Regional point prevalence study of healthcare-associated infections and antimicrobial use in acute care hospitals in Liguria, Italy.

BACKGROUND: Given the importance of monitoring healthcare-associated infections (HCAIs) and the consumption of antibiotics, a regional point prevalence survey was conducted in Liguria between March and April 2016. AIM: To measure the overall prevalence of HCAI and describe the use of antibiotics in all public hospitals. METHODS: Data on risk factors and use of antibiotics were collected for each hospitalized patient. To define the variables significantly associated with HCAI, univariate and multivariate analyses were conducted. Standardized infection ratio and standardized antimicrobial use ratio were measured for each participating hospital. FINDINGS: A total of 3647 patients were enrolled. In all, 429 HCAIs were diagnosed in 376 patients, giving a prevalence of HCAI of 10.3%. Respiratory tract (21.7%) and urinary tract (20%) were the most frequent sites of infection. High rates of meticillin-resistant Staphylococcus aureus (47.4%) and Enterobacteriaceae resistant to carbapenems (26.3%) were isolated. Forty-six percent of patients received at least one antibiotic. Combinations of penicillins including ß-lactamase inhibitors (24.1%) were the most widely used; the main indication (46.7%) was the treatment of a community-acquired infection. CONCLUSION: There was an increase in HCAI prevalence compared to a similar survey conducted in 2007; however, the performance of overlapping investigations will enable more reliable considerations. Nevertheless, data on antimicrobial resistance and use of antibiotics are consistent with the national trend. Despite methodological limitations, prevalence studies are useful to monitor HCAI over time and encourage greater awareness of the problem by all stakeholders.

HLA-DQA1 and HLA-DQB1 genes in Tsachilas Indians from Ecuador: new insights in population analysis by Human Leukocyte Antigens.

Human Leucocyte Antigen (HLA) loci are widely known for their role in the generation of immune responses and are often considered to be effective in reconstructing human relationships. This is due to the high degree of polymorphism and the rarity of recombination observed at HLA loci. In this study, we have made an attempt to support the potential of HLA class II loci by analysing DQA1 and DQB1 in 52 Ecuadorians with ties to the Tsachilas community. Little is known about this populations either ethnologically or historically: they are considered retaining much of the ancient Chibchan culture in spite of the lack of significant genetic characterization. A total of 21 alleles were observed, with very low heterozygosity. The obtained data were then assessed for relationship reconstruction. The compiled database of 63 populations was segregated and resolved in clusters corresponding to the ethnogeographic distribution of the populations. This analysis of Central and Southern Amerindians allowed us to support a historical hypothesis related to the origin and migration of Ecuadorian people. Indeed, the relationships with neighbour human groups, especially Cayapas and Colombians, could shed light on the genetic similarity within ancient Chibchan culture that was dispersed by tribes coming up the Barbacoas. This indicates that if an appropriate analysis was to be carried out on a set of populations representative of different geographic locations, and that analysis was properly interpreted, then there would be a high possibility that HLA class II loci could infer accurate assessments, as revealed by uniparental markers.

Genetic response to an environmental pathogenic agent: HLA-DQ and onchocerciasis in northwestern Ecuador.

The aim of this study is to explore human leukocyte antigen (HLA)-DQ variability in two populations (Cayapas Amerindians and Afro-Ecuadorians) who live near one another along the Cayapa River and who are exposed to the same environmental stresses, such as infection by Onchocerca volvulus. HLA-DQA1 and HLA-DQB1 of 149 unrelated individuals (74 Cayapas and 75 Afro-Ecuadorians) have been analyzed. HLA high-resolution molecular typing was performed by sequence-based typing, sequence-specific oligonucleotides hybridization and sequence-specific primer (SSP) amplification. The comparison between affected (cases) and unaffected people (controls) in both populations shows the key role of several HLA-DQA1 alleles in susceptibility and protection against onchocerciasis. In both populations, there is strong evidence related to the protective role of DQA1*0401 against onchocerciasis. Alleles HLA-DQA1*0102 and *0103 seem to represent risk factors in Afro-Ecuadorians, while HLA-DQA1*0301 is only a suggestive susceptibility allele in Cayapas. These findings represent new positive/negative associations with onchocerciasis in South America, whereas previous findings pertained only to African populations.

FMRI activation with an "affective speech" paradigm in vegetative and minimally conscious States: applicability and prognostic value.

