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Extensive clinical studies have documented the effectiveness of recombinant human erythropoietin (rHuEPO) in correcting the anemia of adult dialysis patients, but the safety and efficacy of rHuEPO in children with renal anemia cannot yet be confirmed, due to the relative deficiency of reported studies involving pediatric subjects. To date, published experience with rHuEPO therapy in children has totaled 257 patients, although the majority of these reports have appeared only as abstracts. Overall experience has been favorable, with renal anemia and transfusion dependency successfully resolved in almost all pediatric patients reported. However, controlled clinical trials have not been performed, so it is not yet possible to clearly define the risks associated with rHuEPO therapy in children. Hypertension appears to occur or become worse in up to one third of treated children, but it is unclear to what extent rHuEPO therapy is accompanied by an increased risk of seizures, thrombosis of vascular access, hyperkalemia, hyperphosphatemia, or peritonitis (when administered via the intraperitoneal route). Only preliminary and somewhat conjectural recommendations can be offered regarding pediatric rHuEPO dosing, route of administration, special precautions, and adjunctive monitoring and therapy. Fortunately, a multicenter controlled clinical trial is underway that is designed to address these issues. Because the harmful effects of renal anemia are typically more profound for children than they are for adults, the benefits of rHuEPO promise to be even greater among pediatric patients. Whether rHuEPO therapy will substantially improve growth and neurologic and psychosocial development remains to be seen, but the potential is there for rHuEPO to dramatically improve the lives of children who suffer from the effects of the anemia of chronic renal failure. Other non-renal anemias that afflict pediatric patients, such as the anemia of prematurity, also may be amenable to rHuEPO therapy.
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PMID:Pediatric uses of recombinant human erythropoietin: the outlook in 1991. 192 79

Recombinant human erythropoietin represents a potential therapeutic alternative to red blood cell transfusions in a number of pediatric anemias. It is effective in correcting anemia associated with chronic renal failure and may significantly reduce the morbidity associated with childhood CRF. Most exposures to allogeneic blood products in pediatrics for treatment of anemia with blood transfusions occur in neonatal intensive care units. If proven effective in treating anemia in premature babies, r-HuEPO will be responsible for a major reduction in the use of blood transfusions in clinical neonatology. Carefully designed, placebo-controlled clinical trials will be required to establish the role of r-HuEPO in anemia of prematurity. Recombinant human erythropoietin also may be useful to increase the amount of blood that can be collected before elective surgical procedures. Another potential indication is to raise the hematocrits of infants with large intracardiac shunts who develop congestive heart failure coincident with the developmental fall in hemoglobin concentration after birth. Finally, r-HuEPO may one day play a role in modifying the expression of globin genes and, thereby, ameliorate the course of sickle cell disease and beta thalassemia. Many questions surrounding the use of r-HuEPO in infancy and childhood are being addressed in ongoing clinical trials.
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PMID:Recombinant erythropoietin in pediatrics: a clinical perspective. 218 91

Epoetin (recombinant human erythropoietin) is now a widely available though expensive treatment for the anaemia of chronic renal failure, and is effective in more than 95% of patients. Complications of epoetin in this context include hypertension in a third of cases, including hypertensive encephalopathy in a few, and thrombosis of shunts or vascular access devices. Fears that epoetin would cause progression of renal failure have not generally been confirmed, but hyperkalaemia may be a problem in the initial phase of treatment. Epoetin is up to twice as effective when administered subcutaneously rather than intravenously. Responding patients will normally do so within 3 months of starting epoetin. Failures to respond are usually due to iron deficiency or intercurrent disease. Other diseases associated with anaemia and an inappropriately low serum epoetin level include prematurity, the anaemia of cancer and rheumatoid arthritis. The baseline serum endogenous erythropoietin may provide a guide to response in some of these cases. Some encouraging results are being published. Situations where the serum erythropoietin levels are normal or elevated where epoetin has been employed include boosting of haematocrit presurgery as an adjunct to autologous blood donation, treatment of anaemic patients with myelodysplastic syndromes, and improvement of athletic performances.
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PMID:Controversies in selection of epoetin dosages. Issues and answers. 778 87

The red-cell mass is continuously adjusted to the optimal size for its function as an oxygen carrier by messages transmitted to the bone marrow from an oxygen sensor in the kidney. These messages are mediated by the hormone erythropoietin. Erythropoietin is a glycoprotein growth factor synthesized by cells adjacent to the proximal renal tubule in response to signals from a renal oxygen-sensing device, probably a heme protein (1). In the bone marrow, erythropoietin binds to and activates specific receptors on the erythroid progenitor cells (2). In the presence of this erythropoietin-receptor complex the progenitor cells continue their predestined development into mature erythrocytes. Erythropoietin was the first hemopoietic growth factor to be molecularly cloned in 1985 (3). Our understanding of the biology and physiology of erythropoietin has been considerably improved with the advent of recombinant human erythropoietin (rHuEpo). During the past 7 years, rHuEpo has undergone extensive testing in clinical trials. It has been approved for treatment of the anemia of chronic renal failure, both in progressive renal failure and endstage renal failure (ESRD). In these instances, the administration of rHuEpo has been used in effect as a substitutive therapy, since patients' erythropoietin levels are very low despite severe anemia, due to the failure of affected kidneys to produce adequate amounts of the hormone. However, the application of rHuEpo has now moved largely from the primitive indication of renal diseases, and the hormone is currently under study in a number of anemic states of different etiologies, even with relatively high serum erythropoietin levels. Among these, some of the best documented indications are the anemia associated with malignancies, either due to neoplastic bone marrow infiltration or to chemotherapy-related myelosuppression, the anemia of myelodysplastic syndromes and AIDS, the anemia of chronic inflammatory diseases, prematurity, and bone marrow transplantation (4). The purpose of this review is to provide a summary of our present knowledge regarding rHuEpo therapy for the anemia of renal failure. We provide some clues for the correct use of rHuEpo in the treatment of the anemia of chronic inflammatory diseases. In addition, we address a series of new issues in the attempt to better understand the relationship between erythropoietin and liver disease.
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PMID:Erythropoietin and the anemia of chronic diseases. 840 91

