Increased Mortality Despite Successful Multifactorial Cardiovascular Risk Reduction in Healthy Men: 40-Year Follow-Up of the Helsinki Businessmen Study Intervention Trial.

OBJECTIVES: In a 5-year multifactorial risk reduction intervention for healthy men with at least one cardiovascular disease (CVD) risk factor, mortality was unexpectedly higher in the intervention than the control group during the first 15-year follow-up. In order to find explanations for the adverse outcome, we have extended mortality follow-up and examined in greater detail baseline characteristics that contributed to total mortality. DESIGN: Long-term follow-up of a controlled intervention trial. SETTING: The Helsinki Businessmen Study Intervention Trial. PARTICIPANTS AND INTERVENTION: The prevention trial between 1974-1980 included 1,222 initially healthy men (born 1919-1934) at high CVD risk, who were randomly allocated into intervention (n=612) and control groups (n=610). The 5-year multifactorial intervention consisted of personal health education and contemporary drug treatments for dyslipidemia and hypertension. In the present analysis we used previously unpublished data on baseline risk factors and lifestyle characteristics. MAIN OUTCOME MEASURES: 40-year total and cause-specific mortality through linkage to nation-wide death registers. RESULTS: The study groups were practically identical at baseline in 1974, and the 5-year intervention significantly improved risk factors (body mass index, blood pressure, serum lipids and glucose), and total CVD risk by 46% in the intervention group. Despite this, total mortality has been consistently higher up to 25 years post-trial in the intervention group than the control group, and converging thereafter. Increased mortality risk was driven by CVD and accidental deaths. Of the newly-analysed baseline factors, there was a significant interaction for mortality between intervention group and yearly vacation time (P=0.027): shorter vacation was associated with excess 30-year mortality in the intervention (hazard ratio 1.37, 95% CI 1.03-1.83, P=0.03), but not in the control group (P=0.5). This finding was robust to multivariable adjustments. CONCLUSION: After a multifactorial intervention for healthy men with at least one CVD risk factor, there has been an unexpectedly increased mortality in the intervention group. This increase was especially observed in a subgroup characterised by shorter vacation time at baseline. Although this adverse response to personal preventive measures in vulnerable individuals may be characteristic to men of high social status with subclinical CVD, it clearly deserves further investigation.

ViPAR: a software platform for the Virtual Pooling and Analysis of Research Data.

BACKGROUND: Research studies exploring the determinants of disease require sufficient statistical power to detect meaningful effects. Sample size is often increased through centralized pooling of disparately located datasets, though ethical, privacy and data ownership issues can often hamper this process. Methods that facilitate the sharing of research data that are sympathetic with these issues and which allow flexible and detailed statistical analyses are therefore in critical need. We have created a software platform for the Virtual Pooling and Analysis of Research data (ViPAR), which employs free and open source methods to provide researchers with a web-based platform to analyse datasets housed in disparate locations. METHODS: Database federation permits controlled access to remotely located datasets from a central location. The Secure Shell protocol allows data to be securely exchanged between devices over an insecure network. ViPAR combines these free technologies into a solution that facilitates 'virtual pooling' where data can be temporarily pooled into computer memory and made available for analysis without the need for permanent central storage. RESULTS: Within the ViPAR infrastructure, remote sites manage their own harmonized research dataset in a database hosted at their site, while a central server hosts the data federation component and a secure analysis portal. When an analysis is initiated, requested data are retrieved from each remote site and virtually pooled at the central site. The data are then analysed by statistical software and, on completion, results of the analysis are returned to the user and the virtually pooled data are removed from memory. CONCLUSIONS: ViPAR is a secure, flexible and powerful analysis platform built on open source technology that is currently in use by large international consortia, and is made publicly available at [http://bioinformatics.childhealthresearch.org.au/software/vipar/].

Efficacy of stabilisation splint treatment on facial pain - 1-year follow-up.

