1 The purpose of the present study is to compare the capacity of opioid antagonists to elicit withdrawal jumping in mice following two acute pretreatment doses of the opioid agonist morphine. Antagonists that precipitate vigorous withdrawal jumping across both morphine treatment doses are hypothesized to be strong inverse agonists at the m-opioid receptor, whereas antagonists that elicit withdrawal jumping in mice treated with the high but not the low dose of morphine are hypothesized to be weak inverse agonists. 2 Male, Swiss-Webster mice (15-30 g) were acutely treated with 56 or 180 mg kg À1 morphine 4 h prior to injection with naloxone, naltrexone, diprenorphine, nalorphine, or naloxonazine. Vertical jumping, paw tremors, and weight loss were recorded. Naloxone, naltrexone, and diprenorphine produced withdrawal jumping after 56 and 180 mg kg À1 morphine pretreatment. Nalorphine and naloxonazine produced moderate withdrawal jumping after 180 mg kg À1 morphine pretreatment, but failed to elicit significant withdrawal jumping after 56 mg kg À1 morphine pretreatment. Nalorphine and naloxonazine blocked the withdrawal jumping produced by naloxone. All antagonists produced paw tremors and weight loss although these effects were generally not dose-dependent. 3 Taken together, these findings reveal a rank order of negative intrinsic efficacy for these opioid antagonists as follows: naloxone ¼ naltrexoneXdiprenorphine4nalorphine ¼ naloxonazine. Furthermore, the observation that nalorphine and naloxonazine blocked the naloxone-induced withdrawal jumping provides additional evidence that nalorphine and naloxonazine are weaker inverse agonists than naloxone.

Objective To compare overall and cancer‐specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron‐sparing measures (NSM) using a large population‐based dataset. Patients and Methods Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low‐ or moderate‐grade, localised non‐invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy). Cancer‐specific mortality (CSM) and other‐cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all‐cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively. Results Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low‐ or moderate‐grade, low‐stage UTUC from 1992 to 2008. Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well‐differentiated tumours (26.3% vs 18.0%, P = 0.001). While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non‐cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26). Conclusions Patients with low‐ or moderate‐grade, low‐stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU. These data may be useful when counselling patients with UTUC with significant competing comorbidities.

D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH 2 (CTAP) is a peptide antagonist that demonstrates potent and selective affinity for -opioid receptors in radioligand binding assays and in vitro bioassays. However, previous studies indicate that CTAP may possess unusual pharmacology under certain conditions. Therefore, CTAP was evaluated as an antagonist of the antinociceptive effects of a range of structurally diverse high-and low-efficacy peptide and alkaloid opioid agonists and compared with the traditional antagonist naltrexone. Male SpragueDawley rats (N ϭ 227) were loosely restrained and the latency for tail withdrawal from 55°C water was measured. Morphine s

In what is to our knowledge the largest published report of unilateral synchronous multifocal renal masses we document low pathological concordance rates. As such, percutaneous biopsy of a single renal mass in these patients may not help inform treatment decisions. Nephron sparing surgery may be performed with acceptable oncological and functional results in patients with unilateral synchronous multifocal renal masses.