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Pharmaceutical Chemistry Journal - Eulophia nuda Lindl. (Orchidaceae) is a small perennial terrestrial herb found in central and Southeast Asian regions usually known for its ethnomedicinal uses by...  相似文献   
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Introduction

Pelvic Organ Prolapse Quantification (POP-Q) system, measured in centimetres using a ruler (e.g. POPstix®), is recommended to quantify prolapse severity. POPstix® are costly (US $1/ruler). Home-made devices are used instead, but these have not been shown to be reproducible.

Hypothesis

Digitally assessed POP-Q (DPOP-Q) is as reliable, reproducible and acceptable as POP-Q assessed using POPstix®.

Methods

In this randomised crossover diagnostic agreement trial, each assessor measured the index finger of their dominant hand using a ruler. At visit one, patients were randomised to either POPstix® POP-Q assessment in a modified lithotomy position or DPOP-Q in both modified a lithotomy and a standing position. After the first clinician conducted this assessment, a second blinded clinician then carried out the remaining assessment on the same patient. For each examination, duration was recorded, along with a patient-completed discomfort score. Twenty-five women were invited for visit two, at which DPOP-Q was recorded by the same clinician who undertook DPOP-Q at the first visit. This allowed evaluation of inter- and intraobserver agreement together with examination acceptability.

Results

One hundred and nine women were recruited [median age 55 years, parity 2, body mass index (BMI) 27.1]. Of the 25 patients invited, 23 returned for visit two. DPOP-Q had high interobserver reliability [κ?=?0.94, 95 % confidence interval (CI) 0.878–0.996] and intraobserver reliability (α?=?0.96) with POPstix®. DPOP-Q was significantly quicker (p?=?0.02) and less uncomfortable (p?<?0.01) than POPstix® POP-Q.

Conclusion

DPOP-Q is reliable, acceptable and cost effective.
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Background

Most studies of acute necrotizing pancreatitis (ANP) focus on short-term outcomes. We evaluated long-term survival and outcomes following ANP.

Methods

Patients treated for ANP at the University of Pittsburgh Medical Center from 2001 to 2008 were studied. Data on presentation and course during initial hospitalization and follow-up (median 34 months) was extracted.

Results

Mean age of patients (n?=?167) was 53?±?16 years; 70 % were male, 94 % white, 71 % transfers, 52 % biliary etiology, and 78 % had first-attack of acute pancreatitis. Majority had severe disease with high Acute Physiology and Chronic Health Evaluation II (APACHE-II) score (median 11), length of stay (median 26 days), intensive care unit (ICU) admission (87 %), presence of systemic inflammatory response syndrome (SIRS) (90 %), persistent organ failure (60 %), and infected necrosis (50 %). Intervention was needed in 74 %. Eighteen (10.8 %) patients died during index hospitalization, 9 (5.4 %) during the first year, and 13 (7.8 %) after 1 year. Median survival was significantly shorter when compared with age- and sex-matched US general population (9.1 vs. 26.1 years, p?<?0.001). Increasing age (HR 1.05), persistent organ failure (HR 4.5), and >50 % necrosis (HR 3.8) were independent predictors of death at 1 year. In eligible patients, new-onset diabetes, oral pancreatic enzyme replacement therapy, and disability were noted in 45, 25, and 53 %, respectively.

Conclusion

ANP significantly impacts long-term survival. A high proportion of patients develop functional derangement and disability following ANP.
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This study was designed to test the hypothesis that inhibition of agonist-induced delta-receptor down-regulation would block the development of opioid tolerance in a cell-based model. A human embryonic kidney 293 cell line was established that expressed an epitope-tagged delta-opioid receptor (DOR). Treatment of DOR cells with Tyr-d-Ala-Gly-Phe-d-Leu-enkephalin (DADL) resulted in a time-dependent decrease in the B(max) of delta-opioid receptor binding sites and immunoreactive receptor protein. When cells were coincubated with the proteasome inhibitor N-benzyloxycarbonyl-l-leucyl-l-leucyl-l-leucinal (ZLLL) and DADL, the magnitude of the agonist-induced decrease in B(max) and immunoreactive receptor protein was reduced compared with DADL treatment alone. Acute treatment of DOR cells with DADL caused a 3-fold increase in the level of phosphorylated mitogen-activated protein (MAP) kinase. Prior exposure of DOR cells to DADL completely abrogated the agonist-induced activation of MAP kinase. When DOR cells were coincubated with DADL and ZLLL, the proteasome inhibitor prevented the loss of agonist activation of MAP kinase. Acute treatment of DOR cell membranes with DADL stimulated [(35)S]guanosine 5'-3-O-(thio-)triphosphate (GTPgammaS) binding. When DOR cells were preincubated with DADL, the agonist-induced increase in [(35)S]GTPgammaS binding was attenuated. Coincubation of ZLLL and agonist partially prevented the decreased responsiveness to agonist stimulation. The results of this study demonstrated that inhibition of agonist-induced down regulation with a proteasome inhibitor attenuated opioid tolerance in a cellular model, and suggest that coadministration of a proteasome inhibitor with chronic opioid agonist treatment may be useful for limiting opioid tolerance in vivo.  相似文献   
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