Publications by authors named "Elizabeth Owen"

15 Publications

  • Page 1 of 1

Incorporating Internal and External Training Load Measurements in Clinical Decision Making After ACL Reconstruction: A Clinical Commentary.

Int J Sports Phys Ther 2021 Apr 2;16(2):565-578. Epub 2021 Apr 2.

High Point University.

Background And Purpose: Poor outcomes after anterior cruciate ligament reconstruction (ACLr), including the relatively high risk of suffering a subsequent ACL injury, suggest the need to optimize rehabilitation and return-to-sport testing. The purpose of this commentary is to introduce clinicians to the concept of monitoring training load during rehabilitation, to review methods of quantifying internal and external loads, and to suggest ways that these technologies can be incorporated into rehabilitation progressions and return-to-sport decisions after anterior ACLr.

Description Of Topic With Related Evidence: Quantifying and identifying the effects of training load variables, external (distance, impacts, decelerations) and internal (heart rate, heart rate variability) workload, during rehabilitation can indicate both positive (improved physical, physiological, or psychological capacity) or negative (heightened risk for injury or illness) adaptations and allow for the ideal progression of exercise prescription. When used during return-to-sport testing, wearable technology can provide robust measures of movement quality, readiness, and asymmetry not identified during performance-based testing.

Discussion / Relation To Clinical Practice: Researchers have reported the actual in-game demands of men and women of various ages and competition levels during multi-directional sport. Wearable technology can provide similar variables during rehabilitation, home exercise programs, and during on-field transition back to sport to ensure patients have met the expected fitness capacity of their sport. Additionally, clinicians can use internal load measures to objectively monitor patient's physiological responses to rehabilitation progressions and recovery rather than relying on subjective patient-reported data.

Level Of Evidence: 5.
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http://dx.doi.org/10.26603/001c.21152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016425PMC
April 2021

Growth, Body Composition, and Lung Function in Prepubertal Children with Cystic Fibrosis Diagnosed by Newborn Screening.

Nutr Clin Pract 2020 Dec 10. Epub 2020 Dec 10.

Department of Population, Policy and Practice, University College London Great Ormond Street Institute of Child Health, London, UK.

Background: Children with cystic fibrosis (CF) are at risk of altered body composition (BC). Newborn screening (NBS) may lead to improved BC outcomes. We investigated BC and its relationship with lung function in prepubertal children diagnosed with CF by NBS. Secondary aims explored predictors of fat-free mass (FFM) and lung function.

Methods: Thirty-seven screened (non-meconium ileus) children with CF (20 boys) born 2007-2012 had a dual-energy x-ray absorptiometry scan at 5-8 years to determine whole-body (WB) and appendicular BC. Anthropometry was performed and routine spirometry recorded. Results were converted to z-scores, height-adjusted (fat mass index [FMI] and FFM index [FFMI]) and compared with population mean values. Predictors of forced expiratory volume in 1 second (FEV ) were assessed using linear regression.

Results: Height, body mass index (BMI), and FEV were within normal limits, however, weight and BC were significantly low compared with reference data (weight, P = .03; WB FMI, P = .001; WB FFMI, P = .009). Gender differences were detected, with lower appendicular BC in boys and lower weight, BMI, and BC in girls. The association between FEV and WB FFMI (r = 0.38; P = .02) was stronger than with BMI (r = 0.29; P = .08). WB FFMI was the only significant predictor of FEV in a multivariable model (95% CI, 0.11-0.99; P = .016).

Conclusion: In this NBS CF population, gender differences in growth and BC were apparent despite preserved lung function. These results support BC assessment in prepubertal children, particularly girls, with an opportunity to direct interventions to optimize FFM.
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http://dx.doi.org/10.1002/ncp.10604DOI Listing
December 2020

Mitochondrial molecular genetic results in a South African cohort: divergent mitochondrial and nuclear DNA findings.

J Clin Pathol 2020 Oct 28. Epub 2020 Oct 28.

Division of Paediatric Neurology, Department of Paediatrics and Child Health, University of Cape Town, Cape Town, Western Cape, South Africa.

Aims: Mitochondrial diseases form one of the largest groups of inborn errors of metabolism. The birth prevalence is approximately 1/5000 in well-studied populations, but little has been reported from Sub-Saharan Africa. The aim of this study was to describe the genetics underlying mitochondrial disease in South Africa.

