Nerve growth factor (NGF) plays a critical role in the development and survival of neurons in the peripheral nervous system. Following treatment with NGF but not epidermal growth factor, rat pheochromocytoma (PC12) cells undergo neural differentiation. We have cloned a nervous system-specific mRNA, NGF33.1, that is rapidly and relatively selectively induced by treatment of PC12 cells with NGF and basic fibroblast growth factor in comparison with epidermal growth factor. Analysis of the nucleic acid and predicted amino acid sequences of the NGF33.1 cDNA clone suggested that this clone corresponded to the NGF-inducible mRNA called VGF (A. Levi, J. D. Eldridge, and B. M. Paterson, Science 229:393-395, 1985; R. Possenti, J. D. Eldridge, B. M. Paterson, A. Grasso, and A. Levi, EMBO J. 8:2217-2223, 1989). We have used the NGF33.1 cDNA clone to isolate and characterize the VGF gene, and in this paper we report the complete sequence of the VGF gene, including 853 bases of 5' flank revealed TATAA and CCAAT elements, several GC boxes, and a consensus cyclic AMP response element-binding protein binding site. The VGF promoter contains sequences homologous to other NGF-inducible, neuronal promoters. We further show that VGF mRNA is induced in PC12 cells to a greater extent by depolarization and by phorbol-12-myristate-13-acetate treatment than by 8-bromo-cyclic AMP treatment. By Northern (RNA) and RNase protection analysis, VGF mRNA is detectable in embryonic and postnatal central and peripheral nervous tissues but not in a number of nonneural tissues. In the cascade of events which ultimately leads to the neural differentiation of NGF-treated PC12 cells, the VGF gene encodes the most rapidly and selectively regulated, nervous-system specific mRNA yet identified.
OBJECTIVES To examine the effect of a multi-component intervention on pain and function following orthopedic surgery. DESIGN Controlled prospective propensity score matched clinical trial. SETTING New York City acute rehabilitation hospital. PARTICIPANTS 249 patients admitted to rehabilitation following hip fracture repair (N=51) hip (N=64) or knee (N=134) arthroplasty. INTERVENTION Pain assessment at rest and with physical therapy (PT) by staff using numeric rating scales (1 to 5). Physician protocols for standing analgesia and pre-emptive analgesia prior to PT were implemented on the intervention unit. Control unit patients received usual care. MAIN OUTCOME MEASURES Pain, analgesic prescribing, gait speed, transfer time, and percent of PT sessions completed during admission. Pain and difficulty walking at 6, 12, 18, and 24 weeks following discharge. RESULTS In multivariable analyses compared to controls, intervention patients were significantly more likely to report no or mild pain at rest (66% versus 49%, P=.004) and with PT (52% versus 38%, P=.02) on average for the first 7 days of rehabilitation; had faster 8 foot walk times on days four (9.3 seconds versus 13.2 seconds, P=.02) and seven (6.9 versus 9.2 seconds, P=.02); received more analgesia (8.0 milligrams of morphine sulfate equivalents/day, P<0.001); were more likely to receive standing analgesia (98% versus 48%, P<.001); and had significantly shorter lengths of stay (10.1 versus 11.3 days, P=.005). At 6 months compared to controls, intervention patients were less likely to report moderate/severe pain with walking (15% versus 4%, P=.02), that pain did not interfere with walking (7% versus 18%, P=.004), and were less likely to be taking analgesics (35% versus 51%, P=.03). CONCLUSION The intervention improved post-operative pain, reduced chronic pain, and improved function.
Context Intensive palliative care consultations for plan of care may reduce racial differences in end-of-life care. Objectives To compare cancer patients’ hospice referrals and code status changes after inpatient palliative care consultations by patient ethnicity and consultation intensity. Methods This observational cohort study prospectively recorded data for all adult cancer patients receiving palliative care consultations at the largest teaching hospital in Hawaii from 2005 through 2009. Chi-square analyses compared hospice referral and code status changes to “Do Not Attempt Resuscitation” by patient characteristics and consultation intensity (more intensive plan of care versus pain and/or symptom management without plan of care). Multiple logistic regression models analyzed factors associated with hospice referral and code status change. Results The 1362 consultations generated 454 (33.3%) hospice referrals and 234 (17.2%) code status changes. Controlling for age, gender, Karnofsky score and pre-consultation hospital days, Asian, Pacific Islander, and “other” ethnicities demonstrated increased likelihood of hospice referral versus whites (adjusted odds ratios [AOR] 1.46–2.34, P<0.05). Intensive plan of care consultations were strongly associated with hospice referral (AOR 3.08, 95% confidence interval [CI] 2.33–4.07, P<0.0001). Controlling for consultation intensity reduced the association between ethnicity and hospice referral (AORs 1.35–2.06, P=0.03, “other” ethnicity; P=nonsignificant, Asian and Pacific Islander). Intensive consultations were strongly associated with code status change (AOR 2.96; 95%CI 2.08–4.22, P<0.0001). Ethnicity was not significantly associated with code status change. Conclusion Consultation intensity was the strongest predictor of hospice referrals and code status changes, and reduced the ethnic variations associated with hospice referral.
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