Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The efficacy and tolerance of intravenous and subcutaneous administrations of recombinant human erythropoietin (r-HuEPO) have been compared in 50 maintenance hemodialysis patients. A 2 month course of intravenous r-HuEPO given at stable dosage was followed by a 6 month course of subcutaneous r-Hu EPO. We reduced r-HuEPO dosage by 50% when starting subcutaneous administration and regularly adapted the dosage to achieve hematocrit levels between 30 and 35%. At the end of the study, mean r-HuEPO dosage was 82 +/- 8 (mean +/- SEM) IU/kg/week, which represented 70 +/- 7% of intravenous r-HuEPO dosage. Mean hematocrit value was 32.9 +/- 0.5% when starting subcutaneous administration and also at the end of this study. Arterial blood pressure remained stable over the whole trial period as did most biological blood tests which were not influenced by the route of administration. In 98% of cases, patients expressed either pain-free (50%) or slight to moderate pain (48%) at the injection site. This trial confirms a substantial dosage economy when using r-HuEPO by subcutaneous route rather than by intravenous route. Moreover, objective and subjective tolerance was excellent on r-HuEPO subcutaneous administration.
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PMID:[Comparison of the efficacy and tolerance of recombinant human erythropoietin between intravenous and subcutaneous administration in chronic hemodialysis. Prospective multicenter study]. 160 2

The effect of a six months therapy with human recombinant erythropoietin (rHu-EPO) on blood pressure and on several parameters of sympathetic nervous activity was studied in chronic haemodialysis patients in a controlled and randomized trial in order to gain further insight into the mechanism of rHu-EPO-induced blood pressure elevation. Treatment was started at a dose of 3 X 80 IE/kg/week in eleven patients aiming to increase the initial hemoglobin concentration (7.0 +/- 0.3 [SEM] g%) to 10.0 g% by dose adjustments, while another untreated eleven patients served as a control group. Diastolic arterial pressure measured before and after haemodialysis increased on rHu-EPO treatment by 7 and 8 mm Hg respectively (p less than 0.05). Plasma noradrenaline concentration was increased (p less than 0.05) after the six months treatment period in the presence of unchanged dry weights. Conversely platelet alpha 2-adrenoceptor density (3H-yohimbine binding) and the fraction of high affinity binding sites for alpha 2-agonists (3H-UK 14.304) decreased (p less than 0.01) along with a decrease in reactivity to exogenous noradrenaline (p less than 0.05). None of these parameters changed in the control group compared to pretreatment values. The results obtained demonstrate that increased plasma noradrenaline concentrations may participate in rHu-EPO induced blood pressure increases. The decrease in platelet alpha 2-adrenoceptor densities and the decrease in noradrenaline reactivity in the presence of increased plasma noradrenaline concentrations suggest an intact regulation of alpha 2-adrenoceptors in chronic haemodialysis patients on chronic rHu-EPO therapy.
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PMID:[Effect of erythropoietin therapy on alpha receptor density in chronic dialysis patients]. 165 81

