Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cerebral blood flow (CBF ml/100g/min) was measured by 133Xenon in 24 patients before and after haemodialysis (HD) and in 27 normal persons. A wide scatter of the absolute CBF values were observed to correlate with the haematocrit, whereas blood pressure, pCO2 and weight loss during HD did not. Before HD, when compared with the control group, the patients showed a distinct elevation of CBF due to the severe anaemia of this group. Though there was only a slight increase in haematocrit post-dialysis a return to normal of the post-dialysis CBF was observed. In order to achieve comparative data the CBF values were corrected mathematically to a normal haemoglobin (160g/L) and the adjusted mean pre-dialysis CBF value was within the normal range and decreased to the lowest limit of normal after HD. A significant decline in CBF was observed with increasing age and length of time on HD. When compared with normal the age-dependent decline was about twice as high and showed a 10-fold decrease with the time on HD treatment. When we grouped the patients with regard to the CBF values the following results were obtained: in eight patients CBF was elevated before HD and showed a return to normal after HD. These were younger patients with greater predialysis over-hydration and lower blood pressure. A distinctly reduced CBF was observed in nine patients and remained unchanged after HD. This group included older patients with a higher blood pressure. The reaction of CBF suggests three types of patients with different vascular reactivity to fluid excess: young normotensive patients with high vascular fluid storage capacity, patients with hypertensive vascular reactivity and patients with vascular damage.
Proc Eur Dial Transplant Assoc 1981
PMID:The effects of haemodialysis on cerebral blood flow. 732 59

The anaemia of chronic disease is the second most common anaemia in the world and is an underproduction anaemia with relatively low erythropoietin (EPO) values for the degree of the anaemia. This anaemia occurs with inflammation, infection, or malignancy and a principle question has been whether it would respond to recombinant human EPO (r-HuEPO). Several studies are now available to answer this question. In one study 12 of 16 patients with rheumatoid arthritis receiving r-HuEPO increased their haematocrits 6 percentage points or more and 11 of 12 reached normal haematocrits. Investigations of the effect of r-HuEPO on the anaemia of AIDS showed that patients with EPO levels of 500 U/L or less had an increase in the mean haematocrit of 4.6 percentage points with a decrease in red cell transfusions from 5.3 to 3.2 units per patient. Quality of life indices significantly improved in responders. When 413 patients with anaemia due to a wide variety of malignancies were randomized to r-HuEPO treatment, 58% of those receiving chemotherapy increased their haematocrits by at least 6 points over 12 weeks. Quality of life parameters of responders also significantly improved. Anaemia in three patients with inflammatory bowel disease also responded in 8-14 weeks to r-HuEPO and two of the three reached normal haemoglobin levels. It is clear that r-HuEPO can correct the anaemia of chronic disease and can improve the quality of life of responders.
Nephrol Dial Transplant 1995
PMID:Erythropoietin and the anaemia of chronic disease. 764

Erythropoietin (EPO) is the primary hormone responsible for the growth and maturation of red blood cells in mammals. In contrast to many other growth factors, the specificity of EPO for mature erythroid cells has lead to its development as a safe and efficacious therapeutic, EPREX. The medical benefits of EPREX have been well established in the treatment of anaemic chronic renal failure patients, anaemic HIV patients treated with AZT, cancer chemotherapy patients, and patients wishing to donate their own blood prior to elective surgery (autologous predonation). Due to the chronic nature of EPO therapy, it would be desirable to have an orally administered 'second generation' molecule. An understanding of the structural basis of the interaction of EPO with its receptor will aid in the design of an oral anaemia drug. In this study, a series of mutations have been generated in a truncated form of the receptor comprising the extracellular region, termed EPO binding protein (EBP). One mutant, in which alanine replaces phenylalanine at position 93 (F93A) has a 500-fold reduction in binding compared to wild-type EBP. A neutralizing anti-EBP antibody binds poorly to the F93A mutant, while a non-neutralizing anti-EBP antibody binds wild-type and F93A equally well. Information from this mutational analysis can be applied to a receptor 3-D model and ultimately used in drug development.
Nephrol Dial Transplant 1995
PMID:Erythropoietin receptor: application in drug development. 764 2

