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ABSTRACT: To define the effect of intravenous recombinant human erythropoietin (rHuEPO) in patients with anaemia caused by chronic renal failure. Data collection included bone marrow response, ferrokinetics, red cell survival as well as the influence on red cell mass and plasma volume.
A convenience sample of stable individuals on haemodialysis, with haemoglobin (Hb) levels of less than 80 g/l, was surveyed over a 12-week period while they were receiving the hormone. Blood counts and iron studies were monitored serially, while 51Cr-labelled red cells and 59Fe (III) citrate were used in the radionuclide investigations carried out before and after the course of replacement therapy was completed (pre and post injection). Bone marrow aspiration and trephine biopsy were performed at each of these times.
The actual mean trial period was 14 weeks. Eight patients were enrolled but 1 was withdrawn after developing tuberculosis at the start of the study. Haemoglobin levels rose from 59 g/l (SD 8.8) to 96 g/l (SD 13.9) (P < 0.0001); mean red cell mass rose from 675 ml to 954 ml (P < 0.01). Concurrently, the serial studies in 6 patients showed prominent erythroid hyperplasia. Plasma iron turnover increased insignificantly from 42.5 to 118.9 mumol/l/day; erythron turnover increased from 42.5 to 87.3 mumol/l/day (P < 0.01). There was a marked shortening of the marrow transit time from 4.4 to 3.3 days (P < 0.03). Efficacy of erythropoiesis decreased from 1.17 to 0.65 (P < 0.05). Red cell survival was not altered.
The patient with end-stage renal failure remains fully responsive to erythropoietin therapy. This is reflected in improved ferrokinetics, red cell hyperplasia in the marrow and rise in haemoglobin level without alteration in mean erythrocyte lifespan. Simple hormonal replacement is therefore a rational approach to management.
South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde 09/1996; 86(8):952-5. · 2.04 Impact Factor
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ABSTRACT: Metal chelate ions are commonly used in medical diagnostic imaging as MRI contrast or imaging agents. The efficacy of these metals depends on their in vivo behavior, which in turn depends on their in vivo speciation.
A computer model has been used to simulate the speciation of Ga3+ and Gd3+ in blood plasma. The model has been tested against known clinical data and then used to investigate Ga3+ uptake by tumor cells. The iatrogenic effect of a gadopentetic acid enhanced MRI scan upon the biodistribution of 67Ga citrate has also been calculated.
The speciation of Ga3+ calculated using the computer model is concordant with clinical data. The results support transferrin mediated uptake of Ga3+ by tumor cells but also account for Ga(III) biodistribution observed in hypotransferrinemic subjects. In a study of the effect of gadopentetic acid upon 67Ga gallium citrate, neither residual DTPA nor [Gd(DTPA)]2- cause significant changes in the speciation of Ga(III). The calculations show that dissociation of 4% of the administered gadopentetic acid results in the formation of a mixed, Gd(III) and Ga(III), metal transferrin complex and a 100-fold increase in the concentration of [Ga(OH)4]-.
Computer simulation is a valuable tool which can be used to explain/understand in vivo behavior of radioactive metal ions.
Journal of Nuclear Medicine 03/1996; 37(2):379-86. · 6.38 Impact Factor
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ABSTRACT: Fe-52 scintigraphy was used to confirm extramedullary hematopoiesis in a patient with beta-thalassemia and intrathoracic masses. Imaging was performed on a standard gamma camera with a high-energy collimator. Tc-99m labeled tin colloid and In-111 chloride scintigraphy failed to reveal uptake by the masses. The exclusion of malignancy obviated the need for invasive diagnostic measures.
Clinical Nuclear Medicine 08/1995; 20(7):619-22. · 3.67 Impact Factor
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ABSTRACT: To investigate and compare the prevalence, associations, and severity of retinopathy and nephropathy in patients with pancreatic diabetes (PD) and insulin-dependent diabetes mellitus (IDDM).
Thirty patients with PD due to alcohol-induced chronic pancreatitis were matched for age, sex, and duration of diabetes with 30 patients with IDDM. Retinopathy was assessed by fluorescein angiography using the Wisconsin classification. Renal function was assessed by albumin excretion rates (AERs) in at least two timed overnight urine collections and glomerular filtration rates (GFRs) by single injection of 51Cr-EDTA. Microalbuminuria was defined as AER 20-200 micrograms/min and nephropathy as AER > 200 micrograms/min.
Retinopathy was found in 33% of patients with PD and in 40% with IDDM. The spectrum of disease was similar in the two groups. The geometric mean of AER was 15 micrograms/min (range 1-1,541) in the PD group and 24 micrograms/min (2-2,288) in the IDDM group. Nephropathy was found in 7 PD and in 5 IDDM patients, and a reduced GFR was present in 8 (26%) and 4 (13%) of the two groups, respectively. Microalbuminuria occurred in 9 (33%) and hyperfiltration in 3 (10%) in each group. These differences were insignificant. Retinopathy correlated with AER in both groups. Retinopathy and AER correlated with duration of diabetes in the IDDM but not in the PD group.
Microvascular complications are equally common and severe in PD and IDDM, and improved glycemic control should be the goal in both.
Diabetes Care 07/1995; 18(7):971-4. · 8.09 Impact Factor
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ABSTRACT: The synthesis and labelling of a new bis-amide-oxime ligand E,E-2,9-bis(hydroxyimino)-4,7-diaza 5,6-dioxodecane (AdO) with 99mTc has been achieved. Protein binding, partition coefficient and tissue distribution of this complex and two related bis-amine-oxime ligands is reported. The biodistribution of the complexes are disappointing with only limited brain and myocardial uptake. Structures for the complex are postulated.
