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Biomedical subjects

I C Macdougall

Publications and source records attributed to I C Macdougall.

At least 73 records · Page 4Linked to original sources
PubMed1992

The ventilatory cost of exercise compared in chronic heart failure and chronic renal anaemia.

The cardiorespiratory responses to maximal treadmill exercise were compared in matched groups of patients with chronic renal anaemia or treated chronic heart failure, and in normal controls. Exercise capacity was similarly reduced in both patient groups compared to normal controls, the raised respiratory exchange ratio at peak exercise implying anaerobic metabolism due to limited oxygen delivery in heart failure and limited oxygen carrying capacity in anaemia. Minute ventilation (VE) was related linearly to minute CO2 production (VCO2) in all subjects (each r > 0.92) from all three groups. The slope of the VE/VCO2 relationship was normal in anaemia but steeper in heart failure, reflecting ventilation/perfusion mismatching in chronic heart failure.

Adolescent↗
PubMed1991

Experience with a new method for percutaneous renal biopsy.

Between January 1989 and August 1990 a new technique for percutaneous renal biopsy was evaluated in all patients undergoing native kidney biopsy in our hospital. The method combines the use of an automated biopsy device, disposable biopsy needles, and a needle guide attached to an ultrasound probe. This allows real-time ultrasound scanning throughout the procedure. All biopsies were performed by trainee nephrologists. The success of the technique was evaluated by analysis of histopathological data, and the complications of the procedure from case-notes and nursing records. During the study 192 biopsies were attempted, of which 188 (97.8%) were successful. For each biopsy a mean of 2.8 needle passes were required and 75% of these obtained cores of tissue. An average of 25 glomeruli (range 1-90) were seen per biopsy. Although microscopic haematuria was almost invariable, there were no episodes of frank haematuria and no blood transfusion or surgical intervention was required. The new method is simple, providing accurate localisation of the kidney coupled with direct visualisation of the biopsy, and results in a very high success rate. Intrarenal needle dwell time is kept to a minimum and there were only minor complications. This technique deserves more widespread use.

Adult↗
PubMed1991

Coagulation studies and fistula blood flow during erythropoietin therapy in haemodialysis patients.

An increased incidence of fistula thrombosis has been reported in haemodialysis patients treated with recombinant human erythropoietin (rHuEpo). The present study sought to investigate this problem by measuring fistula blood flow, blood viscosity, and a variety of tests of coagulation and haemostasis in a group of ten haemodialysis patients treated with rHuEpo. Fistula blood flow did not alter during the first 12 months of rHuEpo despite a significant increase in whole-blood viscosity. Bleeding time improved in all ten patients after 4 months of therapy, and this improvement was maintained at 12 months. There were no significant changes in one-stage prothrombin time, kaolin cephalin clotting time, whole-blood clotting time, prothrombin consumption index, plasma fibrinogen factor VII, factor VIII, antithrombin III, or platelet aggregability to ADP over the first 4 months of rHuEpo. In contrast, protein C decreased from 84.3 to 66.4% (P less than 0.01) and protein S from 124.1 to 68.3% (P less than 0.001) over the first 4 months. By 8 and 12 months, the concentrations of these substances had returned to pretreatment values. The levels of protein C and S attained at 4 months are known to predispose to thrombosis, and it is possible that this effect may contribute to the increased incidence of fistula thrombosis observed in haemodialysis patients treated with rHuEpo.

Adult↗
PubMed1991

Rheological studies during treatment of renal anaemia with recombinant human erythropoietin.

Whole blood, plasma, and serum viscosity together with red cell deformability were measured before and during treatment of renal anaemia with recombinant human erythropoietin (EPO). Whole blood viscosity (WBV) progressively increased during the first 4 months of treatment in association with the rise in haemoglobin concentration. When the WBV was corrected to a standard haemoglobin concentration no change in blood viscosity was observed, neither was there any alteration in a derived index of red cell deformability, or in the plasma and serum viscosities. In addition, a direct measurement of red cell deformability using a filtration technique before EPO therapy was similar to that obtained in 30 healthy volunteers. There was no significant change in this parameter over the first 9 months of treatment. The rheological changes which occur with correction of anaemia with EPO can be explained solely by the increase in circulating haemoglobin mass rather than to any change in the properties of the plasma or red cells themselves.

Adult↗
PubMed1991

The use of erythropoietin in renal failure.

