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ObjectiveTo assess Doppler ultrasound (US) and tenosynovial fluid (TSF) characteristics in tenosynovitis within common rheumatic conditions, as well as their diagnostic utility.MethodsSubjects with tenosynovitis underwent Doppler US and US-guided TSF aspiration for white cell count (WCC) and crystal analysis. Tenosynovial Doppler scores (DS) were semiquantitatively graded. TSF WCC and DS were compared using Kruskal-Wallis tests and logistic regression between non-inflammatory conditions (NIC), inflammatory conditions (IC) and crystal-related conditions (CRC). Receiver operating curves, sensitivity and specificity assessed the ability of WCC and DS to discriminate IC from NIC.ResultsWe analysed 100 subjects from 14 sites. The mean age was 62 years, 65% were female, and the mean TSF volume was 1.2 mL. Doppler signal was present in 93.7% of the IC group and was more frequent in IC than in NIC group (OR 6.82, 95% CI 1.41 to 32.97). The TSF median WCC per 109/L was significantly higher in the IC (2.58, p9/L optimally discriminated IC versus NIC with a sensitivity and specificity each of 81.3%. In the IC group, 20 of 48 (41.7%) subjects had a TSF WCC 9/L.ConclusionsA negative DS helps rule out IC in tenosynovitis, but a positive DS is non-specific and merits TSF testing. Unlike synovial fluid, a lower TSF WCC better discriminates IC from NIC. US guidance facilitates aspiration of minute TSF volume, which is critical for diagnosing tenosynovial CRC.

Objective European rheumatology and radiology-determined standards have largely driven the execution of ultrasound in rheumatology (RhUS). How this translates to American rheumatologic practice has not been examined. A rheumatology-driven consensus on documentation, scanning conventions, and tiered-mastery designation for anatomic region views was developed in 2011 and served as the framework for training and clinical research validation. The present study was undertaken to update this consensus to reflect current utilization of musculoskeletal RhUS evaluation in the US. Methods A 3-round Delphi method study was conducted using a 96-item questionnaire sent via Qualtrics survey software to 101 respondents experienced in RhUS education and scholarship. The target participant number was 38. High agreement was defined as ≥85% agreement on each item. McNemar's chi-square test was used to analyze changes in agreement in the responses. Comments were reviewed for content analysis. Results A total of 46 respondents completed all 3 rounds. Of documentation and scanning convention statements, 80% and 100%, respectively, reached high agreement. Comments reflected the need for rheumatology-defined and disease-specific complete scan and limited scan definitions, separate from radiology-defined definitions. Conclusion Many scanning conventions from 2011 remain relevant in current practice. There is a need to determine rheumatology-defined descriptions for common procedural terminology codes for complete and limited scans that accurately reflect the current state of RhUS.

Objective.To examine the clinical and ultrasonographic (US) outcomes of reducing methotrexate (MTX) dosage upon initiating adalimumab (ADA) in MTX-inadequate responders with moderately to severely active rheumatoid arthritis (RA).Methods.MUSICA (NCT01185288) was a double-blind, randomized, parallel-arm study of 309 patients with RA receiving MTX ≥ 15 mg/week for ≥ 12 weeks before screening. Patients were randomized to high dosage (20 mg/week) or low dosage (7.5 mg/week) MTX; all patients received 40 mg open-label ADA every other week for 24 weeks. The primary endpoint was Week 24 mean 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP) to test for noninferiority of low-dosage MTX using a 15% margin. US images were scored using a 10-joint semiquantitative system incorporating OMERACT definitions for pathology, assessing synovial hypertrophy, vascularity, and bony erosions.Results.Rapid improvement in clinical indices was observed in both groups after addition of ADA. The difference in mean DAS28-CRP (0.37, 95% CI 0.07–0.66) comparing low-dosage (4.12, 95% CI 3.88–4.34) versus high-dosage MTX (3.75, 95% CI 3.52–3.97) was statistically significant and non-inferiority was not met. Statistically significant differences were not detected for most clinical, functional, and US outcomes. Pharmacokinetic and safety profiles were similar.Conclusion.In MUSICA, Week 24 mean DAS28-CRP, the primary endpoint, did not meet non-inferiority for the low-dosage MTX group. Although the differences between the 2 MTX dosage groups were small, our study findings did not support routine MTX reduction in MTX inadequate responders initiating ADA.