The aim of this randomised controlled trial was to assess the efficacy of stabilisation splint treatment on TMD-related facial pain during a 1-year follow-up. Eighty patients were randomly assigned to two groups: splint group (n = 39) and control group (n = 41). The patients in the splint group were treated with a stabilisation splint and received counselling and instructions for masticatory muscle exercises. The controls received only counselling and instructions for masticatory muscles exercises. The outcome variables were the change in the intensity of facial pain (as measured with visual analogue scale, VAS) as well as the patients' subjective estimate of treatment outcome. The differences in VAS changes between the groups were analysed using variance analysis and linear regression models. The VAS decreased in both groups, the difference between the groups being not statistically significant. The group status did not significantly associate with the decrease in VAS after adjustment for baseline VAS, gender, age, length of treatment and general health status. The only statistically significant predicting factor was the baseline VAS, which was also confirmed by the mixed-effect linear model. After 1-year follow-up, 27.6% of the patients in the splint group and 37.5% of the patients in the control group reported 'very good' treatment effects. The findings of this study did not show stabilisation splint treatment to be more effective in decreasing facial pain than masticatory muscle exercises and counselling alone in the treatment of TMD-related facial pain over a 1-year follow-up.

Positron emission tomography with [18F]flutemetamol and [11C]PiB for in vivo detection of cerebral cortical amyloid in normal pressure hydrocephalus patients.

BACKGROUND AND PURPOSE: This study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [(18) F]flutemetamol and amyloid-ß measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. METHODS: Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous brain biopsy obtained during intracranial pressure monitoring underwent [18F]flutemetamol PET. Seven of these patients also underwent [11C] Pittsburgh compound B (PiB) PET. [18F]Flutemetamol and [11C]PiB uptake was quantified using standardized uptake value ratio (SUVR) with the cerebellar cortex as a reference region. Tissue amyloid-ß was evaluated using the monoclonal antibody 4G8, Thioflavin-S and Bielschowsky silver stain. RESULTS: [18F]Flutemetamol and [11C]PiB SUVRs correlated with biopsy specimen amyloid-ß levels contralateral (r = 0.86, P < 0.0001; r = 0.96, P = 0.0008) and ipsilateral (r = 0.82, P = 0.0002; r = 0.87, P = 0.01) to the biopsy site. Association between cortical composite [(18) F]flutemetamol SUVRs and [11C]PiB SUVRs was highly significant (r = 0.97, P = 0.0003). CONCLUSIONS: [18F]Flutemetamol detects brain amyloid-ß in vivo with moderate to high sensitivity and high specificity. This agent, therefore, represents a valuable new tool to study and verify the presence of amyloid-ß pathology, both in patients with possible NPH and among the wider population.

Take action to prevent diabetes--the IMAGE toolkit for the prevention of type 2 diabetes in Europe.

When we ask people what they value most, health is usually top of the list. While effective care is available for many chronic diseases, the fact remains that for the patient, the tax payer and the whole of society: prevention is better than cure. Diabetes and its complications are a serious threat to the survival and well-being of an increasing number of people. It is predicted that one in ten Europeans aged 20-79 will have developed diabetes by 2030. Once a disease of old age, diabetes is now common among adults of all ages and is beginning to affect adolescents and even children. Diabetes accounts for up to 18 % of total healthcare expenditure in Europe. The good news is that diabetes is preventable. Compelling evidence shows that the onset of diabetes can be prevented or delayed greatly in individuals at high risk (people with impaired glucose regulation). Clinical research has shown a reduction in risk of developing diabetes of over 50 % following relatively modest changes in lifestyle that include adopting a healthy diet, increasing physical activity, and maintaining a healthy body weight. These results have since been reproduced in real-world prevention programmes. Even a delay of a few years in the progression to diabetes is expected to reduce diabetes-related complications, such as heart, kidney and eye disease and, consequently, to reduce the cost to society. A comprehensive approach to diabetes prevention should combine population based primary prevention with programmes targeted at those who are at high risk. This approach should take account of the local circumstances and diversity within modern society (e.g. social inequalities). The challenge goes beyond the healthcare system. We need to encourage collaboration across many different sectors: education providers, non-governmental organisations, the food industry, the media, urban planners and politicians all have a very important role to play. Small changes in lifestyle will bring big changes in health. Through joint efforts, more people will be reached. The time to act is now.

Quality indicators for the prevention of type 2 diabetes in Europe--IMAGE.

