Search PubMedSearch

Biomedical subjects

W K Stewart

Publications and source records attributed to W K Stewart.

At least 19 recordsLinked to original sources

Effect of nifedipine on changes in fibrinogen and von Willebrand factor in haemodialysis patients treated with recombinant human erythropoietin.

Erythropoietin (EPO) therapy in haemodialysis patients may be associated with the development of hypertension and vascular access thrombosis. Raised levels of fibrinogen and von Willebrand factor have been implicated in the pathophysiology of thrombosis under these circumstances. The effect of nifedipine, used to treat EPO therapy-related hypertension, on levels of fibrinogen and von Willebrand factor antigen (vWf) was studied in a group of 21 EPO-treated haemodialysis patients. Significant increments in both fibrinogen and vWf following EPO therapy were observed in the 13 patients who did not receive nifedipine (fibrinogen (median range), pre-EPO: 3.73 (2.41-6.38) mg/ml, post-EPO: 4.59 (3.03-8.80) mg/ml, P < 0.05; vWf pre-EPO: 183 (118-374)% normal, post-EPO: 253 (124-392)% normal, P < 0.01). Similar changes were not seen in the eight nifedipine-treated patients (fibrinogen, pre-EPO: 3.35 (2.58-6.32) mg/ml, post-EPO: 3.36 (2.69-7.20) mg/ml, P = NS; vWf, pre-EPO: 176 (104-298)% normal, post-EPO: 175 (82-371)% normal, P = NS). These effects were independent of blood pressure control. The use of nifedipine to treat EPO therapy-related hypertension may therefore potentially help to reduce the risk of vascular access thrombosis.

Erythropoietin

Microbial growth and blockage of sub-floor drains in a renal dialysis centre: a problem highlighted.

The accumulation of microorganisms embedded in biofilm within the drainage pipework leading from individual dialysis monitors in a renal dialysis centre, represents a significant threat to the safe operation of the whole centre due to blockage of the pipes and overflow of waste water. Attempts to disperse the growth with chemicals and disinfectants have been unsuccessful. Only mechanical rodding has removed the deposit, and regrowth has occurred. Those planning new dialysis centres should ensure that effluent pipework is readily accessible with multiple rodding eyes and is made of material able to withstand rodding and chemicals.

Bacteria

Effect of dialyzer geometry during hemodialysis with cuprophane membranes.

The effect of dialyzer geometry, both flat plate (FP) and hollow fiber (HF), on platelet and granulocyte activation during dialysis with cuprophane membranes was studied in 12 patients. A subset of six patients was restudied after correction of their anemia with recombinant human erythropoietin (EPO). Granulocyte count and aggregation in vitro fell significantly (P less than 0.01) at 20 minutes of dialysis, followed by a gradual return towards pre-dialysis values at 240 minutes. Malondialdehyde (MDA), a product of free radical reactions generated by activated granulocytes, increased significantly during dialysis [predialysis MDA (median, range): 8.4 (5.8 to 11.6) nmol/ml, 240 minutes MDA: 9.7 (6.6 to 12.5) nmol/ml, P less than 0.01 Wilcoxon test). This increase, however, was not affected by dialyzer geometry or EPO therapy. Neither type of dialyzer was associated with significant platelet loss at the end of dialysis. Whole blood platelet aggregation in vitro (spontaneous and collagen-induced) decreased significantly, (P less than 0.01) during dialysis, the fall in spontaneous aggregation being significantly less following EPO therapy [spontaneous aggregation 240 minutes; pre-EPO: 34 (13 to 52)%; post-EPO 50: (16 to 76)%, P less than 0.01)]. The ratio of the platelet release proteins beta-thromboglobulin and platelet factor 4 increased significantly during dialysis, indicating platelet activation in vivo, although there was no effect of dialyzer geometry or EPO. Factor VIII von Willebrand Factor antigen, a putative marker of endothelial damage, was raised pre-dialysis, and increased further during dialysis, irrespective of dialyzer geometry or EPO. In conclusion, dialyzer geometry had no significant effect on granulocyte and platelet counts and activity during hemodialysis with cuprophane membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Prothrombotic effect of erythropoietin in dialysis patients.