Primary as well as secondary hyperparathyroidism may be associated with anemia, and parathyroidectomy (PTx) may improve or even heal it. The precise link between the two conditions is still matter of discussion. The purpose of the present study was to investigate possible effects of PTx on serum immunoreactive erythropoietin (iEPO) in secondary (group I, n = 23), and primary (group II, n = 16) hyperparathyroidism patients, and in 3 patients undergoing cervicotomy for thyroid mass removal (group III). In group I patients, circulating iEPO levels rose from 23.1 +/- 4.8 mU/ml before PTx to 28.2 +/- 5.0 and 245 +/- 125 mU/ml (mean +/- SEM) at day 7 (p = NS) and 14 after PTx (p less than 0.003), respectively. Reticulocyte count increased 2 weeks after PTx: from 61,000 +/- 13,317 to 86,533 +/- 13,462/mm3 (p less than 0.05, n = 23). In 4 of these patients serum iEPO levels could be measured again 12-24 months after PTx. They were slightly higher than those determined before PTx: 37.0 +/- 8.4 versus 31.8 +/- 13.5 mU/ml. Their hematocrits were also higher than before PTx: 12.8 +/- 0.9 versus 11.0 +/- 0.9 g/dl. In group II patients, serum iEPO levels remained unchanged after PTx: 17.5 +/- 2.0 mU/ml before PTx and 20.0 +/- 3.0 mU/ml 14 days PTx. The reticulocyte count, however, increased significantly 2 weeks after PTx: from 25,103 +/- 3,000 to 40,827 +/- 4,080/mm3 (p less than 0.01). In group III patients, serum iEPO, reticulocyte count, and hemoglobin remained stable after surgery. Since all group I patients had received vitamin D supplementation after PTx, we studied an additional group of 14 chronic dialysis patients (group IV) who received either calcitriol (1 micrograms/day, n = 7) or placebo (n = 7) during 14 days. The patients on calcitriol treatment, but not those on placebo, had a significant decrease of serum iEPO: 18.6 +/- 4.9 versus 16.0 +/- 4.2 mU/ml (p less than 0.03). In conclusion, PTx led to a striking increase of serum iEPO and blood reticulocytes in uremic patients with secondary hyperparathyroidism, and an increase of reticulocyte count, but not of iEPO, in patients with primary hyperparathyroidism. Marked changes of circulating PTH, extra-or intracellular calcium and phosphorus concentrations as well as of tissue sensitivity to EPO after PTx could all be responsible. In contrast, the surgical procedure and the therapeutic increase in plasma calcitriol do not appear to be involved.
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PMID:Serum erythropoietin and erythropoiesis in primary and secondary hyperparathyroidism: effect of parathyroidectomy. 175 26

In vitro experiments were performed to analyze problems with the determination of erythropoietin in dialysate. Human recombinant erythropoietin (EPO; 4000 U/L) was added to several fluids, to glass or polystyrene tubes with or without addition of bovine serum albumin (BSA) and to dialysate bags. The recovery in peritoneal effluent was 4120 +/- 203 U/L (mean +/- SEM). The recovery in the other fluids was less than 50% but in glass tubes it increased to 96% after addition of BSA. Binding was also found to the dialysate bag, therefore reducing the amount available for absorption. We recommend that EPO samples from the dialysate are drawn within BSA coated glass tubes.
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PMID:Accuracy of erythropoietin determination in the dialysate of CAPD patients. 198 29

Serum erythropoietin (S-EPO) levels were measured in 50 patients with anaemia of chronic disorders (ACD), classified into three groups according to their aetiology: inflammatory (n = 20), infectious (n = 15) and neoplastic (n = 15). The inflammatory group showed a higher mean S-EPO level (mean value +/- SEM, 69 +/- 11 mU ml-1) than the neoplastic (43 +/- 5 mU ml-1; P less than 0.05) and infectious groups (27 +/- 4 mU ml-1; P less than 0.01). The S-EPO level in the inflammatory group also differed from that of 32 healthy controls (36 +/- 3 mU ml-1; P less than 0.05). Fourteen patients with added iron deficiency (12 subjects from the inflammatory group) showed the highest S-EPO concentration (72 +/- 17 mU ml-1). Conversely, S-EPO levels were lower in febrile subjects (12 patients with infection and five with malignancy) than in non-febrile patients (28 +/- 4 mU ml-1 vs. 55 +/- 7 mU ml-1; P less than 0.01). In the infectious group, the logarithm of S-EPO correlated directly with the haemoglobin and haematocrit values. We conclude that differences in S-EPO concentration in ACD may be further related to the patient's iron stores and temperature. A decrease in EPO production may contribute to the pathogenesis of ACD secondary to infection.
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PMID:Serum erythropoietin levels in the anaemia of chronic disorders. 199 63