Vegetative state (VS) and minimally conscious state (MCS) are considered different clinical entities but their differential diagnosis remains challenging. Some VS patients can show an MCS-like activation in functional magnetic resonance imaging (fMRI) studies that seems to predict recovery from VS. We studied fMRI activation with an affective speech paradigm in a cohort of non-communicative brain-injured individuals consecutively admitted to a post-acute neurorehabilitation facility in five years. Among 93 eligible subjects, 65 met the clinical criteria for VS and 28 for MCS. Because of exclusion criteria, activation studies were performed in only 30 cases out of 93 and analysed in only 24 (about » of the eligible cases): 19 VS and five MCS patients. The passive acoustic stimulus consisted in a familiar voice narrating a significant episode in the patient's life, administered by nonmagnetic earphones. All the MCS patients showed an activation spread to secondary associative cortices but also 52.7% of the VS patients displayed an "atypical" large-scale activation pattern. Regarding the clinical outcome, 80% of the patients with large-scale network activation (LSNA) had some recovery of consciousness. Our results confirm that the VS patients with LSNA at fMRI study have potential for further recovery of consciousness, whereas no patient without activation or only typical activation improved. fMRI study with an affective speech paradigm, when applicable, seems to have a valuable prognostic value in VS patients, even if there are major limitations in terms of applicability.

Hospital-acquired infections and leading pathogens detected in a regional university adult acute-care hospital in Genoa, Liguria, Italy: results from a prevalence study.

BACKGROUND: A prevalence study aimed to update the epidemiological scenario of Hospital-Acquired Infections (HAI) was performed at the San Martino University Hospital of Genoa, the Regional Reference Adult-care Center in Liguria, Italy, with more than 1300 beds. MATERIALS AND METHODS: The investigation was performed in all the wards, except the Psychiatric Units, between 19th March and 6Ih April, 2007, using a one-day monitoring system for each ward. International standardized criteria and definitions for the surveillance of HAI were used for the collection of data, which were recorded in specific software for subsequent consolidation, analysis and quality control. RESULTS: The hospital infection control staff actively monitored 912 inpatients: a total of 84 HAI among 72 patients were diagnosed, with an overall prevalence of infections and affected cases of 9.2% (95% CI: 7.3-11.1) and 7.9% (95% CI: 6.1-9.7), respectively. Urinary Tract Infections (UTI) (30.9%), Respiratory Tract Infections (RTI) (28.6%) and Blood Stream Infections (BSI) (21.4%) were found to be the most frequent infections. As expected, both specific prevalence and localization of HAI varied considerably between wards, with the highest values recorded in Intensive Care Units (ICU) and in Functional Rehabilitation wards. RTI (26.3%) and BSI (13.2%) were found primarily represented in ICU, while the highest values of UTI (13.3%) were registered in Functional Rehabilitation Units. Enterococcus spp. (16.8%), Candida spp. (14%), Pseudomonas spp. (12.2), Staphylococcus aureus (10.7%), Escherichia coli (10.3%) and Coagulase-negative staphylococci (CNS) (9.3%) were the most frequent pathogens isolated. The overall rate of administration of antibiotics was 55.3% and penicillin (26.7%), cephalosporins (22.8%) and fluoroquinolones (17.9%) were found to be the leading antibacterial administered. CONCLUSION: Results of the present study have been, and are currently, used for orientating surveillance and control hospital policies, planning activities according to a rational and evidence-based approach.

Three-dimensional quantitative assessment of lung parenchyma in cystic fibrosis: preliminary results.

PURPOSE: The aim of this study was to assess the feasibility of three-dimensional (3D) reconstructions and quantitative analysis of the volume of each component of the lung with cystic fibrosis (CF). MATERIALS AND METHODS: Twenty-two patients with CF (mean age 17+/-8 years) were included in the study. The patients underwent an unenhanced single-slice spiral computed tomography (CT) chest scan with the following parameters: collimation 3 mm, table feed 6 mm x rot(-1), reconstruction interval 1 mm, soft tissue reconstruction kernel. Four image data sets were obtained: native axial slices, cine-mode display, virtual bronchographic volume-rendered images with algorithm for tissue transition display and virtual endoluminal views. The lungs were segmented manually from the hilum to the visceral pleura on the axial images, and the entire lung volume was calculated. A histogram was generated representing the fractional volume of tissues, the density of which was within a preset range. A curve was then obtained from the histogram. RESULTS: Native axial images and cine-mode display allowed complete evaluation of lung volumes. Virtual bronchography allowed a better assessment of the distribution of bronchiectasis. Virtual bronchoscopy was limited by the fact that it visualised only the surface, without differentiating mucus from the bronchial wall. Manual segmentation and generation of density-volume curves required 41+/-7 min for each lung. Three curve patterns were identified depending on disease severity. CONCLUSIONS: Volume-density analysis of lungs with CF is feasible. Its main advantage is that image analysis is not analogical, as the assessment is not performed using scoring systems or similar ordinal scales. This technique cannot differentiate acute from chronic findings, and the predictive value of the curve should be assessed.

