study of some genetic ameliorating factors in beta thalassemia

There are over 150 mutations affecting the beta globin gene that can lead to an altered expression of the gene and a decrease [beta [0]] or an absence [beta [+]] of beta globin production. The genes can be inherited in a homozygous or a heterozygous fashion. The result of inheritance of these genes can be diverse, ranging from beta thalassemia trait with no hematological disease to thalassemia major requiring repeated blood transfusions. There are co-inherited variables that can also influence the expression of this inheritance. Alpha gene deletion or the inheritance of the G gamma Xmn-1 gene sequence [C-T variation] at position -158 upstream of the G [gamma]-globin gene which is detectable by the restriction enzyme XmnI, are among these variables. The aim of this study is to clarify the effect of the above two variables as ameliorating factors in homozy-gous/double heterozygous beta thalassemia among a group of Egyptian thalassemic children. Thirty two cases of beta thalassemia were screened for common Mediterranean mutations [IVS1-110, 1-6,1-1, 11-745, codon 39, -87] alpha-gene deletions, and presence of G gamma Xmn-1 polymorphic site. As regards allele frequency, IVSI-6 showed the highest incidence [40.6%] followed by IVSI-110 [18.75%], IVSII-745 [12.5%], -87[9.37%], IVSI-1[3.12%] and codon 39 [0%]. 7 cases [21.87%] were uncharacterized as regards to the 6 screened mutations. The co-inheritance of a-thalassemia was found in 5 cases out of 32 cases [15.63%] and DNA polymorphism at -158 [C-T] of the gamma globin gene was demonstrated in 2/32 cases [6.25%]. Both variables ameliorated the severity of the disease either in the form of decreased frequency of blood transfusion or delay in age of presentation or an amelioration of clinical severity of a known severe allele

Monocytes expressing tissue factor as a diagnostic marker for neonatal sepsis

In neonatal sepsis, several clinical and laboratory parameters have been proposed for its diagnosis, however, with variable sensitivity and specificity. The bacterial products in sepsis including endotoxin induce the production of proinflammatory cytokines that evoke the expression of tissue factor [TF] on monocytes and endothelial cells. To estimate the percentage of monocytes expressing tissue factor [TF%] by flowcytometry in patients with neonatal sepsis and to delineate its significance to diagnose neonatal sepsis. Twenty-seven neonates with neonatal sepsis and positive blood culture were recruited and evaluated clinically for their risk factors. Laboratory investigations including complete blood picture, C-reactive protein [CRP] and estimation of the monocytes TF expression by flowcytometry were done. Twenty-four normal newborns were included as a control for the laboratory data. The monocytes expressing TF% of the studied patients was significantly higher than that of the controls, p-value = 0.0001. The level of TF% was significantly influenced positively by premature rupture of membrane [PROM], Multiplicity, WBC count, staff/segment ratio, CRP and negatively by gestalional age, body weight, and platelet count. The sensitivity and overall accuracy of the TF% were higher than those of the staff/segment ratio and the WBC count for diagnosing neonatal sepsis. The areas under the receiver operating characteristic curve [AUC] of TF%, staff/segment ratio and WBC count were 0.84, 0.79 and 0.60 respectively, 95% confidence interval]. The monocytes expressing TF% is a promising diagnostic and prognostic marker of infection in neonatal sepsis with high sensitivity and overall accuracy. Adding the estimation of monocytes expressing TF% to the sepsis screen may improve the diagnosis of neonatal sepsis

Serum prostacyclin levels in unstable coronary heart disease

To examine the diagnostic value of abnormal serum Prostacyclin [PG12] level as a marker of instability of coronary heart disease, 30 patients [[12 with unstable angina [UA], 8 with acute myocardial infarction [AMI], and 10 with stable effort angina [EA]], and 10 normal adults were studied. Clinical evaluation, as well as estimation of plasma 6-keto-prostaglandin F1 alpha have been carried out for all subjects. Statistical analysis of the results showed the wide dispersion of the prostacyclin values. Median, 25th, and 75th percentiles were adopted for measuring central and dispersion tendencies. The median together with the 25th and 75th percentiles of the 3 ischemic groups were clearly lower than those of the control group. No significant differences in prostacyclin values were present between different subsets of patients with coronary heart disease [CHD]. In spite of the limited number of patients, this study points to a limited diagnostic value for this test in patients with CHD

Altered prostaglandin metabolism as a cause of pre-eclampsia: an implication on therapy

In a trial to declare the possible role of altered prostaglandin metabolism in the pathogenesis of pre-eclampsia, the plasma levels of 2 major antagonistic compounds have been estimated using enzyme immunoassay method; namely thromboxane A2 and prostacyclin, along with estimations of platelet count and ADP induced platelet aggregation. The study comprised 10 normal pregnant and 10 pre eclamptic females of comparable parity and gestational periods, as well as 10 normal age matched non-pregnant females for comparision. Mean platelet count was significantly lower in pre-eclamptic cases as compared to both normal pregnant and control groups, with no significant difference between the later 2 groups. Mean platelet aggregation percent was only significantly higher in normal pregnant females as compared to both pre-eclamptic and non-pregnant controls, using either low or usual doses of ADP. A significantly higher mean plasma thromboxane-B2 and a significantly lower mean plasma prostacyclin levels were observed in both normal pregnant and pre-eclamptic groups as compared to controls, with no significant difference in the level of either compound between the former 2 groups. A significant positive correlation between TXB2 level and each of systolic and diabolic blood pressures was observed in pre-eclamptic patients. A significant positive correlation was similarly observed between TXB2 level and ADP induced aggregation percent using both low and usual doses, only in non-pergnant controls. Moreover the levels of both TXB2 and PCI2 showed a direct significant correlation in both pregnant groups. The ratio of thromboxane B2/prostacyclin was however, significantly highrt in both pregnant groups as compared to controls as well as in pre-eclamptic patients as compared to normal pregnant females. A disturbed prostaglandin metabolism, with unchecked thrombogenic effect of thromboxane A2 was suggested as a potential mechanism for pre-eclampsia. The therapeutic use of low dose asprin as a selective cyclo-oxygenase inhibitor might be of help in prevention of the microcirculatory complications observed in this condition