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F Galacteros

Publications and source records attributed to F Galacteros.

At least 19 recordsLinked to original sources
PubMed2001

Endothelial dysfunction in patients with sickle cell disease is related to selective impairment of shear stress-mediated vasodilation.

Interactions between the endothelium and erythrocytes may contribute to the vascular complications of sickle cell disease (SCD). Endothelium-derived nitric oxide (NO) plays a major role in the regulation of vasomotor tone in response to wall shear stress (WSS) variations and pharmacologic stimuli. However, little is known about endothelial NO production in patients with steady-state SCD. We investigated endothelial NO production in response to flow or vasoactive agonists in 16 homozygous patients with steady-state SCD and 15 controls. Flow-mediated dilation (FMD), arterial diameter changes in response to 100% oxygen inhalation, blood viscosity, and calculated WSS were determined in all patients and controls. At baseline, WSS was higher in SCD patients than in controls, whereas arterial diameter was similar. In patients with SCD, FMD was impaired (1.73% +/- 0.44% vs 3.97% +/- 0.24% in the controls, P <.001) and vasoconstriction in response to 100% oxygen was abolished. Using venous occlusion plethysmography, forearm blood flow (FBF) was evaluated in response to acetylcholine, nitro-monomethyl-L-arginine (L-NMMA), and sodium nitroprusside (SNP) in subgroups of 9 controls and 7 patients with SCD. Acetylcholine induced a significantly greater FBF increase in the patients (9.7 +/- 2.9 mL/min/100 mL of forearm volume vs 2.5 +/- 1.5 mL/min/100 mL in the controls, P <.001), whereas responses to L-NMMA and SNP were similar. These results suggest that endothelial dysfunction may prevent the arterial diameter of patients with SCD from adapting to chronic or acute shear stress elevations. This may contribute to the pathophysiology of vaso-occlusive crisis in patients with SCD.

Acetylcholine↗
PubMed2001

Resveratrol, a natural dietary phytoalexin, possesses similar properties to hydroxyurea towards erythroid differentiation.

Resveratrol, a natural dietary polyphenol, has been postulated to be implicated in the cardioprotective effect of red wine and the low incidence of breast and prostate cancers among vegetarians and Orientals respectively. This compound inhibits ribonucleotide reductase as does hydroxyurea, the first therapeutic agent used in the treatment of sickle cell disease. Using the human erythroleukaemic K562 cell line as an in vitro model, we show here that 50 micromol/l of resveratrol induced a higher haemoglobin production (sevenfold) in K562 cells than 500 micromol/l of hydroxyurea (3.5-fold). This erythroid differentiation was linked to a dose- and time-dependent inhibition of cell proliferation associated with an equivalent increased expression of p21 mRNA, but with a higher increased level of p21 protein (sixfold) for cells treated with resveratrol than for those treated with hydroxyurea (1.5-fold). We also show that 50 micromol/l of resveratrol and 25 micromol/l of hydroxyurea induced variable but similar enhancements of fetal haemoglobin synthesis in cultured erythroid progenitors for the majority of the sickle cell patients studied. These inductions were linked to, but not correlated with, a variable decrease in erythroid burst-forming unit clone number. Taken together, these results show that resveratrol merits further investigations in sickle cell disease therapy.

Anemia, Sickle Cell↗
PubMed2001

[Physiopathological basis of sickle cell disease, management and current therapeutics].

Physiopathological knowledge in the area of sickle cell disease underwent a first major development three decades ago, some 15 years after the discovery of the molecular nature of the disease. Several physiopathological areas can be distinguished: physiopathology of polymerisation which has been successfully approached by fundamental biophysicists and biochemists alike; physiopathology of the red blood cell; more recently, the characterisation of red blood sickle cells by extra-hemoglobin aspects: the red blood cell is not a passive recipient for hemoglobin but carries out a series of functions which can contribute to physiopathology; the phenomenon of vaso-obstruction is still poorly understood, whereas clinical secondary manifestations of the disease, the physiopathology of infectious risk and severe anaemic manifestations have been well understood. The treatment of sickle cell patients continues to evolve and progress. There are certain characteristics which remain, however, permanent: there is continual interaction between preventive and therapeutic measures; treatment must be both medical and social, given the impact of the disease of the individual and his family or vice-versa; treatment is centred around the hospital with more than ever the necessity to ensure excellence in internal medicine or paediatrics, intensive care and transfusion. Finally, the distinction among three periods for the natural history of the disease remain: before 7 years of age, from 7 years to adult age, adulthood. An integrated, pilot centre for treating patients with sickle cell disease is of crucial importance and can contribute to therapeutic innovations in the area.

