Khalid I. Elsayh

Sublingual versus vaginal misoprostol for induction of labor at term: A randomized prospective placebo-controlled study

Aims:  To assess the effectiveness and safety of sublingual misoprostol (50 µg), compared with the same dose administered vaginally every 6 h for cervical ripening and labor induction in women with a viable fetus in the third trimester of pregnancy.

Hypoxia Biomarkers, Oxidative Stress, and Circulating Microparticles in Pediatric Patients With Thalassemia in Upper Egypt:

This study aimed to investigate the oxidative stress, hypoxia biomarkers, and circulating microparticles (MPs) in β thalassemia major. The study included 56 children with thalassemia and 46 healthy controls. Hypoxia biomarkers, oxidative stress biomarkers, and total plasma fragmented DNA (fDNA) were detected by the standard methods. The MPs were assessed by flow cytometry. Hypoxia and oxidative stress biomarkers, fDNA, and MPs were higher and total antioxidant capacity (TAC) was lower in patients with thalassemia than the controls. In splenectomized patients and those who had complications, vascular endothelial growth factor (VEGF), malondialdehyde, fDNA, endothelial, platelet, and activated platelet MP levels were higher while, TAC was lower than the nonsplenectomized patients. In conclusion, the increased tissue hypoxia, oxidative stress in β thalassemia, and its relationship with DNA damage and MPs release could explain many complications of thalassemia and may have therapeutic implications. The VEGF could serve as an important indicator for adequacy of blood transfusion in thalassemia.

Tissue Factor Pathway Inhibitor and P-Selectin as Markers of Sepsis-Induced Non-overt Disseminated Intravascular Coagulopathy

Inflammation and coagulation occur concomitantly in sepsis. Thrombin activates platelet that leads to P-selectin translocation, which upregulate tissue factor (TF) generation. Tissue factor pathway inhibitor (TFPI) is an anticoagulant that modulates coagulation induced by TF. The term non-overt disseminated intravascular coagulation (DIC) refers to a state of affairs prevalent before the occurrence of overt DIC. It was suggested that an initiation of treatment in non-overt DIC has better outcome than overt DIC. This study investigated the role of TFPI level, P-selectin, and thrombin activation markers in non-overt and overt DIC induced by sepsis and its relationship to outcome and organ dysfunction as measured by the Sequential Organ Failure Assessment (SOFA) score. It included 176 patients with sepsis. They were admitted to the pediatric intensive care unit (ICU).They included 144 cases of non-overt DIC and 32 cases of overt DIC. There was a significant difference in hemostatic markers, platelet count, partial thromboplastin time (PTT), P-selectin, thrombin activation markers, TFPI, and DIC score between overt and non-overt DIC in both groups. It was noticed that P-selectin was positively correlated with DIC score, fibrinogen consumption, fibrinolysis (D-dimer), thrombin activation markers, and TFPI. Tissue factor pathway inhibitor was significantly correlated with fibrinolysis, DIC score, and prothrombin fragment 1+2. Sequential Organ Failure Assessment score was correlated with DIC score and other hemostatic markers in patients with overt DIC. To improve the outcome of patients with DIC, there is a need to establish more diagnostic criteria for non-overt-DIC. Plasma levels of TFPI and P-selectin may be helpful in this respect.

CD4+ CD25+High Foxp3+ regulatory T cells, B lymphocytes, and T lymphocytes in patients with acute ITP in Assiut Children Hospital.

We aimed to examine the levels of lymphocyte subsets and regulatory T cells in patients with newly diagnosed immune thrombocytopenia (ITP) and their correlation with the course of ITP. The study included 40 pediatric patients with acute ITP and 30 controls. Lymphocytes and regulatory T cells were analyzed by flow cytometry. The percentages of CD19+ and CD8+ cells were significantly increased while that of CD4+ cells and CD4+/CD8+ ratio were significantly decreased. The percentages of CD4+CD25+High and CD4+CD25+High forkhead box protein 3 (Foxp3+) cells and the expression of Foxp3+ in CD4+CD25+High cells were significantly decreased in patients. Age, platelet count, and mean platelet volume (MPV) in patients with brief duration of thrombocytopenia were significantly decreased than in those with prolonged duration. The percentages of CD8+, CD4+CD25+High, and CD4+CD25+High Foxp3+ were significantly increased in patients with brief duration. Age, platelet count and MPV, and CD8+ cells had prognostic significance. CD4+CD25+High Foxp+ T cells may be a helpful prognostic marker in children with acute ITP.

Leukocytes apoptosis and adipocytokines in children with beta thalassemia major.

Abstract β-Thalassemia is a significant public health problem in Egypt. Infectious complications represent the second most common cause of mortality and the major cause of morbidity in β-thalassemia major (BTM). The increased susceptibility of these patients to infectious diseases has been attributed to the abnormalities of the immune system, which is evident by systemic inflammation and immune deficiency. In a case control study, 35 patients with BTM were compared with 30 sex- and age-matched children who served as controls. Serum ferritin, high-sensitive CRP (hsCRP), leptin and adiponectin levels were determined in all subjects. Apoptosis of neutrophils and lymphocytes was measured by the Annexin V-fluoroisothiocyanate binding assay. Serum leptin was significantly lower in patients when compared to controls. In contrast, adiponectin and hsCRP levels were significantly higher in the patients than the controls. Positive correlation was found between adiponectin and hsCRP. BTM patients had significantly higher total leukocytes, neutrophils and lymphocytes compared with controls. BTM children exhibited a significantly increased apoptosis in T-lymphocytes; however, there was no significant difference in the percentage of apoptosis of B-lymphocytes and neutrophils between the patients and the controls. There was a significant negative correlation between serum leptin and the percentage of apoptotic T-lymphocytes. Our BTM patients had a high percentage of apoptotic T-lymphocyte in comparison with controls. In addition, they had disturbed serum levels of adipocytokines and inflammatory markers. These derangements could have a role in the immunological disturbance observed in thalassemic patients.

