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)

Decreased production of erythropoietin (Epo) as a result of reduced renal mass is considered the main factor underlying the anaemia that is invariably associated with chronic renal failure (CRF). Other mechanisms such as accumulation of inhibitors of Epo also contribute. In this study we show that supernatant from peripheral blood mononuclear cells (PBMC) cultured from patients with CRF inhibits Epo release by Hep G2 cells in vitro. Ten patients (5 male) with CRF (mean age 42 years, range 25-60) were studied. Five were approaching end-stage renal failure and five were maintained on haemodialysis (HD). Ten apparently healthy volunteers were used as controls. Full blood counts and serum Epo (RIA) levels were determined and adherent PBMC were cultured for 48 h with and without LPS. There was a significant rise in TNF-alpha and IL1-beta levels measured in monocyte supernatant (MS) from patients and controls after LPS stimulation (P < 0.05) and in IL-1 alpha levels in patients (P < 0.05). IL-1 beta levels were higher in patients compared to controls both before and after stimulation with LPS (P < 0.05). Hep G2 cells were cultured in 5% CO2 and 20% O2 and incubated with MS from patients and controls for 24 h. Hep G2 harvest fluids were then analysed for Epo levels, which were expressed as a function of total cell protein (mU/mg). Epo production was inhibited by MS from patients compared to controls both before and after stimulation with LPS (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1994
PMID:Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro. 797 Jan 19

Correction of anemia with recombinant human erythropoietin (rHuEPO) in patients with end-stage renal disease (ESRD) has been associated with improvement of several endocrine abnormalities. However, long-term effects of this therapy on pituitary secretion in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The aim of the present work was to assess the growth hormone (GH) and cortisol responses to insulin-induced hypoglycemia before and after the correction of anemia with rHuEPO therapy in CAPD patients. Five well-nourished and clinically stable patients were studied before and after 12-24 weeks of rHuEPO treatment. Seven normal volunteers were studied as controls. Insulin-induced hypoglycemia tests were performed prior to starting rHuEPO therapy and again after partial correction of anemia. Blood samples for GH, cortisol, and glucose were collected between -30 and 120 min after insulin (0.1 U/kg bw) administration. GH responses to hypoglycemic stress were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (10.6 +/- 4.8 micrograms/L and 15.4 +/- 6.1 micrograms h/L, respectively) did not differ from those obtained in control subjects (14.3 +/- 4.1 micrograms/L and 19.4 +/- 3.5 micrograms h/L, respectively). The study, after correction of anemia, showed an evident decrease of GH values at each time point on the response curve in 4 patients, and no modification in 1 patient. Mean values of GH peak and AUC were 8.8 +/- 2.8 micrograms/L and 9.6 +/- 2.3 micrograms h/L.(ABSTRACT TRUNCATED AT 250 WORDS)
Adv Perit Dial 1994
PMID:Growth hormone and cortisol secretion before and after erythropoietin therapy in CAPD patients. 799 45

As already reported short-term rHuEpo treatment influences plasma insulin, glucagon, pancreatic polypeptide (PP), and gastrin secretion in haemodialysed patients. The present study aimed to assess the influence of long-term rHuEpo treatment on secretion of above mentioned hormones. A total of 27 haemodialysed patients and nine healthy subjects were examined. Nine patients with uraemic anaemia were treated with rHuEpo for 12 months (Epo group) while another nine patients did not receive rHuEpo (non-Epo group), but were monitored biochemically and clinically as patients of the Epo group. The third group (HD) comprised nine haemodialysed patients with a haematocrit value of > or = 30% without rHuEpo therapy. In all subjects plasma levels of insulin, glucagon, gastrin, and PP were estimated before and after administration of a test meal. Patients of the Epo group were examined before and after 6 and 12 months of rHuEpo treatment (patients of the Epo group) or clinical monitoring (patients of the non-Epo group) respectively, while only one test was performed in patients of the HD group and healthy subjects. Six months of rHuEpo treatment was followed by an increase of fasting insulinaemia and a decrease of basal plasma level of glucagon and PP. At that time point rHuEpo therapy also increased the response of insulin, glucagon, and gastrin to the test meal.(ABSTRACT TRUNCATED AT 250 WORDS)
Nephrol Dial Transplant 1994
PMID:Influence of long-term erythropoietin treatment on insulin, glucagon, pancreatic polypeptide, and gastrin secretion in haemodialysed patients. 807 22