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

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

The effect of human recombinant erythropoietin (rhEPO) was investigated in 29 anemic patients with myelodysplastic syndromes (MDS). A rhEPO dosage of 150 U/kg was administered subcutaneously three times weekly for a minimum of 6 weeks. Seven out of 27 evaluable patients (26%) had an effective clinical response to therapy by increasing hemoglobin concentrations by more than 15 g/l (reaching at least 105 g/l) or by eliminating transfusion requirements. Six out of the seven patients responded within four weeks. Three of the responders successfully continued rhEPO treatment 15 months or more. To determine whether it may be possible to predict response to rhEPO, various clinical parameters were examined. Responders were found to be significantly different from non-responders in five aspects: They had less elevated baseline serum EPO levels (92 +/- 33 versus 515 +/- 108 U/l, mean +/- SEM; p = 0.023) and were more often transfusion-independent (71% versus 20% of non-responders; p = 0.022). Furthermore, responders were more often females (71% versus 40% in the non-responding group; p = 0.025), of subtype RA rather than RAEB (four patients and one patient, respectively, compared to seven and nine patients in the non-responding group; p = 0.025), and they predominantly displayed normal karyotypes or a 5q- aberration (86% versus 47%; p = 0.005). We conclude, that rhEPO treatment can reduce anemia in MDS and that certain pre-treatment clinical parameters may be used to predict response.
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PMID:Prediction of response to treatment with human recombinant erythropoietin in myelodysplastic syndromes. 837 82

To assess the efficacy of blood pressure control in continuous ambulatory peritoneal dialysis (CAPD), blood pressure was examined sequentially in 63 CAPD patients transferred from hemodialysis (HD), and in 97 patients started de novo on CAPD (NEW), over periods ranging from 3 to 63 months. Blood pressure changes were related to changes in body weight, hematocrit, and treatment with recombinant human erythropoietin (rHu-EPO), as well as to changes in antihypertensive drug requirements. Both groups of patients showed an immediate improvement in blood pressure control at 1 month, as manifested by an absolute decrease in blood pressure in HD patients (-4.3% +/- 2.1% [SEM], P < 0.05) and by a decrease in antihypertensive drug requirements in NEW patients (from 78% to 43.3%). This early improvement in blood pressure appeared to be volume-related, as reflected by changes in body weight. Both groups showed an additional decrement in blood pressure at approximately 6 months (-7.8% +/- 2.6% [SEM], P < 0.05, HD group; -3.4% +/- 2.4% [SEM], P < 0.05, NEW group). Treatment of anemia with rHu-EPO in 22 of the CAPD patients had no effect on blood pressure. CAPD thus appears to be more effective than HD in controlling blood pressure.
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PMID:Effect of continuous ambulatory peritoneal dialysis on blood pressure control. 843 Jun 80

Sensitisation to HLA antigens, formed as a result of transfusion, previous allografts or pregnancy, remains a significant problem in transplantation. The aim of this study was to define the causes of sensitisation of potential renal allograft recipients in Ireland in the post-EPO era. A retrospective survey of all patients who were active on the renal transplant waiting list during 1996 was performed evaluating the panel reactive antibodies (PRA), history of sensitising events, and waiting time for transplantation. Of a total of 244 patients (151 males, 93 females), 163 (67%) were not sensitised (PRA < 10%), and 35 (14%) were sensitised (PRA 10-59%), 15 subjects (6%) were significantly sensitised (60-79%) and 31 (13%) were highly sensitised (PRA > 80%). Only 59 (24%) patients had no sensitising events recorded. Fifty-eight (24%) subjects had previous allografts. Transfusion was documented in 173 (71%) subjects. Pregnancy was noted in 55/93 (59%) female subjects. All highly sensitised patients had been transfused. Eighty per cent (12/15) significantly sensitised and 97 (60%) of the non-sensitised subjects had been transfused. The level of sensitisation clearly increased with the number of units transfused. Non-sensitised subjects received a mean of 5.65 units (SEM 1.38), sensitised subjects a mean of 9.8 units (SEM 3.17), significantly sensitised a men of 18.2 units (SEM 6.51), while highly sensitised subjects received a mean of 37.8 units, (SEM 8.4). There was a direct relationship between the waiting time for transplantation and the degree of sensitisation. The percentage of patients who had been transfused in the 1996 cohort (71%) was similar to the percentage of patients transfused on the waiting list in August 1999 (75%). These data demonstrate that transfusion remains an important cause of sensitisation, despite the use of EPO. Measures to further reduce the use of transfusion or the use of immunosuppression at the time of transfusion in potential allograft recipients may be of value in the future.
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PMID:Causes of sensitisation in patients awaiting renal transplantation in Ireland. 1279 72


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