39 results on '"Fassett, R. G."'
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2. Hydration and endocrine responses to intravenous fluid and oral glycerol
- Author
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van Rosendal, S. P., Strobel, N. A., Osborne, M. A., Fassett, R. G., and Coombes, J. S.
- Published
- 2015
- Full Text
- View/download PDF
3. Arterial stiffness, central blood pressure and body size in health and disease
- Author
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Kolade, O O, O'Moore-Sullivan, T M, Stowasser, M, Coombes, J S, Fassett, R G, Marwick, T H, and Sharman, J E
- Published
- 2012
- Full Text
- View/download PDF
4. Central blood pressure measurement may improve risk stratification
- Author
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Sharman, J E, Stowasser, M, Fassett, R G, Marwick, T H, and Franklin, S S
- Published
- 2008
- Full Text
- View/download PDF
5. Response to ‘More fuel in the obesity paradox debate’: fatness, fitness, stiffness and blood pressure
- Author
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Sharman, J E, Stowasser, M, Kolade, O O, Coombes, J S, Fassett, R G, and Marwick, T H
- Published
- 2013
- Full Text
- View/download PDF
6. Bile pigment pharmacokinetics and absorption in the rat: therapeutic potential for enteral administration
- Author
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Bulmer, A C, Coombes, J S, Blanchfield, J T, Toth, I, Fassett, R G, and Taylor, S M
- Published
- 2011
- Full Text
- View/download PDF
7. Antioxidant Supplementation Enhances Erythrocyte Antioxidant Status and Attenuates Cyclosporine-Induced Vascular Dysfunction
- Author
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Lexis, L. A., Fenning, A., Brown, L., Fassett, R. G., and Coombes, J. S.
- Published
- 2006
8. Repeated Renal Failure With Captopril
- Author
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Fassett, R. G., Walker, R. G., Whitworth, Judith A., and Kincaid-Smith, Priscilla
- Published
- 1983
9. Serum 25-hydroxy vitamin D concentrations are more deficient/insufficient in peritoneal dialysis than haemodialysis patients in a sunny climate
- Author
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Hanna, K., primary, Fassett, R. G., additional, Gill, E., additional, Healy, H., additional, Kimlin, M., additional, Ross, L., additional, and Ash, S., additional
- Published
- 2014
- Full Text
- View/download PDF
10. Statins in acute kidney injury: friend or foe?
- Author
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Fassett, R. G., primary and Coombes, J. S., additional
- Published
- 2013
- Full Text
- View/download PDF
11. Response to ‘More fuel in the obesity paradox debate’: fatness, fitness, stiffness and blood pressure
- Author
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Sharman, J E, primary, Stowasser, M, additional, Kolade, O O, additional, Coombes, J S, additional, Fassett, R G, additional, and Marwick, T H, additional
- Published
- 2012
- Full Text
- View/download PDF
12. Effects of atorvastatin on NGAL and cystatin C in chronic kidney disease: a post hoc analysis of the LORD trial
- Author
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Fassett, R. G., primary, Robertson, I. K., additional, Ball, M. J., additional, Geraghty, D. P., additional, Cardinal, J. W., additional, and Coombes, J. S., additional
- Published
- 2011
- Full Text
- View/download PDF
13. Arterial stiffness, central blood pressure and body size in health and disease
- Author
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Kolade, O O, primary, O'Moore-Sullivan, T M, additional, Stowasser, M, additional, Coombes, J S, additional, Fassett, R G, additional, Marwick, T H, additional, and Sharman, J E, additional
- Published
- 2011
- Full Text
- View/download PDF
14. Glutathione peroxidase, superoxide dismutase and catalase genotypes and activities and the progression of chronic kidney disease
- Author
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Crawford, A., primary, Fassett, R. G., additional, Coombes, J. S., additional, Kunde, D. A., additional, Ahuja, K. D. K., additional, Robertson, I. K., additional, Ball, M. J., additional, and Geraghty, D. P., additional
- Published
- 2011
- Full Text
- View/download PDF
15. Pulmonary oedema and hyponatraemia after an ironman triathlon
- Author
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Stefanko, G., primary, Lancashire, B., additional, Coombes, J. S, additional, and Fassett, R. G, additional
- Published
- 2009
- Full Text
- View/download PDF
16. Hydration and endocrine responses to intravenous fluid and oral glycerol.
- Author
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Rosendal, S. P., Strobel, N. A., Osborne, M. A., Fassett, R. G., and Coombes, J. S.
