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Biomedical subjects

I C Macdougall

Publications and source records attributed to I C Macdougall.

At least 55 records · Page 3Linked to original sources

Technetium-99m methoxy isobutyl isonitrile (MIBI) imaging of the parathyroid glands in patients with renal failure.

BACKGROUND: Technetium-99m methoxy isobutyl isonitrile (Tc-99m MIBI) scintigraphy has been reported to be at least as reliable as thallium-technetium subtraction imaging in the preoperative localization of hyperplastic parathyroid glands in patients with renal failure. Reports have suggested that 50% of glands can be identified correctly by this method. The aim of this study was to improve on previous results and demonstrate that Tc-99m MIBI imaging has an important place in the preoperative work-up of these patients. METHODS: Eighteen patients on renal replacement therapy were studied. All had tertiary hyperparathyroidism and had Tc-99m MIBI imaging prior to parathyroidectomy. A refined reporting method was employed. The imaging results were compared to the subsequent surgical and histological findings. RESULTS: In the 12 patients in whom serum parathyroid hormone levels fell postoperatively to within or below the normal range, 38 of 46 glands (82.6%) were correctly identified and located in the correct quadrant of the thyroid gland. There were two false positive results where the imaging predicted glands not subsequently found by the surgeon. In the patients who had post-operative hyperparathyroidism, repeat Tc-99m MIBI imaging was able to locate accurately the site of the residual parathyroid tissue. CONCLUSIONS: Tc-99m MIBI imaging is able to identify more than 80% of hyperplastic parathyroid glands in renal failure patients if this reporting process is used, and locate them in the correct quadrant of the thyroid gland. Tc-99m MIBI imaging is of particular value when re-exploration of the neck is required for post-parathyroidectomy hyperparathyroidism. These results represent a significant improvement on the sensitivity of this imaging technique when compared to previous published data.

Adult↗

Management of iron deficiency in renal anemia: guidelines for the optimal therapeutic approach in erythropoietin-treated patients.

Much progress has been made in recent years in the management of anemia associated with chronic and renal failure with recombinant human erythropoietin (r-Hu EPO). However, there remains much debate surrounding the diagnosis and treatment of iron deficiency. To ensure that full benefit from erythropoietin therapy is received, most patients require iron supplement during treatment. There are, however, few guidelines for the use of iron therapy. Iron deficiency results in an inadequate response to r-Hu EPO and is the main cause of resistance to this treatment. Oral iron therapy is of limited value in patients receiving r-Hu EPO. Thus, intravenous iron supplementation should be administered only in patients who do not tolerate available intravenous iron preparations or who are on continuous ambulatory peritoneal dialysis with no evidence of functional iron deficiency. This article provides guidelines for the diagnosis of absolute or functional iron deficiency in patients with renal anemia and suggests treatment schedules for intravenous iron supplementation. We hope that all dialysis patients will be able on this basis to achieve a satisfactory iron status and benefit fully from r-Hu EPO therapy.

Anemia↗

Serum C-reactive protein as a marker for infection and inflammation in regular dialysis patients.

Serum C-reactive protein (CRP) concentration was measured in 98 hemodialysis (HD) patients and 68 continuous ambulatory peritoneal dialysis patients (CAPD). The effect, if any, of a HD session on serum CRP level and the usefulness of CRP in diagnosing and monitoring proven inflammatory disease were studied. Seventy-five percent of CAPD patients without evidence of inflammation had CRP levels within the quoted normal range (< 10 mg/l), as compared with only 47% of HD patients also without evidence of overt inflammation (p < 0.001). No significant change in the CRP level was detected during a hemodialysis session. Twenty-four patients with overt inflammation (due mainly to infection) were studied, 22 of whom had CRP levels of > 50 mg/l. These increased CRP levels fell with treatment. A CRP level of > 50 mg/l proved highly suggestive of a significant inflammatory process and a value of < 10 mg/l always excluded it. The total period of time on the regular dialysis program was not related to the CRP level. A subclinical inflammatory response resulting in a raised CRP is very common in our hemodialysis patients and less so in CAPD patients. Possible reasons for this are discussed. However, CRP is still useful in the diagnosis and monitoring of response to treatment of inflammatory disease if the level is > 50 mg/l or serial/baseline measurements are available for comparison. Whether any relationship exists between elevation of CRP and the well-documented increased risk of cardiovascular death in dialysis patients is currently unknown.

Adolescent↗

A randomized controlled study of iron supplementation in patients treated with erythropoietin.