BACKGROUND: The marked increase of type 2 diabetes necessitates active development and implementation of efficient prevention programs. A European level action has been taken by launching the IMAGE project to unify and improve the various prevention management concepts, which currently exist within the EU. This report describes the background and the methods used in the development of the IMAGE project quality indicators for diabetes primary prevention programs. It is targeted to the persons responsible for diabetes prevention at different levels of the health care systems. METHODS: Development of the quality indicators was conducted by a group of specialists representing different professional groups from several European countries. Indicators and measurement recommendations were produced by the expert group in consensus meetings and further developed by combining evidence and expert opinion. RESULTS: The quality indicators were developed for different prevention strategies: population level prevention strategy, screening for high risk, and high risk prevention strategy. Totally, 22 quality indicators were generated. They constitute the minimum level of quality assurance recommended for diabetes prevention programs. In addition, 20 scientific evaluation indicators with measurement standards were produced. These micro level indicators describe measurements, which should be used if evaluation, reporting, and scientific analysis are planned. CONCLUSIONS: We hope that these quality tools together with the IMAGE guidelines will provide a useful tool for improving the quality of diabetes prevention in Europe and make different prevention approaches comparable.

Fluxes of nitrous oxide and methane on an abandoned peat extraction site: effect of reed canary grass cultivation.

Drained organic soils are among the most risky soil types as far as their greenhouse gas emissions are considered. Reed canary grass (RCG) is a potential bioenergy crop in the boreal region, but the atmospheric impact of its cultivation is unknown. The fluxes of N(2)O and CH(4) were measured from an abandoned peat extraction site (an organic soil) cultivated with RCG using static chamber and snow gradient techniques. The fluxes were measured also at an adjacent site which is under active peat extraction and it is devoid of any vegetation (BP site). The 4-year average annual N(2)O emissions were low being 0.1 and 0.01 g N(2)O m(-2)a(-1) at the RCG and BP sites, respectively. The corresponding mean annual CH(4) emissions from the RCG and BP sites were also low (0.4 g and 0.9 g CH(4) m(-2)a(-1)). These results highlight for the first time that there are organic soils where cultivation of perennial bioenergy crops is possible with low N(2)O and CH(4) emissions.

Emission of the greenhouse gases nitrous oxide and methane from constructed wetlands in europe.

The potential atmospheric impact of constructed wetlands (CWs) should be examined as there is a worldwide increase in the development of these systems. Fluxes of N(2)O, CH(4), and CO(2) have been measured from CWs in Estonia, Finland, Norway, and Poland during winter and summer in horizontal and vertical subsurface flow (HSSF and VSSF), free surface water (FSW), and overland and groundwater flow (OGF) wetlands. The fluxes of N(2)O-N, CH(4)-C, and CO(2)-C ranged from -2.1 to 1000, -32 to 38 000, and -840 to 93 000 mg m(-2) d(-1), respectively. Emissions of N(2)O and CH(4) were significantly higher during summer than during winter. The VSSF wetlands had the highest fluxes of N(2)O during both summer and winter. Methane emissions were highest from the FSW wetlands during wintertime. In the HSSF wetlands, the emissions of N(2)O and CH(4) were in general highest in the inlet section. The vegetated ponds in the FSW wetlands released more N(2)O than the nonvegetated ponds. The global warming potential (GWP), summarizing the mean N(2)O and CH(4) emissions, ranged from 5700 to 26000 and 830 to 5100 mg CO(2) equivalents m(-2) d(-1) for the four CW types in summer and winter, respectively. The wintertime GWP was 8.5 to 89.5% of the corresponding summertime GWP, which highlights the importance of the cold season in the annual greenhouse gas release from north temperate and boreal CWs. However, due to their generally small area North European CWs were suggested to represent only a minor source for atmospheric N(2)O and CH(4).

Abnormal crossing of the optic fibres shown by evoked magnetic fields in patients with ocular albinism with a novel mutation in the OA1 gene.