- Subjects
DEHYDRATION ,GLYCERIN ,ALDOSTERONE ,ANALYSIS of variance ,BLOOD plasma ,BLOOD volume ,CROSSOVER trials ,CYCLING ,DIURESIS ,EXERCISE ,FLUID therapy ,HEMATOCRIT ,HEMOGLOBINS ,HYDROCORTISONE ,INTRAVENOUS therapy ,ORAL drug administration ,HEALTH outcome assessment ,PROBABILITY theory ,STATISTICS ,URINE ,VASOPRESSIN ,DATA analysis ,BODY movement ,RANDOMIZED controlled trials ,REPEATED measures design ,OXYGEN consumption ,ERGOMETRY ,BLIND experiment ,OSMOLAR concentration ,THERAPEUTICS - Abstract
Athletes use intravenous ( IV) saline in an attempt to maximize rehydration. The diuresis from IV rehydration may be circumvented through the concomitant use of oral glycerol. We examined the effects of rehydrating with differing regimes of oral and IV fluid, with or without oral glycerol, on hydration, urine, and endocrine indices. Nine endurance-trained men were dehydrated by 4% bodyweight, then rehydrated with 150% of the fluid lost via four protocols: (a) oral = oral fluid only; (b) oral glycerol = oral fluid with added glycerol (1.5 g/kg); (c) IV = 50% IV fluid, 50% oral fluid; and (d) IV with oral glycerol = 50% IV fluid, 50% oral fluid with added glycerol (1.5 g/kg), using a randomized, crossover design. They then completed a cycling performance test. Plasma volume restoration was highest in IV with oral glycerol > IV > oral glycerol > oral. Urine volume was reduced in both IV trials compared with oral. IV and IV with oral glycerol resulted in lower aldosterone levels during rehydration and performance, and lower cortisol levels during rehydration. IV with oral glycerol resulted in the greatest fluid retention. In summary, the IV conditions resulted in greater fluid retention compared with oral and lower levels of fluid regulatory and stress hormones compared with both oral conditions. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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17. Hypercalcaemia associated with inflammatory pseudotumour of the spleen
- Author
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Shepherd, J J, primary, Fassett, R G, additional, and Challis, D, additional
- Published
- 1992
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18. Changes in bone histoquantitative parameters and histochemical staining reactions for aluminium in a group of patients with chronic renal failure following a reduction in the aluminium concentration of the haemodialysis fluid.
- Author
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McClure, J, Fazzalari, N L, Fassett, R G, and Pugsley, P G
- Abstract
Bone biopsies from a group of 16 patients in chronic renal failure treated by intermittent haemodialysis were available for histoquantitative and histochemical assessment before and after the introduction of reverse osmosis treatment of the dialysis fluid. This treatment reduced the aluminium concentration of the fluid from 1.15 mg/l to less than 0.06 mg/l. After the changeover there was an increase in the extent of calcification fronts. Overall, there was a decrease in the histochemical staining reactions for aluminium, although a few cases showed increased reactions. A large percentage of cases showing decreased reactions also had decreased osteoid volumes. It is concluded that reduction of the concentration of aluminium in the dialysis fluid is associated with an improvement in mineralisation state, and this is further evidence of the importance of minimising the aluminium burden of patients with chronic renal failure. [ABSTRACT FROM PUBLISHER]
- Published
- 1984
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19. Bone histoquantitative findings and histochemical staining reactions for aluminium in chronic renal failure patients treated with haemodialysis fluids containing high and low concentrations of aluminium.
- Author
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McClure, J, Fazzalari, N L, Fassett, R G, and Pugsley, D J
- Abstract
A total of 112 undecalcified bone biopsies from 67 patients under treatment for chronic renal failure by maintenance haemodialysis was available for retrospective study. The patients were divided into three groups. Group I (15 cases) had been dialysed for the majority of the time in their own homes with a fluid containing a low concentration of aluminium. Group II (28 cases) had been dialysed exclusively in hospital (prior to 1978) with a fluid containing a high concentration of aluminium and group III (24 cases) had been treated exclusively in hospital (from 1978 onwards) with a fluid of low aluminium concentration. The tissues from these groups were subjected to histoquantitative assessment and stained by a histochemical technique to demonstrate aluminium salt. In group II, 71.4% of cases showed positive aluminium staining reactions (at the osteoid/mineralised tissue interface) compared to 26.6% in group I and 37.5% in group III. Staining reactions were also more extensive in group II cases. The osteoid volume was significantly increased and the calcification front extents significantly decreased in group II compared to both groups I and III. A comparison of histochemically positive with negative cases in each group showed a significantly increased osteoid volume and significantly decreased calcification fronts in the positive cases. It was, therefore, concluded that haemodialysis against a fluid containing a high concentration of aluminium leads to intraosseous aluminium accumulation of greater degree in a larger number of patients than a fluid with low aluminium content and that there is an accompanying osteomalacia manifest by an increase in osteoid volume together with diminution in the extent of the calcification fronts. [ABSTRACT FROM PUBLISHER]
- Published
- 1983
20. Repeated renal failure with captopril
- Author
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Fassett, R G, Walker, R G, Whitworth, J A, and Kincaid-Smith, P
- Subjects
Letter - Published
- 1983
21. Urinary red-cell morphology during exercise.
- Author
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Fassett, R G, primary, Owen, J E, additional, Fairley, J, additional, Birch, D F, additional, and Fairley, K F, additional
- Published
- 1982
- Full Text
- View/download PDF
22. Case Report. Hypercalcaemia associated with inflammatory pseudotumour of the spleen.
- Author
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Shepherd, J. J., Fassett, R. G., and Challis, D.
