Publications by authors named "Michael N Fahie-Wilson"

13 Publications

  • Page 1 of 1

Identification of IgG-K type macroprolactin found in the serum of an 8-year-old girl.

Clin Chim Acta 2015 Feb 12;441:10. Epub 2014 Dec 12.

Department of Endocrinology, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

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February 2015

Circulating immunoreactive cardiac troponin forms determined by gel filtration chromatography after acute myocardial infarction.

Clin Chem 2010 Jun 8;56(6):952-8. Epub 2010 Apr 8.

Department of Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Kent and Canterbury Hospital, Canterbury, Kent, UK.

Background: Cardiac troponin I (cTnI) and cTnT measurements are used in the diagnosis of acute myocardial infarction (AMI). Together with troponin C (TnC), the cTnI and cTnT forms make up the ternary cTnT-cTnI-TnC (TIC) complex found within myocardium. Whether cTn occurs in the circulation after AMI as ternary TIC, binary cTnI-TnC (IC) complexes, or free troponin forms has not been thoroughly investigated.

Methods: Blood samples from 10 AMI patients were collected at hospital admission and then at 12, 24, and 48 h after onset of chest pain. Serum was subjected to gel filtration chromatography and cTnT (Roche cTnT) and cTnI (Siemens Centaur UltraTnI and Beckman Access AccuTnI) concentrations were measured in the gel filtration chromatography fractions.

Results: cTnT was present predominantly as free cTnT and cTnI as binary IC complex. These 2 forms were present at every time point. Lesser quantities of TIC complex (6%-32% of total cTnT and <50% of total cTnI) were detected in 4 patients at varying times. Minor quantities of a high molecular mass form of cTnI were detected occasionally. No free cTnI was found. Both cTnI assays identified a similar pattern of cTnI forms.

Conclusions: After AMI, cTnI is present in serum as TIC and IC complexes. cTnT may be present as a combination of TIC and free cTnT or exclusively as free cTnT.
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June 2010

Serum total prolactin and monomeric prolactin reference intervals determined by precipitation with polyethylene glycol: evaluation and validation on common immunoassay platforms.

Clin Chem 2008 Oct 21;54(10):1673-81. Epub 2008 Aug 21.

Department of Clinical Chemistry, Southend Hospital, Westcliff-on-Sea, Essex SSOORY, UK.

Background: Macroprolactin is an important source of immunoassay interference that commonly leads to misdiagnosis and mismanagement of hyperprolactinemic patients. We used the predominant immunoassay platforms for prolactin to assay serum samples treated with polyethylene glycol (PEG) and establish and validate reference intervals for total and monomeric prolactin.

Methods: We used the Architect (Abbott), ADVIA Centaur and Immulite (Siemens Diagnostics), Access (Beckman Coulter), Elecsys (Roche Diagnostics), and AIA (Tosoh) analyzers with samples from healthy males (n = 53) and females (n = 93) to derive parametric reference intervals for total and post-PEG monomeric prolactin. Concentrations of immunoreactive prolactin isoforms in serum samples from healthy individuals were established by gel filtration chromatography (GFC). We then used samples from 22 individuals whose hyperprolactinemia was entirely attributable to macroprolactin and 32 patients with true hyperprolactinemia to compare patient classifications and prolactin concentrations measured by GFC with the newly derived post-PEG reference intervals.

Results: Parametric reference intervals for post-PEG prolactin in male and female serum samples, respectively, were (in mIU/L): 61-196, 66-278 (Centaur); 63-245, 75-381 (Elecsys); 70-301, 92-469 (Access); 72-229, 79-347 (Architect); 73-247, 83-383 (AIA); and 78-263, 85-394 (Immulite). Concordance between GFC and immunoassay-specific post-PEG reference intervals was observed in 311 of 324 cases and for 31 of 32 patients with true hyperprolactinemia and 17 of 22 patients with macroprolactinemia. Results leading to misclassification occurred in a few analyzers for 5 macroprolactinemia patient samples with relatively minor increases in post-PEG prolactin (mean 61 mIU/L).

Conclusions: Our validated normative reference data for sera pretreated with PEG and analyzed on the most commonly used immunoassay platforms should facilitate the more widespread introduction of macroprolactin screening by clinical laboratories.
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October 2008

What is the role of cerebrospinal fluid ferritin in the diagnosis of subarachnoid haemorrhage in computed tomography-negative patients?

