Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Iron studies were performed in 22 pregnant and 18 non-pregnant women with haemoglobinopathies. Mean packed cell volume and mean haemoglobin concentration were significantly lower (p < 0.001) in haemoglobin SS patients than in haemoglobin SC patients, in both the pregnant and non-pregnant groups. Transferrin saturation was significantly lower in pregnant patients (haemoglobin SS and SC) than in the non-pregnant group (p < 0.001). Serum ferritin values in the haemoglobin SS and SC pregnant patients were not significantly different (p > 0.05). There was a strong correlation between serum ferritin levels and transferrin saturation in the pregnant group (r = 0.71; p < 0.001). Fourteen of the 22 pregnant women (63 per cent) and 9 of the 18 non-pregnant women (50 per cent) had scanty or no iron in the bone marrow; the serum ferritin levels increased progressively with greater amount of haemosiderin in the bone marrow. There was evidence of iron deficiency in both the pregnant and non-pregnant women with haemoglobinopathies and this suggests the need for further study on the routine administration of iron in the management of patients with sickle cell disease.
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PMID:Iron studies in pregnant and non-pregnant women with haemoglobin SS or SC disease. 743 71

In clinical studies, frequent hepatic dysfunction associated with crises in sickle cell disease has been noted, but whether irreversible morphologic changes arise from these transient episodes is uncertain. We studied 70 patients with sickle cell disease (57 SS, 12 SC and one S-thalassemia (S-thal) hemoglobin) autopsied at The Johns Hopkins Hospital. They ranged in age from five months to 75 years (average 21 years) and 35 (50 percent) were female, In 64 patients (91 percent), livers were enlarged and had distention of Kupffer cells with phagocytized sickled red cells; this was massive in 10. In 19 patients (27 percent) the sinusoids were markedly distended with sickled red cells and appeared obstructed. Focal parenchymal necroses were present in 24 patients (34 percent) and were explained in 12, eight by cardiac dysfunction and four by sepsis. Reparative changes, portal fibrosis and regenerative nodules were each found in 14 patients (20 percent), only one of whom had a known history of viral hepatitis despite the frequency of transfusions. Cirrhosis of unknown cause was present in seven patients and cardiac cirrhosis in one. Cirrhosis with hemochromatosis was present in three patients and 30 others had parenchymal iron accumulation. Thus, unexplained hepatic necroses, portal fibrosis, regenerative nodules and cirrhosis were frequently encountered in these patients. This spectrum of liver disease appears to be best understood as a consequence of recurrent vascular obstruction, necrosis and repair arising as a component of sickle cell disease.
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PMID:The liver in sickle cell disease. A clinicopathologic study of 70 patients. 744 49

Severe anemia has remained a major cause of morbidity and mortality in children of Southern Ghana since the early 1960s. Cases of anemia and anemia-associated mortality in the Korle Bu Teaching Hospital (KBTH), Accra, that occurred from January to December 1991 were reviewed. Data on hemoglobin levels, hypochromia, and malaria parasitemia of children referred from January to December 1991 were collected and analyzed to determine the prevalence of moderate/severe malaria parasitemia, anemia, and severe anemia. 10,989 (71.1%) of 15,450 children attending KBTH referred to the laboratory for hematological studies had hemoglobin (Hb) levels below 11.0 g/dl; while 3049 children (27.7%) of anemic patients had Hb levels below 7.0 g/dl. Of these 3049 children with severe anemia, 2185 (71.7%) had Hb levels below 5.0 g/dl, thus requiring urgent blood transfusion. Though the Department of Child Health alone utilized 32.2% of total blood processed by the National Blood Transfusion Service at KBTH, as many as 259 (58.1%) of the 554 deaths (306 male and 248 female) in the emergency room in children beyond the neonatal period were related to severe anemia. The main causes were nutritional anemia (n = 135), anemia associated with severe malaria (n = 56), anemia associated with sickle cell disease (n = 28), anemia associated with protein-energy malnutrition (n = 22), and 18 cases of anemia complicating gastroenteritis, pneumonia, meningitis, and convulsions. 108 (19.5%) deaths occurred because of neonatal sepsis, severe neonatal hyperbilirubinemia, meningitis and bronchopneumonia, severe anemia secondary to hemorrhage of the newborn, and faulty cord ligation. A significant decline occurred in the prevalence of childhood anemia in the developed world following improved counseling in nutrition, fortification of foods with iron, and iron supplementation to infants and schoolchildren with the attendant improvement in growth velocity and intellectual performance. A planned national anemia survey and early consideration of iron supplementation to older infants and preschool children at risk are recommended.
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PMID:Childhood deaths from anaemia in Accra, Ghana. 749 16

