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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare but severe, potentially life threatening adverse drug reactions characterized by skin blistering. Previous studies have identified drug-specific and population-specific genetic risk factors with large effects. In this study, we report the first genome-wide association study (GWAS) of SJS/TEN induced by a variety of drugs. Our aim was to identify common genetic risk factors with large effects on SJS/TEN risk. We conducted a genome-wide analysis of 96 retrospective cases and 198 controls with a panel of over one million single-nucleotide polymorphisms (SNPs). We further improved power with about 4000 additional controls from publicly available datasets. No genome-wide significant associations with SNPs or copy number variants were observed, although several genomic regions were suggested that may have a role in predisposing to drug-induced SJS/TEN. Our GWAS did not find common, highly penetrant genetic risk factors responsible for SJS/TEN events in the cases selected. [ABSTRACT FROM AUTHOR]

We report the results of a three-year surveillance program of Klebsiella spp. in six hospitals in Florence (Italy). A total of 172 Klebsiella isolates were identified and typed by AFLP: 122 were K. pneumoniae and 50 were K. oxytoca. Most K. pneumoniae (80%) and K. oxytoca (93%) showed unrelated AFLP profiles. Beside this heterogeneous population structure, we found five small epidemic clonal groups of K. pneumoniae. Four of these groups were involved in outbreak events, three of which occurred in neonatal ICUs. The fifth clonal group spread in three different wards of two hospitals. Only one non-epidemic clonal group of K. oxytoca was detected. The frequencies of isolates with multiple antibiotic resistances increased with time; at the end of the study period, most K. pneumoniae were resistant to all the antibiotics tested. A PCR analysis of seven ertapenem resistant isolates was unable to detect any of the major genes known to underlie carbapenem resistance in K. pneumoniae. [ABSTRACT FROM AUTHOR]

In 2007, three strains of Salmonella enterica serotype Rissen ( S. Rissen) were isolated in the laboratory of diagnostic microbiology of the General Hospital of Prato, Tuscany, Italy, over a 1 month and half interval of time. The first isolate was recovered on January 26 from an outpatient with enteritis. Then, two strains were isolated on February 16 and March 11 respectively, from central venous catheters of patients who were being hospitalized in two departments of the Hospital. An epidemiologically linked cluster of cases of salmonellosis was suspected. The three strains were submitted to single enzyme-amplified fragment length polymorphism (SE-AFLP) and XbaI macrorestriction and pulsed-field gel electrophoresis (PFGE) that yielded undistinguishable profiles. Epidemiological investigations failed to identify a common source of infection within the Hospital. Moreover, the third patient had been exclusively total parenteral nutrition fed since his admission with a stomach cancer diagnosis. The first patient had a community-acquired infection, but the source of her illness was uncertain. Twenty-five further isolates identified in the years 2004-2007 in the same geographical area showed distinctly different PFGE and SE-AFLP patterns. The three patients seemed to represent a cluster of epidemiologically unrelated cases caused by a previously never recognized S. Rissen strain. Rapid subtyping of isolates is essential in the early investigation of potential outbreaks, but synthesis of conventional and molecular epidemiological investigation and availability of surveillance data is often critical to prevent the initiation of time-consuming, expensive and ineffective further investigations and control interventions. [ABSTRACT FROM AUTHOR]

From May to October 2006, six severe Pseudomonas aeruginosa infections were diagnosed in patients undergoing SCT in the SCT unit of the Careggi hospital (Florence, Italy). Four of the infected patients were treated consecutively in the same room (room N). On the hypothesis of a possible environmental source of infection, samples were collected from different sites that had potential for cross-contamination throughout the SCT unit, including the electrolytic chloroxidant disinfectant used for hand washing (Irgasan) and the disinfectant used for facilities cleaning. Four of the environmental samples were positive for P. aeruginosa: three Irgansan soap samples and a tap swab sample from the staff cleaning and dressing room. The AFLP (amplified fragment length polymorphism) typing method employed to evaluate strain clonality showed that the isolates from the patients who had shared the same room and an isolate from Irgasan soap had a significant molecular similarity (dice index higher than 0.93). After adequate control measures, no subsequent environmental sample proved positive for P. aeruginosa. These data strongly support the hypothesis of the clonal origin of the infective strains and suggest an environmental source of infection. The AFLP method was fast enough to allow a ‘real-time’ monitoring of the outbreak, permitting additional preventive measures.Bone Marrow Transplantation (2009) 43, 335–338; doi:10.1038/bmt.2008.319; published online 13 October 2008 [ABSTRACT FROM AUTHOR]

