Surgical management of a laryngeal rhabdomyosarcoma in a cat.

Case Summary: An 11-year-old male castrated British Shorthair was referred for investigations into an upper respiratory tract mass. A partial laryngectomy was performed to excise the mass. Marginal resection of the mass involved excision of parts of the thyroid cartilage and left arytenoid cartilage.

Serum cortisol assay performance following the 1 mg overnight dexamethasone suppression test.

Background: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended for the differential diagnosis of Cushing's syndrome and the investigation of adrenal incidentalomas. Despite documented variation in serum cortisol immunoassay performance, little has been published regarding its effect on the ONDST.

Aims: Assess the performance of three immunoassay platforms (Roche Elecsys II, Abbott Alinity & Siemens Centaur) when compared to a liquid chromatography tandem mass spectrometry (LC-MS/MS) method.

Development of a total serum testosterone, androstenedione, 17-hydroxyprogesterone, 11β-hydroxyandrostenedione and 11-ketotestosterone LC-MS/MS assay and its application to evaluate pre-analytical sample stability.

Background Classically, serum testosterone (T) and androstenedione (A4) have been the mainstay for the biochemical assessment of hyperandrogenism. However, recent evidence suggests 11β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) may also be important. Here, we describe the development of a liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for quantitation of total serum T, A4, 17-hydroxyprogesterone (17OHP), 11OHA4 and 11KT.

Oestradiol measurement during fulvestrant treatment for breast cancer.

Biochemical evaluation of menopausal status is used to inform treatment decisions, including clinical trial eligibility in women with oestrogen receptor positive breast cancer. However, fulvestrant may interfere with oestradiol immunoassays and confound accurate assessment in this context. We conducted a service evaluation of two immunoassays and an LC-MS/MS assay to determine the extent of the interference.

Development of a rapid liquid chromatography tandem mass spectrometry method for the quantitation of serum dexamethasone and its clinical verification.

Background Measurement of serum dexamethasone during the overnight dexamethasone-suppression test has been recommended to reduce false-positive results when investigating Cushing's syndrome or increasingly commonly found adrenal incidentalomas. Despite this, there remains a paucity of well-validated dexamethasone methods currently available. Here, we describe the development of a rapid and sensitive liquid chromatography tandem mass spectrometry serum dexamethasone assay and verify its utility in a cohort of postmenopausal females.

Evaluation of an Axial Pattern Flap Based on the Cranial Cutaneous Branch of the Saphenous Artery: A Cadaveric Perfusion Study.

Objectives: To confirm the anatomic location of the cranial cutaneous branch of the saphenous artery (CCSA), delineate the angiosome of the CCSA, and provide guidelines for clinical use of an axial pattern flap based on the CCSA.

Study Design: Anatomic study.

Animals: Greyhound cadavers (n=10).

Serum Cortisol: An Up-To-Date Assessment of Routine Assay Performance.

Background: Accurate serum cortisol quantification is required for the correct diagnosis and management of adrenal pathologies. Presently, most laboratories use immunoassay to measure serum cortisol with proficiency schemes demonstrating a wide dispersion of results. Here, we investigate the effects of sex, matrix, and antibody specificity on serum cortisol quantification in 6 routine assays.

A direct assay for the routine measurement of testosterone, androstenedione, dihydrotestosterone and dehydroepiandrosterone by liquid chromatography tandem mass spectrometry.

Background: The measurement of androgens in many laboratories is often limited to testosterone. To more accurately determine the androgen status in both sexes, the measurement of other androgens such as dihydrotestosterone, the more potent metabolite of testosterone, and androstenendione and dehydroepiandrosterone, the most abundant circulating androgens in women would be informative. We report a combined liquid chromatography tandem mass spectrometry method for the measurement of these androgens.

Candidate Reference Measurement Procedure for the Quantification of Total Serum Cortisol with LC-MS/MS.

Background: Accurate measurement of serum cortisol is required to diagnose and treat adrenal disorders. Although certified reference materials (CRMs) are available to standardize cortisol measurements, External Quality Assessment (EQA) schemes still demonstrate a wide dispersion of results. We present a serum cortisol candidate reference measurement procedure that, through analysis of a Joint Committee for Traceability in Laboratory Medicine-listed panel of higher-order CRMs, provides metrologically traceable results.

Liquid chromatography tandem mass spectrometry in the clinical laboratory.

Clinical laboratory medicine has seen the introduction and evolution of liquid chromatography tandem mass spectrometry in routine clinical laboratories over the last 10-15 years. There still exists a wide diversity of assays from very esoteric and highly specialist manual assays to more simplified kit-based assays. The technology is not static as manufacturers are continually making improvements.

A widely applicable plasma renin activity assay by LC-MS/MS with offline solid phase extraction.

Background: The measurement of plasma renin activity using LC-MS/MS is an attractive alternative to radioimmunoassay techniques. A published method for renin activity by LC-MS/MS uses equipment that is not available in all LC-MS/MS laboratories. Here, we present an offline modification to allow users of LC-MS/MS to perform this analysis without specialist equipment.

A rapid direct assay for the routine measurement of oestradiol and oestrone by liquid chromatography tandem mass spectrometry.

Background: Liquid chromatography tandem mass spectrometry (LC-MS/MS) is rapidly becoming the technology of choice for measuring steroid hormones. We have developed a rapid LC-MS/MS assay for the routine analysis of serum oestradiol and oestrone. The assay uses a relatively small volume and has a rapid run time.

