Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a result of the AIDS crisis, public and physician pressure have increased the utilization of autologous blood products. Attitudes about homologous blood transfusion, however, have changed dramatically in recent years. A large segment of the population undergoing elective surgery is elderly and therefore has a significant incidence of cardiovascular disease and a slow response of the erythropoietic system when acute anemia occurs. However, preoperative autologous blood donation programs require 2-5 weeks to complete; the average yield is only 2.2 units per patient. As a consequence, autologous predonation is underused and homologous transfusion cannot be completely avoided in all patients. For several years recombinant human erythropoietin (rHuEPO) has been available and has been successfully used in the treatment of patients with renal anemia. This study evaluated the effect of r-HuEPO on patients with preoperative autologous blood collection. METHODS. Ten patients of both sexes scheduled for hip arthroplasty underwent a preoperative autologous program. During a period of 23 days prior to surgery autologous blood donation was performed with 7.5 ml/kg withdrawal on four occasions, the last one 5 days prior to surgery. Five patients were randomly treated with subcutaneous injections of rHuEPO (Erypo, Cilag GmbH, Sulzbach; Distributor: Fresenius AG, Oberursel, FRG) 200 IU/kg seven times, starting 3 days after the first blood withdrawal. All patients (n = 10) received oral iron therapy with iron sulphate 304 mg/die (= 100 mg iron/die). Patients with hypertension or recent myocardial infarction were excluded from the study. The hemoglobin level before donation had to be at least 11.0 g/dl. On each study day, a complete blood count and platelets, differential, and reticulocyte count were determined by standard methods as were transferrin, ferritin, and total iron-binding capacity. Blood loss and blood consumption during and after the operation were registered. The indication for blood transfusion (autologous/homologous) was based on hemoglobin values, which were not acceptable below 8.5 g/dl. RESULTS. No side effects of rHuEPO treatment were observed. Blood loss ranged from 650 to 1100 ml intraoperatively and 400 to 950 ml postoperatively with no differences between the groups. Patients with rHuEPO had no autologous red cell concentrates (aRCC) during the operation; two of them had two units of aRCC on the 2nd postoperative day. Two of the patients in the control group had intraoperative blood transfusions (2 and 3 units aRCC, respectively); all patients in this group were transfused postoperatively: 12 of the 20 units collected were utilized. At the onset of the operation the mean hemoglobin value in patients with rHuEPO was 13.5 +/- 0.4 g/dl compared to 11.3 +/- 0.3 g/dl in the controls. Reticulocytes increased significantly during the investigation period. On the 2nd, 3rd, and 4th days of autologous blood collection and before the onset of surgery, the number of reticulocytes was significantly greater in rHuEPO patients than in the controls. Further laboratory variables such as transferrin, ferritin, and total iron-binding capacity did not change significantly during the investigation period; there were no significant differences between the two groups. DISCUSSION. The results of the present study show that rHuEPO leads to an increase in reticulocytes with maintenance of hemoglobin levels during the phlebotomy program. As a consequence, patients with anemia and particular contraindications to homologous blood derivatives (irregular antibodies, Jehovah's Witnesses) may be able to undergo major surgery successfully. The possibility of shortening the intervals between phlebotomies would seem to be of major advantage; our data also suggest that an aggressive autologous blood collection program would increase yields over present programs. In our institute a minimum hemoglobin level of 11.5 g/dl is accepted for autologous donation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Recombinant erythropoietin in autologous blood donation]. 192 12

Anemia (hematocrit less than 25%) predictably accompanies chronic renal failure and is present in over 90% of patients on chronic dialysis. Relative erythropoietin deficiency is the proximate cause. Recombinant human erythropoietin recently became available for research and clinical use. Erythropoietin production is regulated by a single copy gene located on chromosome 7; its expression has been shown in the kidney, liver, and macrophages. It is glycosylated protein of 166 amino acids with a molecular weight of 34,000 D. When given to patients with the anemia of renal failure, erythropoietin causes a dose-dependent rise in hematocrit to the normal range within 8 to 14 weeks. Complications of this response are minimal except for a significant incidence of hypertension. When the anemia is corrected, the patient's quality of life, cognitive function, and brain electrophysiology improve dramatically. Recombinant human erythropoietin represents a major breakthrough in the treatment of patients with chronic renal failure. Current reimbursement constraints limit its full application.
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PMID:Recombinant human erythropoietin and renal anemia: molecular biology, clinical efficacy, and nervous system effects. 202 6

