Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0085584 (encephalopathy)
18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The uremia of chronic renal failure (CRF) can alter brain electrophysiology and cognitive function, even in the well-dialyzed patient. The effect of uremia on brain function can be assessed by electrophysiologic techniques such as electroencephalogram (EEG), sensory-evoked potentials (EPs), and cognitive event-related potentials (ERPs), and through a series of neuropsychologic tests. Five tests have been used clinically to measure the speed and efficiency of cognitive functioning and include the following: Number Cancellation, Trailmaking Test, Symbol Digit Modalities Test, Rey Auditory Verbal Learning Test, and Controlled Oral Word Association Test. Test performance by patients with CRF is often below that of healthy controls. Auditory ERPs, a sensitive indicator of subtle changes in central nervous system (CNS) function in uremia, result in the generation of a P300 component wave that varies in amplitude and latency with patient variables such as attention and effort. Although dialysis tends to normalize P300 latencies, the waves remain somewhat prolonged in most patients. The anemia often observed in patients receiving chronic dialysis appears to aggravate uremic encephalopathy. This effect can be reversed when anemia is corrected following administration of recombinant human erythropoietin (epoetin). Improvement in P300 amplitudes, and, in some cases, decreases in P300 latencies correlated well with epoetin-induced increases in hematocrit levels. With the correction of anemia, that component of brain dysfunction not attributable to retention of uremic toxins can largely be reversed.
...
PMID:Epoetin and cognitive function. 162 53

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.
...
PMID:Recombinant human erythropoietin to correct uremic bleeding. 206 54

We evaluated the need for erythropoietin (EPO) treatment in 134 end-stage renal disease patients assuming a level of hemoglobin below 6 mmol/l (9.6 g/dl) as indication for treatment. 91 patients (68%) fulfilled this criterion. Absolute contraindications in 2 patients were previous thrombotic encephalopathy and refusal of treatment. Relative contraindications due to cardiac disease were found in 3 patients. In 15 patients additional treatment was required because of hypertension (5) or deficiency states (10). The implications of elevated serum PTH and aluminum overload are discussed.
...
PMID:On the need for erythropoietin treatment in dialysis patients. A Copenhagen City Dialysis Unit study. 222 88

Recombinant human erythropoietin raises serum erythropoietin concentrations to adequate levels and restores the hematocrit to normal values in the vast majority of anemic, end stage renal disease patients undergoing regular hemodialysis. It can eliminate the need for transfusions and thus the risk of immunologic sensitization, infection and iron overload. Erythropoietin not only alters laboratory findings but improves the well being and performance of patients on hemodialysis as well. Side effects are minimal and neither antibodies nor resistance to the recombinant hormone have been observed so far. Along with the rise in hematocrit and blood viscosity some patients developed increased blood pressure and a few hypertensive encephalopathy, but after brief interruption of therapy erythropoietin treatment could be continued in combination with antihypertensive drugs. The pathophysiology of the increase in blood pressure, the risk of encephalopathy and the possibly somewhat higher risk of thrombosis remain to be elucidated. Nevertheless, the first recombinant hematopoietic hormone has passed its first clinical trials with success.
...
PMID:[Erythropoietin--the first hematologic hormone in clinical use]. 328 1

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)
...
PMID:Historical review on the use of recombinant human erythropoietin in chronic renal failure. 764 3

