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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several hemoglobinopathies are associated with abnormalities in the permeability of the red cell membrane, in some cases leading to permanent alterations of the intracellular milieu. Homozygous sickle cell disease is the most thoroughly studied example. Deoxygenation of sickle cells causes a transient increase in the permeability to monovalent cations and Ca; prolonged deoxygenation can lead to a permanent accumulation of Ca and loss of total cations and water. Although the mechanisms for the permeability changes are not yet defined, mechanical stress on the membrane, with subsequent damages by excess Ca or membrane-associated hemoglobin have been suggested to play a role. Loss of cell water and increase in mean cell hemoglobin concentration causes massive reduction of cell deformability in the oxygenated state and makes the hemoglobin more likely to undergo sickling because of the strong concentration dependence of the sickling process. Limited evidence suggests the occurrence of permeability defects in other hemoglobinopathies and the thalassemias. The suggested alterations range from a slight increase in K permeability of incubated thalassemia cells to substantial dehydration of cells from patients with homozygous hemoglobin C disease. Oxidative damage to the membrane, involving an abnormal hemoglobin-membrane association, may underly the permeability changes in these cells.
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PMID:The effect of abnormal hemoglobins on the membrane regulation of cell hydration. 703 77

The separation of alpha, beta, G gamma and A gamma globin chains by reversed phase high pressure liquid chromatography has been studied using columns of octadecylsilyl-silica. All separations were performed in solvent mixtures of water and acetonitrile acidified with phosphoric acid or the hydrophobic ionpairing reagent trifluoroacetic acid. The addition of trifluoroacetic acid or the chaotropic agent NaClO4 to the mobile phase increased the resolution and the peak sharpness of the eluted globin chains. The use of decreasing gradients of TFA or NaClO4 and chromatography at 40 degree were useful steps for the separation of alpha and beta globin chains, a prerequisite for the successful application of this method for the prenatal diagnosis of beta-thalassemia. The beta/gamma synthetic ratio obtained from blood samples taken by fetoscopy from normal fetuses and fetuses with beta-thalassemia trait were measured simultaneously by CM-cellulose chromatography and high pressure liquid chromatography. The values obtained by HPLC were very similar but slightly lower than those obtained by CM-cellulose chromatography. The new method is fast and accurate and will prove to be useful for prenatal diagnosis involving globin chain separation.
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PMID:Reversed-phase high pressure liquid chromatography of globin chains: its application for the prenatal diagnosis of beta-thalassemia. 727 70

Vibrio vulnificus infection, which is a rare and fatal disease, can be categorized clinically as either primary septicemia or wound infection. The clinical presentation of patients with primary septicemia can vary from fever alone to a more severe illness including high-grade bullous lesions, hypotension, and shock. Wound infection typically results from either injury to the skin in a marine environment or contact of a preexisting wound with sea water. We reported eight cases with Vibrio vulnificus infection in Chang gung Memorial Hospital and reviewed ten other cases previously reported with details in Taiwan. Fourteen patients presented with primary septicemia, and four with wound infection. Thirteen patients had alcoholism or chronic liver disease, two had peptic ulcer disease, one was steroids abuser, and one patient had thalassemia and chronic liver disease. Overall mortality was 55.6% (ten patients). Patients with hypotension within 48 hours of admission had higher mortality than normotensive patients (77% vs. 0%, P = 0.007). Patients with chronic liver disease or liver cirrhosis also had tendency to a higher mortality than not (64% vs. 25%, P = 0.274). Chronic liver diseases and liver cirrhosis are common disease in Taiwan. They take a high risk for Vibrio vulnificus infection. Clinician should keep in mind of this potentially fatal infection in these patients reporting a history of recent raw oyster consumption and presented with sepsis and characterized skin lesions. Prompt empirical antibiotics treatment and aggressive surgical treatment may be lifesaving for this acute and fatal disease.
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PMID:Vibrio vulnificus infection--report of 8 cases and review of cases in Taiwan. 785 Jun 49