The contractile properties of recombinant human erythropoietin (rHuEPO) on isolated resistance vessels of renal and mesenteric vascular beds were studied in an in vitro model using a small vessel myograph. Under isometric conditions, rHuEPO caused a contraction of this vasculature in a concentration range between 10 U/ml and 200 U/ml. A maximal active wall tension of 1.52 +/- 0.19 mN/mm was obtained under a rHuEPO dose of 200 U/ml. In Ca2+ free solution, the pressor response to high rHuEPO-concentrations was attenuated, and the response to low rHuEPO concentrations was abolished. In the presence of verapamil, phentolamine and saralasin, rHuEPO-induced contractions were not affected significantly. A dose-dependent vasodilatation of mounted vasculature to acetylcholine (ACh) indicated that endothelium remained intact in our preparations. rHuEPO-induced vessel contraction was not abrogated after an enzymatical removal of endothelium by collagenase, confirming that the described contractile responses are endothelial independent. These findings suggest that a direct vasopressor effect of rHuEPO on proximal resistance vessels may contribute to development of hypertension seen in rHuEPO-treated hemodialysis patients.
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PMID:Direct vasopressor effect of recombinant human erythropoietin on renal resistance vessels. 200 40

We investigated the hemodynamic effects of the correction of anemia with recombinant human erythropoietin (rHuEPO) in 28 hemodialysis patients with severe anemia. Echocardiograms were recorded before the administration of rHuEPO (period I) with a hematocrit of 19.2 +/- 1.5% (mean +/- SD) and repeated twice (periods II and III) when the hematocrit was increased to 25.7 +/- 1.1% and to 30.0 +/- 1.0%. Left ventricular end-diastolic dimension (LVDd) decreased from 51.0 +/- 6.1 to 48.8 +/- 5.8 and to 48.3 +/- 7.1 mm, but no changes were observed in left ventricular end-systolic dimension. Cardiac output (CO) decreased from 5.89 +/- 1.46 to 5.00 +/- 1.44 and to 4.67 +/- 1.33 l/min. The thickness of the interventricular septum and the left ventricular posterior wall remained unchanged. Blood pressure was kept rather constant, although antihypertensive therapy needed to be adjusted to prevent the occurrence or aggravation of hypertension. Total peripheral resistance increased from 1481 +/- 359 to 1832 +/- 487 and to 1946 +/- 493 dynes.sec/cm5. The decreases in LVDd and CO were significant between periods I and II, without further changes between periods II and III. More antihypertensive therapy was needed in period III than in period II. Similar echocardiographic results were observed in 10 patients in whom antihypertensive therapy was not required throughout the study. In conclusion, an increase in hematocrit to 25% would be appropriate in order to obtain an effective hemodynamic improvement with rHuEPO therapy in dialysis patients although a higher hematocrit level might be desirable in order to improve working capacity.
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PMID:Echocardiographic findings in hemodialysis patients treated with recombinant human erythropoietin: proposal for a hematocrit most beneficial to hemodynamics. 200 94

We evaluated changes in hematocrit in patients on continuous ambulatory peritoneal dialysis (CAPD) before and after the administration of erythropoietin (EPO). Thirty-five patients were evaluated at the beginning of treatment with CAPD and after an average of 3.5 years on CAPD; mean hematocrit (Hct) rose from 25.4 +/- 5.4% to 28.1 +/- 6.7% (P less than 0.001). In the period before EPO administration 11 patients required a total of 44 transfusions (one patient needed 23 transfusions). Fifteen patients were started on subcutaneous erythropoietin 3,000 units 3 times a week and were followed for a mean period of 6.3 months. Hct rose from 23.8 +/- 1.8% to 25.2 +/- 2.4% (P less than 0.01) within the first 2 weeks and up to 27.5 +/- 3.7% (P less than 0.01) in the fourth week. By the eighth week the target Hct (30 to 35%) was reached. During the next 5 months the EPO doses were adjusted to each patient's needs ranging between 2,000 U per week to 4,000 U 3 times per week. Mild hypertension was the only side effect seen in some of the patients. In conclusion low dose subcutaneous EPO is effective in managing the anemia of patients on CAPD with only minor side effects.
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PMID:Low-dose subcutaneous erythropoietin in continuous ambulatory peritoneal dialysis. 202 37

