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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent observations indicate that angiotensin-converting enzyme (ACE) inhibition corrects renal transplant erythrocytosis (RTE). The mechanism for this association is not known. We examined the effect of ACE inhibition on hematocrit, erythropoietin (EPO), and renin substrate. ACE inhibition has been reported to suppress renin substrate, which is known to stimulate EPO and erythropoiesis. In 15 patients with RTE, hematocrit dropped from 52.8 +/- 0.6 (SEM) to 45.8 +/- 1.4% after 8 weeks of treatment with Enalapril, 2.5-20 mg/day. Serum EPO (normal range: 9-30 mU/ml) was high in one, normal in seven, and low in seven patients. ACE inhibition reduced EPO in patients with initial high or normal levels but induced no change in patients with initial low levels. ACE inhibition had no significant effect on renin substrate. In one patient who rejected his first graft, erythrocytosis recurred following a second, successful transplant. Treatment was discontinued because of cough in two patients and symptomatic drop in blood pressure in one patient. We conclude RTE is not caused by hypererythropoietinemia. In patients with normal circulating EPO, erythrocytosis may result from an increase sensitivity to EPO, and ACE inhibition lowered hematocrit by further reduction of this hormone. However, the finding of erythrocytosis in half our patients with suppressed EPO, suggests the participation of non-EPO-mediated mechanism(s). The recurrence of RTE in a patient after a second transplant raises the additional possibility of patient-specific factors in the pathogenesis of this disorder. In contrast to other reports, we documented side-effects (cough, hypotension) in three (20%) of our patients. Our clinical experience, coupled with prior reports of spontaneous resolution of RTE in some patients, suggests that intermittent courses of ACE-inhibition may be the optimal strategy in the use of this form of therapy for RTE.
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PMID:Angiotensin-converting enzyme inhibition in the treatment of renal transplant erythrocytosis. Clinical experience and observation of mechanism. 762 54

Anemia of prematurity (AOP) has been conventionally treated with erythrocyte transfusions. Recent investigations have reported the use of recombinant human erythropoietin (rHuEPO) as an alternative for treating AOP. The potential of rHuEPO in increasing erythropoiesis implies its clinical usefulness. The effect of rHuEPO on reticulocyte count as well as other parameters of blood cells was examined in 14 premature babies with AOP. The average birth body weight and gestational age of these premature babies were 1533.71 +/- 61.66 g (Mean +/- SEM) and 31.36 +/- 0.49 weeks respectively. They received the first dose of rHuEPO at age 26.14 +/- 2.03 days with a hemoglobin level by 9.40 +/- 0.27 g/dL and hematocrit level of 28.20 +/- 0.81%. They were given rHuEPO 200 U/kg subcutaneously every other day for 10 doses, and iron 3 mg/kg and vitamin E 25 IU/kg per os every day. Average erythropoietin level of the patients on entry into this study was low (7.66 +/- 1.10 mu/mL). After treatment with rHuEPO for 20 days, the corrected reticulocyte count increased from 0.64 +/- 0.10% to 1.68 +/- 0.42% on Day 5 (P < 0.05), 1.96 +/- 0.41% on Day 12 (P < 0.05), 1.77 +/- 0.43% on Day 20 (P < 0.05), and hematocrit increased from 28.2 +/- 0.81% to 29.58 +/- 1.02% (p < 0.05) on Day 20. Bone marrow aspirates on Day 10 for 9 infants revealed moderate to high cellularity, mostly with erythroblasts (47.89 +/- 1.78%); the M/E ratio was low (0.57 +/- 0.05). The granulocyte series and megakaryocyte could be well visualised.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of recombinant human erythropoietin in treating the anemia of prematurity. 779 77