Adolescent↗
PubMed2001

[Sickle cell disease: laboratory and hemoglobin study].

The diagnosis of any sickle cell disease syndrome is based on the unambiguous identification of HbS. Electrophoretic tests are usually the first to be performed. A much better resolution is obtained with isoelectricfocusing than with the more conventional cellulose acetate electrophoresis at alkaline pH. In some laboratories the first test is cation exchange HPLC. The diagnosis of HbS should never be accepted if not confirmed by a second test, more specific of this Hb such as the solubility test or electrophoresis on agar in citrate buffer. The laboratory should also evaluate other factors interacting with HbS, such as HbF level, sickle cell restriction haplotype, association with alpha-thalassemias. It should also evaluate other cellular factors and, in case of symptomatic heterozygous patients, help to understand of the underlying mechanisms.

Anemia, Sickle Cell↗
PubMed2000

Oral magnesium pidolate: effects of long-term administration in patients with sickle cell disease.

Prevention of erythrocyte dehydration by specific blockade of the transport pathways promoting loss of potassium (K) is a potential therapeutic strategy for sickle cell (SS) disease. Dietary magnesium (Mg) pidolate supplementation over a 4-week period has been shown to inhibit K-Cl co-transport and reduce dehydration. We report here the results in 17 of 20 patients with SS disease treated in an open-label unblinded study of the effects of long-term (6 months) oral Mg pidolate administration (540 mg Mg/d). A significant decrease (P < 0.0025) was observed with Mg therapy in the distribution widths for red cell mean cell haemoglobin concentration (MCHC) (haemoglobin distribution width; HDW), reticulocyte mean cell volume (red cell distribution width of reticulocytes; RDWr) and MCHC (reticulocyte HDW; HDWr), activity of red cell K-Cl co-transport, Na/Mg exchanger and Ca2+-activated (Gardos) K+ channel, whereas red cell K and Mg contents were significantly increased. Hb levels and absolute reticulocyte counts did not change with Mg therapy. Two patients did not complete the trial because of diarrhoea and one did not complete the trial for unrelated reasons. Although the median number of painful days in a 6-month period decreased from 15 (range 0-60) in the year before the trial to 1 (range 0-18; P < 0.0005) during the period of Mg therapy, no firm conclusion on therapeutic efficacy could be drawn from this unblinded open-label trial.

Administration, Oral↗
PubMed2000

Acute chest syndrome in adults with sickle cell disease.

STUDY OBJECTIVES: Acute chest syndrome (ACS) is a frequent and potentially severe pulmonary illness in sickle cell disease (SCD). The aim of the study was to report the clinical features and outcome of consecutive ACS episodes in adult patients in a French SCD center. All patients were treated according to an uniform therapeutic protocol applying transfusion only in the more severe clinical form of ACS. RESULTS: There were 107 consecutive episodes in 77 adult patients (mean age, 29 +/- 7 years; 78% hemoglobin [Hb] SS; 14% Hb SC; and 8% Hb Sbeta + thalassemia) over a 6-year period. Seventy-eight percent of our patients had an associated vaso-occlusive crisis that preceded the chest signs in half of the cases. Comparison between acute and baseline levels showed a statistically significant difference in Hb levels (drop of 1.6 to 2. 25 g/dL depending on Hb genotype), WBC count (increase of 9.2 +/- 8. 3 x 10(9)/L); platelet count (increase of 67 +/- 209 x 10(9)/L); and lactate dehydrogenase values (increase of 358 +/- 775 IU/L) in ACS patients. Hypercapnia was detected in 42% of patients without sign of narcotic abuse. We identified a high percentage of alveolar macrophages containing fat droplets in 31 of 43 (77%) patients who underwent BAL. Bacterial culture findings were almost always negative, but were performed after starting antibiotic therapy that was administered in 96 episodes. Transfusion was required in 50 of 107 ACS events (47%). Five patients died, and all were transfused. CONCLUSIONS: These results confirm that fat embolism is probably a frequent mechanism of ACS in adult patients. However, fat embolism was not associated with a more severe clinical course, suggesting that bronchoscopy and BAL have little impact on the management of these patients. Restricting transfusion to the most severe ACS cases does not seem to increase the mortality rate.

Acute Disease↗
PubMed1998

Hemoglobins in Togolese newborns: Hb S, Hb C, Hb Bart's, and alpha-globin gene status.

