J K Powrie

Guy's and St Thomas' NHS Foundation Trust, Londinium, England, United Kingdom

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Publications (32)120.37 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Chronic low-dose cabergoline treatment for microprolactinoma may cause cardiac valve pathology, but the evidence is contradictory. We investigated whether the expectation of the echocardiographer could influence the report. Transthoracic echocardiograms from 40 patients aged 49·3 ± 9·6 (mean ± SD) years (Men:Women 7:33) on long-term cabergoline and bromocriptine therapy (duration 9·94 ± 4·5 years) were randomly assigned to two groups of echocardiographers so that each echocardiogram was reported twice. One group was told that 'the patients were control subjects' (Group A) and the other that 'the patients were on dopamine agonist therapy which is known to cause valve disease' (Group B). An observer who was blind to the group scored the reports for regurgitation at each valve (scores 0-4; max 16 per case). Mean total regurgitation score was significantly higher in Group B (1·43 ± 1·28; P = 0·014) than in Group A (0·73 ± 1·30). The difference was mainly from reporting trivial regurgitation: (mitral 16 vs 5, P = 0·005; tricuspid 17 vs 6, P = 0·007 and pulmonary 8 vs 1, P = 0·013). Mild regurgitation was uncommon (mitral 1 vs 1 and tricuspid 3 vs 6). Moderate regurgitation occurred in only one case and was associated with restriction of the leaflets consistent with the effects of cabergoline. Valve thickening was not reported in Group A, but in 9 (23%) mitral and 4 (10%) aortic valves in Group B. Long-term, low-dose dopamine agonist therapy rarely causes cardiac valve disease, but operator bias can lead to over-reporting of both valve thickening and trivial regurgitation.
    Clinical Endocrinology 12/2010; 74(5):608-10. · 3.40 Impact Factor
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    ABSTRACT: Withdrawal of dopamine agonist (DA) therapy in the management of microprolactinoma is common practice, but it is unclear which patients are likely to attain long-term remission. To identify predictive factors for long-term remission. Prospective cohort study. Forty subjects (39 female, aged 24-60 years) with microprolactinoma; all had been normoprolactinaemic on DA therapy for at least 2 years [mean duration of therapy 9 years (range 2-27)]. A pituitary magnetic resonance imaging (MRI) was performed on 36 (90%) subjects before DA withdrawal. Relapse was defined as prolactin greater than 480 mIU/l (22.8 microg/l) on two occasions. Nine out of 40 (22.5%) subjects were normoprolactinaemic 12 months after DA withdrawal. Amongst the relapse group, 24 of 31 subjects (79.4%) had already relapsed at 3 months. Normalization of MRI prior to DA withdrawal (P = 0.0006) and longer duration of DA treatment (P = 0.032) were significant predictors of remission. Age, pre-treatment prolactin, nadir prolactin, previous failure of DA withdrawal, pregnancy, dose and type of DA were not significant predictors of remission. The nine patients who were in remission at 12 months were then followed up for 58.0 +/- 5.8 months; all remained in remission. As many as 22.5% of subjects with microprolactinoma remained normoprolactinaemic 12 months after DA withdrawal and these subjects stayed in remission for up to 5 years. Significant predictive factors were normalization of MRI prior to discontinuation, and duration of DA treatment. Our findings support intermittent DA withdrawal after a period of normoprolactinaemia, particularly where MRI appearances have normalized.
    Clinical Endocrinology 07/2009; 72(4):507-11. · 3.40 Impact Factor
  • L Leelarathna, J K Powrie, P V Carroll
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    ABSTRACT: Thomas Addison was first to describe adrenocortical failure in 1855. Despite advances in the treatment of this condition, the diagnosis is still often delayed and sometimes missed with potentially fatal consequences. From the same institution where Thomas Addison performed his original autopsy studies, we present four recent cases highlighting the wide clinical spectrum and discuss how modern biochemical and immunological tests could be utilized in early diagnosis and aetiological classification.
