Increased frequency of interleukin-1beta (-511) allele 2 in febrile seizures

Febrile seizures can be the first sign of epilepsy. In a recent study, patients with temporal lobe epilepsy were reported to carry the interleukin-1beta allele 2 at position -511 more often than healthy control subjects. Because pro-inflammatory cytokines, such as interleukin-1, are well-known inducers of fever and therefore could play an important part in the pathogenesis of febrile seizures, we have, in this study, analyzed the cytokine gene polymorphism of interleukin-1beta at position -511 in children with febrile seizures and control subjects. We found a statistically significant increase in the frequency and the carriage of interleukin-1beta (-511) allele 2 in children with febrile seizures (n = 35) compared with healthy blood donors (n = 400) (P = 0.03 and P = 0.05, respectively). In previous studies, this allele has been connected to increased in vitro production of interleukin-1. Children with febrile seizures may therefore have an increased pro-inflammatory reaction during fever. This pro-inflammatory reaction may also predispose some children to the development of epilepsy.     

Processing of changes in visual speech in the human auditory cortex

Seeing a talker's articulatory gestures may affect the observer's auditory speech percept. Observing congruent articulatory gestures may enhance the recognition of speech sounds [J. Acoust. Soc. Am. 26 (1954) 212], whereas observing incongruent gestures may change the auditory percept phonetically as occurs in the McGurk effect [Nature 264 (1976) 746]. For example, simultaneous acoustic /ba/ and visual /ga/ are usually heard as /da/. We studied cortical processing of occasional changes in audiovisual and visual speech stimuli with magnetoencephalography. In the audiovisual experiment congruent (acoustic /iti/, visual /iti/) and incongruent (acoustic /ipi/, visual /iti/) audiovisual stimuli, which were both perceived as /iti/, were presented among congruent /ipi/ (acoustic /ipi/, visual /ipi/) stimuli. In the visual experiment only the visual components of these stimuli were presented. A visual change both in audiovisual and visual experiments activated supratemporal auditory cortices bilaterally. The auditory cortex activation to a visual change occurred later in the visual than in the audiovisual experiment, suggesting that interaction between modalities accelerates the detection of visual change in speech.     

Clinical characteristics of frontotemporal patients with symmetric brain atrophy

In this paper we explored patterns of frontal and temporal asymmetry in frontotemporal dementia (FTD) and tried to isolate clinical correlates associated with asymmetry or lack thereof. Volumes of frontal and temporal lobes, hippocampus and entorhinal cortex were measured using magnetic resonance imaging (MRI) in 10 patients with FTD. Age- and cranial size-specific values were computed through linear regression analysis (W-scores). A subgroup of 3 patients with symmetric frontal and temporal atrophy was identified. When compared to patients with asymmetric atrophy, the former had younger age at onset of the disease (p = 0.02), greater overall frontotemporal (p = 0.02) and greater entorhinal atrophy (p < 0.04). Two of the three patients were apolipoprotein E ɛ4 carriers versus none of the asymmetric patients (p = 0.02). The lack of asymmetry in this small sample of FTD patients was associated with greater brain atrophy, younger age at onset, and presence of the ɛ4 allele of apolipoprotein E. The presence of the ɛ4 allele is consistent with the hypothesis of greater vulnerability of the brain in ɛ4 carriers. Received: 15 April 2002 / Accepted: 2 October 2002 Correspondence to Dr. G. B. Frisoni     

The combination of HSV-tk and endostatin gene therapy eradicates orthotopic human renal cell carcinomas in nude mice

BACKGROUND AND METHODS: Gene therapy may offer a new tool for the treatment of renal cell carcinoma (RCC). We have tested a combination of cytotoxic and antiangiogenic gene therapy for wild-type orthotopic human RCC xenografts in nude mice using intratumoral adenovirus-mediated herpes simplex virus thymidine kinase (HSV-tk) and endostatin (ES) gene therapy. In vivo magnetic resonance imaging, morphometry, immunocytochemistry, and survival were used to evaluate the treatment effect. Adenovirus-mediated marker gene transfers (GFP) were used as controls. Results: In vivo transduction efficiency, measured using GFP gene transfer, was 27+/-7%. The combination gene therapy with HSV-tk and ES adenoviruses resulted in a significant antitumor effect (P<.01) compared to single HSV-tk (n.s.) or ES (n.s.). In the survival study, all tumors with single gene therapy using HSV-tk, ES, and marker gene adenoviruses showed progression in magnetic resonance imaging. In contrast, the majority of the tumors in the combination treatment group remained dormant or were eradicated (57%). Survival of these mice equaled healthy nude mice, and was significantly prolonged (P<.0001) compared to HSV-tk (P<.028) and ES (n.s.) groups. Conclusions: It is concluded that the inhibition of angiogenesis using ES gene transfer together with the cytotoxic HSV-tk gene therapy results in a significantly improved treatment effect in RCC compared to the single gene treatments.     

