Biomedical subjects
Publications and source records attributed to D Loukopoulos.
We have studied three compound heterozygotes for Hb Lepore ("Pylos")/HbS hemoglobin, a combination quite uncommon in the literature. It is of interest that while two of these cases are clinically similar to those thus far reported, the third one is free of symptoms and the diagnosis was put incidentally. This mild condition may be due to the high level of fetal hemoglobin produced.
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Pure red cell aplasia was diagnosed in a 35-year-old otherwise healthy woman. Chest computed tomography (CT)-imaging investigation, detected an upper mediastinal mass corresponding to the thymus gland. A thoracotomy was performed and an enlarged thymus mass was removed, rapidly followed by a full hematologic recovery. Thymic histology confirmed a significant degree of hyperplasia. We conclude that not only thymomas but also other types of thymic pathology may be associated with this type of hematologic dyscrasia.
Cytogenetic analysis of bone marrow cells from a patient with anemia, marked leukocytosis with eosinophilia, and thrombocytopenia showed monosomy 7 in all metaphases examined. The patient has refractory anemia (RA) according to FAB classification. Because of the hypereosinophilia of the patient, PCR technique was performed and no bcr-abl mRNA, specific for chronic myelogenous leukemia, was detected. Monosomy 7 has not been previously described in cases with hypereosinophilia. We assume, according to previous reports, that multiple genetic lesions can be involved in the pathogenesis of hypereosinophilia in this patient.
The use of hypervariable tandem repeat loci for population genetic studies, genetic analysis of inherited disease and individual identification purposes requires establishment of a genetic database for each reference population. In the present study we have analysed variability at five tandem repeat loci (D1S80, D17S5, 3'-hvr/apoB, F8vWF and D6S89)in a representative sample (88 to 156 individuals of greek ancestry), using polymerase chain reaction amplification. Between nine and 19 alleles were resolved throughout the five polymorphic loci. Heterozygosity indices for these loci in the greek population ranged from 0.68 to 0.85. Allele frequencies follow a bimodal discrimination (pd) and allelic diversity (h) values ranged from 0.84 to 0.94 and 0.85 to 0.91, respectively, and indicated that these loci are highly informative and can be used for population studies, forensic purposes and parentage and family testing. Comparison of observed and expected genotype frequencies by the conventional chi-square test indicated conformity to Hardy-Weinberg predictions.
Hydroxyurea (HU), a widely used cytostatic, has been given over a long period of time to 14 adult Caucasian compound heterozygotes for beta s and various beta-thalassaemia genes. All patients had severe pain crises and other complications prior to receiving the drug. After 4-8 weeks on high 'sub-toxic' doses of HU all patients responded with a multifold increase of fetal haemoglobin (HbF) and a marked increase of MCV and MCH; they also felt significantly better and ceased having pains or other complaints. Haematological toxicity was minimal and rapidly reversible. Follow-up of the patients has now exceeded 100 weeks and goes up to 180 weeks in two of them. Pain crises have never recurred. Maintenance of high levels of HBF requires continuous administration of high doses of HU; whenever the latter were decrease in various attempts to avoid potential long-term toxicity, the observed changes gradually faded. The effect of HU in HbS/beta-thalassaemia may be better than that reported for homozygous HbS disease because the synthesized gamma-chains not only inhibit the sickling process but they also neutralize the noxious effects of the excess alpha-chains and cut down the ineffective erythropoiesis of the patients.
A Greek family is presented in which seven members suffered from benign hereditary chorea (a rare autosomal dominant non-progressive chorea without dementia). All patients and three informative healthy relatives were submitted to DNA analysis using probes from loci linked to Huntington's disease. The results confirm one previous suggestion that these two disorders are not allelic and that they should be considered as two distinct genetic entities.
We analyzed seven patients with beta-thalassemia intermedia presenting with congestive heart failure secondary to pulmonary hypertension. This condition has been recognized only recently as part of the clinical spectrum of beta-thalassemia. Our group of patients included two men and five women with the clinical picture and laboratory data typical of beta-thalassemia intermedia. The mean age was 37.7 +/- 11.4 years, mean hematocrit value was 28.5 +/- 1.8%, mean number of transfused blood units was 171 +/- 153, and mean serum ferritin levels were 4,428 +/- 2,006 ng/mL. All but one of these patients had undergone splenectomy. Common findings of the investigative procedures include the following: dilation of the main pulmonary artery and cardiac enlargement in the chest radiograph; signs of right ventricular hypertrophy in the ECG; and dilated right ventricle with good left ventricular function in the echo study. Right heart catheterization showed the pulmonary systolic pressure to range from 55 to 90 mm Hg (74.1 +/- 10.3), pulmonary diastolic pressure from 25 to 50 mm Hg (37.7 +/- 8.7), mean pressure from 35 to 60 mm Hg (49.7 +/- 7.9), and pulmonary vascular resistance from 267 to 667 dynes.s.cm-5. Pulmonary capillary wedge pressure was within the normal range of values. The pathophysiologic condition of pulmonary hypertension in these patients is most probably associated with beta-thalassemia. There are mechanisms that increase cardiac output and at the same time restrict the pulmonary vascular bed. The results of this study imply that treatment decisions should be reconsidered for such patients.