Erythropoietin (EPO) given subcutaneously (SC) once per week has been successful in the treatment of anemia in continuous ambulatory peritoneal dialysis (CAPD) patients. We have identified a population of CAPD patients that requires EPO administration once per week or less often. To determine if specific variables could be identified that would predict which CAPD patients would require infrequent EPO dosing, we reviewed the charts of all our CAPD patients who were receiving EPO as of 1 June 1992. Patients had to have been on CAPD for 3 months and EPO for 3 months to be considered for analysis. We identified 12 patients who required EPO once per week or less frequently (infrequent EPO) and 9 patients who required EPO more than once per week (frequent EPO). Parameters that were analyzed included age, gender, race, time on CAPD, history of gastrointestinal bleeding, exit-site infection or peritonitis in the last 60 days, diabetes, amount of dialysate instilled per day, and the number of exchanges per day. Laboratory data that were analyzed included hemoglobin, hematocrit, serum iron, total iron-binding capacity, ferritin, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, albumin, total protein, parathyroid hormone, and aluminum. Categorical data were analyzed via chi-square, and numerical data were analyzed via the t-test. The infrequent EPO group required only 35% as much EPO as the frequent group to maintain hemoglobin and hematocrit, which were significantly greater. The only parameter that was different between the two groups was age (infrequent EPO 42 +/- 13.2 vs frequent EPO 55.8 +/- 11.9 years, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Adv Perit Dial 1993
PMID:Infrequent dosing of subcutaneous erythropoietin for the treatment of anemia in patients on CAPD. 810 57

Changes in blood pressure and haemoglobin concentration before and after renal transplantation were compared in 15 patients with renal failure due to chronic pyelonephritis who had undergone pretransplant bilateral nephrectomy and 15 control patients whose primary renal disease was chronic pyelonephritis and who were matched for age, sex and graft function but had not undergone nephrectomy. Bilateral nephrectomy resulted in a significant worsening of anaemia prior to transplantation and a decline in blood pressure. However, by 6 and 12 months after renal transplantation both haemoglobin and blood pressure were similar in nephrectomized and non-nephrectomized patients and in the normal range. We conclude that in patients with renal failure due to chronic pyelonephritis, pretransplant nephrectomy has no major impact on long-term blood pressure and haemoglobin levels achieved after successful renal transplantation.
Nephrol Dial Transplant 1993
PMID:Effect of prior bilateral nephrectomy on haemoglobin and blood pressure outcome after transplantation. 827 31

The efficacy of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia is well established. To assess the effect of rHuEpo treatment on physical performance we evaluated physical working capacity, oxygen uptake and red cell 2,3-diphosphoglycerate (DPG) values at rest and during and after exercise on a bicycle spiroergometer in eight chronically haemodialysed patients. Follow-up examination was carried out after a mean of 14 weeks (range 9-19 weeks), when mean haemoglobin had increased from 7.8 to a stable value of 13.0 g/dl in response to rHuEpo treatment (P < 0.001). Physical working capacity and oxygen uptake at the anaerobic threshold (4 mmol/l blood lactate concentration) increased from 68 +/- 12 to 80 +/- 16 watts and 0.95 +/- 0.14 to 1.10 +/- 0.20 l/min, respectively (P < 0.01). DPG, which determines oxygen affinity to haemoglobin in red cells, increased by 13% from 13.7 +/- 1.5 to 15.5 +/- 2.2 mumol/g Hb (P < 0.05). With maximal exercise mean DPG values significantly decreased to a much lower level without rHuEpo treatment than after correction of anaemia. Therefore rHuEpo treatment results both in better oxygen transport capacity and reduced intraerythrocytic oxygen affinity, which is followed by improved oxygen delivery to tissues per unit of haemoglobin. These effects may explain the improvement of exercise capacity observed in dialysis patients after rHuEpo treatment.
Nephrol Dial Transplant 1993
PMID:Increased red cell 2,3-diphosphoglycerate levels in haemodialysis patients treated with erythropoietin. 830 59

