Plasminogen activator inhibitor-1 4G/5G polymorphism and risk of ischemic stroke: a meta-analysis.

This study investigated the hypothesis that the insertion/deletion (4G/5G) polymorphism of the plasminogen activator inhibitor type-1 gene affects the risk for ischemic stroke, since results concerning this association have been controversial. We therefore performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out until January 2006. The analysis was performed using random-effects models and meta-regression. Eighteen eligible studies were retrieved (15 case-control studies and three cohort studies). The case-control studies included 3104 cases and 4870 control individuals concerning the contrast of 4G/4G versus remaining genotypes. The 4G pooled allele frequencies in cases and controls were 54.21 and 54.75%, respectively. Overall, the per-allele odds ratio of the 4G allele was 0.98 (95% confidence interval, 0.858-1.121). Regarding genotypes, we derived nonsignificant odds ratios in all contrasts. The subanalysis including the three studies with a prospective design in the 4G/4G versus 5G/5G contrast derived a significant result (relative risk, 0.523; 95% confidence interval, 0.353-0.775), but the estimated effect size was insignificant when cohort and case-control studies were analyzed together (relative risk, 0.848; 95% confidence interval, 0.662-1.087). We failed to demonstrate a significant association between the 4G/5G polymorphism and ischemic stroke under basal conditions. Determination of plasminogen activator inhibitor type-1 function seems of much higher clinical value than determination of the 4G/5G polymorphism. The effect of this genotype on risk of ischemic stroke in acute stressful diseases and the role of cohort studies in genetic epidemiology, however, warrant further investigation.     

Molecular characterization of G6PD deficiency in Cyprus

In the present study, we determined the frequency of glucose-6-phosphate dehydrogenase (G6PD) deficiency in Cyprus using two different procedures in two separate adult population groups: a semiquantitative fluorescence test on blood spotted on filter paper and a quantitative spectrophotometric test on liquid blood. The frequency of G6PD deficiency among healthy adult males was found to be 5.1% using the semiquantitative procedure and 6.4% using the quantitative procedure. Neither method was able to detect all the expected female heterozygotes (5.3% and 47.1% of the expected number, respectively). A total of 21 male hemizygotes, 1 female homozygote and 9 female heterozygotes that tested positive for G6PD deficiency were studied at the molecular level. All 32 chromosomes were genotyped and five different mutations were identified. The Mediterranean mutation in exon 6 (563C-->T) (Ser188Phe) was found to be the most common variant in the Cypriot population, accounting for 52.6% of the deficient alleles. In the remaining chromosomes, four different mutations were identified: three known mutations, Kaiping 1388G-->A (Arg463His), Chatham 1003G-->A (Ala335Thr) and Acrokorinthos 463C-->G (His155Asp), and one previously undescribed mutation in exon 3, 148C-->T (Pro50Ser), which we called G6PD Kambos. We conclude that the frequency of G6PD deficiency in Cypriot males is 6.4%, and that this deficiency is the result of several different mutations. Although all the individuals carrying the Mediterranean variant can be detected using a semiquantitative screening method, a quantitative enzyme measurement is required to detect the G6PD variants with less severe enzyme deficiencies, while the most appropriate method for heterozygote detection is DNA analysis.     

Thrombomodulin as a regulator of the anticoagulant pathway: implication in the development of thrombosis

Thrombomodulin is a cell surface-expressed glycoprotein that serves as a cofactor for thrombin-mediated activation of protein C (PC), an event further amplified by the endothelial cell PC receptor. The PC pathway is a major anticoagulant mechanism that downregulates thrombin formation and hedges thrombus formation. The objectives of this review were to review recent findings regarding thrombomodulin structure, its involvement in the regulation of hemostasis and further discuss the implication, if any, of the genetic polymorphisms in the thrombomodulin gene in the risk of development of thrombosis. We performed a literature search by using electronic bibliographic databases. Although the direct evaluation of risk situations associated with thrombomodulin mutations/polymorphisms could be of clinical significance, it appears that mutations that affect the function of thrombomodulin are rarely associated with venous thromboembolism. However, several polymorphisms are reported to be associated with increased risk for arterial thrombosis. Additionally studies on knock out mice as well studies on humans bearing rare mutations suggest that thrombomodulin dysfunction may be implicated in the pathogenesis of myocardial infraction.     

Neuromuscular differences between boys with and without intellectual disability during squat jump

The purpose of this study was to identify the differences in vertical squat jump (SJ) between volunteers with and without intellectual disability (ID). Thirteen boys with ID (average intelligence quotient, estimated by Wisk III test: 55.6 ± 11.2) and 13 peers without disabilities performed maximal SJ on a force platform. Kinematic data were captured using a six-camera 3D motion analysis system and electromyographic (EMG) activity was recorded using surface electrodes. Unpaired T-test determined the statistical difference between the two groups. The obtained results indicated that the group with ID, jumped lower, developed lower vertical ground reaction forces, knee power output, knee angular velocity, and take-off velocity, and showed longer propulsion duration, decreased mean to maximum agonist EMG activity and higher antagonist/agonist activity ratio. The deficit in the SJ observed in individuals with ID was attributed to a deficit in the examined mechanical and neuromuscular parameters, and especially to the agonist and antagonist co-contraction.     