Detection of gunshot residues on cadaveric skin using sodium rhodizonate and a counterstain.

We report a staining method for cadaveric tissue using sodium rhodizonate as a skin marker for gunshot residues and a counterstain for the surrounding connective tissue. We studied six well preserved subjects who had died of close range gunshot injury. Skin fragments were removed from the bullet entrance hole including both the disrupted area and adjacent macroscopically intact tissue. Because microscopic examination of postmortem material is difficult after histomorphologic alterations already have occurred as a consequence of postmortem tissue changes, it is necessary to use a staining method that, while detecting gunshot residues, can also make skin cell constituents recognizable from both qualitative and quantitative perspectives. Triphenylmethane dyes (acid fuchsin, aniline blue WS, light green SF yellowish, brilliant green and ethyl green) have proven appropriate for the purpose.

IRF-1 deficiency skews the differentiation of dendritic cells toward plasmacytoid and tolerogenic features.

Members of the IFN regulatory factors (IRFs) family are transcriptional regulators that play essential roles in the homeostasis and function of the immune system. Recent studies indicate a direct involvement of some members of the family in the development of different subsets of dendritic cells (DC). Here, we report that IRF-1 is a potent modulator of the development and functional maturation of DC. IRF-1-deficient mice (IRF-1(-/-)) exhibited a predominance of plasmacytoid DC and a selective reduction of conventional DC, especially the CD8alpha(+) subset. IRF-1(-/-) splenic DC were markedly impaired in their ability to produce proinflammatory cytokines such as IL-12. By contrast, they expressed high levels of IL-10, TGF-beta, and the tolerogenic enzyme indoleamine 2,3 dioxygenase. As a consequence, IRF-1(-/-) DC were unable to undergo full maturation and retained plasmacytoid and tolerogenic characteristics following virus infection ex vivo and in vivo. Accordingly, DC from IRF-1(-/-) mice were less efficient in stimulating the proliferation of allogeneic T cells and instead, induced an IL-10-mediated, suppressive activity in allogeneic CD4(+)CD25(+) regulatory T cells. Together, these results indicate that IRF-1 is a key regulator of DC differentiation and maturation, exerting a variety of effects on the functional activation and tolerogenic potential of these cells.

[Family pediatricians and obstructive sleep disorders]. / Il pediatra di famiglia e i disturbi respiratori ostruttivi nel sonno.