AIM: To perform genealogical and clinical studies in Finnish families with X linked ocular albinism (OA1), including characterisation of the potential misrouting of optic fibres by evaluating visual evoked magnetic fields (VEFs), and to determine the mutation behind the disease. METHODS: Three families with OA1 were clinically examined. VEFs were measured in two affected males and in one female carrier to characterise the cortical activation pattern after monocular visual stimulation. The neuronal sources of the VEFs were modelled with equivalent current dipoles (ECDs) in a spherical head model. All coding exons of the OA1 gene were screened for mutations by single strand conformation analysis and direct polymerase chain reaction sequencing. RESULTS: Genealogical studies revealed that the three families were all related. The affected males had foveal hypoplasia with reduced visual acuity varying from 20/200 to 20/50, variable nystagmus, iris transillumination, and hypopigmentation of the retinal pigment epithelium. The ECD locations corresponding to the VEFs revealed abnormal crossing of the optic fibres in both affected males, but not in the carrier female. A novel point mutation, leading to a STOP codon, was identified in the fifth exon of the OA1 gene. CONCLUSIONS: The data indicate that the novel mutation 640C>T in the OA1 gene is the primary cause of the eye disease in the family studied. VEFs with ECD analysis was successfully used to demonstrate abnormal crossing of the optic fibres.

Interaction of mobile phones with superficial passive metallic implants.

The dosimetry of exposure to radiofrequency (RF) electromagnetic (EM) fields of mobile phones is generally based on the specific absorption rate (SAR, W kg(-1)), which is the electromagnetic energy absorbed in the tissues per unit mass and time. In this study, numerical methods and modelling were used to estimate the effect of a passive, metallic (conducting) superficial implant on a mobile phone EM field and especially its absorption in tissues in the near field. Two basic implant models were studied: metallic pins and rings in the surface layers of the human body near the mobile phone. The aim was to find out 'the worst case scenario' with respect to energy absorption by varying different parameters such as implant location, orientation, size and adjacent tissues. Modelling and electromagnetic field calculations were carried out using commercial SEMCAD software based on the FDTD (finite difference time domain) method. The mobile phone was a 900 MHz or 1800 MHz generic phone with a quarter wave monopole antenna. A cylindrical tissue phantom models different curved sections of the human body such as limbs or a head. All the parameters studied (implant size, orientation, location, adjacent tissues and signal frequency) had a major effect on the SAR distribution and in certain cases high local EM fields arose near the implant. The SAR values increased most when the implant was on the skin and had a resonance length or diameter, i.e. about a third of the wavelength in tissues. The local peak SAR values increased even by a factor of 400-700 due to a pin or a ring. These highest values were reached in a limited volume close to the implant surface in almost all the studied cases. In contrast, without the implant the highest SAR values were generally reached on the skin surface. Mass averaged SAR(1 g) and SAR(10 g) values increased due to the implant even by a factor of 3 and 2, respectively. However, at typical power levels of mobile phones the enhancement is unlikely to be problematic.

Superresolution ultrasound imaging using back-projected reconstruction.

An ultrasound technique for imaging objects significantly smaller than the source wavelength is investigated. Signals from a focused beam are recorded over an image plane in the acoustic farfield and backprojected in the wave-vector domain to the focal plane. A superresolution image recovery method is then used to analyze the Fourier spatial frequency spectrum of the signal in an attempt to deduce the location and size of objects in this plane. The physical foundation for the method is rooted in the fact that high spatial frequencies introduced by the object in fact affect the lower (nonevanescent) spatial frequencies of the overall signal. The technique achieves this by using a priori measurements of the ultrasound focus in water, which gives full spectral information about the image source. A guess is then made regarding the size and location of the object that distorted the field, and this is convolved with the a priori measurement, thus creating a candidate image. A large number of candidates are generated and the one whose spectrum best matches the uncorrected image is accepted. The method is demonstrated using 0.34- and 0.60-mm wires with a focused 1.05-MHz ultrasound signal and then a human hair (approximately 0.03 mm) with a 4.7-MHz signal.

EEG minimum-norm estimation compared with MEG dipole fitting in the localization of somatosensory sources at S1.