Methods: An audit was performed on all mitochondrial disease genetic testing performed in Cape Town, South Africa.

Results: Of 1614 samples tested for mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) variants in South Africa between 1994 and 2019, there were 155 (9.6 %) positive results. Pathogenic mtDNA variants accounted for 113 (73%)/155, from 96 families. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes, 37 (33%)/113, Leber's hereditary optic neuropathy, 26 (23%)/113, and single large mtDNA deletions, 22 (20%)/113, accounted for 76%. Thirty eight of 42 nDNA-positive results were homozygous for the pathogenic variant c.106C>T (p.[Gln36Ter, Ser25Profs*49]) causing infantile neurohepatopathy, one of the largest homozygous groups reported in the literature. The other nDNA variants were in and . None were identified in or .

Conclusions: Finding a large group with a homozygous nuclear pathogenic variant emphasises the importance of looking for possible founder effects. The absence of other widely described pathogenic nDNA variants in this cohort may be due to reduced prevalence or insufficient testing. As advances in therapeutics develop, it is critical to develop diagnostic platforms on the African subcontinent so that population-specific genetic variations can be identified.
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http://dx.doi.org/10.1136/jclinpath-2020-207026DOI Listing
October 2020

INCORPORATING WORKLOAD MEASURES INTO REHABILITATION AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION: A CASE REPORT.

Int J Sports Phys Ther 2020 Oct;15(5):823-831

Department of Physical Therapy, High Point University, High Point, NC, USA.

Background: and purpose: Second anterior cruciate ligament (ACL) injury rates continue to be high, with a majority of injuries occurring soon after return-to-play, potentially because athletes may not be ready for the external load demands of the sport. Load metrics, tracked through wearable technology, may provide complementary information to standard limb symmetry indices in the return-to-play decision making process. The purpose of this case report was to quantify and monitor load using innovative technology during physical therapy rehabilitation after ACL reconstruction (ACLr) and compare to normative sport participation data.Case Description: The subject was a 12-year-old female soccer player that suffered an ACL injury followed by surgical reconstruction with a hamstring autograft and standard rehabilitation. Single-leg hop performance, isokinetic strength, and external loads (using wearable technology) were measured longitudinally during rehabilitation and analyzed at the time of return-to-play.Outcomes: The subject successfully achieved >90% LSI for isometric quadriceps strength (week 14), single leg hop battery (week 23), and isokinetic hamstrings (week 26) and quadriceps (week 31) strength by the time of return-to-play (week 39). At the time of return to play, external load metrics indicated that the subject's most intense rehabilitation session consisted of 36% less frequent movements, 38% lower total distances, and activity durations that were 29% lower than the expected demands of a match.

Discussion: Standard rehabilitation may underload patients relative to required sport demands. Measuring external load during the rehabilitation period may help clinicians adequately progress workload to the necessary demands of the patient's sport. With the current emphasis on restoring limb symmetry, clinicians may need to shift focus towards load preparation when returning a patient to their sport.Level of Evidence: 4Keywords: anterior cruciate ligament, load, rehabilitation, return to play, step count, movement system.
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http://dx.doi.org/10.26603/ijspt20200823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575154PMC
October 2020

Hyperbaric oxygen therapy for cerebral air gas embolism following orthotopic heart transplant: case report.

Undersea Hyperb Med 2018 Nov-Dec;45(6):685-688

University of California, San Diego, Department of Emergency Medicine, Division of Hyperbaric and Undersea Medicine, San Diego, California U.S.

Air gas embolism (AGE) is a rare complication of cardiac surgery, with high morbidity and mortality. We present a case of suspected AGE following orthotopic heart transplant. The patient received hyperbaric oxygen therapy with near-complete resolution of symptoms at follow-up. This case exemplifies the difficulty in diagnosis of AGE, the considerations involved in the treatment of a critical care patient in a hyperbaric chamber, and utility in treating a patient for AGE even after a delay in diagnosis.
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October 2019

A novel role for myeloid endothelin-B receptors in hypertension.

Eur Heart J 2019 03;40(9):768-784

BHF Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, UK.