Supported liquid extraction as an alternative to solid phase extraction for LC-MS/MS aldosterone analysis?

Background: Supported liquid extraction (SLE) techniques are relatively new compared to other sample preparation approaches such as solid phase extraction (SPE), liquid-liquid extraction (LLE) and protein precipitation (PPE). We investigated the use of SLE as an alternative to SPE for the liquid chromatography tandem mass spectrometry (LC-MS/MS) measurement of aldosterone.

Methods: Samples (n = 83) were analysed by the routine method using SPE.

Development of a rapid assay for the analysis of serum cortisol and its implementation into a routine service laboratory.

Background: LC-MS/MS is rapidly becoming the technology of choice for measuring steroid hormones. We have developed a rapid LC-MS/MS assay for the routine analysis of serum cortisol. We have used this assay to investigate the effects of gender and exogenous steroid interference on the immunoassay measurement of serum cortisol.

Quantitation of aldosterone in human plasma by ultra high performance liquid chromatography tandem mass spectrometry.

Aldosterone is a mineralocorticoid steroid hormone whose measurement in the clinical laboratory is principally performed for the investigation of primary hyperaldosteronism. Traditionally measurement of aldosterone has been performed by radioimmunoassay, however these assays lack specificity as they are prone to interference from structurally related steroid hormones. Herein, we have developed a novel, sensitive and specific method utilising solid phase extraction and quantitation of aldosterone from human plasma by UPLC-MS/MS.

Ranolazine stabilizes cardiac ryanodine receptors: a novel mechanism for the suppression of early afterdepolarization and torsades de pointes in long QT type 2.

Background: Ranolazine (Ran) is known to inhibit multiple targets, including the late Na(+)current, the rapid delayed rectifying K(+)current, the L-type Ca(2+)current, and fatty acid metabolism. Functionally, Ran suppresses early afterdepolarization (EADs) and torsades de pointes (TdP) in drug-induced long QT type 2 (LQT2) presumably by decreasing intracellular [Na(+)](i) and Ca(2+)overload. However, simulations of EADs in LQT2 failed to predict their suppression by Ran.

Simultaneous analysis of cortisol and cortisone in saliva using XLC-MS/MS for fully automated online solid phase extraction.

Salivary cortisol measurements are increasingly being used in the investigation of disorders of the hypothalamic-pituitary-adrenal axis. In the salivary gland, cortisol is metabolised to cortisone by the action of 11β-hydroxysteroid dehydrogenase type 2, and cortisone is partly responsible for the variable interference observed in current salivary cortisol immunoassays. The aim of this study was to validate an assay for the simultaneous analysis of salivary cortisol and cortisone using the Spark Holland Symbiosis™ in eXtraction liquid chromatography-tandem mass spectrometry (XLC-MS/MS) mode for fully automated online solid phase extraction (SPE).

Designing calcium release channel inhibitors with enhanced electron donor properties: stabilizing the closed state of ryanodine receptor type 1.

New drugs with enhanced electron donor properties that target the ryanodine receptor from skeletal muscle sarcoplasmic reticulum (RyR1) are shown to be potent inhibitors of single-channel activity. In this article, we synthesize derivatives of the channel activator 4-chloro-3-methyl phenol (4-CmC) and the 1,4-benzothiazepine channel inhibitor 4-[-3{1-(4-benzyl) piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine (K201, JTV519) with enhanced electron donor properties. Instead of activating channel activity (~100 μM), the 4-methoxy analog of 4-CmC [4-methoxy-3-methyl phenol (4-MmC)] inhibits channel activity at submicromolar concentrations (IC(50) = 0.

Comparison of serum cortisol measurement by immunoassay and liquid chromatography-tandem mass spectrometry in patients receiving the 11β-hydroxylase inhibitor metyrapone.

Background: The accurate measurement of cortisol by immunoassay is compromised by the potential for cross-reactivity of reagent antibodies with structurally related steroids present in serum. This susceptibility is potentiated when normal steroid metabolism is altered pharmaceutically by antisteroidogenic drugs utilized in the management of Cushing's syndrome to moderate cortisol production. The clinical implications of falsely elevated cortisol results include over-treatment and unrecognized hypoadrenalism.

Simultaneous measurement of cortisol and cortisone in human saliva using liquid chromatography-tandem mass spectrometry: application in basal and stimulated conditions.

Immunoassays used for the measurement of salivary cortisol are limited by variable interference from cortisone. Salivary cortisone is a consequence of the salivary glands expressing 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) which converts cortisol to cortisone. We report a combined salivary cortisol and cortisone (SalF and SalE respectively) liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay to address the cortisone cross-reactivity in cortisol immunoassays and as a tool to study 11beta-HSD2 activity.

Efficacy of adhesive incise drapes in preventing bacterial contamination of clean canine surgical wounds.

Objective: To investigate the efficacy of adhesive incise drapes in reducing bacterial contamination of clean canine surgical wounds.

Study Design: Randomized clinical trial.

Animals: Dogs (n=100) having elective ovariohysterectomy or stifle surgery.

Measurement of salivary cortisol with liquid chromatography-tandem mass spectrometry in patients undergoing dynamic endocrine testing.

Objective: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) eliminates cross-reactivity, which is a major limitation of immunoassays used for the measurement of salivary cortisol (SalC). We aimed to evaluate the potential of SalC measured by LC-MS/MS in patients undergoing assessment of the HPA axis.

Design And Patients: Cross-sectional study of 78 patients admitted for routine testing in a specialized endocrine unit.