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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors have followed 140 patients with sickle cell disease anemia (101 cases) or related hemoglobinopathies (39 cases). Among them hip involvement was noted in 55 (104 hips). Forty three times the hip involvement occurred in childhood and twelve times in adult life. When the necrosis appeared in childhood (84 hips) the average age was twelve. The deformity involved the femoral head (coxa plana, coxa magna) as well as the neck (short neck, coxa vara). After an average follow-up of nineteen years, clinical and radiological examinations evidenced 64 functional impairments and 25 arthrosis, 10 of which have already been operated on. The necrosis appearing during adult life (20 hips) had the same outcome as idiopathic necroses, leading rapidly to arthrosis after collapse of the sequestrum. It seems that the etiology of the necroses is linked to rheologic disorders, the deformity of the red cells causing arteriolar thromboses. In this series the hip disease was correlated with sickle cell retinopathy as defined after angiography. On the contrary there was no correlation with the severity of anemia, its treatment, the ethnical origin of the patient.
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PMID:[Natural history of hip necrosis in sickle cell disease. Apropos of 104 necroses]. 269 46

DNA samples from numerous subjects of different racial and ethnic backgrounds, with or without various hemoglobinopathies (classical beta-thalassemia; silent beta-thalassemia, Hb E, sickle cell anemia), were studied for a rearrangement (+ATA; -T) at nucleotide -530 in the 5' flanking region of the beta-globin gene using amplified DNA and 32P-labeled synthetic oligonucleotide probes. The data show that this unusual sequence is a common feature among East-Asians and Blacks (particularly SS patients), and is not associated with mild thalassemic features typical for the silent form of beta-thalassemia, as has been suggested (5).
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PMID:High frequencies of a rearrangement (+ATA; -T) at -530 to the beta-globin gene in different populations indicate the absence of a correlation with a silent beta-thalassemia determinant. 270 62

Foremost among the beneficial effects of screening umbilical cord blood is the optimized quality of care that can follow the immediate involvement of an infant with sickle cell disease and his or her family in an appropriate health care system. This is exemplified by the reduction in the case fatality rate of pneumococcal septicemia that has been achieved. Appropriate follow-up of screening also includes transmission of information about the diagnosis of a hemoglobinopathy trait or alpha-thalassemia to affected families and their physicians, with ready availability of education and counseling.
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PMID:Value of screening umbilical cord blood for hemoglobinopathy. 271 9

Human alpha- and beta-globin genes were separately fused downstream of two erythroid-specific deoxyribonuclease (DNase) I super-hypersensitive sites that are normally located 50 kilobases upstream of the human beta-globin gene. These two constructs were coinjected into fertilized mouse eggs, and expression was analyzed in transgenic animals that developed. Mice that had intact copies of the transgenes expressed high levels of correctly initiated human alpha- and beta-globin messenger RNA specifically in erythroid tissue. An authentic human hemoglobin was formed in adult erythrocytes that when purified had an oxygen equilibrium curve identical to the curve of native human hemoglobin A (Hb A). Thus, functional human hemoglobin can be synthesized in transgenic mice. This provides a foundation for production of mouse models of human hemoglobinopathies such as sickle cell disease.
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PMID:Synthesis of functional human hemoglobin in transgenic mice. 277 49

Prenatal diagnoses for sickle cell disease in the United States and Canada numbered at least 1065 through the end of 1987. The 272 prenatal diagnoses in the United States in 1987 constituted only about 4.1% of the estimated pregnancies at risk. The termination rate for diagnosed fetuses was 39% for sickle cell anemia and 23% for hemoglobin SC disease. Prenatal hemoglobinopathy screening programs should not be judged solely on the number of terminations for affected fetuses. Other benefits are reassurance for couples shown to have an unaffected fetus and, for couples shown to have an affected fetus, preparation for the birth of a child requiring special care and information relevant to future childbearing.
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PMID:Prenatal diagnosis for sickle cell disease. A survey of the United States and Canada. 277 29

Restriction site polymorphisms are normal inherited variations in DNA that can be readily detected by restriction endonuclease analysis. Currently, 17 such polymorphisms are recognized within a 60 kb (kilobase) stretch of DNA which includes the beta-globin gene complex. Because of their proximity to the beta-globin gene, often these restriction site polymorphisms can be used to predict inheritance of beta-globin variants that produce disease. For example, restriction site polymorphisms can be used for prenatal diagnosis for the large majority of couples at risk of having a child with beta-thalassemia. When each member of such a couple is heterozygous at one or more of these 17 sites, family studies are usually successful in determining which forms of the polymorphism are co-inherited with the beta-thalassemia genes in that particular family. Subsequently, study of fetal DNA isolated from amniocytes obtained by midtrimester amniocentesis or from chorionic villi obtained by first trimester chorion biopsy will reveal which DNA polymorphisms that fetus has inherited. By deductive reasoning one can then predict which beta-globin genes it has co-inherited. Because of the general nature of these polymorphisms, which are related to the beta-globin gene and its variants only because of their proximity on chromosome 11, they are potentially useful in the prenatal diagnosis of any beta-chain hemoglobinopathy. Some hemoglobinopathies (including alpha-thalassemia, sickle cell anemia, and some cases of beta-thalassemia) can be detected directly by DNA analysis. In these cases in utero diagnosis does not need to rely on restriction site polymorphisms, which require preliminary family studies and are not applicable in all at risk pregnancies. Recently, genetic probes, which are necessary for detecting restriction site polymorphisms, have been isolated for sequences of several genes whose protein products are important in blood coagulation. These include probes for all three genes whose polypeptide products combine to form the fibrinogen molecule as well as probes for the prothrombin, Factor IX, Factor VIII, and antithrombin III genes. Defects in these genes are expected to be the causes of afibrinogenemia, prothrombin deficiency, hemophilia B, hemophilia A, and antithrombin III deficiency, respectively. From experience with other genes, it is expected that restriction site polymorphisms within and/or flanking these genes will be found.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prenatal diagnosis of hemoglobinopathies by DNA analysis. 299 37

