William Waring - Academia.edu (original) (raw)

Papers by William Waring

Spinal Cord, 1991

Fifty two patients with traumatic quadriplegia admitted to a spinal cord injury program within 6 ... more Fifty two patients with traumatic quadriplegia admitted to a spinal cord injury program within 6 months of injury were studied retrospectively. Seventy five per cent had shoulder pain documented in their medical records during initial rehabilitation, and 60% had shoulder pain for 2 weeks or more. When shoulder pain was documented it was bilateral in 61% of the cases. Age greater than 50 years, decreased shoulder range of motion, and not receiving shoulder exercise during the first 2 weeks after injury were positive risk factors associated with the onset of shoulder pain. At discharge 42% of the patients with shoulder pain were pain-free, 35% were noted to have improvement of their pain, and 23% had the same or worse shoulder pain. Study results demonstrate the high incidence of shoulder pain during initial rehabilitation of patients with traumatic quadriplegia and the importance of starting shoulder exercises during early acute care.

The journal of spinal cord medicine

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) w... more The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

Heart (British Cardiac Society), 2004

To investigate the possibility that uric acid (UA) can impair endothelial function, an important ... more To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide depen...

QJM : monthly journal of the Association of Physicians, 2000

BMJ case reports, 2009

Liver impairment is a recognised adverse effect of long-term sodium valproate treatment, but ther... more Liver impairment is a recognised adverse effect of long-term sodium valproate treatment, but there are few reports concerning its occurrence after acute overdose. This report describes a 36-year-old woman who deliberately ingested 32 g of sodium valproate (Epilim). Serum valproate concentration was 4370 μmol/l (630 mg/l) at 4.3 h post-ingestion (therapeutic reference range: 300-600 μmol/l), and the elimination half-life was 14.1 h. Liver biochemistry tests were initially normal but gradually became impaired, and highest alanine aminotransferase (761 U/l) occurred 2.3 days after ingestion. Supportive measures alone were sufficient to allow recovery of liver function. This case indicates that sodium valproate overdose may cause acute hepatocellular injury, even in the absence of pre-existing liver disease.

Journal of Urology, 2008

in high-risk myelomeningocele (MMC) patients is well established.

The journal of spinal cord medicine, 2010

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) w... more The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

American Journal of Hypertension, 2003

The aim of this study was to characterize the acute effects of caffeine on peripheral and central... more The aim of this study was to characterize the acute effects of caffeine on peripheral and central blood pressure (BP) in healthy individuals, using validated noninvasive techniques. Methods: In a randomized double-blind study, 300 mg caffeine or matching placebo was administered orally to 20 healthy adults and hemodynamic responses were observed. Central BP and augmentation index (AIx) were determined by pulse wave analysis; cardiac index (CI) was estimated by transthoracic bioimpedance; and heart rate variability (HRV) given by power spectral analysis of pulse interval. Pressure amplification (peripheral to central pulse pressure ratio) and systemic vascular resistance index were also calculated. Results: Caffeine administration increased central systolic and diastolic BP by 7 Ϯ 3 (P Ͻ .01) and 3 Ϯ 2 mm Hg (P Ͻ .05), respectively (mean Ϯ SEM) at 45 min, but had no effect on peripheral BP. Caffeine caused AIx to increase by 7 Ϯ 2 and 0 Ϯ 1%, respectively (P Ͻ .05), and pressure amplification to decrease by 1.0 Ϯ 0.1 v 0.2 Ϯ 0.2 (P Ͻ .001) placebo at 45 min. Conclusions: Acute caffeine intake significantly increases central BP and large artery waveform transmission and diminishes pressure amplification in healthy adults. Therefore, the effects of caffeine on BP may be significantly underestimated by measurement of BP at the brachial artery. Am J Hypertens 2003;16:919 -924

Rehabilitation Nursing, 2014

Pediatric specialists have successfully improved the longevity and quality of life of many childr... more Pediatric specialists have successfully improved the longevity and quality of life of many children with chronic health conditions. As these children reach adolescence and young adulthood, the scope of their concomitant medical problems often include those typically seen in older patients. As a result, these individuals need continuing quality health care in focused adult healthcare facilities. This article describes the effective partnership between pediatric and adult healthcare providers to create and implement an exemplar Spina Bifida Transition Program. The processes, strategies and tools discussed are likely to be useful to other healthcare professionals interested in developing pediatric to adult transition programs for adolescents and young adults with chronic health conditions. Successful pediatric to adult healthcare transition programs are needed.