- Published
- 1992
- Full Text
- View/download PDF
23. Contrasting approaches to end of life and palliative care in end stage kidney disease.
- Author
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Koshy AN, Mace R, Youl L, Challenor S, Bull R, and Fassett RG
- Abstract
With increased numbers of the elderly, including nursing home patients, being accepted for end-stage kidney disease (ESKD) management, there is heightened interest and focus on end of life decisions, advanced care planning and directives, withdrawal from dialysis and palliative care in this setting. Despite this, care at the individual patient level can vary greatly. Here, we present two contrasting cases to highlight the importance of early and ongoing involvement of palliative care in patients with ESKD. In the first case, a high quality of life was preserved before the patient died with dignity, with early interdisciplinary palliative care involvement. In the second case there was a long protracted period of poor quality of life prior to death. This was associated with resistance to the involvement of palliative care, mainly from the family. Addressing end of life care issues early in the chronic kidney disease (CKD) trajectory and ensuring patients, their families and health care providers are well informed, may contribute to a better outcome for the patient and their family.
- Published
- 2012
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24. Effects of a gliadin-combined plant superoxide dismutase extract on self-perceived fatigue in women aged 50-65 years.
- Author
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Houghton CA, Steels EL, Fassett RG, and Coombes JS
- Subjects
- Activities of Daily Living, Aged, Antioxidants metabolism, Antioxidants pharmacology, Dehydroepiandrosterone blood, Double-Blind Method, Drug Combinations, F2-Isoprostanes blood, Fatigue blood, Female, Gliadin pharmacology, Hormones blood, Humans, Hydrocortisone blood, Malondialdehyde blood, Mental Fatigue blood, Mental Fatigue drug therapy, Middle Aged, Motivation drug effects, Oxidative Stress drug effects, Perception, Plant Extracts pharmacology, Self Concept, Superoxide Dismutase blood, Superoxide Dismutase pharmacology, Antioxidants therapeutic use, Cucumis chemistry, Dietary Supplements, Fatigue drug therapy, Gliadin therapeutic use, Plant Extracts therapeutic use, Superoxide Dismutase therapeutic use
- Abstract
Fatigue syndromes exist on a continuum of severity from mild and transient to the disabling chronic fatigue syndrome, with oxidative stress linked to its pathogenesis. A thermolabile gliadin-combined plant superoxide dismutase (SOD) extract has shown potential in clinical trials as a therapeutic antioxidant. This study investigated the effects of 12 weeks of 500 mg/day of a SOD/gliadin supplement on fatigue. Thirty-eight women aged 50-65 years with self-perceived fatigue entered this randomized, double-blind, placebo-controlled trial. The primary outcome measure was general fatigue determined by the Multidimensional Fatigue Inventory (MFI). Secondary outcome measures included other measures of fatigue from the MFI and blood measures of oxidative stress, antioxidant status and hormones. There were no significant (P>0.05) differences between, or within groups, for decreases in general fatigue (active=1.6%, placebo=4.1%). There were no within or between group differences (P>0.05) in other measures of fatigue (physical fatigue, reduced activity, reduced motivation, mental fatigue and total fatigue score). In regard to the biochemical measures, there were non-significant (P>0.05) differences in increases in plasma SOD activity (active=7.1%, placebo=12.2%), plasma GPx activity (active=2.4%, placebo=0.7%), red blood cell GPx activity (active=9.8%, placebo=4.4%). Markers of oxidative stress were decreased but there were no differences (P>0.05) within or between groups; malondialdehyde (active=4.1%, placebo=1.6%), F-2 isoprostanes (active=14.7%, placebo=22.4%). There was a trend (P=0.08) for a decrease in cortisol in the active group (24.6%), however this was not significantly different from the decrease in the placebo participants (4.1%). DHEA differences were not significant (P<0.05) and declined 1.3% in the active group and 14.4% in the placebo group. In summary, the thermolabile SOD/gliadin supplement had no significant effect on self-perceived fatigue, antioxidants, oxidative stress or hormones in women aged 50-65 years., (Copyright © 2010 Elsevier GmbH. All rights reserved.)
