Publications

While it is well established that acute stress can produce antinociception, a phenomenon referred to as stress-induced analgesia, repeated exposure to stress can have the opposite effect. Since, chronic pain syndromes, such as fibromyalgia and rheumatoid arthritis, may be triggered and/or exacerbated by chronic stress, we have evaluated the effect of repeated stress on mechanical nociceptive threshold and inflammatory hyperalgesia. Using the Randall-Selitto paw pressure test to quantify nociceptive threshold in the rat, we found that repeated non-habituating sound stress enhanced the mechanical hyperalgesia induced by the potent inflammatory mediator, bradykinin, which, in normal rats, produces hyperalgesia indirectly by stimulating the release of prostaglandin E2 from sympathetic nerve terminals. Hyperalgesia induced by the direct-acting inflammatory mediator, prostaglandin E2 as well as the baseline nociceptive threshold, were not affected. Adrenal medullectomy or denervation, reversed the effect of sound stress. In sound stressed animals, bradykinin-hyperalgesia had a more rapid latency to onset and was no longer inhibited by sympathectomy, compatible with a direct effect of bradykinin on primary afferent nociceptors. In addition, implants of epinephrine restored bradykinin-hyperalgesia in sympathectomized non-stressed rats, lending further support to the suggestion that increased plasma levels of epinephrine can sensitize primary afferents to bradykinin. These results suggest that stress-induced enhancement of inflammatory hyperalgesia is associated with a change in mechanism by which bradykinin induces hyperalgesia, from being sympathetically mediated to being sympathetically independent. This sympathetic-independent enhancement of mechanical hyperalgesia is mediated by the stress-induced release of epinephrine from the adrenal medulla.

UNLABELLED

Although epinephrine (EPI) has been suggested to contribute to the pain and hyperalgesia associated with inflammation and nerve injury, there have been very few in vivo electrophysiologic studies of the effects of EPI on nociceptors. We found with the single-unit recording technique that the intradermal administration of EPI resulted in excitation of a group of C fibers and a decrease in the mechanical activation threshold in a non-overlapping group. Unexpectedly, the fibers that were neither excited nor demonstrated a decrease in threshold demonstrated as a group a significant increase in response to sustained suprathreshold mechanical stimuli, an effect not observed in the other 2 groups of C fibers. This identifies a novel response of C-fiber nociceptors to an inflammatory mediator and suggests it is present in a class of C fibers previously considered unresponsive to hyperalgesic inflammatory mediators.

PERSPECTIVE

Our study provides support for the suggestion that EPI, a neuroendocrine stress hormone as well as an inflammatory mediator, might contribute to pain syndromes, especially in the setting of chronic stress.

Genetic association studies in admixed populations may be biased if individual ancestry varies within the population and the phenotype of interest is associated with ancestry. However, recently admixed populations also offer potential benefits in association studies since markers informative for ancestry may be in linkage disequilibrium across large distances. In particular, the enhanced LD in admixed populations may be used to identify alleles that underlie a genetically determined difference in a phenotype between two ancestral populations. Asthma is known to have different prevalence and severity among ancestrally distinct populations. We investigated several asthma-related phenotypes in two ancestrally admixed populations: Mexican Americans and Puerto Ricans. We used ancestry informative markers to estimate the individual ancestry of 181 Mexican American asthmatics and 181 Puerto Rican asthmatics and tested whether individual ancestry is associated with any of these phenotypes independently of known environmental factors. We found an association between higher European ancestry and more severe asthma as measured by both forced expiratory volume at 1 second (r=-0.21, p=0.005) and by a clinical assessment of severity among Mexican Americans (OR: 1.55; 95% CI 1.25 to 1.93). We found no significant associations between ancestry and severity or drug responsiveness among Puerto Ricans. These results suggest that asthma severity may be influenced by genetic factors differentiating Europeans and Native Americans in Mexican Americans, although differing results for Puerto Ricans require further investigation.

Dispensing limits, which ration prescriptions to 30-day supplies when filled at community pharmacies, is a strategy commonly used to control prescription drug costs. Yet, little is known about drug dispensing patterns. Prescription dispensing patterns may have important influences on adherence, therapeutic and preventive health outcomes, and costs. This study examined dispensing patterns for five drug classes commonly prescribed for chronic conditions.

