Endotoxin preconditioning protects against the cytotoxic effects of TNFalpha after stroke: a novel role for TNFalpha in LPS-ischemic tolerance.

Lipopolysaccharide (LPS) preconditioning provides neuroprotection against subsequent cerebral ischemic injury. Tumor necrosis factor-alpha (TNFalpha) is protective in LPS-induced preconditioning yet exacerbates neuronal injury in ischemia. Here, we define dual roles of TNFalpha in LPS-induced ischemic tolerance in a murine model of stroke and in primary neuronal cultures in vitro, and show that the cytotoxic effects of TNFalpha are attenuated by LPS preconditioning. We show that LPS preconditioning significantly increases circulating levels of TNFalpha before middle cerebral artery occlusion in mice and show that TNFalpha is required to establish subsequent neuroprotection against ischemia, as mice lacking TNFalpha are not protected from ischemic injury by LPS preconditioning. After stroke, LPS preconditioned mice have a significant reduction in the levels of TNFalpha (approximately threefold) and the proximal TNFalpha signaling molecules, neuronal TNF-receptor 1 (TNFR1), and TNFR-associated death domain (TRADD). Soluble TNFR1 (s-TNFR1) levels were significantly increased after stroke in LPS-preconditioned mice (approximately 2.5-fold), which may neutralize the effect of TNFalpha and reduce TNFalpha-mediated injury in ischemia. Importantly, LPS-preconditioned mice show marked resistance to brain injury caused by intracerebral administration of exogenous TNFalpha after stroke. We establish an in vitro model of LPS preconditioning in primary cortical neuronal cultures and show that LPS preconditioning causes significant protection against injurious TNFalpha in the setting of ischemia. Our studies suggest that TNFalpha is a twin-edged sword in the setting of stroke: TNFalpha upregulation is needed to establish LPS-induced tolerance before ischemia, whereas suppression of TNFalpha signaling during ischemia confers neuroprotection after LPS preconditioning.     

Phonological features of child African American English.

The production of phonological features of African American English (AAE) was examined for 64 typically developing African American children in the 2nd through the 5th grade. Students read aloud passages written in Standard American English. Sixty of the students read the passages using AAE, and 8 different phonological features were represented in their readings. Phonological features were more frequent than morphosyntactic features. The findings as a whole support use of the taxonomy developed for this investigation in characterizing the phonological features of child AAE.     

Inhibition of allergic airways inflammation and airway hyperresponsiveness in mice by dexamethasone: role of eosinophils,IL-5, eotaxin,and IL-13

BACKGROUND: Glucocorticoids inhibit allergen-induced airway eosinophilia and airway hyperresponsiveness (AHR). Whether glucocorticoids mediate their effects on AHR by inhibiting eotaxin and IL-5, 2 of the principal mediators of eosinophilia, or through IL-13, an important mediator of AHR, has not been established. OBJECTIVE: We sought to investigate the effects of glucocorticoids on airway eosinophilia and the expression of IL-5, eotaxin, and IL-13 in relation to the induction of AHR in a murine model of allergic asthma. METHODS: Dexamethasone (4 mg/kg) and mAbs against eotaxin (80 micro g/kg) and IL-5 (100 micro g/kg) singly and in combination were administered to immunized mice before antigen challenge. Airway responsiveness to methacholine was measured in anesthetized and mechanically ventilated animals. Eotaxin, IL-5, and IL-13 in bronchoalveolar lavage fluid (BALF), lung homogenates, or both were measured by means of ELISA. RESULTS: A single antigen challenge induced AHR that lasted at least 10 days. Eotaxin protein and mRNA levels increased in lung tissue but not in BALF after challenge. IL-5 protein and mRNA levels increased both in BALF and in lung tissue. Dexamethasone reduced airway eosinophilia, AHR, and protein and mRNA for eotaxin and IL-5. Anti-murine eotaxin and anti-IL-5 antibodies alone and in combination reduced the ovalbumin-induced airway eosinophilia significantly but failed to inhibit AHR. Both dexa-methasone and anti-IL-5/anti-eotaxin inhibited the increases in lung IL-13 levels after ovalbumin challenge to a similar extent. CONCLUSION: These findings suggest that the inhibition of AHR by the glucocorticoid dexamethasone does not appear to be explained by effects on eosinophilia, eotaxin, IL-5, or IL-13.     

Variation in perceived competence, glycemic control, and patient satisfaction: relationship to autonomy support from physicians

There is considerable variation in care provided to patients with diabetes related to metabolic control, preventive services, and degree of patient-centered support. This study evaluates the relation of self-determination theory (SDT) constructs of clinician autonomy support, and patient competence to glycemic control, depressive symptoms, and patient satisfaction from baseline surveys of 634 patients of 31 Colorado primary care physicians participating in a program to improve diabetes care. Spearman correlations of autonomy support from one's clinician with patient competence, HbA1c, depressive symptoms and satisfaction were significant (R = -0.11 to 0.55, P < 0.005). Structural equation modeling demonstrated that autonomy support was significantly related to perceived competence, depressive symptoms, patient satisfaction, and indirectly to glycemic control. Perceived competence was significantly related to depressive symptoms, patient satisfaction and glycemic control. Further, the motivation constructs from SDT accounted for 5% of the variance in glycemic control, 8% of the variance in depression, and 42% of the variance in patient satisfaction. Quality improvement efforts need to pay greater attention to patient competence, satisfaction, and depression, in addition to glycemic control. Clinician autonomy support was found to be reliably measured and moderately correlated with psychosocial and biologic outcomes related to diabetes self-management. These results suggest training clinicians to increase their support of patient autonomy may be one important avenue to improve diabetes outcomes.     