Musculoskeletal ultrasound (MSUS) in rheumatology in the US has advanced by way of promotion of certifications and standards of use and inclusion of core fellowship curriculum. In order to inform endeavors for curricular integration, the objectives of the present study were to assess current program needs for curricular incorporation and the teaching methods that are being employed.A needs-assessment survey (S1) was sent to 113 rheumatology fellowship program directors. For programs that taught MSUS, a curriculum survey (S2) was sent to lead faculty. Programs were stratified according to program size and use of a formal written curriculum.S1 (108 of 113 respondents; response rate 96%) revealed that 94% of programs taught MSUS, with 41% having a curriculum. Curricular implementation was unaffected by program size. Formal curricular adoption of MSUS was favored by 103 directors (95.3%), with 65.7% preferring such adoption to be optional. S2 (74 of 101 respondents; response rate 73%) showed that 41% of programs utilized a formal curriculum. Multiple teaching strategies were used, with content that was generally similar. Use of external courses, including the Ultrasound School of North American Rheumatologists course, was prevalent. Fewer barriers were noted compared to past surveys, but inadequate time, funding, and number of trained faculty still remained. Lack of divisional interest (P = 0.046) and interest of fellows (P = 0.012) were noted among programs without a formal curriculum.MSUS is taught by a significantly larger number of rheumatology fellowship programs today. Multiple teaching strategies are used with common content, and barriers still remain for some programs. Most program directors favor inclusion of a standardized MSUS curriculum, with many favoring inclusion to be optional.

Objective To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS). Methods A 9-station OSCE was administered to 35 rheumatology fellows trained in MSUS and to 3 expert faculty (controls). Participants were unaware of joint health (5 diseased/4 healthy). Faculty assessors (n = 9) graded image quality with predefined checklists and a 0–5 global rating, blinded to who performed the study. Interrater reliability, correlation between a written multiple choice question examination (MCQ) and OSCE performance, and comparison of fellow OSCE results with those of the faculty were measured to determine OSCE reliability, concurrent validity, and construct validity. Results Assessors' interrater reliability was good (intraclass correlation coefficient [ICC] 0.7). Score reliability was good in the normal wrist and ankle stations (ICC 0.7) and moderate in the abnormal wrist and ankle stations (ICC 0.4). MCQ grades significantly correlated with OSCE grades (r = 0.52, P < 0.01). The fellows in the bottom quartile of the MCQ scored 3.07 on the OSCE, significantly worse than the top quartile fellows (3.32) and the faculty (3.29; P < 0.01). Scores also significantly discriminated bottom quartile fellows from faculty in the normal wrist and ankle stations (3.38 versus 3.78; P < 0.01), but not in the abnormal stations (3.37 versus 3.49; P = 0.08). Conclusion MSUS OSCE is a reliable and valid method for evaluation of MSUS skill. Normal joint assessment stations are more reliable than abnormal joint assessment stations and better discriminate poorly performing fellows from faculty. Therefore, MSUS OSCE with normal joints can be used for the assessment of MSUS skill competency.

Objectives The purpose of this study was to establish standards for musculoskeletal ultrasound competency through knowledge and skills testing using criterion-referenced methods. Methods Two groups of rheumatology fellows trained in musculoskeletal ultrasound through a standardized curriculum, which required submission of ultrasound studies for review over 8 months. Both groups then completed written and practical examinations in musculoskeletal ultrasound. Instructors, advanced users, and intermediate users of musculoskeletal ultrasound served as comparison groups. A passing score (competency) was established for the written examination by the Angoff procedure and for the practical examination by the borderline method. Results Thirty-eight fellows (19 in each group) took the final examination. Five fellows failed the written examination, and 1 failed the practical examination, whereas none of the advanced users failed. Written examination scores did not differ between the two fellow groups (74% versus 70%; P > .05), were reliable, and were able to discriminate between the intermediate and advanced groups. Practical and written examination results correlated in both groups (first group, r = 0.70; P = .0008; second group, r = 0.59; P = .009). Conclusions Criterion-referenced methods were used for the first time to determine fellow musculoskeletal ultrasound competency. The examination used to determine competency was reproducible, was reliable, and could differentiate musculoskeletal ultrasound users with different levels of experience. Most rheumatology fellows completing our program passed the written and practical examinations, suggesting achievement of basic musculoskeletal ultrasound competency.