- Published
- 2011
- Full Text
- View/download PDF
25. Cardiovascular disease in peritoneal dialysis patients.
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Fassett RG, Driver R, Healy H, and Coombes JS
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- Cardiovascular Diseases mortality, Evidence-Based Medicine, Humans, Kidney Diseases mortality, Peritoneal Dialysis mortality, Renal Dialysis adverse effects, Risk Assessment, Risk Factors, Time Factors, Treatment Outcome, Cardiovascular Diseases etiology, Kidney Diseases therapy, Peritoneal Dialysis adverse effects
- Abstract
Patients on peritoneal dialysis have a high level of morbidity and mortality associated with atherosclerotic cardiovascular disease and they also have an increased risk of sudden death. The atherosclerosis seen in peritoneal dialysis patients is associated with both traditional cardiovascular risk factors such as low levels of physical activity, hyperlipidemia, hypertension, diabetes and smoking as well as non-traditional risk factors such as elevated oxidative stress and inflammation. The atherosclerosis may be preceded by endothelial dysfunction and increased arterial stiffness. Measures of arterial stiffness such as aortic pulse wave velocity predict morbidity and mortality. Numerous studies have reported that the elevated levels of oxidative stress and inflammation in this population are associated with arterial stiffness and in turn with the development of cardiovascular disease. A number of studies have reported that peritoneal dialysis is associated with lower levels of oxidative stress and inflammation compared to haemodialysis. A small number of trials have extended this work to determine associations between oxidative stress and inflammation with vascular or myocardial structure and function with equivocal results. The decision to undergo either peritoneal or haemodialysis is based on many factors which include the differential damage the renal replacement therapy may have on the cardiovascular system. Current evidence suggests this may vary over time. Previous randomised controlled trials and many other observational studies have produced conflicting results as to which therapy may have a cardiovascular advantage. Some registry data suggests peritoneal dialysis is associated with a lower mortality than haemodialysis in the first one-two years but thereafter may be higher on peritoneal dialysis than haemodialysis. Other registry data do not support this. Further long-term studies assessing surrogate and hard endpoint cardiovascular outcomes in peritoneal dialysis are required.
- Published
- 2009
26. Baseline serum lipids and renal function in chronic kidney disease patients entering the LORD trial.
- Author
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Fassett RG, Ball MJ, Robertson IK, Geraghty DP, and Coombes JS
- Subjects
- Blood Pressure, Creatinine blood, Diet, Double-Blind Method, Female, Glomerular Filtration Rate, Humans, Kidney Diseases blood, Kidney Diseases urine, Male, Middle Aged, Motor Activity, Proteinuria, Kidney Diseases physiopathology, Lipids blood
- Abstract
Objective: Previous studies investigating associations between serum lipids and renal disease have generally not taken into account dietary intake or physical activity both known to influence circulating lipids. Furthermore, inclusion of patients on HMG-CoA reductase inhibitors may also have influenced findings due to the pleiotropic effect of this medication. Therefore, the aim of this study is to determine the relationships between serum lipids and renal function in a group of patients not taking lipid-lowering medication and taking into account dietary intake and physical activity., Methods: Data from 100 patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial were used in this study. Patients were included with serum creatinine > 120 micromol/l, and excluded if they were taking lipid-lowering medication. Unadjusted and adjusted relationships were determined between fasting serum lipid concentrations (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol/HDL ratio) and measures of renal function (estimated glomerular filtration rate (eGFR), creatinine clearance and serum creatinine) and urinary protein excretion., Results: Significant (p < 0.05) negative unadjusted relationships were found between lipids (total cholesterol, LDL and HDL cholesterol) and serum creatinine. In support of these findings, logarithmically-transformed lipids (total cholesterol, LDL and HDL cholesterol) were significantly associated with eGFR and creatinine clearance although the effects were of a smaller magnitude. Adjustment for dietary saturated fat intake and physical activity did not substantially change these effects., Conclusion: These data do not support the premise that lipids are associated with renal dysfunction in patients with normocholesterolemia.
- Published
- 2006
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27. Folate supplementation fails to affect vascular function and carotid artery intima media thickness in cyclosporin A-treated renal transplant recipients.
- Author
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Austen SK, Fassett RG, Geraghty DP, and Coombes JS
- Subjects
- Brachial Artery pathology, Carotid Arteries pathology, Cross-Over Studies, Cyclosporine blood, Double-Blind Method, Female, Folic Acid blood, Homocysteine blood, Homocysteine drug effects, Humans, Immunosuppressive Agents blood, Male, Middle Aged, Treatment Outcome, Tunica Intima pathology, Tunica Media pathology, Brachial Artery drug effects, Carotid Arteries drug effects, Cyclosporine therapeutic use, Folic Acid therapeutic use, Immunosuppressive Agents therapeutic use, Kidney Transplantation, Tunica Intima drug effects, Tunica Media drug effects
- Abstract
Background: Cyclosporin A (CsA)-treated renal transplant recipients (RTR) exhibit relative hyperhomocystinemia and vascular dysfunction. Folate supplementation lowers homocysteine and has been shown to improve vascular function in healthy subjects and patients with coronary artery disease. The aim of this study was to assess the effects of 3 months of folate supplementation (5 mg/day) on vascular function and structure in RTR., Methods: A double-blind, placebo-controlled crossover study was conducted in 10 CsA-treated RTR. Vascular structure was measured as carotid artery intima media thickness (IMT) and function was assessed as changes in brachial artery diameter during reactive hyperemia (RH) and in response to glyceryl trinitrate (GTN). Function data were analyzed as absolute and percent change from baseline and area under the diameter/time curve. Blood samples were collected before and after supplementation and analyzed for total plasma homocysteine, folate, vitamin B12 and asymmetric dimethyl arginine (ADMA) in addition to regular measures of hemoglobin, hematocrit, mean corpuscular volume (MCV) and serum creatinine., Results: Folate supplementation significantly increased plasma folate by 687% (p < 0.005) and decreased homocysteine by 37% (p < 0.05) with no changes (p > 0.05) in vitamin B12 or ADMA. There were no significant (p > 0.05) changes in vascular structure or function during the placebo or the folate supplementation phases; IMT; placebo pre mean +/- SD, 0.52 +/- 0.12, post 0.50 +/- 0.11; folate pre 0.55 +/- 0.17, post 0.49 +/- 0.20 mm, 5% change in brachial artery diameter (RH, placebo pre 10 +/- 8, post 6 +/- 5; folate pre 9 +/- 7, post 7 +/- 5; GTN, placebo pre 18 +/- 10, post 17 +/- 9, folate pre 16 +/- 9, post-supplementation 18 +/- 8)., Conclusion: Three months of folate supplementation decreases plasma homocysteine but has no effect on endothelial function or carotid artery IMT in RTR.