The gene frequency of the most important hemoglobin (Hb) abnormalities is reported in a population of 171 Togolese newborns. Hb phenotypes, hematological parameters, and the more frequently described alpha-gene deletions were analyzed. Structural abnormalities of beta-globin were observed in 35.7% of the children with a gene frequency of 0.105 for beta(S) and 0.091 for beta(C). The frequency of the different alpha-globin genotypes was alpha alpha/ = 0.71, -alpha/ = 0.28, and alpha alpha alpha/ = 0.01. All of the individuals homozygous for the -alpha genotypes, and most of the heterozygous individuals, carried Hb Bart's. Within the alpha alpha/alpha alpha and the -alpha/alpha alpha groups, several individuals with or without Hb Bart's were found; they did not differ from the others by their red blood cell (RBC) parameters but by their levels of fetal hemoglobin (Hb F). The African alpha2 polymorphism marker, characterized by the replacement of G by TCGGCCC at position 7238 (EMBL HSHBA4, 1993) and of T 7174 by G, was found in 21 newborns. The mean value of Hb F was calculated for each genotype, the mean (G)gamma percentage was 69.4 +/- 4.0%, and the gene frequency of the AgammaT marker was 0.10; this marker was linked to the normal beta-globin cluster.

Blood Cell Count↗
PubMed1998

Early glomerular dysfunction in patients with sickle cell anemia.

The purpose of this study was to analyze the determinants of glomerular filtration in nonnephrotic young adult patients with sickle cell anemia (SCA). We prospectively screened 14 patients with homozygous SCA who had normal plasma creatinine concentrations and normal or moderately elevated albuminuria (< 1 g/d). Inulin, paraaminohippuric acid, and dextran clearances were evaluated and compared with values obtained from a control group (age-matched healthy volunteers). SCA patients had a significantly higher glomerular filtration rate and effective renal plasma flow than controls (146 +/- 9 mL/min/1.73 m2 v 120 +/- 3 mL/min/1.73 m2 [P < 0.01] and 1,052 +/- 69 mL/min/1.73 m2 v 709 +/- 38 mL/min/1.73 m2 [P < 0.001], respectively). We found no correlation between glomerular filtration rate or effective renal plasma flow and hematocrit. Fractional clearance of neutral dextran was significantly elevated in SCA patients for all radii between 3.4 and 5.4 nm. Theoretical analysis of dextran transport through a heteroporous membrane model revealed a slight increase in the mean radius (ro) of restrictive pores (5.68 nm v5.50 nm; P < .001) and no significant difference in shunt pathway (omega o) values. Among the other hemodynamic parameters, the most significant change was a dramatic increase in ultrafiltration coefficient (41.3 +/- 3.6 mL/mm Hg/min/1.73 m2 v 25.1 +/- 2.6 mL/mm Hg/min/1.73 m2; P < 0.001). Our results suggest that hyperfiltration in SCA patients is associated not only with enhanced renal perfusion but also with an alteration in glomerular permeability and with an increase in Kf. This change in Kf is fully in agreement with the large increase in glomerular area previously described in SCA patients. Based on our results and those of previous morphologic studies, we propose that enhanced transglomerular trafficking of macromolecules associated with podocyte stretch lesions (defects) induced by glomerular hypertrophy may play a role in the genesis of this particular form of focal segmental glomerulosclerosis, which is associated with SCA.

Adult↗
PubMed1998

Pulmonary function in sickle cell disease with or without acute chest syndrome.

Recurrent acute chest syndrome (ACS) has been suggested as a risk factor for chronic lung dysfunction in sickle cell disease. To investigate this hypothesis, lung function tests were performed in 49 sickle cell disease outpatients whose condition was stable, including 23 patients with a history of two to four episodes of ACS (ACS+) and 26 with no history of ACS (ACS-). The two groups were comparable regarding the sex ratio, body mass index, smoking history, physical characteristics, clinical history and usual lung function tests. Respiratory resistance (Rrs), measured using the forced oscillation technique, increased with the number of ACS episodes (r=0.55, p<0.0001) and a significant relationship was observed between Rrs as an independent variable and the expiratory flow rates at 25, 50 and 25-75% of the forced vital capacity as explanatory variables (r= 0.36, p<0.02; r=0.35, p<0.02; and r=0.4, p<0.006, respectively), with higher Rrs being associated with lower expiratory flow rates. The transfer factor (TL,CO) and transfer coefficient (KCO) for CO were significantly higher in the ACS+ group than in the ACS-group (TL,CO=84+/-4 versus 71+/-3%, p<0.004 and KCO=102+/-5 versus 90+/-3%, p<0.05, respectively). The data demonstrate that obstructive lung dysfunction is fairly common in sickle cell disease and suggest that recurrent acute chest syndrome may contribute specific obstructive defects. The increase in respiratory resistance associated with acute chest syndrome was accompanied by an increase in diffusion capacity, suggesting that it may have been related to an increase in lung blood volume.

