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Article: L-lactic acidosis: not just an hypoxic disorder.

Worthley, L I G

Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine

2002 Volume 4, Issue 1, Page(s) 13–15

Language	English
Publishing date	2002-03
Publishing country	Australia
Document type	Comment ; Editorial
ZDB-ID	2401976-8
ISSN	1441-2772
ISSN	1441-2772
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Article: Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives.

Heresztyn, Tamila / Worthley, Matthew I / Horowitz, John D

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2004 Volume 805, Issue 2, Page(s) 325–329

Abstract: A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' ... dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N ... on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard ...

Abstract	A new HPLC assay for the detection of L-arginine, NG, NG-dimethyl-L-arginine (ADMA) and NG, NG' -dimethyl-L-arginine (SDMA) in plasma using the derivatisation reagent AccQ-Fluor (6-aminoquinolyl-N-hydroxysuccinimidyl carbamate) is described. The fluorescent derivatives produced are extremely stable enabling routine processing of large numbers of samples. Arginine and its metabolites are extracted from plasma on strong cation exchange (SCX) cartridges with NG-monomethyl-L-arginine (NMMA) as internal standard, derivatised and separated on a C18 column with acetonitrile in 0.1M sodium acetate buffer pH 6. Separation of the stereoisomers ADMA and SDMA was excellent and improvements to the solid phase extraction (SPE) procedure enabled good recovery (>80%) of arginine, ADMA and SDMA. The utility of the method is exemplified by comparison of plasma concentrations of ADMA, SDMA and arginine in healthy volunteers and diabetic/ischaemic patients.
MeSH term(s)	Arginine/analogs & derivatives ; Arginine/blood ; Chromatography, High Pressure Liquid/methods ; Female ; Humans ; Male ; Reference Values
Chemical Substances	dimethylarginine ; Arginine (94ZLA3W45F)
Language	English
Publishing date	2004-06-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1570-0232
ISSN	1570-0232
DOI	10.1016/j.jchromb.2004.03.020
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Article: Effect of systemic administration of the nitric oxide synthase inhibitor L-NMMA on the human ventilatory response to hypoxia.

Ide, Kojiro / Worthley, Matthew / Anderson, Todd / Poulin, Marc J

Advances in experimental medicine and biology

2008 Volume 605, Page(s) 41–45

MeSH term(s)	Blood Pressure/drug effects ; Carbon Dioxide/blood ; Enzyme Inhibitors/pharmacology ; Heart Rate/drug effects ; Humans ; Hypoxia/chemically induced ; Hypoxia/physiopathology ; Kinetics ; Nitric Oxide Synthase/antagonists & inhibitors ; Oxygen/blood ; Partial Pressure ; Respiratory Physiological Phenomena/drug effects ; Tidal Volume ; omega-N-Methylarginine/pharmacology
Chemical Substances	Enzyme Inhibitors ; Carbon Dioxide (142M471B3J) ; omega-N-Methylarginine (27JT06E6GR) ; Nitric Oxide Synthase (EC 1.14.13.39) ; Oxygen (S88TT14065)
Language	English
Publishing date	2008
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-0-387-73693-8_7
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Article: Effects of the nitric oxide synthase inhibitor L-NMMA on cerebrovascular and cardiovascular responses to hypoxia and hypercapnia in humans.

Ide, Kojiro / Worthley, Matthew / Anderson, Todd / Poulin, Marc J

The Journal of physiology

2007 Volume 584, Issue Pt 1, Page(s) 321–332

Abstract: ... inhibitor N(G)-monomethyl-l-arginine (l-NMMA), attenuates the sensitivity of middle cerebral artery blood ... respectively. At baseline (isocapnic euoxia), following intravenous administration of l-NMMA, mean ... similar with and without l-NMMA (5.0 +/- 0.7 versus 7.1 +/- 1.0 mmHg, 11.5 +/- 1.4 versus 12.4 +/- 1.5 ...

