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  1. Article ; Online: Urine copper by colorimetry.

    Handley, S A / Wanandy, T

    Annals of clinical biochemistry

    2023  Volume 61, Issue 2, Page(s) 157–158

    MeSH term(s) Humans ; Colorimetry ; Copper
    Chemical Substances Copper (789U1901C5)
    Language English
    Publishing date 2023-12-27
    Publishing country England
    Document type Letter
    ZDB-ID 390309-6
    ISSN 1758-1001 ; 0004-5632
    ISSN (online) 1758-1001
    ISSN 0004-5632
    DOI 10.1177/00045632231224244
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Verification of the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site Optilite benchtop analyser.

    Handley, S A / Dote, N P / Wanandy, T / Prentice, L

    Practical laboratory medicine

    2023  Volume 36, Page(s) e00318

    Abstract: Objectives: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are increasingly prevalent disorders. Faecal calprotectin is useful in the differential diagnosis of IBD from IBS and monitoring IBD activity. We verified the Bühlmann fCAL ... ...

    Abstract Objectives: Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) are increasingly prevalent disorders. Faecal calprotectin is useful in the differential diagnosis of IBD from IBS and monitoring IBD activity. We verified the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site, Optilite benchtop analyser.
    Design: Accuracy, precision, lower limit of quantitation (LLoQ), and linearity of the Bühlmann fCAL turbo faecal calprotectin assay on the Binding Site, Optilite benchtop analyser were ascertained. Comparison with the Bühlmann Quantum Blue fCAL extended and DiaSorin, Liaison calprotectin assays were also undertaken. Difference between assays was evaluated using the Wilcoxon signed-rank test and method comparison was undertaken using Spearman's rank correlation (rs), difference plots and Passing-Bablok regression analyses.
    Results: The fCAL turbo assay was linear between 25 and 10,000 μg/g, and the LLoQ was 25 μg/g. Intra-, and inter-assay imprecision was <5%. There was a good agreement (rs = 0.96) and no significant bias (3%, p = 0.10) present between the fCAL turbo and Quantum Blue extended assays. Between the fCAL turbo and DiaSorin, liaison assays there was a good agreement (rs = 0.97), but a significant bias (53%, p = <0.01) was present.
    Conclusions: The fCAL turbo assay performs well on the Binding Site, Optilite benchtop analyser. Calprotectin results are commutable between with Bühlmann fCAL turbo and Quantum Blue fCAL extended assays, but not between Bühlmann and DiaSorin calprotectin assays.
    Language English
    Publishing date 2023-06-24
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 2834973-8
    ISSN 2352-5517
    ISSN 2352-5517
    DOI 10.1016/j.plabm.2023.e00318
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Clozapine-induced gastrointestinal hypomotility: presenting features and outcomes, UK pharmacovigilance reports, 1992-2017.

    Handley, S A / Every-Palmer, S / Ismail, A / Flanagan, R J

    The British journal of psychiatry : the journal of mental science

    2022  , Page(s) 1–9

    Abstract: Background: Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine.: Aims: To document the incidence of potentially harmful CIGH in the UK.: Method: We studied spontaneous UK pharmacovigilance ... ...