Toenail selenium concentration and lung cancer in male smokers (Finland)

Background: The objective of this investigation was to evaluate the association between toenail selenium concentration and lung cancer risk in male smokers. Methods: We conducted a nested case–control study within the Alpha–Tocopherol Beta–Carotene Cancer Prevention Study cohort. This substudy included 250 randomly selected incident lung cancer cases and 250 controls matched on age (up to ± 5 years), intervention group assignment, and date or randomization (±15 days). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression methods. Finland began fortification of argricultural fertilizers in the fall of 1984, increasing the dietary intake, plasma, and toenail selenium concentrations for the population. The present analyses were based on the calculated residual of toenail selenium after regressing it on date of randomization. The selenium residual and the interaction of the residual with date of randomization were included in models with smoking status and body mass index as covariates. Results: We observed a suggestion of a protective association for higher selenium status among men who entered the trial early (when the range of selenium values included very low levels). The OR for men with adjusted toenail selenium concentrations at the 75th percentile compared to those with the lowest selenium concentrations ranged between 0.20 (0.09–0.44) for men randomized earliest in the trail and 0.61 (0.27–1.41) for men randomized in the fifth year. Conclusions: These results suggest that low selenium status may be associated with increased risk for lung cancer.     

Increased plasma levels of pro- and anti-inflammatory cytokines in patients with febrile seizures

PURPOSE: Pro- and antiinflammatory cytokines regulate the febrile response during infection. Febrile seizures (FSs) conversely are associated with rapid onset of high fever. Activation of the cytokine network has been shown in previous studies of FSs and cytokines. In this study, the association between cytokines and FSs was further investigated. METHODS: Interleukin-1beta (IL-1beta), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), interleukin-10, and tumor necrosis factor-alpha plasma levels were measured with enzyme-linked immunosorbent assay in 55 children with FSs and in 20 age-matched febrile controls immediately on arrival at the hospital. Cerebrospinal fluid cytokine levels also were measured in 16 FS children. RESULTS: The plasma IL-1RA/IL-1beta ratio (mean, 2,133 vs. 119; median, 790 vs. 105; p < 0.0001) and plasma IL-6 (mean, 41.7 pg/ml vs. 16.1 pg/ml; median, 19.6 pg/ml vs. 10.5 pg/ml; p = 0.005) were significantly higher in FS patients compared with control children. Logistic regression analysis was used to find the most significant predisposing factors for FSs. In this analysis, the high plasma IL-1RA/IL-1beta ratio was the most significant factor connected to FSs (OR, 41.5; 95% CI, 4.9-352.8), but high plasma IL-6 also was significantly associated with FSs (OR, 5.3; 95% CI, 1.4-20.3). CONCLUSIONS: Present results support the hypothesis that the cytokine network is activated and could have a role in the pathogenesis of FS.     

Clinical applicability of heart rate variability analysis by methods based on nonlinear dynamics

Analysis of heart rate (HR) variability has become an important widely used method for assessingcardiac autonomic regulation. Conventionally, HR variability has been analyzed with time and frequency domainmethods. Analysis of HR dynamics by methods based on nonlinear systems theory has opened a novel approach forstudying the abnormalities in HR behavior. Recent studies have shown that these measures, particularly scalinganalysis methods of HR dynamics, are altered among various patients populations with cardiovascular diseases, andthey provide prognostic information. Altered long-term scaling properties of HR dynamics and more random short-termHR fluctuation has been observed, e.g., among patients with previous myocardial infarction, and these alterationshave been shown to be associated with increased mortality rate. A relatively large body of data indicate thataltered scaling properties of R-R intervals are physiologically deleterious. These findings support the notion thatsome nonlinear methods, such as scaling and complexity measures, give clinically valuable information for riskstratification among various patient populations. This article provides a review of our current knowledge of theusefulness of dynamical measures of HR fluctuation.     

Cancer incidence in a cohort of Finnish male smokers.

A total of 29,133 male smokers, aged 50-69 years, were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in 1984-1988. The nationwide Finnish Cancer Registry (FCR) recorded 5944 incident cases of cancer in this cohort through the end of 1999. Compared with the FCR data of the entire Finnish male population of same age the standardized incidence ratio (SIR) of total cancer in the ATBC cohort was 1.55 [95% confidence interval (CI) 1.51-1.59]. There was a significant excess of established smoking-related malignancies, such as lung cancer (SIR 2.45, 95% CI 2.35-2.56), and cancers of the tongue, mouth, pharynx, larynx, oesophagus, pancreas, stomach, liver, urinary bladder and kidney. In addition to these sites, cancers of the prostate and colon were slightly more common in the ATBC cohort than in the total Finnish male population (SIR 1.10, 95% CI 1.04-1.18 and SIR 1.14, 95% CI 1.00-1.30, respectively). In conclusion, the risk of many cancers was significantly higher in the ATBC Study cohort compared with the total Finnish male population of same age. In addition to the well known smoking-related cancers, cigarette smoking may increase slightly the risk of colon and prostate cancer, too.