Abstract	Cerebral blood flow is highly sensitive to alterations in the partial pressures of O(2) and CO(2) (P(O(2)) and P(CO(2)), respectively) in the arterial blood. In humans, the extent to which nitric oxide (NO) is involved in this regulation is unclear. We hypothesized that the NO synthase (NOS) inhibitor N(G)-monomethyl-l-arginine (l-NMMA), attenuates the sensitivity of middle cerebral artery blood velocity (V(p)) to isocapnic hypoxia (end-tidal P(O(2)) = 50 Torr) and euoxic hypercapnia (end-tidal P(CO(2)) = +9 Torr above resting values) in 10 volunteers (age, 28.7 +/- 1.3 years; height, 179.2 +/- 2.4 cm; weight, 78.0 +/- 3.7 kg; mean +/- s.e.m.). The techniques of transcranial Doppler ultrasound and dynamic end-tidal forcing were used to measure(V(p)), and control end-tidal P(O(2)) and end-tidal P(CO(2)), respectively. At baseline (isocapnic euoxia), following intravenous administration of l-NMMA, mean arterial blood pressure (MAP) increased (76.3 +/- 7.3 to 86.2 +/- 9.4 mmHg) and heart rate (HR) decreased (59.5 +/- 9.0 to 55.2 +/- 9.5 beats min(-1)) but (V(p)) was unchanged. Hypoxia-induced increases in MAP, HR and were similar with and without l-NMMA (5.0 +/- 0.7 versus 7.1 +/- 1.0 mmHg, 11.5 +/- 1.4 versus 12.4 +/- 1.5 beats min(-1), 6.5 +/- 0.8 versus 6.6 +/- 0.8 cm s(-1) for DeltaMAP, DeltaHR and Delta , respectively). Hypercapnia-induced increases in MAP, HR and (V(p)) were similar with and without l-NMMA (7.4 +/- 3.1 versus 8.1 +/- 2.2 mmHg, 10.4 +/- 4.6 versus 10.0 +/- 4.2 beats min(-1), 16.5 +/- 1.5 versus 17.6 +/- 1.5 cm s(-1) for DeltaMAP, DeltaHR and Delta(V(p)) , respectively) but the sensitivity of the(V(p)) response at the removal of hypercapnia was attenuated with l-NMMA. In young healthy humans, pharmacological blockade of nitric oxide synthesis does not affect the increases in cerebral blood flow with hypoxia and hypercapnia, suggesting that nitric oxide is not required for the cerbrovascular responses to hypoxia and hypercapnia.
MeSH term(s)	Adrenergic alpha-Agonists ; Adult ; Blood Flow Velocity/physiology ; Blood Pressure/physiology ; Cerebrovascular Circulation/physiology ; Heart Rate/physiology ; Humans ; Hypercapnia/physiopathology ; Hypoxia/physiopathology ; Male ; Nitric Oxide Synthase/antagonists & inhibitors ; Nitric Oxide Synthase/physiology ; Phenylephrine ; Respiration ; Ultrasonography, Doppler, Transcranial ; Vascular Resistance/physiology ; omega-N-Methylarginine
Chemical Substances	Adrenergic alpha-Agonists ; Phenylephrine (1WS297W6MV) ; omega-N-Methylarginine (27JT06E6GR) ; Nitric Oxide Synthase (EC 1.14.13.39)
Language	English
Publishing date	2007-10-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3115-x
ISSN	1469-7793 ; 0022-3751
ISSN (online)	1469-7793
ISSN	0022-3751
DOI	10.1113/jphysiol.2007.138206
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Article: Predicting Complicated Mild Traumatic Brain Injury in Adolescent Trauma to Enhance Clinical Decisions in Imaging.

Rhodes, Heather X / Berg, Gina / Shadiack, Anthony L / Thomas, Kevin D / Horawski, Jennifer L / Boyer, Geoff / Kleist, Sara M / Worthley, Aaron I / Rosenberg, David I / Gutovitz, Scott B / Helmrich, George A / Biswas, Saptarshi / Pepe, Antonio P

Journal of trauma nursing : the official journal of the Society of Trauma Nurses

2023 Volume 30, Issue 3, Page(s) 150–157

Abstract: Background: The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury algorithm is used to identify children at low risk of clinically significant traumatic brain injuries to reduce computed tomography (CT) exposure. Adapting ...

