Citations

Abstract Previous research has suggested that nicotine may be therapeutically useful in the treatment of sleep-disordered breathing. The development of transdermal nicotine delivery systems has allowed us to test the overnight effectiveness of nicotine. Twenty nonsmoking subjects (10 men, 10 women) were recruited on the basis of a history of habitual snoring that was confirmed by overnight laboratory monitoring. Subjects were then randomized (double-blind crossover design) to receive either placebo or an active patch that delivers 11 mg of nicotine over a 24-h period. Patches were applied at 6 P.M. and removed at 6 A.M. the following morning, at which time venous blood was obtained for determination of serum nicotine concentrations. Polysomnography was performed using standard techniques to assess sleep architecture and sleep-disordered breathing. Snoring was monitored with a sound-level meter and quantitatively analyzed to determine the snoring index (SI) (number of snores per hour of sleep) and mean and maximum snoring intensities. The age of the subjects was 46.9 +/- 11.4 yr (mean +/- SD) and their mean body mass index (BMI) 33.3 +/- 4.6 kg/m2. A mean nicotine level was nondetectable with placebo and 7.8 +/- 2.3 ng/ml with wearing of an active patch. Nicotine decreased total sleep time (TST) by 33 min (p < or 0.01), sleep efficiency from 89.7 to 83.5% (p < or = 0.01), and percent rapid eye movement (REM) sleep from 18.8 to 15.1% (p < or = 0.01), and prolonged initial sleep latency (ISL) from 6.7 to 18.2 min (p < or = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract The effects of an anti-CD23 monoclonal antibody (B3B4) in CD23-deficient and CD23-overexpressing mice were compared in a murine model of allergic sensitization. After sensitization and challenge with OA, mice developed increased serum levels of OA-specific IgE and IgG1 with airway eosinophilia and AHR when compared with nonsensitized animals. Anti-CD23 treatment was studied under two protocols: 10-d OA aerosol exposure and intraperitoneal sensitization followed by aerosol challenge. In both protocols anti-CD23 significantly reduced IgE and IgG1 levels, abolished eosinophilia, and normalized AHR in BALB/c and wild-type CD23+ / + mice but not in CD23− / − mice. These changes were associated with increases in IFN- γ and decreases in IL-4 production, suggesting that CD23 binding may affect not only IgE production but also the Th1/Th2 imbalance during the development of allergic AHR. Absence of CD23 in gene-deficient mice significantly enhanced OA-specific IgE and IgG1 levels, airway eosinophilia, and AHR when compared with CD23+ / + wild-type littermates after sensitization and airway challenge. Sensitized and challenged CD23 transgenic mice also developed eosinophilic airway inflammation and methacholine hyperresponsiveness. However, the extent of AHR, BAL, and tissue eosinophilia in these animals showed a significant negative correlation with levels of CD23 expression on splenic T and B cells, demonstrating a limiting role of CD23 in the development of allergic AHR. Haczku A, Takeda K, Hamelmann E, Loader J, Joetham A, Redai I, Irvin CG, Lee JJ, Kikutani H, Conrad D, Gelfand EW. CD23 exhibits negative regulatory effects on allergic sensitization and airway hyperresponsiveness.

Abstract Interleukin-2 (IL-2), a product of activated T-cells, is now being used in a number of protocols for cancer immunotherapy. In one stem cell transplantation protocol for breast cancer, IL-2 is used together with interferon- γ (IFN- γ ) and cyclosporine to stimulate a graft-versus-tumor response and improve the likelihood of a prolonged remission. We present the case of a patient who developed peripheral eosinophilia, perihilar infiltrates, and hypoxemia after autologous stem cell transplantation and the use of recombinant IL-2 and IFN- γ. Histologic analysis of transbronchial lung biopsies demonstrated a few eosinophils within the bronchial submucosa. Immunostaining using antibodies directed against eosinophil major basic protein (MBP), however, revealed massive extracellular deposition of this toxic granule protein throughout the lung parenchyma. IL-2 therapy is well known to induce a peripheral eosinophilia and to be associated with the capillary leak syndrome characterized by weight gain, edema, and oliguria. The findings noted in this case report suggest that the eosinophil activation that accompanies immunologic therapy with IL-2 can result in direct toxicity to the lung and a localized vascular leak syndrome. This syndrome should be considered in the differential diagnosis of pulmonary infiltrates that occur acutely after bone marrow transplantation with cytokine augmentation.

