Experimental characterization of the AISHa ion source.

The Advanced Ion Source for Hadrontherapy (AISHa) has been designed to generate high brightness multiply charged ion beams for hadron therapy applications. AISHa is a compact electron cyclotron resonance ion source whose hybrid magnetic system consists of a permanent Halbach-type hexapole magnet and a set of independently energized superconducting coils. This has allowed us to achieve high performances in a cost effective way. During the commissioning phase, a few criticalities have been observed and fixed in 2018/19; the improvements will be briefly described and the results of the operations with a single 18 GHz generator will be presented. Particular relevance will be given to the production of high intensity beams of oxygen, argon, and carbon, the latter having huge importance for hadron therapy applications. Perspectives for further improvements, including double frequency heating, will also be highlighted.

Chronic inflammation: A key role in degeneration of bicuspid aortic valve.

INTRODUCTION: Bicuspid aortic valve (BAV) is the most common congenital valvular heart defect resulting from abnormal aortic cusp formation during heart development, where two of the three normal and equal sized cusps fuse into a single large cusp resulting in a two cusps aortic valve. Over the past years, much interest has been given in understanding the pathogenesis of BAV and its complications. In this review, we focused on the role of inflammation, involved in the degeneration of BAV and the development of its complications. ROLE OF INFLAMMATION: From a pathophysiological point of view, BAV may rapidly progress into aortic stenosis (AS) and is related to aortopathy. Several histopathologic studies have demonstrated that the development and progression of alterations in bicuspid aortic valve are related to an active process that includes: oxidative stress, shear stress, endothelial dysfunction, disorganized tissue architecture, inflammatory cells and cytokines. These factors are closely related one to each other, constituting the basis of the structural and functional alterations of the BAV. CONCLUSION: Chronic inflammation plays a key role in the degeneration of BAV. Severe aortic stenosis in bicuspid aortic valves is associated with a more aggressive inflammatory process, increased inflammatory cells infiltration and neovascularization when compared to tricuspid AS. These findings might help to explain the more frequent onset and rapid progression of AS and the heavy aortic valve calcification seen in patients with BAV.

Application of multiplex single nucleotide primer extension (mSNuPE) to the identification of bacteria: the Burkholderia cepacia complex case.

Burkholderia cepacia complex (BCC) is characterized by a complex taxonomy constituted by seventeen closely related species of both biotechnological and clinical importance. Several molecular methods have been developed to accurately identify BCC species but simpler and effective strategies for BCC classification are still needed. A single nucleotide primer extension (SNuPE) assay using gyrB as a target gene was developed to identify bacteria belonging to the B. cepacia (BCC) complex. This technique allows the successful detection and distinction of single nucleotide polymorphisms (SNPs) and is effectively applied in routine medical diagnosis since it permits to analyze routinely many samples in a few times. Seven SNuPE primers were designed analyzing the conserved regions of the BCC gyrB sequences currently available in databases. The specificity of the assay was evaluated using reference strains of some BCC species. Data obtained enabled to discriminate bacteria belonging to the species B. multivorans, B. cenocepacia (including bacteria belonging to recA lineages III-A, III-C, and III-D), B. vietnamiensis, B. dolosa, B. ambifaria, B. anthina and B. pyrrocinia. Conversely, identification failed for B. cepacia, B. cenocepacia III-B and B. stabilis. This study demonstrates the efficacy of SNuPE technique for the identification of bacteria characterized by a complex taxonomical organization as BCC bacteria.

Use of the E test to assess synergy of antibiotic combinations against isolates of Burkholderia cepacia-complex from patients with cystic fibrosis.

Treatment of Burkholderia cepacia-complex infections in cystic fibrosis patients is problematic, since the microorganism is often resistant to most antimicrobial agents. In this study, the Epsilometer test, or E test, was used to assess the activity of antimicrobial combinations against Burkholderia cepacia-complex. In a preliminary evaluation, the E test was compared to the checkerboard method using 10 test organisms. Synergy testing by the E test was then performed on 131 clinical isolates of Burkholderia cepacia-complex using various combinations of antimicrobial agents. Agreement between the E test and the checkerboard method was 90%. The rate of resistance to individual agents ranged from 48% for meropenem to 100% for tobramycin, chloramphenicol, and rifampin. In 71.6%, 15.6%, and 12.6% of the test evaluations performed, the combinations tested resulted in additivity/indifference, synergism, and antagonism, respectively. The highest rates of synergy were observed with combinations of ciprofloxacin-piperacillin (44%), rifampin-ceftazidime (33%), chloramphenicol-ceftazidime (22%), cotrimoxazole-piperacillin/tazobactam (22%), and ciprofloxacin-ceftazidime (21%). Rates of antagonism for cotrimoxazole and chloramphenicol in combination with beta-lactam agents were higher than those observed for ciprofloxacin plus beta-lactam agents. These results suggest that the E test is a valuable and practical method to be considered for improving the identification of possible therapeutic options in cystic fibrosis patients infected with organisms belonging to the Burkholderia cepacia-complex.

Erythromycin resistance in Streptococcus pyogenes in Italy.