The evaluation of patients with subcutaneous nodules remains a diagnostic challenge. The presence of nodules can be a clue to an underlying systemic disease; however, the varied presentations of nodules and numerous disease associations make the assessment of patients with nodules far from simple. With further investigation into the appearance, location, and symptoms associated with nodules, the clinical significance of these lesions can become clearer and aid in logical diagnostic evaluation. We have reviewed the causes of nodules with emphasis on those associated with rheumatic disease and provide guidelines for nodule evaluation to better characterize disease association and lead to directed diagnostic assessment.

In euryhaline crabs, ion-transporting cells are clustered into osmoregulatory patches on the lamellae of the posterior gills. To examine changes in the branchial osmoregulatory patch in the blue crab Callinectes sapidus in response to change in salinity and to correlate these changes with other osmoregulatory responses, crabs were acclimated to a range of salinities between 10 and 35 ppt. When crabs that had been acclimated to 35 ppt were subsequently transferred to 10 ppt, both the size of the osmoregulatory patch on individual gill lamellae and the specific activity of Na+, K+-ATPase in whole-gill homogenates increased only after the first 24 h of exposure to dilute seawater. Enzyme activity and size of patch area increased gradually and reached their maxima (increasing by 200% and 60%, respectively) 6 days following transfer to 10 ppt seawater and then remained at these levels. Patch size at acclimation varied inversely with the salinity for seawater dilutions below 26 ppt (the isosmotic point of the crab), although it did not vary in salinities at or above 26 ppt. Thus, the size of the patch clearly is modulated with acclimation salinity, but it increases only in those salinities in which the crab hyperosmoregulates. An increase in the total RNA/DNA ratio in gill homogenates, the lack of mitotic figures in the lamellae, and the lack of incorporation of bromodeoxyuridine into nuclei of lamellar epithelial cells during acclimation to dilute seawater were interpreted as evidence that no cell proliferation had occurred and that increases in the size of the osmoregulatory patch occurred through differentiation of existing gas exchange cells or of undifferentiated epithelial cells into ion-transporting cells.

Imaging can play a vital role in the evaluation of patients with early arthritis. Various imaging methods can be utilized to aid with diagnosis, predict prognosis and follow disease progression and treatment response. Previously, conventional radiography was the principal method used to evaluate and follow bone damage in patients with inflammatory arthritis. More recently the use of magnetic resonance imaging and ultrasonography has gained wider acceptance and popularity due to the ability of these multiplanar techniques to image both bone changes and soft tissue abnormalities, including synovitis. This chapter discusses the current imaging modalities used in the evaluation of patients with early arthritis, as well as the use of imaging in establishing the extent of disease, in prognosis and in monitoring disease course. Current data on imaging of patients with early arthritis due to rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis is reviewed.

The synthesis, resolution, and stereochemical characterization of novel piperazino-, thiazino-, and oxazinobenzodiazepines are described. The absolute stereochemistry of the heterotricycles was determined by using X-ray crystallography and the enantiomeric purity was determined by using Pirkle-solvent NMR techniques and chiral HPLC.

Beginning from the screening hit and literature alpha(1)-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective alpha(1a)-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective alpha(1a)-AR antagonists were discovered. In all cases, binding affinity and selectivity at the alpha(1a)-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at alpha(1a)-AR but gained more than 2-fold selectivity for alpha(1a)-AR over alpha(1b)-AR, and 2- to 6-fold selectivity for alpha(1a)-AR over alpha(1d)-AR. They also had less cross activities against a panel of 25-35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (K(i) = 0.29 nM, 0.33 nM; alpha(1b)/alpha(1a)5690,6060; alpha(1d)/alpha(1a) = 186, 158, respectively) were slightly less potent but much more selective at alpha(1a)-AR than tamsulosin (K(i) = 0.13 nM, alpha(1b)/alpha(1a) = 14.8, alpha(1d)/alpha(1a) = 1.4). In the functional assay, the S-hydroxy enantiomers 20, 23, and 24 were less potent than tamsulosin in inhibiting contractions of rat prostate tissue but more selective in the inhibition of tissue contractions of rat prostate versus rat aorta. Compound 24 was selected as the development candidate for the treatment of BPH.