Microvascular dysfunction accounts for the major morbidity and contributes to the mortality among patients with sickle cell hemoglobinopathies. We summarize the microcirculatory dynamics of red cells in sickle cell disease. An overview of the physiological attributes of the microcirculation is presented. The microcirculatory module is a unique organic entity within the tissue domain, which is concerned with the functional exchange of substances between the blood and the tissue environment. The impairment in deformability of sickle red cells and their heterogeneity cause them to show abnormal microvascular flow dynamics that, in turn, contribute to derangement of the microvascular bed. Studies of experimental models in animals have employed the microcirculation of the mesentery, the cremaster muscle, and the mesoappendix. These studies showed the rheological disequilibrium that results as sickle cells course through successive segments of the arterioles, capillaries, and venules. Direct in vivo microscopic observations in human subjects, with analysis and quantitation of the nailfold and bulbar conjunctival capillaries, have also provided useful information as to the adverse effects of sickling on the microcirculation. Sickle cell vaso-occlusion has three phases--initiation, propagation, and resolution. This framework provides a basis for testable hypotheses for verification in appropriately designed experiments. In this context, the determinants of the microvascular flow of erythrocytes in sickle cell disease are emphasized.
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PMID:Vaso-occlusion in sickle cell disease: pathophysiology of the microvascular circulation. 307 Nov 70

Children with sickle cell anemia have an increased susceptibility to bacterial infections, especially to those caused by Streptococcus pneumoniae. We therefore conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial to test whether the regular, daily administration of oral penicillin would reduce the incidence of documented septicemia due to S.pneumoniae in children with sickle cell anemia who were under the age of three years at the time of entry. The children were randomly assigned to receive either 125 mg of penicillin V potassium (105 children) or placebo (110 children) twice daily. The trial was terminated 8 months early, after an average of 15 months of follow-up, when an 84 percent reduction in the incidence of infection was observed in the group treated with penicillin, as compared with the group given placebo (13 of 110 patients vs. 2 of 105; P = 0.0025), with no deaths from pneumococcal septicemia occurring in the penicillin group but three deaths from the infection occurring in the placebo group. On the basis of these results, we conclude that children should be screened in the neonatal period for sickle cell hemoglobinopathy and that those with sickle cell anemia should receive prophylactic therapy with oral penicillin by four months of age to decrease the morbidity and mortality associated with pneumococcal septicemia.
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PMID:Prophylaxis with oral penicillin in children with sickle cell anemia. A randomized trial. 308 21

The light-microscope finding of red cell membrane fragments in the form of long filamentous processes and myelin bodies in the blood smears of a patient with sickle cell anemia has recently been described. This phenomenon has been termed erythrocytic ecdysis. We examined the blood smears of all sickle cell anemia patients admitted to the Cook County Hospital and those attending the hemoglobinopathy clinic between October 1979 and December 1981. Nine instances of erythrocytic ecdysis were uncovered. Associated clinical conditions included congestive heart failure, acute viral syndrome, pneumonia, and metastatic malignancy. Transient ecdysis associated with congestive heart failure was noted for one patient during two separate admissions one year apart. Ecdysis is a transient form of erythrocytic fragmentation occurring in sickle cell anemia. Its pathogenesis is unknown. The role of regional circulatory stasis and hypoxia in the induction of erythrocyte membrane damage in sickle cell anemia needs investigation.
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PMID:Erythrocytic ecdysis in smears of EDTA venous blood in eight patients with sickle cell anemia. 311 41

Beginning in 1970, a cohort of 74 sickle trait-carrying couples was identified who risked producing children with sickle cell anemia or other serious hemoglobinopathies. They were counseled concerning the disease and their risk, and their initial reactions, their stated intentions concerning birth control and childbearing, and their subsequent childbearing histories were documented. Initial responses to the risk information varied widely, and stated intentions of birth control or childbearing did not accurately predict subsequent childbearing. Among 25 couples for whom there were complete childbearing data, there were 31 pregnancies with 13 affected children prior to counseling. After counseling, there were 25 pregnancies resulting in 10 affected children. The majority of the subsequent pregnancies occurred in the group who had not borne children or an affected child before counseling. In young couples, concern for producing a child with sickle cell anemia is often offset by a strong desire to have children regardless of risk.
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PMID:Genetic counseling in sickle cell anemia: experiences with couples at risk. 312 34


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