Delayed onset of liver injury after intentional chloroform overdose: a case report and literature review.

Chloroform is a recognised cause of acute liver injury, although now rarely encountered in clinical practice. We present a case of inhalational chloroform self-poisoning in a 47-year-old man that presented to hospital initially with reduced conscious level and later developed acute liver injury that was treated with intravenous acetylcysteine. This paper reviews the existing literature and presents a summary of the mechanisms of chloroform hepatotoxicity. Published cases show that there is a characteristic delay of 24 to 48 hours between chloroform exposure and elevation of liver transaminase activity. Therefore, clinicians need to provide an appropriate duration of monitoring in order to detect the occurrence of this important toxic effect.

Global research production in glyphosate intoxication from 1978 to 2015: A bibliometric analysis.

BACKGROUND: Glyphosate (N-phosphonomethylglycine) has been used as a broad-spectrum herbicide that has been widely used in the agricultural industry and also available for home use. The main aim of this study is to present a general overview of glyphosate intoxication-related publications from its introducing since the early 1970s using bibliometric technique. METHODS: On June 23, 2016, a literature search of the Scopus database was performed. We then extracted and analyzed the data using well-established qualitative and quantitative bibliometric indices: Publication year, affiliation, document type, country name, subject category, journal name, publishing language, and collaboration and citation patterns. RESULTS: We recognized a total of 3735 publications on glyphosate published between 1973 and 2015. There were 875 publications related to glyphosate intoxication in the Scopus database published between 1978 and 2015. Articles (757) comprised 86.5% of the total publications, followed by reviews (41; 4.7%). Most publications were published in English (87.9%), followed by Portuguese (6.6%). The number of publications related to glyphosate intoxication increased from 44 in 1978-1987 up to 152 in 1996-2005 and then quadrupled in 2006-2015. The United States was the leading country with 180 documents representing 20.6%, followed by Brazil (120; 13.7%), Canada (78; 8.9%), Argentina (61; 7.0%), and France (57; 6.5%). The 85.6% of the publications was cited, and the average of citation per document was 17.13 with h-index of 55. Furthermore, the United States achieved the highest h-index of 33. Most of the global international collaborations are made with researchers from the United States, who collaborated with 23 countries/territories in 44 publications. CONCLUSIONS: The trends in global glyphosate-related research between 1978 and 2015 were evaluated by a bibliometric technique. Results showed that English was the leading publishing language, and the major publication type was original article. Findings showed that number of research publications related to glyphosate intoxication increased significantly in the last decade. The United States and Brazil are the two most productive countries in research on glyphosate intoxication. This study will be beneficial to policy makers by identifying areas that need greater investment and research funding to target appropriate agriculture sectors so as to improve glyphosate safety in a global setting.

Global research productivity of N-acetylcysteine use in paracetamol overdose: A bibliometric analysis (1976-2012).

PURPOSE: The main objective of this study was to examine the publication pattern of N-acetylcysteine (NAC) research output for paracetamol overdose at the global level. METHODS: Data were searched for documents that contained specific words regarding NAC and paracetamol as keywords in the title and/or abstract and/or keywords. Scientific output was evaluated based on a methodology developed and used in other bibliometric studies. Research productivity was adjusted to the national population and nominal gross domestic product per capita. RESULTS: The criteria were met by 367 publications from 33 countries. The highest number of articles associated with the use of NAC in paracetamol overdose was from the United States of America (USA; 39.78%), followed by the United Kingdom (UK; 11.99%). After adjusting for economy and population power, USA (2.822), Iran (1.784) and UK (1.125) had the highest research productivity. The total number of citations at the time of data analysis (14 March 2014) was 8785 with an average of 23.9 citations per document and a median (interquartile range) of 6 (1-22). The h-index of the retrieved documents was 48. The highest h-index was 32 for USA, followed by 20 for UK. Furthermore, the highest number of collaborations with international authors for each country was held by USA with 11 countries, followed by Canada with 7 countries. CONCLUSION: The amount of NAC-based research activity was low in some countries, and more effort is needed to bridge this gap and to promote better evaluation of NAC use worldwide. Our findings demonstrate that NAC use for paracetamol overdose remains a hot issue in scientific research and may have a larger audience compared with other toxicological aspects. Editors and authors in the field of toxicology might usefully promote the submission of work on NAC in future to improve their journal's impact.