Ann Clin Biochem 2008 Mar;45(Pt 2):189-92

Department of Neurobiochemistry, The Walton Centre for Neurology and Neurosurgery, Liverpool L9 7LJ, UK.

Background: Spectrophotometry of cerebrospinal fluid (CSF) for bilirubin is the recommended method for investigation in suspected cases of subarachnoid haemorrhage (SAH), when a computed tomography (CT) of the head is negative for blood. There is a potential need for a simpler alternative. Measurement of CSF ferritin might fulfil this need.

Method: We have measured ferritin in the CSF from 252 patients with suspected SAH who were negative on a CT of the head for blood, recruited on a consecutive intention to recruit basis from four centres. CSF spectrophotometry was performed on all samples. A positive outcome was taken as an aneurysm found on angiography that was treated or a discharge diagnosis of non-aneurysmal SAH.

Results: A final diagnosis of aneurysmal SAH was made in six patients, an arteriovenous malformation in one and non-aneurysmal SAH in nine. Receiver operating characteristic (ROC) analysis showed that at 6.4 microg/L, sensitivity, specificity, positive and negative predictive values were 1.0, 0.48, 0.12 and 1.0, respectively. At 12 microg/L, these values were 0.81, 0.91, 0.38 and 0.98, respectively.

Conclusions: At an appropriate negative predictive value (1.0) for a rule-out test, ferritin has too low a specificity to function as a stand-alone test and we cannot recommend it as an initial screen to be followed by spectrophotometry.
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March 2008

Prevalence of increased serum creatine kinase activity due to macro-creatine kinase and experience of screening programmes in district general hospitals.

Ann Clin Biochem 2007 Jul;44(Pt 4):377-83

Department of Clinical Biochemistry, Southend Hospital, Westcliff-on-Sea, Essex, UK.

Background: Macro creatine kinase type 1 (MCK1) may be the cause of elevated total serum CK activity, which can lead to diagnostic confusion. There is evidence that this problem is poorly recognized perhaps due to a lack of information on its prevalence. Precipitation with polyethylene glycol (PEG) has been described for the detection of MCK1 but has not been fully evaluated.

Methods: We introduced a screening programme to detect elevated serum total CK due to MCK1 and determine the prevalence of this problem using PEG precipitation with confirmation by gel filtration chromatography (GFC). The results were compared with those from a laboratory which selected samples for further investigation during the clinical validation process. We also studied characteristics of the PEG precipitation test including sensitivity and specificity when compared with GFC.

Results: Over 2 years we screened 368 patients. In 17 cases the proportion of CK activity precipitated by PEG was relatively high and the presence of MCK1 was confirmed in seven by GFC. In a second laboratory, over a period of 5 years, 11 samples were selected during the clinical validation process for further study and MCK1 was the cause of the elevated CK activity in six cases. PEG precipitates a proportion of normal, uncomplexed CK and this is increased by increasing serum globulin concentration and by higher concentrations of PEG.

Conclusions: The prevalence of elevated serum CK activity due to MCK1 was approximately 2%. Laboratories should consider introducing a systematic screening programme based on PEG precipitation.
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July 2007

Specificity and clinical utility of methods for the detection of macroprolactin.

Clin Chem 2006 Jul 4;52(7):1366-72. Epub 2006 May 4.

Department of Investigative Endocrinology, St. Vincent's University Hospital, Dublin, Ireland.

Background: Increased serum concentrations of macroprolactin are a relatively common cause of misdiagnosis and mismanagement of hyperprolactinemic patients.

Methods: We studied sera from a cohort of 42 patients whose biochemical hyperprolactinemia was explained entirely by macroprolactin. Using 5 pretreatments, polyethylene glycol (PEG), protein A (PA), protein G (PG), anti-human IgG (anti-hIgG), and ultrafiltration (UF), to deplete macroprolactin from sera before immunoassay, we compared residual prolactin concentrations with monomer concentrations obtained by gel-filtration chromatography (GFC). A monomeric prolactin standard was used to assess recovery and specificity of the pretreatment procedures.