    Abstract Background: Clozapine-induced gastrointestinal hypomotility (CIGH) affects some 75% of patients treated with clozapine.
    Aims: To document the incidence of potentially harmful CIGH in the UK.
    Method: We studied spontaneous UK pharmacovigilance reports recorded as clozapine-related gastrointestinal adverse drug reactions, 1992-2017.
    Results: There were 527 patients reported with potentially harmful CIGH; 33% (n = 172) died. Deaths averaged 1 per year 1992-1999, 5 per year 2000-2009 and 15 per year 2010-2017. Those who died were older (median 52 years v. 49 years) and had been prescribed clozapine for longer than those who recovered (median 11.3 years v. 4.8 years), but there was no difference in prescribed dose. Within the first 4 years of clozapine treatment, there were 169 reports of CIGH, of which 3% (n = 5) were fatal. At 10-14 years there were 63 reports of CIGH, of which 25% (n = 16) were fatal. Among the deaths, males were younger (median 51, range 22-89 v. median 57, range 24-89 years) with higher clozapine doses (median 450, range 100-900 v. median 300, range 12.5-800 mg/d) than females. In non-fatal CIGH, surgery was the most frequent outcome (n = 92). The procedures included appendectomy, ileostomy, total/partial colectomy, colostomy/stoma and proctosigmoidectomy. Clozapine dosage was reduced in 6 patients, stopped and restarted in 23, 'continued' in 6 and discontinued permanently in at least 76 patients.
    Conclusions: The risk of serious morbidity/mortality from CIGH is substantial. The need to actively monitor bowel function and give laxatives to patients treated with clozapine is clear.
    Language English
    Publishing date 2022-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 218103-4
    ISSN 1472-1465 ; 0007-1250
    ISSN (online) 1472-1465
    ISSN 0007-1250
    DOI 10.1192/bjp.2022.24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Drugs and other chemicals involved in fatal poisoning in England and Wales during 2000 – 2011.

    Handley, S A / Flanagan, R J

    Clinical toxicology (Philadelphia, Pa.)

    2014  Volume 52, Issue 1, Page(s) 1–12

    Abstract: Context: Fatal poisoning data can reveal trends in the poisons encountered, which can help guide prescribing practices and product safety and other legislation, and more recently has helped to monitor the use of emerging drugs of abuse ( ‘ legal highs ’ ...

    Abstract Context: Fatal poisoning data can reveal trends in the poisons encountered, which can help guide prescribing practices and product safety and other legislation, and more recently has helped to monitor the use of emerging drugs of abuse ( ‘ legal highs ’ ).
    Methods: We searched Mortality Statistics – Injury and poisoning, Series DH4 (2000 – 2005), Mortality Statistics – Deaths registered in England and Wales, Series DR (2006 – 2011), and the Office for National Statistics drug poisoning database for information on fatal poisoning during 2000 – 2011. We also searched the Pubmed database for ‘ fatal ’ and ‘ poisoning ’ and ‘ England ’ and ‘ Wales ’ : this search yielded seven papers that gave relevant information on deaths reported during 2000 – 2011 that were not superseded by later publications. DEATHS FROM POISONING: The annual number of deaths from poisoning fell from 2000 (3092) to 2010 (2749), before increasing to 3341 in 2011. This increase was due in part to a change in the ICD coding relating to alcohol poisoning, suggesting that such deaths had been under-recorded previously. Although fatalities from dextropropoxyphene declined (287 in 2004 and 18 in 2011) following the withdrawal of co-proxamol (paracetamol [acetaminophen] and dextropropoxyphene [propoxyphene] mixture) during 2005 – 2007, deaths involving codeine and most notably tramadol (836 deaths during 2000 – 2011) increased. Deaths from paracetamol poisoning either alone, or with alcohol reached 89 in 2011, the lowest annual figure since 1974. However, in reality there has been no marked downward trend since 1999 despite reductions in pack size, continued publicity as to the dangers of paracetamol overdose, and improved liver failure treatment, including transplantation. The annual number of deaths from antidepressants remained relatively stable (median: 397, range: 335 – 469). Although the number of deaths from dosulepin [dothiepin] decreased (186 in 2000 and 49 in 2011), the number of deaths involving selective serotonin reuptake inhibitors increased (50 in 2000 and 127 in 2011). Although annual numbers of deaths involving diamorphine/morphine (88% unintentional) declined, deaths involving methadone (89% unintentional) increased and the total annual number of deaths from these drugs showed little change (2000: 1061, 2011: 995). Deaths involving amfetamine/metamfetamine remained relatively constant at about 50 annually, and whilst cocaine-related deaths fell by 48% during 2008 – 2011, and deaths involving MDMA and related compounds fell by 69% over this same period, deaths involving ‘ legal highs ’ , notably γ -hydroxybutrate/ γ -butyrolactone and ketamine, increased.
    Conclusions: Alterations in the availability of paracetamol and of prescription drugs such as dextropropoxyphene and dosulepin have not been accompanied by decreases in the number of deaths from poisoning. Despite intense media and other interest, the annual number of deaths (250 – 300) involving ‘ recreational ’ drugs remains small in relation to the 1000 or so deaths a year from diamorphine and/or methadone.
    MeSH term(s) Accidents/statistics & numerical data ; Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Analgesics, Opioid/poisoning ; Antidepressive Agents/poisoning ; Central Nervous System Depressants/poisoning ; Child ; Child, Preschool ; Data Collection ; Databases, Factual ; Death Certificates ; Designer Drugs/poisoning ; England/epidemiology ; Ethanol/poisoning ; Female ; Gas Poisoning/mortality ; Humans ; Infant ; International Classification of Diseases ; Male ; Middle Aged ; Poisoning/mortality ; Registries ; Sex Factors ; Wales/epidemiology ; Young Adult
    Chemical Substances Analgesics, Opioid ; Antidepressive Agents ; Central Nervous System Depressants ; Designer Drugs ; Ethanol (3K9958V90M)
    Language English
    Publishing date 2014-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 204476-6
    ISSN 1556-9519 ; 0009-9309 ; 0731-3810 ; 1556-3650
    ISSN (online) 1556-9519
    ISSN 0009-9309 ; 0731-3810 ; 1556-3650
    DOI 10.3109/15563650.2013.872791
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Plasma and Urine Levamisole in Clinical Samples Containing Benzoylecgonine: Absence of Aminorex.

