1/47. Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy.We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the y chromosome. female genitalia without uterus in a subject with y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.- - - - - - - - - - ranking = 1keywords = amplification, rna (Clic here for more details about this article) |
2/47. The beta -thalassemia mutation [IVS-II-5 (G-->C] creates an alternative splicing site in the second intervening sequence.We report a beta-thalassemia mutation [IVS-II-5 (G-->C)] in a Chinese family. Recently we cloned this beta-globin gene and studied its transient expression in murine erythroleukemia (MEL) cells. Both the thalassemic and normal beta-globin genes were isolated by polymerase chain reaction and TA-vector cloning. When the cloned beta-thalassemic globin gene was introduced into MEL cells, two kinds of spliced cytoplasmic beta-globin RNAs were detected. The predominant RNA was normally spliced, while the less abundant RNA contained an insertion of the first 47 nucleotides of the second intervening sequence localized between exons 2 and 3. These results suggest that the mutation [IVS-II-5 (G-->C)] causes a beta -thalassemia.- - - - - - - - - - ranking = 0.0076573302733029keywords = rna (Clic here for more details about this article) |
3/47. A home blood transfusion programme for beta-thalassaemia patients.Although home transfusion programmes are relatively common in the USA (Anon, 1990, Home Care in the 1990s. Council on Scientific Affairs. Journal of the american medical association, 263, 1241-1244), this type of treatment has only recently been considered in Britain and, where it is in operation, is generally supervised by trained nursing staff or via a hospice. North Middlesex Hospital now has 3 years experience of a home transfusion programme operating for beta-thalassaemia major patients, in which relatives are trained and responsible for supervision of the red-cell transfusions at home. For families who request this service, and who are willing and able to undertake it responsibly, the scheme offers the advantages of improved patient comfort, reduced absences from education or employment and reduced hospital bed usage. patients and their carers express improved satisfaction with the treatment delivered in this way.- - - - - - - - - - ranking = 0.0019143325683257keywords = rna (Clic here for more details about this article) |
4/47. Dominant beta-thalassaemia: a highly unstable haemoglobin is caused by a novel 6 bp deletion of the beta-globin gene.Beta-thalassaemia is inherited as an autosomal recessive trait in most families. Particular interest has recently been focused on the molecular pathology of the rare forms with a dominant mode of inheritance. The index patient and her mother, who are described in this report, displayed typical clinical and haematological features of beta-thalassaemia intermedia with significant ineffective erythropoiesis and additional peripheral haemolysis. Molecular analysis demonstrated a heterozygous genotype for a novel 6 bp (TGGTCT) deletion of the beta-globin gene involving codons 33-35. This deletion results in the removal of two valine residues from the beta-globin chain at position 33/34 (B15/B16) and the substitution of the tyrosine residue at position 35 (C1) by an aspartic acid (beta 33-35 [B15-C1] Val-Val-Tyr-->0-0-Asp). According to the index patient's place of birth, this abnormal haemoglobin has been termed Hb Dresden. The stability of the variant and the normal beta-globin chains were similar during the incubation period of in vitro globin chain synthesis analysis. However, Hb Dresden is exquisitely unstable and cannot be detected in the peripheral blood by haemoglobin electrophoresis, high-performance liquid chromatography (HPLC) or isoelectric focusing. This instability can be explained by the vital structural role of the three affected amino acids that, in normal haemoglobin, establish a total of nine intermolecular bonds (five hydrophobic and four polar) at both the alpha1beta1 (alpha2beta2) and the alpha1beta2 (alpha2beta1) interface.- - - - - - - - - - ranking = 0.00022473671473908keywords = acid (Clic here for more details about this article) |
5/47. Partial splenic embolization in beta-thalassemia major. A case report.Partial splenic arterial embolization was performed in a thalassemic child for hypersplenism manifested by splenomegaly, leukopenia, thrombocytopenia, and anemia requiring frequent erythrocyte transfusion. During a follow-up period of 11 months, his hematological parameters improved significantly and the spleen size decreased. Partial splenic embolization could be an alternative therapy to surgical splenectomy for thalassemic children with hypersplenism.- - - - - - - - - - ranking = 0.0019143325683257keywords = rna (Clic here for more details about this article) |
