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Background Patients with Crohn's disease ( CD) may experience disease relapse on maintenance infliximab. Anti-drug antibodies likely contribute to loss of response, and serum infliximab levels likely correlate with efficacy. Aim To prospectively evaluate the relationship between trough serum infliximab concentration and disease activity. Methods Adult patients ( N = 327) with a diagnosis of CD who had received at least five consecutive infliximab infusions and who planned to receive at least two additional infusions were enrolled. The Crohn's Disease Activity Index ( CDAI), serum infliximab, C-reactive protein ( CRP) and antibodies-to-infliximab ( ATI) were assessed at baseline, week 4 and week 8. Receiver operating characteristic ( ROC) analysis examined the relationship between infliximab concentrations and disease activity. Results The mean CDAI score, which decreased 1.05 points between infusions, did not correlate with the mean change in trough infliximab concentration (+0.39 μg/mL; r = 0.099, P = 0.083), but was associated with the mean change in CRP concentration ( r = 0.19, P < 0.001). Trough infliximab concentrations below 2.8-4.6 μg/mL best predicted a ≥ 70 point increase in the CDAI between infusions, and those below 2.7-2.8 μg/mL best predicted CRP >5 mg/mL at the second infusion. ATI at either visit decreased the proportion of patients with therapeutic infliximab trough levels compared with patients who were ATI negative (17.5% vs. 77.3% at visit 1 and 13.8% vs. 75.6% at visit 3; P < 0.001 for both comparisons). Conclusions This prospective study confirms the relationship between trough infliximab concentrations, inflammation and antibodies-to-infliximab. Infliximab trough concentrations below 3 μg/mL may increase the likelihood of symptoms and inflammation (ClinicalTrials.gov identifier: NCT00676988). [ABSTRACT FROM AUTHOR]

OBJECTIVE: We sought to assess the impact of the integration of the new roles of primary health care nurse practitioners (NPs) and physician assistants (PAs) on patient flow, wait times and proportions of patients who left without being seen in 6 Ontario emergency departments (EDs). METHODS: We performed a retrospective review of health records data on patient arrival time, time of initial assessment by a physician, time of discharge from the ED and discharge status. RESULTS: Whether a PA or NP was directly involved in the care of patients or indirectly involved by being on duty, the wait times, lengths of stay and proportion of patients who left without being seen were significantly reduced. When a PA or NP were directly involved in patients' care, patients were 1.6 (95% confidence interval [CI] 1.3-2.1, p < 0.05) and 2.1 (95% CI 1.6-2.8, p < 0.05) times more likely to be seen within the wait time benchmarks, respectively. Lengths of stay were 30.3% (95% CI 21.6%-39.0%, p < 0.01) and 48.8% (95% CI 35.0%-62.7%, p < 0.01) lower when PAs and NPs, respectively, were involved. When PAs and NPs were not on duty, the proportion of patients who left without being seen were 44% (95% CI 31%-63%, p < 0.01) and 71% (95% CI 53%-96%, p < 0.05), respectively. CONCLUSION: The addition of PAs or NPs to the ED team can improve patient flow in medium-sized community hospital EDs. Given the ongoing shortage of physicians, use of alternative health care providers should be considered. These results require validation, as their generalizability to other locations or types of EDs is not known. [ABSTRACT FROM AUTHOR]

A 21-year-old man with Marfan syndrome and known aortic root aneurysm presented to our emergency department with symptoms suggestive of acute aortic dissection. The patient was hemodynamically stable and bilateral upper extremity blood pressures were similar. There was no mediastinal widening on portable chest radiograph. Both contrast CT and retrograde angiography of the aorta failed to identify dissection. Subsequent transesophageal echocardiography demonstrated a Stanford classification type A dissection. This case demonstrates the utility of multiple imaging modalities for identifying aortic dissection in high-risk patients. [ABSTRACT FROM AUTHOR]

This study was initiated to characterize the metabolism and pharmacokinetics of SNC80 in rats and to evaluate the impact of Freund's complete adjuvant (FCA)-induced inflammation on its body disposition. In vitro, the disappearance and intrinsic clearance (CLint) of SNC80 were measured following incubations in recombinant rat CYPs and in phenotyped liver microsomes from naive and 24-h FCA-treated rats. The unbound fraction (fu) was assessed by ultrafiltration. Based on the Clint values, in vivo blood clearance of 3.35 and 2.48 L/h/kg were predicted in naive and FCA-treated rats. In vivo, SNC80 was administered to naive and 24-h FCA-treated rats at 10 µmol/kg i.v. and 50 µmol/kg p.o. The naive animals showed high plasma clearance (3.1 L/h/kg), low renal clearance (<0.02 L/h/kg) and poor bioavailability (<4%). Following i.v. administration, plasma clearance was lower (22%) in FCA-treated vs. untreated rats. Despite the decreases in fu (∼30%) and CLint (∼40%) in vitro, in vivo the apparent bioavailability and oral clearance were not significantly different between FCA-treated and naive rats. Hepatic and possibly intestinal losses contribute to the low bioavailability of SNC80. Non-hepatic mechanisms may compensate for the decrease in plasma clearance found in FCA-treated rats, preventing an increase in the oral bioavailability of SNC80. [ABSTRACT FROM AUTHOR]

