Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 34 year old woman with sickle cell (SS) anemia and chronic renal failure of unknown etiology was maintained on dialysis for 11 months before she received a cadaveric renal transplant. After 24 months, transplant function is excellent although a mild urinary concentrating defect (Umax = 532 mOsm/liter) is present. Renal biopsies five and 11 months after transplant revealed mild focal interstitial infiltrates and mesangial thickening. A major complication has been the reemergence of numerous severe painful crises, inferred to be caused by an increased blood viscosity consequent to a rising hematocrit value, after a hiatus of many years. The succession of crises was stopped with a prophylactic partial exchange transfusion program, reemerged when the program was discontinued, and was stopped again when the transfusion program was reinstituted. We conclude that renal transplantation may be successfully performed in patients with sickle cell disease. Complications of the hemoglobinopathy may develop, but painful crises can be successfully managed with judicious transfusion therapy.
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PMID:Painful crises following renal transplantation in sickle cell anemia. 34 34

Arterio-venous fistula of Brescia was created in 112 consecutive patients during a five year period from May 1983 at King Fahd University Hospital of King Faisal University, Al-Khobar, Saudi Arabia. These fistulae were created for hemodialysis in patients with chronic renal failure. There were 67 males and 45 females. The youngest patient was 13 years and the oldest 75 years. Complications were negligible (0.85%), even-though 31% were diabetics and 24% had sickle cell hemoglobinopathy. The arteriovenous fistula failed in 6 patients and the patency rate was 94.6%. The minimum follow up was three months and the maximum fifty-two months. The end-to-side anastomosis gave better results. For long term dialysis arterio-venous fistula of Brescia should remain as the first choice.
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PMID:Arteriovenous fistula for hemodialysis. A report of 112 consecutive cases. 234 17

There are multiple conditions associated with the development of osteonecrosis including trauma, hemoglobinopathies, Caisson disease, local infiltrative lesions, hypercortisolism, alcohol consumption, chronic renal failure, and autoimmune disease.
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PMID:Avascular necrosis. 962 82

Iron deficiency is the most frequently encountered cause of suboptimal response to recombinant human erythropoietin (rHuEPO). Carefully assessing iron status is of paramount importance in chronic renal failure patients prior to or during rHuEPO therapy. Because there is great need for iron in the EPO-stimulated erythroid progenitors, it is essential that serum ferritin and transferrin saturation levels should be maintained over 300 microg/liter and 30%, respectively. Investigators have shown that oral iron is unlikely to keep pace with the iron demand for an optimal rHuEPO response in uremics. Therefore, patients with iron deficiency will always require intravenous iron therapy. The early and prompt iron supplementation can lead to reductions in rHuEPO dose and hence cost. After the iron deficiency has been corrected or excluded, we must remember all of the possible causes of hyporesponsiveness in every rHuEPO-treated patient. As dose requirements vary, it is not clear which dose of rHuEPO causes this hyporesponsiveness. However, if the patient with iron repletion does not respond well after the induction period, the major causes blunting the response to rHuEPO should be investigated. Most factors are reversible and remediable, except resistant anemia associated with hemoglobinopathy or bone marrow fibrosis, which requires a further increase in the rHuEPO dose. By means of early detection and correction of the possible causes, the goal of increasing therapeutic efficacy can be achieved. Iron overload may lead to an enhanced risk for infection, cardiovascular complication, and cancer. Over-treatment with iron should be avoided in dialysis patients, despite the fact that the safe upper limit of serum ferritin to avoid iron overload is not clearly defined. On the other hand, functional iron deficiency may develop even when serum ferritin levels are increased. Controversy remains as to whether intravenous iron therapy can overcome this form of hyporesponsiveness in iron-overloaded patients. Moreover, a treatment option of iron supplementation is not warranted in these patients, as the potential hazards of iron overload will be worsened. We demonstrated that the mean hematocrit significantly increased from 25.1+/-0.9% to 31+/-1.2% after eight weeks of intravenous ascorbate therapy (300 mg three times a week) in 12 hemodialysis patients with serum ferritin levels of more than 500 microg/liter. The enhanced erythropoiesis paralleled with a rise in transferrin saturation (27.8+/-2.5% vs. 44.8+/-9.5%, P < 0.05) and reductions in erythrocyte zinc protoporphyrin (130+/-32 vs. 72+/-19 micromol/mol heme, P < 0.05) and monthly rHuEPO dose (24.2+/-4.5 vs. 16.8+/-3.4 x 10(3) units, P < 0.05) at the end of study. It is speculated that ascorbate supplementation not only facilitates the iron release from storage sites and its delivery to hematopoietic tissues, but also increases iron utilization in erythroid cells. Our study provides a more complete understanding of the pathogenesis of iron overload-related anemia and the development of an adjuvant therapy, intravenous ascorbic acid, to the existing treatments.
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PMID:Erythropoietin hyporesponsiveness: from iron deficiency to iron overload. 1008 94