Scientific research related to calcium channel blockers poisoning: Bibliometric analysis in Scopus, 1968-2012.

PURPOSE: Calcium channel blockers (CCBs) were the most common agents associated with a significant morbidity and mortality rate. The main objective of this study was to examine the publication pattern related to CCBs poisoning at the global level using bibliometric analysis of articles published in SciVerse Scopus online database. METHODS: Data were searched for documents that contained specific words regarding CCB poisoning as keywords in the title. No time period limitations were specified in the search regarding the starting year. The ending date of the search was 31 December 2012. RESULTS: The criteria were met by 713 publications from 53 countries. The largest number of articles associated with CCBs was from the United States (30%), followed by the United Kingdom (7.4%), Japan (6%), and Germany (5.6%). No data related to CCBs were published from 159 (75%) of 212 countries registered in World Bank online database. There was no correlation between the number of published articles in the country and its population size (r = 0.03, p > 0.926). United Kingdom and Australia were the leading countries in terms of number of CCBs publications per million inhabitants (0.83 and 0.82 articles per million inhabitants, respectively), followed by the United States (0.68). Countries with a large population, such as India, tended to rank relatively low (0.01 articles per million inhabitants). The total number of citations at the time of data analysis (23 October 2014) was 6462, with an average of 9.1 citations per document. The highest median (interquartile range) number of citations was 8 (8-18) for the United States, followed by 6 (1-21) for Australia, 5 (1-15) for the United Kingdom, and 5 (1-24) for Canada. The h-index of the retrieved documents was 37. CONCLUSIONS: Scientific production on CCBs poisoning is increasing; nonetheless, the international collaboration is still rare. The amount of CCBs-based research activity was low or not available in most countries. More regional epidemiological studies are required to bridge the gap in CCBs-based research and to promote better evaluation of CCBs poisoning worldwide.

Impact of amending the acetylcysteine marketing authorisation on treatment of paracetamol overdose.

In September 2012, the Medicines and Healthcare products Regulatory Agency (MHRA) substantially amended the Marketing Authorisation for acetylcysteine following an extensive review. The present study examined the impact of this license change on patterns of acetylcysteine use in patients presenting to hospital after paracetamol (acetaminophen) overdose. Between September 2011 and April 2013, 785 consecutive patients presented to York Hospital due to paracetamol overdose, and a before-after analysis was used to compare outcomes. There were 483 patients before and 302 patients after the license amendment, and age, gender, acute or staggered overdose pattern, and dose were similar in both groups. In the patients with paracetamol concentrations between the "100-line" and "200-line," a significantly higher proportion received acetylcysteine treatment (51% before versus 98% after, P = 0.0029), as expected. A modest increase was also observed in relation to late or staggered overdose or cases where the time of ingestion was uncertain (53% versus 74%, P = 0.0430). The median duration of hospital stay increased across the entire study population, from 15 to 24 hours (P = 0.0159) due to the increased proportion of patients requiring acetylcysteine treatment. The findings indicate that the MHRA amendment is a financially costly intervention, and further studies are needed to examine clinical outcomes so that its cost effectiveness might be addressed.

Citalopram and cardiac toxicity.

PURPOSE: Citalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant that is widely used in clinical practice. Recent data have indicated that high therapeutic citalopram doses may cause electrocardiographic abnormalities, and the regulatory authorities have amended its licenced dosage. The present manuscript reviews the available data concerning citalopram and cardiac toxicity. METHODS: Published data concerning the cardiac effects of citalopram were ascertained, and clinical data were considered separately between adverse effects arising from therapeutic use versus toxicity in the setting of intentional overdose. RESULTS: The occurrence of electrocardiographic abnormalities has long been recognised as a complication of acute citalopram overdose; a dose-effect relationship for QT prolongation has been described in a number of large case series, including several cases of torsades de pointes. In contrast, few data indicate the occurrence of QT prolongation and arrhythmia after therapeutic doses, and a dose-effect relationship within the therapeutic range has only recently been established. Citalopram is more likely to cause QT prolongation in patients with metabolic disturbance or pre-existing cardiac disease. CONCLUSIONS: A dose-effect relationship for QT prolongation exists across a broad range of citalopram doses, such that caution must be exercised when prescribing high doses or if there are co-existent risk factors for QT effects. The available data illustrate how clinical toxicity data may offer an earlier signal of cardiac effects than ascertained from conventional pharmacovigilance methods.