UNLABELLED: BREATHING: Problems related to the Obstructive Sleep Disordered Breathing (OSDB) are so many: 1) a noso- graphic setting has still to be defined and this leads to contrasting results concerning the prevalence of the OSDB; 2) the absence of a single pathogenetic trigger which can explain the sudden increase of the number of cases of the OSDB since the 1980's; 3) a poor integration between clinical and diagnostic tests; 4) a not well defined role of the family pediatrician in approaching the OSDB. OBJECTIVES: From the above introduction we can deduce four objectives of the study: 1) verifying the prevalence of the OSDB; 2) studying if an early development of the adenotonsillar tissues can influence the on-set of the OSDB; 3) a better definition of the clinical diagnosis; 4) knowing what decisions the family pediatrician do take as concerns the diagnostic tests and therapy. MATERIAL AND METHOD: This study was carried out on questionnaires completed by 8 family pediatricians which consisted of two parts: the first section regarded the whole population interviewed (2.271 children) and the second more specific was reserved only to the 42 children classified as affected by the OSDB. These 42 children presented at least 3 of the following 4 features during sleep: (1) the parents are worried about the way their child breaths (2) snoring (3) apnea (4) paradoxical rib cage movement in inspiration. RESULTS: The prevalence of the OSDB was 1.8%. However considering how suggested by some authors even those children who snored and also presented oral respiration, the prevalence increased to 10.3%. These values are similar to the international results with a prevalence of 2-3% for the more severe forms defined as Obstructive Sleep Apnea Syndromes (OSAS) and of 8-11% considering all the forms of the OSDB. Grouping these patients according to their ages, it resulted that the highest incidence of the OSDB was in children between 3-5 years. This observation supports the hypothesis that at the base of the OSDB is an early development of the adenotonsillar tissues, thus in constrast which the classical course which identifies the peak of adenotonsillar hypertrophy between 4 and 6 years of age. The frequency of the single signs and symptoms in the various ages permits the improvement of the clinical diagnosis: in particular snoring, oral respiration and tonsillar hypertrophy are less frequent in the first three years of life, while in the older children the percentage of growth inhibition decreased and it becomes more difficult observing paradoxical rib cage movement in inspiration. Concerning the diagnostic tests, the family pediatrician asks only exceptionally specific test during sleep (5% of the patients). Concerning therapy, many were the indications for adenotonsillectomy even during the first three years of age (82% of the patients) proving that the family paediatrician has overcome the old attitude of not indicating operation in the first 4-5 years of age. CONCLUSION: The confirmed high prevalence of the OSDB, the possibility of further improving the clinical diagnosis, the good capacity of the family pediatrician concerns diagnosis and therapy are all factors which favour the direct management of most of the children with adenotonsillar hypertrophy by the family pediatrician. The diagnosis and therapeutic choice can find support in sleep tests when necessary. These tests have to be carried out in a specialized laboratory and the results be interpreted together with the clinical signs and symptoms. Patients who have to be managed by Pediatric sleep laboratory are: 1) children with OSDB due to organic and functional alterations on genetic basis; 2) children in whom adenotonsillectomy presents a high risk such as a severe respiratory insufficiency and the young age of the patient (less 12-18 months of life).

Impaired myelopoiesis in mice devoid of interferon regulatory factor 1.

Interferon regulatory factor (IRF)-1 is a transcription factor controlling the expression of several genes, which are differentially induced depending on the cell type and signal. IRF-1 modulates multiple functions, including regulation of immune responses and host defence, cell growth, cytokine signalling and hematopoietic development. Here, we investigated the role of IRF-1 in granulocytic differentiation in mice with a null mutation in the IRF-1 gene. We show that IRF-1(-/-) bone marrow cells exhibit an increased number of immature granulocytic precursors, associated with a decreased number of mature granulocytic elements as compared to normal mice, suggestive of a defective maturation process. Clonogenetic analyses revealed a reduced number of CFU-G, CFU-M and CFU-GM colonies in IRF-1(-/-) mice, while the number of BFU-E/CFU-E colonies was unchanged. At the molecular level, the expression of CAAT-enhancer-binding protein (C/EBP)-epsilon, -alpha and PU.1 was substantially lower in the CD11b(+) cells from the bone marrow of IRF-1(-/-) mice as compared to cells from wild-type mice. These results, together with the fact that IRF-1 is markedly induced early during granulo-monocytic differentiation of CD34+ cells, highlight the pivotal role of IRF-1 in the early phases of myelopoiesis.

IRF regulation of HIV-1 long terminal repeat activity.

Interferon (IFN) regulatory factors (IRF) constitute a family of transcriptional activators and repressors implicated in multiple biologic processes, including regulation of immune responses and host defense, cytokine signalling, cell growth regulation, and hematopoietic development. All members are characterized by well-conserved DNA binding domains at the N-terminal region that recognize similar DNA sequences termed IRF-binding element/IFN-stimulated response element (IRF-E/ISRE) present on the promoter of the IFN-alpha/beta genes and of some IFN-stimulated genes (ISG). Recently, a sequence homologous to the ISRE has been identified downstream of the 5' human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR). This sequence is a binding site for IRF-1 and IRF-2. Deletion of the LTR-ISRE results in impaired LTR promoter activity and decreased synthesis of viral RNA and proteins. Here, we briefly summarize characteristics of IRF-1 and IRF-2 binding to the HIV-1 LTR-ISRE and the data obtained to date on the functionality of this cis-element and on the role of IRF in the regulation of HIV-1 LTR transcriptional activity.