Aims: Hypertension is common. Recent data suggest that macrophages (Mφ) contribute to, and protect from, hypertension. Endothelin-1 (ET-1) is the most potent endogenous vasoconstrictor with additional pro-inflammatory properties. We investigated the role of the ET system in experimental and clinical hypertension by modifying Mφ number and phenotype.

Methods And Results: In vitro, Mφ ET receptor function was explored using pharmacological, gene silencing, and knockout approaches. Using the CD11b-DTR mouse and novel mice with myeloid cell-specific endothelin-B (ETB) receptor deficiency (LysMETB-/-), we explored the effects of modifying Mφ number and phenotype on the hypertensive effects of ET-1, angiotensin II (ANG II), a model that is ET-1 dependent, and salt. In patients with small vessel vasculitis, the impacts of Mφ depleting and non-depleting therapies on blood pressure (BP) and endothelial function were examined. Mouse and human Mφ expressed both endothelin-A and ETB receptors and displayed chemokinesis to ET-1. However, stimulation of Mφ with exogenous ET-1 did not polarize Mφ phenotype. Interestingly, both mouse and human Mφ cleared ET-1 through ETB receptor mediated, and dynamin-dependent, endocytosis. Mφ depletion resulted in an augmented chronic hypertensive response to both ET-1 and salt. LysMETB-/- mice displayed an exaggerated hypertensive response to both ET-1 and ANG II. Finally, in patients who received Mφ depleting immunotherapy BP was higher and endothelial function worse than in those receiving non-depleting therapies.

Conclusion: Mφ and ET-1 may play an important role in BP control and potentially have a critical role as a therapeutic target in hypertension.
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http://dx.doi.org/10.1093/eurheartj/ehy881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396028PMC
March 2019

Evaluations of Urban Sovereign Citizens' Competency to Stand Trial.

J Am Acad Psychiatry Law 2018 Jun;46(2):158-166

Drs. Paradis and Owen are Associate Clinical Professors, State University of New York, Downstate Medical Center, Brooklyn, NY. Dr. Paradis is Professor, Marymount Manhattan College, New York, NY. Dr. Owen is Director, Forensic Psychiatry Service, Kings County Hospital Center, New York City Health and Hospitals, Brooklyn, NY, and Adjunct Associate Professor, Columbia University Teachers College, New York, NY. Mr. McCullough is a Psychiatric Nurse Practitioner in the Department of Psychiatry at Mount Sinai West Hospital, New York, NY.

There are few studies of sovereign citizens undergoing competency-to-stand-trial evaluations and little has been written about African-American or urban sovereign citizens. In this study, we examined competency-to-stand-trial reports of 36 New York City defendants who declared themselves to be sovereign citizens during their evaluations. All were men and 33 were African American. The majority denied recent or remote histories of psychiatric hospitalizations or substance use. Sixty-nine percent were deemed competent. Compared with those deemed competent, those deemed not competent were significantly more likely to have diagnosed psychotic disorders and to have reported histories of psychiatric hospitalizations. The 36 who declared themselves sovereign citizens were compared with 200 who did not, from a study conducted in the same forensic clinic. The sovereign citizens were significantly more likely to be male, African American, and high school graduates and were significantly less likely to report a history of psychiatric hospitalization or substance use. Compared with the nonsovereign citizens, they were less likely to receive a diagnosis of psychotic or mood disorders during the competency evaluation and were more likely to be deemed competent. Included are suggestions to assist forensic examiners conducting evaluations of these difficult cases.
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http://dx.doi.org/10.29158/JAAPL.003758-18DOI Listing
June 2018

Competency to stand trial evaluations in a multicultural population: Associations between psychiatric, demographic, and legal factors.

Int J Law Psychiatry 2016 Jul-Aug;47:79-85. Epub 2016 Apr 13.

Department of Psychiatry, Mount Sinai-Roosevelt Hospital, 1111Amsterdam Avenue, New York, NY 10025, USA.