Acute Disease↗
PubMed1998

Abnormalities of the adult shoulder due to sickle cell osteonecrosis during childhood.

PATIENTS AND METHODS: A retrospective study of 110 adults with sickle cell anemia (SS genotype) was conducted to determine the frequency of complications of sickle cell osteonecrosis of the shoulder in childhood. The glenohumeral joint was evaluated on plain anteroposterior and lateral radiographs of the shoulder. RESULTS: Mean time since osteonecrosis of the shoulder was 24 years. Radiographic abnormalities were seen in 106 of the 220 shoulders (48.2%). Both shoulders were affected in 86% of cases and at least one hip in 96%. Radiographic abnormalities included isolated caput magna, caput plana, a short humeral neck and ascension of the tuberosities. Twelve shoulders exhibited glenoid fossa abnormalities, which consisted in complete or partial hypoplasia. Evidence of glenohumeral osteoarthritis was seen in 11 shoulders. DISCUSSION: The shoulder abnormalities seen in our patients were probably due to growth disturbances in the proximal humerus secondary to osteonecrosis of the humeral head during childhood. They were common but less likely to produce functional impairment than osteonecrosis-related lesions of the hip. However, some patients had premature osteoarthritis and geometric shoulder abnormalities responsible for functional loss in adulthood.

Adolescent↗
PubMed1997

Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.

Intracellular polymerization and sickling depend markedly on the cellular concentration of sickle hemoglobin (Hb S). A possible therapeutic strategy for sickle cell disease is based on reducing the cellular concentration of Hb S through prevention of erythrocyte dehydration. The K-Cl cotransporter is a major determinant of sickle cell dehydration and is inhibited by increasing erythrocyte Mg content. We studied 10 patients with sickle cell disease before treatment and after 2 and 4 wk of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hematological parameters, erythrocyte Na, K, and Mg content, erythrocyte density, membrane transport of Na and K, and osmotic gradient ektacytometry were measured. We found significant increases in sickle erythrocyte Mg and K content and reduction in the number of dense sickle erythrocytes. Erythrocyte K-Cl cotransport was reduced significantly. We also observed a significant reduction in the absolute reticulocyte count and in the number of immature reticulocytes. Ektacytometric analysis showed changes indicative of improved hydration of the erythrocytes. There were no laboratory or clinical signs of hypermagnesemia. Mild, transient diarrhea was the only reported side effect. We conclude that oral Mg supplementation reduces the number of dense erythrocytes and improves the erythrocyte membrane transport abnormalities of patients with sickle cell disease.

Adolescent↗
PubMed1997

[Ambulatory treatment and prevention of priapism using alpha-agonists. Apropos of 172 cases].

From 1985 to 1995, 172 patients (149 on self intracavernous injection of vasoactive drugs, 16 with Sickle cell disease, 6 surgical patients under heparin therapy, and 1 after oral administration of trazodone), having experienced one or several episodes of priapism, lasting from 3 h to 8 days have been treated or submitted to self medication with alpha-agonist agents (eprephrine, phenylephrine or etilefrine) with an eventual drainage of the corporae. All episodes have disappeared and sexual function was preserved. A conservative treatment of priapism has been designed using corporal drainage and intracavernous etilefrine for acute priapism; as well as preventive treatment for those of the patients exposed to Sickle cell disease to avoid surgery and its frequent fribrotic sequelae, leading to impotence in 50% of the cases.

Adolescent↗
PubMed1996

Perfusion chromatography on reversed-phase column allows fast analysis of human globin chains.

Human globin chain analysis provides important information on the genetics and molecular pathophysiology of hemoglobinopathies. We propose using perfusion chromatography on the reversed-phase stationary phase to perform these studies. The technique, herein described, involves a high-velocity flow of the mobile phase through a porous chromatographic stationary phase made of microspheres of poly(styrene-divinylbenzene) having throughpores of 6000-8000 A diameter with short diffusive pores of 500-1000 A diameter connected to them. The composition of fetal hemoglobin (Ggamma:Agamma ratio) is determined, using this method, as an order of magnitude faster than with conventional HPLC. Elution is performed by developing a linear gradient of acetonitrile at a flow rate of 3 ml/min (or more), easily obtained on any HPLC machine. Analyses may be done on samples containing as low as 3.0% Hb F. Results are similar to those obtained with the reference HPLC technique, which uses a C4 column. In addition, reversed-phase perfusion chromatography, using a shallow curvilinear gradient, may help in the characterization of Hb variants. This technique allowed us to discriminate several alpha and beta chain mutants from variants that have closely similar patterns of electrophoretic mobilities.

Chromatography↗