In a prospective study of acute pharyngitis in Italian children, 69 (38.3%) of 180 isolates of Streptococcus pyogenes were resistant to macrolides. S. pyogenes was eradicated in 12 (63.1%) of 19 patients with erythromycin-resistant S. pyogenes treated with clarithromycin and in 22 (88%) of 25 patients with erythromycin-susceptible strains. The constitutive-resistant phenotype was correlated with failure of macrolide treatment.

[Epidemiology and sensitivity to antibiotics in paediatric respiratory infections over a 4-year period. Retrospective study of 460 H. influenzae, S. pneumoniae and M. catarrhalis strains] / Epidemiologia e sensibilita agli antibiotici in infezioni respiratorie di pazienti pediatrici in un periodo di 4 anni. Studio retrospettivo su 460 ceppi di H. influenzae, S. pneumoniae e M. catarrhalis.

H. influenzae, S. pneumoniae and M. catarrhalis are the most common bacterial pathogens causing respiratory infections in children. Resistance to antibiotics may vary according to the geographical area. It is therefore important that the resistance pattern of such pathogens is determined by surveillance studies carried out both on a national scale and by individual laboratories. In this study, we determined retrospectively the prevalence of H. influenzae, S. pneumoniae and M. catarrhalis in upper respiratory tract infections involving subjects of paediatric age, with reference to the type of clinical sample (pharingeal swab and nasal swab), symptomatology and age group. Moreover, for the above micro-organisms the pattern of sensitivity to antibiotics was assessed. In the observation period (January 1996-December 1999), at the day hospital of the Paediatric Pneumology Division of the Gaslini Institute in Genova, in 476 patients between 0 and 15 years of age a total of 460 respiratory pathogens were isolated: 164 S. pneumoniae strains, 163 of H. influenzae (96 belonging to type B and 67 non-attributable to any type) and 133 of M. catarrhalis. As regards sensitivity to antibiotics, ceftriaxone and amoxycillin/clavulanic acid proved to be the most active molecules in all the studied strains.

[Fungal infections in pediatric oncology]. / Infezioni fungine in oncologia pediatrica.

The clinical charts of cancer patients with documented fungal infections hospitalized at G. Gaslini Children's Hospital, Italy, from 1980 to 1990 were reviewed. Thirty-seven episodes developing in 37 patients were identified, based on microbiological and/or histological documentation. Patients' age ranged from 3 months to 18 years (median 7 years). Twenty patients were treated for hematological malignancy and 17 had solid tumor. Seven patients (3 with leukemia and 4 with solid tumours), developed mycosis after bone marrow transplantation procedure. A history of neutropenia in the month preceding the documentation of fungal infection was present in 76% of cases (28 of 37). However, only 16 of 28 (55%) of these patients were still neutropenic at time of diagnosis. In 40% of the cases the fungal infection developed as primary infection not preceded by any febrile and/or infectious episode. Fungemias without evident organ localization accounted for the 40% of episodes with a mortality rate of 20%. The other 22 cases (60%) were classified as invasive mycoses; 9 of these patients died (41%). Mortality was higher among patients with mold infection (5 of 7, 72%), than in those with yeast infection (7 of 29.24%). Molds infections and invasive mycoses were virtually absent in the first part of our period of observation (1980-84), but emerged in the second period (1985-90) when also the incidence rate of fungal disease increased (from 2.67/10,000 person/day to 5.93), probably in relation with extensive construction works and with the implementation of a bone marrow transplantation program.

[Otilonium bromide-diazepam in the treatment of the irritable colon. A controlled study versus otilonium bromide]. / L'ottilonio bromuro+diazepam nel trattamento del colon irritabile. Studio controllato versus ottilonio bromuro.

Octylonium bromide (OB) is a drug with spasmolytic properties acting selectively on the smooth muscle of the gastrointestinal tract by interfering with calcium mobilization from extra- and intra-cellular deposits. The etiopathogenetic implications of a psychosomatic nature of the irritable bowel syndrome amply justify the use of a spasmolytic (OB) with a benzodiazepine. In our study, we compared the combination OB + DZ (20 mg + 2 mg) T.I.D. versus OB alone (20 mg) in 30 patients suffering from irritable bowel syndrome. The double-blind study lasting 3 weeks was aimed at evaluating gastrointestinal symptoms (bowel motions, aspect of faeces, abdominal pain, pre-evacuation pain, bloating) during the three days preceding the study and during the last five days of treatment, as well as the anxiogenic situation as assessed by the STAI scale (State Tract Anxiety Inventory) before and at the end of the treatment period. The results obtained showed that both treatments considerably reduced gastrointestinal symptoms even though OB alone did not appear to be equally effective and the anxiety component was significantly reduced only by treatment with the combination. The absence of side effects and the perfect tolerability of both treatments showed the OB + D combination T.I.D. to be the treatment of choice for patients suffering from irritable bowel syndrome.

Myeloablative therapy and unpurged autologous bone marrow transplantation for poor-prognosis neuroblastoma: report of 34 cases.