The breakpoints on chromosome 22 in CML occur within a 5.8 kb region called the Major breakpoint cluster region (M-bcr). DNA mapping within the M-bcr region was performed in 41 long term followed Ph1-positive CML patients using the Southern blot technique. The purpose of this study was to determine whether localization of M-bcr breakpoint correlates with the length of chronic phase of the disease, blastic crisis lineage and thrombocytosis at the time of initial diagnosis. Our results fail to indicate any correlation between breakpoint localization and duration of chronic phase, blastic crisis lineage and platelet count at diagnosis.
We report a case of thalassaemia intermedia complicated during two consecutive pregnancies by two episodes of spastic paraparesis due to compression of the spinal cord by extramedullary paravertebral masses. The patient was successfully treated by hypertransfusion and local irradiation. Compression of vital organs by the extramedullary masses must always be considered in chronic haemolytic anaemias during periods of increased haemopoietic demands like pregnancy. As relapses can not be excluded, a closer follow-up is needed. A dose of irradiation preventing from recurrences in the same anatomical area, seems necessary.
Oral salivary secretion and oral histology in 15 multi-transfused adult thalassaemia homozygotes was studied. Iron stores of minor salivary glands were also histochemically determined. Salivary secretion in multi-transfused thalassaemia patients was subclinically decreased, but no clear correlation was evident between salivary secretion impairment and salivary gland destruction by iron deposition, lymphocyte infiltration and fibrosis. The underlying mechanism remains to be determined.
Angioid streaks have been described in a diverse group of diseases including hemoglobinopathies such as sickle cell anemia and beta-thalassemia. We investigated the prevalence of angioid streaks and pseudoxanthoma elasticum in the rare situation of patients who had compound heterozygous traits for hemoglobin S and beta-thalassemia. We examined 58 consecutive patients with sickle-thalassemia. Of these, 25 were men and 33 were women, and they ranged in age from 19 to 58 years (mean, 32.6 years). Angioid streaks were identified in six of 58 patients (10%), and of these three also displayed the cutaneous lesions of pseudoxanthoma elasticum, which were confirmed by skin biopsy. An expanded study on several relatives of the patients with angioid streaks failed to identify any similar cases. Statistical evaluation of the main hematologic and biochemical parameters in the patients with and without angioid streaks did not demonstrate any significant differences, except that the thalassemic component in all six patients with angioid streaks was beta(0) (that is, did not allow the synthesis of hemoglobin A). We conclude that angioid streaks and pseudoxanthoma elasticum skin lesions occur with an increased frequency in patients with sickle-thalassemia.
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Shape changes of abnormally deformed red cells in aperture impedance haematology analysers are known to affect MCV, MCHC and haematocrit estimation. However, different counters vary in the manifestation of this effect. We performed a comparative study among five analysers. Three of them are based on impedance without hydrodynamic focusing (Coulter STKR, Cell-Dyn3000 Abbott and K-1000 Sysmex). The other two use hydrodynamic focusing, either with impedance (NE-8000 Sysmex) or two angle laser scatter (H*1 Bayer). A novel method of analysis was applied. Two hundred and three specimens with abnormal red cells and 50 normal specimens (according to ICSH criteria) were assayed. In all samples the PCV was estimated by the reference method without correction for trapped plasma. A true MCHC value was estimated from the mean haemoglobin value and the PCV. The shape effect was assessed by three linear regressions: 1) haematocrit deviations from PCV (corrected for any calibration bias) versus true MCHC; 2) analyser MCHC vs. true MCHC; 3) MCV vs. MCH. The regressions for the analysers with hydrodynamic focusing indicated no significant shape effect. Aperture impedance analysers without focusing varied in their behaviour. The Coulter STKR and the Cell-Dyn3000 both showed strong correlation of haematocrit deviations with true MCHC, poor MCHC correlations and linear MCV-MCH regressions. The K-1000 showed minor indications of such an effect. We conclude that comparative studies are needed to quantitate red cell shape effect errors among various impedance analysers.
The molecular defect was defined in 38 delta beta-thalassemic chromosomes from 30 unrelated heterozygous and 4 homozygous patients of Greek origin. Restriction fragment beta-gene cluster haplotypes were studies in 23 delta beta-thalassemic chromosomes. The molecular lesion was identical in all studied cases and corresponds to the 'Sicilian' type of delta beta-thalassemia. Restriction haplotypes analysis has shown that, with one exception only, all Greek delta beta-thalassemic chromosomes bear the polymorphic sites which characterize haplotypes I or VII, the former being probable by indirect evidence. The striking similarities of the molecular lesion and the underlying haplotypes are consistent with two theories: (1) The deletion occurred once on a chromosome and spread all over Greece and the Mediterranean area thereafter; (2) the 5' subhaplotype +----favors the deletional event in the delta-beta gene area.