Association of Serum Osteoprotegerin Level With Myocardial Injury and Cardiovascular Calcification in Chronic Kidney Disease Patients.

Background: Chronic kidney disease has emerged as a significant independent risk factor for cardiovascular disease. Cardiovascular calcification is an active process involving a complex interaction of inducers and inhibitors. High sensitivity cardiac troponin T assay detects troponin T with higher sensitivity and precision at an earlier point of time than the conventional assays, and is associated with poor outcomes. Serum osteoprotegerin is classed as an inhibitory factor for cardiovascular calcification. It is involved in the pathological processes of vascular damage and linked to the excess cardiovascular morbidity. The aim of the present study was to evaluate the extent of cardiovascular calcification and serum high sensitivity cardiac troponin T level, and their association with serum osteoprotegerin level in patients with chronic kidney disease stages 3-5. Methods: 90 chronic kidney disease patients were enrolled in this study, and they were divided into two groups: group (1) included 45 non-dialysis-dependent chronic kidney disease patients (stages 3-5) and group (2) included 45 chronic hemodialysis patients. Each group further subdivided according to the presence of cardiovascular calcification into subgroup A and B. Vascular calcifications were assessed by lateral lumbar, pelvis and hands X-ray radiographs. Valvular calcification was assessed by echocardiography. Serum cardiac troponin T was measured by high sensitivity assay and serum osteoprotegerin was measured by ELISA. Results: Cardiovascular calcification distribution was 22.2% in group (1) and 33.3% in group (2). Serum osteoprotegerin and troponin T in calcification groups (1A and 2A) were significantly higher than non-calcification groups (1B and 2B; P < 0.001). Osteoprotegerin correlated positively with high sensitivity cardiac troponin T (rs = 0.72, P < 0.001). cardiovascular calcification correlated positively with osteoprotegerin, troponin T, and phosphorus. osteoprotegerin and phosphorus were significant independent predictors of cardiovascular calcification at cut-off values ≥4.6 ng/L and ≥6.95 mg/dl, respectively (P < 0.001). Serum phosphorus and creatinine were independent predictors of osteoprotegerin (P < 0.001 and 0.048, respectively). Conclusion: Osteoprotegerin is strongly associated with cardiovascular calcification and high sensitivity cardiac troponin T. In addition, there is a positive association between calcification and troponin T. This suggests a role for osteoprotegerin in the pathogenesis and risk stratification of cardiovascular calcification and myocardial injury in chronic kidney disease patients with a potential role as a therapeutic target.

Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding.

BACKGROUND/AIMS: The development of esophageal varices (EV) and resultant bleeding are the most critical complications of portal hypertension. Upper gastrointestinal endoscopy is the gold standard for diagnosis of EV. To find a non-invasive method for diagnosis of EV and to predict the bleeding risk is appealing and would decrease the cost and discomfort of upper endoscopy. The aim of our study was to evaluate the blood ammonia level as a predictor of the presence of EV and of a high risk of bleeding. MATERIALS AND METHODS: In this cross-sectional study, a total of 359 patients with cirrhosis were examined for the presence of EV by upper endoscopy. Abdominal ultrasonography, calculation of the Child-Pugh score, and measurement of blood ammonia were performed for each patient. RESULTS: The blood ammonia level was significantly higher in patients with EV than in those without it (p<0.001), and in patients with a high risk of variceal bleeding than in those with a low risk (p=0.026). CONCLUSION: An increased blood ammonia level and splenic vein diameter are predictors for the presence of EV and bleeding risk factors. The blood ammonia level may be clinically useful as it correlates with and is an independent predictor for both the endoscopic risk signs and risk factors of bleeding, and therefore, it could be used in patients with cirrhosis to decrease the number of screening endoscopies they are subjected to.

Association of Interleukin-2-330T/G and Interleukin-10-1082A/G Genetic Polymorphisms with B-Cell Non-Hodgkin Lymphoma in a Cohort of Egyptians.

