Osteoporosis in beta-thalassemia major patients: role of COLIA1 gene G-T polymorphism

Growth impairment and osteoporosis are serious causes of morbidity in patients with beta-thalassemia major [beta-TM]. Desferoxamine [DFO] toxicity and iron overload have been proposed as the main underlying reasons. G-T polymorphism in regulatory region of COLIA1 gene has recently been associated with reduced bone mass and osteoporotic fractures in postmenopausal women. To detect the possible implication of COLIA1 gene polymorphism in pathogenesis of osteoporosis in beta-TM. Twenty five patients with beta-TM and 20 healthy controls were investigated for the G-T polymorphism of COLIA1 gene using restriction enzyme analysis. Bone mineral density [BMD], growth parameters, serum ferritin level and duration of chelation therapy were also assessed. We detected a heterozygous polymorphism of COLIA1 gene in 12% of beta-TM patients and 25% of the control group. Thalassemic patients had significant lower BMD than normal controls [p < 0.01]. Significant correlation was observed between low BMD and both duration of DFO intake and high ferritin level. Within the control group: Subjects with G/T genotype had significantly lower femoral and lumber BMD than those with G/G genotype. In thalassemic patients: No significant difference was found in BMD between the two COLIA 1 genotypes. We cannot detect evident role for COLIA1 gene polymorphism in the pathogenesis of osteoporosis in this group of beta-TM patients although this role has been detected in the control group. Further studies that include higher number of patients and more than one genetic polymorphism are needed in order to evaluate the role of genetic factors in the pathogenesis of osteoporosis in thalassemic patients

Nitric oxide synthase gene polymorphism and in-stent restenosis: clinical and angiographic follow-up

Coronary stent deployment is a major advance in the treatment of ischaemic heart disease, but angiographic in stent restenosis still occurs in 10-40% at 6 months due to neointimal hyperplasia. Patient specific factors, including genetic factors, can contribute to this process. Was to examine the 894 G/T single nucleotide polymorphism [SNP] of the endothelial nitric oxide synthase [eNOS] in causing adverse angiographic and clinical events after coronary artery stenting. Our study included 47 patients [40 males, 7 females, mean age 54.4 +/- 8.1] who underwent elective and successful coronary artery stenting to de novo lesions in the Critical Care Department [Cairo University]. Patients were followed up for major adverse cardiac event [MACE] defined as death, acute coronary syndromes and target vessel revascularization; and restudied by coronary angiography at 6 months. The stented lesions were assessed using an automated quantitative angiography system. Genotype was determined by real time polymerase chain reaction [PCR] and restriction enzyme digestion. Restenosis rate was defined as >/= 50% diameter stenosis. The pts were distributed into two groups, Group linvolved pts of the G allele carriers i.e. patients of genotype PG or GT [n=40] and group II consisting of patients genotype IT, which represented the proposed risk genotype [n=7]. Patients in group I showed greater prevalence of diabetes mellitus [DM] and greater severity of lesions. Patients with GGIGT genotype presented with higher incidence of acute coronary syndromes compared to patients with TT genotype [45% vs 14.3%, p: 0.004]. The same genotype group had significantly higher incidence of MACE [45% compared to 28 0.001]. Patients with TI' genotype had insignificantly higher restenosis rate [42.9% in comparison to 37.5% in group GG/GT genotype, p: 0.8]. Although GG/GT genotype showed higher incidence of acute coronary syndromes and MACE compared to patients with TI genotype, yet the latter had in significantly higher restenosis rate

Altered coagulation in systemic inflammatory response syndrome: role of protein C as a diagnostic and prognostic marker