The aim of this study was to examine the cytotoxicity and the antibacterial effects of a variety of essential oils on major respiratory tract pathogens. The cytotoxicity of 13 essential oils was evaluated on Vero cells. The antibacterial activity was evaluated by the Kirby Bauer paper method, minimum inhibitory and bactericidal concentration against Streptococcus pyogenes, agalactiae, pneumoniae and Klebsiella pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Stenotrophomonas maltophilia isolated from clinical specimens. The antibiotic sensitivity of these isolates was examined. Some oils showed inhibition of bacterial growth against most of the organisms examined. Cinnamon and thyme showed the strongest action followed by clove. The results reported in this paper indicate that thyme can be considered as a potential antimicrobial agent for the treatment of some respiratory tract infections in man. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A fluorescence polarization assay (FPA) for detection of antibody to Bruce//a abortus in individual milk samples was developed and validated. Samples from 190 cattle from which B. abortus was isolated; milk samples from cattle in herds infected with B. abortus (n= 1086) and positive in the milk ring test (MRT), as well as milk samples from Canadian cattle (with no evidence of brucellosis, n = 2974) were tested by the indirect enzyme immunoassay (IELISA) and the FPA. The sensitivity (based on samples from culture positive cattle) and specificity (based on Canadian milk samples) of the IELISA and the FPA were 100%. The relative sensitivity value obtained with milk from cattle of infected herds and the specificity values of the IELISA were 98.5 and 99.9%, respectively. The relative sensitivity and specificity of the FPA with the same samples were 82.2 and 99.4% using a cutoff value of 90 millipolarization units (mP). The low relative sensitivity value of the FPA was shown, by competitive enzyme immunoassay (CELISA), to be due to vaccinal antibody (assumed as vaccinal antibody against B. abortus S19 is excluded by the FPA and CELISA but not by the MRT and the IELISA), present in some of the milk samples. The FPA is a homogeneous assay which, unlike the MRT and the IELISA, may be used for testing in the field. [ABSTRACT FROM AUTHOR]

To assess the spread of the new M phenotype, various erythromycin-resistant Streptococcus pyogenes strains from three Italian cities (Verona, Monza, Florence) were characterised. Each strain was analysed for the presence of genes ermAM and mefA, for the ability to accumulate radioactive erythromycin in the absence of sodium arsenate, for the protein T serological type, and for the DNA macrorestriction profile identified by means of pulsed-field gel electrophoresis. In a number of strains, the presence of the inducible ermAM gene was demonstrated; all these strains were negative in the efflux-pump detection assay, did not possess the mefA gene, and had similar restriction profiles. The strains with the efflux mechanism and mefA gene belonged to different serotypes. Of these, only one serotype, T4, was isolated in all three cities. The restriction profile analysis with SmaI and SfiI revealed a very close correlation between strains with the same serotype. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate peripheral blood progenitor cell mobilization by disease-specific chemotherapy in heavily pretreated patients with germ cell tumor (GCT), scheduled for high-dose chemotherapy. Thirty-four consecutive patients, 29 males and five females, with advanced GCT referred to our department for high-dose chemotherapy were evaluated retrospectively. Sixteen patients were mobilized by vinblastine 0.11 mg/kg on days 1 and 2, ifosfamide 1200 mg/m2 days 1–5 and cisplatin 20 mg/m2 days 1–5 (VeIP). In 10 patients, etoposide 75 mg/m2 days 1–5 was used instead of vinblastine (VIP), while in eight patients the mobilization was attempted by administering 7 g/m2 of cyclophosphamide. The choice of either etoposide or vinblastine was predicated upon which of these two drugs was associated with best results during premobilization chemotherapy. Cyclophosphamide was selected in patients refractory to previous cisplatin-based salvage chemotherapy. Twenty-five out of 34 patients underwent a successful PBPC collection. In 17 of them one leukapheresis procedure was sufficient to collect the target number of CD34+ cells, while in eight patients a double procedure was necessary. Altogether 33 aphereses were performed in 25 patients. In nine patients leukapheresis was not attempted. This was due to the fact that the chemotherapy failed to mobilize the target number of CD34+ cells in eight of them, treated with the VeIP mobilizing regimen, while one patient treated with high-dose cyclophosphamide rapidly progressed during therapy and for this reason leukapheresis was not undertaken. In conclusion, in heavily pretreated patients with GCT, PBPC mobilization is feasible by a further course of salvage chemotherapy. The choice of either etoposide (VIP) or vinblastine (VeIP) can be predicated upon which of these two drugs was associated with best results during premobilization... [ABSTRACT FROM AUTHOR]