Unplanned alcohol withdrawal: a survey of consecutive admissions to an acute medical unit in 2010 and 2011.

BACKGROUND: Alcohol-related presentations to hospital have been increasing in the UK in recent years, including the occurrence of acute withdrawal. This study sought to better characterize the clinical features, patterns of treatment and outcomes in this patient group. METHODS: Patients admitted to the Acute Medical Unit of York Hospital due to acute alcohol withdrawal are normally treated according to a protocol that involves both fixed-dose and symptom-triggered drug administration. Admissions between 2010 and 2011 inclusive were studied. RESULTS: There were 211 admission episodes solely due to acute alcohol withdrawal, involving 127 patients (97 men, 76.4%) with median age of 45 years (interquartile range: 39-52 years). There was a high prevalence of depression (34%), alcoholic liver disease (22%) and drug misuse (12%). Total dose of chlordiazepoxide varied between 0 and 610 mg and tapered rapidly after the first day of admission. Vitamin supplements were administered to >90% of patients, including parenteral and oral in 74%, parenteral alone in 9% and oral alone in 9%. A specialist alcohol nurse reviewed patients while in hospital in 40% of cases. Approximately one-third of patients had multiple admissions for alcohol withdrawal during the study period. CONCLUSION: A high prevalence of physical and mental health disorders was observed. The local policy permitted high initial chlordiazepoxide doses and prompt downward titration, with a broad range of doses between individuals. Approximately 10% required no specific therapy, and there may be opportunities for developing alternative pathways for delivery of care in an ambulatory setting for these patients.

Delayed onset of acute renal failure after significant paracetamol overdose: A case series.

Acute renal failure is a recognized manifestation of paracetamol toxicity, but comparatively little data is available concerning its onset and duration. The present study sought to characterize the time course of rising serum creatinine concentrations in paracetamol nephrotoxicity. Renal failure was defined by serum creatinine concentration >or=150 micromol/L (1.69 mg/dL) or >or=50% increase from baseline. Serum creatinine concentrations and alanine aminotransferase activity were considered with respect to the interval after paracetamol ingestion. There were 2068 patients with paracetamol overdose between March 2005 and October 2007, and paracetamol nephrotoxicity occurred in 8 (0.4%). All had significant hepatotoxicity, and peak serum alanine aminotransferase activity occurred at 2.5 days (2.2 to 2.9 days) after ingestion. Peak serum creatinine concentrations did not occur until 5.5 days (4.4 to 5.9 days) after ingestion (p = .031 by Wilcoxon test). Serum creatinine concentrations slowly restored to normal, and renal replacement was not required. In this patient series, rising serum creatinine concentrations only became detectable after more than 48 hours after paracetamol ingestion. Therefore, renal failure might easily be missed if patients are discharged home before this. Further work is required to establish the prevalence of paracetamol-induced nephrotoxicity, and its clinical significance.

Interpretation of clinical guidelines for poisoned patients: positive and negative effects of standard phrases used in TOXBASE.

INTRODUCTION: Electronic information sources are increasingly relied upon for clinical management advice. TOXBASE is a standardised online resource that offers clinical advice on the management of poisoned patients and is the first point of contact between clinicians and the National Poisons Information Service in the United Kingdom. Advice is delivered using a series of standard phrases. The present study examined how healthcare professionals interpret the phrases and studied their impact on clinical decision-making. METHODS: A structured prospective written questionnaire was offered to healthcare staff in the Lothian region, and an electronic questionnaire issued to TOXBASE users across the United Kingdom. Participants were asked to respond to a variety of scenarios representing acutely poisoned patients. Clinical management advice was offered via TOXBASE using a variety of standard phrases, and participants were asked to express the likelihood that they would then administer gut decontamination treatment. RESULTS: There were 70 respondents to written questionnaires, and 119 respondents to the electronic version. Phrases that included didactic instructions, for example 'give', 'contraindicated', 'do' and 'perform' were associated with strongly positive or strongly negative responses. In contrast, advice that consisted of open phrases such as 'consider', 'benefit uncertain', and 'few data' were associated with inconsistent responses. CONCLUSION: Didactic words and phrases are associated with more consistent interpretation and response than open-ended words and phrases. The choice of words and phrases used in electronic systems can have an independent impact on clinical decision-making and require further consideration.

Acute caffeine ingestion: clinical features in patients attending the emergency department and Scottish poison centre enquiries between 2000 and 2008.