Two groups of subjects were studied. The group A consisted of 40 patients treated by HD (haemodialysis) (mean age--x +/- SEM 38.6 +/- 1.47 years, duration of haemodialysis treatment 36.8 +/- 3.7 months, cuprophan dialyzers and acetate containing solution--38 mEg/l--were used, time of HD--4 hours 3 times weekly, predialysis serum creatinine was 900.8 +/- 32.1 mumol/l (10.2 +/- 0.4 mg%) postdialysis serum creatinine was 467.8 +/- 28.3 mumol/l (5.3 +/- 0.3 mg%). Patients were not treated with erythropoietin. The control group comprised 20 healthy subjects (mean age 36.7 +/- 2.7 years and serum creatinine level 76.7 +/- 3.5 mumol/l (0.9 +/- 0.1 mg%). In all examined subjects the following experimental protocol was used. In both group blood pressure (BP) and heart rate (HR) were determined at about 8 a.m. after an overnight rest. Then blood samples were withdrawn for estimation of ANP, endothelin, haematocrit value (Ht), haemoglobin (Hb) and creatinine concentrations. Between 8 and 12 a.m. all examined subjects of the group A were dialysed. After each hour of dialysis BP and HR were measured and blood samples were withdrawn ANP (Peninsula Lab.Kids.) and endothelin (Amersham Kids) were measured using RIA methods, but other biochemical parameters using routine methods. Serum creatinine and plasma ANP levels significantly decreased after HD. Plasma endothelin level was significantly higher than in the control subjects. After first hour of HD a significant decrease of plasma endothelin was observed and than plasma endothelin level started to increase. No significant correalations between creatinine, ANP and endothelin levels in examined group was observed.
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PMID:[Levels of endothelin and atrial natriuretic peptide (ANP) in plasma of patients with chronic renal failure treated by hemodialysis]. 814 34

The diurnal variations of serum-erythropoietin concentration ([s-EPO]) were investigated in six physically trained (T) and eight untrained (UT) men. The T subjects had a higher mean maximal oxygen uptake than UT subjects [75.7 (SEM 1.6) ml.min-1.kg-1 versus 48.3 (SEM 1.4) ml.min-1.kg-1, P < 0.0001] and a lower mean body mass index [BMI, 21.7 (SEM 0.7) kg.m-2 versus 24.4 (SEM 0.6) kg.m-2, P = 0.02]. Each subject was followed individually for 24 h as they performed their normal daily activities. Venous blood samples were collected from awakening (0 min) until the end of the 24-h period (1440 min). Both T and UT had a nadir of [s-EPO] 120 min after awakening [10.0 (SEM 0.3) U.l-1 versus 11.5 (SEM 2.1) U.l-1, P > 0.05]. The UT and T increased their [s-EPO] to peak values at 960 min and 960-1200 min, respectively (ANOVA P = 0.03) after awakening [UT: 18.4 (SEM 2.8) U.l-1; T: 16.2 (SEM 2.5) U.l-1, P > 0.05]. The mean 24-h [s-EPO] were 14.5 (SEM 1.0) U.l-1 and 14.9 (SEM 0.9) U.l-1 in T and UT, respectively (P > 0.05). The individual mean 24-h [s-EPO] were not correlated to body mass, BMI or maximal oxygen uptaken. Significant diurnal variations in [s-EPO] occurred in these healthy subjects irrespective of their levels of physical activity.
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PMID:Diurnal variations of serum erythropoietin in trained and untrained subjects. 814 35

To evaluate the effects of erythropoietin (EPO) therapy on the lipid profile in end-stage renal failure, we undertook a prospective study in patients on both hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD). One hundred and twelve patients (81 HD, 31 CAPD) were enrolled into the study. Lipid parameters [that is, total cholesterol and the LDL and HDL subfractions, triglycerides, lipoprotein (a), apoproteins A and B], full blood count, iron studies, B12, folate, blood urea, aluminium and serum parathyroid hormone were measured prior to commencement of EPO therapy. Ninety-five patients were reassessed 5.2 +/- 0.3 (mean +/- SEM) months later and 53 patients underwent a further assessment 13.1 +/- 0.6 months after the commencement of EPO, giving an overall follow-up of 10.0 +/- 0.6 months in 95 patients. As expected, EPO treatment was associated with an increase in hemoglobin (7.7 +/- 0.1 vs. 9.9 +/- 0.2 g/dl; P < 0.001) and a decrease in ferritin (687 +/- 99 vs. 399 +/- 69 micrograms/liter; P < 0.01). A significant fall in total cholesterol occurred (5.8 +/- 0.1 vs. 5.4 +/- 0.2 mmol/liter; P < 0.05) in association with a fall in apoprotein B (1.15 +/- 0.04 vs. 1.04 +/- 0.06; P < 0.05) and serum triglycerides (2.26 +/- 0.14 vs. 1.99 +/- 0.21; P < 0.05) during the course of the study. Other lipid parameters did not change, although there was a trend towards improvement.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of erythropoietin therapy on the lipid profile in end-stage renal failure. 819 94

