BACKGROUND. During the time of lowest white blood cell count (nadir) of allogeneic hematopoietic stem cell transplantation (allo‐HSCT), cancer patients suffer from tremendous symptom burden related to therapy that requires intensive patient care. However, the mechanism underlying the development of multiple symptoms has not been established. METHODS. To explore the role of inflammatory cytokines in the development of treatment‐related symptoms, we studied dynamic changes in symptoms and in serum concentrations of inflammatory cytokines (interleukin [IL]‐6, IL‐8, soluble tumor necrosis factor receptor 1 [sTNF‐R1], IL‐1 receptor antagonist, and IL‐12p40p70) from pretherapy throughout the first 30 days of allo‐HSCT in 30 patients with acute myelogenous leukemia or myelodysplastic syndrome. We measured multiple symptoms repeatedly using the M. D. Anderson Symptom Inventory. Mixed‐effects modeling was used to analyze longitudinal data. RESULTS. In response to conditioning and stem‐cell infusion, serum levels of IL‐6 and the severity of multiple symptoms increased rapidly and peaked at nadir. From baseline to nadir (approximately Day 8 post‐transplantation), increase in IL‐6 was significantly associated with worsening of the most severe symptoms (fatigue, poor appetite, pain, drowsiness, dry mouth, and disturbed sleep; P< .01). During the first 30 days after transplantation, increases in IL‐6 (P< .001) and sTNF‐R1 (P< .05) significantly predicted the increasing severity of these symptoms. CONCLUSIONS. These results suggest that release of systemic inflammatory cytokines, mainly IL‐6, corresponds to an increase in treatment‐related multiple‐symptom burden during the nadir period of allo‐HSCT. Cancer 2008. © American Cancer Society.
Summary In human athletes, conditioning, training and competition are commenced before skeletal maturity. Yet in equine athletics, racing of young (age 2 years) horses remains contentious. Tendon injury persists as major causes of wastage in equine athletes. Minimising injury and associated welfare issues could involve a radical approach to the timing and implementation of conditioning and training. Tendons were examined from Thoroughbreds, Dutch Warmblood foals, working horses and also a group of wild horses to evaluate effects of age, function and exercise. Gross mechanical properties did not differ significantly with age or exercise, but showed a high variance within each group. Mechanical properties of tendon tissue showed significant differences as a function of age and location. The collagen fibril crimp angle and length showed a regional reduction in the central core with exercise and age, with a synergistic effect. Regional differences in collagen fibril diameter were seen in long‐term exercised older horses, but not in short‐term exercised, or younger, horses. The higher proportion of small fibrils in the central region of the long‐term exercised horses did not correlate with new collagen formation and therefore appear to result from disassembly of the larger diameter fibrils. Fibril diameter distributions were influenced by exercise regimens in the growing foal. Changes in molecular composition occurred in longer‐term exercise and older horses, in the centre of the tendon, with higher levels of type III collagen and changes in glycosaminoglycan (GAG) content. Cartilage Oligomeric Matrix Protein (COMP) levels also appear to be modulated by age, function and superimposition of exercise. These changes were all exacerbated with age and exercise, suggesting appropriate exercise in young horses may lead to a lower incidence of injury than in older horses. An hypothesis is advanced that immature tendon can respond to exercise while mature tendon has limited, if any, ability to do so. These findings support potentially controversial earlier conditioning and racing of younger, rather than older, equine athletes.
BackgroundTraffic-related air pollution has been associated with adverse health outcomes, and the immune system may be a biologic mediator of health effects.ObjectivesWe analyzed associations between living near major roads and immune status as measured by five immune assays. We hypothesized that living near a freeway, arterial, or truck route would be associated with increased inflammation and decreased immune function.MethodsWe used a geographic information system (GIS) to determine residential proximity to major roads among 115 postmenopausal, overweight women in the greater Seattle, Washington (USA), area whose immunity was assessed at the baseline visit of an exercise intervention trial. We evaluated three inflammatory markers (C-reactive protein, serum amyloid A, and interleukin-6) and two functional assays of cellular immunity [natural killer (NK) cell cytotoxicity and T-lymphocyte proliferation].ResultsWomen living within 150 m of arterial roads had 21% lower NK cytotoxicity compared with women who lived farther from an arterial [mean cytotoxicity, 19.5%; 95% confidence interval (CI), 15.6–23.5%; vs. mean cytotoxicity, 24.8%; 95% CI, 22.0–27.5%], after adjustment for both individual-level and census tract–level demographic characteristics. This association was limited to women who reported exercising near traffic. Fewer women lived near freeways and truck routes. Markers of inflammation and lymphocyte proliferation did not consistently differ according to proximity to major roads.ConclusionsIf the observed association between residential proximity to traffic and decreased NK cytotoxicity is confirmed in other populations, our results may have implications for local land use policy.
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