    QJM: monthly journal of the Association of Physicians 06/2009; 102(8):569-73. · 2.36 Impact Factor
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    ABSTRACT: To develop a test for GH abuse in sport. A double blind placebo controlled study of one month's GH administration to 102 healthy non-competing but trained subjects. Blood levels of nine markers of GH action were measured throughout the study and for 56 days after cessation of GH administration. Blood samples were also taken from 813 elite athletes both in and out of competition. GH caused a significant change in the nine measured blood markers. Men were more sensitive to the effects of GH than women. IGF-I and N-terminal extension peptide of procollagen type III were selected to construct formulae which gave optimal discrimination between the GH and placebo groups. Adjustments were made to account for the fall in IGF-I and P-III-P with age and the altered distribution seen in elite athletes. Using a cut-off specificity of 1:10,000 these formulae would allow the detection of up to 86% of men and 60% of women abusing GH at the doses used in this study. We report a methodology that will allow the detection of GH abuse. This will provide the basis of a robust and enforceable test identifying those who are already cheating and provide a deterrent to those who may be tempted to do so.
    Growth Hormone & IGF Research 07/2007; 17(3):220-6. · 2.26 Impact Factor
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    ABSTRACT: Oral oestrogen preparations increase total cortisol concentration by increasing circulating cortisol-binding globulin (CBG) levels. Transdermal oestrogen treatments are being used increasingly in clinical practice. These topical preparations may have less of an effect on CBG and hence on total serum cortisol levels by reducing hepatic oestrogen exposure. The purpose of this study was to compare the effects of oral and topical oestrogen treatments on CBG, total serum cortisol and salivary cortisol levels. This was a single-centre, cross-sectional study of 37 women aged 33 +/- 6 years (mean +/- SD). Fourteen women were using oral oestrogen therapy, eight were using transdermal therapy and 15 were oestrogen-naïve control subjects. Following a screening visit, the subjects attended the endocrine investigation unit following an overnight fast. Blood and salivary samples were taken from 0830 to 0930 h between days 10 and 18 of the menstrual cycle (where appropriate). Total serum cortisol concentrations were 67% higher in those receiving oral oestrogen when compared to control subjects (660.9 +/- 89.9 vs. 395.4 +/- 53.2 nmol/l, P < 0.001). Values in those receiving transdermal oestrogen (334.7 +/- 72.0 nmol/l) were no different from the control group. CBG levels were higher in those on oral oestrogen therapy (110.9 +/- 19.6 mg/l, P < 0.001) when compared with either those on transdermal oestrogen (51.0 +/- 5.4 mg/l) or the control population (49.0 +/- 11.8 mg/l). Similar salivary cortisol concentrations were recorded in the three groups (controls 13.8 +/- 2.6 nmol/l, oral oestrogen 15.5 +/- 2.6 nmol/l, transdermal oestrogen 15.7 +/- 3.9 nmol/l). Oral oestrogen-containing preparations increase total cortisol levels by increasing circulating CBG concentration. These effects were not seen in patients using transdermal oestrogen replacement. Although further studies are indicated, it is probably unnecessary to routinely discontinue transdermal oestrogen replacement when performing an assessment of the hypothalamic-pituitary-adrenal (HPA) axis or evaluating adequacy of hydrocortisone replacement.
    Clinical Endocrinology 05/2007; 66(5):632-5. · 3.40 Impact Factor
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    ABSTRACT: Neuroendocrine tumours (NET) are a rare cause of Cushing's syndrome. These tumours can be very small and therefore difficult to identify. Current localization techniques include CT, MRI and radioisotope scanning, but in a proportion of cases the NET remains occult. Positron emission tomography (PET) scanning, is a relatively new imaging modality that is increasingly used to detect and monitor lesions with high metabolic activity. We report on the use of PET scanning in the evaluation of the ectopic ACTH syndrome. Three patients with ectopic ACTH-dependent Cushing's syndrome with varying difficulty in NET localization are included in the report. Positron emission tomography scanning using 18flurodeoxyglucose (FDG) identifies tissue with high metabolic activity. 18FDG-PET scanning was used in each of these patients and the imaging is presented along with biochemical data. In each case the NET was easily identified using 18FDG-PET, aiding clinical decision making and therapeutic outcome. A cure was identified by clinical resolution of symptoms and undetectable ACTH levels postsurgery. 18FDG-PET assisted in localizing small metabolically active NETs, suggesting this imaging modality may have a useful role in identifying NET causing Cushing's syndrome as a result of ectopic ACTH production.