T lymphocytes from malnourished infants are short-lived and dysfunctional cells.

To investigate T-cell functional molecules and inflammatory cytokines and to assess T-cell apoptosis in malnourished infants, 64 infants from undernourished women and 28 healthy control infants were recruited to the study. Malnourished infants showed a significant decrease in the levels of circulating IL-2 and IL-7 and increases in the levels of IL-1β, IL-6, IL-10 and TNF-α, as measured by flow cytometry. There was a significant reduction in the number of CD3(+) T cells and an increase in apoptotic T cells, which was associated with an up-regulation of CD95 and PD-1 expression on CD3(+) T cells in malnourished compared to control infants. Significant reductions were also observed in the phosphorylation of AKT and STAT5 and in the expression of CCR7 and CXCR4 receptors in malnourished children, and these reductions were associated with a significant reduction in T-cell migratory capacity to their ligands CCL21 and CXCL12, respectively, as measured using an in vitro chemotaxis assay. Taken together, these data suggest that lymphocytes from malnourished infants are short-lived and dysfunctional.

Dendritic cells in childhood sepsis.

PURPOSE Our aim was to investigate the level and the maturation status of dendritic cells (DCs) in pediatric patients with sepsis and its relation to prognosis. MATERIALS AND METHODS The study included 16 children with sepsis, 24 children with complicated sepsis, and 40 healthy control children. The patients were investigated within 24 hours of intensive care unit admission and after 28 days. Flow cytometric detection of DCs was done. RESULTS Within 24 hours, the levels of both plasmoid DCs and monocytoid DCs and the expression of CD86 and CD83 on DCs were significantly lower in patients than in controls, and the difference was marked in patients with complicated sepsis. The amount of CD86 and CD83 per cell was significantly lower in patients with complicated sepsis. The baseline numbers of monocytoid DCs and plasmoid DCs were higher in the survival patients than in nonsurvival patients. In addition, the expression of CD86 and CD83 on the entire DCs was significantly higher in the survival patients with sepsis. CONCLUSION Sepsis is associated with reduced level of DCs and decreases their maturation. The estimation of DCs number and maturation state may be used as prognostic makers of sepsis.

Oxidative Stress, Trace Elements, and Circulating Microparticles in Patients With Gaucher Disease Before and After Enzyme Replacement Therapy

We studied the level of lipid peroxide, nitric oxide (NO), trace elements (TEs), and microparticles (MPs) in Gaucher disease (GD) before and after 1 year of enzyme replacement therapy (ERT). A total of 15 children with GD and 15 healthy controls were enrolled in this study. Serum level of lipid peroxide, NO, and TEs was determined. The MPs were detected by flow cytometry. The level of lipid peroxide was significantly higher in the patients than in the controls even after ERT. Although NO level was normalized in the patients after ERT, zinc and copper were still lower in the patients after ERT. The percentages of various MPs were significantly higher in the patients than in the controls both before and after ERT. There were positive correlations between chitotriosidase and both lipid peroxide and total MPs. Conclusion: The GD is associated with alteration in oxidant and antioxidant status and high level of circulating MPs.

Circulating Endothelial Cells and Endothelial Progenitor Cells in Pediatric Sepsis.

ObjectivesThe aim of the study was to measure the number of circulating endothelial cells (CECs) and circulating endothelial progenitor cells (CEPs) in pediatric patients with sepsis and correlating it with the severity of the disease and its outcome. MethodsThe study included 19 children with sepsis, 26 with complicated sepsis, and 30 healthy controls. The patients were investigated within 48 hours of pediatric intensive care unit admission together with flow cytometric detection of CECs and CEPs. ResultsThe levels of both CECs and CEPs were significantly higher in patient with sepsis and complicated sepsis than the controls. The levels of CECs were higher in patients with complicated sepsis, whereas the levels of CEPs were lower in patients with complicated sepsis. Comparing the survival and nonsurvival septic patients, the levels of CEPs were significantly higher in the survival than in nonsurvival patients, whereas the levels of CECs were significantly lower in the survival than in nonsurvival patients. Serum albumin was higher in survival than in nonsurvival patients. ConclusionsEstimation of CECs and CEPs and their correlation with other parameters such as serum albumen could add important information regarding prognosis in septic pediatric patients.

Effects of royal jelly supplementation on regulatory T cells in children with SLE.

Background and objective To our knowledge, no previous studies have focused on the immunomodulatory effects of fresh royal jelly (RJ) administration on systemic lupus erythematosus (SLE) in humans. Our aim was to study the effect of fresh RJ administration on the disease course in children with SLE with some immunological markers (CD4+ and CD8+ regulatory T cells and T lymphocytes apoptosis). Methods This was an open-label study in which 20 SLE children received 2 g of freshly prepared RJ daily, for 12 weeks. Results The percentages of CD4+ CD25+high FOXP3+cells (CD4+ regulatory T cells) and CD8+CD25+high FOXP3+cells (CD8+ regulatory T cells) were significantly increased after RJ treatment when compared with baseline values. Apoptotic CD4 T lymphocytes were significantly decreased after RJ therapy when compared with baseline values and the control group. Conclusion This is the first human study on the effect of RJ supplementation in children with SLE. Our results showed improvements with 3-month RJ treatment with regard to the clinical severity score and laboratory markers for the disease. At this stage, it is a single study with a small number of patients, and a great deal of additional wide-scale randomized controlled studies are needed to critically validate the efficacy of RJ in SLE.