We report the hematologic and clinical features of four adult patients (Pts.) with sickle cell anemia and iron-limited erythropoiesis. Two of the Pts. had spontaneous iron deficiency (chronic GI bleeding, low-grade hemoglobinuria). In the other two Pts. iron restriction was induced by periodic RBC aphereses as part of a pilot protocol designed to decrease intracellular HbS polymerization by MCHC reduction. Iron-limited erythropoiesis was defined by reduction in red cell indices (MCV range 60.4-67 fl) in the presence of low serum ferritin (range < 10-20 ng/ml). In these Pts. iron restriction did not cause clinically significant worsening of the anemia (Hb 7.8-9.0 g/dl). In two Pts. the anemia actually improved. Other hematologic effects of iron restriction were: decreased MCHC, reticulocyte count, RDW, and dense cells. A reduced hemolytic rate was suggested by a lowering of serum bilirubin and LDH. In one of the Pts. the 51Cr RBC T1/2 survival increased from 12 to 16 days. The intracellular HbS polymer fractions (fp) were determined at 25% O2 by Csat and with the use of the conservation of mass equation. The baseline fp values ranged from 0.48-0.53. After iron restriction they ranged from 0.33-0.48. The fp decreased even though iron-limited erythropoiesis also lowered the Hb F concentration in three of our Pts. In one of the two Pts. with induced iron depletion, hospitalization days for pain crises decreased from an average of 4.5 days/month (2 year baseline period) to an average of 0.5 days/month in the 3 year follow-up after iron depletion. The second patient with induced iron restriction experienced the rapid healing of a leg ulcer. Controlled iron restriction should be explored as a therapeutic strategy in selected SS patients.
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PMID:Improvement of sickle cell anemia by iron-limited erythropoiesis. 766 35

Hydroxyurea (HU) and recombinant human erythropoietin (rHuEpo) have been used in several studies to elevate Hb F level in sickle cell disease (SCD) patients and hence to ameliorate the clinical presentations of the disease. The treatment protocol and doses have varied in the different studies. We studied the effects of HU+rHuEpo combination therapy in sickle cell anaemia (SCA patients) to investigate the Hb F manipulation and hence treatment of SCA. Six patients with severe SCA were selected for treatment with HU (20-25 mg/kg body weight) and rHuEpo (400-800 U/kg body weight) combination therapy for 4 weeks followed by HU (20-25 mg/kg body weight) maintenance therapy for 6 months to 1 year. Iron and folic acid were administered during HU+rHuEpo treatment. Signs, symptoms and complications were recorded to obtain the severity index. Only patients with a severity index > or = 6 were included in the study. Haematological and biochemical parameter values, Hb A2, Hb F, Hb F distribution, Hb F cells, bilirubin level and reticulocyte count were assessed at least on 2-3 occasions prior to initiation of the therapy protocol to establish baseline values. During the treatment period, the clinical presentations were monitored and the estimation of the laboratory parameters was carried out every 4-8 weeks. The results of these parameters during HU and rHuEpo combination therapy and HU maintenance therapy were compared with baseline values using paired t test. The elevation in the level of Hb F, Hb F cells, total haemoglobin, red cell count and MCV were significant (p < 0.005), while reticulocyte count and total bilirubin were significantly decreased (p < 0.05). Each patient showed an individual pattern of Hb F elevation. The increase in Hb F level was correlated with the haematological and biochemical parameters using the General Linear Model Programme of Statistical Analysis System. In general, the clinical presentation improved as Hb F level increased in each patient. In addition, the positive correlation with the haematological parameters and negative correlation with reticulocytes and total bilirubin confirmed the beneficial effect of elevated Hb F level on reducing red cell haemolysis. No correlation could be demonstrated between the pretreatment Hb F level and the increase in Hb F during the treatment period. Daily doses of HU with a single intravenous rHuEpo and iron supplementation elevate Hb F and Hb F cells in SCA patients. The Hb F level can be maintained high on HU therapy alone.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The pharmacological manipulation of fetal haemoglobin: trials using hydroxyurea and recombinant human erythropoietin. 754 19

