Evaluation of homocysteine level in children with cerebrovascular stroke

Cerebrovascular stroke is an important cause of morbidity and mortality in children. Recent epidemiologic data suggest that 3200 cases of stroke occur per year in the population aged between 30 days and 18 years in the US alone. Although outcome for stroke in children is significantly better than in adults, 20% die and 50%to 80% are left with significant disability. Moderately elevated homocysteine status is considered an independent risk factor for occlusive arterial disease in the peripheral arteries and cerebral vessels. Higher homocysteine levels could cause either isehemic stroke by it s procoagulative effects and induces endothelial damage or hemorrhagic stroke by promoting vascular inflammation and plaque rupture. To evaluate the role of homocysteine as a risk factor of cerebrovascular stroke in children. The study was conducted in intensive care and emergency units in Pediatric Assiut University Hospital during the period between October 2005 and September 2006 and included 52 children with stroke [65.4%ischemic and 34.6% hemorrhagic] and contained 34 boys and 18 girls, aged 30 days to 4.5 years after exclusion of stroke due to trauma and tumor as vell as 20 apparently healthy children with matchable age and sex as control group. All cases were evaluated by Pediatric National Institute of Health Stroke Scale on admission as a measure of stroke severity, besides meticulous history taking and thorough clinical examination. Evaluation of plasma levels of homocysteine, random blood glucose, serum sodium and potassium were done for all cases and controls. The annual frequency rate of stroke was 0.3%. The mean +/- SD of random blood glucose was significantly higher in children with ischemic compared to hemorrhagic stroke and in both compared to control. The mean +/- SD of serum sodium was significantly higher in ischemc compared to hemorrhagic and control groups. The mean +/- SD of serum potassium was significantly lower in ischemic and hemorrhagic stroke compared to control The mean +/- SD of homocysteine in children with ischemic and hemorrhagic strokes were more than control group with a statistical significant difference while, no statistical significant difference was detected between the two groups. The odds ratio of homocysteine for ischemic and hemorrhagic stroke were [3.3, CI 2.38-26.9] and [1.9, CI 2.3-46.8] respectively. The mean +/- SD of homocysteine was significantly higher in children with hospital stay more than 2 weeks, in children with PedNIHSS >/= 12 and in non survivors. Hyperhomocysteinemia is significant risk factor of stroke in children

Impact of HLA-C matching on acute graft-versus-host disease in allogenic hematopoietic stem cell transplantation

Outcome of unrelated donor marrow transplantation is influenced by donor/recipient matching for HLA. Prior studies assessing the effect of mismatch at specific HLA loci have yielded conflicting results. Disparity for HLA-A or HLA-B antigens increases the risk of poor marrow graft outcome, but little is known about the relevance of HLA-C matching. This work aimed to evaluate the effect of HLA-C matching on hematopoietic stem cell transplant, outcome specifically on the acute graft versus host disease [aGVHD]. Seventy patients given hematopoietic stem cell transplant [HSCT] in different transplant centers with their relevant donors were included in the study, HLA class I [HLA-A, -B] and class II [DRB1, DQR1, DPB1] typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe [PCR-SSOP] and HLA-C typed by PCR-sequence specific priming [PCR-SSP] technique. The risk of aGVHD during the first three months after HSCT was estimated. Fifty two [74.3%] donor/recipient pairs were mismatched for HLA class I alleles, eighteen [34.6%] of them experienced aGVHD. While no history ofaGVHD was reported in eighteen HLA class I full matched pairs [25.7%]. Higher incidence of aGVHD was observed with isolated HLA-A mismatch [28.6%], and for isolated HLA-B and HLA-C locus mismatch, the incidence were 25% and 16.7% respectively. The incidence of aGVHD was elevated if HLA-A or HLA-B mismatch is associated with HLA-C mismatch [40% and 37.5% respectively]. Much higher incidence of aGVHD was associated with combined HLA-A-B and-C mismatch [44.4%]. The estimated odds ratio [OR] of aGVHD for total HLA-C mismatch relative to matched pairs [univariable model] was 5.0 [95% CI 1.3-19.4; P= 0.01]. The degree of HLA-C allele mismatch [one or two alleys mismatch] were significantly related to aGVHD outcome [OR, 3.9, P= 0.03; OR, 10.8; P .009 respectively]. HLA-A or HLA-B allele disparity was also associated with aGVHD. As regard the analysis of total HLA-A and -B mismatched pairs with their corresponding matched locus, they demonstrated significant adverse effect on aGVHD [OR, 2.8; P=0.04; OR 3.0; P=0.03]. It was concluded that HLA-C may function as a powerful transplantation antigen. HLA-C compatibility should be incorporated into algorithms for donor selection to improve the outcome especially in patients who have an increased risk. The presence of HLA-C mismatch with either HLA-A or HIA-B mismatch leads to a synergistic increase in cytotoxic responses and poor graft outcomes [the development of aGVHD]; however, isolated HLA-C mismatch may be acceptable with respect to T-cell mediated alloreactivity

Impact of type 2 diabetes mellitus on cardiac structure and function: the association with microalbuminuria and hyperinsulinemia