QJM, 2008

Background: Initial management of patients who were presented to hospital after acute paracetamol... more 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 41.3 or alanine transaminase 51000 U/l. Results: There were 987 patients, and the stated quantity of paracetamol ingested was 0-12 g in 475 (48.1%), 412 g in 349 (35.4%) and unknown in 163 (16.5%). Ingestion of 412 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 2 proportional test, and associated with hepatotoxicity in 6.9% (4.6-10.1%) vs. 1.3% (0.5-2.8%), P ¼ 0.0001. Conclusions: Therefore, ingestion of412 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.

Pediatric Asthma, Allergy & Immunology, 2009

PEDIATRIC ASTHMA, ALLERGY & IMMUNOLOGY Volume 17, Number 3, 2004 © Mary Ann Liebert, Inc. ...... more PEDIATRIC ASTHMA, ALLERGY & IMMUNOLOGY Volume 17, Number 3, 2004 © Mary Ann Liebert, Inc. ... Reed Army Medical Center and work at the Walter Reed Army Institute of Research and the NIH, I went to New Orleans to work for the late John Salvaggio, a distinguished ...

The Journal of Urology, 2008

in high-risk myelomeningocele (MMC) patients is well established.

Plastic and reconstructive surgery, 2012

Despite a 12 to 82 percent pressure ulcer recurrence rate, no standard protocol exists for postop... more Despite a 12 to 82 percent pressure ulcer recurrence rate, no standard protocol exists for postoperative management. The authors reviewed a single surgeon's experience using a standard protocol: surgery and immediate reconstruction regardless of nutrition, intraoperative bone culture guiding postoperative antibiotic use, and hospital admission for 3 weeks of flat bedrest before graduated sitting.

The Journal of Hand Surgery, 1989

Thirty-three patients with long-term sequelae of poliomyelitis with a diagnosis of carpal tunnel ... more Thirty-three patients with long-term sequelae of poliomyelitis with a diagnosis of carpal tunnel syndrome established by either abnormal nerve conduction studies or previous carpal tunnel surgery were surveyed. There was no significant long-term resolution of symptoms in the patients who had surgery (n = 9) or were currently using wrist orthoses (n = 11) compared with patients without such treatment (n = 13). In patients who used a single cane or those who used crutches (N = 10), there was a direct correlation between the hand holding the cane or crutch and the hand in which carpal tunnel syndrome developed. The chronic use of cane and crutch predisposes these patients to development of carpal tunnel syndrome, and caution should be used when considering wrist surgery. (J HAND SURG 1989;14A:865-9.)

European Journal of Clinical Pharmacology, 2009

Background Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying ... more 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.

Diabetologia, 2007

Aims/hypothesis Endothelial dysfunction contributes to excess cardiovascular risk in patients wit... more 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 intrabrachial 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.

Diabetes, 2006

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in ... more Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.

Spinal Cord, 1991

Fifty two patients with traumatic quadriplegia admitted to a spinal cord injury program within 6 ... more Fifty two patients with traumatic quadriplegia admitted to a spinal cord injury program within 6 months of injury were studied retrospectively. Seventy five per cent had shoulder pain documented in their medical records during initial rehabilitation, and 60% had shoulder pain for 2 weeks or more. When shoulder pain was documented it was bilateral in 61% of the cases. Age greater than 50 years, decreased shoulder range of motion, and not receiving shoulder exercise during the first 2 weeks after injury were positive risk factors associated with the onset of shoulder pain. At discharge 42% of the patients with shoulder pain were pain-free, 35% were noted to have improvement of their pain, and 23% had the same or worse shoulder pain. Study results demonstrate the high incidence of shoulder pain during initial rehabilitation of patients with traumatic quadriplegia and the importance of starting shoulder exercises during early acute care.

The journal of spinal cord medicine

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) w... more The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

Heart (British Cardiac Society), 2004

To investigate the possibility that uric acid (UA) can impair endothelial function, an important ... more To investigate the possibility that uric acid (UA) can impair endothelial function, an important surrogate for atherosclerosis. UA was administered locally or systemically to healthy adult men and women in a series of randomised placebo controlled studies. This temporarily raised serum UA concentrations, so that the potential effects of hyperuricaemia on mechanisms of cardiovascular disease could be studied. The effects of UA administration on basal blood flow and responses to locally administered acetylcholine, sodium nitroprusside, and L-N(G)-monomethylarginine were studied in the forearm vascular bed with venous occlusion plethysmography. The effects of hyperuricaemia on systemic vascular resistance, large artery compliance, and baroreflex sensitivity were examined by validated non-invasive techniques. UA administration caused a twofold increase in serum concentrations. However, there were no acute effects on haemodynamic variables, basal forearm blood flow, or nitric oxide depen...