Objective: To compare the results of urine cultures and reagent strip testing in 2 groups of elderly emergency department (ED) patients: an asymptomatic group unlikely to have urinary tract infection (UTI), and a group who had vague symptoms and were considered at risk for UTI.Methods: We performed a prospective observational convenience study with 2 groups of 100 patients aged 65 or older. The asymptomatic group consisted of afebrile patients presenting to the ED with non-infectious complaints, while the symptomatic group included patients presenting with acute confusion, weakness or fever but no apparent urinary symptoms. We defined a positive urine culture as a single organism count greater than 100 000 CFU/mL in mid-stream specimens, or greater than 1000 CFU/mL in catheter specimens. We considered reagent strips positive if they demonstrated any reaction to the leukocyte-esterase assay, the nitrite assay or both.Results: Of the 33 positive cultures, 10 had negative reagent strips. Thirteen of the 14 positive nitrite tests were culture positive for a specificity of 92.8% and a sensitivity of 36.1%. Positive cultures did not infer a diagnosis of UTI. Of the 67 positive reagent strips, 41 (61.2%) were associated with negative cultures. Likelihood ratios (LRs) in both groups affirmed the inability of the reagent strips to help significantly in decision making, with positive and negative LR in the indeterminate range (control group: 2.8 and 0.31, symptomatic group: 2.7 and 0.46, respectively).Conclusion: In the elderly, reagent testing is an unreliable method of identifying patients with positive blood cultures. Moreover, positive urine culture rates are only slightly higher in patients with vague symptoms attributable to UTI than they are in (asymptomatic) patients treated for non-urologic problems, which suggests that many positive cultures in elderly patients with non- focal systemic symptoms are false-positive tests reflecting asymptomatic bacteriuria and not UTIs. Blood cultures, regarded by many as the criterion standard for UTI, do not have sufficient specificity to confirm the diagnosis of UTI in elderly patients with non-specific symptoms. [ABSTRACT FROM AUTHOR]

1. The aim was to identify the cytochrome P450 (CYP) enzymes responsible for the N -demethylation of morphine in vitro . 2. In human liver microsomes, normorphine formation followed Michaelis-Menten kinetics with mean K m and V max of 12.4 ± 2.2 mM and 1546 ± 121 pmol min -1 mg -1 , respectively. In microsomes from a panel of 14 human livers phenotyped for 10 CYP enzymes, morphine N -demethylation correlated with testosterone 6β-hydroxylation ( r = 0.91, p <0.001) and paclitaxel 6-α hydroxylation ( r = 0.72, p <0.001), two specific markers of CYP3A4 and CYP2C8, respectively. Normorphine formation decreased when incubated in the presence of troleandomycin or quercetin (by 46 and 33-36%, respectively), which further corroborates the contribution of CYP3A4 and CYP2C8. 3. Among eight recombinant human CYP enzymes tested, CYP3A4 and CYP2C8 exhibited the highest intrinsic clearance. More than 90% of morphine N -demethylation could be accounted for via the action of both CYP3A4 and CYP2C8. 4. The in vitro findings suggest that hepatic CYP3A4, and to a lesser extent CYP2C8, play an important role in the metabolism of morphine into normorphine. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of the R and S enantiomers of ifosfamide (IFF) and of its 2- and 3-N-dechloroethylated metabolites (2-DCE-IFF and 3-DCE-IFF) were investigated in 14 cancer patients treated with a 3-h infusion of (R,S)-IFF (3 g/m2) with mesna uroprotection. An enantioselective gas chromatographic-mass spectrometric (GC-MS) assay was used to determine the concentrations in plasma and urine. The AUCs of (R)-IFF were significantly larger than those of (S)-IFF (2480 +/- 200 vs 1960 +/- 150 microM.h). The terminal half-lives (7.57 +/- 0.99 h) and mean residence times (11.17 +/- 1.10 h) of (R)-IFF were significantly longer than those of (S)-IFF, 6.03 +/- 0.82 h and 9.37 +/- 0.88 h, respectively. The mean volume of distribution at steady rate of (R)-IFF (25.68 +/- 0.80 l/m2) was slightly smaller than that of (S)-IFF (27.35 +/- 0.89 l/m2). While the renal clearances of (R)-IFF and (S)-IFF were similar, the nonrenal clearance was significantly lower for (R)-IFF (30.20 +/- 2.70 vs 41.40 +/- 3.55 ml/m2 per min) as was total clearance (41.52 +/- 2.90 vs 52.37 +/- 3.75 ml/m(2) per min). The AUC values for all of the DCE metabolites from (S)-IFF were significantly greater than those from (R)-IFF with 47% of the measured AUC accounted for by DCE from (S)-IFF compared to only 20% for (R)-IFF. Therefore, the enantioselective difference in IFF elimination can be partially explained by differences in N-dechloroethylation. [ABSTRACT FROM AUTHOR]

Primary aldosteronism in children under 16 years of age is usually due to adrenal hyperplasia. We could find only seven cases in the literature where it was caused by a solitary adrenal adenoma; all but one were female. We describe the case of a 10-year-old Caucasian boy in whom a unilateral adrenal adenoma was demonstrated by high resolution computed tomography (CT) alone. The literature is reviewed. [ABSTRACT FROM AUTHOR]