Chromatographic retention factors (k′) of a series of eight β-adrenoceptor antagonist compounds (β-adrenolytic drugs) were determined employing an immobilized artificial membrane column (IAM.PC.DD). The influence of mobile phase pH, ionic strength, and organic modifier composition was studied in order to examine column performance. After the IAM.PC.DD columns were exposed to approximately 7000 column volumes of a 0.01 M PBS mobile phase, five out of six columns tested showed significant peak broadening and decreased k′ values indicative of premature column failure. The data suggested that the immobilized phospholipids stationary phase was removed by the 0.01 M PBS mobile phase. The β-adrenolytic drug's log k′IAM values obtained with an IAM.PC.DD column were compared to an esterIAM.PC.MG column for predicting drug membrane interactions. For the linear regression analysis between log k′IAM and the logarithm of the n-octanol–water partition coefficients (rIAM.PC.DD=0.8710 vs. rIAM.PC.MG=0.9538), the C18 HPLC retention factors (rIAM.PC.DD=0.8408 vs. rIAM.PC.MG=0.9380), the liposome partition coefficients (rIAM.PC.DD=0.8887 vs. rIAM.PC.MG=0.9187), and various pharmacokinetic parameters, significantly better correlations were obtained with the esterIAM.PC.MG column than the IAM.PC.DD column.

To determine the reliability and validity of an objective structured clinical examination (OSCE) for musculoskeletal ultrasound (MSUS).A 9-station OSCE was administered to 35 rheumatology fellows trained in MSUS and to 3 expert faculty (controls). Participants were unaware of joint health (5 diseased/4 healthy). Faculty assessors (n = 9) graded image quality with predefined checklists and a 0-5 global rating, blinded to who performed the study. Interrater reliability, correlation between a written multiple choice question examination (MCQ) and OSCE performance, and comparison of fellow OSCE results with those of the faculty were measured to determine OSCE reliability, concurrent validity, and construct validity.Assessors' interrater reliability was good (intraclass correlation coefficient [ICC] 0.7). Score reliability was good in the normal wrist and ankle stations (ICC 0.7) and moderate in the abnormal wrist and ankle stations (ICC 0.4). MCQ grades significantly correlated with OSCE grades (r = 0.52, P0.01). The fellows in the bottom quartile of the MCQ scored 3.07 on the OSCE, significantly worse than the top quartile fellows (3.32) and the faculty (3.29; P0.01). Scores also significantly discriminated bottom quartile fellows from faculty in the normal wrist and ankle stations (3.38 versus 3.78; P0.01), but not in the abnormal stations (3.37 versus 3.49; P = 0.08).MSUS OSCE is a reliable and valid method for evaluation of MSUS skill. Normal joint assessment stations are more reliable than abnormal joint assessment stations and better discriminate poorly performing fellows from faculty. Therefore, MSUS OSCE with normal joints can be used for the assessment of MSUS skill competency.

