Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the last 18 years, we have observed 24 cases of hypoparathyroidism (HPT) in beta-thalassemia major. At present, 4.5% of patients followed regularly in our department have this complication. HPT is thought to be mainly the consequence of iron deposition in the parathyroid glands. The age of our patients when HPT was diagnosed ranged from 11 to 24 years (mean 16.5 years). Their serum ferritin levels ranged from 810 to 15,200 ng/ml (mean 3,772 ng/ml). The severity of HPT varied widely. In only 3 patients was hypocalcemia severe with signs of tetany, seizures or cardiac failure. The onset of HPT was preceded or followed in most patients by other endocrine and/or cardiac complications. We found no clear relationship between HPT and serum ferritin levels in our patients, suggesting either an individual sensitivity to iron toxicity or early damage of the parathyroid gland before chelation had reduced the iron overload. However, the diagnosis of no new cases of HPT in the last 3 years coinciding with the much improved regime of chelation therapy suggests that chelation may have helped to prevent the development of HPT.
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PMID:Hypoparathyroidism in beta-thalassemia major. Clinical and laboratory observations in 24 patients. 146 90

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.
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PMID:Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile. 179 95

Seizures, hypertensive encephalopathy, transient ischemic attacks, and thrombosis of hemodialysis accesses occurred in early clinical trials with recombinant human erythropoietin. To determine if these events may be caused by the increased hematocrit value or some direct effect of the recombinant human hormone, 10 transfusion-dependent hemodialysis patients were divided into two groups of five according to their serum ferritin concentration: group A. less than 800 microgram/liter, and group B. greater than 800 micrograms/liter. After a month of placebo administration, recombinant human erythropoietin was given (150 U/kg intravenously thrice weekly) for four months and then stopped for one month. Hematocrit values were maintained at 0.33 +/- 0.02 (mean +/- SD) by dose adjustment in group A and at 0.26 +/- 0.02 by thrice weekly phlebotomies in group B, who received a constant dose of erythropoietin. Viscosity increased from subnormal to normal in group A (P less than 0.02) and cerebral blood flow decreased from above normal to normal (P less than 0.02). In group B minor, statistically insignificant, changes in viscosity and reciprocal changes in cerebral blood flow also occurred. There was no change in either group in transcutaneous oxygen tension. Bleeding time decreased toward normal in both groups during recombinant human erythropoietin administration but the changes did not reach statistical significance. Fibrinogen levels were increased in all patients but remained unchanged. No other significant coagulation-related changes were observed. Recombinant erythropoietin in the dosage and schedule of administration described in this study did not lead directly or indirectly to changes likely to precipitate seizures or intravascular thrombosis.
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PMID:Effects of recombinant human erythropoietin on cerebral and cutaneous blood flow and on blood coagulability. 226 76

The treatment of severe anemia related to end-stage renal disease with recombinant human erythropoietin (r-HuEPO; EPOGEN, [epoetin alfa] AMGEN Inc, Thousand Oaks, CA) has been investigated in more than 1,500 hemodialysis patients worldwide. The goal of r-HuEPO therapy is to maintain the hematocrit level at 35%, with a recommended starting dose of 150 mg/kg of body weight, administered intravenously after each dialysis three times a week for 6 to 12 weeks. Hematocrit levels should be measured at least once a week and the dose adjusted in increments or decrements of 10 mg/kg to 25 mg/kg to keep the hematocrit level between 33% and 40%. Patients receiving r-HuEPO must be normotensive. A history of seizures has been cause for exclusion from clinical trials. Patients' iron status should also be adequate at the onset of therapy, which is defined as a serum ferritin level of 100 ng/mL or more, and a transferrin saturation of more than 20%. Iron status and BP must be carefully monitored, and abnormalities corrected with iron supplementation, ultrafiltration, or antihypertensive medication. The lack of controlled studies makes determination of the actual incidence of side effects difficult, but it appears to be minimal. Possible side effects of r-HuEPO therapy include hypertension, seizures, myalgia, malaise, headache, gastrointestinal distress, and injected conjunctiva. The major benefits of r-HuEPO therapy are reduced need for transfusion and marked improvement in quality-of-life parameters.
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PMID:Who should receive recombinant human erythropoietin? 266 84