Results: Residual prolactin concentrations in all pretreated sera differed significantly (P < 0.001) from monomeric concentrations obtained after GFC. PEG underestimated (mean, 75%), whereas PA, PG, anti-hIgG, and UF overestimated (means, 178%, 151%, 178%, and 112%, respectively) the amount of monomer present. Of the 5 methods examined, PEG correlated best with GFC (r = 0.80) followed by PG (r = 0.78), PA (r = 0.72), anti-hIgG (r = 0.70), and UF (r = 0.61). After UF or pretreatment with anti-hIgG or PEG, recovery of monomeric prolactin standard was low: 60%, 85%, and 77% respectively. In contrast, pretreatment with PA or PG gave almost quantitative recovery.

Conclusions: None of the methods examined yielded results identical to the GFC method. PEG pretreatment yielded results that correlated best and is recommended as the first-choice alternative to GFC.
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July 2006

Cardiac troponin T circulates in the free, intact form in patients with kidney failure.

Clin Chem 2006 Mar 12;52(3):414-20. Epub 2006 Jan 12.

Department of Clinical Biochemistry, Southend Hospital, Westcliff-on-Sea, United Kingdom.

Background: The clinical significance of the increased concentrations of cardiac troponins observed in patients with end stage renal disease (ESRD) in the absence of an acute coronary syndrome (ACS) is controversial. One proposed explanation is that immunoreactive fragments of cardiac troponin T (cTnT) accumulate in ESRD. We used gel-filtration chromatography (GFC) to ascertain whether fragments of cTnT, which could cross-react in the commercial diagnostic immunoassay (Roche Diagnostics), were the cause of the increased cTnT in the serum of patients with ESRD.

Methods: We subjected sera from ESRD patients (n = 21) receiving dialysis and having increased cTnT concentrations to size-separation GFC. We detected cTnT in the chromatography fractions by use of the same antibodies used in the commercial assay for serum cTnT.

Results: In all patients, cTnT immunoreactivity eluted as a major, homogeneous peak in an identical position between the peaks of serum prolactin [relative molecular mass (Mr) 23,000] and albumin (Mr 67,000): the elution pattern of cTnT in samples obtained from ACS patients was identical to that of the ESRD patients. There was no evidence that low-molecular-mass (Mr < 23,000) cTnT fragments were the cause of the increased cTnT in the patients studied.

Conclusions: The form of cTnT observed in the serum of patients with kidney failure and immunoreactive in the diagnostic assay is predominantly the free intact form, as in patients with ACS. Our data are consistent with the view that circulating cTnT in renal failure reflects cardiac pathology.
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March 2006

Hyperprolactinaemia due to macroprolactins: some progress but still a problem.

Clin Endocrinol (Oxf) 2003 Jun;58(6):683-5

Department of Biochemistry, Southend Hospital, Westcliff-on-Sea, UK.

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June 2003

Gross variability in the detection of prolactin in sera containing big big prolactin (macroprolactin) by commercial immunoassays.

J Clin Endocrinol Metab 2002 Dec;87(12):5410-5

Department of Endocrinology and Diabetes Mellitus, St. Vincent's University Hospital, Elm Park, Dublin 4, Ireland.

A high molecular mass form of prolactin (PRL), macroprolactin, accumulates in the sera of some subjects. Although macroprolactin exhibits limited bioactivity in vivo, it retains immunoreactivity. We examined the frequency of macroprolactinemia in clinical practice and the ability of immunoassay systems to distinguish between macroprolactin and monomeric PRL. Of 300 hyperprolactinemic sera identified, 71 normalized following treatment of sera with polyethylene glycol, indicating that 24% of hyperprolactinemia could be accounted for by macroprolactin. Ten of these macroprolactinemic sera were circulated to 18 clinical laboratories. Two sets of PRL measurements of the 10 untreated sera were obtained from each of the nine most commonly used immunoassay systems. Across the nine assay systems, differences in the PRL estimates ranged from 2.3- to 7.8-fold. Elecsys users reported the highest PRL levels. Somewhat lower values were reported for DELFIA systems followed by Immuno-1, AxSYM, and Architect assays. The Immulite 2000 assay generated PRL levels equivalent to approximately 50% of those reported by the high-reading methods. The lowest PRL levels were reported by Access, ACS:180, and Centaur systems. To avoid confusion caused by the frequent presence of macroprolactin accounting for hyperprolactinemia, secondary screening for the presence of macroprolactin is recommended.
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December 2002