Two series of nonpeptide turn mimetics were designed by analysis of the solution NMR structure of the 385-411 sequence of the y-chain of fibrinogen. These compounds, based on the KQAGD (Lys-Gln-Ala-Gly-Asp, 406-410) sequence, were synthesized and studied in vitro. The most interesting compound from our study, RWJ 50042 (25), exhibits potent inhibition of fibrinogen binding to GPIIbDIIa (ICs0 = 0.009 pM), as well as thrombin- or collagen-induced platelet aggregation (ICs0 = 0.76, 0.14 pM). Since the 400-411 sequence is required for y-chain bioactivity and is a unique recognition sequence among ligands for integrins, vis-a-vis other RGD (Arg-Gly-Aspbpresenting proteins, these turn mimetics may represent a new, selective approach to antagonism of the fibrinogen receptor. Platelet aggregation constitutes an important response to curtail bleeding induced by vascular injury. However, pathological extension of this normal hemostatic process can lead to total occlusion of a vessel. Platelet aggregation is mediated by fibrinogen binding to platelet receptor glycoprotein IIbAIIa (GPIIbAIIa). Because this binding is the final common pathway leading to platelet aggregation, a fibrinogen receptor antagonist has become well-recognized as a potentially useful drug in the treatment of thrombotic disorders. Fibrinogen interacts with binding sites on GPIIbAIIa through peptide domains present on the a- and y-chains: RGDF (Arg-Gly-Asp-Phe, a95-98), RGDS (Arg-Gly-AspSer, a572-5751, and HHLGGAKQAGDV (His-His-LeuGly-Gly-Ala-Lys-Gln-Ala-Gly-Asp-Val, 112 Although the RGD motifs and the y-chain dodecapeptide appear to have unique binding sites on GPIIbAIIa (i.e., 109-171 of IIIa and 294-314 of IIb, respectively), the RGD binding site is not mutually exclusive from the dodecapeptide site, which implies either cross-binding or close proximity of these two sites.3 In our biochemical assays, RGDS and HHLGGAKQAGDV have comparable ICs0 values for the inhibition of fibrinogen binding to immobilized GPIIbAIIa, 1.0 and 4.1 pM, respectively

Normal- and reversed-phase preparative chromatography methods were developed to isolate gram quantities of analytically pure 6-amino-2-chloro-9-(2-deoxy-2-fluoro-β- d -arabinofuranosyl)-9H-purine (arafluoro-2-CdA; RWJ 29727) and its α-anomer (RWJ 48667). The complex reaction mixture (ca. 171 g), from a Parr Bomb synthesis, was prepurified by normal-phase chromatography to yield ca. 40 g. Twelve reversed-phase preparative isolations were run on a custom-packed YMC column to yield ca. 12 g of arafluoro-2-CdA (99.7%) and ca. 3 g of the α-anomer (99.2%).

Etanercept is a recombinant dimeric fusion protein consisting of a tumor necrosis factor-alpha receptor ligand-binding region linked to the Fc portion of human IgG. It is approved for use in the treatment of rheumatoid arthritis, ankylosing spondylitis, juvenile rheumatoid arthritis, psoriasis, and psoriatic arthritis. Since 1998, there have been reports of vasculitic adverse events, including necrotizing vasculitis and leukocytoclastic vasculitis. In addition, the adverse events reporting system of the U.S. Food and Drug Administration has recorded 35 cases of leukocytoclastic vasculitis, 20 after etanercept therapy and 15 after infliximab. Most cases of cutaneous vasculitis describe development of symptoms within 3 months of etanercept use. In only one case report was direct immunofluorescence performed on tissue and no specific immunoreactivity found. We describe the first case of Henoch-Schonlein purpura with acute renal failure associated with increase in etanercept dose after 11 months of use for treatment of psoriasis. Discontinuation of the drug and treatment with a course of systemic steroids led to the complete resolution of the vasculitis and improvement of renal function. Vasculitis occurring even during chronic use of antitumor necrosis factor agents must be considered as possibly related to the therapy.