- Published
- 2006
- Full Text
- View/download PDF
28. Acute exposure to cyclosporine does not increase plasma homocysteine in rats.
- Author
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Austen SK, Fletcher LA, Fassett RG, Booth C, and Coombes JS
- Subjects
- Animals, Creatinine blood, Cyclosporine blood, Female, Rats, Rats, Sprague-Dawley, Cyclosporine pharmacology, Homocysteine blood
- Abstract
There is interest in the postulate that cyclosporine a (CsA) contributes to the elevated homocysteine levels seen in organ transplant recipients, as hyperhomocysteinemia is now considered an independent risk factor for cardiovascular disease (CVD) and may partially explain the increased prevalence of CVD in this population. The main purpose of this investigation was to determine the effect of CsA administration on plasma homocysteine. Eighteen female Sprague Dawley rats (4 months old) were randomly assigned to either a treatment or a control group. For 18 days the treatment group received of CsA (25 mg/kg/d) while the control group received the same volume of the vehicle. Blood samples obtained following sacrifice to measure CsA, total homocysteine, and plasma creatinine. There were no significant differences in plasma homocysteine (mean values +/- SD: treatment = 4.79 +/- 0.63 micromol/L, control = 4.46 +/- 0.75 micromol/L; P = .37). Homocysteine was not significantly correlated with final CsA concentrations (r = .17; P = .69). There was a significant difference in plasma creatinine values between the two groups (treatment = 60.44 +/- 7.68 micromol/L, control = 46.33 +/- 1.66 micromol/L; P < .001). Furthermore, plasma homocysteine and creatinine were positively correlated with the treatment group (r = .73; P < .05) but not the controls (r = -.10; P = .81). In conclusion, CsA does not influence plasma homocysteine concentrations in rats.
- Published
- 2005
- Full Text
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29. Homocysteine-lowering therapy in renal disease.
- Author
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Austen SK, Coombes JS, and Fassett RG
- Subjects
- Humans, Kidney Transplantation, Folic Acid therapeutic use, Hyperhomocysteinemia blood, Hyperhomocysteinemia drug therapy, Kidney Failure, Chronic blood, Vitamin B 6 therapeutic use
- Abstract
Hyperhomocysteinemia is a potential risk factor for vascular disease and is associated with endothelial dysfunction, a predictor of adverse cardiovascular events. Renal patients (end-stage renal failure (ESRF) and transplant recipients (RTR)) exhibit both hyperhomocysteinemia and endothelial dysfunction with increasing evidence of a causative link between the 2 conditions. The elevated homocysteine appears to be due to altered metabolism in the kidney (intra-renal) and in the uremic circulation (extra-renal). This review will discuss 18 supplementation studies conducted in ESRF and 6 in RTR investigating the effects of nutritional therapy to lower homocysteine. The clinical significance of lowering homocysteine in renal patients will be discussed with data on the effects of B vitamin supplementation on cardiovascular outcomes such as endothelial function presented. Folic acid is the most effective nutritional therapy to lower homocysteine. In ESRF patients, supplementation with folic acid over a wide dose range (2 - 20 mg/day) either individually or in combination with other B vitamins will decrease but not normalize homocysteine. In contrast, in RTR similar doses of folic acid normalizes homocysteine. Folic acid improves endothelial function in ESRF patients, however this has yet to be investigated in RTR. Homocysteine-lowering therapy is more effective in ESRF patients than RTR.
- Published
- 2003
- Full Text
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30. Pathogenesis of sodium and water retention in cardiac failure.