The monitoring of diabetic patients by evaluating glycated protein levels is now widely accepted and performed. The microchromatographic version of the high performance liquid chromatography method is the technique most frequently used in clinical practice. The DCA 2000 instrument (Bayer Diagnostics, Milan, Italy), based on an immunochemical technique, has been proposed for the rapid and simple evaluation of HbAlc, using even capillary blood. We evaluated 171 subjects including 22 healthy volunteers, 78 type 2 diabetic patients with different degrees of metabolic control, 11 women affected by gestational diabetes mellitus (GDM), 6 patients with hyperlipemia, 38 patients with chronic renal failure, 13 diabetic patients with chronic renal failure, and 3 patients with hemoglobinopathies. The DCA 2000 model was compared with the Diamat HPLC system. Data from within-run imprecision studies showed excellent precision, for both DCA 2000 and the HPLC system. The correlation between the two different systems, as shown by other statistical evaluations, was good (y = 0.911x + 0.462, r = 0.923). Results from the control group and diabetic patients were used to compare the two methods. Values obtained using the DCA 2000 were significantly lower (p < 0.0001) than those obtained with the HPLC system, in both healthy subjects and diabetic patients. To detect possible interferences, selected samples were analyzed from patients with hyperlipemia, diabetes and chronic renal failure, and hemoglobinopathies. While in the case of hyperlipemia, an acceptable correlation coefficient between the two systems was confirmed (y = 1.047x - 1.236, r = 0.876), in the case of chronic renal failure the correlation turned out to be very low (y = 0.254x + 3.456, r = 0.203). Our results indicate that the DCA 2000 gives accurate and reliable results in the clinical field of interest.
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PMID:Evaluation of diagnostic reliability of DCA 2000 for rapid and simple monitoring of HbA1c. 1092 29

Erythropoietin (Epo) is a glycoprotein hormone produced by genetic engineering. Many pathologic conditions could benefit from its administration, such as chronic renal failure or hemoglobinopathies. Epo secretion from genetically modified tissued could be proposed to patients only if the protocol is low cost and low risk. For that purpose, retroviral vectors and adeno-associated vectors expressing the Epo cDNA were developed. Gene transfer was performed into skeletal muscles. To avoid polycythemia, a tetracycline-regulated system was used to control the levels of protein secretion in vivo. beta-thalassemias are among diseases that could benefit from an Epo gene transfer. beta-thalassemias are attributable to deficient synthesis of beta-globin and accumulation of unpaired alpha-chains. Stimulation of fetal globin synthesis is one strategy to correct the globin chain imbalance. There is evidence that Epo could play this role. In a mouse model of beta-thalassemia, an adeno-associated vector expressing the Epo cDNA was injected intramuscularly. Epo was secreted continuously during at least 1 yr. Erythropoiesis was improved in those mice by increasing the synthesis of fetal hemoglobin.
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PMID:Delivering erythropoietin through genetically engineered cells. 1106 50

The major form of glycohemoglobin is hemoglobin A1c (HbA1c). The HbA1c fraction is abnormally elevated in chronic hyperglycemic diabetic patients and correlates positively with glycemic control. Previous studies suggest that iron deficiency anemia (IDA) affects the levels of HbA1c. The aim of this study was to determine the effect of IDA on HbA1c levels in nondiabetic patients. The population studied consisted of 50 patients (30 women, 20 men, mean age 35.7 +/- 11.9 years) with IDA and 50 healthy subjects that were matched for age and sex. Patients who had glucose tolerance abnormalities (impaired glucose tolerance or diabetes mellitus), hemoglobinopathies, hemolytic anemia, chronic alcohol ingestion and chronic renal failure were excluded from the study. Hematologic investigations, fasting and postprandial glucose and HbA1c levels were measured in all subjects before iron therapy. All patients with IDA were treated with iron 100 mg/day for 3 months. We repeated the laboratory investigation after iron therapy. Before iron treatment, the mean HbA1c (7.4 +/- 0.8%) level in patients with IDA was higher than in a healthy group (5.9% +/- 0.5) (p < 0.001). In patients with IDA, HbA1c decreased significantly after iron treatment from a mean of 7.4% +/- 0.8 to 6.2% +/- 0.6 (p < 0.001). Iron deficiency must be corrected before any diagnostic or therapeutic decision is made based on HbA1c.
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PMID:Effect of iron deficiency anemia on the levels of hemoglobin A1c in nondiabetic patients. 1534 93