Data were examined from an archival sample of Competency to Stand Trial (CST) reports of 200 consecutive New York City pre-trial defendants evaluated over a five-month period. Approximately a fourth of defendants in the present study were immigrants; many required the assistance of interpreters. The examiners conducting the CST evaluation diagnosed approximately half of the defendants with a primary diagnosis of a psychotic disorder and deemed over half not competent. Examiners reached the same conclusion about competency in 96% of cases, about the presence of a psychotic disorder in 91% of cases, and affective disorder in 85% of cases. No significant differences between psychologists and psychiatrists were found for rates of competency/incompetency opinions. Compared to those deemed competent, defendants deemed not competent had significantly higher rates of prior psychiatric hospitalization and diagnosis of psychotic illness at the time of the CST evaluation but lower rates of reported substance abuse.
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http://dx.doi.org/10.1016/j.ijlp.2016.02.039DOI Listing
January 2018

An unusual cause for epigastric pain in pregnancy. Spontaneous uterine rupture with herniation of the amniotic sac in a 33-week primigravida.

BMJ Case Rep 2014 Mar 5;2014. Epub 2014 Mar 5.

Department of Obstetrics and Gynaecology, West Middlesex University Hospital, London, UK.

A 29-year-old in vitro fertilisation patient presented at 33 weeks of gestation with abdominal pain. An abdominal ultrasound revealed a cystic lesion adjacent to the fundus. During caesarean section, a defect at the fundus was identified with herniation of the amniotic sac through this defect. There were no complications postoperatively and the patient made an unremarkable recovery. With at least one maternal death reported in the most recent confidential enquiry into maternal death, uterine rupture is an obstetric emergency and can have catastrophic outcomes. The incidence of uterine rupture as a result of previous perforation is unclear with little published data and few case reports. Cases of uterine rupture after perforation following hysteroscopic resection of fibroids, uterine septum are well published but the authors found no known previous cases related to laparoscopy. Counselling patients post perforation should include discussion regarding the management of future pregnancies and the risk of uterine rupture.
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http://dx.doi.org/10.1136/bcr-2013-202973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3948010PMC
March 2014

Glucocorticoid receptor is required for foetal heart maturation.

Hum Mol Genet 2013 Aug 16;22(16):3269-82. Epub 2013 Apr 16.

Centre for Cardiovascular Science, University of Edinburgh, Queen’s Medical Research Institute, Edinburgh EH16 4TJ, UK.

Glucocorticoids are vital for the structural and functional maturation of foetal organs, yet excessive foetal exposure is detrimental to adult cardiovascular health. To elucidate the role of glucocorticoid signalling in late-gestation cardiovascular maturation, we have generated mice with conditional disruption of glucocorticoid receptor (GR) in cardiomyocytes and vascular smooth muscle cells using smooth muscle protein 22-driven Cre recombinase (SMGRKO mice) and compared them with mice with global deficiency in GR (GR(-/-)). Echocardiography shows impaired heart function in both SMGRKO and GR(-/-) mice at embryonic day (E)17.5, associated with generalized oedema. Cardiac ultrastructure is markedly disrupted in both SMGRKO and GR(-/-) mice at E17.5, with short, disorganized myofibrils and cardiomyocytes that fail to align in the compact myocardium. Failure to induce critical genes involved in contractile function, calcium handling and energy metabolism underpins this common phenotype. However, although hearts of GR(-/-) mice are smaller, with 22% reduced ventricular volume at E17.5, SMGRKO hearts are normally sized. Moreover, while levels of mRNA encoding atrial natriuretic peptide are reduced in E17.5 GR(-/-) hearts, they are normal in foetal SMGRKO hearts. These data demonstrate that structural, functional and biochemical maturation of the foetal heart is dependent on glucocorticoid signalling within cardiomyocytes and vascular smooth muscle, though some aspects of heart maturation (size, ANP expression) are independent of GR at these key sites.
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http://dx.doi.org/10.1093/hmg/ddt182DOI Listing
August 2013

A pilot outreach physiotherapy and dietetic quality improvement initiative reduces IV antibiotic requirements in children with moderate-severe cystic fibrosis.

J Cyst Fibros 2013 Dec 17;12(6):766-72. Epub 2013 Feb 17.

Cystic Fibrosis Unit, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom; Portex Respiratory Unit, University College London Institute of Child Health, London, United Kingdom. Electronic address:

Background: At our hospital the current model of care for children with moderate-severe CF is focused on intensive inpatient intervention, regular outpatient clinic review and specialist outreach care as required. An alternative model providing more regular physiotherapy and dietetic outreach support, in addition to these specialist services, may be more effective.