Abstract	Background: The Pediatric Emergency Care Applied Research Network (PECARN) traumatic brain injury algorithm is used to identify children at low risk of clinically significant traumatic brain injuries to reduce computed tomography (CT) exposure. Adapting PECARN rules based on population-specific risk stratification has been suggested to improve diagnostic accuracy. Objective: This study sought to identify center-specific patient variables, beyond PECARN rules, that may enhance the identification of patients requiring neuroimaging. Methods: This single-center, retrospective cohort study was conducted from July 1, 2016, to July 1, 2020, in a Southwestern U.S. Level II pediatric trauma center. The inclusion criteria were adolescents (10-15 years), Glasgow Coma Scale (13-15), with a confirmed mechanical blow to the head. Patients without a head CT were excluded. Logistic regression was performed to identify additional complicated mild traumatic brain injury predictor variables beyond the PECARN. Results: There were 136 patients studied; 21 (15%) presented with a complicated mild traumatic brain injury. Relative to motorcycle collision or all-terrain vehicle trauma (odds ratio [OR] 211.75, 95% confidence interval, CI [4.51, 9931.41], p < .001), an unspecified mechanism (OR 42.0, 95% CI [1.30, 1350.97], p = .03) and consult activation (OR 17.44, 95% CI [1.75, 173.31], p = .01) were significantly associated with complicated mild traumatic brain injury. Conclusions: We identified additional factors associated with complex mild traumatic brain injury, including motorcycle collision and all-terrain vehicle trauma, unspecified mechanism, and consult activation that are not in the PECARN imaging decision rule. Adding these variables may aid in determining the need for appropriate CT scanning.
MeSH term(s)	Adolescent ; Child ; Humans ; Brain Concussion/diagnostic imaging ; Craniocerebral Trauma/diagnosis ; Decision Support Techniques ; Adverse Childhood Experiences ; Retrospective Studies ; Emergency Service, Hospital ; Brain Injuries, Traumatic/diagnostic imaging
Language	English
Publishing date	2023-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1281159-2
ISSN	1078-7496
ISSN	1078-7496
DOI	10.1097/JTN.0000000000000720
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Article ; Online: Advancing translational research for colorectal immuno-oncology.

Thomas, Elaine M / Wright, Josephine A / Blake, Stephen J / Page, Amanda J / Worthley, Daniel L / Woods, Susan L

British journal of cancer

2023 Volume 129, Issue 9, Page(s) 1442–1450

Abstract: Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA ... ...

Abstract	Colorectal cancer (CRC) is a common and deadly disease. Unfortunately, immune checkpoint inhibitors (ICIs) fail to elicit effective anti-tumour responses in the vast majority of CRC patients. Patients that are most likely to respond are those with DNA mismatch repair deficient (dMMR) and microsatellite instability (MSI) disease. However, reliable predictors of ICI response are lacking, even within the dMMR/MSI subtype. This, together with identification of novel mechanisms to increase response rates and prevent resistance, are ongoing and vitally important unmet needs. To address the current challenges with translation of early research findings into effective therapeutic strategies, this review summarises the present state of preclinical testing used to inform the development of immuno-regulatory treatment strategies for CRC. The shortfalls and advantages of commonly utilised mouse models of CRC, including chemically induced, transplant and transgenic approaches are highlighted. Appropriate use of existing models, incorporation of patient-derived data and development of cutting-edge models that recapitulate important features of human disease will be key to accelerating clinically relevant research in this area.
MeSH term(s)	Animals ; Mice ; Humans ; Translational Research, Biomedical ; Medical Oncology ; Brain Neoplasms ; Colorectal Neoplasms ; Microsatellite Instability ; DNA Mismatch Repair
Language	English
Publishing date	2023-08-10
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-023-02392-x
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Article ; Online: Trends in myocardial infarction and coronary revascularisation procedures in Australia, 1993-2017.

Lin, Richard Z / Gallagher, Celine / Tu, Samuel J / Pitman, Bradley M / Nelson, Adam J / Roberts-Thomson, Ross L / Worthley, Matthew I / Lau, Dennis H / Sanders, Prashanthan / Wong, Christopher X

Heart (British Cardiac Society)

2023 Volume 109, Issue 4, Page(s) 283–288

Abstract: Objective: Prior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI ... ...