In view of current uncertainty regarding the optimum route for iron supplementation in patients receiving recombinant human erythropoietin (EPO), a prospective randomized controlled study was designed to investigate this issue. All iron-replete renal failure patients commencing EPO who had a hemoglobin concentration < 8.5 g/dl and an initial serum ferritin level of 100 to 800 micrograms/liter were randomized into three groups with different iron supplementation: Group 1, i.v. iron dextran 5 ml every 2 weeks; Group 2, oral ferrous sulphate 200 mg tds; Group 3, no iron. All patients were treated with 25 U/kg of EPO thrice weekly subcutaneously. The hemoglobin concentration, reticulocyte count, serum ferritin, transferrin saturation, and EPO dose were monitored every two weeks for the first four months. Thirty-seven patients entered the study (12 i.v., 13 oral, 12 no iron). The three groups were equivalent with regard to age, sex, and other demographic details. Even allowing for dosage adjustments, the hemoglobin response in the group receiving i.v. iron (7.3 +/- 0.8 to 11.9 +/- 1.2 g/dl) was significantly greater than that for the other two groups (7.2 +/- 1.1 to 10.2 +/- 1.4 g/dl and 7.3 +/- 0.8 to 9.9 +/- 1.6 g/dl for Groups 2 and 3, respectively; P < 0.005 for both groups vs. Group 1 at 16 weeks). There was no difference between the groups supplemented with oral iron and no iron. Serum ferritin levels remained constant in those receiving i.v. iron (345 +/- 273 to 359 +/- 140 micrograms/liter), in contrast to the other two groups in which ferritin levels fell significantly (309 +/- 218 to 116 +/- 87 micrograms/liter and 458 +/- 206 to 131 +/- 121 micrograms/liter for Groups 2 and 3, respectively; P < 0.0005 for Group 1 vs. Group 2, and P < 0.005 for Group 1 vs. Group 3 at 16 weeks). Dosage requirements of EPO were less in Group 1 (1202 +/- 229 U/kg/16 weeks) than in Group 2 (1294 +/- 314 U/kg/16 weeks) or Group 3 (1475 +/- 311 U/kg/16 weeks; P < 0.05 vs. Group 1). The results of this study suggest that, even in iron-replete patients, those supplemented with i.v. iron have an enhanced hemoglobin response to EPO with better maintenance of iron stores and lower dosage requirements of EPO, compared with those patients receiving oral iron and no iron supplementation.

Cost-Benefit Analysis↗

How to get the best out of r-HuEPO.

Recombinant human erythropoietin (r-HuEPO) therapy is expensive, and it is therefore important to optimize its use to satisfy the health economist as well as the prescriber. Five main issues can be considered in helping to achieve this goal: (i) Route and site of administration. Much evidence suggests that subcutaneous (s.c.) administration of r-HuEPO is more cost-effective than intravenous (i.v.) administration, i.e. lower s.c. doses may be used to achieve the same effect. There are, however, some studies which suggest that there is little to choose between the two routes. One pharmacokinetic study in normal volunteers found that s.c. injection of r-HuEPO into the thigh resulted in greater peak values and greater bioavailability than s.c. injection into the arm or abdomen. (ii) Frequency of injection. There are now reports of dialysis patients being variously treated with once-weekly, twice-weekly, thrice-weekly, and once-daily s.c. administration of r-HuEPO. Despite some comparative studies, the optimum dosing frequency for s.c. r-HuEPO remains unclear. (iii) Iron status. Failure of an adequate supply of iron to the erythron is probably the most common and most easily treated cause of sub-optimal response to r-HuEPO. Effective and regular monitoring of iron status by measurement of serum ferritin, transferrin saturation, and per cent hypochromic red cells is critical to the management of the patient receiving r-HuEPO, and there is increasing evidence that liberal use of i.v. iron may enhance the response to this treatment. (iv) Other factors affecting response to r-HuEPO.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Identification of auto-transplanted parathyroid tissue by Tc-99m methoxy isobutyl isonitrile scintigraphy.

Parathyroid tissue is sometimes auto-transplanted into the forearm after 'total' parathyroidectomy in patients with renal failure. Recurrent hyperparathyroidism demands identification of the source of PTH secretion which cannot be assumed to be the forearm. To this end, Tc-99m methoxy isobutyl isonitrile (MIBI) scintigraphy was used to identify functioning auto-transplanted parathyroid tissue in seven patients undergoing renal replacement therapy (five with functioning renal transplants and two on haemodialysis). Serum PTH was estimated in venous blood taken proximal and distal to the forearm graft and from the contralateral arm, and subsequent Tc-99m MIBI scanning was carried out without knowledge of the PTH results. Five patients had a significant gradient in PTH levels between sites proximal and distal to the graft, and between the proximal site and the contralateral arm, suggesting functioning parathyroid tissue in the graft. Subsequent Tc-99m MIBI scintigraphy confirmed the activity of the auto-transplanted parathyroid tissue in these five patients. In the remaining two patients without a significant PTH gradient between the sampling sites, Tc-99m MIBI scintigraphy did not identify any functioning forearm parathyroid tissue. The scan results therefore correlated well with the gradients in PTH levels, suggesting that MIBI scintigraphy can be used to identify functioning auto-transplanted parathyroid tissue. The results also indicate that any patient who has undergone auto-transplantation of parathyroid tissue must have blood samples taken from veins proximal to the graft and either distal to it, or from the contralateral arm when parathyroid status is re-assessed, particularly when surgery is being considered for recurrent hyperparathyroidism.