Methods: 16 children (4 male; 12 female; mean age 10.9±2.93; range 4-15 years) who required >40days of IV antibiotics in the 12-months pre-intervention were enrolled. Physiotherapy included weekly-supervised exercise sessions, alongside regular review of home physiotherapy regimens. Dietetic management included 1-2 monthly monitoring of growth, appetite, intake and absorption, and nutrition education sessions.

Results: There was a 23% reduction in inpatient IV antibiotic requirement and 20% reduction in home IV antibiotic requirement during the intervention year. Cost-benefit analyses showed savings of £113,570. VO(2Peak) increased by 4.9 ml·kg·min(-1) (95%CI 1.01 to 8.71; p=0.02), and 10 m-MSWT distance and increment achieved increased by 229 m (95%CI 109 to 350; p<0.001) and 2 levels (95%CI 1 to 3; p<0.002) respectively. No significant differences in physiological and patient reported outcomes were demonstrated, although there was a possible trend towards improvement in outcomes when compared to the pre-intervention year.

Conclusion: This pilot programme demonstrated a reduction in IV and admission requirements with a cost benefit in a small group of children with moderate-severe CF. A fully powered clinical trial is now warranted.
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http://dx.doi.org/10.1016/j.jcf.2013.01.003DOI Listing
December 2013

Glutaric aciduria type 1 in South Africa-high incidence of glutaryl-CoA dehydrogenase deficiency in black South Africans.

Mol Genet Metab 2010 Oct-Nov;101(2-3):178-82. Epub 2010 Aug 3.

Division of Chemical Pathology, Groote Schuur and Red Cross Children's Hospitals, University of Cape Town, Cape Town, South Africa.

Glutaric Aciduria type 1 (GA 1) is an inherited disorder of lysine and tryptophan catabolism that typically manifests in infants with acute cerebral injury associated with intercurrent illness. We investigated the clinical, biochemical and molecular features in 14 known GA 1 patients in South Africa, most of whom were recently confirmed following the implementation of sensitive urine organic acid screening at our laboratory. Age at diagnosis ranged from 3days to 5years and poor clinical outcome reflected the delay in diagnosis in all but one patient. Twelve patients were unrelated black South Africans of whom all those tested (n=11) were found homozygous for the same A293T mutation in the glutaryl-CoA dehydrogenase (GCDH) gene. Excretion of 3-hydroxyglutarate (3-OHGA) was >30.1μmol/mmol creatinine (reference range <2.5) in all cases but glutarate excretion varied with 5 patients considered low excretors (glutarate <50μmol/mmol creatinine). Fibroblast GCDH activity was very low or absent in all of five cases tested. Heterozygosity for the A293T mutation was found 1 in 36 (95% CI; 1/54 - 1/24) unrelated black South African newborns (n=750) giving a predicted prevalence rate for GA 1 of 1 in 5184 (95% CI; 1/11664 - 1/2304) in this population. GA 1 is a treatable but often missed inherited disorder with a previously unrecognised high carrier frequency of a single mutation in the South African black population.
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http://dx.doi.org/10.1016/j.ymgme.2010.07.018DOI Listing
January 2011

A pilot study to investigate patients reported knowledge, awareness, and beliefs on health care-associated infection.

Am J Infect Control 2008 Feb;36(1):63-9

Background: Health care-associated infections (HCAIs) remain a concern for patients, staff, and health care organizations. There is a lack of relevant literature on patients' views and opinions of infection control services.

Method: A descriptive study of 110 patients was undertaken utilizing a developed questionnaire to investigate patients' knowledge, perceptions, and beliefs around HCAIs.

Results: Respondents believed they were well aware of the risks of HCAI before hospital admission, but their knowledge on routes of transmission and prevention of infection was poor. Twenty-eight percent of the respondents were able to name Methicillin-resistant Staphylococcus aureus (MRSA) as contributing to HCAIs. Patients' main sources of information about infections were newspapers and television.

Conclusion: Patients have a high level of awareness of the risk of HCAI but have little knowledge about how infections spread or about their prevention.
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http://dx.doi.org/10.1016/j.ajic.2007.01.008DOI Listing
February 2008

Identification and characterization of a temperature-sensitive R268H mutation in the human succinyl-CoA:3-ketoacid CoA transferase (SCOT) gene.