    Handley, S A / Belsey, S L / Couchman, L / Flanagan, R J

    Journal of analytical toxicology

    2018  Volume 43, Issue 4, Page(s) 299–306

    Abstract: Aminorex has been reported as a metabolite of levamisole in man, but data on the aminorex concentrations in clinical samples are scant. We thus measured levamisole, aminorex and benzoylecgonine in urine, and levamisole and aminorex in plasma using ... ...

    Abstract Aminorex has been reported as a metabolite of levamisole in man, but data on the aminorex concentrations in clinical samples are scant. We thus measured levamisole, aminorex and benzoylecgonine in urine, and levamisole and aminorex in plasma using achiral liquid chromatography-high resolution mass spectrometry. Centrifuged urine (50 μL) was diluted with LC eluent containing internal standard (benzoylecgonine-D3, 25 μg/L) (450 μL). For plasma, sample (200 μL) and Tris solution (2 mol/L, pH 10.6, 100 μL) were added to a 60.5 × 7.5 mm i.d. glass test tube. Internal standard solution (ketamine-D4, 200 μg/L) (10 μL) was added and the tube contents vortex-mixed (5 s). Butyl acetate:butanol (9 + 1, v/v; 200 μL) was added and after vortex-mixing (30 s) and centrifugation (13,680 × g, 4 min), the extract was evaporated to dryness and reconstituted in 10 mmol/L aqueous ammonium formate containing 0.1% (v/v) formic acid (150 μL). Prepared samples and extracts (100 μL) were analyzed using an AccucoreTM Phenyl-Hexyl column (2.6 mm a.p.s., 100 × 2.1 mm i.d.) maintained at 40°C. MS detection was in positive mode using heated electrospray ionization (ThermoFisher Q-ExactiveTM). Intra- and inter-assay accuracy and precision were ±20%, and ≤11%, respectively, for all analytes in both matrices. Lower limits of quantitation were 0.1 and 1 μg/L (all analytes) in plasma and urine, respectively. Of 100 consecutive urine samples submitted for drugs of abuse screening containing benzoylecgonine, levamisole was detected in 72 (median 565, range 4-72,970 μg/L). Levamisole was also measured in eight plasma samples (median 10.6, range 0.9-64.1 μg/L). A number of metabolites of levamisole (4-hydroxylevamisole, levamisole sulfoxide, levamisole glucuronide, and hydroxylevamisole glucuronide) were tentatively identified in urine. Neither aminorex, nor any of its reported metabolites were detected in any sample.
    MeSH term(s) Adult ; Aged ; Agranulocytosis/etiology ; Aminorex/blood ; Aminorex/urine ; Antinematodal Agents/adverse effects ; Antinematodal Agents/blood ; Antinematodal Agents/chemistry ; Antinematodal Agents/urine ; Appetite Depressants/blood ; Appetite Depressants/urine ; Chromatography, Liquid ; Cocaine/analogs & derivatives ; Cocaine/urine ; Drug Contamination ; Female ; Half-Life ; Humans ; Levamisole/adverse effects ; Levamisole/blood ; Levamisole/chemistry ; Levamisole/urine ; Male ; Middle Aged ; Osmolar Concentration ; Street Drugs ; Substance Abuse Detection/methods ; Tandem Mass Spectrometry ; Vasculitis/etiology ; Vasoconstrictor Agents/urine ; Young Adult
    Chemical Substances Antinematodal Agents ; Appetite Depressants ; Street Drugs ; Vasoconstrictor Agents ; Levamisole (2880D3468G) ; Aminorex (2SH16612I9) ; benzoylecgonine (5353I8I6YS) ; Cocaine (I5Y540LHVR)
    Language English