Although the haemostatic defects that occur in uraemia are complex, a major factor is the anaemia of renal failure. This may now be corrected by recombinant human erythropoietin (rHuEpo) therapy rather than by repeated blood transfusion. Platelet reactivity to shear stress and collagen was measured using non-anticoagulated blood to study the effect of erythropoietin or blood transfusion on platelet function. Twenty dialysis patients were commenced on 25-50 U/kg rHuEpo twice weekly. The dose was adjusted after 3 months to maintain target Hb 10-10.5 g/dl. A further 15 patients were studied before and 10-12 days after receiving blood transfusion. Baseline platelet reactivity was subnormal in both groups versus control (P < 0.0001). In the rHuEpo group, a significant increase in platelet reactivity was observed at 2 months (P < 0.005) which disappeared at 3 months. This was not related to the increase in Hb (7.3 +/- 0.3 to 10.2 +/- 0.3 g/dl, P < 0.0001). There was no change in platelet reactivity after transfusion, despite an increase in Hb (6.2 +/- 0.2 to 8.8 +/- 0.2 g/dl, P < 0.0001) similar to that occurring in the rHuEpo group. We conclude that after rHuEpo therapy but not after transfusion a transient increase in platelet reactivity occurs which is dissociated from changes in platelet and red cell numbers.
Nephrol Dial Transplant 1993
PMID:Enhanced platelet reactivity with erythropoietin but not following transfusion in dialysis patients. 838 86

Fatigue and lethargy, common symptoms in uraemia, have been attributed to many factors. To assess possible bioenergetic contributions to this, we examined the forearm muscle of five patients in end-stage renal failure using 31P-magnetic resonance spectroscopy. There was a small increase in the ratio of intracellular inorganic phosphate to ATP in resting muscle, suggesting an increased cytosolic phosphate concentration. During exercise, increased phosphocreatine breakdown was accompanied by rapid intracellular acidification and an increase in calculated lactic acid accumulation in the muscle of the uraemic subjects, suggesting glycolysis dominating over oxidative phosphorylation as a source of ATP. After exercise, the half-time of phosphocreatine (PCr) recovery was longer in the uraemic subjects, suggesting diminished mitochondrial function. The initial rate of PCr resynthesis was not significantly decreased, but when account was taken of the high cytosolic ADP concentration (which drives mitochondrial oxidative ATP synthesis) the calculated maximum oxidative capacity was significantly reduced in the uraemic subjects. Thus there was evidence of mitochondrial dysfunction in uraemia due either to limitation of oxygen supply, reduced mitochondrial content, or an intrinsic mitochondrial defect. This resulted in increased phosphocreatine depletion and increased glycolytic ATP production during exercise and there was partial compensation of the mitochondrial abnormality by increased ADP concentration. In three of these patients studied after elevation of haemoglobin with erythropoeitin (from 8 to 12 g/dl), initial phosphocreatine breakdown and lactic acid accumulation during exercise were normalized, while exercise duration and calculated maximum oxidative capacity remained significantly abnormal. This suggests that anaemia contributes to these metabolic abnormalities but does not fully explain them.
Nephrol Dial Transplant 1993
PMID:Effect of chronic uraemia on skeletal muscle metabolism in man. 838 87

Treatment of the anaemia of predialysis patients with recombinant human erythropoietin (rHuEpo) is likely to become a widely accepted practice during the coming years. We estimated the impact on health care expenditures with the example of the French population of end-stage renal disease patients. Using retrospective data, we calculated the percentage of predialysis patients with advanced chronic renal failure who would be eligible for treatment according to two different criteria based on haemoglobin and clinical condition, the total duration of treatment, and the total amount of rHuEpo delivered. We estimate that the total cost of treating French predialysis patients could vary between 2.2 and 6.5 million Swiss francs, or 50,000 to 140,000 Swiss francs per million population, using rHuEpo dosage from 50 to 150 IU/kg week.
Nephrol Dial Transplant 1993
PMID:Cost of treating predialysis patients with recombinant human erythropoietin. 839 4

Recombinant human erythropoietin (rHuEpo) was used to treat the anaemia of four haemodialysed patients (3 males, 1 female) with advanced multiple myeloma; the type of serum M component was IgG kappa in all cases. During the 6-month period preceding rHuEpo therapy the patients received multiple blood transfusions (range 4-22 units of packed red cells per patient). After the first month of treatment haematocrit increased from 23 +/- 3 (SD) to 32 +/- 4% and during the last 3 months the maintenance dose of rHuEpo was 143 +/- 37 U/kg per week to achieve a mean haematocrit of 35 +/- 1%. After introduction of rHuEpo, blood transfusions were no longer required and the patients reported an improvement in wellbeing. No apparent worsening of multiple myeloma has been observed over the treatment period ranging from 5 to 34 months (cumulative duration of treatment 55 months). Anti-hypertensive therapy was started in one case and increased in two patients. We conclude that rHuEpo appears to be effective and safe in treating anaemia associated with multiple myeloma in patients requiring haemodialysis.
Nephrol Dial Transplant 1993
PMID:Safety and efficacy of recombinant human erythropoietin treatment of anaemia associated with multiple myeloma in haemodialysed patients. 781 13


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