Striopallidodentate calcinosis (Fahr's disease) is characterized clinically by seizures, rigidity, and dementia and pathologically by mineral deposition in the basal ganglia, dentate nucleus, and cerebral cortex. Disorders of iron and calcium-phosphate metabolism are thought to play a role in its pathogenesis. We present the case of a patient with familial striopallidodentate calcinosis who had porphyria cutanea tarda, refractory anemia, and pseudohypoparathyroidism type 2. The serum level of ferritin was markedly increased, serum iron and iron-binding capacity were below normal, and at autopsy she had deposition of iron in liver, spleen, bone marrow, and brain. She showed intermittent mild hypocalcemia, increased serum values of parathyroid hormone, elevated renal tubular reabsorption of phosphate, and low serum levels of 1,25-dihydroxyvitamin D, suggesting blunted renal responsiveness to endogenous parathyroid hormone. Pseudohypoparathyroidism type 2 was confirmed by infusion of synthetic parathyroid hormone, which gave a normal urinary cyclic adenosine monophosphate response, but a blunted phosphaturic response. After splenectomy for hypersplenism and weekly phlebotomies, she showed progressive improvement in function, mental status, weight, and seizure control. The hypothesis advanced is that the underlying pathophysiology of the separate diseases contributed to the formation of the brain stones through mechanisms of defective iron transport and free radical production.
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PMID:Abnormal systemic metabolism of iron, porphyrin, and calcium in Fahr's syndrome. 281 30

Postmortem human brain analyses have been performed to further evaluate pathogenetic aspects of the Rett syndrome. While there are no significant abnormalities with respect to amino acid concentrations in putamen, caudate nucleus, red nucleus and thalamus, the concentration of kynurenine is increased in putamen, caudate nucleus, gl. pallidus, raphe and amygdaloid n. In contrast, serotonin and its metabolite 5-hydroxyindole acetic acid are below normal levels. D2-receptor number is decreased and there is a significant drop in the concentration of the iron-binding protein ferritin. It can be concluded, that reduction of D2-receptors is due to loss of cholinergic and GABA-ergic cell bodies in the striatum or may be a response to iron deficiency. Low serotonergic and high kynurenergic activity may be of pathogenetic importance in the frequently observed cerebral seizures in Rett syndrome.
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PMID:Preliminary brain autopsy findings in progredient Rett syndrome. 308 91

The recombinant human erythropoietin (rHuEPO) by subcutaneous route has been considered the drug of choice for the correction of the anemia of chronic renal patients. PURPOSE--To evaluate the efficacy of a new preparation of rHuEPO in the correction of the anemia of chronic renal patients maintained by haemodialysis, exclusively administered by subcutaneous route, studying the adverse effects and searching for predictive factors for the response to this medication. METHODS--Twelve patients in regular haemodialysis were treated with freeze-dried rHuEPO by subcutaneous route during 18 months with initial doses of 20U/kg/dialysis. They were submitted to a careful clinical and laboratory monitoring for all this study. RESULTS--Eleven patients ended the study reaching the target hematocrit (Htc) of 30% and keeping it during the whole period of the study. The mean correction and maintenance doses of rHuEPO were 65U/kg/dialysis and 51U/kg/dialysis respectively. At the 12th week of the study a significative increase of Htc (18.4 +/- 3.5% vs. 25.4% +/- 3.8%, p < 0.05) was demonstrated. An increase of the erythrocytes and hemoglobin was concomitantly observed. Leucocytes and platelets increased significantly from the 24th week and kept steadily until the end of study. Just potassium increased in the biochemistry analysis of the patients at the 4th and the 12th week of the study returning to the basal values at the 24th week. The evolution of the iron metabolism parameters demonstrated an intermitent and statistically significant decrease of transferrin saturation at the 1st, 12th and 24th week, returning to the basal levels at the end of study. The serum ferritin did not change (582.7 +/- 700, 9ng/mL vs. 700.0 +/- 651, 6ng/nL). The weight and the blood pressure did not change either, although 2 normotensive patients became hypertensive and 2 others with controlled hypertension needed drug rearrange for blood pressure control (36%). A patient had a seizure episode with a full recovery. CONCLUSION--The rHuEPO has proved to be a safe and an efficient drug with easily controlled adverse effect.
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PMID:[Correction of anemia in chronic kidney failure with lyophilized recombinant human erythropoietin using a subcutaneous approach]. 782 Jan 45