    Clinical Endocrinology 05/2006; 64(4):371-4. · 3.40 Impact Factor
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    ABSTRACT: Exercise is a potent physiological stimulus of GH secretion. We hypothesized that exogenous recombinant human growth hormone (rhGH) administration through an increase in GH and IGF-I levels would blunt the GH response to exercise. The aim of the study was to examine and compare the impact of rhGH on the exercise-induced GH response in healthy normal men and women. Sixty-nine subjects (36 men, 33 women) were randomized to receive low-dose rhGH (0.1 U/kg/day), high dose rhGH (0.2 U/kg/day), or placebo. Subjects were matched for age (24 +/- 3.1), and body mass index (BMI). rhGH was given as a single subcutaneous (s.c.) injection for the first 28 days. All subjects exercised to exhaustion (maximal oxygen consumption--VO2max) before rhGH treatment (Test 1), and on day 28 (Test 2). GH was measured before exercise (time 0), immediately after exercise (time 0') and at 15, 30, 60, 90 and 120 min postexercise. Baseline IGF-I levels were measured before exercise on days 0 and 28. Baseline IGF-I levels showed no gender differences (42.3 women vs. 38.8 nmol/l men) but basal GH values were higher in women (9.9 vs. 1.8 mU/l, P < 0.001). The areas under the GH response curve, for Test 1 were similar in men and women. Peak GH values were higher in women than men (37.9 vs. 23.5 mU/l, but this did not quite reach statistical significance (P = 0.055). In men, administration of rhGH resulted in a significant increase in IGF-I levels over the basal state in both the LD and HD groups (P < 0.0001). In women, the increase in lGF-I levels reached significance only in the HD group (P < 0.0001). On day 28, GH secretion in response to exercise was calculated from the areas under the GH response curve correcting for an exogenous rhGH component (delta AUC). In men, the delta AUC, for Test 2 were similar in all three groups. In women, the delta AUC was higher in the placebo group, than in the HD group (P < 0.02). Free T4 levels decreased significantly in men, and free T3 increased in both men and women, in HD group after the rhGH administration. TSH levels were suppressed only in women. No changes in sex hormones were found in men or women in any of the treatment groups. Conclusions In terms of IGF-I, men are more responsive to rhGH treatment than women. In addition, as men, but not women, were able to overcome the negative feedback control of the elevated IGF-I levels, it seems that exercise may be a more robust stimulus to GH release in men compared to women.
    Clinical Endocrinology 04/2005; 62(3):315-22. · 3.40 Impact Factor
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    ABSTRACT: Elevated serum sialic acid (SSA) predicts cardiovascular disease in the non-diabetic population and is also associated with the presence of microalbuminuria and clinical proteinuria in patients with insulin-dependent diabetes (IDDM). We have studied 121 patients with IDDM of long duration (mean duration 25.2 years) to investigate the relationship of SSA concentrations to the presence of retinopathy, nephropathy, and neuropathy. SSA levels were elevated in patients with retinopathy (0.578 ± 0.161 g l−1, n = 98) when compared with those without retinopathy (0.468 ± 0.145 g l−1, n = 23, p = 0.002). Patients with nephropathy (urinary albumin:creatinine ratio of > 3 mg mmol−1 in all of three early morning specimens of urine) also had raised SSA levels (0.625 ± 0.169 g l−1, n = 30) compared with those without nephropathy (0.533 ± 0.160 g l−1, n = 91, p = 0.006). There was a significant correlation of SSA with urinary albumin:creatinine ratio (correlation coefficient 0.33, p < 0.001). SSA levels were not related to the presence or absence of neuropathy (0.567 ± 0.181 g l−1, n = 28, vs 0.533 ± 0.160 g l−1, n = 93, p = 0.92, respectively). In conclusion, retinopathy and nephropathy but not neuropathy are associated with increased SSA levels in patients with IDDM. The significance of this is not yet clear but it is possible that sialic acid is involved in the pathophysiology of microvascular disease in IDDM.