Interferon-gamma receptor 2 expression as the deciding factor in human T, B, and myeloid cell proliferation or death.

The heterodimeric interferon (IFN)-gamma receptor (IFN-gammaR) is formed of two chains. Here we show that the binding chain (IFN-gammaR1) was highly expressed on the membranes of T, B, and myeloid cells. Conversely, the transducing chain (IFN-gammaR2) was highly expressed on the surfaces of myeloid cells, moderately expressed on B cells, and poorly expressed on the surfaces of T cells. Differential cell membrane expression of IFN-gammaR2 determined the number of receptor complexes that transduced the IFN-gamma signal and resulted in a different response to IFN-gamma. After IFN-gamma stimulation, high IFN-gammaR2 membrane expression induced rapid activation of signal transducer and activator of transcription-1 (STAT-1) and high levels of interferon regulatory factor-1 (IRF-1), which then triggered the apoptotic program. By contrast, low cell membrane expression resulted in slow activation of STAT-1, lower levels of IRF-1, and induction of proliferation. Because the forced expression of IFN-gammaR2 on T cells switched their response to IFN-gamma from proliferative to apoptotic, we concluded that the surface expression of IFN-gammaR2 determines whether a cell stimulated by IFN-gamma undergoes proliferation or apoptosis.

Ectopic expression of interferon regulatory factor-1 potentiates granulocytic differentiation.

Numerous transcription factors allow haematopoietic cells to respond to lineage- and stage-specific cytokines and to act as their effectors. It is increasingly evident that the interferon regulatory factor-1 (IRF-1) transcription factor can selectively regulate different sets of genes depending on the cell type and/or the nature of cellular stimuli, evoking distinct responses in each. In the present study, we investigated mechanisms underlying the differentiation-inducing properties of granulocytic colony-stimulating factor (G-CSF) and whether IRF transcription factors are functionally relevant in myeloid differentiation. Both normal human progenitors and murine 32Dcl3 myeloblasts induced to differentiate along the granulocytic pathway showed an up-regulation of IRF-1 expression. Ectopic expression of IRF-1 did not abrogate the growth factor requirement of 32Dcl3 cells, although a small percentage of cells that survived cytokine deprivation differentiated fully to neutrophils. Moreover, in the presence of G-CSF, granulocytic differentiation of IRF-1-expressing cells was accelerated, as assessed by morphology and expression of specific differentiation markers. Down-modulation of c-Myb protein and direct stimulation of lysozyme promoter activity by IRF-1 were also observed. Conversely, constitutive expression of IRF-2, a repressor of IRF-1 transcriptional activity, completely abrogated the G-CSF-induced neutrophilic maturation. We conclude that IRF-1 exerts a pivotal role in granulocytic differentiation and that its induction by G-CSF represents a limiting step in the early events of differentiation.

HHV-8 encoded vIRF-1 represses the interferon antiviral response by blocking IRF-3 recruitment of the CBP/p300 coactivators.

Human herpes virus 8 (HHV-8) has developed unique mechanisms for altering cellular proliferative and apoptotic control pathways by incorporating viral homologs to several cellular regulatory genes into its genome. One of the important pirated genes encoded by the ORF K9 reading frame is a viral homolog of the interferon regulatory factors (IRF), a family of cellular transcription proteins that regulates expression of genes involved in pathogen response, immune modulation and cell proliferation. vIRF-1 has been shown to downregulate the interferon- and IRF-mediated transcriptional activation of ISG and murine IFNA4 gene promoters. In this study we demonstrate that vIRF-1 efficiently inhibited virus-induced expression of endogenous interferon B, CC chemokine RANTES and CXC chemokine IP-10 genes. Co-expression analysis revealed that vIRF-1 selectively blocked IRF-3 but not IRF-7-mediated transactivation. vIRF-1 was able to bind to both IRF-3 and IRF-7 in vivo as detected by coimmunoprecipitation analysis, but did not affect IRF-3 dimerization, nuclear translocation and DNA binding activity. Rather, vIRF-1 interacted with the CBP/p300 coactivators and efficiently inhibited the formation of transcriptionally competent IRF-3-CBP/p300 complexes. These results illustrate that vIRF-1 is able to block the early stages of the IFN response to virus infection by interfering with the activation of IRF-3 responsive, immediate early IFN genes.