Analogues of the iron (III) chelator, pyridoxal isonicotinoyl hydrazone (PIH) show high potential as orally active agents for the treatment of iron-overload diseases, such as thalassemia. In the present study, the n-octanol-water partition coefficients of 30 analogues of PIH were measured by thin-layer chromatography and also calculated using the additive schemes of Rekker. The purpose was to examine the relationship between lipophilicity of the apochelator and its ability to promote the release of 59Fe from reticulocytes loaded with nonheme 59Fe. Interestingly, maximum activity occurred when the partition coefficient of the apochelator was approximately 1 (log P = 0). Considering the results in the context of the design and synthesis of more active analogues of PIH, it can be suggested that before initiating synthesis, a useful indication of biological activity can be determined by examining the lipophilicity of the molecule, using the schemes of Rekker to calculate the partition coefficient. By using this strategy, analogues of PIH with inappropriate lipophilicity can be excluded before initiating the expensive process of screening in biological models.
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PMID:Iron chelators of the pyridoxal isonicotinoyl hydrazone class. Relationship of the lipophilicity of the apochelator to its ability to mobilise iron from reticulocytes in vitro. 795 97

As thalassaemia patients live longer, compliance with chelation therapy becomes more and more of a problem. Teenagers rebel against the continual need for treatment, and young adults with jobs, active social lives and families, find it hard to find the time to prepare and deliver their treatments. In an effort to find a solution to this problem, we evaluated a non-electronic, disposable pump (Infusor 5 ml/h, Baxter Healthcare) to determine its suitability for high dose desferrioxamine (DFO) infusions. We wanted an infusion time of 12 h to support overnight delivery in the patient's home. Because of DFOs viscosity, infusion times vary at different concentrations. We found the optimal prescription for total delivery within 12 h to be a dose of 70 mg/kg x patient's body weight diluted in constant volume of 40 ml of water for injection. Our tests were carried out in vitro and the results show that the 5 ml/h Infusor may be used to deliver high dose DFO chelation therapy within 12 h. The variability of the flow rate, dependent on the concentration of the solution, and the absence of a warning system, are more than compensated for by the simplicity of the pump.
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PMID:Laboratory evaluation of a new delivery system to improve patient compliance with chelation therapy. 911 97

Single cell polymerase chain reaction (PCR) for preimplantation genetic diagnosis (PGD) needs to be highly efficient and accurate. In some single cells from human embryos presumed to be heterozygous for the delta F508 deletion causing cystic fibrosis (CF), we recently observed random amplification failure of one of the two parental alleles following nested PCR. To investigate allele dropout (ADO), we have examined two different lysis protocols and the effect of altering the denaturation temperature in the primary PCR using single lymphocytes heterozygous for delta F508 or for two beta-thalassaemia mutations IVS 1 nt 1 (G/T) and 5 (G/C) using a nested PCR protocol to amplify the 5' region of the beta-globin gene. Amplification rates were high after lysis in either water or lysis buffer and at all denaturation temperatures studied (> or = 92%). With a typical denaturation temperature (93 degrees C), ADO was detected at both loci. When the denaturation temperature was lowered to 90 degrees C, however, ADO increased substantially and conversely by raising the denaturation temperature to 96 degrees C during the first 10 cycles ADO was reduced but not eliminated. ADO was also reduced with cells in lysis buffer. We suggest that ADO may be caused by a combination of inefficient denaturation and degradation of one of the genomic alleles in the first cycles of PCR. For autosomal recessive conditions in which both parents are carrying the same mutation, ADO would not cause serious misdiagnosis. For compound heterozygotes or autosomal dominant conditions, however, extensive testing of the amplification protocol with single heterozygous cells and individual calibration of each thermocycler for the effect of denaturation temperature on ADO is essential before clinical application.
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PMID:Increasing the denaturation temperature during the first cycles of amplification reduces allele dropout from single cells for preimplantation genetic diagnosis. 923 82