    Diabetic Medicine. 07/2004; 13(3):238 - 242.
  • S Mehmet, J K Powrie
    Clinical Endocrinology 02/2003; 58(1):111-3. · 3.40 Impact Factor
  • Medicine and Science in Sports and Exercise - MED SCI SPORT EXERCISE. 01/2002; 34(5).
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    R I Holt, J K Powrie, P H Sönksen
    Journal of the Royal Society of Medicine 01/2001; 93(12):636-8. · 1.72 Impact Factor
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    ABSTRACT: Self-monitoring of blood or urine glucose is widely used by subjects with Type 2 diabetes mellitus. This study evaluated the effectiveness of the technique at improving blood glucose control through a systematic review and meta-analysis. Randomized controlled trials were identified that compared the effects of blood or urine glucose monitoring with no self-monitoring, or blood glucose self-monitoring with urine glucose self-monitoring, on glycated haemoglobin as primary outcome in Type 2 diabetes. Eight reports were identified. These were rated for quality and data were abstracted. The mean (SD) quality score was 15.0 (1.69) on a scale ranging from 0 to 28. No study had sufficient power to detect differences in glycated haemoglobin (GHb) of less than 0.5%. One study was excluded because it was a cluster randomized trial of a complex intervention and one because fructosamine was used as the outcome measure. A meta-analysis was performed using data from four studies that compared blood or urine monitoring with no regular monitoring. The estimated reduction in GHb from monitoring was -0.25% (95% confidence interval -0.61 to 0.10%). Three studies that compared blood glucose monitoring with urine glucose monitoring were also combined. The estimated reduction in GHb from monitoring blood glucose rather than urine glucose was -0.03% (-0.52 to 0.47%). The results do not provide evidence for clinical effectiveness of an item of care with appreciable costs. Further work is needed to evaluate self-monitoring so that resources for diabetes care can be used more efficiently.
    Diabetic Medicine 12/2000; 17(11):755-61. · 3.24 Impact Factor
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    ABSTRACT: To test whether a thyroxyl-insulin analog with restricted access to receptor sites in peripheral tissues displays relative hepatoselectivity in humans. Five normal human subjects received a subcutaneous bolus injection of either N(alphaBl) L-thyroxyl-insulin (Bl-T4-Ins) or NPH insulin in random order. Insulin kinetics, relative effects on hepatic glucose production, and peripheral glucose uptake were studied using euglycemic clamp and stable isotope [D-6,6-(2)H2]glucose) dilution techniques. Blood samples were taken for the determination of total immunoreactive insulin/analog concentrations and for liquid chromatography to assess the protein binding of the analog in the circulation. After subcutaneous administration, Bl-T4-Ins was well tolerated and rapidly absorbed. The analog had a long serum half-life and was highly protein bound (approximately 86%). Its duration of action, as judged by the duration of infusion of exogenous glucose to maintain euglycemia, was similar to that of NPH insulin. The effect of the analogs on hepatic glucose production was similar to that of NPH insulin, indicating equivalent hepatic potency. The analog demonstrated less effect on peripheral glucose uptake than NPH insulin (P = 0.025), had no effect on metabolic clearance rate of glucose, and exhibited a reduced capacity to inhibit lipolysis (P < 0.05). When injected subcutaneously into normal human subjects, Bl-T4-Ins is well tolerated, quickly absorbed, and highly protein bound, resulting in a long plasma halflife. This analog appears to have a hepatoselective action, and, therefore, has the potential to provide more physiological insulin action than the insulin preparations currently used.