The effects of short and long duration exercise on serum erythropoietin concentrations [EPO]s were studied in seven male cross-country skiers of national team standard and eight male marathon runners, respectively. The short duration exercise was performed as 60 min of cycling at an intensity of 80%-95% of maximal heart rate. Arterial blood oxygen saturations monitored by pulse-oximetry remained unchanged throughout exercise. The partial pressure of O2 at which haemoglobin was half-saturated with O2 calculated from forearm venous blood gas tension and blood O2 saturation, and the erythrocyte 2,3-diphosphoglycerate did not change significantly during the exercise. Blood lactate concentrations were increased at the end of exercise [from 1.3 (SEM 0.1) to 3.6 (SEM 0.3) mmol.l-1]. The [EPO]s determined (by enzyme-linked immunosorbent assay) pre-exercise, 5 min, 6 h, 19 h, and 30 h after the exercise were unchanged [from 16.1 (SEM 2.6) to 19.1 (SEM 3.2), 17.9 (SEM 3.0), 17.0 (SEM 2.5), and 18.6 (SEM 2.9) U.l-1, respectively]. The [EPO]s were not correlated to the earlier parameters. The long duration exercise consisted of habitual training, a 3 week break from training followed by 2 and 4 weeks of re-training. The [EPO]s, body fat (BF), and serum free-testosterone concentrations determined at the end of each period remained unchanged. The maximal oxygen uptakes were decreased after the break from training and increased during retraining (P = 0.04). Body mass (mb) increased after the break in training (P = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of short and long duration exercise on serum erythropoietin concentrations. 822 32

Because anemia in patients with bronchopulmonary dysplasia is characterized by inappropriately low serum concentrations of erythropoietin but increased in vitro sensitivity of erythroid progenitors to erythropoietin, we speculated that administration of human recombinant erythropoietin would correct this anemia. Fifteen infants with the anemia of bronchopulmonary dysplasia were randomly assigned to receive erythropoietin or placebo subcutaneously for 10 days. Changes in reticulocyte count, hematocrit, blood lactate concentration, neutrophil count, platelet count, heart rate, oxygen requirement, weight gain, and number of transfusions were assessed. In the 10 erythropoietin recipients (99 +/- 12 days of age), hematocrit values increased from 0.325 +/- 0.006 to 0.381 +/- 0.013 (mean +/- SEM; p < 0.005) and reticulocyte counts from 122 +/- 20 to 446 +/- 48 x 10(3)/microliters (p < 0.005); lactate values remained unchanged. In the five placebo recipients (91 +/- 12 days of age), hematocrits and reticulocyte counts remained unchanged, and lactate values increased from 0.73 +/- 0.14 to 1.34 +/- 0.25 mumol/gm (p < 0.05). During the 30 days after the treatment period, one erythropoietin recipient and four placebo recipients were given transfusions. Other measured variables remained unchanged in both groups. We conclude that erythropoietin is effective in treatment of the anemia of bronchopulmonary dysplasia.
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PMID:A randomized, double-blind, placebo-controlled trial of recombinant erythropoietin in treatment of the anemia of bronchopulmonary dysplasia. 822 37