OBJECTIVE: Polymorphisms in the interleukin (IL)-2 and IL-10 genes are known to be associated with susceptibility to different immune-dysregulated disorders and cancers such as non-Hodgkin lymphoma (NHL). To explore the possible association between IL-2-330T/G and IL-10-1082A/G single-nucleotide polymorphisms and the susceptibility to B-cell NHL (B-NHL) in Egyptians, we conducted a case-control study. MATERIALS AND METHODS: Genotyping of the studied genetic variations was done for 100 B-NHL patients as well as 100 age- and sex-matched healthy controls. RESULTS: The IL-2 variant allele occurred at a significantly higher rate in patients than controls and was associated with susceptibility to B-NHL [odds ratio (OR): 1.91, 95% confidence interval (CI): 1.28-2.85]. It was also associated with advanced performance status score. IL-2 polymorphism conferred an almost threefold increased risk of diffuse large B-cell lymphoma (OR: 2.64, 95% CI: 1.35-5.15) and a fourfold increased risk of indolent subtypes (OR: 4.34, 95% CI: 1.20-15.7). The distribution of IL-10-1082A/G genotypes in our patients was close to that of the controls. Co-inheritance of the variant genotypes of IL-2 and the common genotype of IL-10 conferred an almost sixfold increased risk (OR: 5.75, 95% CI: 1.39-23.72), while co-inheritance of the variant genotypes of IL-2 and IL-10 conferred fivefold increased risk of B-NHL (OR: 5.43, 95% CI: 1.44-20.45). The variant genotypes of IL-2-330T/G and IL-10-1082A/G had no effect on the disease-free survival of B-NHL patients. CONCLUSION: The present study highlights the possible involvement of the IL-2-330T/G genetic polymorphism in the susceptibility to B-NHL in Egypt, especially indolent subtypes. Moreover, IL-10-1082A/G is not a molecular susceptibility marker for B-NHL in Egyptians.

Relationship between Trace Elements and Premature Hair Graying.

CONTEXT: Hair is said to gray prematurely when a minimum of five gray hairs occurs before the age of 20 in fair skinned, 25 in Asians, and 30 in Africans. It may be genetically associated with autoimmune syndromes or certain environmental factors. AIMS: The aim of this study was to evaluate the serum level of iron, copper, and calcium and to assess their role in premature hair graying. SUBJECTS AND METHODS: This study was carried out on 60 patients with premature hair graying (PHG) and 30 age- and sex-matched healthy individuals served as a control group. The severity of PHG was assessed by the hair whitening scoring system. Serum iron, copper, and calcium concentrations were measured using Beckman Coulter instrument and spectrophotometric method. RESULTS: There was a reduction in serum levels of iron, copper, and calcium in patients with PHG in comparison with controls. There was a statistically negative significant correlation between the severity of PHG and serum iron and calcium levels. There was a negative nonsignificant correlation between body mass index and serum iron, copper, and calcium levels. CONCLUSIONS: Serum iron, copper, and calcium levels were reduced in association with PHG and correlated with its severity. Premature graying may be an indicator that hair is not getting enough nutrients and minerals, and supplementation with these trace elements might reverse and is expected to prevent progression of canities; however, further studies are needed to find the underlying mechanism of this relationship.

Heamostatic and genetic predisposing factors for stroke in children with sickle cell anemia.

Sickle cell disease (SCD) is a group of genetic disorders characterized by the production of the abnormal hemoglobin S (HbS). Sickle cell anemia (SCA) is the most common type of SCD and represents the homozygous form, in which the individual inherits a double dose of the abnormal gene that codes for hemoglobin S. This study was done to detect cases of silent and clinically overt strokes in children with sickle cell anemia (SCA) and examine predisposing factors for stroke development. The study included 20 children with clinically and hematologically confirmed SCA and 10 controls. They were divided into two groups, group I; included 10 steady state cases and group II; included 10 cases with thrombotic crisis. All subjects were subjected to full clinical examination, measurements of plasma level of: fibrinopeptid A (FPA), thrombin-antithrombin III (TAT), fibrin degradation product (D-dimer) and serum level of platelet endothelial cell adhesion molecule-1 (PECAM-1), and analysis of the ACE gene polymorphism by polymerase chain reaction (PCR). Patients were further subjected to Brain computed axial tomography (CT) scan and/or magnetic resonance imaging (MRI) as well as electro-encephalographic studies (EEG). Silent ischemic brain infarction as evidenced by CT scan and/or MRI was present in one patient in group I (10%) and one patient in group II (10%). On the other hand, two patients in group II (20%) showed clinically overt strokes. Thus, 4 children had silent or clinically overt stroke and the remaining 16 were non-stroke cases. Laboratory results showed that the levels of FPA, TAT, D-dimer and PECAM-1 were significantly elevated in SCA patients both in the steady and crisis states as compared to control, with more evident significant elevation in group II (thrombotic crisis) as compared to group I (steady state). The stroke group showed significant elevation; FPA, TAT, D-dimer and PECAM-1 as compared with non-stroke group. The PCR results showed that the frequencies of both DD genotype and D allele of ACE gene in the thrombotic crisis are significantly higher than in the control group and that all stroke children are of DD genotype. In conclusion, significant increase in FPA, TAT, D-dimer and PECAM-1 levels as well as the presence of ACE D allele of the ACE gene are significant predisposing factors for stroke in children with SCA. Regular follow-up by thorough neurological examination and neuro-imaging studies for early detection of silent brain infarction is recommended.