Thrombin-antithrombin III complex concentrations (TAT-III) were measured in 18 anaemic haemodialysis patients treated with erythropoietin (Epo) and in four haemodialysis patients treated with i.v. iron dextran. There was a significant early increase in thrombin-antithrombin III in erythropoietin-treated patients which appeared to be independent of the response to erythropoietin (Epo responders (n = 14), pretreatment TAT-III median (range) 3.10 (2.70-9.10) micrograms/l; maximum TAT-III 19.48 (11.18-60.00) micrograms/l, P less than 0.001, Wilcoxon; Epo non-responders (n = 4), pretreatment TAT-III 3.15 (2.90-4.50) micrograms/l, maximum TAT-III 16.00 (10.31-36.12) micrograms/l, P less than 0.001). This was not seen in iron-dextran-treated patients (Pretreatment TAT-III 2.05 (1.90-9.48) micrograms/l, maximum TAT-III 5.60 (2.10-14.50) micrograms/l). The change was not related to haemoglobin, erythropoietin dose, or method of administration, and was transient in nature, thrombin-antithrombin III returning to pretreatment values after approximately 6 months in all patients (Epo responders 6.0(4.0-9.0) months, TAT-III 2.47 (1.30-9.23) micrograms/l; Epo non-responders 7.0 months, TAT-III 5.04 (2.10-7.00) micrograms/l). Increased thrombin-antithrombin III complex may reflect an effect of erythropoietin on microcirculatory factors, which could be relevant to the occurrence of adverse events during treatment.

Adult

Atrial natriuretic factor improves renal function and lowers systolic blood pressure in renal allograft recipients treated with cyclosporin A.

OBJECTIVE: Atrial natriuretic factor (ANF) has several properties which suggest that it may ameliorate cyclosporin A nephrotoxicity. We therefore investigated the response to a pharmacological dose of ANF in renal transplant recipients treated with cyclosporin A. DESIGN: A single-blind randomized crossover design comparing the renal and haemodynamic effects of D-glucose (placebo) with ANF. METHODS: Seven patients with stable renal function following renal transplantation were studied under maximal water diuresis. Glomerular filtration rate and effective renal plasma flow were estimated from clearances of inulin and para-aminohippurate, respectively. RESULTS: Plasma ANF levels increased significantly in association with increased diuresis and natriuresis. Glomerular filtration rate was unchanged after placebo but increased significantly after ANF fusion. Likewise, effective renal plasma flow increased significantly with ANF infusion. There was a significant fall in systolic blood pressure, with no apparent change in heart rate and diastolic blood pressure. CONCLUSIONS: These results suggest that ANF may have beneficial effects in protecting against cyclosporin A-induced nephrotoxicity and hypertension.

Atrial Natriuretic Factor

Urine transparency as an index of absence of infection.

A visual assessment of the clarity of urine was used as an exclusion test to indicate the absence of infection; verified by dipslide culture, it was applied to 363 urine samples collected from patients attending 2 adult nephrology clinics over a period of 6 months. The crimped aluminium bowl used for collection of samples assisted the assessment of clarity. The sensitivity of the method compared with dipslide culture was 73%, with specificity and efficiecy both 58%. The predictive value of a negative test (clarity) was 97% with a false negative rate of 3%, enabling this simple examination to be used as an exclusion test for further testing. In simple terms, a clear urine is unlikely to be infected. It is also an advantage to have an immediate indicator of the absence of infection available at the clinic. Analysis of only those urines assessed as cloudy could result in financial savings and, from the clinics, a 56% reduction in workload.

Adolescent

Parathyroidectomy in uraemic hyperparathyroidism: a clinical study.