    Publishing date 2018-12-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 752391-9
    ISSN 1945-2403 ; 0146-4760
    ISSN (online) 1945-2403
    ISSN 0146-4760
    DOI 10.1093/jat/bky102
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  6. Article ; Online: Measurement of serum lanthanum in patients treated with lanthanum carbonate by inductively coupled plasma-mass spectrometry.

    Handley, S A / Raja, K B / Sharpe, C / Flanagan, R J

    Annals of clinical biochemistry

    2011  Volume 48, Issue Pt 2, Page(s) 178–182

    Abstract: Background: Lanthanum carbonate is used as a phosphate binder in patients with stage V chronic kidney disease (CKD). While well tolerated in clinical trials, with no toxicity reported as regards bone and liver metabolism, and cognitive function, ... ...

    Abstract Background: Lanthanum carbonate is used as a phosphate binder in patients with stage V chronic kidney disease (CKD). While well tolerated in clinical trials, with no toxicity reported as regards bone and liver metabolism, and cognitive function, concerns remain over possible toxicity. Published methods for the measurement of lanthanum ion in biological samples include aggressive and complicated sample preparation steps that are unsuitable for routine use. A simple method has been developed and validated for the measurement of serum lanthanum.
    Method: A ThermoFisher Scientific XSERIES-II inductively coupled plasma-mass spectrometer was used to monitor ¹³⁹La. Validation was undertaken using internal quality control solutions containing lanthanum ion (0.20, 0.70 and 4.00 μg/L). Lanthanum was measured in patients (number = 20) with CKD prescribed lanthanum carbonate (500-1500 mg/d) and patients undergoing haemodialysis not prescribed lanthanum carbonate (number = 20).
    Results: Accuracy and imprecision were >95% and <5%, respectively. Calibration was linear (range 0.1-5 μg/L, R² = 0.99). The lower limit of quantification (LLoQ) was 0.1 μg/L lanthanum ion. In patients with CKD not prescribed lanthanum carbonate, serum lanthanum was below the LLoQ. Out of 20 CKD patients prescribed lanthanum carbonate, serum lanthanum was measurable in only 12 (range 0.11-0.60 μg/L lanthanum ion). There was no apparent relationship between dose and serum lanthanum in these patients.
    Conclusions: A lack of relationship between the dose of lanthanum carbonate and the serum lanthanum concentration may have been due to poor adherence to the treatment regimen. However the concentrations measured were close to the LLoQ.
    MeSH term(s) Adult ; Aged ; Blood Chemical Analysis/methods ; Drug Contamination ; Female ; Humans ; Kidney Diseases/drug therapy ; Lanthanum/blood ; Lanthanum/therapeutic use ; Limit of Detection ; Male ; Mass Spectrometry/methods ; Middle Aged ; Renal Dialysis ; Reproducibility of Results
    Chemical Substances lanthanum carbonate (490D9F069T) ; Lanthanum (6I3K30563S)
    Language English
    Publishing date 2011-03
    Publishing country England
    Document type Journal Article
    ZDB-ID 390309-6
    ISSN 1758-1001 ; 0004-5632
    ISSN (online) 1758-1001
    ISSN 0004-5632
    DOI 10.1258/acb.2010.010162
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  7. Article: Differentiation of pathogenic Bartonella species by infrequent restriction site PCR.