Molecular detection of survivin expression, antiapoptotic gene, and other prognostic markers, how they are correlated and how it could be of prognostic value in chronic myeloid leukemia patient.

Chronic myeloid leukemia (CML) is a malignant disease of heampoitic stem cell resulting from clonal expansion of leukemic myeloid cells. Survivin is a recently identified member of the inhibitor of apoptosis protein family. The aim of the work is to analyze the expression of survivin in CML patient in chronic, accelerated and blastic phases and its correlation with other prognostic markers. The study included 50 CML patients (24 females and 26 males) and 10 healthy individuals (4 female and 6 male) as a control group. The studied groups were classified into group (I), 10 healthy individuals as a control group, group (II), 20 CML patients in chronic phase, Group (III), 15 CML patients in accelerated phase and Group (IV), 15 CML patients in blastic phase. The groups were subjected to clinical history and examination, CBC, ESR, BM aspiration (only patients), determination of serum survivin, IL-6 and beta2M levels by ELISA and survivin gene expression by quantitative real time PCR. There was a significant increase of survivin expression in patients as compared to controls (p < 0.001). The accelerated and blastic phases of the disease showed the highest significance (p < 0.001) than the chronic phase. Serum markers; survivin, IL6 and beta2M showed significant increase in the blastic phase, accelerated phase and chronic phase (p < 0.001, p < 0.001 and p < 0.001) respectively. A significant positive correlation was found between level of survivin expression and the other prognostic markers; high leucocytic count (r = 0.52), high peripheral basophile count (r= 0.81) and high peripheral blast cell count (r = 0.66), high level of serum survivin (r = 0.87), beta2 M (r = 0.76) and IL-6 (r= 0.90). On the other hand, a significant negative correlation was found between the survivin expression and hemoglobin concentration (r = 0.50). In conclusion, survivin is expressed in most cases of CML patients and its over expression is associated with bad prognosis.

Alpha-fodrin autoantibodies are reliable diagnostic markers for juvenile and adult Sjogren's syndrome.

Sjogren's syndrome (SS) is like other systemic autoimmune diseases, characterized by a large number of autoantigens and autoantibodies and infiltration of glandular tissue by predominantly CD4 T lymphocytes. The presence of certain autoantibodies is required for the diagnosis to be made, especially Anti-Ro/SSA and anti-La/SSB. The aim of this study is to investigate the prevalence of anti-alpha fodrin and its association with anti-Ro and anti-La in juvenile and adult SS. Thirteen cases with juvenile SS and 11 old SS patients were examined. Selection and classification of the patients was based on the revised European Community Criteria. The Juvenile SS group included 10 girls and 3 boys, their age ranged from 7 to 14 years. Adult SS group included 2 males and 9 female, their age ranged from 21 to 54 years. Blood samples were subjected to Erythrocyte sedimentation rate (ESR) mm/1 degree h, Complete blood count (CBC), Latex agglutination test for estimating rheumatoid factor (RF) and antinuclear antibodies (ANA), and assessment of Anti-alpha Fodrin IgG/IgA, anti-Ro and anti-La using ELISA. The two groups were matched for sex ratio. There was a significant difference of age (10.1 +/- 2.4 vs 35.1 +/- 9.3 yr) between both groups (P < 0.05). There was no statistically significant difference of levels of ESR, ANA and anti-Ro, anti-La and anti-alpha fodrin IgG/IgA autoantibodies concentration in the sera of SS patients in both groups (P > 0.05) although their levels were elevated. The percentage of detection of anti-Ro, anti- La and anti-alpha fodrin IgG and IgA antibodies in the sera of Juvenile SS was 61.5%, 53.8%, 53.8% and 61.5% respectively, while in adult SS was 63.6%, 45.5%, 45.5% and 81.8%, respectively. Anti alpha fodrin IgA and IgG were positively detected in SS patients who had negative anti-Ro and/or anti-La. The anti-alpha fodrin IgG and IgA antibodies did not significantly correlated with antibodies against Ro and La, ESR and ANA (r < 0.25, P > 0.05). The detection of anti-alpha fodrin antibodies may prove to be a useful sensitive marker for SS. Routine screening of alpha fodrin antibodies is a valuable tool for the diagnosis of SS.