of being closely related to a real physical system and therefore more directly accessible to experiments.

Journal Article↗

PubMed2001

Perturbative approach to the Bak-Sneppen model.

We study the Bak-Sneppen model in the probabilistic framework of the run time statistics (RTS). This model has attracted a large interest for its simplicity being a prototype for the whole class of models showing self-organized criticality. The dynamics is characterized by a self-organization of almost all the species fitnesses above a nontrivial threshold value, and by a lack of spatial and temporal characteristic scales. This results in avalanches of activity power law distributed. In this Letter we use the RTS approach to compute the value of x(c), the value of the avalanche exponent tau, and the asymptotic distribution of minimal fitnesses.

Journal Article↗

PubMed2001

Oxidative stress in scleroderma: maintenance of scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway.

OBJECTIVE: To explore the role of reactive oxygen species (ROS) in the in vitro activation of skin fibroblasts from patients with systemic sclerosis (SSc). METHODS: Fibroblasts were obtained from involved skin of patients with limited or diffuse SSc. Oxidative activity imaging in living cells was carried out using confocal microscopy. Levels of O2- and H2O2 released from fibroblasts were estimated by the superoxide dismutase (SOD)-inhibitable cytochrome c reduction and homovanilic acid assays, respectively. To verify NADPH oxidase activation, the light membrane of fibroblasts was immunoblotted with an anti-p47phox-specific antibody. Fibroblasts were stimulated with various cytokines and growth factors to determine whether any of these factors modulate ROS generation. Cell proliferation was estimated by 3H-thymidine incorporation. Northern blot analysis was used to study alpha1 and alpha2 type I collagen gene expression. RESULTS: Unstimulated skin fibroblasts from SSc patients released more O2- and H2O2 in vitro through the NADPH oxidase complex pathway than did normal fibroblasts, since incubation of SSc fibroblasts with diphenylene iodonium, a flavoprotein inhibitor, suppressed the generation of ROS. This suppression was not seen with rotenone, a mitochondrial oxidase inhibitor, or allopurinol, a xanthine oxidase inhibitor. Furthermore, the cytosolic component of NADPH oxidase, p47phox, was translocated to the plasma membrane of resting SSc fibroblasts. A transient increase in ROS production was induced in normal but not in SSc fibroblasts by interleukin-1beta (IL-1beta), platelet-derived growth factor type BB (PDGF-BB), transforming growth factor beta1 (TGFbeta1), and H2O2. Treatment of normal and SSc fibroblasts with tumor necrosis factor a (TNFalpha), IL-2, IL-4, IL-6, IL-10, interferon-alpha (IFNalpha), IFNgamma, granulocyte-macrophage colony-stimulating factor (GM-CSP), G-CSF, or connective tissue growth factor (CTGF) had no effect on ROS generation. Constitutive ROS production by SSc fibroblasts was not inhibited when these cells were treated with catalase, SOD, IL-1 receptor antagonist, or antibodies blocking the effect of TGFbeta1, PDGF-BB, and other agonists (IL-4, IL-6, TNFalpha, CTGF). In contrast, treatment of SSc fibroblasts with the membrane-permeant antioxidant N-acetyl-L-cysteine inhibited ROS production, and this was accompanied by decreased proliferation of these cells and down-regulation of alpha1(I) and alpha2(I) collagen messenger RNA. CONCLUSION: The constitutive intracellular production of ROS by SSc fibroblasts derives from the activation of an NADPH oxidase-like system and is essential to fibroblast proliferation and expression of type I collagen genes in SSc cells. Our results also exclude O2-, H2O2, IL-1beta, TGFbeta1, PDGF-BB, IL-4, IL-6, TNFalpha, or CTGF as mediators of a positive, autocrine feedback mechanism of ROS generation.

Acetylcysteine↗

PubMed2001

The respiratory system during resuscitation: a review of the history, risk of infection during assisted ventilation, respiratory mechanics, and ventilation strategies for patients with an unprotected airway.