The Canadian Erythropoietin Study Group conducted a randomized, placebo-controlled trial to examine the effect of human recombinant erythropoietin on the treatment of anemia in 118 hemodialysis patients. The effectiveness of therapy on hemoglobin concentration and quality of life has been reported elsewhere. Herein is reported the effect of erythropoietin therapy on blood pressure. Patients receiving erythropoietin had a significant increase in diastolic blood pressure (DBP; p = 0.001) and required increased antihypertensive medication. There was no difference in the incidence of severe hypertension (DBP greater than 110 mm Hg or hypertension-related seizure) between placebo-treated patients (13%) and those receiving erythropoietin (14%). The development of severe hypertension in erythropoietin-treated patients was associated with a history of receiving antihypertensive medication or having native kidneys in situ. In the first 5 weeks of the study, there was a correlation between the change in hemoglobin concentration and the change in DBP (r = 0.42, p less than 0.001). Although erythropoietin therapy was associated with a significant increase in DBP, there was no difference between placebo- and erythropoietin-treated patients with respect to severe hypertension or hypertension-related seizures.
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PMID:Effect of recombinant human erythropoietin therapy on blood pressure in hemodialysis patients. Canadian Erythropoietin Study Group. 204 74

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.
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PMID:The use of erythropoietin in renal failure. 205 40

Using fura-2 cytosolic free calcium concentrations were measured in intact washed platelets from 9 spontaneously hypertensive rats (SHR) and from 9 age-matched normotensive Wistar-Kyoto rats (WKY). In resting platelets cytosolic free calcium concentration was significantly higher in SHR than in WKY (171.8 +/- 64.4 nM vs 93.1 +/- 59.0 nM, p less than 0.05). After preincubation with erythropoietin cytosolic free calcium concentration was significantly higher in SHR than in WKY (197.5 +/- 83.2 vs 93.0 +/- 60.1, p less than 0.01). Using platelets from SHR erythropoietin increased mean resting cytosolic free calcium concentration by 14.9% (p less than 0.05) and mean thrombin induced changes of cytosolic free calcium by 58.3% (p less than 0.01). In contrast, erythropoietin caused no significant increase in the resting calcium concentration or in thrombin induced changes of cytosolic free calcium in platelets from WKY. It is concluded that erythropoietin is involved in the pathogenesis of hypertension by elevating cytosolic free calcium concentration.
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PMID:Erythropoietin increases cytosolic free calcium concentration and thrombin induced changes in cytosolic free calcium in platelets from spontaneously hypertensive rats. 205 26

Recombinant human erythropoietin may improve hemostasis of uremic patients by correcting anemia. However, a complete correction of renal anemia carries the risk of hypertension, encephalopathy, thrombosis, and hyperkalemia. Our aim was to establish the minimum level of packed cell volume (PCV) achieved with recombinant human erythropoietin that corrects the prolonged bleeding time in uremia. Twenty patients with chronic renal failure, anemia, and very prolonged bleeding time (greater than or equal to 15 minutes) were randomly allocated to erythropoietin or no specific treatment. The initial dose of erythropoietin was 50 U/kg intravenously (IV) three times a week. Every 4 weeks, the dose was increased by 25 U/kg until a normalization of bleeding time was achieved. Erythropoietin at a dose ranging from 150 to 300 U/kg/wk induced an increase in PCV to a range of 27% to 32% in all patients but one, and normalized bleeding time in all patients. A significant negative correlation (r = 0.898, P less than 0.001) was found between PCV and bleeding time measurements. Erythropoietin also significantly (P less than 0.01) increased values for red blood cell (RBC) distribution width (basal, 11.3 +/- 0.6; 12 weeks, 13.1 +/- 1.3). Platelet count and platelet function parameters did not significantly change. In untreated patients, no changes were recorded in all the parameters considered. These results establish in a controlled fashion that erythropoietin shortens bleeding time of uremic patients and indicate that a partial correction of renal anemia is enough to normalize bleeding time.
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PMID:Recombinant human erythropoietin to correct uremic bleeding. 206 54

One hundred seventeen patients with anemia related to chronic renal failure not severe enough to require maintenance dialysis were randomly assigned to receive recombinant human erythropoietin (rHuEPO; 50, 100, or 150 U/kg body weight) or placebo intravenously (IV) three times a week for 8 weeks or until their anemia was corrected. Correction of anemia (hematocrit of 40% for males, 35% for females) occurred in 87% of those given 150 U/kg, 64% of those given 100 U/kg, 46% of those given 50 U/kg rHuEPO and in 3% of the placebo group. Energy levels and work capacity improved significantly in the group with corrected anemia compared with the group with uncorrected anemia. rHuEPO appeared to be well tolerated. There was no evidence that rHuEPO therapy accelerated the deterioration of renal function as measured by serum creatinine and reciprocal of serum creatinine compared with placebo treatment. However, it is essential that blood pressure and hematocrit be carefully monitored, particularly in hypertensive patients, to prevent the development of complications associated with hypertension.
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PMID:Double-blind, placebo-controlled study of the therapeutic use of recombinant human erythropoietin for anemia associated with chronic renal failure in predialysis patients. The US Recombinant Human Erythropoietin Predialysis Study Group. 206 55


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