    Diabetes Care 08/2000; 23(8):1124-9. · 7.74 Impact Factor
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    ABSTRACT: The effects of GH on bone remodeling in healthy adults have not been systematically investigated. An analysis of these effects might provide insights into GH physiology and might yield data useful for the detection of GH doping in sports. The aim of this study was to evaluate the effects of GH administration on biochemical markers of bone and collagen turnover in healthy volunteers. Ninety-nine healthy volunteers of both sexes were enrolled in a multicenter, randomized, double blind, placebo-controlled study and assigned to receive either placebo (40 subjects) or recombinant human GH (0.1 IU/kg day in 29 subjects and 0.2 IU/kg x day in 30 subjects). The treatment duration was 28 days, followed by a 56-day wash-out period. The biochemical markers evaluated were the bone formation markers osteocalcin and C-terminal propeptide of type I procollagen, the resorption marker type I collagen telopeptide, and the soft tissue marker procollagen type III. All variables increased on days 21 and 28 in the two active treatment groups vs. levels in both the baseline (P < 0.01) and placebo (P < 0.01) groups. The increment was more pronounced in the 0.2 IU/kg-day group and remained significant on day 84 for procollagen type III (from 0.53 +/- 0.13 to 0.61 +/- 0.14 kU/L; P < 0.02) and osteocalcin (from 12.2 + 2.9 to 14.6 +/- 3.6 UG/L; P < 0.02), whereas levels of C-terminal propeptide of type I procollagen and type I collagen telopeptide declined after day 42 and were no longer significantly above baseline on day 84 (from 3.9 +/- 1.2 to 5.1 +/-1.5 microg/L and from 174 +/- 60 to 173 +/- 53 microg/L, respectively). Gender-related differences were observed in the study; females were less responsive than males to GH administration with respect to procollagen type III and type I collagen telopeptide (P < 0.001). In conclusion, exogenous GH administration affects the biochemical parameters of bone and collagen turnover in a dose- and gender-dependent manner. As GH-induced modifications of most markers, in particular procollagen type III and osteocalcin, persist after GH withdrawal, they may be suitable markers for detecting GH abuse.
    Journal of Clinical Endocrinology &amp Metabolism 04/2000; 85(4):1505-12. · 6.43 Impact Factor
  • Health technology assessment (Winchester, England) 02/2000; 4(12):i-iv, 1-93. · 4.03 Impact Factor
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    ABSTRACT: The accuracy of calculations of pre-hepatic insulin secretion were investigated, to provide independent validation of a population model of C-peptide kinetics. The effects of sampling frequency were also assessed. Five normal subjects (aged 28 to 43 years; BMI (kg/m2) 20.5 to 24.5) and five subjects with non-insulin-dependent diabetes mellitus (NIDDM) treated by diet alone (aged 34 to 57 years; BMI 22.6 to 25.6) were given a variable intravenous infusion of biosynthetic human C-peptide (BHCP) (t=-60 to 240 min) mimicking meal stimulated C-peptide secretion, with short-term oscillations (peak approximately every 12 min) superimposed on the infusion profile. Plasma C-peptide was measured every 5 min (t=0 to 240 min). The BHCP infusion was reconstructed from C-peptide measurements using a population model of C-peptide kinetics and a deconvolution method. Bias, defined as the percentage difference between the total amount of calculated BHCP and the total amount of infused BHCP (t=0 to 240 min), indicated that overall C-peptide secretion can be measured with 14% [95% confidence interval (CI) -11 to 39%] and 21% (95% CI -3 to 45%) accuracy in normal subjects and subjects with NIDDM respectively. Accuracy was not reduced by reducing the sampling frequency to every 30 min. The root mean square error, measuring the average deviation between the infused and normalised calculated BHCP profiles, was also independent of the sampling frequency [mean (95% CI) 0.9 (0.3 to 1.6) pmol/kg per min in normal subjects; 1.0 (0.9 to 1.1) pmol/kg per min in subjects with NIDDM]. Deconvolution employing a population model of C-peptide kinetics can be used to estimate postprandial total C-peptide secretion with biases of 14% and 22% respectively in normal subjects and subjects with NIDDM. Plasma C-peptide samples need only be drawn every 30 minutes.