The fear of acquiring infectious diseases has resulted in reluctance among healthcare professionals and the lay public to perform mouth-to-mouth ventilation. However, the benefit of basic life support for a patient in cardiopulmonary or respiratory arrest greatly outweighs the risk for secondary infection in the rescuer or the patient. The distribution of ventilation volume between lungs and stomach in the unprotected airway depends on patient variables such as lower oesophageal sphincter pressure, airway resistance and respiratory system compliance, and the technique applied while performing basic or advanced airway support, such as head position, inflation flow rate and time, which determine upper airway pressure. The combination of these variables determines gas distribution between the lungs and the oesophagus and subsequently, the stomach. During bag-valve-mask ventilation of patients in respiratory or cardiac arrest with oxygen supplementation (> or = 40% oxygen), a tidal volume of 6-7 ml kg(-1) ( approximately 500 ml) given over 1-2 s until the chest rises is recommended. For bag-valve-mask ventilation with room-air, a tidal volume of 10 ml kg(-1) (700-1000 ml) in an adult given over 2 s until the chest rises clearly is recommended. During mouth-to-mouth ventilation, a breath over 2 s sufficient to make the chest rise clearly (a tidal volume of approximately 10 ml kg(-1) approximately 700-1000 ml in an adult) is recommended.

History, Ancient↗

PubMed2001

Early recognition of acute cardiovascular beriberi by interpretation of hemodynamics.

Acute fulminant cardiovascular beriberi is an acute thiamine deficiency, which, if not recognized and treated, can lead to high cardiac output failure and death. The symptoms of acute thiamine deficiency include severe lactacidemia, and the presence of a high cardiac output and extremely low oxygen consumption in a patient who is hemodynamically stable. In this case conference, we describe a patient who was diagnosed with acute cardiovascular beriberi.

Adult↗

PubMed2001

Diltiazem to treat sinus tachycardia in critically ill patients: a four-year experience.

OBJECTIVES: To determine whether an intravenous infusion of the calcium channel blocker diltiazem was effective and safe in treating sinus tachycardia in critically ill adult patients with contraindications to beta-blockers or in whom beta-blockers were ineffective. DESIGN: Retrospective chart review. SETTING: University medical center. PATIENTS: The records of 171 surgical intensive care unit patients with sinus tachycardia treated with intravenous diltiazem were evaluated. INTERVENTIONS: In all patients with sinus tachycardia (heart rate >100 beats/min), heart rate control with intravenous diltiazem was attempted after adequate intravascular volume expansion, pain, and anxiety control. In all patients, beta-blockade either was contraindicated or (in 7%) had failed. Intravenous diltiazem was administered as a slow 10-mg bolus dose (0.1-0.2 mg/kg ideal body weight), and then an infusion was started at 5 or 10 mg/hr and increased up to 30 mg/hr, as needed, to decrease heart rate to <100 beats/min. Variables retrospectively collected included demographic data, preinfusion blood pressure, mean arterial pressure, heart rate, and preinfusion pressure-rate quotients (pressure-rate quotient = mean arterial pressure / heart rate). Intravenous bolus dose, when given, and diltiazem infusion rate and time necessary to achieve the target heart rate also were recorded. The lowest heart rate recorded within 24 hrs from the initiation of the infusion and the time necessary to achieve the lowest heart rate after beginning the infusion were recorded. MEASUREMENTS AND RESULTS: Of 171 patients studied, 97 (56%) were classified as responders. Multiple linear regression suggested that response could be predicted by age, pressure-rate quotients, baseline mean arterial pressure, and central nervous system failure. In the responders, a heart rate <100 beats/min was achieved in an average of 2 hrs, at a mean diltiazem infusion of 13.3 mg/hr. The lowest rate reached by the responders in a 24-hr period averaged 86 beats/min and was achieved in 4.8 hrs with a mean infusion rate of 14.8 mg/hr. Both target and lowest rate values were statistically different from baseline heart rate. CONCLUSION: Diltiazem was effective in achieving short-term control of heart rate in 56% of the patients, virtually without adverse effects, where beta-blockade was contraindicated or ineffective.