From October 1984 to November 1987, 34 patients aged from 1 year 1 month to 7 years 7 months with resistant or relapsed neuroblastoma (NB) (group 1, 10 patients), unselected disseminated NB (group 2, 14 patients), or selected disseminated NB (group 3, 10 patients) received myeloablative therapy (MAT) followed by unpurged autologous bone marrow transplantation (ABMT) at the end of an intensive protocol, which included high-dose chemotherapy and surgery to the primary tumor. Median time from diagnosis to MAT and ABMT was 6 months (5 months from last relapse to MAT and ABMT in the relapsed patients). The MAT regimen included vincristine, fractionated total body irradiation (TBI), and melphalan. Seventeen patients were grafted in complete remission (CR), five in very good partial remission (VGPR), 10 in partial remission (PR), and two in progressive disease (PD). The acute toxic death rate was 2.9%. The overall progression-free survival was 29%. The median progression-free survival was 20 months for the 17 patients grafted in CR, 6 months for the five patients grafted in VGPR, and 12 months for the 10 patients grafted in PR.

Listeria monocytogenes brain abscesses in a girl with acute lymphoblastic leukaemia after late central nervous system relapse.

A case of Listeria monocytogenes bacteraemia and meningitis with intracerebral abscesses in a girl with acute lymphoblastic leukaemia in relapse is reported. The clinical features included subacute onset with fever and marked irritability followed by seizures, meningism and confusion. The pathogen was isolated from blood and cerebrospinal fluid. Computerised tomography of the brain showed two intracerebral parenchymal localisations, in the left frontal lobe and in the right occipital lobe, respectively. The patient survived this severe infection without neurological sequelae. 2 months later she underwent allogeneic bone marrow transplantation without major complications. This case report should alert pediatric oncologists about the possible occurrence of severe intracerebral listerial infections in the immunocompromised child and suggests that this infection can be treated successfully and should not necessarily preclude continuation of antineoplastic treatments.

Infection with Fusarium species in two children with neuroblastoma.

Two cases of Fusarium infection in children with neuroblastoma are reported. One of the patients had an overwhelming infection and the diagnosis was based on isolation of Fusarium moniliforme from blood and skin biopsy, and histological findings. The second patient developed chronic polyarthritis and Fusarium solani was cultured from synovial fluid samples taken from two different joints four months apart. No histological documentation of infection was obtained. The response to antifungal therapy was unfavourable. Both patients died, but in the second case the relationship between fungal infection and death was not established.

Emerging microorganisms in cystic fibrosis.

Pseudomonas aeruginosa is the most common bacterial isolate obtained from patients with cystic fibrosis of the lungs. Recently, however, new multiresistant organisms have emerged, whose identification may be difficult and whose pathogenic role proves hard to define. Of the 71 strains isolated from 24 patients with cystic fibrosis during acute flareups of pulmonary symptoms, 48 turned out to be Pseudomonas aeruginosa (67.6%); 11 were Pseudomonas non-aeruginosa (15.5%); and 12 were Achromobacter xylosoxidans (16.9%). Each bacterial isolate was tested for sensitivity to nine antibiotics (ceftazidime, azlocillin, piperacillin, aztreonam, cefsulodin, cefoperazone, amikacin, tobramycin, and sisomycin) in terms of minimum inhibitory concentration and minimum bactericidal concentration values. In this series, Achromobacter xylosoxidans proved the species least responsive to treatment, and ceftazidime the most active antibiotic both against Achromobacter and against strains of the genus Pseudomonas. Twenty-three different associations of ceftazidime with aminoglycosides, tested for activity on the multiresistant strains, failed to show synergism of action.

Susceptibility of enterococci. I. Inhibitory and bactericidal activity of several chemoantibiotics against Streptococcus faecalis and Streptococcus faecium.

The authors present a microbiological study of 100 strains of Enterococcus (70 strains of Streptococcus faecalis and 30 strains of Streptococcus faecium) tested for susceptibility to the following antibiotics, amoxicillin, ampicillin + flucloxacillin, piperacillin, rifampicin, vancomycin, netilmicin, ofloxacin, and norfloxacin. The assessment of minimum inhibitory and minimum bactericidal concentrations of these substances indicates that all have good inhibitory activity except netilmicin, which is active at higher concentrations; with rifampicin and vancomycin showing very poor bactericidal activity. The bactericidal activity of penicillins was hard to assess because of tolerance and paradoxical effect phenomena. The quinolones showed good inhibitory and bactericidal activity.

Susceptibility of enterococci. II. Inhibitory and bactericidal activity of drugs in combination against Streptococcus faecalis and Streptococcus faecium.

The microbiological utility of antibiotic combinations against Streptococcus faecalis and Streptococcus faecium strains was studied. The drugs used were netilmicin + amoxicillin (20 strains); netilmicin + piperacillin (20 strains); netilmicin- + vancomycin (20 strains); netilmicin + rifampicin (20 strains). Netilmicin used in combination with the penicillins was advantageous against Streptococcus faecalis, but not uniformly against Streptococcus faecium. The combinations of netilmicin with vancomycin or rifampicin were no more effective than the single drugs in most cases, although the response varied for the different strains of the two species.