Citations

Patients with Alzheimer's disease (AD) have abnormally low positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) in regions of the precuneus and the posterior cingulate, parietotemporal, and frontal cortex. Apolipoprotein E (APOE) ε4 gene dose (i.e., the number of ε4 alleles in a person's APOE genotype) is associated with a higher risk of AD and a younger age at dementia onset. We previously found that cognitively normal late-middle-aged APOE ε4 carriers have abnormally low CMRgl in the same brain regions as patients with probable Alzheimer's dementia. In a PET study of 160 cognitively normal subjects 47–68 years of age, including 36 ε4 homozygotes, 46 heterozygotes, and 78 ε4 noncarriers who were individually matched for their gender, age, and educational level, we now find that ε4 gene dose is correlated with lower CMRgl in each of these brain regions. This study raises the possibility of using PET as a quantitative presymptomatic endophenotype to help evaluate the individual and aggregate effects of putative genetic and nongenetic modifiers of AD risk.

Background— Onset of myocardial relaxation is highly energy dependent. Perfusion and therefore energy substrate delivery are predominantly reduced in the subendocardial myocardium in the early stages of progressive ischemia. We hypothesized that delayed onset of subendocardial diastolic thinning will functionally identify regionally hypoperfused resting myocardium. Methods and Results— Progressive left anterior descending coronary artery stenosis was induced by an ameroid occluder and maintained for 1 or 2 weeks (end point) in 12 dogs. M-mode tissue Doppler images of the anterior apical and middle segments (testing region) and middle inferior segment (control region) were acquired selectively in the subendocardium and subepicardium. The time to the onset of thinning was measured with the use of tissue Doppler velocity (TOTv) and a thickness function (TOTt). At the end point in the testing region, myocardial flow was significantly lower in the subendocardial layer ( P <0.05) in all animals, whereas viability staining showed preserved transmural viability in 10 dogs and thin subendocardial necrosis in 2 dogs. Both TOTv and TOTt were significantly ( P <0.01) prolonged in the testing region. The mean difference between subendocardial and subepicardial TOTv values versus that in the control region identified the ischemic region, even when only dogs with hypoperfused but transmurally viable myocardium were considered ( P <0.05). Systolic and diastolic myocardial velocities did not identify subendocardial hypoperfusion. Conclusions— In resting myocardium subtended to progressive coronary stenosis, a delayed onset of subendocardial thinning suggests an early stage of hypoperfusion, before the development of local wall motion abnormalities.

Purpose To determine, in a randomized comparison, whether the addition of paclitaxel to etoposide and cisplatin improves the time to progression and overall survival in patients with extensive small-cell lung cancer (SCLC) compared with standard etoposide and cisplatin and to compare the regimens' toxicity. Patients and Methods Eligible patients (N = 587) with untreated extensive SCLC were randomly assigned to receive either cisplatin 80 mg/m2 on day 1 and etoposide 80 mg/m2 on days 1 through 3 administered every 3 weeks for six cycles (EP) or cisplatin 80 mg/m2 on day 1, paclitaxel 175 mg/m2 over 4 hours on day 1, and etoposide 80 mg/m2 on days 1 to 3 followed by recombinant human granulocyte colony-stimulating factor on days 4 to 18 administered every 3 weeks for six cycles (PET). Results Reporting of demographics, response, and survival included 565 patients, of whom 282 were randomly assigned to receive EP and 283 were assigned to receive PET. Overall response rates were 68% for the EP arm and 75% for the PET arm. Median failure-free survival time was 5.9 months for the EP arm and 6 months for the PET arm (P = .179). Median overall survival time was 9.9 months for patients on EP and 10.6 months for patients on PET (P = .169). Toxic deaths occurred in 2.4% of the patients on EP and 6.5% of patients on PET. Conclusion PET did not improve the time to progression or survival in patients with extensive SCLC compared with EP alone and was associated with unacceptable toxicity.

ABSTRACT Exposure of ciprofloxacin- and cefepime-susceptible Pseudomonas aeruginosa isolates to increasing concentrations of ciprofloxacin selected for ciprofloxacin resistance in 26/27 and cefepime nonsusceptibility in 7/27 isolates. Exposure of the isolates to increasing concentrations of cefepime selected for cefepime nonsusceptibility in 20/27 isolates but not for ciprofloxacin resistance.

Purpose This study explored patients’ perceptions of barriers to diabetes education among a mostly African American population of adults with diabetes. Methods A survey was conducted among 605 new patients attending an urban outpatient diabetes clinic. The questionnaire gathered information on issues patients believed would adversely affect their ability to learn about diabetes. The type and frequency of education barriers were evaluated, and variables associated with reporting an obstacle were analyzed. Results Average patient age was 50 years, diabetes duration was 5.6 years, body mass index was 32 kg/m2, and hemoglobin A1C was 9.1%. The majority (56%) were women, 89% were African American, and 95% had type 2 diabetes. Most respondents (96%) had received some prior instruction in diabetes care; however, 53% anticipated future difficulties learning about diabetes. The most commonly cited concerns were poor vision (74%) and reading problems (29%). Patients with a perceived barrier to diabetes education were older (P < .001) than were persons without a barrier, and they differed in both employment and educational status (both P < .001). In adjusted analyses, older age, male gender, being disabled, and having an elementary education or less were associated with a significantly increased likelihood of having a barrier to diabetes education, whereas having a college education decreased the odds. Higher hemoglobin A1C levels also tended to be associated with a greater chance of reporting an education barrier (P = .05). Conclusions A substantial number of persons anticipated a barrier to diabetes education. Interventions at multiple levels that address the demographic and socioeconomic obstacles to diabetes education are needed to ensure successful self-management training.