High prevalence of decreased cortisol reserve in brain-dead potential organ donors

OBJECTIVE: To investigate the adrenocortical function in brain-dead patients, potential organ donors. DESIGN: Prospective study. SETTING: Intensive care units in two teaching hospitals. PATIENTS: A total of 37 patients (28 men, nine women) with severe brain injury, having a mean age of 42 +/- 18 yrs, were included in the study. Group A consisted of 20 brain-injured patients who did not deteriorate to brain death. Group B included 17 brain-injured patients who were brain dead; of these, ten patients developed brain death during ICU stay and seven patients were admitted to the ICU after clinical brain death. INTERVENTIONS: In all patients (group A and group B), a morning blood sample was obtained at admission to the ICU to determine baseline plasma cortisol. Subsequently, 1 microg of corticotropin (adrenocorticotropic hormone, Synacthen) was administered intravenously, and a blood sample was taken 30 mins after the injection. In group B patients who became brain dead while being treated in the ICU (n = 10), the same procedure was repeated the morning after the confirmation of brain death. Patients having a cortisol level of at least 18 microg/dL after the administration of adrenocorticotropic hormone were defined as responders. MEASUREMENTS AND MAIN RESULTS: After the occurrence of brain death, group B patients had significantly lower values for baseline (8.5 +/- 6.2 vs. 17.0 +/- 6.6 microg/dL, p <.001) and stimulated (16.9 +/- 6.3 vs. 23.9 +/- 5.7 microg/dL, p =.001) plasma cortisol compared with group A patients. Thirteen group B patients (76%) and two group A patients (10%) were nonresponders to adrenocorticotropic hormone (p <.001). In group B patients, baseline and stimulated cortisol concentrations were significantly related (r =.71, p =.001), whereas there was no correlation between baseline cortisol and the increment in cortisol (r = -.37, p =.15). Mean hormonal data of the ten brain-dead patients studied at admission in the ICU and after the occurrence of brain death were the following: baseline plasma cortisol (23.5 +/- 11.4 vs. 6.8 +/- 4.2 microg/dL, p =.003) and stimulated serum cortisol (28.8 +/- 9.9 vs. 16.3 +/- 4.3 microg/dL, p =.008). CONCLUSIONS: Adrenal cortisol secretion after dynamic stimulation is deficient in a substantial proportion of brain-dead potential organ donors.     

Gastroesophageal reflux in children with cerebral palsy and its relationship to erosion of primary and permanent teeth

Patients with cerebral palsy are known to have a high incidence of feeding difficulties, including problems with swallowing, vomiting, recurrent chest infections, and irritability. Gastroesophageal reflux (GER) is an involuntary passage of the gastric contents into the esophagus. It has been found in a higher prevalence (up to 75 percent) in cerebral palsy patients. Long-term gastric acid attacks teeth and can cause dental erosion. Bargen and Austin first discovered the relationship between GER and dental erosion in 1937 when they concluded that the loss of dental hard tissue could be an indicator and the predominant oral manifestation of GER. The purpose of this study is to investigate the correlation between GER and dental erosion in primary and permanent teeth in cerebral palsy patients. Twenty-one patients participated in this study. Results showed that out of the 21 patients, 15 had erosion and 11 of them had GER history. The chi-square analysis with the p value of less than or equal to 0.025 showed the distribution to be significant. The severity of the erosion was correlated to the duration of the disease, frequency of vomiting, pH of the acid, type of acid, and quantity and quality of saliva. The study revealed that children with cerebral palsy have an increased prevalence of tooth erosion, which may be attributed to the existing gastroesophageal reflux.     

Magnetic resonance imaging findings and novel mutations in GM1 gangliosidosis

Two unrelated children and their siblings of Arab origin were diagnosed as having GM1 gangliosidosis on the basis of clinical features and markedly low levels of beta-galactosidase. The T2-weighted magnetic resonance images of the brain revealed certain characteristic features, including delayed myelination and abnormal appearance of the subcortical white matter, internal capsule, and basal ganglia. Their mutation analysis showed two novel mutations, which have not been described in an Arabic population.     

Association between the plasminogen activator inhibitor-1 4G/5G polymorphism and venous thrombosis. A meta-analysis

The effect of the 675 insertion/deletion (4G/5G) polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene on the risk of venous thromboembolism (VTE) remains controversial. In this study, we performed a meta-analysis of published data regarding this issue. A comprehensive electronic search was carried out up until September 2006. A total of 22 articles were included in the analysis that was performed using random effects models. Eighteen papers, concerning patients without another known risk factor, comprised 2,644 cases and 3,739 controls. The alleles contrast (4G vs. 5G allele) yielded a statistically significant odds ratio (OR) of 1.153 (95% confidence interval [CI]: 1.068-1.246). In a sub-analysis of five studies that included 256 cases with another genetic risk factor and 147 controls, the combined per-allele OR was still significant (OR: 1.833,95% CI: 1.325-2.536). On the contrary, the analysis of five studies regarding cases with a non-genetic risk factor for VTE (antiphospholipid antibody syndrome, Behcet disease) provided insignificant results in all aspects. There was no evidence for heterogeneity and publication bias in all analyses. Based on our findings, the 4G allele appears to increase the risk of venous thrombosis, particularly in subjects with other genetic thrombophilic defects. Recommendation for detection of this polymorphism in evaluating thrombophilia in such patients might be considered.