We have studied the prevalence and molecular nature of hereditary anaemias (abnormal haemoglobins, beta-thalassaemia, alpha-thalassaemia, and Glucose 6 phosphate dehydrogenase (G6PD) deficiency) in a primitive central Indian tribe, the Baiga. 43% of the population appear to be iron-deficient. Hereditary anaemia gene frequencies are, sickle cell 0.0824, G6PD deficiency (in males) 0.0457, beta-thalassaemia 0.0057, and deletional alpha-plus thalassaemia 0.65. Both -alpha 3.7 and -alpha 4.2 deletions were observed and non-deletional alpha-thalassaemia was suspected. The overall gene frequency of Xmn I+polymorphism (C-->T - 158 cap site; upstream of G gamma region) is 0.35. This polymorphism is preferentially linked to beta s genes. It appears that sickle cell disease covers a wide range of severity in the Baiga tribe based on higher mortality in the offspring of AS x AS parents (2.5/couple) compared to AA x AS (0.75/couple) and AA x AA (0.76/couple) parents. This is compatible with the high frequency of genetic modifying factors, i.e., the Xmn I polymorphism and alpha-thalassaemia. The results also indicate that "normal" red cell values must be defined for each population where thalassaemias, G6PD deficiency and iron deficiency are common.
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PMID:Hereditary anaemias and iron deficiency in a tribal population (the Baiga) of central India. 762 84

Red blood cell (RBC) membranes from patients with the thalassemic and sickle hemoglobinopathies carry abnormal deposits of iron presumed to mediate a variety of oxidative-induced membrane dysfunctions. We hypothesized that the oral iron chelator deferiprone (L1), which has an enhanced capacity to permeate cell membranes, might be useful in chelating these pathologic iron deposits from intact RBCs. We tested this hypothesis in vitro by incubating L1 with RBCs from 15 patients with thalassemia intermedia and 6 patients with sickle cell anemia. We found that removal of RBC membrane free iron by L1 increased both as a function of time of incubation and L1 concentration. Thus, increasing the time of incubation of thalassemic RBCs with 0.5 mmol/L L1 from 0.5 to 6 hours, enhanced removal of their membrane free iron from 18% +/- 9% to 96% +/- 4%. Dose-response studies showed that incubating thalassemic RBC for 2 hours with L1 concentrations ranging from 0.125 to 0.5 mmol/L resulted in removal of membrane free iron from 28% +/- 15% to 68% +/- 11%. Parallel studies with sickle RBCs showed a similar pattern in time and dose responses. Deferoxamine (DFO), on the other hand, was ineffective in chelating membrane free iron from either thalassemic or sickle RBCs regardless of dose (maximum, 0.333 mmol/L) or time of incubation (maximum, 24 hours). In vivo efficacy of L1 was shown in six thalassemic patients whose RBC membrane free iron decreased by 50% +/- 29% following a 2-week course of L1 at a daily dose of 25 mg/kg. As the dose of L1 was increased to 50 mg/kg/d (n = 5), and then to 75 mg/kg/d (n = 4), 67% +/- 14% and 79% +/- 11%, respectively, of their RBC membrane free iron was removed. L1 therapy--both in vitro and in vivo--also significantly attenuated the malondialdehyde response of thalassemic RBC membranes to in vitro stimulation with peroxide. Remarkably, the heme content of RBC membranes from L1-treated thalassemic patients decreased by 28% +/- 10% during the 3-month study period. These results indicate that L1 can remove pathologic deposits of chelatable iron from thalassemic and sickle RBC membranes, a therapeutic potential not shared by DFO. Furthermore, membrane defects possibly mediated by catalytic iron, such as lipid peroxidation and hemichrome formation, may also be alleviated, at least in part, by L1.
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PMID:Deferiprone (L1) chelates pathologic iron deposits from membranes of intact thalassemic and sickle red blood cells both in vitro and in vivo. 765 28