BACKGROUND AND AIMS: Little information is available regarding the healthcare burden associated with deliberate caffeine ingestion. The present study sought to establish the impact of caffeine ingestion on hospital attendances and Poisons Centre enquiries in Scotland. METHODS: Retrospective analyses of clinical data from patients attending the Royal Infirmary of Edinburgh after acute caffeine ingestion, and TOXBASE enquiries from Scotland regarding caffeine poisoning between 2000-2008 inclusive. Cochran-Armitage trend tests were used to evaluate changes in annual admissions and TOXBASE enquiries. RESULTS: There were 43 hospital attendances due to deliberate caffeine ingestion, representing 0.2% of all poisoning cases. The median (interquartile range) stated dose was 1040 mg (600-1500 mg). Minor gastrointestinal symptoms were common, and no patient developed features of severe toxicity. There were 1418 enquiries to TOXBASE concerning caffeine poisoning, representing 0.2% of all poisoning enquiries from Scotland. The proportions of hospital admissions and TOXBASE enquiries due to caffeine ingestion have remained constant. CONCLUSION: Caffeine ingestion is uncommon, and results in only a small number of hospital attendances and Poisons Centre enquiries. In contrast to patterns reported elsewhere, the prevalence of caffeine abuse has not increased in Scotland over recent years.

Renal injury at first presentation as a predictor for poor outcome in severe paracetamol poisoning referred to a liver transplant unit.

BACKGROUND: Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying indices of poor prognosis at first presentation is key to both improving clinical care and determining targets for intervention. Renal failure is a feature of severe paracetamol poisoning. The aim of this study was to investigate the relationship between renal function (serum creatinine, Cr) at first hospital presentation and time of tertiary referral to outcomes in severe paracetamol poisoning. METHODS: This was a retrospective cohort analysis of patients referred to the Scottish Liver Transplant Unit due to paracetamol poisoning between 1992 and 2004. The relation between degree of renal injury and outcomes, including worst prothrombin time, Kings College Hospital Criteria (KCHC) and death were examined. The effects of age, nature (single or multiple) and stated size of overdose, hepatic enzyme induction (gamma-glutamyl transpeptidase, GGT), degree of liver injury (aspartate aminotransferase, prothrombin time), blood pressure and renal injury were assessed. RESULTS: Data from 522 patients were included. Renal impairment (Cr >120 mmol/l) was present in 48.8% of patients with liver injury at time of first presentation. Creatinine at first admission predicted poorer outcome in terms of worse prothrombin time, KCHC and death (p < 0.001). Associated risk factors for renal dysfunction included later presentation, staggered ingestion, increased age, hypotension and elevated GGT at first admission. CONCLUSIONS: Creatinine at first admission appears to be a predictor of poor outcome in paracetamol overdose. A better understanding of mechanisms involved in causing renal dysfunction may offer potential therapeutic targets for improving outcome in this common poisoning.

Patterns of antiepileptic drug overdose differ between men and women: admissions to the Edinburgh Poisons Unit, 2000-2007.

BACKGROUND AND AIMS: Antiepileptic drugs are increasingly used in patients with psychiatric disorders who are at increased risk of self-harm. This might increase the likelihood that these agents are used as a means of overdose. This study was designed to examine the rate of occurrence of antiepileptic drug overdose between 2000 and 2007. METHODS: A retrospective observational study examined patterns of antiepileptic drug overdose in patients admitted to the Edinburgh Poisons Unit, and compared prescription data for the corresponding region. Data were compared using chi-square trend tests. RESULTS: There were 18 010 admissions to the Toxicology Unit, and 613 patients ingested at least one antiepileptic drug (3.4%). The most frequently implicated were carbamazepine, sodium valproate, phenytoin and lamotrigine, which corresponded with those most commonly prescribed. Women were more likely to ingest lamotrigine than men (P < 0.0001), and less likely to ingest sodium valproate (P = 0.0234). Patients that ingested antiepileptic drugs were more likely to be admitted to hospital for >1 day (22% vs. 8%, P < 0.0001) and need transfer to a psychiatric facility (14% vs. 7%, P < 0.0001). CONCLUSIONS: Patients that ingested antiepileptic drugs required more intensive medical and psychiatric intervention compared to ingestion of other agents. Significant gender differences were noted in the specific antiepileptic drug ingested. Further work is required to establish whether this discrepancy may be explained by gender-based prescribing practices.