It is well known that the effects of human recombinant erythropoietin (rHuEPO) are dose-dependent. However, when higher doses of rHuEPO are used, the frequency of the side effects also increases. The aim of our study was to analyze the hematologic parameters and blood pressure response in hemodialysis patients treated with low initial and gradually increased rHuEPO. Sixteen regular hemodialysis patients were treated with 3 x 20 U/kg/week of rHuEPO subcutaneously during the first month. Every fourth week the dose was increased by 3 x 20 U/kg/week if the hematocrit did not rise by 2%. If the elevation was 2% or more, the dose of the rHuEPO was not changed. Blood count and blood pressure were checked every week. The antihypertensive treatment was also reviewed weekly. The hematocrit increased significantly from the second week, and 11 patients achieved the target level (30%) between Weeks 8 and 24. Two patients reached the 30% hematocrit level between Weeks 2 and 8, and another 2 patients reached the target level between Weeks 25 and 28. There was 1 nonresponder. The average rHuEPO dose needed to achieve the target hematocrit was 56.3 U/kg/week. We did not observe significant changes in the mean arterial or diastolic blood pressure. It was necessary to increase the doses of antihypertensive drugs, namely nifedipine and captopril, to control blood pressure. Encephalopathy occurred in none of the cases. The low initial dose and the gradual increase of rHuEPO treatment were beneficial to the hemodialysis patients. Although the target hematocrit took longer to achieve, high blood pressure and encephalopathy were prevented by close monitoring and administration of suitable antihypertensive treatment.
...
PMID:The beneficial effect of low initial dose and gradual increase of erythropoietin treatment in hemodialysis patients. 774 44

Surfactant administration for respiratory distress syndrome continues to make an impact on neonatal care as large controlled trials are published. Although considered safe, synthetic surfactant administration has been associated with a rare complication in the form of pulmonary hemorrhage. Despite this, significant benefits have been shown. With the approval by the FDA of two surfactant preparations, this treatment is now in widespread use. Although the mortality rate from respiratory distress syndrome and the number of ventilator days are generally decreased, surfactant effect on the incidence of bronchopulmonary dysplasia has been disappointing. Studies of steroid administration for bronchopulmonary dysplasia and steroid side effects have been published in the past year. Steroid use has become widespread for this condition, although many details of its administration and side effects have yet to be worked out. A new area of promise is the use of erythropoietin for anemia of prematurity. Natural historic data on the retinopathy of prematurity have added to our understanding of this condition and have raised new questions on its pathogenesis. Review articles and studies in the area of neonatal encephalopathy stress the need for a more accurate definition of asphyxia and discuss possible prenatal causes of this condition. An extensive review of neonatal jaundice and new recommendations for its treatment in healthy term newborns has been published but remains controversial.
...
PMID:Care of the neonate. 842 28

Human recombinant erythropoietin is used to treat chronic anemia in patients with end-stage renal failure. Erythropoietin causes hypertension, and hypertensive encephalopathy has been associated with its use. We describe six dialysis-dependent, chronic renal failure patients who developed hypertension, headache, and seizures while on erythropoietin. Four of the six patients had posterior white matter changes on neuroimaging. The encephalopathy was managed by prompt antihypertensive and anticonvulsant treatment and by discontinuation of erythropoietin. Hypertensive posterior leukoencephalopathy is associated with erythropoietin use.
...
PMID:Erythropoietin-associated hypertensive posterior leukoencephalopathy. 971 75

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p < 0.001), Group 3 (p < 0.01), and Group 4 (p < 0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p < 0.05) and Group 4 (p < 0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p < 0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p < 0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p < 0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.
...
PMID:Oral phosphate binders: phosphate binding capacity of iron (III) hydroxide complexes containing saccharides and their effect on the urinary excretion of calcium and phosphate in rats. 1051 89

Hypoxic-ischemic encephalopathy seen in survivors of perinatal asphyxia is a frequently encountered and a major clinical problem for which there is currently no effective treatment. Hematopoietic neuroprotective agents, such as erythropoietin (EPO) may rescue neurons from cell death in this setting. EPO is a cytokine hormone that has neuroprotective effect in vitro and in vivo. In this study, we evaluated the effect of posthypoxic EPO administration in an animal model of neonatal hypoxic-ischemic injury. Our results show that a single intracerebroventricular injection of EPO immediately after hypoxic-ischemic insult in neonatal rat model of hypoxic-ischemia reduced the extent of hypoxic-ischemic brain damage. The mean infarct volume assessed 7 days after hypoxia was significantly smaller in EPO-treated group than in the control group. These findings suggest that EPO may provide benefit after hypoxic-ischemic events in the developing brain, a major contributor to static encephalopathy and cerebral palsy.
...
PMID:Erythropoietin exerts neuroprotective effect in neonatal rat model of hypoxic-ischemic brain injury. 1312 93


1 2 3 4 5 Next >>