Adult↗

Monitoring of iron status and iron supplementation in patients treated with erythropoietin.

Patients receiving erythropoietin therapy require large quantities of iron to keep pace with the demands of the bone marrow during active erythropoiesis. If this iron supply to the marrow is not maintained, the response to erythropoietin is impaired, and indeed iron insufficiency is the most common cause of a poor response to this drug. Iron deficiency may be either absolute, which is defined as a reduction in total body iron stores, or functional, which implies adequate iron stores but a failure to supply available iron to the marrow or a failure in the utilization of this iron in the process of erythropoiesis. The detection of absolute or functional iron deficiency is difficult because there is no absolutely reliable marker of iron status, with the exception of an unequivocally low serum ferritin level. Measurement of serum ferritin and transferrin saturation are the most widely used methods, but both have drawbacks. Monitoring of the percentage of hypochromic erythrocytes in the circulation also seems promising, but the technology is of limited availability, and other methods (eg, monitoring erythrocyte ferritin, free erythrocyte protoporphyrin, and erythrocyte zinc protoporphyrin levels) lack widespread validation. Treatment of iron insufficiency is accomplished by intensifying iron supplementation either orally or intravenously, and in many instances the latter route becomes necessary. The high cost of erythropoietin demands that iron deficiency be screened for on a regular basis and treated to maximize the benefits of this drug.

Anemia, Iron-Deficiency↗

Effects of the correction of renal anaemia by erythropoietin on physiological changes during exercise.

The effects of treating the anaemia of end-stage renal failure with erythropoietin were studied in nine dialysis patients. The increase in haemoglobin concentration (by 59% from 7.0 +/- 1.2 to 11.1 +/- 1.1 g dl-1) was associated with increases in exercise duration (by 41%) and maximum oxygen consumption (by 34%). Treatment reduced resting heart rate but did not significantly alter heart rate at maximum exercise, nor resting or exercise blood pressure. Resting arterial potassium concentrations were slightly increased after treatment, but they increased similarly in relation to minute ventilation during exercise. Lactic acidaemia developed during exercise at both levels of haemoglobin, and was accompanied by similar reductions in arterial pH and bicarbonate levels but constant PaO2 and PaCO2. Ventilation was coupled to the metabolic rate of carbon dioxide production, ventilatory dead-space and arterial PCO2 before and after treatment of anaemia, the ventilatory requirement for carbon dioxide elimination being unchanged. Treatment of anaemia did not alter resting arterial lactate concentration; the concentration of lactate at maximum exercise was increased slightly following treatment but this increase did not reach statistical significance. The rate of increase in arterial lactate concentration as a function of oxygen consumption, assessed both with respect to the 'lactate threshold' and 'lactate slope index', was significantly delayed by treatment. Treatment of anaemia also delayed the 'anaerobic threshold', and there was good correlation between lactate and anaerobic thresholds. Treatment of renal anaemia by erythropoietin thus results in improved tissue oxygen supply during exercise, reflected by delay in the onset of lactic acidaemia.

Adolescent↗

Treatment of renal anemia with recombinant human erythropoietin.

It has been 6 years since the first reports of the use of recombinant human erythropoietin for the treatment of renal anemia appeared in the medical literature. During this period, erythropoietin has become established as a safe and highly effective therapy, and it is currently being evaluated for other nonrenal types of anemia. The initial clinical trials were in hemodialysis patients, followed by patients receiving continuous ambulatory peritoneal dialysis, and its use in predialysis and renal transplant patients is increasing. Various treatment schedules have been tried and compared; there are now reports of dosage frequencies varying from once daily to once weekly. Information has accumulated on the secondary effects of correction of renal anemia, particularly in relation to quality of life, exercise capacity, and cardiac function. Large multicenter trials have documented the safety profile of erythropoietin, whereas smaller studies have sought to elucidate the pathophysiology of its side effects, eg, hypertension and thrombotic events. This article reviews the latest developments in the use of erythropoietin in renal failure, concentrating particularly on those that have been published within the past year. Although there have been exciting advances in our understanding of the physiology and molecular biology of erythropoietin, these are amply described elsewhere and are beyond the scope of the present review.

Anemia↗