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OBJECTIVE -- To investigate the role of dietary factors in the development of type 2 diabetes. RESEARCH DESIGN AND METHODS -- In the context of the Multinational MGSD Nutrition Study, [...]

A prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceae and to evaluate the clinical significance of integron carriage. Consecutive patients with Enterobacteriaceae BSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of Enterobacteriaceae BSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P < 0.001) or to produce extended-spectrum {szligbeta}-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P < 0.001) or a VIM-type metallo-{szligbeta}-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P < 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying ENTEROBACTERIACEAE: Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P < 0.001) and a Pitt bacteremia score of ≥4 (OR, 23.36; 95% CI, 7.97 to 68.44; P < 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

ABSTRACTA prospective observational study was conducted to identify factors associated with bloodstream infections (BSIs) caused by integron-carrying Enterobacteriaceaeand to evaluate the clinical significance of integron carriage. Consecutive patients with EnterobacteriaceaeBSIs were identified and followed up until discharge or death. Identification of blood isolates and susceptibility testing were performed by the Wider I automated system. int-1-specific PCR, conserved-segment PCR, and DNA sequencing were used to determine the presence, length, and content of integrons. The relatedness among the isolates was examined by pulsed-field gel electrophoresis. Two hundred fifty episodes of EnterobacteriaceaeBSI occurred in 233 patients; 109 (43.6%) were nosocomial, 82 (32.8%) were community acquired, and 59 (23.6%) were health care associated. Integrons were detected in 11 (13.4%) community-acquired, 24 (40.7%) health care-associated, and 46 (42.2%) nosocomial isolates. Integron-carrying organisms were more likely to exhibit resistance to three or more classes of antimicrobials (odds ratio [OR], 9.84; 95% confidence interval [95% CI], 5.31 to 18.23; P< 0.001) or to produce extended-spectrum β-lactamases (OR, 5.75; 95% CI, 2.38 to 13.89; P< 0.001) or a VIM-type metallo-β-lactamase (P, 0.003). Inter- or intraspecies integron transfer and cross-transmission of integron-carrying clones were observed. Use of cotrimoxazole (OR, 4.77; 95% CI, 1.81 to 12.54; P< 0.001) and a nosocomial or other health care setting (OR, 3.07; 95% CI, 1.30 to 7.22; P, 0.01) were independently associated with BSIs caused by integron-carrying Enterobacteriaceae. Patients with a nonurinary source of bacteremia (OR, 9.46; 95% CI, 2.77 to 32.32; P< 0.001) and a Pitt bacteremia score of ≥4 (OR, 23.36; 95% CI, 7.97 to 68.44; P< 0.001) had a significantly higher 14-day mortality rate, whereas integron carriage did not affect clinical outcomes. These findings may have implications affecting antibiotic policies and infection control measures.

Abstract: In the present study we investigated whether acute glucose administration could be protective against hypoxic stress. H9c2 cells were exposed to either 4.5,mM or 22,mM of glucose for 15,min and then were submitted to simulated ischemia. Cell death was microscopically assessed by combined staining with propidium iodide (PI) and Hoeschst 33358. Intracellular content of glucose was measured by enzymatic analysis. Clucose content of H9c2 cells was 48.24± 7.94,μmol/L in the 22,mM vs 23.86± 4.8,μmol/L in the 4.5,mM group (p < 0.05). PKCε expression was increased 1.6 fold in the membrane fraction after pretreatment with high glucose (p < 0.05), while was decreased 1.6 fold in the cytosol (p < 0.05). In addition, no difference to PKCδ translocation was observed after pretreatment with low glucose. After hypoxia, in the 22,mM group, cell death was found to be 17.36± 2.66% vs 38.2± 5.4% in the 4.5,mM group (p < 0.05). In the presence of iodoacetic acid, a glycolytic inhibitor, cell death was not different between the two groups (23.54± 3.2% in 22,mM vs 22.06± 5.3% in 4.5,mM). Addition of chelerythrine did not change the protective effect of high glucose (13.4± 1.7% cell death in 22,mM vs 27.5± 5.5% in 4.5,mM, p < 0.05). In conclusion, short pretreatment with high glucose protects H9c2 cells against hypoxia. Although this protective effect is associated with translocation of PKCε and increased glucose uptake, it was abrogated only by inhibition of glycolysis. (Mol Cell Biochem xxx: 1–7, 2005)

OBJECTIVE: This study assessed the efficacy and safety of combination (COMB) of cyclosporine (CSA) and leflunomide (LEF) versus each drug alone, in the treatment of severe rheumatoid arthritis (RA). METHODS: One hundred six patients with active RA refractory to at least one disease modifying antirheumatic drug (methotrexate obligatorily) were entered into a 12-month open, prospective trial and were randomly allocated to receive either CSA 2.5 to 5 mg/kg/day, or LEF 20 mg/day, or the combination of both at the same initiating dose. RESULTS: The American College of Rheumatology 50% (ACR50) response rates for the 3 groups were COMB 80%, CSA 40%, and LEF 42% (p = 0.001). Combination therapy was also significantly better than CSA and LEF at the more stringent 70% response rate (69% vs 34% vs 30%, respectively; p = 0.001). Comparable Disease Activity Score 28 reduction rates were noted at trial termination for all 3 treatment arms: COMB –2.74 vs CSA –2.53 vs LEF –2.28 (p nonsignificant). Discontinuation rates were more common in LEF vs CSA arm (p = 0.046). No unexpected or serious adverse drug effects were identified in the combination group during the 12-month period. CONCLUSION: The combination of CSA and LEF in patients with refractory RA provided statistically significant benefit in ACR50 and ACR70. Adverse events were not substantially increased.