Academic Medical Centers↗

PubMed2001

Mapping B-cell epitopes of hepatitis C virus E2 glycoprotein using human monoclonal antibodies from phage display libraries.

Clinical and experimental evidence indicates that the hepatitis C virus (HCV) E2 glycoprotein (HCV/E2) is the most promising candidate for the development of an effective anti-HCV vaccine. Identification of the human epitopes that are conserved among isolates and are able to elicit protective antibodies would constitute a significant step forward. This work describes the mapping of the B-cell epitopes present on the surface of HCV/E2, as recognized by the immune system during infection, by the analysis of the reciprocal interactions of a panel of human recombinant Fabs derived from an HCV-infected patient. Three unrelated epitopes recognized by antibodies with no neutralization-of-binding (NOB) activity were identified; a fourth, major epitope was defined as a clustering of minor epitopes recognized by Fabs endowed with strong NOB activity.

Antibodies, Monoclonal↗

PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. I. Clinical and epidemiological features of 290 patients from 19 centres.

OBJECTIVE: To investigate the existence of differences among European referral centres for systemic sclerosis (SSc) in the pattern of attendance and referral and in the clinical and therapeutical approaches. METHODS: In 1995 the European Scleroderma Study Group initiated a multicentre prospective one year study whose aim was to define the disease activity criteria in SSc. During the study period each participating European centre was asked to enroll consecutive patients satisfying American College of Rheumatology criteria for SSc and to fill out for each of them a standardised clinical chart. Patients from various centres were compared and differences in epidemiological, clinical, and therapeutical aspects were analysed. RESULTS: Nineteen different medical research centres consecutively recruited 290 patients. The patients could be divided into two subgroups: 173 with the limited (lSSc) and 117 with the diffuse (dSSc) form of the disease. The clinical and serological findings for the series of 290 patients seemed to be similar to data previously reported. However, when the data were analysed to elicit any differences between the participating centres, a high degree of variability emerged, in both epidemiological and clinical features and in the diagnostic and therapeutic approaches to the disease. CONCLUSIONS: The clinical approach to SSc, not only in different countries but also in different centres within the same country, is not yet standardised. To overcome this problem, it will be necessary for the scientific community to draw up a standardised procedure for the management of patients with SSc. This would provide a common research tool for different centres engaged in research on this complex disease.

Adolescent↗

PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes.

OBJECTIVE: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Adolescent↗

PubMed2001

Intravenous N-acetylcysteine for treatment of Raynaud's phenomenon secondary to systemic sclerosis: a pilot study.

OBJECTIVE: To assess the efficacy and tolerability of N-acetylcysteine (NAC) in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma; SSc). METHODS: Twenty-two patients with RP secondary to SSc were enrolled in a multicenter, open clinical trial lasting 11 weeks and conducted in winter. Primary outcome measures were frequency and severity of RP attacks, and number of digital ulcers. Secondary outcome measure was improvement in digital cold challenge test assessed by photoelectric plethysmography. Patients received a continuous 5 day intravenous infusion of NAC starting with a 2 h loading dose of 150 mg/kg subsequently adjusted to 15 mg/kg/h. RESULTS: All 22 patients completed the 5 day infusion and 20 of them the posttreatment followup. Both frequency and severity of RP attacks decreased significantly compared to pretreatment values. Active ulcers were significantly less numerous at all followup visits (25.18% of baseline count on Day 33 from the beginning of infusion). In the cold challenge test mean recovery time fell by 69.56%, 67.70%, 71.42%, and 71.05% on Days 12, 19. 33, and 61 from the beginning of treatment. Side effects were minor, easily controlled, and reversible. CONCLUSION: N-acetylcysteine appears to be safe for the treatment of RP secondary to SSc. These preliminary data warrant further controlled studies.