- Author
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Schrier RW and Fassett RG
- Subjects
- Heart Failure complications, Humans, Renal Insufficiency complications, Water-Electrolyte Imbalance complications, Heart Failure metabolism, Renal Insufficiency metabolism, Sodium metabolism, Water-Electrolyte Imbalance metabolism
- Abstract
The pathophysiology of sodium and water retention in heart failure is discussed in the context of a unifying hypothesis of body fluid volume regulation. Critical to this hypothesis is the maintenance of arterial circulatory integrity, which can be disturbed by either a reduction in cardiac output or a fall in systemic vascular resistance secondary to arterial vasodilatation, as seen in high output heart failure. The filling of the arterial circulation is sensed by receptors in the left ventricle, carotid artery, aortic arch and renal afferent arteriole. Effector mechanisms involve non-osmotic vasopressin synthesis and release, the renin-angiotensin-aldosterone system and the sympathetic nervous system. In low output heart failure non-peptide selective orally active vasopressin V2-receptor antagonists correct the hyponatremia, hypoosmolality, and water retention and decrease urinary aquaporin-2 water channels, supporting the role of vasopressin in the water retention seen in heart failure. In advanced heart failure aldosterone escape does not occur because of diminished distal delivery of sodium which also contributes to the resistance to atrial natriuretic peptide seen in heart failure. In high output cardiac failure arterial underfilling associated with arterial vasodilation stimulates activation of neurohumoral systems. Tailored specific selective inhibition of these neurohumoral systems, perhaps in combination, may enable more effective treatment of cardiac failure.
- Published
- 1998
- Full Text
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31. Vasopressin release, water channels, and vasopressin antagonism in cardiac failure, cirrhosis, and pregnancy.
- Author
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Schrier RW, Fassett RG, Ohara M, and Martin PY
- Subjects
- Animals, Antidiuretic Hormone Receptor Antagonists, Aquaporin 2, Aquaporin 6, Female, Humans, Mechanoreceptors metabolism, Osmotic Pressure, Pregnancy, Rats, Vasopressins antagonists & inhibitors, Vasopressins biosynthesis, Aquaporins metabolism, Heart Failure metabolism, Liver Cirrhosis metabolism, Vasopressins metabolism
- Abstract
Vasopressin (AVP) is released in response to both osmotic and nonosmotic stimuli. Nonosmotic-stimulated AVP release occurs in cardiac failure, cirrhosis, and pregnancy in response to alterations in arterial circulatory integrity. Cardiac failure in rats is associated with increased plasma AVP and hypothalamic AVP mRNA, and in humans, it is associated with cardiac failure. Plasma AVP concentrations are elevated when measured with a sensitive radioimmunoassay. Urinary concentrations of AVP-responsive aquaporin-2 water channels are also elevated in cardiac failure. V2 receptor antagonists correct the impaired solute-free water excretion seen in rats with low-output cardiac failure and reverse the upregulation of renal aquaporin-2 water channels. Orally active non-peptide-selective V2 receptor antagonists administered to patients with congestive cardiac failure decrease urinary concentrations of aquaporin-2, increase solute-free water clearance, and correct the hyponatremia. Cirrhosis of the liver results in splanchnic arterial vasodilation and increased vascular capacity, most likely secondary to increased nitric oxide production. This relative underfilling of the arterial circulation stimulates nonosmotic AVP release with resultant water retention. Aquaporin-2 gene expression is upregulated in the kidneys of rats with cirrhosis of the liver. AVP-2 receptor antagonists administered to animals with cirrhosis reverse the water retention. Human studies using orally active, non-peptide-selective V2 receptor antagonists in patients with cirrhosis are currently underway. Pregnancy is another state of nitric oxide-mediated arterial vasodilation that is associated with plasma AVP concentrations that are relatively high for the degree of hypoosmolality. Upregulation of the water channel aquaporin-2 in the renal papillae of pregnant rats has also been demonstrated, and this effect is reversed by administration of a V2 receptor antagonist.
- Published
- 1998
32. Pathophysiology of renal fluid retention.
- Author
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Schrier RW, Fassett RG, Ohara M, and Martin PY
- Subjects
- Animals, Female, Humans, Pregnancy, Heart Failure physiopathology, Kidney physiology, Pregnancy Complications, Hematologic physiopathology, Water-Electrolyte Balance physiology
- Abstract
Central to a unifying hypothesis of body fluid regulation is maintenance of arterial circulatory integrity. This may be disturbed by arterial underfilling, either from reduction in cardiac output or by peripheral arterial vasodilation. In cardiac failure (CF), cardiac output falls and the nonosmotic release of arginine vasopressin (AVP) and expression of AVP mRNA in the hypothalamus are stimulated. V2 AVP receptor antagonists correct the impaired water excretion in rats with low-output CF, increase solute free water clearance, correct the hyponatremia in congestive CF patients, and normalize urinary concentrations of the aquaporin-2 (AQP-2) water channels. In conditions associated with peripheral vasodilation, such as cirrhosis, nonosmotic release of AVP also occurs, and AQP-2 gene expression in the rat kidney is up-regulated. In cirrhosis, nitric oxide-mediated vasodilation occurs early prior to water retention. V2 antagonists reverse the latter. In normal pregnancy, plasma AVP is relatively high for the degree of hypoosmolality. Pregnant rats up-regulate AQP-2 in the renal papilla, an effect reversed by V2 receptor antagonists. This supports the hypothesis that AVP is an important mediator of renal water retention in pregnancy. In summary, AVP-mediated water retention through collecting duct AQP-2 water channels is important in both low-output CF and high-output states such as cirrhosis and pregnancy. V2 receptor antagonists reverse the water retention and down-regulate AQP-2 water channels.
