In members of the family Enterobacteriaceae, ampC, which encodes a -lactamase, is regulated by an upstream, divergently transcribed gene, ampR. However, in Pseudomonas aeruginosa, the regulation of ampC is not understood. In this study, we compared the characteristics of a P. aeruginosa ampR mutant, PAOampR, with that of an isogenic ampR ؉ parent. The ampR mutation greatly altered AmpC production. In the absence of antibiotic, PAOampR expressed increased basal -lactamase levels. However, this increase was not followed by a concomitant increase in the P ampC promoter activity. The discrepancy in protein and transcription analyses led us to discover the presence of another chromosomal AmpR-regulated -lactamase, PoxB. We found that the expression of P. aeruginosa ampR greatly altered the -lactamase production from ampC and poxB in Escherichia coli: it up-regulated AmpC but down-regulated PoxB activities. In addition, the constitutive P ampR promoter activity in PAOampR indicated that AmpR did not autoregulate in the absence or presence of inducers. We further demonstrated that AmpR is a global regulator because the strain carrying the ampR mutation produced higher levels of pyocyanin and LasA protease and lower levels of LasB elastase than the wild-type strain. The increase in LasA levels was positively correlated with the P lasA , P lasI , and P lasR expression. The reduction in the LasB activity was positively correlated with the P rhlR expression. Thus, AmpR plays a dual role, positively regulating the ampC, lasB, and rhlR expression levels and negatively regulating the poxB, lasA, lasI, and lasR expression levels.
Development of β-lactam resistance, production of alginate and modulation of virulence factor expression that alters host immune responses are the hallmarks of chronic Pseudomonas aeruginosa infection in cystic fibrosis patients. In this study, we propose that a co-regulatory network exists between these mechanisms. We compared the promoter activities of ampR, algT/U, lasR, lasI, rhlR, rhlI and lasA genes, representing the β-lactam antibiotic resistance master regulatory gene, the alginate switch operon, the las and rhl quorum-sensing (QS) genes, and the LasA staphylolytic protease, respectively. Four isogenic P. aeruginosa strains, the prototypic Alg− PAO1, Alg− PAOampR, the mucoid Alg+ PAOmucA22 (Alg+ PDO300) and Alg+ PAOmucA22ampR (Alg+ PDOampR) were used. We found that in the presence of AmpR regulator and β-lactam antibiotic, the extracytoplasmic function sigma factor AlgT/U positively regulated PampR, whereas AmpR negatively regulated PalgT/U. On the basis of this finding we suggest the presence of a negative feedback loop to limit algT/U expression. In addition, the functional AlgT/U caused a significant decrease in the expression of QS genes, whereas loss of ampR only resulted in increased PlasI and PlasR transcription. The upregulation of the las QS system is likely to be responsible for the increased lasA promoter and the LasA protease activities in Alg− PAOampR and Alg+ PDOampR. The enhanced expression of virulence factors in the ampR strains correlated with a higher rate of Caenorhabditis elegans paralysis. Hence, this study shows that the loss of ampR results in increased virulence, and is indicative of the existence of a co-regulatory network between β-lactam resistance, alginate production, QS and virulence factor production, with AmpR playing a central role.
Adverse drug events occur often in hospitals. They can be prevented to a large extent by minimizing the human errors of prescription writing. To evaluate the efficacy of a computerized prescription order entry (CPOE) system with the help of ancillary support in minimizing prescription errors. Retrospective study carried out in a community-based urban teaching hospital in south Brooklyn, NY from January 2004 to January 2005. Errors were categorized into inappropriate dosage adjustment for creatinine clearance, duplication, incorrect orders, allergy verification, and incomplete orders. The pharmacists identified the type of error, the severity of error, the class of drug involved, and the department that made the error. A total of 466,311 prescriptions were entered in the period of 1 year. There were 3513 errors during this period (7.53 errors per 1000 prescriptions). More than half of these errors were made by the internal medicine specialty. In our study, 50% of the errors were severe errors (overdosing medications with narrow therapeutic index or over-riding allergies), 46.28% were moderate errors (overdosing, wrong dosing, duplicate orders, or prescribing multiple antibiotics), and 3.71% were not harmful errors (wrong dosing or incomplete orders). The errors were also categorized according to the class of medication. Errors in antibiotic prescription accounted for 53.9% of all errors. The pharmacist detected all these prescription errors as the prescriptions were reviewed in the CPOE system. Prescription errors are common medical errors seen in hospitals. The CPOE system has prevented and alerted the prescriber and pharmacist to dosage errors and allergies. Involvement of the pharmacist in reviewing the prescription and alerting the physician has minimized prescription errors to a great degree in our hospital setting. The incidence of prescription errors before the CPOE has been reported to range from 3 to 99 per 1000 prescriptions. The disparity could be due to the definition of medical errors, which has changed over the years, and also number of prescriptions included in the study and the study design.
Introduction: Gastric polyps exist in a wide variety of types, most of which are small and often benign. Discovery of gastric polyps during Endoscopy necessitates biopsies.
The legend and labels for Fig. 1 on page 151 are incorrect. The last line of the legend should read one milliunit (mU) of b-lactamase is defined as 1 nmol nitrocefin hydrolysed min 21 (mg protein) 21 , not one Miller unit of b-lactamase is defined as 1 nmol nitrocefin hydrolysed min 21 (mg protein) 21. The y-axis of Fig. 1 should be labelled b-lactamase activity (mU), not b-lactamase activity (Miller units).
Astrocytomas are central nervous system neoplasms, which are derived predominately from astrocytes. On the basis of the histopathologic characteristics astrocytomas are graded from I to IV. The cells that demonstrate the greatest degree of anaplasia are used to determine the histologic grade of the tumor. The mean age of survival are approximately 10 years from the time of diagnosis for pilocystic astrocytomas (World Health Organization grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2 to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV). The treatment is a combination of surgery, radiation, and chemotherapy depending of the grade of astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of his chronic myelogenous leukemia treatment failing to show recurrence of the astrocytoma 10 years after standard treatment for astrocytoma.
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