Acetylcysteine↗

PubMed2000

Biasing in Gaussian Random Fields and Galaxy Correlations.

In this Letter, we show that in a Gaussian random field, the correlation length-the typical size of correlated structures-does not change with biasing. We interpret the amplification of the correlation functions of subsets identified by different thresholds as being caused by the increasing sparseness of peaks over threshold. This clarifies a long-standing misconception in the literature. We also argue that this effect does not explain the observed increase of the amplitude of the correlation function xi(r) when galaxies of brighter luminosity or galaxy clusters of increasing richness are considered.

Journal Article↗

PubMed2000

Expression and production of the long pentraxin PTX3 in rheumatoid arthritis (RA).

PTX3 is a secreted molecule which consists of a C-terminal domain similar to classical pentraxins (e.g. C-reactive protein (CRP)) and of an unrelated N-terminal domain. Unlike the classical pentraxins, the long pentraxin PTX3 is expressed in response to IL-1beta and tumour necrosis factor-alpha (TNF-alpha), but not to IL-6, in various cell types. The present study was designed to investigate the expression of PTX3 in RA. Dissociated RA and osteoarthritis (OA) type B synoviocytes were cultured in the presence and in the absence of inflammatory cytokines. PTX3 mRNA expression in synoviocytes was evaluated by Northern analysis. PTX3 protein levels in synovial cell cultures and synovial fluid were estimated by ELISA, and PTX3 distribution in synovial tissues by immunohistochemical techniques. OA synoviocytes were induced to express high levels of PTX3 mRNA by TNF-alpha, but not by other cytokines including IL-1beta and IL-6. RA synoviocytes, unlike OA synoviocytes, constitutively expressed high levels of PTX3 in the absence of deliberate stimulation. The constitutive expression of PTX3 in RA synoviocytes was not modified by anti-TNF-alpha antibodies, IL-1 receptor antagonist or a combination of the two agents. In contrast, interferon-gamma and transforming growth factor-beta inhibited PTX3 constitutive expression in RA synoviocytes. The joint fluid from RA patients contained higher levels of immunoreactive PTX3 than controls and the synovial tissue contained endothelial cells and synoviocytes positive for PTX3 by immunohistochemistry. In conclusion, PTX3 may play a role in inflammatory circuits of RA, and its relevance as a marker of disease activity deserves further study.

Arthritis, Rheumatoid↗

PubMed2000

Anti-topoisomerase II alpha autoantibodies in systemic sclerosis-association with pulmonary hypertension and HLA-B35.

We have previously detected autoantibodies against topoisomerase II alpha (anti-topo II alpha) in sera from patients with idiopathic pulmonary fibrosis. To determine whether anti-topo II alpha is also present in systemic sclerosis (SSc) patients with pulmonary involvement, we screened sera from 92 patients and 34 healthy controls. Presence of anti-topo II alpha was investigated with respect to clinical and serological features, including the frequencies of HLA class I and II alleles. Anti-topo II alpha was detected in 20/92 (21.7%) patients. No association was found with either anti-topoisomerase I (Scl-70 or anti-topo I) or anti-centromere antibodies. However, anti-topo II alpha was associated with the presence of pulmonary hypertension (PHT) (as opposed to pulmonary fibrosis), and with a decrease of carbon monoxide diffusing capacity. Anti-topo II alpha was strongly associated with the presence of the class I antigen HLA-B35. No significant association was found with HLA class II antigens. HLA-B35 also turned out to be associated with the presence of PHT. These results indicate that in SSc patients, the presence of anti-topo II alpha is associated with PHT, and that the simultaneous presence of HLA-B35 seems to add to the risk of developing PHT.

Adult↗

PubMed2000

The traumatic airway: the anesthesiologist's role in the emergency room.