Renal ultrasound appearances have been examined in 315 patients with sickle cell disease aged 10-20 years, followed in a cohort study from birth. There were three different echo patterns. A normal appearance (type 1) occurred in 235 (75%) of all subjects, and in 159/179 (89%) with homozygous sickle cell (SS) disease. A diffuse increase in reflectivity throughout the kidney (type 2), similar to that of adjacent liver, occurred in 17 patients (5%). Widespread confluent or focal increase in reflectivity confined to the renal medulla (type 3) occurred in 63 (20%) of the total group, and was much more common in the mild genotypes of sickle cell-haemoglobin C disease (41/111, 37%) and sickle cell-beta+ thalassaemia (15/19, 79%) than in SS disease (5/179, 3%). We speculate that type 2 changes may reflect diffuse glomerular and interstitial fibrosis, and that type 3 resembles changes seen in sub-clinical nephrocalcinosis, and could be due to iron deposition.
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PMID:Increased renal reflectivity in sickle cell disease: prevalence and characteristics. 860 61

Pathogenic organism can be considered as pro-oxidant agents because they produce cell death and tissue damage. In addition organism can be eliminated by specific cell defense mechanism which utilize in part, reactive oxygen radicals formed by oxidative stress responses. The cause of the necessarily defense process results in cell damage thereby leading to development of inflammation, a characteristic oxidative stress situation. This fact shows the duality of oxidative stress in infections and inflammation: oxygen free radicals protect against microorganism attack and can produce tissue damage during this protection to trigger inflammation. Iron, a transition metal which participates generating oxygen free radicals, displays also this duality in infection. We suggest also that different infectious pathologies, such as sickle cell anemia/malaria and AIDS, may display in part this duality. In addition, it should be noted that oxidative damage observed in infectious diseases is mostly due the inflammatory response than to the oxidative potential of the pathogenic agent, this last point is exemplified in cases of respiratory distress and in glomerulonephritis. This review analyzes these controversial facts of infectious pathology in relation with oxidative stress.
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PMID:[Oxidative stress and infectious pathology]. 779 23

The effect of Plasmodium falciparum malaria on the iron status was determined in 80 children: normal children without malaria (20) and with malaria (20), and sickle cell anaemia without malaria (17) and with malaria (23). Iron status was assessed using serum transferrin, serum iron, transferrin saturation and haemoglobin. The non-malaria sickle cell anaemia (SCA) group had lower transferrin (234.0 +/- 21.0) and haemoglobin (8.1 +/- 0.4) than non-malaria normal group (260.6 +/- 17.1 mg/100 ml, and 12.5% respectively). Serum iron was higher in sickle cell anaemia (125.1 +/- 17.1) than non-malaria normals (119.2 +/- 1 microgram/100 ml). Malaria caused an increase in serum transferrin, TIBC and serum iron in both normal and SCA children; these changes were more dramatic in normal than in SCA children.
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PMID:Plasmodium falciparum malaria: its effects on some haematological parameters in normal and sickle cell Nigerian children. 789 91


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