Mol Genet Metab 2007 Nov 13;92(3):216-21. Epub 2007 Aug 13.

Department of Pediatrics, Graduate School of Medicine, Gifu University, Gifu, Gifu 501-1194, Japan.

Succinyl-CoA:3-ketoacid CoA transferase (SCOT) deficiency causes episodic ketoacidosis. We encountered a case of siblings in South Africa in whom a novel homozygous mutation (R268H) was found in genomic DNA. Mutant SCOT protein was very faintly detected in their fibroblasts using immunoblot analysis. Transient expression analysis of R268H mutant cDNA at 37 degrees C revealed that the R268H mutant protein was clearly detected, as much as 50% wild-type, together with 40% residual SCOT activities, hence R268H was first regarded as not being a disease-causing mutation. Since no other mutation was identified, R268H mutation was re-evaluated by further transient expression analysis. Accumulation of the R268H mutant protein was revealed to be strongly temperature dependent; residual SCOT activities were calculated to be 59.7%, 34%, and 4%, respectively, in expression at 30 degrees C, 37 degrees C, and 40 degrees C in SV40-transformed fibroblasts of GS01(a homozygote of S283X). SCOT activity of the R268H protein was more vulnerable than the wild-type to heat treatment at 50 degrees C. These results indicated that the R268H mutant protein was clearly more unstable than the wild-type in a temperature-sensitive manner. Furthermore, an analysis of the three-dimensional structure of SCOT showed that the R268H mutation was expected to break a conserved salt bridge between R268 and D52, which would be expected to lead to decreased stability of the protein. Hence we finally concluded that the R268H mutation is a disease-causing one. The stability of mutant protein in transient expression analysis does not always reflect the condition in patients' fibroblasts.
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http://dx.doi.org/10.1016/j.ymgme.2007.07.005DOI Listing
November 2007

Thiopurine methyltransferase (TPMT) heterozygosity and enzyme activity as predictive tests for the development of azathioprine-related adverse events.

J Neurol Sci 2005 Apr;231(1-2):71-80

Division of Neurology, Department of Medicine, E8-74 Neurology, Groote Schuur Hospital and University of Cape Town, Observatory 7925, South Africa.

Thiopurine methyltransferase (TPMT) is a key enzyme in azathioprine metabolism mediating both immunosuppression and cytotoxicity. TPMT activity may be influenced by a mutation in the TPMT gene resulting in individual differences in azathioprine metabolism. Individuals heterozygous for TPMT mutations or with low TPMT activity may be susceptible to azathioprine toxicity. We evaluate TPMT genotyping and TPMT enzyme activity as predictive tests for developing azathioprine-related adverse events. Neurological patients (n=129) observed whilst taking azathioprine therapy were genotyped for the TPMT*2, *3A and *3C mutations; TPMT enzyme activity was analysed in 92 of these patients. Ethnic appropriate controls (Black, Mixed-Ancestry and White) were genotyped (n=465) and of these controls TPMT activity was also measured in 115. Azathioprine-related adverse events developed in 21.7% of the patients; early (within 1 week) events included gastrointestinal symptoms (n=8/28). Haematological toxicity, hepatotoxicity, arthralgia, rashes and pancreatitis developing between 4 and 240 weeks. Genotyping showed that only four of 28 cases who developed adverse events, were heterozygous for TPMT*3A or *3C. Heterozygous patients developed either haematological or hepatic toxicity. In an ethnically heterogeneous society TPMT enzyme activity proved difficult to interpret as measurements amongst controls showed significant ethnic variation (p=1 x 10(-6)); cut-points between "low" and "normal" TPMT activity correlated with indigenous African genetic ancestry. Ethnic appropriate cut-points were determined but due to the ambiguity in interpreting TPMT enzyme results in heterogeneous societies, we favour genotyping as a predictive test. The positive predictive value of genotyping was low, but the likelihood ratio for developing either haematological or hepatotoxicity by identifying TPMT heterozygosity, was 9.75. In our patient population this translates into an improvement from a pre-test probability of developing haematological or hepatotoxicity of 11%, to a post-test level of 50%. Heterozygous patients may then be targeted for a more "tailored" increase in dosing and regular laboratory monitoring.
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http://dx.doi.org/10.1016/j.jns.2005.01.003DOI Listing
April 2005