Abstract	Objective: Prior data have shown rising acute myocardial infarction (MI) trends in Australia; whether these increases have continued in recent years is not known. This study thus sought to characterise contemporary nationwide trends in MI hospitalisations and coronary procedures in Australia and their associated economic burden. Methods: The primary outcome measure was the incidence and time trends of total MI, ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) hospitalisations from 1993 to 2017. The incidence and time trends of coronary procedures were additionally collected, alongside MI hospitalisation costs. Results: Adjusted for population changes, annual MI incidence increased from 216.2 cases per 100 000 to a peak of 270.4 in 2007 with subsequent decline to 218.7 in 2017. Similarly, NSTEMI incidence increased from 68.0 cases per 100 000 in 1993 to a peak of 192.6 in 2007 with subsequent decline to 162.6 in 2017. STEMI incidence decreased from 148.3 cases per 100 000 in 1993 to 56.2 in 2017. Across the study period, there were annual increases in MI hospitalisations of 0.7% and NSTEMI hospitalisations of 5.6%, and an annual decrease in STEMI hospitalisations of 4.8%. Angiography and percutaneous coronary intervention increased by 3.4% and 3.3% annually, respectively, while coronary artery bypass graft surgery declined by 2.2% annually. MI hospitalisation costs increased by 100% over the study period, despite a decreased average length of stay by 45%. Conclusions: The rising incidence of MI hospitalisations appear to have stabilised in Australia. Despite this, associated healthcare expenditure remains significant, suggesting a need for continual implementation of public health policies and preventative strategies.
MeSH term(s)	Humans ; ST Elevation Myocardial Infarction/epidemiology ; ST Elevation Myocardial Infarction/surgery ; Non-ST Elevated Myocardial Infarction/diagnosis ; Non-ST Elevated Myocardial Infarction/epidemiology ; Non-ST Elevated Myocardial Infarction/surgery ; Myocardial Infarction/epidemiology ; Myocardial Infarction/therapy ; Hospitalization ; Australia/epidemiology ; Percutaneous Coronary Intervention
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1303417-0
ISSN	1468-201X ; 1355-6037
ISSN (online)	1468-201X
ISSN	1355-6037
DOI	10.1136/heartjnl-2022-321393
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Article: Carnitine balance and effects of intravenous L-carnitine in two patients receiving long-term total parenteral nutrition.

Worthley, L I / Fishlock, R C / Snoswell, A M

JPEN. Journal of parenteral and enteral nutrition

1984 Volume 8, Issue 6, Page(s) 717–719

Abstract: ... 2500 mumol) of L-carnitine for 7 days, followed by 40 mg (240 mumol) daily continuously. One patient ... parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients ...

Abstract	Two patients requiring total parenteral nutrition for 34 and 39 months, had plasma and urinary carnitine assays and plasma lipid assays performed before and during intravenous administration of 400 mg (2500 mumol) of L-carnitine for 7 days, followed by 40 mg (240 mumol) daily continuously. One patient had generalized lethargy and weakness which resolved within the first 5 days of carnitine administration. The plasma-free carnitine levels in this patient rose significantly. The other patient was asymptomatic and while there was no significant change in the plasma-free carnitine levels during carnitine administration, this patient remained in positive carnitine balance throughout the study. There were no significant changes in plasma lipid levels in either patient. In adult patients requiring long-term total parenteral nutrition who are otherwise normal, intravenous L-carnitine may be required to supplement the patients endogenous carnitine production.
MeSH term(s)	Adult ; Carnitine/administration & dosage ; Carnitine/metabolism ; Energy Intake ; Female ; Food, Formulated ; Home Nursing ; Humans ; Intestinal Obstruction/therapy ; Intestinal Pseudo-Obstruction/therapy ; Middle Aged ; Parenteral Nutrition ; Parenteral Nutrition, Total ; Scleroderma, Localized/therapy ; Time Factors
Chemical Substances	Carnitine (S7UI8SM58A)
Language	English
Publishing date	1984-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	800861-9
ISSN	0148-6071
ISSN	0148-6071
DOI	10.1177/0148607184008006717
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Article ; Online: Cancer-associated fibroblasts-heroes or villains?

