Fever, genes, and epilepsy

About 13% of patients with epilepsy have a history of febrile seizures (FS). Studies of familial forms suggest a genetic component to the epidemiological link. Indeed, in certain monogenic forms of FS, for which several loci have been reported, some patients develop epilepsy with a higher risk than in the general population. Patients with generalised epilepsy with febrile seizures plus (GEFS+) can have typical and isolated FS, FS lasting more beyond age 6 years, and subsequent afebrile (typically generalised) seizures. Mutations associated with GEFS+ were identified in genes for subunits of the voltage-gated sodium channel and the gamma2 subunit of the ligand-gated GABAA receptor. Screening for these genes in patients with severe myoclonic epilepsy in infancy showed de novo mutations of the alpha1 subunit of the voltage-gated sodium channel. Antecedent FS are commonly observed in temporal-lobe epilepsy (TLE). In sporadic mesial TLE-characterised by the sequence of complex FS in childhood, hippocampal sclerosis, and refractory temporal-lobe seizures-association studies suggested the role of several susceptibility genes. Work on some large pedigrees also suggests that FS and temporal-lobe seizures may have a common genetic basis, whether hippocampus sclerosis is present or not. The molecular defects identified in the genetic associations of FS and epileptic seizures are very attractive models to aid our understanding of epileptogenesis and susceptibility to seizure-provoking factors, especially fever.     

Impact on health care workers employed in high-risk areas during the Toronto SARS outbreak

BACKGROUND: A number of publications focusing on health care workers (HCWs) during a severe acute respiratory syndrome (SARS) outbreak have suggested that HCWs experienced psychological distress, particularly increased levels of posttraumatic stress symptomatology (PTSS). Factors contributing to increased distress in HCWs working in high-risk areas treating patients with SARS have not been fully elucidated. The goal of this study was to quantify the psychological effects of working in a high-risk unit during the SARS outbreak. METHODS: HCWs in a Toronto hospital who worked in high-risk areas completed a questionnaire regarding their attitude toward the SARS crisis along with the Impact of Event Scale-Revised, which screens for PTSS. The comparison group consisted of clinical units that had no contact with patients infected with SARS. RESULTS: Factors that were identified to cause distress in the 248 respondent HCWs were the following: (a) perception of risk to themselves, (b) impact of the SARS crisis on their work life, (c) depressive affect, and (d) working in a high-risk unit. In addition, HCWs who cared for only one SARS patient in comparison to those caring for multiple SARS patients experienced more PTSS. CONCLUSIONS: As expected, HCWs who were working in high-risk units experienced greater distress. Contrary to expectations, HCWs who experienced greater contact with SARS patients while working in the high-risk units were less distressed. This suggests that HCW experience in treating patients infected with SARS may be a mediating factor that could be amenable to intervention in future outbreaks.     

Additional chromosome 1q aberrations and der(16)t(1;16), correlation to the phenotypic expression and clinical behavior of the Ewing family of tumors

The cytogenetic hallmark of the Ewing family of tumors is t(11;22)(q24;q12) in its simple, complex or variant forms and/or its molecular equivalent EWS/FLI, EWS/ERG rearrangement. Additional secondary consistent chromosomal aberrations include the der(16)t(1;16) and, frequently, other chromosome 1q abnormalities leading to 1q overdosage. We studied whether these secondary cytogenetic changes are correlated to clinical features and phenotypic expression which may have a prognostic impact.Successful cytogenetic evaluation was performed in eight patients with a Ewing family tumor. In four of these, in addition to the primary aberration, chromosome 1q overdosage (including two with der(16)t(1;16)) was noted. Out of these four patients, two had metastatic disease at the time of evaluation, while in the other four, disease was localized. Morphologically, the tumors with the additional 1q aberration, revealed the pPNET subtype more frequently than the typical Ewing. They also expressed a higher degree of neural differentiation by neural marker immunocytochemistry, in comparison to tumors without the 1q aberration.Determination of the prognostic significance of this finding requires a longer follow-up with a larger group of patients.     

Accuracy of ECG electrode placement by emergency department clinicians

Objectives: Misplaced ECG electrodes can cause changes in ECG recordings, which could have an impact on clinical decisions. We aimed to determine the inter‐rater reliability of ECG electrode placement by senior clinical staff in the ED. Methods: A prospective observational study was conducted in adult patients undergoing an ECG as part of their routine ED care. Adhesive electrodes were left in place after an ECG had been performed by the treating nurse, and subsequently each patient was assessed by two of the three investigators. Each investigator independently recorded the location of the chest electrodes relative to the recommended standard positions. Displacement of the electrodes from the standard positions was measured in the vertical and horizontal planes. The age, sex, weight, height and chest circumference was also recorded. Comparisons were made between investigators to determine variability in assessment of the standard positions. Results: Measurement of horizontal and vertical displacement for each of the six chest leads in the 77 patients resulted in 924 paired measurements. There was substantial inter‐rater variation in the measurement of both vertical (mean 13.5 mm, range 0–105 mm) and horizontal (mean 16.5 mm, range 0–120 mm) displacement. This variation was greater in the lateral chest leads and was more marked in women than in men, especially in the vertical plane (lead V6: men 14.5 mm vs women 27.0 mm, P < 0.01). Conclusion: Among clinical ‘experts’, there is wide variation in the identification of the correct location for electrode placement, particularly in the lateral leads and in women. This has significant implications when comparing ECG in which electrodes have been placed by different clinicians.     