Purpose By using data from North Central Cancer Treatment Group Phase III Trial N0147, a randomized adjuvant trial of patients with stage III colon cancer, we assessed the relationship between smoking and cancer outcomes, disease-free survival (DFS), and time to recurrence (TTR), accounting for heterogeneity by patient and tumor characteristics. Patients and Methods Before random assignment to infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or FOLFOX plus cetuximab, 1,968 participants completed a questionnaire on smoking history and other risk factors. Cox models assessed the association between smoking history and the primary trial outcome of DFS (ie, time to recurrence or death), as well as TTR, adjusting for other clinical and patient factors. The median follow-up was 3.5 years among patients who did not experience events. Results Compared with never-smokers, ever smokers experienced significantly shorter DFS (3-year DFS proportion: 70% v 74%; hazard ratio [HR], 1.21; 95% CI, 1.02 to 1.42). This association persisted after multivariate adjustment (HR, 1.23; 95% CI, 1.02 to 1.49). There was significant interaction in this association by BRAF mutation status (P = .03): smoking was associated with shorter DFS in patients with BRAF wild-type (HR, 1.36; 95% CI, 1.11 to 1.66) but not BRAF mutated (HR, 0.80; 95% CI, 0.50 to 1.29) colon cancer. Smoking was more strongly associated with poorer DFS in those with KRAS mutated versus KRAS wild-type colon cancer (HR, 1.50 [95% CI, 1.12 to 2.00] v HR, 1.09 [95% CI, 0.85 to 1.39]), although interaction by KRAS mutation status was not statistically significant (P = .07). Associations were comparable in analyses of TTR. Conclusion Overall, smoking was significantly associated with shorter DFS and TTR in patients with colon cancer. These adverse relationships were most evident in patients with BRAF wild-type or KRAS mutated colon cancer.

ObjectiveTo study left ventricular (LV) geometry in patients with rheumatoid arthritis (RA) and no history of heart failure compared with that in subjects with neither RA nor a history of heart failure, and to determine the impact of RA on LV remodeling.MethodsA cross‐sectional, community‐based study was conducted among adult (age ≥50 years) patients with RA and age‐ and sex‐matched subjects with neither RA nor a history of heart failure. All participants underwent standard 2‐dimensional Doppler echocardiography. LV geometry was classified into the following 4 categories based on relative wall thickness and sex‐specific cutoffs for the LV mass index: concentric remodeling, concentric hypertrophy, eccentric hypertrophy, or normal geometry.ResultsAmong 200 patients with RA and 600 age‐ and sex‐matched subjects without RA, the mean age was 65 years, and 74% of the individuals in both cohorts were female. Compared with subjects without RA, patients with RA were significantly more likely to have abnormal LV geometry (odds ratio [OR] 1.44, 95% confidence interval [95% CI] 1.03–2.00), even after adjusting for cardiovascular risk factors and comorbidities. Among subjects with abnormal LV geometry, the odds of concentric LV remodeling were significantly increased in patients with RA (OR 4.73, 95% CI 2.85–7.83). In linear regression analyses, the LV mass index appeared to be lower in patients with RA who were currently receiving corticosteroids (β ± SE −0.082 ± 0.027, P = 0.002), even after adjusting for cardiovascular risk factors and comorbidities.ConclusionRA was strongly associated with abnormal LV remodeling (particularly concentric LV remodeling) among RA patients without heart failure. This association remained significant after adjustment for cardiovascular risk factors and comorbidities. RA disease–related factors may promote changes in LV geometry. The biologic mechanisms underlying LV remodeling warrant further investigation.