The success of maintenance haemodialysis in the 1960s was blighted by the problem of anaemia. Treatment with iron, folic acid, androgens and transfusions did no more than minimize its effects. The need for a renewable source of erythropoietin was appreciated very early but the hope took 25 years to realize. Cloning and expression of the human gene was achieved in 1984 and clinical trials planned even before the descriptions of the recombinant hormone were published. The Amgen material was tested in parallel studies in Seattle and England and by the end of 1986 the efficacy of recombinant human erythropoietin (r-HuEPO) given in large intravenous bolus doses in reversing the anaemia of uraemia was established. The benefits were immediately obvious: relief from transfusion dependence was the unequivocal evidence but the effect on 'wellbeing' though subjective was remarkable. Large clinical trials were completed in Europe and the USA so that r-HuEPO was licensed as a therapeutic drug less than two years later. The pilot studies flagged a number of key issues: hypertension, sometimes with encephalopathy, occurred in patients whose blood pressure was labile before treatment; vascular access failure seemed more frequent and hyperkalaemia was thought to reflect less efficient dialysis. Failure to respond focused attention on iron balance as well as on factors such as infection, aluminium, and hyperparathyroidism. A more clear understanding of the pathogenesis of the anaemia of uraemia was made possible by dissection of the specific effects of the exogenous erythropoietin on erythroid function.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1995
PMID:Historical review on the use of recombinant human erythropoietin in chronic renal failure. 764 3

Quality of life is closely linked to our ability to meet the exercise challenges imposed on us by our daily round of activities and those we select as leisure time activities. Aerobic metabolism of fat and carbohydrates provides the energy to support our activities. An increase in aerobic capacity extends the range and duration of activities we can undertake without the premature onset of fatigue. An adequate oxygen delivery, especially to skeletal muscles, is central to the effective aerobic support of energy metabolism. Frequent exercise improves our aerobic capacity by a relatively modest increase in oxygen transport and a large improvement in the capacity of muscle to use oxygen delivered. This is achieved by an increase in mitochondrial density as well as an increase in capillarisation of skeletal muscles. A decrease in oxygen delivery, in active people, produces the same type of adaptive increases in aerobic capacity. Therefore, even though more haemoglobin is clearly better for active healthy individuals, frequent exercise can improve the capacity of renal patients to make the most effective use of their anaemia-imposed reduced oxygen delivery system.
Nephrol Dial Transplant 1995
PMID:Haemoglobin--is more better? 764 6

Since the introduction of recombinant human erythropoietin (r-HuEPO) 9 years ago, there have been tremendous physiological improvements in patients with various anaemias due to absolute and relative erythropoietin (Epo) deficiencies. However, not all patients that could benefit from r-HuEPO are being treated, not all are responding who should be responding, and most dialysis patients (who comprise the single largest group of treatment recipients) are being inadequately treated. The future of r-HuEPO will depend upon whether clinicians can optimize the use of r-HuEPO and determine what should be the optimal haematocrit. These issues will, in turn, depend upon whether three interdependent variables are addressed: the need for more scientific studies to evaluate various aspects of the use and effectiveness of r-HuEPO; the need for physician education to better understand the role of r-HuEPO in optimizing health in patients with anaemia in chronic renal failure and in the anaemia of chronic disease; and the need for less costly r-HuEPO therapy so that more patients can be treated and receive optimal therapy. Better use of r-HuEPO could result in significantly improved morbidity and perhaps improved survival of patients with Epo-deficient anemias.
Nephrol Dial Transplant 1995
PMID:The future of r-HuEPO. 764 14

Erythropoietin therapy for uraemic anaemia is associated with a high rate of hypertensive and thrombotic complications. The mechanism is unknown, but a change in cellular calcium control may be relevant to changes in blood pressure and thrombosis. Platelets were utilized as a model of vascular smooth muscle cells. The effects of erythropoietin therapy on platelet cellular calcium, assessed by fura-2, were measured in 25 patients receiving renal replacement therapy during a 6-month treatment period. Three patients failed to reach a target haemoglobin and were excluded from the analysis. Blood pressure increased in 11 of the remaining 22 subjects, eight requiring an increase in antihypertensive medication. There were no differences in cellular calcium control between the group in whom blood pressure rose and patients with stable blood pressure. Overall there was a fall of 24% in resting cytosolic calcium (baseline 69.2 +/- 5.1 to 52.5 +/- 3.0 nmol/l, P < 0.05) after 3 months of erythropoietin therapy. There was no change in the thrombin-stimulated peak response in the presence of extracellular calcium during therapy, although thrombin-stimulated intracellular release also fell at 3 months (baseline 769 +/- 61 versus 3 months 559 +/- 49 nmol/l, P < 0.01). This study suggests that intracellular free calcium control within platelets improves in response to erythropoietin therapy. However these changes appear not to be related to the development of hypertension.
Nephrol Dial Transplant 1994
PMID:Modulation of platelet cytosolic calcium during erythropoietin therapy in uraemia. 780 Feb 9