Xenogenic bone matrix extracts induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells

Colloss and Colloss-E are sterile acellular lyophilizates extracted from bovine and equine bone matrix, respectively. Animal and clinical studies have shown that these xenogenic bone matrix extracts (BMEs) are effective as bone graft substitutes. In this report, we investigated the effect of Colloss and Colloss-E on human adult in vitro-expanded bone marrow-derived mesenchymal stem cells (BMMSCs). Specifically, we assessed whether these xenogenic BMEs induced osteoblastic differentiation of cultured BMMSC. We show that BMMSCs treated with either Colloss or Colloss-E exhibited characteristic osteoblastic morphological changes accompanied by the expression of osteoblast-specific markers, such as alkaline phosphatase activity, osteopontin secretion and calcium deposits, explicitly demonstrating that these bone matrix extracts induce osteoblastic differentiation of BMMSCs in vitro. Hence, xenogenic BMEs induce bone-specific differentiation of BMMSCs, presumably through providing stem cells with structural and soluble mediators that mimic the in vivo microenvironment. These results may explain the in vivo mode of action of these medical devices, and potentially provide a novel tissue engineering-based treatment of bone defect, using autologous BMMSCs pretreated with BMEs.     

Cigarette and nargileh smoking practices among school students in Beirut, Lebanon

OBJECTIVES: To determine the prevalence and predictors of smoking nargileh and/or cigarettes among school students in Greater Beirut, Lebanon. METHODS: A proportionate random sample of 2443 students from 13 public and private schools was selected and asked to complete self-administered anonymous questionnaires. RESULTS: The prevalence of smoking cigarettes only, nargileh only, and both was 2.5%, 25.6%, and 6.3%, respectively. Stepwise regression analyses revealed that the predictors of smoking for either type are different, whereby nargileh smoking is more culturally accepted than cigarette smoking. CONCLUSIONS: Design interventions to increase awareness towards the hazards of the misconceived harmless effects of nargileh smoking.     

Comprehensive molecular screening strategy of OCLN in band‐like calcification with simplified gyration and polymicrogyria

Occludin (OCLN) is an important component of the tight junction complex, providing apical intercellular connections between adjacent cells in endothelial and epithelial tissue. In 2010 O'Driscoll et al reported mutations in OCLN to cause band‐like calcification with simplified gyration and polymicrogyria (BLC‐PMG). BLC‐PMG is a rare autosomal recessive syndrome, characterized by early onset seizures, progressive microcephaly, severe developmental delay and deep cortical gray matter and basal ganglia calcification with symmetrical, predominantly fronto‐parietal, polymicrogyria. Here we report 4 additional cases of BLC‐PMG with novel OCLN mutations, and provide a summary of the published mutational spectrum. More generally, we describe a comprehensive molecular screening strategy taking into account the technical challenges associated with the genetic architecture of OCLN, which include the presence of a pseudo‐gene and copy number variants.     

The risk of venous thromboembolism associated with the factor V Leiden mutation and low B-vitamin status.

Venous thromboembolism (VTE) is a multi-factorial disease involving numerous genetic and environmental risk factors. In this study we investigated the occurrence and the risk associated with factor V Leiden, hyperhomocysteinemia and low folate and vitamin B12 levels in young patients with thrombosis. We studied 78 patients (33 females/45 males, mean age 33 years) with a history of thrombosis in a lower limb. Additionally, 98 healthy subjects (45 females/54 males, mean age 44 years) were included. Serum levels of homocysteine (Hcy), folate and vitamin B12 were assayed. Factor V Leiden and methylenetetrahydrofolate reductase (MTHFR) C677T mutations were investigated in all subjects. Factor V Leiden was highly prevalent in the patients (39% heterozygous, 10% homozygous vs. 6.3% heterozygous in controls). An increase in the risk of idiopathic VTE was associated with Hcy levels > 15.2 micromol/l (odds ratio, OR = 2.83), folate < 15.1 nmol/l (OR = 7.49) and vitamin B12 < 182 pmol/l (OR = 11.97). Low levels of folate or vitamin B12 were independently and strongly associated with the risk of VTE in a multivariate model (OR for idiopathic thrombosis = 16.44 and 10.76, respectively). Twenty patients (53%), carriers of factor V Leiden, had low levels of vitamin B12, compared to 28% of patients who were non-carriers of the mutation (p = 0.03). In contrast, none of the control carriers of the mutation had a low level of vitamin B12. The risk of VTE associated with lower levels of vitamin B12 and folate was stronger than that introduced by elevated Hcy levels. The increased risk of VTE, accompanied by factor V Leiden, may be related to confounding environmental factors.