6/47. Differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia by protein and dna analyses.dna analysis was used to confirm the Hb EE genotype and to differentiate from the possible genotype of Hb E-beta(0)-thalassemia in two Malay patients. The first patient was a 13-year-old Malay girl, whose parents were available for family studies. The second patient was a 69-year-old Malay woman with no living family members. The presence of Hb E in both propositi was confirmed by: (1) its characteristic electrophoretic mobilities on alkaline/acid gels; (2) its chromatographic properties on anion/cation exchangers, and (3) its mildly insoluble properties. However, differential diagnosis of Hb EE and Hb E-beta(0)-thalassemia was challenging in these two cases. In the former, this was because of the possible interactions of the parents' phenotypes; i.e., the mother had a similar phenotype. In the latter, it was due to the lack of any living family members for family studies. In this communication, we present the protein and dna analyses, including data on the use of the restriction enzyme Mnl I, for the definitive diagnosis of the Hb EE genotype in the propositi of these two Malay families.- - - - - - - - - - ranking = 0.00011236835736954keywords = acid (Clic here for more details about this article) |
7/47. Effective treatment of beta-thalassemia intermedia during pregnancy with rHuEpo. A case report.The anemia of pregnancy in presence of beta-thalassemia intermedia usually aggravates pregnancy procedure. In the present study we investigated whether the administration of recombinant human erythropoietin (rHuEpo) recombinant human erythropoietin in combination with iron and folic acid may ameliorate blood indices as an alternative choice to blood transfusion.- - - - - - - - - - ranking = 0.0020267009256953keywords = rna, acid (Clic here for more details about this article) |
8/47. Distinct phenotypic expression associated with a new hyperunstable alpha globin variant (Hb heraklion, alpha1cd37(C2)Pro>0): comparison to other alpha-thalassemic hemoglobinopathies.Clinical phenotypes associated with abnormal globin chain biosynthesis may result in thalassemia (deficient quantity) or hemolytic anemia (abnormal hemoglobins). However, the phenotypic expression of hyperunstable hemoglobin variants often includes features of thalassemia, along with variable peripheral hemolysis. hemoglobinopathies caused by highly unstable beta-chain variants have a dominant thalassemia-like phenotype, in which carriers have a clinical expression of thalassemia intermedia, but highly unstable alpha-globin variants are usually only phenotypically apparent when they interact with other alpha-thalassemia mutations. In a child with clinical and hematological features consistent with beta-thalassemia intermedia, dna analysis excluded any beta-globin gene mutations but characterized a novel deletion cd37(C2)Pro>0 (Hb Heraklion) in the alpha1 globin gene, in trans to a common Mediterranean nondeletion alpha-thalassemia mutation (alpha(Hph)alpha). The deletion of proline at alpha37(C2) is predicted to result in severe instability of the variant hemoglobin, which on interaction with a synthesis-deficient alpha-thalassemia mutation causes a relatively severe dyserythropoietic anemia, representing an alternative phenotype associated with highly unstable alpha-chain variants. Hb Heraklion is the fourth highly unstable alpha-globin variant that we have observed in patients from greece and albania. Two variants involve the alpha2-globin gene: Hb Agrinio (alpha29(B10)Leu>Pro) and Hb Adana (alpha59(E8)Gly>Asp), and two the alpha1-gene: Hb Aghia Sophia (alpha62(E11)Val>0) and (Hb Heraklion a37(C2)Pro>0). Each has been observed on interaction with a different alpha-thalassemia mutation and the phenotypes associated with these highly unstable alpha-variants are presented.- - - - - - - - - - ranking = 0.0019143325683257keywords = rna (Clic here for more details about this article) |
9/47. Endogenous endophthalmitis and necrotising pneumonia caused by klebsiella pneumoniae in a child with beta-thalassaemia major.A case beta-thalassaemia major complicated with klebsiella pneumoniae endogenous endophthalmitis is presented to increase physician awareness of the association of the two clinical conditions. Severe morbidity including subretinal abscess and retinal detachment may develop despite aggressive intravenous and intravitreal ceftriaxone therapy, along with vitrectomy and external drainage.- - - - - - - - - - ranking = 0.0019143325683257keywords = rna (Clic here for more details about this article) |
10/47. diabetic ketoacidosis and hypogonadotropic hypogonadism in association with transfusional hemochromatosis in a man with beta-thalassemia major.We report a 23-year-old man with beta-thalassemia major and transfusional hemochromatosis, which manifested as diabetic ketoacidosis and hypogonadotropic hypogonadism. This unusual presentation of diabetic ketoacidosis in hemochromatosis has rarely been reported. magnetic resonance imaging of the abdomen showed decreased signal intensity in the liver, spleen, and pancreas. In addition, the pituitary gland also showed heterogeneous low signal intensity, compatible with hemochromatosis. He was treated with insulin supplements and pulsatile human chorionic gonadotropin administration. Clinical improvement was noted after hormone replacement. Intensive iron chelation therapy was given to prevent cardiac complications, and to restore his gonadal function. During follow-up, the patient experienced improvement in libido and sexual potency.- - - - - - - - - - ranking = 0.00067421014421725keywords = acid (Clic here for more details about this article) |
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