Treatment of the anaemia of renal disease with recombinant human erythropoietin results in an improvement of haemostasis and an increased risk of thrombovascular accidents. In this prospective, placebo-controlled, double-blind, and cross-over study, the effects of low-dose acetylsalicylic acid (30 mg daily) on thrombotic and bleeding events during the initial period of treatment with erythropoietin in anaemic haemodialysis patients without previous thrombovascular accidents or known increased risk for thrombosis were investigated. During correction of the haematocrit and the first 3 months thereafter, group A (n = 68) received placebo and group B (n = 69) 30 mg acetylsalicylic acid daily. Cross-over took place after the 3rd month of a stable haematocrit. The study ended 3 months later. Target haematocrit (30-35%) was reached in 12.4 +/- 8 weeks (M +/- SD). In group A the bleeding time was 382 +/- 285 s, decreasing to 282 +/- 208 before cross-over (P < 0.01), and increasing to 395 +/- 271 (P < 0.05) thereafter. In group B the bleeding time was 390 +/- 381 s, 406 +/- 267 (NS), and 285 +/- 238 (P < 0.05) respectively. Twenty-two thrombovascular accidents were seen (16%, 13 during acetylsalicylic acid and 9 during placebo, NS), including 17 fistula thromboses. The incidence of bleeding events was not significantly different between regimens. In conclusion, erythropoietin treatment resulted in a reduction of the bleeding time. When 30 mg acetylsalicylic acid was taken during the treatment, the bleeding time did not decrease.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1994
PMID:Low-dose aspirin does not prevent thrombovascular accidents in low-risk haemodialysis patients during treatment with recombinant human erythropoietin. 780 Feb 10

Recombinant human erythropoietin (rHuEpo) is used to correct anaemia in dialysis patients. Subcutaneous administration of rHuEpo may be associated with pain at the injection site. This study assessed the pain of subcutaneous infiltration of two different preparations of rHuEpo, alpha and beta, and the value of a local anaesthetic (Emla) cream, in reducing the pain of infiltration. Forty-eight haemodialysis patients were enrolled into a double-blind, placebo-controlled, paired-comparison study. Pain was assessed using a visual analogue scale, a verbal descriptive scale and a direct comparison between paired treatments. Subcutaneous injection of rHuEpo alpha was more painful than rHuEpo beta (P < 0.001); using placebo cream 42% of patients described the pain of rHuEpo alpha as severe or very severe, whereas none of the patients found rHuEpo beta so painful. Application of Emla for at least 2 h prior to injection resulted in a significant reduction in the pain of both preparations, but was unable to reduce the pain of rHuEpo alpha to that of rHuEpo beta. Subcutaneous injection of rHuEpo alpha is more painful than rHuEpo beta, even after application of Emla. Although the discomfort of rHuEpo beta is graded as very mild by most adult patients the use of Emla is associated with a significant reduction in discomfort, which may be of benefit to paediatric patients.
Nephrol Dial Transplant 1994
PMID:Pain after subcutaneous injection of recombinant human erythropoietin: does Emla cream help? 955 Jun 87

The availability of recombinant EPO has greatly improved the lives of patients with end-stage renal disease. Knowledge is still accumulating regarding the use and effects of EPO in patients on PD, and several critical questions remain to be answered: 1. At what hematocrit level and when in the predialysis or dialysis course should EPO be started in PD patients? Recent studies by Golper suggest that the concomitant initiation of EPO and PD results in an increased hematocrit response compared to starting EPO after PD has been initiated for some time (63). 2. What is the best route of administration of EPO in PD patients? It is apparent that i.v., SC, and IP EPO can be effective in this population if utilized properly. The goal should be to tailor the route to the needs of the patient. Perhaps the daily SC route, for example, might be best for minimizing hypertension because of the slow, steady rise of hematocrit, while the IP route would be best tolerated by children (33,64). 3. What should the target hematocrit level be? This may vary depending on which organ function is being assessed. For the whole patient data are not currently available on appropriate hematocrit targets to maximize oxygen utilization, but near normal levels have recently been reported to be safe and beneficial (65-67). 4. What are the end-organ effects of anemia and its correction in PD patients? There is a dearth of information in this area for PD as well as HD patients. Additional research of this kind will increase our understanding of the pathophysiology of anemia as well as uremia.(ABSTRACT TRUNCATED AT 250 WORDS)
Perit Dial Int 1994
PMID:Erythropoietin treatment in peritoneal dialysis patients. 794 80


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