Early determination of myocardial manifestations of diabetes mellitus [DM] is of a major importance, since myocardial involvement considerably influence the prognosis of diabetic patients. Microalbuminuria [MA] and hyperinsulinemia [HI] have been shown to predict cardiovascular [CV] disease in patients with DM. However the relationship between these risk factors and both cardiac structure and function is still unclear. To assess the Echocardiographic evidence of cardiomyopathy in asymptomatic patients with type 2 DM; to relate these findings to MA and fasting plasma insulin level [FI]; and to investigate whether these observations are independent of glycemic control and other clinical CV risk factors. 63 type 2 diabetic patients without known cardiac diseases, duration of DM [mean 52.4 +/- 51.4 month], age [47.4 +/- 807 year], body mass index [BMI] [26.6 +/- 3.2], men [41/63], in addition to 20 healthy subjects matched for age, sex and BMI served as control were enrolled in the present study. Based on MA and FI, patients were subgrouped into [microalbuminuric and normoalbuminuric] and [hyperinsulinemic and normoinsulinemic] respectively. We compared Echo- derived indices of left ventricular [LV] structure and LV systolic and diastolic functions in patients versus control subjects and between the different patient subgroups. Diabetic patients had greater LV posterior wall thickness [PWT], interventricular septal thickness [IVST], and LV mass index [LVMI] [p<0.0001 for each]. LV diastolic dysfunction, manifested as reduction in E velocity and E/A ratio and prolongation in isovolumic relaxation time [IVRT] [p<0.001 for each], was documented in diabetic patients as compared with control subjects. MA was diagnosed in 15/63 [24%] patients. As compared with normoalbuminuric patients, MA was associated with higher fasting blood glucose [FBG] and FI [p<0.05 for each], greater LVPWT [p<0.05], and LVMI [p=0.02], and lower fractional shortening [FS], ejection fraction [EF], and E/A ratio [p<0.001, p=0.006 and p<0.05 respectively]. Patients with HI had lower FS [p=0.02] and lower E velocity [p=0.04] than in patients with normal FI. In multi-variate analysis, the associated findings either with MA or FI has been unchanged after adjusting for the duration of DM, glycemic control, age, gender, BMI, and BP. Type 2 diabetic patients without overt heart disease have increased LV wall thickness and LVMI and LV diastolic dysfunction suggesting subclinical diabetic cardiomyopathy [DCM]. MA and HI are independently associated with these changes, which may contribute to the relation of albuminuria and HI with increased rate of CV event among diabetics. Thus, screening of either MA or HI may identify patients at CV high risk

Hypermethylation of the PAX 5 gene promoter and its implication in the pathogenesis of multiple myeloma

This study aimed to clarify the mechanism of silencing of the PAX5 gene. The genetic analysis of the coding region and promoter by southern blot analysis did not show growth structural abnormalities in human multiple myeloma [MM] cell lines when compared with PAX5 expressing B cells. Several transcription factors like Ikaros-1 [IK-1] and SRY-related high mobility group [HMG] box [SOX4 and SOX5] showed a similar expression pattern in B cells and MM cells. Therefore, it was suggested that epigenetic factors could be involved in PAX5 silencing. The examination of the methylation pattern in PAX5 promoter revealed some areas of hypermethylation in methylation sensitive Southern blot analysis. Moreover, the treatment of MM cell lines by methylation blocking cytidine analogue 5-aza-2 deoxycytidine [5-aza-2dC] could restore the expression of PAX5 gene. It was postulated that hypermethylation of the PAX5 gene promoter may be responsible for its silencing in human MM. It was proposed that PAX5 gene silencing could be related to the oncogenesis of human MM

Endothelial dysfunction an doxidative stress in gestational diabetes [a follow-up study]

Gestational diabetes is characterized by glucose intolerance first recognized during pregnancy. Women with gestational diabetes are more prone to develop type II diabetes later in life. The increased risk of premature endothelial dysfunction with hyperglycemia might be related in part to augmented expression of cell adhesion molecules. Diabetes is also characterized by oxidative stress which in turn determines endothelial dysfunction via nitric oxide synthase linked pathway. Aim: To evaluate the effect of gestational diabetes on the adhesive molecules and status of oxidative stress. Subjects and Five hundred and eighty seven pregnant women [24-28 weeks of gestation] with no risk factors and normal renal and liver functions were tested for serum glucose by screen test and-when necessary- glucose tolerance curve. Thirty three cases [5.6%] who have gestational diabetes constituted the patients group. Twenty healthy pregnant women with negative screen test and glucose tolerance curve were taken as a control group. Both patients and controls were investigated for serum E- selectin, VCAM-1, endothelin-1, nitric oxide, lipid peroxidation and superoxide dismutase [SOD], during gestation and after delivery. During gestation, sE-selectin was higher and sVCAM-1 was lower in diabetic cases than controls but with no significant differences, while significant elevations of lipid peroxidation [p < 0.01] and SOD [p < 0.001] in patients group compared to control group. Three months after delivery, significant elevations of sE-selectin [p < 0.001], sVCAM-1 [p < 0.001], and SOD [p < 0.001] were observed in women with gestational diabetes compared to the controls. There were significant reduction in lipid peroxidation and SOD [p < 0.001] in the patients after delivery as compared to that during pregnancy, while sE-selectin, sVCAM-1 and NO were higher after delivery than during pregnancy but the difference was statistically insignificant. The controls showed significant decrease in levels of endothelin-1, sE-selectin and sVCAM-l with longitudinal follow up. The follow up study revealed that six cases [patients group A] continued with impaired glucose toerance curve [31.6%] and thirteen cases [patients group B] returned with normal glucose curve. In group A, there were significant elevation of E-selectin [p < 0.05] and significant decrease of endothelin-l [p < 0.01] as compared to group B, while NO and SOD were reduced but the difference was statistically insignificant. Sustained elevations of sE-selectin and sVCAM-1 in cases with gestational diabetes even after delivery may reflect vascular injury or risk factor for endothelial dysfunction. Furthermore the elevations of lipid peroxidation and SOD in the patients group during pregnancy may be implicated this pathogenesis of gestational diabetes and may be considered as sensitive indicators of oxidative stress in gestational diabetes