Recombinant human erythropoietin (rHuEPO) has transformed the management chronic renal failure (CKD) and considerably improved the outcome of patients on regular chronic dialysis. However, a significant number of patients fail to respond to high of Erythropoiesis-stimulating agents (ESAs) and several causes of inadequate response to epoetin therapy have been identified. Some factors, such as gender, age, length of time on dialysis, type of dialysis and co-morbidities such as hemoglobinopathy, are not susceptible to clinical intervention. However, many other factors can be adjusted. Iron deficiency, whether functional or absolute, is the most common factor that limits the response to rHuEPO. Monitoring of iron parameters and a large use of iron supplementation result in an efficient epoetin response. Infection and inflammation have been shown to reduce responsiveness to ESAs by disrupting iron metabolism and increasing the release of pro-inflammatory cytokines that inhibit erythropoiesis. Increase dialysis dose is associated with improvements in anemia correction and reduced requirements for ESAs. Severe hyperparathyroidism and aluminum overload lead to a reduced number of responsive erythroid progenitor cells. Finally, a number of nutritional factors, such as deficiencies of carnitine, vitamin B12, folic acid, and vitamin C, are susceptible to alter erythropoiesis. Optimizing patient response to ESAs therefore requires consideration of many of well-established factors and is important for both patient outcomes and cost of treatment.
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PMID:[Factors affecting the response to erythropoiesis-stimulating agents]. 1737 70

Anemia can result from deficient erythropoiesis [aplastic anemia, myelodysplastic syndromes (MDS), iron deficiency anemia, anemia of chronic disease (ACD), thalassemia, megaloblastic anemia, chronic renal failure, hematological malignancies, etc.], excessive RBC destruction [hereditary spherocytosis, inherited enzyme deficiency, hemoglobinopathies, autoimmune hemolytic anemia (AIHA), paroxysmal nocturnal hemoglobinuria (PNH), etc.], and blood loss. Based on the measured red cell size(MCV), anemia is classified as microcytic, normocytic, or macrocytic. Iron parameters (serum iron, serum ferritin, etc.), reticulocyte count, bone marrow examination, Coombs test, serum vitamin B12 level, and Ham test are also useful in the differential diagnosis of anemia. Novel treatment of anemia includes lenalidomide for 5q(-)MDS, azacitidine for high-risk MDS, and eculizumab for PNH. Oral iron chelator(deferasirox) developed for the treatment of transfusional iron overload is also very useful for the management of patients with bone marrow failure syndromes.
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PMID:[Pathophysiology, diagnosis and treatment of anemia]. 1832 12

Diabetes mellitus is a heterogeneous and dysmetabolic chronic disease in which the laboratory plays a fundamental role, from diagnosis to monitoring therapy and studying complications. Early diagnosis and good glycemic control should start as early as possible to delay and prevent metabolic and cardio-vascular complications secondary to this disease. Glycated hemoglobin is currently used as the reference parameter. The accuracy of the glycated hemoglobin dosage may be compromised in subjects suffering from chronic renal failure and terminal nephropathy, affected by the reduction in the survival of erythrocytes, with consequent decrease in the time available for glucose to attach to the hemoglobin. In the presence of these renal comorbidities as well as hemoglobinopathies and pregnancy, glycated hemoglobin is not reliable. In such conditions, dosage of glycated albumin can help. Glycated albumin is not only useful for short-term diagnosis and monitoring but predicts the risk of diabetes, even in the presence of euglycemia. This protein is modified in subjects who do not yet have a glycemic alteration but, as a predictive factor, heralds the risk of diabetic disease. This review summarizes the importance of glycated albumin as a biomarker for predicting and stratifying the cardiovascular risk linked to multiorgan metabolic alterations.
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PMID:Recent Updates and Advances in the Use of Glycated Albumin for the Diagnosis and Monitoring of Diabetes and Renal, Cerebro- and Cardio-Metabolic Diseases. 3318 72


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