Applied Radiation and Isotopes 06/1994; 45(5):581-6. · 1.17 Impact Factor
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ABSTRACT: Inadvertent hypothermia due to massive infusion of stored blood can be prevented by pretransfusion warming. One approach is the heating of individual packs by means of electromagnetic conduction, which is a method safely used over the last 25 years. The prototype instrument, which has now been re-engineered, can effectively raise the temperature of a unit of blood to approximately 33 degrees C in less than 3 minutes. Using this new model, we found, in vitro, a modest increase in free plasma haemoglobin, but this was not accompanied by any change in potassium or lactic dehydrogenase levels and the mean red cell fragility was unaltered. In vivo, the survival of autologous red cells that had been stored for 33 days and then infused as a concentrate, having a mean haematocrit of 0.60, was measured at 24 hours and 21 days. Each donor acted as his own control. In paired studies, pretransfusion radiofrequency heating was shown to have no deleterious effect when compared to measurements using the unwarmed blood pack. It is concluded that this method can be recommended as safe.
Journal of Clinical Apheresis 02/1992; 7(1):12-7. · 1.93 Impact Factor
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ABSTRACT: 1. Exercise-induced haemolysis has been implicated in the sub-optimal iron status of endurance-trained athletes. Accordingly, erythrocyte survival studies using 51Cr were performed on male and female distance runners (n = 20) and sedentary control subjects (n = 10) in order to determine whether the rate of erythrocyte destruction was altered as a consequence of repetitive exercise training. 2. The chromium half-disappearance time of the male (25.4 +/- 3.6 days, mean +/- SD) but not the female (28.3 +/- 4.6 days) athletes was significantly lower than that of the male (33.1 +/- 4.5 days) and female (32.3 +/- 2.6 days) control subjects (P less than 0.01). The mean erythrocyte lifespan of the male and female distance runners (67.2 +/- 22.2 and 72.4 +/- 26.0 days, respectively) was significantly shorter than that of the non-exercising male and female subjects (113.4 +/- 31.0 and 114.1 +/- 29.0 days, respectively) (P less than 0.01). 3. There was no correlation between the mean erythrocyte lifespan and the haemoglobin concentration, serum ferritin levels, body mass, weekly training distance, number of years running or daily protein intake. The mean cell volume and reticulocyte count measured in the same athletes before and after completing a standard 42 km marathon race were within the normal range, whereas the plasma haemoglobin levels were elevated (77.0 +/- 50.5 mg/l) and the serum haptoglobin levels were decreased (0.89 +/- 0.4 g/l) at rest, with a further significant decrease after running (0.69 +/- 0.4 g/l) in the latter measurement (P less than 0.05). 4. It is concluded that the demonstrated increase in erythrocyte turnover may be sufficient to precipitate an iron deficiency in endurance athletes when dietary intake or absorption does not meet the accelerated erythropoietic demands.
Clinical Science 09/1991; 81(2):147-52. · 4.61 Impact Factor
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ABSTRACT: The synthesis and T1 and T2 relaxivities of the Cr(III)-(NH2)-Sar-cage complex is reported. An outer-sphere relaxation mechanism is postulated for the relaxivity of the complex. Tissue distribution studies in mice using a [57Co]cobalt analogue as a radioactive tracer showed that the complex is excreted rapidly in the urine. Some renal uptake of the complex is seen. Appreciable uptake of labelled cage complex was observed in 3-methylcholanthrene induced murine rhabdomyosarcoma.
International Journal of Radiation Applications and Instrumentation Part B Nuclear Medicine and Biology 02/1991; 18(8):855-8.
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ABSTRACT: This case report describes 99mTc(V)-dimercaptosuccinic acid (DMSA) accumulation in a pheochromocytoma in a patient with Sipple's syndrome. Scintigraphy with 99mTc(V)-DMSA demonstrated uptake in medullary carcinoma of the thyroid gland (MCT). Iodine-131 metaiodobenzylguanidine (MIBG) scintigraphy showed the bilateral pheochromocytomas but did not demonstrate uptake in the MCT.
Journal of Nuclear Medicine 02/1990; 31(1):106-8. · 6.38 Impact Factor
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ABSTRACT: Conventional creatinine clearance studies in the pig are complicated by difficulties with catheterisation, infection, accurate collection and active creatinine renal tubular reabsorption. We compared a single injection, 99mTc-DTPA elimination method with creatinine clearance. Nineteen pairs of GFR estimations were performed in 10 pigs: 7 in normal pigs and 12 following bile duct ligation and/or nephrectomy. Red cell and plasma protein binding of the isotope and its hepatobiliary excretion was assessed. Absolute and weight normalised endogenous creatinine clearances correlated significantly with 99mTc-DTPA elimination. 99mTc-DTPA red cell binding and hepatobiliary excretion were negligible. Thus, 99mTc-DTPA elimination is a valid indicator of changes in renal function in grouped porcine studies, particularly in the biliary obstruction model. However, isotope plasma protein binding was high in the 2 normal pigs assessed. Individual accuracy would be improved by routine protein binding correction, unless consistently low for a particular preparation.
Urological Research 02/1988; 16(6):449-54. · 1.23 Impact Factor