We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg. Three sets of parameters were examined in this homogenous patient population: (1) factors that affect the plasma kinetics of busulfan, such as age and pre-transplant liver status defined by liver function tests, ferritin levels and liver biopsy; (2) busulfan-related toxicity: occurrence of veno-occlusive disease, seizures and idiopathic interstitial pneumonitis; and (3) the relationship between busulfan exposure and transplant outcome: engraftment delay or rejection, aplasia, occurrence of mixed chimeras and mortality. Kinetic analysis of first and 10th dose (using area under the curve (AUC), maximum and minimum concentration) as comparable, showing no sign of accumulation or decline in busulfan plasma levels over time. Age and liver status did not influence busulfan metabolism. No relationship was found between busulfan exposure and toxicities or transplant outcome. We conclude that busulfan monitoring is not predictive in children and young adults with homozygous beta-thalassemia receiving busulfan and high-dose cyclophosphamide along with histocompatable sibling donor marrow.
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PMID:Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia. 942 69

Although previous results have shown unequivocally that pre-ischaemic hyperglycaemia aggravates brain damage due to transient ischaemia, several questions have remained unanswered. First, is the effect of hyperglycaemia due to a further fall in intra- and extracellular pH? Second, is aggravation of damage a step function of a continuous function of plasma glucose concentration or of pH? Third, which are the mechanisms responsible for aggravation of damage, notably for the transformation of selective neuronal damage to infarction, for oedema development, and for post-ischaemic seizures? Recent results have provided new information on all of these issues. Thus, normoglycaemic animals with superimposed hypercapnia showed a similar, albeit not identical, aggravation of ischaemic damage, suggesting that acidosis is one major mediator. Furthermore, experiments with graded increase in plasma glucose concentration revealed a threshold effect at values of 10-12 mM, while microelectrode measurements showed a narrow extracellular pH range (6.4-6.5) for post-ischaemic seizure development. These results suggest that aggravation of damage due to excessive acidosis is due to mechanisms with a steep pH dependence. Finally, results are now at hand suggesting that the effect of acidosis is not mediated by a further perturbation of cell calcium metabolism. The more likely mediators are free radicals. Thus, acidosis is known to enhance iron-catalysed production of reactive oxygen species, probably by releasing iron from its bindings to transferrin, ferritin and other proteins.
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PMID:Role of hyperglycaemia-related acidosis in ischaemic brain damage. 942 66

All patients (48) followed by the chronic dialysis program on either peritoneal dialysis or incenter hemodialysis who received epoetin were included in this 1 year retrospective study. Variables evaluated included appropriateness of patient selection, drug dosage, monitoring of epoetin therapy as well as treatment outcome, incidence of side effects, cost versus reimbursement of epoetin, and need for iron supplementation. The target hematocrit of 30 to 36% was reached by 84.6% of patients. The difference between the baseline and treatment hematocrits was statistically significant (p less than 0.01). The average number of transfusions dropped significantly from 0.66 to 0.11 per patient per month (p less than 0.01) and the mean percentage of cytotoxic panel reactivity antibody was also significantly reduced (p less than 0.01) during treatment with epoetin. Serious side effects of epoetin therapy were rare, but four hemodialysis patients experienced five episodes of clotted accesses. The incidence of hypertension requiring addition or change of antihypertensive medication was 17.1%. No seizures were observed during the study period. The results of this study also revealed that more careful attention to iron status was needed during the period of data collection. A nomogram for prediction of iron need based on initial hemoglobin and ferritin levels was also studied and found to be accurate in 87.5% of patients.
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PMID:Drug usage evaluation of epoetin in chronic renal failure. 1012 21


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