Six-minute walking test in cystic fibrosis adults with mild to moderate lung disease: comparison to healthy subjects.

The six-minute walking test (6MWT) has been widely utilized to evaluate global exercise capacity in patients with cystic fibrosis. The aim of this study was to assess the exercise capacity by 6MWT, measuring four outcome measures: walk distance, oxygensaturation and pulse rate during the walk, and breathlessness perception after the walk, in a group of cystic fibrosis adults with mild to moderate lung disease, and in healthy volunteers, as the control group. Moreover, the study examined the relationship between 6MWT outcome measures and pulmonary function in patients. Twenty-five adults (15 females, age range 18-39 years) with cystic fibrosis and 22 healthy volunteers (14 females, age range 20-45 years) performed a 6MWT following a standard protocol. Walk distance, oxygen saturation (SpO2) and pulse rate at rest and during walk, and breathlessness perception after walk assessed by visual analogue scale (VAS) were measured. Cystic fibrosis patients did notdiffer from healthy volunteers in walk distance (626 +/- 49 m vs. 652 +/- 46 m) and pulse rate. Patients significantly differed from healthy volunteers in SPO2 during the walk (mean SpO2) (P < 0.0001) and VAS (P < 0.0001). In patients, SPO2 during the walk significantly correlated with forced expiratory volume in 1 sec (FEV1) (P < 0.0001), residual volume (RV) (P < 0.001), resting SPO2 (base SpO2) (P < 0.001), and inspiratory capacity (IC) (P < 0.01). In addition, VAS significantly correlated with resting SPO2 (P < 0.01) and IC (P < 0.01). On the basis of regression equations by stepwise multiple regression analysis, SpO2 during walk was predicted by FEV1 (r2 = 0.60) and VAS by IC (r2 = 0.31), whereas walk distance was not reliably predicted by any assessed variables. This study showed that cystic fibrosis adults with mild to moderate lung disease covered a normal walk distance with unimpaired cardiac adaptation, but experienced a significant fall in oxygen saturation and an increased breathlessness perception during exercise. Resting pulmonary function was related to oxygen saturation and breathlessness perception during walk, but contributed significantly only tothe prediction of oxygen saturation. We suggest that 6MWT could be valuable for identifying patients who might experience oxygen desaturation and dyspnoea during demanding daily activities.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

IFN-gamma and IL-4 differently regulate inducible NO synthase gene expression through IRF-1 modulation.

NO is a labile radical involved in several immunological, antimicrobial and inflammatory processes. In macrophages, NO formation is catalyzed by the cytokine-inducible enzyme inducible NO synthase (iNOS). The importance of IFN regulatory factor (IRF)-1 and of the signal transducers and activators of transcription (STAT)-1 for the induction of iNOS gene expression in response to IFN-gamma has been well defined. Here, we investigated the molecular events responsible for the inhibition of iNOS gene expression by IL-4 in the murine macrophage cell line RAW264.7. Unidirectional deletion analysis on iNOS promoter demonstrated that an IFN-stimulated responsive element (ISRE), contained in the -980 to -765 bp region of the iNOS promoter, may be involved in the IL-4-mediated inhibition of IFN-gamma-inducible iNOS transcription. Accordingly, the IFN-gamma-induced binding activity of IRF-1 to the ISRE sequence was reduced in cells pre-treated with IL-4, while the binding activity of STAT-1 to the STAT-binding element (SBE) within the same region of the iNOS promoter remained unaffected. Moreover, IL-4 even down-regulated IFN-gamma-inducible expression of IRF-1 mRNA. This could be related to a transcriptional mechanism by which IL-4 and IFN-gamma differentially influence the trans-acting activity of the STAT factors binding to SBE within the IRF-1 promoter. SBE is targeted by IFN-gamma-inducible STAT-1 and by IL-4-inducible STAT-6. Although STAT-6 has no trans-acting function on iNOS gene expression, it is able to inhibit the IFN-gamma-induced expression of IRF-1. Thus, IL-4 may down-regulate IFN-gamma-inducible iNOS transcription by activation of STAT-6 which in turn inhibits IRF-1 expression.

[Medical treatment of respiratory emergencies]. / Terapia medica delle urgenze respiratorie.