The treatment of renal anaemia by recombinant human erythropoietin (EPO) is now well established. Several studies have examined the pharmacokinetics and efficacy of the drug given intravenously, intraperitoneally and subcutaneously and there is increasing evidence that the subcutaneous route has several advantages including the requirement for a lower dose. It is also important to stress the need for careful determination of baseline iron status of all patients before commencing EPO therapy. In the long term the extremely high iron stores of transfusion dependent patients will disappear. In the short term, however, the majority of the patients whose serum ferritin is less than 100 micrograms/l will require iron supplementation to allow an appropriate haemoglobin response. Alternatively, a fall in transferrin saturation to less than 20% is certainly an indication for iron supplementation and if oral iron therapy is not adequate then intravenous preparations may have to be considered. Although the anaemia of renal failure can be fully corrected by EPO, partial correction may be sufficient to reverse the problems of reduced exercise capacity, myocardial ischaemia and cardiomegaly which are frequently associated with end-stage renal disease. Partial correction will also result in a lesser rise in whole blood viscosity and, in turn, possibly reduce hypertension, thrombosis and increased peripheral resistance and thus lessen the side effects of EPO therapy.

Anemia, Hypochromic↗
PubMed1991

Clinical pharmacokinetics of epoetin (recombinant human erythropoietin).

Epoetin (recombinant human erythropoietin, EPO) is of proven benefit in the treatment of renal anaemia, and preliminary reports suggest that it may have a role in the management of other anaemic conditions. Pharmacokinetic and therapeutic studies have examined the use of epoetin administered intravenously, intraperitoneally and subcutaneously, and there is accumulating evidence that the last route has several advantages. After intravenous administration, epoetin is distributed in a volume comparable to the plasma volume, and plasma concentrations decay monoexponentially with a half-life of between 4 and 12 hours. Administration of epoetin in peritoneal dialysis fluid results in detectable concentrations in the bloodstream after 1 to 2 hours, and peak concentrations of the order of 2 to 4% of those obtained with the same intravenous dose are found after approximately 12 hours. The bioavailability of epoetin administered intraperitoneally in dialysis fluid is about 3 to 8%, but this may be increased by injecting the drug into a dry peritoneal cavity. Subcutaneous administration results in peak concentrations at about 18 hours which are 5 to 10% of those found after the same intravenous dose. The bioavailability of subcutaneous epoetin is about 20 to 30% and detectable serum concentrations are still present 4 days after administration, in contrast to intravenous administration after which concentrations have returned to baseline within 2 to 3 days. Remarkably little is known about the metabolic fate of either erythropoietin or epoetin. In addition, there is much controversy surrounding the relative roles of the kidney and liver in the catabolism of epoetin. About 3 to 10% of epoetin is excreted unchanged in the urine. In common with other glycoproteins, the carbohydrate residues which constitute 40% of its molecular size are essential for maintaining the stability of epoetin in circulation. Desialated epoetin, although biologically active in vitro, is cleared very rapidly from plasma with resultant loss of activity. Further work is required, however, in identifying the pathways of metabolism and elimination of this glycoprotein hormone.

Animals↗
PubMed1990

Treating renal anaemia with recombinant human erythropoietin: practical guidelines and a clinical algorithm.

Treatment with erythropoietin is highly effective and beneficial if given with care. In view of its cost, however, it is essential to exclude and treat other causes of anaemia before considering using this hormone. After treatment is started the important points for success are regular review of iron availability state combined with a slow correction of the anaemia. Failure of response requires a thorough search for a possible cause, which should be corrected before considering an increased dose of the hormone. Regular monitoring for potential complications, particularly a rise in blood pressure, is required.

Algorithms↗
PubMed1990

Long-term cardiorespiratory effects of amelioration of renal anaemia by erythropoietin.