Osteodystrophy is a common and sometimes debilitating complication of renal failure. Hyperparathyroidism plays a crucial role in the development of this condition. Significant morbidity is also incurred by the effects of calcium deposition in other tissues. We report a series of 27 patients undergoing parathyroidectomy between May 1988 and November 1989. All had biochemical, radiological and clinical evidence of hyperparathyroidism. Surgery was well tolerated leading to an improved quality of life and avoidance of the need for aluminium containing phosphate binders.

Adolescent

Evaluation of a nisin-based germicidal formulation on teat skin of live cows.

A purified preparation of the nontoxic antimicrobial peptide, nisin (AMBICIN N), was used in the formulation of a germicidal sanitizer suitable for use on cow teats. The germicidal activity of the formulation against mastitis pathogens was measured on teat skin of live cows. The nisin-based formulation gave a mean log reduction of 3.90 against Staphylococcus aureus and 4.22 log reduction against Escherichia coli after exposure for 1 min to the germicide. This activity was comparable with that exhibited by a 1% iodophor teat dip but was significantly greater than that exhibited by the .1 and .5% iodophors and by the .5% chlorhexidine digluconate teat dips. The nisin-based formulation showed little or no potential for skin irritation after multiple application to skin, but iodophor and chlorhexidine digluconate teat dips showed significant potential for skin irritation in comparable studies.

Animals

Dextran antibodies, complement conversion and circulating immune complexes after intravenous iron dextran therapy in dialysed patients.

Serum immune complexes, plasma dextran antibodies and percentage conversion of complement have been measured in 20 dialysed patients before and after an intravenous infusion of iron dextran providing 600 mg elemental iron. Complement conversion was unmeasurable and there were no changes in circulating immune complexes. The presence of dextran antibodies in nine patients before the infusion was not related to prior exposure to iron dextran. They became undetectable in these patients within hours after the infusion, reappearing 1 month later in three. Two of three patients reporting mild aches and shivers on the day following the infusion had no detectable dextran antibodies. An adverse reaction involving inflamed joints occurred 1-2 days after a second infusion given to one of the patients studied above. The parameters under study were again measured and did not appear to relate to the reaction. The presence of dextran antibodies does not preclude the giving of iron dextran to patients on dialysis, and the immune complex and complement systems remain undisturbed by iron dextran infusions.

Adolescent

Dialysis efficiency in continuous ambulatory peritoneal dialysis patients treated with erythropoietin.

OBJECTIVE: To determine the effect of subcutaneous erythropoietin treatment on dialysis efficiency in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Dialysis efficiency, platelet and white cell aggregation, and red cell deformability were measured monthly for six months in nine anaemic CAPD patients treated with erythropoietin, and on a single occasion in seven control CAPD patients with intrinsically high haemoglobin concentrations. SETTING: Renal dialysis unit. PATIENTS: Nine patients stable on CAPD for a minimum of six months and with haemoglobin concentrations less than 8.5 g/dl were treated with erythropoietin. Seven CAPD patients matched for age and renal function, with haemoglobins greater than 9.0 g/dl served as controls. RESULTS: Daily peritoneal clearances and net ultrafiltration volumes were unchanged when haematocrit increased from 25.0 +/- 2.2% to 36.5 +/- 3.5%. Spontaneous whole blood platelet aggregation was significantly increased from week twelve (pre-treatment aggregation 46 +/- 23%; 12 weeks: 67 +/- 19%, p less than 0.05; 16 weeks: 64 +/- 19%, p less than 0.01; 20 weeks: 71 +/- 16%, p less than 0.01; 24 weeks: 73 +/- 10%, p less than 0.01). CONCLUSIONS: The increase in haematocrit and platelet aggregation associated with erythropoietin treatment did not affect peritoneal clearances or ultrafiltration capacity.

Anemia

Lipid peroxidation and antioxidants in continuous ambulatory dialysis patients.

