Recombinant human erythropoietin therapy in a transfusion-dependent beta-thalassemia major patient.

We report on a 28-year-old patient with transfusion-dependent beta-thalassemia major, who was treated effectively with recombinant human erythropoietin (rHuEpo). rHuEpo promotes the differentiation and proliferation of erythroid cells, induces the production of fetal hemoglobin (HbF), and could be useful in the treatment of some selected transfusion-dependent thalassemia patients. Prior to rHuEpo treatment, the patient was on a regular blood transfusion regimen. Splenectomy did not decrease the transfusion requirements. Additionally, red cell alloimmunization had developed; therefore, we decided to start rHuEpo treatment (Eprex, Jansen Cilag, Greece) in an attempt to improve his anemia and the quality of life. Our patient responded well to rHuEpo treatment and was able to extend the intervals between transfusions from 10-14 to 55-65 days and to sustain a pretransfusion hemoglobin level above 7 g/dl. HbF levels were slightly increased from 55% to 60-65%. Indicators of vascular endothelial activation [serum endothelin-3, intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin] were decreased during treatment. rHuEpo was well tolerated without complications. rHuEpo treatment seemed to have had a beneficial effect and to have improved the quality of life in beta-thalassemia major, although it did have a slight effect on HbF levels, suggesting other possible mechanisms of rHuEpo action.

The role of cytokines in sickle cell disease.

Sickle cell disease (SCD) is characterized by chronic hemolysis, frequent infections, and recurrent occlusions of microcirculation, which cause painful crises and result in chronic organ damage and failure. Occlusions of the microcirculation and infections are important factors that stimulate the production of cytokines and acute-phase proteins. Cytokines seem to be involved with several possible mechanisms in the pathogenesis of vasoocclusive phenomena in SCD: vascular endothelial activation, induction of red-cell adhesiveness to vascular endothelium, induction of neutrophil adhesiveness to endothelium, development of vascular intimal hyperplasia, platelet activation, endothelin-1 production, and dysregulation of endothelial apoptosis. Cytokines are also thought to be involved in the regulation of hemopoiesis, the inhibition of immune functions, and the development of growth deficits. Investigation of cytokines in SCD patients will elucidate the pathogenesis of the disease and its complications and may help in assessing disease severity and prognosis.

Alpha-2-macroglobulin and interleukin-6 levels in steady-state sickle cell disease patients.

Endothelial activation and subclinical microvascular occlusions are an ongoing process during steady-state sickle cell disease, leading to interleukin production and an acute-phase response. Alpha-2-macroglobulin (alpha2M) is an acute-phase protein mainly regulated by interleukin-6 (IL-6). On the other hand, alpha2M acts as a carrier protein for IL-6 during inflammatory stress. The purpose of this study is to further assess the interactions between IL-6 and alpha2M as potent modulators of inflammatory reactions during the steady state of sickle cell disease. We measured alpha2M and IL-6 levels in 21 patients (12 male, 9 female; age range 12-44 years) in the steady state of sickle cell disease. Four patients had homozygous sickle cell anaemia and 17 had double heterozygous sickle cell/beta-thalassaemia. Diagnostic quantification of alpha2M was performed by rate nephelometry. Commercial enzyme immunoassay test kits were used for the quantitative measurement of IL-6. The alpha2M and IL-6 levels were compared to the values obtained from healthy volunteers. Mean values (+/- SD) of alpha2M and IL-6 were found to be significantly increased (p < 0.0005) in the patients (alpha2M: 337.2 +/- 104 mg/dl; IL-6: 4 +/- 2.1 pg/ml) compared to the healthy controls (alpha2M: 204.2 +/- 45.8 mg/dl; IL-6: 1.15 +/- 2.5 pg/ml). IL-6 values were positively correlated with alpha2M levels (r = 0.61, p < 0.01). We observed increased alpha2M and IL-6 levels in steady-state sickle cell disease and a positive correlation between these two inflammatory mediators. We suggest that alpha2M is a potent modulator of the inflammatory reaction and tissue repair mechanism during steady-state microvascular occlusions. Elucidating the role of alpha2M in sickle cell disease could lead to the development of novel strategies and therapies for preventing the harmful systemic or local effects of excess cytokine production.

Serum beta-2-microglobulin, TNF-alpha and interleukins in myeloproliferative disorders.

Whereas beta-2-microglobulin (beta2M) has mainly been used as a prognostic factor in patients with lymphoproliferative disorders, some studies have reported the value of beta2M in myeloproliferative disorders (MPD). In order to investigate a potential role in the pathogenesis of MPD and to find a possible value as indicators in monitoring the course of the disease, we measured beta2M, TNF-alpha, IL-1alpha, IL-1beta, IL-2, sIL-2R, IL-6 and IL-10 in 55 patients with MPD, at diagnosis and during the course of the disease. In progressive disease and particularly when transformation to acute leukemia occurred, high levels of beta2M, IL-2 and sIL-2R were found in all patients; the elevation was progressive, which suggests a potential prognostic usefulness in the individual patient.

Incidence and other epidemiological characteristics of sudden cardiac death in northwest Greece.

Sudden cardiac death (SCD) has not been investigated separately in Greece. The aim of this study is to describe the epidemiological characteristics of people dying suddenly out of hospital in an area of Greece. In 1990, a population based study was started to detect the cases of people dying suddenly out of hospital (< 1 h after onset of acute symptoms or < 6 h after being seen alive) in a closed population in Northwest Greece (Ioannina area: 160,000 inhabitants). During a 3.5 year period, 283 potential cases aged 30-70 years were identified by monitoring the mortality in the emergency rooms of the two hospitals of the area, the coroner's office and the death certificates from the Government Department of Statistics. The diagnosis of SCD was established in 223 (183 men, 40 women; mean ages 59 and 61 years respectively) after visiting and interviewing the relatives and/or the family doctors within 12 days (range 1-28) after the death. SCD in the study accounts for 50% of all cardiovascular deaths and is the most common cause of death after neoplasia. The most common place of death was home (151 cases, 68%), and in 174 cases (78%) deaths occurred while the patients were relaxing or during routine activities. Prodromal symptoms were reported in 57 cases (26%). The time of day of death showed a circadian variation, with a peak in the late morning from 9:00 to 12:00. Ninety four (42%) had a prior history of heart disease. One hundred and ninety one cases (86%) occurred in the subgroup of age 50-70 years.(ABSTRACT TRUNCATED AT 250 WORDS)