Variability in the quality of overdose advice in Summary of Product Characteristics (SPC) documents: gut decontamination recommendations for CNS drugs.

AIMS: Deliberate self-poisoning is a major cause of morbidity and mortality. The Summary of Product Characteristics (SPC) document is a legal requirement for all drugs, and Section 4.9 addresses the features of toxicity and clinical advice on management of overdose. The quality and appropriateness of this advice have received comparatively little attention. METHODS: Section 4.9 of the SPC was examined for all drugs in the central nervous system (CNS) category of the British National Formulary. Advice concerning gut decontamination was examined with respect to specific interventions: induced vomiting, oral activated charcoal, gastric lavage, and other interventions. Data were compared with standard reference sources for clinical management advice in poisoning. These were graded 'A' if no important differences existed, 'B' if differences were noted but not thought clinically important, and 'C' if differences were thought to be clinically significant. RESULTS: SPC documents were examined for 258 medications from 67 manufacturers. The overall agreement was 'A' in 23 (8.9%), 'B' in 28 (10.9%) and 'C' in 207 (80.2%). Discrepancies were due to inappropriate recommendation of induced emesis in 21.7% (95% confidence interval 17.1, 27.1), gastric lavage in 38.4% (32.7, 44.4), other gut decontamination in 5.8% (3.6, 9.4) and failure to recommend oral activated charcoal in 57.4% (51.1, 63.4). CONCLUSIONS: Gut decontamination advice in SPC documents with respect to CNS drugs was inadequate. Possible reasons for the observed discrepancies and ways of improving the consistency of advice are proposed.

Impaired heart rate variability and altered cardiac sympathovagal balance after antidepressant overdose.

PURPOSE: Antidepressant overdose may be associated with significant cardiotoxicity, and recent data have shown that acute toxic effects are associated with impaired heart rate variability. This study was designed to examine the feasibility of non-invasive heart rate variability recording in patients that present to hospital after deliberate antidepressant ingestion. METHODS: This was a prospective study of 72 consecutive patients attending the Emergency Department after deliberate antidepressant overdose and 72 age-matched patients that ingested paracetamol, as a control group. Single time-point continuous electrocardiographic recordings were used to allow spectral analyses of heart rate variability determined in low-frequency (LF) and high-frequency (HF) domains. The LF:HF ratio was used to represent overall sympathovagal cardiac activity. RESULTS: Antidepressant overdose was associated with reduced overall heart rate variability: 1329 vs. 2018 ms(2) (P = 0.0239 by Mann-Whitney test). Variability in the LF domain was higher (64.8 vs. 49.8, P = 0.0006), whereas that in the HF domain was lower (24.3 vs. 36.4, P = 0.0001), and the LF:HF ratio was higher in the antidepressant group (2.4 vs. 1.2, P = 0.0003). CONCLUSIONS: Antidepressant overdose is associated with impaired heart rate variability in a pattern consistent with excess cardiac sympathetic activity. Further work is required to establish the significance of these findings and to explore whether the impairment of heart rate variability may be used to predict the development of arrhythmia in this patient group.

Serum urea concentration and the risk of hepatotoxicity after paracetamol overdose.

BACKGROUND: Glutathione depletion increases the incidence of toxicity after paracetamol overdose. Risk factors for toxicity, including chronic ethanol excess and malnutrition, are associated with low serum urea concentrations. Therefore, we hypothesized that low serum urea concentration might itself be predictive of hepatotoxicity in patients that present to hospital after paracetamol overdose. METHODS: The present study prospectively collected data from 1085 patients attending the Emergency Department after paracetamol overdose. Hepatotoxicity was predefined by prothrombin time ratio >1.3 or alanine transaminase > or = 1000 U/l. Serum urea concentrations were considered in a stepwise multiple regression analysis that included paracetamol dose, co-ingestion of ethanol and other drugs, serum concentration, N-acetylcysteine, interval to treatment, vomiting and serum creatinine. RESULTS: Median (IQR) serum urea concentrations were 3.3 mmol/l (2.7-4.2 mmol/l) in those without risk factors, compared with 3.0 mmol/l (2.4-3.9 mmol/l) in those with chronic excess ethanol intake (P < 0.001 by Mann Whitney test) and 2.5 mmol/l (1.9-2.8 mmol/l) in patients with other risk factors (P < 0.001). Multivariate analysis found that serum urea concentrations were not independently associated with hepatotoxicity. CONCLUSION: Low serum urea concentration is not an independent risk factor for hepatotoxicity after paracetamol overdose.