OBJECTIVE: Oxidative cell damage due to the production of free radical species has been implicated in the pathogenesis of cardiovascular disease for which dialysis patients are at increased risk. Plasma lipid peroxides (malon-dialdehyde), the antioxidants plasma albumin thiol, and red cell superoxide dismutase (SOD) were therefore measured in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 20 hemodialysis patients, and 30 normal controls. SETTING: Renal dialysis unit. RESULTS: Malondialdehyde (MDA) concentrations were significantly higher in dialysis patients compared to controls (p less than 0.001) and were significantly higher in CAPD patients compared to hemodialysis patients, p less than 0.001 (CAPD, median and range: 11.25 (8.4-15.5) nmol/mL; hemodialysis: 8.75 (7.0-12.6) nmol/mL; controls: 6.65 (5.2-9.6) nmol/mL). Plasma thiol and red cell SOD were significantly lower in dialysis patients compared to controls, but there was no significant difference between CAPD and hemodialysis patients (CAPD thiol: 333.5 (282-480) mumol/L; hemodialysis thiol: 344 (203-468) mumol/L; control thiol: 421.5 (351-504) mumol/L; CAPD SOD: 78.2 (42.4-112.8) u/1/2 mL red cells; hemodialysis SOD: 89.4 (44.6-121.1) u/1/2 mL red cells; control SOD: 96.8 (66.8-153.4) u/1/2 mL red cells). Red cell SOD was significantly negatively correlated with duration of dialysis in CAPD patients (r = -0.683, p less than 0.01). CONCLUSION: In dialysis patients there is indirect evidence for increased free radical activity, which may be further influenced by the mode of dialysis.

Erythrocytes

Erythropoietin and spontaneous platelet aggregation in haemodialysis patients.

Erythropoietin significantly, reversibly, and reproducibly increased in-vitro whole-blood spontaneous platelet aggregation in 15 patients on haemodialysis. During erythropoietin treatment, spontaneous platelet aggregation was significantly higher in these subjects than in non-uraemic controls; concomitant treatment with 300 mg aspirin daily reversed platelet hyperaggregability. Erythropoietin may promote thrombosis by an effect on platelet function.

Anemia

Aluminium content of water for injection used with recombinant human erythropoietin.

Human recombinant erythropoietin is of proven value in the treatment of the anaemia of renal failure. The aluminium content of 36 ampoules of water for injection supplied for use with recombinant erythropoietin has been measured and ranged from 24 to 450 micrograms/l, with a median of 251 micrograms/l. In three samples, which may have been contaminated on opening, the range was from 1770 to 6160 micrograms/l. In Water for Injection BP, values ranged from 66 to 140 micrograms/l with a median of 99 micrograms/l. Reconstituted erythropoietin did not contain any more aluminium than could be accounted for by the water. Ampoules of a second brand of erythropoietin, supplied already in solution, contained from 506 to 837 micrograms/l aluminium (median 682 micrograms/l). In view of the lifelong duration of erythropoietin therapy clinicians and pharmaceutical companies should be aware of this potential problem. Although the amount of aluminium delivered with each injection is usually less than 4 micrograms, it is suggested that active steps are taken to establish a British Pharmacopoeia limit on the aluminium content of injections.

Aluminum

Whole blood granulocyte aggregation in vitro in dialysis-dependent patients.

Whole blood granulocyte aggregation in vitro was measured in 17 haemodialysis (HD) patients, 18 continuous ambulatory peritoneal dialysis (CAPD) patients, and 30 age-matched normal controls. Granulocyte aggregation was significantly increased in dialysis-dependent patients compared to controls (P less than 0.001) and was statistically significantly higher in CAPD patients compared to HD patients (P less than 0.01). [CAPD patients, median (range): 56.5 (44-71)%; HD patients: 53.0 (32-67)%; Controls; 42.5 (33-56)%.] Since granulocyte hyperaggregability has been linked with the pathogenesis of ischaemic vascular disease, abnormal granulocyte activity in dialysis-dependent patients may be of many factors contributing to their increased cardiovascular morbidity.

Adult