Citations

ABSTRACT The activity of electrical current against planktonic bacteria has previously been demonstrated. The short-term exposure of the bacteria in biofilms to electrical current in the absence of antimicrobials has been shown to have no substantial effect; however, longer-term exposure has not been studied. A previously described in vitro model was used to determine the effect of prolonged exposure (i.e., up to 7 days) to low-intensity (i.e., 20-, 200-, and 2,000-microampere) electrical direct currents on Pseudomonas aeruginosa , Staphylococcus aureus , and Staphylococcus epidermidis biofilms. Dose- and time-dependent killing was observed. A maximum of a 6-log 10 -CFU/cm 2 reduction was observed when S. epidermidis biofilms were exposed to 2,000 microamperes for at least 2 days. A 4- to 5-log 10 -CFU/cm 2 reduction was observed when S. aureus biofilms were exposed to 2,000 microamperes for at least 2 days. Finally, a 3.5- to 5-log 10 -CFU/cm 2 reduction was observed when P. aeruginosa biofilms were exposed to electrical current for 7 days. A higher electrical current intensity correlated with greater decreases in viable bacteria at all time points studied. In conclusion, low-intensity electrical current substantially reduced the numbers of viable bacteria in staphylococcal or Pseudomonas biofilms, a phenomenon we have labeled the “electricidal effect.”

Purpose Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. Patients and Methods Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m2 daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m2 daily for 5 days every 28 days). The primary end point was survival at 1 year. Results Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. Conclusion Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.

There are opportunities to improve quality and safety of care provided to adult patients. The Plummer Project of the Department of Medicine at the Mayo Clinic (Rochester, MN, USA) is an initiative to redesign outpatient practice. We used multidisciplinary teams to standardize the tasks essential to improve patient care. With the initiative to standardize the rooming process, patient care and safety improved with greater accuracy of the medication list. The standardization also improved physician efficiency because trained clinical assistants helped address the needs of the patient. Physicians were satisfied by the new process and the technology enhancements. Clinical assistants were also highly satisfied by the training process. The quality and safety of patient care can be significantly improved by practice redesign. This practice redesign was satisfying for all, especially the patients, physicians and support team in our practice.

Individuals with amnestic mild cognitive impairment (MCI) currently have few treatment options for combating their memory loss. The Memory Support System (MSS) is a calendar and organization system with accompanying 6-week curriculum designed for individuals with progressive memory impairment. Ability to learn the MSS and its utility were assessed in 20 participants. Participants were significantly more likely to successfully use the calendar system after training. Ninety-five percent were compliant with the MSS at training completion, and 89% continued to be compliant at follow-up. Outcome measures revealed a medium effect size for improvement in functional ability. Subjects further reported improved independence, self-confidence, and mood. This initial examination of the MSS suggests that with appropriate training, individuals with amnestic MCI can and will use a memory notebook system to help compensate for memory loss. These results are encouraging that the MSS may help with the symptoms of memory decline in MCI.

Abstract Previous work has demonstrated that a subset of macrophages expresses a folate receptor (FR) that can mediate internalization of folate-linked molecules, including imaging and therapeutic agents. To characterize this subset, macrophages were collected from peritoneal cavities of mice injected with saline, thioglycolate, zymosan, heat-killed or live bacteria, and cell-surface markers that coexpress with FR were identified. Virtually no F4/80+ peritoneal macrophages from saline-injected mice expressed FR, whereas numerous macrophages from mice injected with each inflammatory stimulus expressed FR. Examination of cell differentiation antigens that are up-regulated in FR+ macrophages revealed markers characteristic of an activated state (CD80, CD86, Ly-6C/G), whereas macrophages lacking these activation markers expressed few or no FR. FR+ macrophages also produced tumor necrosis factor-α (TNF-α) and reactive oxygen species, and production of reactive oxygen species correlated linearly with expression of FR. Synovial macrophages collected from arthritic patients were found to bind and internalize folate-linked dyes. Moreover, a folate-linked radioimaging agent was shown to image inflamed joints of rheumatoid arthritic patients. These results suggest that FR constitutes a marker for macrophage activation and that FR+ macrophages can be targeted with folate-linked drugs without promoting drug uptake by nonactivated macrophages. This trial was registered at www.clinicaltrials.gov as #NCT00588393.