Survey of cases of paracetamol overdose in the UK referred to National Poisons Information Service (NPIS) consultants.

BACKGROUND: Paracetamol is the most common means of drug overdose in the UK. Guidance on management is available to junior doctors through TOXBASE, the online resource managed by the UK National Poisons Information Service (NPIS) and in poster form. TOXBASE is supported by NPIS units and further by a UK national rota of clinical toxicologists. A study was undertaken to examine reasons why calls about paracetamol are referred to consultants to better understand issues in managing this common poisoning. METHODS: Calls relating to paracetamol overdose referred by a poisons information specialist to the duty NPIS consultant between 1 May 2005 and 30 April 2006 were identified from the database and the number of TOXBASE accesses during the same time period was determined. Enquiries that resulted in consultant referral were classified into six categories. RESULTS: Calls referred to NPIS consultants pertain mainly to patients who present late, staggered overdoses, adverse reactions to N-acetylcysteine, and interpretation of blood results. This information has been used to inform the development of TOXBASE so that comprehensive advice is readily available to end users. CONCLUSIONS: The operation of a national consultant rota enables information on difficult or unusual cases of poisoning to be pooled so that treatment guidelines can be developed to optimise treatment throughout the UK.

Does the patient history predict hepatotoxicity after acute paracetamol overdose?

BACKGROUND: Initial management of patients who were presented to hospital after acute paracetamol overdose depends on the suspected amount ingested and more than 12 g is potentially fatal. However, the validity of this approach has received comparatively little attention. METHODS: The present study is sought to establish whether the stated paracetamol dose might predict systemic exposure and risk of hepatotoxicity. A prospective observational study of consecutive patients presenting to the Emergency Department due to acute paracetamol overdose was performed. Serum paracetamol concentrations between 4 and 15 h post-ingestion were compared with the Rumack-Matthew '200-line' nomogram, and hepatotoxicity was defined by prothrombin time ratio >1.3 or alanine transaminase > or =1000 U/l. RESULTS: There were 987 patients, and the stated quantity of paracetamol ingested was 0-12 g in 475 (48.1%), >12 g in 349 (35.4%) and unknown in 163 (16.5%). Ingestion of >12 g was associated with paracetamol concentration above the '200-line' in 31.8% (95% CI 27.1-36.9%) vs. 3.2% (1.9-5.2%), P < 0.0001 by chi2 proportional test, and associated with hepatotoxicity in 6.9% (4.6-10.1%) vs. 1.3% (0.5-2.8%), P = 0.0001. CONCLUSION: Therefore, ingestion of >12 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.

Lowering serum urate does not improve endothelial function in patients with type 2 diabetes.

AIMS/HYPOTHESIS: Endothelial dysfunction contributes to excess cardiovascular risk in patients with type 2 diabetes. There is strong evidence of an association between high serum uric acid concentrations and endothelial dysfunction, and uric acid has been proposed as an independent cardiovascular risk factor in type 2 diabetes. We hypothesised that lowering of uric acid concentrations might allow restoration of endothelial function in this high-risk group. METHODS: Intravenous urate oxidase (1.5 mg) was administered to ten patients with type 2 diabetes and ten healthy participants in a two-way, randomised, placebo-controlled, crossover study. Forearm blood flow responses to intra-brachial acetylcholine, sodium nitroprusside and N(G)-monomethyl-L-arginine (L-NMMA) were measured using venous occlusion plethysmography. The augmentation index (AIx) was determined by pulse wave analysis as a measure of large arterial stiffness. RESULTS: Acetylcholine and L-NMMA evoked lesser responses in patients with type 2 diabetes than in healthy participants. Baseline AIx was higher in patients with type 2 diabetes (mean +/- SD: 13.1 +/- 6.9%) than in healthy participants (2.0 +/- 5.1%; p = 0.006). Urate oxidase lowered serum uric acid concentrations by 64 +/- 11% (p < 0.001), but this had no effect on forearm blood flow responses or AIx in either group. CONCLUSIONS/INTERPRETATION: Substantial short-term lowering of uric acid did not have a direct vascular effect, suggesting that, on its own, this might not be an effective strategy for restoring endothelial function in patients with type 2 diabetes.