This study enrolled 20 patients who had been hospitalized for SIRS as well as 20 age and sex matched subjects served as control group. All patients and control groups were subjected to full clinical evaluation with application of APACHE II scoring, routine laboratory investigations as well as specific investigations; namely, plasma levels of protein C, D-dimer [DD], antithrombin III [ATIII] and thrombin- antithrombin complex [TAT] upon admission, 48 and 96 hours later and on discharge in survivors. The study showed that activated protein C level was consumed significantly in patients with SIRS compared to control subjects. As comparing its levels in survivors and non survivors, the former showed persistent rise of the level to normal values in contrast to the latter in which their levels were persistently low [34.8 +/- 26% vs 40.6 +/- 22% on admission and 82 +/- 13% vs 41 +/- 21% after 144 hrs, respectively]. Patients with septic shock also showed significantly lower levels of APC compared to those without shock [28.8 +/- 12% vs 56.8 +/- 28% on admission and 41.7 +/- 21.8% vs 82 +/- 13% after 144 hrs, respectively]. APC levels also were lower in patients with multiorgan failure syndrome [MODS] as compared to those without MODS [40.8 +/- 27.8% vs 116 +/- 29, respectively] with statistically insignificant lower level in patients with APACHE > 20 as compared to those with APACHE < 20 [35.2 +/- 22 vs 45 +/- 24%, P: NS]. The other coagulopathy markers of sepsis DD, AT III, TAT complex did not show any significant difference between survivors and non-survivors [2 +/- 3.6 vs 4.9 +/- 8 ng/ml for DD, 40.75 +/- 17.6% vs 40 +/- 15.7% for AT III and 24.7 +/- 25 vs 22 +/- 19 ug/ml for TAT, P: NS, respectively]

Nitric oxide and its relation to blood pressure control and target organ damage in hypertensive patients

Patient with essential hypertension have reduced endothelium dependent vasodilatation, this abnormality has been related to decreased activity of endothelium nitric oxide. To estimate nitric oxide level in hypertensive patients to verify its role in relation to blood pressure control and target organ damage in hypertensive patients. Sixty hypertensive patients participated in this study, 40 of whom without clinical evidence of target organ damage of whom 20 had uncontrolled blood pressure and the other 20 were controlled with antihypertensive therapy. Study also included 20 hypertensives with evidence of target organ damage. Ten normal non-hypertensive subjects volunteered as controls. They were all subjected to full clinical assessment and estimation of nitric oxide levels. Each of the hypertensive groups including controlled hypertensives, uncontrolled hypertensives and hypertensives with evidence of target organ damage had statistically significant lower nitric oxide levels compared to normotensive control subjects [p<0.000]. Controlled hypertensive group when compared to the uncontrolled hypertensive group still had a statistically significant difference of nitric oxide [p value 0.000] While hypertensive patients with evidence of target organ damage had a statistically significant low nitric oxide levels compared the controlled hypertensive group [p value < 0.001], they did not have a statistically significant difference in NO levels when compared to the uncontrolled hypertensive group [p value 0.5]. Hypertensive patients whether controlled or not; whether with target organ damage or not have low NO denoting an underlying endothelial dysfunction. Controlled hypertensives with acceptable blood pressure measurements still have evidence of endothelial dysfunction with low NO. Current antihypertensive therapy, though attaining acceptable blood pressure levels does not seem to tackle endothelial dysfunction in hypertensive patients. NO seems to be playing a crucial role in target organ damage in hypertensive patients

Role of decisive markers in diagnosis and outcome of patients with septic shock

This work aimed to assess the potential role of procalcitonin [PCT] and polymorphonuclear [PMN] elastase enzyme in the early diagnosis and early prediction of prognosis in patients with sepsis and septic shock. Twenty patients with septic shock [16 males and 4 females, mean age 50.15 years] together with a second group comprising 10 patients [9 males, mean age 49.2 years] with systemic sepsis without shock were studied. A third group including 20 healthy volunteers matching with age and sex and served as controls. Serum PCT and PMN elastase enzyme levels were estimated on admission for both patients and control groups with other laboratory investigations and clinical parameters. A multivariate discriminate analysis was performed using PCT, PMN elastase enzyme, albumin, alpha-1-antitrypsin, alpha-2 macroglobulin and C-reactive protein [CRP] as independent parameters. The study concluded that serum PCT and PMN elastase enzyme are independent useful diagnostic markers for the early detection of systemic inflammatory response syndrome with or without shock. However, PCT has the advantage over the above mentioned parameters having significantly predictive accuracy of 80%. Procalcitonin, PMN elastase enzyme, alpha-1-antitrypsin, alpha-2-macroglobulin, CRP and albumin could be used for the early prediction of complications of sepsis patients with an overall predictive accuracy of 76.7%