    Diabetologia 06/1998; 41(5):548-54. · 6.49 Impact Factor
  • S F O'Brien, J K Powrie, G F Watts
    Annals of Clinical Biochemistry 04/1997; 34 ( Pt 2):202-4. · 1.92 Impact Factor
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    ABSTRACT: The purpose of the study was to examine the contribution of alterations in lipoprotein metabolism to the progression of very-low-level albuminuria in insulin-dependent diabetes mellitus (IDDM). We measured serum concentrations of lipids, lipoproteins, and apolipoproteins in 53 normoalbuminuric diabetic patients without overt hypertension, whom we restudied after 10 years. Albuminuria was measured as the urinary albumin to creatinine ratio (UA/UC) in repeated early-morning samples. Over 10 years, UA/UC increased significantly (P < .001), and five patients (9.4%) progressed to microalbuminuria. The increase in albuminuria was significantly and positively related to the baseline serum concentrations of total cholesterol (P < .05), low-density lipoprotein (LDL) cholesterol (P = .05), non-high-density lipoprotein (HDL) cholesterol (P < .05), and apolipoprotein (apo) B (P < .001), but no significant associations were found with triglycerides, HDL cholesterol, apo A-1, or lipoprotein(a) [Lp(a)]. The relative risk of developing microalbuminuria for a serum apo B concentration more than 1.1 g/L was 3.8 (95% confidence interval [CI], 1.9 to 7.7). In multiple linear regression analysis, serum apo B (P < .05) and glycated hemoglobin ([HbA] P < .05) at baseline were significant independent predictors of the increase in albuminuria, with no significant associations found for sex, smoking, duration of diabetes, mean arterial blood pressure (BP), or family history of cardiovascular disease and hypertension; the regression model predicted 42% of the variation in UA/UC at 10 years. The findings suggest that an abnormality in the metabolism of apo B may be independently associated with progression of very-low-level albuminuria and possibly with the development of early nephropathy in IDDM patients.
    Metabolism 09/1996; 45(9):1101-7. · 3.10 Impact Factor
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    ABSTRACT: In four patients presenting in childhood with varying degrees of hypopituitarism, magnetic resonance imaging (MRI) showed a reduction in size of the normal pituitary fossa contents and an absent or very narrow stalk. A high signal intensity, enhancing area at the base of the stalk, having the appearances and signal characteristics of the posterior pituitary, was seen in each case. We discuss the case histories and MR findings in our patients and review the relevant literature.
    British Journal of Radiology 06/1996; 69(821):402-6. · 1.22 Impact Factor
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    ABSTRACT: We aimed to examine the relationship of serum lipids, lipoproteins, apolipoproteins and antioxidants with renal dysfunction as measured by urinary excretion of albumin and of retinol binding protein (RBP) in insulin-dependent diabetes mellitus (IDDM). We studied 121 patients with IDDM. Glomerular function was assessed as the urinary albumin/creatinine ratio (UA/UC), and tubular function as the urinary retinol-binding protein/creatinine ratio (UR/UC), both measured in three early morning spot urine samples. The mean (range) UA/UC was 1.95 mg/mmol (0.3-476.5) and UR/UC was 17.5 micrograms/mmol (1.0-1853.8). 17% of the patients had a UA/UC > 3 mg/mmol and 33% had a UR/UC > 20 micrograms/mmol. Significant positive correlations were observed between both UA/UC and UR/UC and the following: serum total cholesterol (P < 0.005); triglycerides (P < 0.001); apolipoproteins A-I (P < 0.05), A-II (P < 0.02) and B (P < 0.002); glycated haemoglobin (P < 0.002). No significant associations were found with serum vitamin E, beta-carotene or total antioxidant activity. In multiple regression, only UA/UC was independently associated with serum apo B and cholesterol concentrations. In conclusion, in IDDM glomerular dysfunction, as measured by UA/UC, is associated with elevated serum cholesterol, triglycerides, apo B, apo A-I and apo A-II, but not with HDL cholesterol or antioxidant status. Tubular dysfunction tends to occur with increasing albuminuria, but it is not independently associated with serum lipid, lipoprotein, apolipoprotein or antioxidant levels.
    Diabetes Research and Clinical Practice 05/1996; 32(1-2):81-90. · 2.74 Impact Factor

Publication Stats

683 Citations
120.37 Total Impact Points

Institutions

  • 2006–2009
    • Guy's and St Thomas' NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2001
    • University of Southampton
      • Developmental Origins of Health and Disease
      Southampton, England, United Kingdom
  • 1996
    • University of Western Australia
      Perth City, Western Australia, Australia
  • 1993–1994
    • City University London
      Londinium, England, United Kingdom