- Published
- 1998
- Full Text
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33. A critique of the overfill hypothesis of sodium and water retention in the nephrotic syndrome.
- Author
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Schrier RW and Fassett RG
- Subjects
- Aldosterone physiology, Animals, Arginine Vasopressin physiology, Disease Models, Animal, Edema etiology, Edema physiopathology, Humans, Nephrotic Syndrome physiopathology, Plasma Volume, Renin-Angiotensin System physiology, Sympathetic Nervous System physiopathology, Water-Electrolyte Imbalance physiopathology, Models, Biological, Nephrotic Syndrome complications, Sodium metabolism, Water-Electrolyte Imbalance etiology
- Abstract
Recent reviews have claimed that the majority of patients with the nephrotic syndrome have plasma volume expansion (that is, they are overfilled). Here we attempt to re-establish balance to the debate on body fluid volume status in nephrotic patients by: (a) discussing the conflicting literature on plasma volume measurements in the nephrotic syndrome; (b) providing alternate explanations for data purporting to support an overfill hypothesis in the nephrotic syndrome; (c) emphasizing secondary neurohumoral responses that support underfilling at least as frequently as overfilling; and (d) emphasizing the clinical importance of fluid assessment in the individual patient with the nephrotic syndrome particularly in relation to diuretic use.
- Published
- 1998
- Full Text
- View/download PDF
34. Mesangiocapillary glomerulonephritis type II (dense-deposit disease): clinical features of progressive disease.
- Author
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Bennett WM, Fassett RG, Walker RG, Fairley KF, d'Apice AJ, and Kincaid-Smith P
- Subjects
- Adolescent, Adult, Child, Child, Preschool, Complement C3 analysis, Female, Glomerulonephritis, Membranoproliferative immunology, Glomerulonephritis, Membranoproliferative surgery, Humans, Kidney ultrastructure, Kidney Transplantation, Male, Middle Aged, Pregnancy, Pregnancy Complications, Prognosis, Glomerulonephritis, Membranoproliferative pathology
- Abstract
Twenty-seven patients presenting to the Royal Melbourne Hospital between 1968 and 1988 with mesangiocapillary glomerulonephritis type II with intramembranous dense deposits (dense-deposit disease, DDD) are analyzed. Patients were divided into two groups on the basis of whether renal function deteriorated (14 patients) or remained stable (13 patients). At presentation or during the course of the disease, heavy proteinuria, macroscopic hematuria, and high quantitative urinary red cell or white cell counts characterized patients with progressive disease. Patients with crescents on their initial renal biopsy or with large numbers of polymorphs in glomerular capillaries corresponding with sterile pyuria were more likely to have deterioration of renal function. The average time from onset of symptoms to development of end-stage renal disease was over 16 years. The patient's clinical course could not be anticipated by serum complement profiles, the presence of C3 nephritic factor, or partial lipodystrophy. Pregnancy did not affect the course of the disease. Six patients underwent renal transplantation and the disease recurred on renal biopsy in four. However, only two individuals lost renal allografts due to recurrent DDD.
- Published
- 1989
- Full Text
- View/download PDF
35. Effect of long-term cimetidine treatment on left ventricular function in haemodialysis patients with active hyperparathyroidism.
- Author
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Lai KN, Fassett RG, and Mathew TH
- Subjects
- Cimetidine therapeutic use, Heart physiopathology, Humans, Hyperparathyroidism drug therapy, Cimetidine pharmacology, Guanidines pharmacology, Heart drug effects, Hyperparathyroidism physiopathology, Renal Dialysis
- Abstract
1 The effect of long-term oral cimetidine on left ventricular function was evaluated in chronic haemodialysis patients with active hyperparathyroidism. 2 Radionuclide ventriculography (seven patients) and echocardiography (five patients) revealed a significant increase in ejection fraction and mean velocity of circumferential fibre shortening six months after treatment. 3 The improved cardiac performance was associated with improvement of bone histology. C-terminal parathyroid hormone, serum calcium, and mean arterial pressure changed little after treatment. 4 The improved cardiac performance is thought to be related to the suppression of uraemic hyperparathyroidism by cimetidine. 5 The present study suggests that uraemic hyperparathyroidism may play an important role in "uraemic cardiomyopathy".
- Published
- 1982
- Full Text
- View/download PDF
36. Left ventricular function in uremia: echocardiographic and radionuclide assessment in patients on maintenance hemodialysis.