    Handley, S A / Regnery, R L

    Journal of clinical microbiology

    2000  Volume 38, Issue 8, Page(s) 3010–3015

    Abstract: Infrequent restriction site PCR (IRS-PCR) is a recently described DNA fingerprinting technique based on selective amplification of restriction endonuclease-cleaved fragments. Bartonella isolates associated with human disease and related nonhuman isolates ...

    Abstract Infrequent restriction site PCR (IRS-PCR) is a recently described DNA fingerprinting technique based on selective amplification of restriction endonuclease-cleaved fragments. Bartonella isolates associated with human disease and related nonhuman isolates were analyzed by IRS-PCR genomic fingerprinting. Preparation of DNA templates began with double digestion using three different restriction endonuclease combinations. Combinations included the frequently cutting endonuclease HhaI in conjunction with an infrequently cutting endonuclease, EagI, SmaI, or XbaI. Digestion was followed by ligation of oligonucleotide adapters designed with ends complementary to the restriction endonuclease sites. Amplification of fragments flanked with an EagI, SmaI, or XbaI site in combination with an HhaI site produced a series of different-sized amplicons resolvable into patterns by polyacrylamide gel electrophoresis (PAGE). The pattern complexity was varied by the addition of selective nucleotides to the 3' ends of the EagI-, SmaI-, or XbaI-specific primers. Amplicons were also generated with fluorescently labeled primers and were subsequently resolved and detected by capillary electrophoresis. Analysis by traditional slab PAGE and capillary electrophoresis provided suitable resolution of patterns produced with the enzyme combinations EagI-HhaI and SmaI-HhaI. However, the combination of XbaI-HhaI produced too many fragments for sufficient resolution by traditional PAGE, thus requiring the better resolving properties of capillary electrophoresis. Due to the flexibility in modulating the pattern complexity and electrophoresis methods, these techniques allow for a high level of experimental optimization. The results provide evidence of the discriminatory power, ease of use, and flexibility of the IRS-PCR method as it applies to the identification of human-pathogenic Bartonella species.
    MeSH term(s) Animals ; Bacterial Typing Techniques ; Bartonella/classification ; Bartonella/genetics ; Bartonella/pathogenicity ; Bartonella Infections/microbiology ; Base Sequence ; DNA Fingerprinting ; DNA Restriction Enzymes/metabolism ; DNA, Bacterial/genetics ; Electrophoresis, Polyacrylamide Gel ; Humans ; Molecular Sequence Data ; Polymerase Chain Reaction/methods
    Chemical Substances DNA, Bacterial ; DNA Restriction Enzymes (EC 3.1.21.-)
    Language English
    Publishing date 2000-08
    Publishing country United States
    Document type Journal Article
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.38.8.3010-3015.2000
    Database MEDical Literature Analysis and Retrieval System OnLINE

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