Of the four treatments that can be used to treat respiratory insufficiency due to laryngitis, two, nebulized adrenaline and O2 therapy, are undoubtedly effective. The inhalation of water vapour appears to be increasingly useless and may be also harmful. The use of steroids is still under debate. In recent literature, however, the utility of steroids seems to be confirmed, especially if administered per Os, and even at a relatively low single oral dose (1-2 mg/kg of prednisone). According to the official organs (see Red Book) and according to the Evidence Based Medicine (see Cochrane Library) the treatment of bronchiolitis should be limited to an eventual support therapy, i.e. O2 therapy and rehydration. However, the approach adopted by North American Hospitals and European specialists in infectious diseases is in contrast and consists in the use of beta 2 agonists and steroids in 90-100% and 40-80% of patients, respectively. This contrast could be due to a deficiency in the researches of the Evidenced Based Medicine which is obliged to retrieve studies done over 10-15 years in order to obtain a sufficient number of data for a statistically valid investigation. These studies unfortunately are not updated with regard to the dose of individual drugs and the immediate association of drugs. In particular, with regard to nebulized beta 2 agonists, the absence of a positive effect could be due to an excessively low dose in relation to the age of the patient. According to the most recent knowledge, in fact, reduced doses are no longer required for babies in consideration of age and weight. In reality an equal and even higher dose than that used in adults would be best. The other reason for a lack of response could be the absence of the association of a steroid with a beta 2 agonists at the right moment. The lack of timing in associating these two drugs could also account for the absent response to the steroid. On the basis of these considerations it would be a mistake to give up the use of beta 2 agonists and steroids. Considering also the severity and frequency of a disease as bronchiolitis. To follow the "fashion" of the Evidence Based Medicine. Recently, magnesium sulphate, ketamine and the association elium-O2 have been suggested as marginal and not revolutionary medical interventions for the treatment of asthma. Among bronchodilators, the subordinate role of anticholinergics (for ex. ipratropium bromide), and of adrenaline has been defined with respect to beta 2 agonists, in particular salbutamol. The optimisation of the administration by nebulizers of the latter has been fundamental as it has a key role in the treatment of acute severe asthma. In detail, traditional nebulizers tend to be substituted by Metered Dose Inhaler + spacer with a ratio in the dose of 5/1. The venous route is used only in very severe cases and is used late and in intensive care although a single initial intravenous administration could determine a more rapid reduction of bronchoconstriction and reduce the number of nebulized bronchodilatators that can become extremely frequent in most severe cases. For steroids, instead, the only safe therapeutic route is by PO, i.v., i.m.: nebulized steroids although used with a definitely higher dose than that used for chronic asthma, can be used only in the milder forms.

[The pediatrician facing the problem of polluted air]. / Il pediatra di fronte al problema dell'aria inquinata.

The enormous amount of data concerning outdoor pollution has allowed quantifying the damage caused by single pollutants. On the basis of these data, and knowing the concentration of a pollutant in a given area, to date it is possible to foresee the expected risk for a given disease in our community. For instance, in an average size town like Parma, it can be calculated that in the middle of the winter, suspended particulate pollution (PM10), one day/three, will increase by 30% the number of symptomatic asthmatic children. In the long term, in a town like Parma, PM10 and NO2 pollution increases the number of children with more than 4 episodes of bronchitis or persistent cough by 30-50%. With regard to the typical summer pollution by O3, extremely harmful as it expands outside towns, in Parma and surroundings in August one should expect in 1/3 days double the number of symptomatic asthmatic patients, and every other day a 25% reduction of the respiratory function in asthmatic children exercising. With regard to indoor pollution besides the well known and severe problem of passive smoking, and that of volatile organic compounds still under investigation, one must consider NO2 pollution originating from the burning processes for heating and cooking. As this latter is extremely important in Italy, as gas is used in practically every house, the Author has done a specific research in which it is shown that if this kind of pollution was eliminated one could reduce the incidence of asthma in childhood from 7 to 5%, and noticeably the severity of the disease in affected subjects. Thus, paediatricians have two new aims. The first is to identify in pollution one of the possible causes of respiratory problems in each single patient, giving recommendations (ex. advise asthmatic children to avoid physical activity in the open and in the sunny hours during the summer, or avoid having children in the kitchen while cooking, or have boilers, heaters, etc. checked). Second, paediatricians should make aware, using the local actual data on pollution, not only the local administrators, but also and may be more important the parents of children with respiratory problems. These are in fact the ones who can and must become the most active in facing the big problem of pollution.