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The nature of lymphocyte subsets activated by soluble and insoluble protein A (SpA) was investigated by testing the ability of human tonsil populations to form rosettes with human red blood cells coated with SpA (SpA-HRBC) and to respond in vitro to SpA. SpA coupled to Sepharose beads (SpA-Seph) and Staphylococcus aureus strain Cowan I (StaCw). Purified human I cells, which were unable to form rosettes with SpA-HRBC, were not activated by SpA-Seph or StaCw, whereas 8-cell enriched suspensions, where the number of lymphocytes forming rosettes with SpA-HRBC was significantly increased in comparison with that found in unfractionated populations, showed DNA synthesis equal to or greater than unseparated lymphocytes. In contrast, soluble SpA was unable to activate highly purified B lymphocytes in 3 day cultures and induced higher DNA synthesis in unseparated than in purified human T cells. Tonsil cell suspensions depleted in cells forming rosettes with SpA-I-IRBC synthesized significantly less DNA in the presence of SpA-Seph and lost the ability to respond to StaCw. The depletion in either IgG-bearing or IgM- and/or IgD-bearing cells induced a reduction in the response of lymphocytes to SpA-Seph and StaCw. Depletion in IgM- and/or IgD-bearing cells induced a more marked decrease in the response to StaCw than depletion in lgG-bearing lymphocytes, while the decrease of the response to SpA-Seph, induced by depletion in IgM- and/or IgD-bearing cells, was lower than that induced by depletion in lgG-bearing lymphocytes. In contrast, soluble SpA-induced proliferation was not significantly affected by depletion of cells forming rosettes with SpA-HRBC' or of IgG-bearing or IgM- and/or IgD-bearing lymphocytes. These results suggest that the mitogenicity of SpA-Seph and StaCw is due to a selective binding of insoluble SpA to components present on the membrane of either IgO- bearing or IgM- and/or IgD-bearing lymphocytes. They also indicate that the potentiation of T-cell response to soluble SpA, induced by the presence in culture of non-T cells, is not due to B lymphocytes which are able to form ,rosettes with SpA-HRBC and to respond to SpA itself when it is presented to the cells on an insoluble matrix. [ABSTRACT FROM AUTHOR]

The new thiazolyl peptide antibiotic MDL 62,879 (GE2270 A) showed excellent in vitro activity in testing against staphylococci and streptococci, with MIC90s ranging from 0.23 to 0.9 mg/l. It was very active against Clostridium difficile and Propionibacterium acnes (MIC90 0.06 mg/l in each case) and had variable activity against Bacteroides spp. MDL 62,879 had exceptionally good activity against Enterococcus faecalis, including against a collection of high-level aminoglycoside-resistant isolates where it had an MIC90 of 0.047. The antibiotic was bacteriostatic for enterococcal isolates but bactericidal for a methicillin-resistant isolate of Staphylococcus aureus. [ABSTRACT FROM AUTHOR]

An indirect enzyme immunoassay (ELISA) for detection of bovine antibody to Brucella abortus was modified by the addition of divalent chelating agents to the serum diluent. This addition resulted in an increase in specificity from 96.0% in the regular assay to 99.4% in the modified procedure. Of the 15 715 sera initially tested by the indirect ELISA, 691 that had given positive reactions were selected for retesting in the indirect ELISA with EDTA/EGTA added. The buffered plate antigen test (BPAT) correctly identified 98.6% of the samples as negative. The addition of chelating agents did not alter the sensitivity of the indirect ELISA, which correctly classified 609 sera from animals from which B. abortus had been isolated as positive. The sensitivity of the BPAT was 97.8%. [ABSTRACT FROM AUTHOR]

Over the last 100 years, the discovery of new analgesics has been a complex and difficult task. However, remarkable progress in the identification of novel molecular targets relevant for pain medicines has been reported. Here we will focus on the neuropeptide calcitonin generelated peptide (CGRP) and its receptors (CGRP-R) because of their role in migraine mechanism and migraine therapy. Recent preclinical and clinical data on the localisation, regulation and plasma levels of CGRP and on the function of CGRP-R will be summarised. The reviewed findings highlight the major function of CGRP in migraine and the use of CGRP-R antagonists as a novel approach for the treatment of migraine attack and, perhaps, as migraine prophylactic medicines. [ABSTRACT FROM AUTHOR]

The need for novel therapeutic strategies for the treatment of migraine and other primary headaches is well recognised. Although the underlying mechanism(s) and the molecular targets that should be tackled by novel medicines are still uncertain, significant improvements have been made in the last decade in the treatment of migraine. Strong evidence in experimental animal models and clinical investigation focus on drugs that limit the phenomena promoted by activation of neurons of the trigeminal ganglion at the level of both their central and peripheral perivascular endings. Identification of compounds that abort the migraine attack by precisely targeting different mechanisms should also help to recompose the puzzle of migraine pathogenesis. [ABSTRACT FROM AUTHOR]