We studied 38 patients (9 haemodialysis, 18 peritoneal dialysis, 11 advanced renal failure) over the first 12 weeks of erythropoietin therapy. In 14 iron-overloaded patients (ferritin > 500 micrograms/l the haemoglobin (+/- SEM) increased from 6.74 +/- 0.27 to 9.85 +/- 0.36 g/dl (P < 0.0001) entirely by mobilizing iron reserves (reduced from 1,220 +/- 73 to 739 +/- 111 mg, P < 0.0001). In the 24 non-overloaded patients (ferritin < 500 micrograms/l) the haemoglobin rose similarly from 7.04 +/- 0.18 to 10.70 +/- 0.36 g/dl (P < 0.0001), partly from iron reserves (depleted from 200 +/- 74 to -44 +/- 77 mg, P = 0.016) and partly from oral iron supplements (305 +/- 110 mg). In the overloaded patients the ferritin declined from 1057 micrograms/l (geometric mean, range 504-3699) to 317 micrograms/l (42-1505, P < 0.0001). In the non-overloaded patients it declined from 82 micrograms/l (8-461) to 45 micrograms/l (5-379, P = 0.016). The transferrin saturation (TS) in the overloaded patients appeared to decline from 38.3 +/- 7.2% to 24.0 +/- 3.7% but this was not statistically significant. In the non-overloaded the TS was unchanged (23.3 +/- 2.4 before and 28.1 +/- 3.6% after treatment). Considering all 38 patients together, the haemoglobin correlated negatively with the ferritin (r = 0.3731, P < 0.001) but not with the TS. The TS correlated with the serum ferritin initially (r = 0.75, P < 0.001) but not after the first 4 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Monitoring of iron requirements in renal patients on erythropoietin. 797 Jan 8

Subcutaneous (SC) recombinant human erythropoietin (EPO) has been reported to correct anemia in hemodialysis patients at lower doses than intravenous (IV) EPO. Those trials involved relatively high doses of EPO or did not control adequately for time-related falls in dose requirements. Therefore, on open-label double-crossover study was performed to compare the hemoglobin (Hb) response to low dose SC versus IV EPO. Ten (4 male) maintenance hemodialysis patients previously stabilised on low dose EPO for 18 +/- 3 months (mean +/- SEM) were given EPO IV for 12 weeks (IV#1), then SC for 24 weeks and then IV for a further 20 weeks (IV#2). Iron status and other factors known to modify response to EPO were kept constant. EPO dose was not changed unless Hb rose above 100 g/l, when the dose was reduced to keep Hb between 90 and 100 g/l. Initial EPO dose was 64 +/- 10 u/kg/week. Mean Hb, measured monthly, was not different during the 3 treatment periods. There was wide interpatient variation in the relative response to IV versus SC EPO. Mean Hb was higher on IV EPO in 5 patients (by 6.1 +/- 2.0 g/l) and higher on SC EPO in 5 patients (by 12.1 +/- 4.1 g/l). The difference in mean Hb during IV versus SC administration was more than 5 g/l in 6 patients, being higher in 3 patients during IV administration (by 8.7 +/- 4.6 g/l) and in 3 during SC (by 17.4 +/- 4.6 g/l). In conclusion, the more efficient route of administration of EPO is not predictable for individual patients, and should be sought to allow possible dose reduction.
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PMID:Interpatient variation in response to subcutaneous versus intravenous low dose erythropoietin. 828 16

We studied the effects of self-administered, daily, low-dose, subcutaneous (SC) erythropoietin (EPO) therapy in 15 uremic patients on continuous ambulatory peritoneal dialysis (CAPD) for 16 weeks to assess its efficacy and safety. The patients had baseline hemoglobin (Hb) levels of < 8 g/dl and were started on 10 u/kg/day of beta-EPO. The dosage of EPO was adjusted every 4 weeks according to hematological response. The patients learned to inject into their thighs themselves. Hb increased significantly from 6.6 +/- 0.2 g/dl (mean +/- SEM) at week 0 to 9.0 +/- 0.3 at week 8 and 10.0 +/- 0.4 at week 16 (p < 0.0001). Hematocrit (Hct) increased significantly from 0.20 +/- 0.01 at week 0 to 0.27 +/- 0.01 at week 8 and 0.29 +/- 0.001 at week 16 (p < 0.0001). The mean EPO dose was 10 u/kg/day at week 0 and 10.5 +/- 0.4 at week 8 and 10.3 +/- 0.5 at week 16. After minor adjustments in antihypertensive therapy had been made no significant differences in mean arterial blood pressure were noted. Six of 15 patients required increased dosage of antihypertensive drugs. All patients were given oral iron supplements. There was a significant decrease in percentage of transferrin saturation and 10 patients required additional intravenous iron supplements. There was no significant difference in the serum levels of creatinine, albumin, potassium, phosphate and urate with EPO treatment. There were no local complications at the sites of injection and the injections themselves were quite painless.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Correction of anemia using self-administered daily subcutaneous erythropoietin in uremic patients on continuous ambulatory peritoneal dialysis. 837 Jun 5


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