The use of complementary and alternative medicines-including a variety of herbal therapies-by patients undergoing cancer chemotherapy has been well documented. Despite such widespread use, however, the benefits and potential mechanisms of such herbal medicines remain largely anecdotal. In this study we examined the effects of a Chinese herbal formula, Bing De Ling, when administered as an adjunct to chemotherapeutic agent 5-fluorouracil (5-FU) in the CT26 mouse colon cancer model. 5-FU and Bing De Ling were administered to both nave and CT26 mouse colon cancer-bearing BALB/c mice. Our results indicate that although the herbal formula alone did not result in antitumor effects under experimental conditions, it significantly enhanced 5-FU-induced tumor growth inhibition. Oral administration of Bing De Ling also increased survival rates of both tumor-bearing and tumor-free mice treated with 5-FU. Furthermore, oral administration of Bing De Ling reduced weight loss in tumor-free mice receiving 5-FU when compared to tumor-free mice that received 5-FU alone. Our data further show that 5-FU upregulates serum levels of IL-6, known to contribute to weight loss, in tumor-free mice, and that this increase in IL-6 is significantly less in mice that received Bing De Ling in addition to 5-FU. These data show Bing De Ling both enhances the antitumor responses of 5-FU and ameliorates side effects.

BACKGROUND

Black elders have a greater frequency of functional decline than do white elders. The impact of cognitive function on explaining black-white disparities in functional decline has not been extensively explored.

METHODS

To compare the extent to which different risk domains (comorbidity, smoking, socioeconomic status (SES), self-rated health, and cognitive function) explain more frequent functional decline in black elders, we studied 779 black and 4892 white community-dwelling adults aged 70 and older from the Assets and Health Dynamics Among the Oldest Old (AHEAD), a population-based cohort study begun in 1993. Our primary outcome was worse functional status at 2 years than at baseline. We used logistic regression to compare the unadjusted with the adjusted black-white odds ratios (ORs) after adjusting for each risk domain.

RESULTS

At baseline black participants aged 70-79 had higher rates of smoking, diabetes, and hypertension; lower SES; and worse cognitive function than did white participants (p <.05 for all). The mean cognitive score was 15.7 in black and 21.8 in white participants (p <.01). Black participants had a higher frequency of 2-year functional decline than did white participants (10.9% vs 4.7%; OR = 2.61, 95% confidence interval [CI], 1.69-4.03 adjusted for age and sex). Adjustment for comorbidity and smoking did not significantly change the black-white OR, whereas self-rated health and SES accounted for about half the risk. Adjustment for cognitive function accounted for nearly all the associated decline (OR = 1.10, 95% CI, 0.67-1.79). Among participants aged 80 and over, those who were black had significantly lower risk for functional decline after adjustment for cognitive function (OR = 0.61, 95% CI, 0.38-0.96 vs OR = 1.08, 95% CI, 0.70-1.66 adjusted for age and sex only).

CONCLUSIONS

Cognitive function mediated the higher frequency of functional decline among black elders. Efforts to understand cognitive function may enhance our understanding of black-white disparities in health outcomes.

Idiopathic interstitial pneumonias comprise usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (RB-ILD), cryptogenic organizing pneumonia (COP), acute interstitial pneumonia (AIP), and lymphoid interstitial pneumonia (LIP). Each of these entities has a typical imaging and histologic pattern, although in practice the imaging patterns may be variable. Each entity may be idiopathic or may be secondary to a recognizable cause such as collagen vascular disease or inhalational exposure. The diagnosis of idiopathic interstitial pneumonia is made by means of correlation of clinical, imaging, and pathologic features. The characteristic computed tomographic (CT) features of UIP are predominantly basal and peripheral reticular pattern with honeycombing and traction bronchiectasis. NSIP is characterized by predominantly basal ground-glass opacity and/or reticular pattern, often with traction bronchiectasis. DIP and RB-ILD are smoking-related lung diseases characterized by ground-glass opacity and centrilobular nodules. COP is characterized by patchy peripheral or peribronchovascular consolidation. AIP manifests as diffuse lung consolidation and ground-glass opacity. LIP is associated with a CT pattern of ground-glass opacity sometimes associated with perivascular cysts.

In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6, and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and C-reactive protein (CRP) were measured to examine the association between these markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the majority of cases were mild (grade I), and severe (grade II or grade III) cases occurred only in male individuals. Compared with individuals without HF, those with severe HF--and, to a lesser degree, those with mild HF--had a significantly lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a higher level of CRP and were more likely to produce IL-6; furthermore, those with severe HF had a significantly higher level of IL-1, compared with those either without HF or with mild HF. These findings suggest that even mild HF is associated with nutritional morbidity and underscore the importance of early recognition and treatment. In addition, our data are consistent with the hypothesis that, by systemically increasing the levels of the proinflammatory cytokines IL-1 and IL-6, HF causes undernutrition and anemia.