Recombinant human erythropoietin has been available for clinical use since 1985. It was an immediate success in treating the anemia of chronic renal failure and has also enjoyed some objective success in the treatment of other anemias in either a therapeutic or prophylactic setting, but the issues of appropriate patient selection and cost-benefit ratios are still unresolved. This review discusses the most recent literature concerning the use of recombinant human erythropoietin for the anemia associated with cancer, HIV infection, myelodysplasia, prematurity, autologous blood transfusion, bone marrow transplantation, and chronic renal failure.
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PMID:Clinical use of erythropoietin. 937 81

The women who are suffering from chronic renal failure in an advanced stage have a deficient fertility but they are not sterile. Hemodialysis has improved considerably the fertility of these patients. The aim of this study is to give the results of our experience, from 1990 to 1996, about pregnancies among the uremic patients, dialysed or no and to make a literature review about this subject. We have noticed that pregnancies in the dialysis patients are rare and their evolution is precarious. We have also noticed more miscarriage or pregnancy interruption. Complications are frequent. Mothers have a high risk of hemorrhagic accident (ablatio placentae), of anemia aggravation, of thrombosis of the vascular approach and a high risk of liver anomalies (gravidic cholestasis). The fetus suffers from the maternal anemia and from chronic hypoxia. He's threatened by hydramnios in the case of bad volemic supervision. The intra uterine delayed developement and the prematurity are usual. The absence of high blood pressure and a residual renal function are representing the favourable elements of the good march of pregnancy. A therapeutic intensification is necessary in order to lead this pregnancies to a viable term. The management is heavy not only for the nephrologic, the obstetrical and the neonatal physicians, but also for the patient who is the only one who can decide to continue or to interrupt the pregnancy. It seems better to inform the patient rather than to procure her abortion by proposing her an effective and inoffensive contraceptive method meanwhile to be pregnant after renal transplantation.
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PMID:[Chronic renal failure and pregnancy]. 1126 43

Pregnancy in dialysis patients is a rare occurrence. When pregnancy does occur, the risk of spontaneous abortion, stillbirth and neonatal complications, such as prematurity and growth retardation, are fairly high. The authors describe their experience in the follow-up of a patient with chronic renal failure who became pregnant during regular dialysis treatment and followed nutritional care. The outcomes were successful and she gave birth to a healthy baby. It is emphasized that special dedication to the nutritional control enabled a good outcome of the pregnancy. The importance of the nutritionist intervention in the follow-up of dialysis patients with the integration of a multidisciplinary staff is stressed.
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PMID:Nutritional intervention in a hemodialysis pregnant woman: a case report. 1270 39

New drugs, recently available for treatment of different forms of anaemia, have somehow changed the therapeutic scenario in paediatric haematology. The aim of this review is to focus on the newest molecules discussing indications, clinical usefulness and related problems. Erythropoietin, the specific growth factor of red cell precursors, is now an established option for anaemia of chronic renal failure, prematurity, bone marrow transplantation and chemotherapy. Anti-CD20 monoclonal antibody, a novel cytotoxic molecule for mature B lymphocytes, has proven to be effective in the treatment of refractory autoimmune cytopenias. Haemoglobin analogues are currently under investigation, in order to obtain a synthetic oxygen-carrier that can substitute blood transfusions. Finally drugs that are able to increase the production of haemoglobin F have been used in thalassemias and haemoglobinopathies. For patients with sickle cell disease, hydroxyurea is no longer an experimental tool; it has given rise to several trials, where it has proven to be effective in terms of both clinical and haematological improvement.
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PMID:New drugs for childhood anemia. 1460 71

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.
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PMID:[Clinical use of erythropoietin]. 1514 48

Children born with very low birth weight have a decreased nephron number. Low nephron mass is associated with adult hypertension, proteinuria, and diabetes mellitus. The histomorphometry and radial glomerular count (RGC) of a total nephrectomy from a child with renal disease associated with extreme prematurity was compared with the kidney from a full-term age-matched child of normal gestation with chronic renal failure due to focal and segmental glomerulosclerosis (FSGS) and to a child without renal disease. Bowman's space area, mesangium and mesangial tuft area were determined in 50 glomeruli of each specimen by computer-assisted morphometry. RGC was 4 in the ex-preterm child, 8 in the patient with FSGS, and 9 in normal control. The patient with FSGS had larger glomerular area expressed as square micrometers (mum(2)) of Bowman's capsule, the mesangium and the mesangial tuft area measurements than the normal control and the child born preterm who subsequently developed renal failure had significantly larger Bowman's capsule and mesangium than the two controls. This case report begins to identify important pathologic findings of decreased nephron numbers and glomerulomegaly associated with preterm birth.
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PMID:Comparative renal histomorphometry: a case study of oligonephropathy of prematurity. 1585 26


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