QJM : monthly journal of the Association of Physicians, 2000

BMJ case reports, 2009

Liver impairment is a recognised adverse effect of long-term sodium valproate treatment, but ther... more Liver impairment is a recognised adverse effect of long-term sodium valproate treatment, but there are few reports concerning its occurrence after acute overdose. This report describes a 36-year-old woman who deliberately ingested 32 g of sodium valproate (Epilim). Serum valproate concentration was 4370 μmol/l (630 mg/l) at 4.3 h post-ingestion (therapeutic reference range: 300-600 μmol/l), and the elimination half-life was 14.1 h. Liver biochemistry tests were initially normal but gradually became impaired, and highest alanine aminotransferase (761 U/l) occurred 2.3 days after ingestion. Supportive measures alone were sufficient to allow recovery of liver function. This case indicates that sodium valproate overdose may cause acute hepatocellular injury, even in the absence of pre-existing liver disease.

Journal of Urology, 2008

in high-risk myelomeningocele (MMC) patients is well established.

The journal of spinal cord medicine, 2010

The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) w... more The International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI) were recently reviewed by the ASIA's Education and Standards Committees, in collaboration with the International Spinal Cord Society's Education Committee. Available educational materials for the ISNCSCI were also reviewed. The last citable reference for the ISNCSCI's methodology is the ISNCSCI Reference Manual, published in 2003 by ASIA. The Standards Committee recommended that the numerous items that were revised should be published and a precedent established for a routine published review of the ISNCSCI. The Standards Committee also noted that, although the 2008 reprint pocket booklet is current, the reference manual should be revised after proposals to modify/revise the ASIA Impairment Scale (AIS as modified from Frankel) are considered. In addition, the Standards Committee adopted a process for thorough and transparent review of requests to revise the ISNCSCI.

American Journal of Hypertension, 2003

The aim of this study was to characterize the acute effects of caffeine on peripheral and central... more The aim of this study was to characterize the acute effects of caffeine on peripheral and central blood pressure (BP) in healthy individuals, using validated noninvasive techniques. Methods: In a randomized double-blind study, 300 mg caffeine or matching placebo was administered orally to 20 healthy adults and hemodynamic responses were observed. Central BP and augmentation index (AIx) were determined by pulse wave analysis; cardiac index (CI) was estimated by transthoracic bioimpedance; and heart rate variability (HRV) given by power spectral analysis of pulse interval. Pressure amplification (peripheral to central pulse pressure ratio) and systemic vascular resistance index were also calculated. Results: Caffeine administration increased central systolic and diastolic BP by 7 Ϯ 3 (P Ͻ .01) and 3 Ϯ 2 mm Hg (P Ͻ .05), respectively (mean Ϯ SEM) at 45 min, but had no effect on peripheral BP. Caffeine caused AIx to increase by 7 Ϯ 2 and 0 Ϯ 1%, respectively (P Ͻ .05), and pressure amplification to decrease by 1.0 Ϯ 0.1 v 0.2 Ϯ 0.2 (P Ͻ .001) placebo at 45 min. Conclusions: Acute caffeine intake significantly increases central BP and large artery waveform transmission and diminishes pressure amplification in healthy adults. Therefore, the effects of caffeine on BP may be significantly underestimated by measurement of BP at the brachial artery. Am J Hypertens 2003;16:919 -924

Rehabilitation Nursing, 2014

Pediatric specialists have successfully improved the longevity and quality of life of many childr... more Pediatric specialists have successfully improved the longevity and quality of life of many children with chronic health conditions. As these children reach adolescence and young adulthood, the scope of their concomitant medical problems often include those typically seen in older patients. As a result, these individuals need continuing quality health care in focused adult healthcare facilities. This article describes the effective partnership between pediatric and adult healthcare providers to create and implement an exemplar Spina Bifida Transition Program. The processes, strategies and tools discussed are likely to be useful to other healthcare professionals interested in developing pediatric to adult transition programs for adolescents and young adults with chronic health conditions. Successful pediatric to adult healthcare transition programs are needed.