Physical Similarity and Twin Resemblance for Eating Attitudes and Behaviors: A Test of the Equal Environments Assumption

The Equal Environments Assumption (EEA) in twin studies of eating pathology was investigated by examining the hypothesis that twin resemblance for eating attitudes and behaviors is affected by their degree of physical similarity. Eating attitudes and behaviors were assessed in 338 female adolescent twin pairs with a revised version of the Eating Disorder Inventory (EDI). General physical similarity as well as body size/shape similarity were assessed using ratings of color photographs, ratings of body shape, and body mass index. All physical similarity assessments were conducted blind to twin zygosity. Significant associations between physical similarity and twin similarity for eating attitudes and behaviors were not found. Mean EDI within-twin pair absolute difference scores did not differ significantly among more versus less physically-similar groups. Additionally, correlation and regression analyses failed to find a significant association between EDI absolute difference scores and physical similarity indices. The current findings provide support for the EEA in twin studies of eating attitudes and behaviors.     

Molecular epidemiology of macrolide resistance in neonatal bloodstream isolates of group B streptococci

Pulsed-field gel electrophoresis (PFGE) was performed on 122 neonatal bloodstream isolates of group B streptococci (GBS) to further examine the relationship between macrolide resistance and serotype V GBS (GBS-V). Over one-third (35%) of macrolide-resistant GBS belonged to a single PFGE subtype of GBS-V, which was also the most common GBS-V subtype noted in previous Centers for Disease Control and Prevention surveillance studies. Erm methylase (ermA and ermB) was the most common resistance mechanism detected, present in 12 of 20 macrolide-resistant GBS.     

Assessing olfaction in the neuropsychological exam: the relationship between odor identification and cognition in older adults.

The relationship between odor identification and cognition has not been previously well characterized. The neuroanatomy of the olfactory system and the frequent finding of olfactory dysfunction in neurodegenerative diseases suggest a likely relationship between odor identification and memory, language, and executive functioning, though previous studies have often failed to demonstrate the expected relationship. The current study examined this relationship in across a continuum of ability levels (N=100). Strongest correlations were found between odor identification and language, most aspects of memory, and a measure of general cognitive functioning. Significant but more modest correlations were seen between odor identification and attention, motor, visuospatial, and executive functions. A regression analysis revealed language as the only significant predictor of olfactory performance. These findings suggest that odor identification is most closely associated with other measures of temporo-limbic functioning. The implications of these findings, particularly in consideration of the assessment of older adults, are discussed.     

A women's health track for internal medicine residents using evidence-based medicine.

OBJECTIVES: Evidenced-based medicine has established itself as an integral part of medical education and practice. The explosion of new knowledge in women's health and the need to teach this to internal medicine residents in an evidence-based fashion have presented a challenge to medical educators. To address this need, we developed and implemented an evidence-based women's health curriculum to be used in addition to clinical training in a women's health center for internal medicine residents. The objectives of the curriculum are to (1) define and utilize basic evidence-based medicine concepts to critically analyze women's health literature, (2) understand recent innovations in women's health from an evidence-based viewpoint, (3) gain clinical experience in women's health, and (4) apply evidence-based medicine to the clinical practice of women's health. DESCRIPTION: We designed our curriculum based on recommendations from the National Academy of Women's Health Medical Education, the American Board of Internal Medicine, the Fifth Report of the Council on Graduate Medical Education, and the results of needs assessments of internal medicine residents at our institution. Using Medline to create a women's health bibliography, an extensive literature search was performed on the following topics: osteoporosis, breast cancer, hormone replacement therapy, domestic violence, coronary artery disease in women, menopause, headaches, substance abuse in women, urinary incontinence, dementia, sexual dysfunction, and evidence-based medicine. Peer-reviewed journal articles were compiled by subject matter for placement in our clinic's resource center and were entered into a computerized database that will link with online journals and be available for electronic access. Most articles were selected based on the criteria of data published since 1990, and randomized, double-blinded, placebo-controlled studies were given preference. Weekly 45-minute sessions preceding the resident clinic in the women's health center are held in a journal-club format to review literature in a systematic fashion. Faculty and residents review and analyze one to two articles weekly. Content experts provide context and clinical expertise to resident discussions. Clinical questions, such as "Should I prescribe hormone replacement therapy to my postmenopausal patient?" are addressed in each session. Evidence-based medicine core concepts are reviewed and applied; these core concepts include the number needed to treat, absolute risk reduction, and relative risk. DISCUSSION: The women's health curriculum, weekly conferences, and clinical experience serve to update residents and clinicians in women's health literature, to exchange ideas for the improvement of women's health as it is taught in internal medicine, and to further elucidate the evidence behind what we practice and teach. The curriculum equips physicians to provide patients with solid, evidence-based interpretations of new scientific knowledge to discern truth from fallacy.     

Circulating levels of placental protein 12 and chorionic gonadotrophin following RU 38486 and Gemeprost for termination of first trimester pregnancy

First trimester termination of pregnancy was successfully inducedin ten patients with RU 38486 followed 2 days later by a prostaglandin(Gemeprost) pessary. Human chorionic gonadotrophin (HCG) valuesremained unaltered until after the abortion. The levels of placentalprotein 12 (PP12) showed an immediate and significant fall followingRU 38486, then rose to values substantially higher than thoseat the initial visit after 2 days. These findings show thatRU 38486 has a direct inhibitory effect on tissues producingPP12 and confirm the progesterone dependency of this protein