- Author
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Lai KN, Ng J, Whitford J, Buttfield I, Fassett RG, and Mathew TH
- Subjects
- Adult, Aged, Echocardiography, Female, Heart diagnostic imaging, Heart Diseases etiology, Hemodynamics, Humans, Hyperparathyroidism etiology, Male, Middle Aged, Myocardial Contraction, Radionuclide Imaging, Uremia complications, Uremia therapy, Heart physiopathology, Renal Dialysis, Uremia physiopathology
- Abstract
Echocardiography and radionuclide ventriculography were performed in 37 uremic patients on maintenance hemodialysis with no apparent coronary artery disease, pericardial effusion, valvular heart disease or heart failure. These non-invasive studies were performed during the interdialytic period (about 18 hours after a dialysis). Sixty-two percent of our patients had abnormal left ventricular function with one or more abnormal echocardiographic parameters. The significant abnormalities were enlargement of the left ventricular cavity, a reduction of myocardial contractility, and thickening of the left ventricular posterior wall. Similar findings were found in 10 undialyzed uremic patients. Measurement of cardiac index and ejection fraction were found to be inadequate for a full assessment of left ventricular function and other parameters such as the mean velocity of circumferential fiber shortening and mean normalized posterior wall velocity should be included. There is a significant number of hemodialysis patients (7/37) with congestive cardiomyopathic features on the echocardiogram. Their clinical features are no different from the other patients in this study, except they have a significantly higher prevalence of uremic hyperparathyroidism. Our findings support that the existence of a specific uremic cardiomyopathy and uremic hyperparathyroidism may play an important role in the pathogenesis.
- Published
- 1985
37. Bone disease in analgesic nephropathy.
- Author
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Fassett RG, Lien JW, McClure J, and Mathew TH
- Subjects
- Alkaline Phosphatase blood, Bone Diseases enzymology, Bone Diseases physiopathology, Bone and Bones analysis, Female, Humans, Kidney Diseases chemically induced, Kidney Failure, Chronic chemically induced, Male, Osteomalacia etiology, Analgesics adverse effects, Bone Diseases etiology, Kidney Diseases complications, Kidney Failure, Chronic complications
- Abstract
Clinical, biochemical, radiological and bone biopsy findings were studied in 15 patients with end stage renal disease due to analgesic nephropathy and compared with data from age and sex matched controls who had end stage renal disease from other causes. Patients with analgesic nephropathy had significantly higher osteoid volume (P less than 0.04), reduced calcification fronts (P less than 0.001) and lower percentage mineralization (P less than 0.04). Serum alkaline phosphatase was significantly higher in the analgesic group (P less than 0.005). It is concluded that osteomalacia is more common and severe in the group of patients with end stage renal disease due to analgesic nephropathy. There was no relationship between osteomalacia and the duration of renal failure, acidosis, aluminium deposition or other serum biochemical abnormalities.
- Published
- 1982
38. Detection of glomerular bleeding by phase-contrast microscopy.
- Author
-
Fassett RG, Horgan BA, and Mathew TH
- Subjects
- Erythrocytes pathology, Glomerulonephritis complications, Hematuria etiology, Humans, Kidney Calculi complications, Microscopy, Phase-Contrast, Urine cytology, Hematuria diagnosis, Kidney Glomerulus
- Abstract
Midstream urine specimens from 303 consecutive patients with haematuria were examined with phase-contrast microscopy to determine whether the source of the haematuria could be predicted on the basis of urinary red-cell morphology. In 253 patients a definite diagnosis was made but the data for the other 50 were inadequate to allow a definite diagnosis. With phase-contrast microscopy the origin of haematuria was considered to be glomerular in 120 patients (115 had proven glomerulonephritis and 5 had lesions of the lower urinary tract) and non-glomerular in 105 patients (100 had lesions of the lower urinary tract and 5 had proven glomerulonephritis). A mixed picture of glomerular and non-glomerular red cells was seen in 28 patients, most commonly in association with IgA nephropathy and renal calculi. The assessment of urinary red-cell morphology by means of phase-contrast microscopy can add importantly to clinical information and, together with the presence of red-cell casts and protein in the urine, can help the clinician decide on initial investigations in patients with haematuria.
- Published
- 1982
- Full Text
- View/download PDF
39. Scanning electron microscopy of glomerular and non glomerular red blood cells.
- Author
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Fassett RG, Horgan B, Gove D, and Mathew TH
- Subjects
- Analgesics adverse effects, Carcinoma, Transitional Cell urine, Humans, Kidney Calculi urine, Kidney Diseases chemically induced, Kidney Neoplasms urine, Microscopy, Electron, Scanning, Erythrocytes, Abnormal ultrastructure, Glomerulonephritis urine, Hematuria blood
- Abstract
Phase contrast microscopic examination of the urine has been recently shown to be of value in predicting whether hematuria is due to glomerulonephritis or lesions of the lower urinary tract. Glomerular red cells show variations in size and shape and have distorted surfaces. Non glomerular red cells are uniform in size and shape and have smooth surfaces. Scanning electron microscopy was performed on urine sediment containing either glomerular or non glomerular red cells to better define their surface characteristics. Glomerular red cells exhibited a variety of forms, most cells having lumpy projections from the surface, some showing fragmentation of the membrane and others showing gross distortion. In contrast non glomerular red cells show smooth surfaces and usually maintain the normal biconcave disc shape of peripheral red blood cells. Scanning electron microscopy can better define surface structural abnormalities of urinary glomerular and non glomerular red blood cells.
- Published
- 1983
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