The clinical application of chemotherapy to brain tumors has been severely limited because antitumor agents are typically unable to penetrate an intact blood-brain barrier (BBB). Although doxorubicin (DOX) has been named as a strong candidate for chemotherapy of the central nervous system (CNS), the BBB often prevents cytotoxic levels from being achieved. In this study, we demonstrate a noninvasive method for the targeted delivery of DOX through the BBB, such that drug levels shown to be therapeutic in human tumors are achieved in the normal rat brain. Using MRI-guided focused ultrasound with preformed microbubbles (Optison) to locally disrupt the BBB and systemic administration of DOX, we achieved DOX concentrations of 886 6 327 ng/g tissue in the brain with minimal tissue effects. Tissue DOX concentrations of up to 5,366 6 659 ng/g tissue were achieved with higher Optison doses, but with more significant tissue damage. In contrast, DOX accumulation in nontargeted contralateral brain tissue remained significantly lower for all paired samples (p < 0.001). These results suggest that targeted delivery by focused ultrasound may render DOX chemotherapy a viable treatment option against CNS tumors, despite previous accessibility limitations. In addition, MRI signal enhancement in the sonicated region correlated strongly with tissue DOX concentration (r 5 0.87), suggesting that contrast-enhanced MRI could perhaps indicate drug penetration during image-guided interventions. Our technique using MRIguided focused ultrasound to achieve therapeutic levels of DOX in the brain offers a large step forward in the use of chemotherapy to treat patients with CNS malignancies. ' 2007 Wiley-Liss, Inc.

OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations. METHODS:Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life.RESULTS: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 mg/L; P , .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P , .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients.

BACKGROUND: Many seniors rely on paid non-familial caregivers to maintain their independence at home. Caregivers often assist with medication reminding and activities of daily living. No prior studies have examined the health literacy levels among paid non-familial caregivers. OBJECTIVES: To determine health literacy levels and the health-related responsibilities of paid non-familial caregivers of seniors. DESIGN: One-on-one face-to-face surveys. The Test for Functional Health Literacy (TOFHLA) was administered to identify health literacy levels. Caregivers were asked to demonstrate their skill in medication use by following directions on pill bottles and sorting medications into pill boxes. PARTICIPANTS: Ninety-eight paid unrelated caregivers of seniors recruited at physician offices, caregiver agencies, senior shopping areas, and independent living facilities. RESULTS: Average age of caregivers was 49.5 years, and 86.7% were female. Inadequate health literacy was found in 35.7% of caregivers; 60.2% of all caregivers made errors with the pillbox test medications, showing difficulty in following label directions. Health-related tasks (i.e., medication reminding, sorting, dispensing, and accompanying seniors to physician appointments) were performed by 85.7% of caregivers. The mean age of their seniors was 83.9 years (range 65-99 years), and 82.1% were female. CONCLUSION: Paid non-familial caregivers are essential for many seniors to remain independent and maintain their health. Many caregivers perform health-related duties, but over 1/3 have inadequate health literacy and have difficulties following medication-related instructions. Educating caregivers and ascertaining their health literacy levels prior to assigning health-related tasks may be an important process in providing optimal care to seniors.

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