The long-term cardiorespiratory effects of recombinant human erythropoietin treatment were investigated in ten haemodialysis patients by means of maximum exercise testing, lung function tests, echocardiography, chest X-ray, and rheological assessment over 12 months. There were significant rises in exercise time (mean [SD] 13.2 [5.5] to 20.0 [6.2] min), maximum oxygen consumption (19.1 [7.0] to 25.0 [6.7] ml.min-1.kg-1), and anaerobic threshold (11.7 [3.6] to 15.4 [4.8] ml.min-1.kg-1) after 2 months of erythropoietin treatment. The improvements were maintained but not augmented on repeat testing after 4, 8, and 12 months of therapy. Carbon monoxide transfer [corrected] rose from 15.5 (2.9) to 18.6 (3.7) ml.min-1.mm Hg-1. There was a substantial reduction in exercise-induced cardiac ischaemia (eight patients had significant ST segment depression before erythropoietin, only one after 2 months' treatment, and none after 12 months' treatment), despite a significant rise in whole blood viscosity. Left ventricular mass, as estimated by echocardiography, progressively decreased from 354 (169) g to 251 (95) g after 12 months' treatment, and four patients showed a reduction in cardiothoracic ratio on chest X-ray.

Adult↗
PubMed1990

The treatment of renal anaemia in CAPD patients with recombinant human erythropoietin.

Fifteen severely anaemic patients receiving CAPD were treated with subcutaneous recombinant human erythropoietin (Epo). Ten subjects had a good response with the haemoglobin concentration increasing from less than 8 g/dl to greater than 10 g/dl within 16 weeks. Four patients had a poor response, which was due to infection in two, myelofibrosis in one and unknown cause in another. Epo was ineffective in the remaining individual, probably due to the presence of occult metastatic carcinoma. Iron supplementation in the form of intravenous iron dextran was given to 12 patients when transferrin saturation decreased below 20%. There was a significant increase in red cell volume (P less than 0.005), with a decrease in plasma volume (P less than 0.005). Red cell iron turnover increased (P less than 0.05) but there was no change in red cell lifespan or deformability. Biochemical parameters remained unaltered, as did peritoneal function. Exercise duration improved (P less than 0.001), as did maximal oxygen consumption (P less than 0.01). Four patients required an increased dose of hypotensive drugs. Epo is a safe effective therapy for the anaemia of CAPD subjects.

Adult↗
PubMed1989

Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis.

To determine the optimum regimen for giving recombinant human erythropoietin (EPO) to patients on continuous ambulatory peritoneal dialysis (CAPD), the pharmacokinetics of single-dose EPO administered intravenously (120 U/kg), intraperitoneally (50,000 U), and subcutaneously (120 U/kg) was investigated. After intravenous administration serum EPO levels decayed exponentially from a peak of 3959 mU/ml, with a half-life of 8.2 h. 2.3% of the total intravenous dose was lost in the dialysate during the first 24 h. Peak serum EPO levels of 375 mU/ml at 12 h and 176 mU/ml at 18 h were attained following intraperitoneal and subcutaneous administration, respectively. The bioavailability of subcutaneous EPO (21.5%) was seven times greater than that of intraperitoneal EPO (2.9%). These results suggest that subcutaneous EPO represents the most satisfactory route of administration for CAPD patients.

Absorption↗
PubMed1988

Overnight clonidine suppression test in the diagnosis and exclusion of pheochromocytoma.

In a prospective study designed to differentiate pheochromocytoma from other forms of hypertension, urinary catecholamines were measured after sleep and clonidine administration in 12 patients with pheochromocytoma, 19 hypertensive patients in whom pheochromocytoma was suspected but later excluded, and 31 hypertensive patients in whom pheochromocytoma was never suspected. The test correctly identified all 12 patients in whom pheochromocytoma was present. Four of these had equivocal plasma levels of both norepinephrine and epinephrine, suggesting that overnight clonidine suppression may be of particular value when tumor secretion is intermittent or low. When pheochromocytoma was not present, urinary norepinephrine and epinephrine levels were suppressed below 60 and 20 nmol/mmol creatinine, respectively, after sleep and clonidine, the two in combination giving better suppression than sleep alone. Since urinary catecholamines can be determined relatively easily by high-pressure liquid chromatography with electrochemical detection, this test may be more widely applicable than suppression tests based on plasma measurements.

Adrenal Gland Neoplasms↗
PubMed1987

Fatal outcome following inhalation of Tipp-Ex.

Recent measures to combat glue sniffing have led to a decrease in the availability of toluene-based glues. As a result, abuse of other more accessible solvents appears to have increased. Of particular concern are the halogenated hydrocarbons which are more likely to cause fatal cardiac arrhythmias than toluene. We wish to report three cases presenting within a period of six months where death occurred following inhalation of Tipp-Ex, a seemingly innocuous preparation of 1,1,1-trichloroethane which is widely available in offices and schools.

Acute Disease↗