Background Methotrexate (MTX) is the recommended first-line disease-modifying antirheumatic drug (DMARD) for the treatment of moderately to severely active rheumatoid arthritis (RA).Whether patients (pts) with inadequate response to MTX initiating combination therapy with adalimumab (ADA) can reduce MTX dose remains unclear. Clinical and ultrasonographic (US) outcomes of MTX dose reduction upon initiating ADA were examined. Methods MUSICA, a double-blind, parallel-arm, randomised, controlled trial, examined the impact of MTX dosage on disease and US outcomes in pts with moderately to severely active RA who have failed prior synthetic DMARDs. MUSICA enrolled 309 pts taking MTX ≥15 mg/week (wk) for ≥12 wks prior to enrollment. Pts received either blinded high- (20 mg/wk) or low-dosage (7.5 mg/wk) MTX; all pts received open-label 40 mg ADA every other wk for 24 wks. Non-inferiority was assessed using the 95% confidence interval (CI) of the difference between high and low dose wk-24 outcomes using a 15% non-inferiority margin; Disease activity score based on 28 joints (DAS28) was the primary endpoint. Ultrasound images acquired every 4 wks were independently read and scored blindly by 2 of 4 ultrasound-experienced rheumatologists. A bilateral 5-joint semi-quantitative scoring system incorporating OMERACT definitions 1 for pathology measured synovial hypertrophy and vascularity; bony erosions were scored as present or absent. Results The study populations for both MTX dosages had similar baseline demographics (mean age 54.8, mean 5.3 years disease duration) and disease characteristics (mean DAS28 of 5.8). After 24 wks of ADA combination therapy, notable improvements in clinical indices were observed in both treatment groups, consistent with other trials including a low-dose MTX group. Differences in clinical, functional, and US outcomes between treatment groups were minimal. Although the wk-24 mean DAS28 difference (0.37) was within the non-inferiority margin (0.56), the primary endpoint was not met because the difference CI crossed the non-inferiority margin. Low-dosage MTX+ADA met non-inferiority for the proportion of pts achieving secondary endpoints, ACR70 and ΔHAQ-DI ≤-0.22. No statistically significant differences were detected for most clinical, functional, and ultrasound outcomes (Table). Excessive fatigue and/or malaise and abnormal hair loss were more prevalent in the low-dose MTX+ADA group. Conclusions Addition of ADA to MTX inadequate responders led to clinically meaningful results consistent with prior studies. Week-24 mean DAS28, the primary endpoint, did not meet non-inferiority; however, the small differences in clinical, functional, and US outcomes suggest MTX dosage reduction might be considered when initiating adalimumab therapy in some MTX inadequate-responders. References D9Agostino MA et al. 2009. J Rheumatol 36: 1829-32 Acknowledgements AbbVie sponsored the study (NCT01185288), participated to its design, the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the final version. Medical writing support was provided by Douglas E. Dylla, PhD of AbbVie Inc. Disclosure of Interest : G. Kaeley Consultant for: AbbVie, Inc., A. Evangelisto Grant/research support: AbbVie, Inc., Speakers bureau: AbbVie, Inc., M. Nishio Speakers bureau: AbbVie, Inc., S. Liu: None declared, H. Kupper: None declared DOI 10.1136/annrheumdis-2014-eular.1133

Beginning from the screening hit and literature α 1 -adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective α 1a -AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1 . Using the Topliss approach, a number of potent and selective α 1a -AR antagonists were discovered. In all cases, binding affinity and selectivity at the α 1a -AR of S -hydroxy enantiomers were higher than the R -hydroxy enantiomers. As compared to the des-hydroxy analogues, the S -hydroxy enantiomers displayed comparable potency and better selectivity at α 1a -AR. The S -hydroxy enantiomer 17 ( K i =0.79 nM; α 1b α 1a =800 ; α 1d α 1a =104 ) was slightly less potent but much more selective at α 1a -AR than tamsulosin ( K i =0.13 nM, α 1b α 1a =15 , α 1d α 1a =1.4 ). Compound 17 displayed higher selectivity in inhibiting rat prostate contraction over rat aorta contraction and also exhibited a higher degree of uroselectivity than tamsulosin in the anesthetized dog model.

Beginning from the screening hit and literature α1-adrenergic compounds, a hybridized basic skeleton A was proposed as the pharmacophore for potent and selective α1a-AR antagonists. Introduction of a hydroxy group to increase the flexibility afforded B which served as the screening model and resulted in the identification of the second-generation lead 1. Using the Topliss approach, a number of potent and selective α1a-AR antagonists were discovered. In all cases, binding affinity and selectivity at the α1a-AR of S-hydroxy enantiomers were higher than those of the R-hydroxy enantiomers. As compared to the des-hydroxy analogues, the S-hydroxy enantiomers had slightly lower binding affinity at α1a-AR but gained more than 2-fold selectivity for α1a-AR over α1b-AR, and 2- to 6-fold selectivity for α1a-AR over α1d-AR. They also had less cross activities against a panel of 25−35 peripheral and CNS receptors. The S-hydroxy enantiomers 23 and 24 (Ki = 0.29 nM, 0.33 nM; α1b/α1a >5690, >6060; α1d/α1a = 186, 158, res...

Health care facilities have many means available to minimize the risk of latex allergy for both patients and workers. A latex-allergy task force should oversee patient and employee safety. Materials and items that contain latex must be identified, and latex-free alternatives must be found.