Dynamics of a nosocomial outbreak of multidrug-resistant Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase

From November 1998 to August 1999, a large outbreak occurred in the general intensive care unit of the Ospedale di Circolo in Varese (Italy), caused by Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase. A total of 108 clinical isolates of P. aeruginosa resistant to broad-spectrum cephalosporins were recovered from 18 patients. Epidemic isolates were characterized by synergy between clavulanic acid and ceftazidime, cefepime, and aztreonam. Isoelectric focusing of crude bacterial extracts detected two nitrocefin-positive bands with pI values of 8.0 and 5.3. PCR amplification and characterization of the amplicons by restriction analysis and direct sequencing indicated that the epidemic isolates carried a bla(PER-1) determinant. The outbreak was of clonal origin as shown by pulsed-field gel electrophoresis analysis. This technique also indicated that the epidemic strain was not related to three other PER-1-positive isolates obtained at the same hospital in 1997. Typing by enterobacterial repetitive intergenic consensus-PCR showed that minor genetic variations occurred during the outbreak. The epidemic strain was characterized by a multiple-drug-resistance phenotype that remained unchanged over the outbreak, including extended-spectrum cephalosporins, monobactams, aminoglycosides, and fluoroquinolones. Isolation of infected patients and appropriate carbapenem therapy were successful in ending the outbreak. Our report indicates that the bla(PER-1) resistance determinant may become an emerging therapeutic problem in Europe.     

Quality of life and psychological distress in locally advanced cervical cancer patients administered pre-operative chemoradiotherapy

ObjectiveThe aim of the study was to analyze the Quality of life (QoL) scores in a single institution series of locally advanced cervical cancer patients (LACC) administered preoperative chemoradiation, compared to early stage disease (ECC) patients undergoing radical surgery.MethodsThe following criteria were required in order to enroll patients: age between 18 and 65years at initial diagnosis, at least 12months from the end of treatment, no evidence of recurrence/second malignancy. The SF-36 questionnaire on general health, and the HADS questionnaire on mental distress were utilized.Results93 subjects were available for the analysis. At time of analysis, median follow-up was 30months (range 12–120). LACC patients showed QoL scores comparable to ECC patients with the exception of physical functioning (mean ± SD = 69.0 ± 13.1 versus mean ± SD = 85.4 ± 16.2, p value = 0.0007). In the group of LACC patients, the presence of co-morbidities was significantly associated with the impairment of almost all subscales of QoL. A low education level and the status of unemployment were documented to negatively impact on the vast majority of SF-36 subscale scores. In the multivariate analysis, the presence of co-morbidities, low educational level, age> 50years, and unemployment maintained their independent negative association with poor QoL scores. The percentage of cases with high levels HADS-anxiety was higher in LACC than ECC patients (27.6% versus 8.6%, p value = 0.034).ConclusionsLACC patients administered preoperative chemoradiation showed QoL scores comparable to EEC patients, and a higher proportion of anxiety disorders; low educational level and unemployment status were mainly associated with poor QoL scores.     

Growth-related oncogene alpha induction of apoptosis in osteoarthritis chondrocytes

OBJECTIVE: To evaluate the apoptotic effect of the chemokine growth-related oncogene alpha (GROalpha), which we recently reported to be up-regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes. METHODS: We investigated the apoptotic effect of GROalpha on isolated human cells and on in vitro-cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of "early" biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c-Jun N-terminal kinase/stress-activated protein kinase). RESULTS: We clearly demonstrated that GROalpha was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROalpha-induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining. CONCLUSION: GROalpha can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROalpha chemokine in the joint space in the course of this rheumatic disease.     

Predictive factors for switching in patients with psoriatic arthritis undergoing anti-TNFα, anti-IL12/23, or anti-IL17 drugs: a 15-year monocentric real-life study

Clinical Rheumatology - We aimed to evaluate the (a) potential predictors of first biological disease-modifying anti-rheumatic drug (bDMARD) failure and (b) factors associated with failure of...     

P-glycoprotein, lung resistance-related protein and multidrug resistance-associated protein in de novo adult acute lymphoblastic leukaemia

P-glycoprotein (P-gp), lung resistance-related protein (LRP) and multidrug resistance-associated protein (MRP) expression, and blast cell intracellular daunorubicin accumulation (IDA) were evaluated in 95 previously untreated cases of adult acute lymphoblastic leukaemia (ALL) using flow cytometry. Forty-five out of 95 (47%) patients were P-gp positive (+), 12/66 (18%) were LRP+ and 11/66 (17%) were MRP+. Eighteen out of 66 (28%) patients showed a simultaneous multidrug resistance (MDR)-related protein expression higher than controls for more than one protein, while 24/66 (36%) cases did not overexpress any protein. Twenty-one out of 24 (87%) cases overexpressing at least one MDR-related protein had a defect in accumulating daunorubicin into their blast cells, while only 4/24 (16%) cases who did not overexpress any protein had similar features. The complete remission rates were similar in MDR-positive and -negative (-) patients but relapses within 6 months were more frequent in P-gp+ cases, and therefore the disease-free survival duration was shorter in P-gp+ than in P-gp- patients (P = 0.01). The number of MRP+ and/or LRP+ cases was too small to be able to draw any conclusion on their role in affecting or predicting therapy outcome. In conclusion, P-gp overexpression associated with a defect in daunorubicin accumulation is a frequent feature in adult ALL at onset and seems to be related to poorer therapy outcome and, consequently, a shorter disease-free survival. LRP and MRP overexpression seems to be a rare event and no conclusion can be drawn on its prognostic role.     

HMGB1 promotes CXCL12-dependent egress of murine B cells from Peyer's patches in homeostasis

High mobility group box-1 protein (HMGB1) is an alarmin that, once released, promotes inflammatory responses, alone and as a complex with the chemokine CXCL12. Here, we report that the HMGB1–CXCL12 complex plays an essential role also in homeostasis by controlling the migration of B lymphocytes. We show that extracellular HMGB1 is critical for the CXCL12-dependent egress of B cells from the Peyer's patches (PP). This promigratory function of the complex was restricted to the PPs, since HMGB1 was not required for B-cell migratory processes in other locations. Accordingly, we detected higher constitutive levels of the HMGB1–CXCL12 complex in PPs than in other lymphoid organs. HMGB1–CXCL12 in vivo inhibition was associated with a reduced basal IgA production in the gut. Collectively, our results demonstrate a role for the HMGB1–CXCL12 complex in orchestrating B-cell trafficking in homeostasis, and provide a novel target to control lymphocyte migration in mucosal immunity.     

Morphometric analysis of dental arch form changes in class II patients treated with clear aligners

Journal of Orofacial Orthopedics / Fortschritte der Kieferorthopädie - The purpose of this study was to evaluate the arch form changes in class II Caucasian patients treated with...     

Identification of New Natural CphA Metallo-β-Lactamases CphA4 and CphA5 in Aeromonas veronii and Aeromonas hydrophila Isolates from Municipal Sewage in Central Italy

Two new natural CphA metallo-β-lactamases, the CphA4 and CphA5 enzymes, were identified in water samples from municipal sewage in central Italy. Compared to CphA, the CphA4 and CphA5 enzymes showed numerous point mutations. These enzymes have a narrow spectrum of substrates focused on carbapenems only. CphA5 showed k_cat values about 40-, 12-, and 97-fold higher than those observed for CphA4 versus imipenem, ertapenem, and biapenem, respectively.