Gieniec, Krystyna A / Butler, Lisa M / Worthley, Daniel L / Woods, Susan L

British journal of cancer

2019 Volume 121, Issue 4, Page(s) 293–302

Abstract: Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in ...

Abstract	Cancer-associated fibroblasts (CAFs) were originally presumed to represent a homogeneous population uniformly driving tumorigenesis, united by their morphology and peritumoural location. Our understanding of CAFs has since been shaped by sophisticated in vitro and in vivo experiments, pathological association and, more recently, ablation, and it is now widely appreciated that CAFs form a group of highly heterogeneous cells with no single overarching marker. Studies have demonstrated that the CAF population contains different subtypes based on the expression of marker proteins with the capacity to promote or inhibit cancer, with their biological role as accomplices or adversaries dependent on many factors, including the cancer stage. So, while CAFs have been endlessly shown to promote the growth, survival and spread of tumours via improvements in functionality and an altered secretome, they are also capable of retarding tumorigenesis via largely unknown mechanisms. It is important to reconcile these disparate results so that the functions of, or factors produced by, tumour-promoting subtypes can be specifically targeted to improve cancer patient outcomes. This review will dissect out CAF complexity and CAF-directed cancer treatment strategies in order to provide a case for future, rational therapies.
MeSH term(s)	Animals ; Cancer-Associated Fibroblasts/drug effects ; Cancer-Associated Fibroblasts/physiology ; Energy Metabolism ; Extracellular Matrix/physiology ; Humans ; Mice ; Neoplasm Invasiveness ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Phenotype ; Prognosis
Language	English
Publishing date	2019-07-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/s41416-019-0509-3
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Article ; Online: Multimodality Tachycardia-Induced Stress Testing Predicts a Low-Risk Group for Early Cardiovascular Mortality After Renal Transplantation.

Montarello, Nicholas J / Salehi, Tania / Bate, Alex P / Pisaniello, Anthony D / Clayton, Philip A / Teo, Karen S L / Worthley, Matthew I / Coates, Patrick T

Kidney international reports

2020 Volume 6, Issue 1, Page(s) 120–127

Abstract: Background: Cardiovascular events remain a major cause of death in kidney transplant recipients. The optimal noninvasive workup to prevent peritransplant cardiac mortality remains contentious.: Methods: We conducted a retrospective analysis to assess ...

Abstract	Background: Cardiovascular events remain a major cause of death in kidney transplant recipients. The optimal noninvasive workup to prevent peritransplant cardiac mortality remains contentious. Methods: We conducted a retrospective analysis to assess the renal transplantation cardiovascular assessment protocol within a single-center population over a 5-year period. Asymptomatic patients aged less than 45 years with no history of cigarette smoking, without diabetes mellitus, and dialysis-dependent for less than 24 months did not undergo cardiac testing before listing. All other asymptomatic patients underwent a noninvasive, tachycardia-induced stress test, where a target heart rate of 85% predicted for age and gender was required. The primary endpoints were rates of acute myocardial infarction (AMI) and cardiovascular death at 30 days after renal transplantation. Results: Between 2015 and 2019, 380 recipients underwent cardiac evaluation: 79 (20.8%) were deemed low cardiovascular risk and placed on the renal transplant waitlist without further assessment; 270 (71.1%) underwent a tachycardia-induced stress test; and 31 (8.1%) were deemed high risk and proceeded directly to invasive coronary angiography (ICA). In the 5-year follow-up, 3 patients (0.8%) experienced an AMI 30 days after renal transplantation, all of which occurred in the high-risk "direct to ICA" cohort. No events were documented in the low-risk cohort or in patients who had a negative tachycardia-induced stress test. There were no cardiovascular deaths within 30 days after transplantation. Conclusion: A negative tachycardia-induced cardiac stress test, achieving 85% of predicted heart rate, was associated with a 0% AMI rate and no cardiovascular deaths at 30 days after renal transplantation.
Language	English
Publishing date	2020-10-22
Publishing country	United States
Document type	Journal Article
ISSN	2468-0249
ISSN (online)	2468-0249
DOI	10.1016/j.ekir.2020.10.006
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