An approach to the airway is addressed in Table 1. A summary of induction/NMB agents and doses is given on Table 2; indications for the different agents are noted on Table 3. The central pharmacological issue is not that any one drug is universally preferred over another. Rather, it is key that one develop a thoughtful rationale for the drugs used, and a plan to get out of trouble if one is suddenly in the sinking situation of a patient with a difficult airway who cannot breathe on his or her own. The backup plan might involve the use of BVM ventilation, blind digital intubation, fiberoptic bronchoscope-aided intubation, retrograde techniques, light wand intubation, laryngeal mask airway techniques, posterior pharyngeal endotracheal tube placement ventilation, or a surgical airway. Most of these approaches are reviewed elsewhere.

Anesthesiology↗

PubMed2000

Surface hardening and self-organized fractality through etching of random solids

When a finite volume of etching solution is in contact with a disordered solid, complex dynamics of the solid-solution interface develop. If the etchant is consumed in the chemical reaction, the dynamics stop spontaneously on a self-similar fractal surface. As only the weakest sites are corroded, the solid surface gets progressively harder and harder. At the same time, it becomes rougher and rougher uncovering the critical spatial correlations typical of percolation. From this, the chemical process reveals the latent percolation criticality hidden in any random system. Recently, a simple minimal model was introduced by Sapoval et al. to describe this phenomenon. Through analytic and numerical study, we obtain a detailed description of the process. The time evolution of the solution corroding power and of the distribution of resistance of surface sites is studied in detail. This study explains the progressive hardening of the solid surface. Finally, this dynamical model appears to belong to the universality class of gradient percolation.

Journal Article↗

PubMed2000

Invasion percolation with temperature and the nature of self-organized criticality in real systems

In this paper we present a theoretical approach that allows us to describe the transition between critical and noncritical behavior when stocastic noise is introduced in extremal models with disorder. Namely, we show that the introduction of thermal noise in invasion percolation (IP) brings the system outside the critical point. This result suggests a possible definition of self-organized criticality systems as ordinary critical systems where the critical point corresponds to set to 0 one of the parameters. We recover both the IP and Eden models for T-->0 and T-->infinity, respectively. For small T we find a dynamical second-order transition with correlation length diverging when T-->0.

Journal Article↗

PubMed1999

A comparison of two antimicrobial-impregnated central venous catheters. Catheter Study Group.

BACKGROUND: The use of central venous catheters impregnated with either minocycline and rifampin or chlorhexidine and silver sulfadiazine reduces the rates of catheter colonization and catheter-related bloodstream infection as compared with the use of unimpregnated catheters. We compared the rates of catheter colonization and catheter-related bloodstream infection associated with these two kinds of antiinfective catheters. METHODS: We conducted a prospective, randomized clinical trial in 12 university-affiliated hospitals. High-risk adult patients in whom central venous catheters were expected to remain in place for three or more days were randomly assigned to undergo insertion of polyurethane, triple-lumen catheters impregnated with either minocycline and rifampin (on both the luminal and external surfaces) or chlorhexidine and silver sulfadiazine (on only the external surface). After their removal, the tips and subcutaneous segments of the catheters were cultured by both the roll-plate and the sonication methods. Peripheral-blood cultures were obtained if clinically indicated. RESULTS: Of 865 catheters inserted, 738 (85 percent) produced culture results that could be evaluated. The clinical characteristics of the patients and the risk factors for infection were similar in the two groups. Catheters impregnated with minocycline and rifampin were 1/3 as likely to be colonized as catheters impregnated with chlorhexidine and silver sulfadiazine (28 of 356 catheters [7.9 percent] vs. 87 of 382 [22.8 percent], P<0.001), and catheter-related bloodstream infection was 1/12 as likely in catheters impregnated with minocycline and rifampin (1 of 356 [0.3 percent], vs. 13 of 382 [3.4 percent] for those impregnated with chlorhexidine and silver sulfadiazine; P<0.002). CONCLUSIONS: The use of central venous catheters impregnated with minocycline and rifampin is associated with a lower rate of infection than the use of catheters impregnated with chlorhexidine and silver sulfadiazine.

Analysis of Variance↗