QJM, 2008

Background: Initial management of patients who were presented to hospital after acute paracetamol... more 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 41.3 or alanine transaminase 51000 U/l. Results: There were 987 patients, and the stated quantity of paracetamol ingested was 0-12 g in 475 (48.1%), 412 g in 349 (35.4%) and unknown in 163 (16.5%). Ingestion of 412 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 2 proportional test, and associated with hepatotoxicity in 6.9% (4.6-10.1%) vs. 1.3% (0.5-2.8%), P ¼ 0.0001. Conclusions: Therefore, ingestion of412 g predicted higher paracetamol exposure and increased risk of hepatotoxicity and supports the validity of patient history in this context.

Pediatric Asthma, Allergy & Immunology, 2009

PEDIATRIC ASTHMA, ALLERGY & IMMUNOLOGY Volume 17, Number 3, 2004 © Mary Ann Liebert, Inc. ...... more PEDIATRIC ASTHMA, ALLERGY & IMMUNOLOGY Volume 17, Number 3, 2004 © Mary Ann Liebert, Inc. ... Reed Army Medical Center and work at the Walter Reed Army Institute of Research and the NIH, I went to New Orleans to work for the late John Salvaggio, a distinguished ...

The Journal of Urology, 2008

in high-risk myelomeningocele (MMC) patients is well established.

Plastic and reconstructive surgery, 2012

Despite a 12 to 82 percent pressure ulcer recurrence rate, no standard protocol exists for postop... more Despite a 12 to 82 percent pressure ulcer recurrence rate, no standard protocol exists for postoperative management. The authors reviewed a single surgeon's experience using a standard protocol: surgery and immediate reconstruction regardless of nutrition, intraoperative bone culture guiding postoperative antibiotic use, and hospital admission for 3 weeks of flat bedrest before graduated sitting.

The Journal of Hand Surgery, 1989

Thirty-three patients with long-term sequelae of poliomyelitis with a diagnosis of carpal tunnel ... more Thirty-three patients with long-term sequelae of poliomyelitis with a diagnosis of carpal tunnel syndrome established by either abnormal nerve conduction studies or previous carpal tunnel surgery were surveyed. There was no significant long-term resolution of symptoms in the patients who had surgery (n = 9) or were currently using wrist orthoses (n = 11) compared with patients without such treatment (n = 13). In patients who used a single cane or those who used crutches (N = 10), there was a direct correlation between the hand holding the cane or crutch and the hand in which carpal tunnel syndrome developed. The chronic use of cane and crutch predisposes these patients to development of carpal tunnel syndrome, and caution should be used when considering wrist surgery. (J HAND SURG 1989;14A:865-9.)

European Journal of Clinical Pharmacology, 2009

Background Paracetamol poisoning remains a leading cause of morbidity and mortality. Identifying ... more 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.

Diabetologia, 2007

Aims/hypothesis Endothelial dysfunction contributes to excess cardiovascular risk in patients wit... more 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 intrabrachial 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.

Diabetes, 2006

Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in ... more Endothelial dysfunction is a characteristic finding in both patients with type 1 diabetes and in regular smokers and is an important precursor to atherosclerosis. The urate molecule has antioxidant properties, which could influence endothelial function. The impact of acutely raising uric acid concentrations on endothelial function was studied in eight men with type 1 diabetes, eight healthy regular smokers, and eight age-matched healthy control subjects in a randomized, four-way, double-blind, placebo-controlled study. Subjects received 1,000 mg uric acid i.v. in vehicle, 1,000 mg vitamin C as a control antioxidant, vehicle alone, or 0.9% saline on separate occasions over 1 h. Forearm blood flow responses to intrabrachial acetylcholine and sodium nitroprusside were assessed using venous occlusion plethysmography. Responses to acetylcholine, but not sodium nitroprusside, were impaired in patients with diabetes (P < 0.001) and in smokers (P < 0.005) compared with control subjects. Administration of uric acid and vitamin C selectively improved acetylcholine responses in patients with type 1 diabetes (P < 0.01) and in regular smokers (P < 0.05). Uric acid administration improved endothelial function in the forearm vascular bed of patients with type 1 diabetes and smokers, suggesting that high uric acid concentrations in vivo might serve a protective role in these and other conditions associated with increased cardiovascular risk.