A case-control study was conducted in four hospitals in northeastern Thailand to identify risk factors for melioidosis and bacteremic melioidosis. Cases were patients with culture-proven melioidosis, and there were two types of controls (those with infections, i.e., with community-acquired septicemia caused by other bacteria, and those without infection, i.e., randomly selected patients admitted with noninfectious diseases to the same hospitals). Demographic data, clinical presentations, and suspected risk factors were analyzed. Diabetes mellitus, preexisting renal diseases, thalassemia, and occupational exposure, classified by the soil and water risk assessment, were confirmed to be significant risk factors for melioidosis and bacteremic melioidosis. Only diabetes mellitus was a significant factor associated with bacteremic melioidosis, as compared with nonbacteremia. A significant interaction was found between diabetes mellitus and occupational exposure. Thus, diabetic rice farmers would be the most appropriate population group for targeted control measures such as vaccination in the future.
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PMID:Risk factors for melioidosis and bacteremic melioidosis. 1047 50

Sodium, potassium, water, and the mean corpuscular haemoglobin concentration were determined in the packed erythrocytes of children with severe thalassaemia. The concentration of sodium in the packed red cells was higher than normal in a significant proportion of children with thalassaemia whereas potassium in the packed cells and sodium and potassium in the plasma were normal. On average, the cell water content was a little higher and the mean corpuscular haemoglobin concentration a little lower than normal. The cation concentrations in the packed cells of thalassaemia are compared with those in other anaemias. Similarities are pointed out between the sodium concentrations in the packed cells of thalassaemia and those from the foetus and children suffering from malnutrition.
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PMID:Sodium potassium, water, and haemoglobin in the packed red cells of severe thalassaemia. 1387 77

Bone injury occurs in human hemolytic disorders associated with thrombosis, such as beta-thalassemia and sickle cell disease. Exposure of rats to 2-butoxyethanol (BE) has been associated with hemolytic anemia, disseminated thrombosis, and infarction in multiple organs including bone. This rat model apparently mimics acute hemolysis and thrombosis in humans. To elucidate the extent of bone injury, male and female Fischer F344 rats were given 4 daily doses of 250 mg BE/5 ml water/kg of body weight. Tail vertebrae were studied by histopathology and magnetic resonance imaging (MRI). Thrombosis and infarction were seen in both sexes, but females were more severely affected. Lesions were characterized by extensive medullary fat necrosis, granulomatous inflammation, fibroplasia, growth plate degeneration, and new woven bone formation adjacent to necrotic bone trabeculae. MRI mean and standard deviation tissue-density data for both sexes indicated a significant (P < or = 0.05) decrease following 4-days treatment and a significant increase (P < or = 0.05) following an additional 24 days without treatment. Thus, MRI was useful in revealing BE-induced bone injury, which was predominantly necrotic initially and subsequently regenerative with proliferation of connective tissue and bone following postischemia recovery.
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PMID:Osteonecrosis in a chemically induced rat model of human hemolytic disorders associated with thrombosis--a new model for avascular necrosis of bone. 1451 20

Hemoglobin (Hb) chains have been analyzed traditionally by cellulose acetate electrophoresis after sample extraction with acetone and denaturation with concentrated urea in order to detect thalassemia (Thal). A few capillary electrophoresis (CE) methods have been also described for separation of Hb chains also after sample extraction. We describe a CE method for analysis of Hb chains without sample preparation. Red blood cells were diluted (hemolyzed) in water and injected directly onto the capillary. The separation was performed in concentrated phosphate buffer at pH 12.6 and 2.15. Under these conditions of pH and buffer concentration, the chains were denatured and separated from the heme during electrophoresis. The common variants of the beta-chains, such as beta(S), beta(C), and beta(E), are also separated from each other. The intact Hb molecule is analyzed using the same sample and CE conditions but in an arginine-Tris buffer, pH 8.6. The data from the three separations are used to complement each other for interpretation of the presence of Hb variants and for thalassemia. The main advantages of this method are simplicity and speed. This method illustrates the flexibility and simplicity of the CE for analysis of the hemoglobinopathies.
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PMID:Simplified hemoglobin chain detection by capillary electrophoresis. 1569 Apr 30


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