OBJECTIVE: Dipole models, which are frequently used in attempts to solve the electromagnetic inverse problem, require explicit a priori assumptions about the cerebral current sources. This is not the case for solutions based on minimum-norm estimates. In the present study, we evaluated the spatial accuracy of the L2 minimum-norm estimate (MNE) in realistic noise conditions by assessing its ability to localize sources of evoked responses at the primary somatosensory cortex (SI). METHODS: Multichannel somatosensory evoked potentials (SEPs) and magnetic fields (SEFs) were recorded in 5 subjects while stimulating the median and ulnar nerves at the left wrist. A Tikhonov-regularized L2-MNE, constructed on a spherical surface from the SEP signals, was compared with an equivalent current dipole (ECD) solution obtained from the SEFs. RESULTS: Primarily tangential current sources accounted for both SEP and SEF distributions at around 20 ms (N20/N20m) and 70 ms (P70/P70m), which deflections were chosen for comparative analysis. The distances between the locations of the maximum current densities obtained from MNE and the locations of ECDs were on the average 12-13 mm for both deflections and nerves stimulated. In accordance with the somatotopical order of SI, both the MNE and ECD tended to localize median nerve activation more laterally than ulnar nerve activation for the N20/N20m deflection. Simulation experiments further indicated that, with a proper estimate of the source depth and with a good fit of the head model, the MNE can reach a mean accuracy of 5 mm in 0.2-microV root-mean-square noise. CONCLUSIONS: When compared with previously reported localizations based on dipole modelling of SEPs, it appears that equally accurate localization of S1 can be obtained with the MNE. SIGNIFICANCE: MNE can be used to verify parametric source modelling results. Having a relatively good localization accuracy and requiring minimal assumptions, the MNE may be useful for the localization of poorly known activity distributions and for tracking activity changes between brain areas as a function of time.

PROD-screen--a screen for prodromal symptoms of psychosis.

The aim of this study was to describe the PROD-screen, an instrument for screening prodromal symptoms indicating risk for psychotic conversion in the near future. PROD-screen consists of 29 questions assessing performance and symptoms. Clinical construct validity was tested by comparing scores from the unselected general population (GP, n = 64) with those of general psychiatric patients from a community mental health centre (CMHC, n = 107). The concordant validity of PROD-screen for prodromal symptoms of psychosis was assessed in a large epidemiologically mixed sample of research subjects (n = 132) by comparing PROD-screen scores with the prodromal diagnosis made by Structured Interview for Prodromal Symptoms as a gold standard. Using the cut-off point of 2/12 specific symptoms, PROD-screen gave correct classification of prodromal status in 77% of cases, distinguishing prodromal from non-prodromal subjects with reasonable sensitivity (80%) and specificity (75%) in the epidemiologically mixed sample. According to subsample analysis PROD-screen functions well with first-degree relatives of schizophrenic patients and probably also with general population samples, but not with psychiatric outpatients. In conclusion, PROD-screen is a useful tool for screening prodromal symptoms of psychosis and selecting subjects for more extensive research interviews.

Enlarged SI and SII somatosensory evoked responses in the CLN5 form of neuronal ceroid lipofuscinosis.

OBJECTIVES: To examine in detail the activation of the primary (SI) and secondary (SII) somatosensory cortex in CLN5, the Finnish variant of late infantile neuronal ceroid lipofuscinoses (NCL). METHODS: Somatory evoked magnetic fields were recorded with a 122-channel planar gradiometer in response to median nerve stimulation in 5 CLN5 patients (aged 8.8-16.7 years) and in 10 healthy age-matched controls. RESULTS: The first two responses from contralateral SI, N20m and P35m, were 6-20 times stronger in the patients than in the controls. The morphology of the subsequent deflections from SI was abnormal in the patients: a prominent N45m was detected, while the normally present P60m deflection was missing. In 4 patients the contra- and in two patients the ipsilateral SII responses were also enlarged. Furthermore, the SII activation was detected at shorter latency in patients than in controls. CONCLUSIONS: At SI, CLN5 is associated with a selective enhancement of the early cortical responses. We propose that the enlargement of N20m most likely reflects increased synchronous input from thalamus, whereas the altered morphology of the following responses may reflect defective interneuronal inhibition at the cortex. The enlargement of SII responses shows that the imbalance between excitation and inhibition in CLN5 extends outside the primary somatosensory areas.

Northern epilepsy syndrome (NES, CLN8)--MRI and electrophysiological studies.

Northern epilepsy syndrome (NES, EPMR, progressive epilepsy with mental retardation, CLN8), an inherited childhood-onset epilepsy with mental retardation, has been recently characterized to belong to the family of neuronal ceroid lipofuscinoses (NCLs). In this study, four patients (ages 26-44 years) with NES and eight healthy controls underwent magnetic resonance imaging (MRI) and electrophysiological evaluation with somatosensory evoked magnetic field (SEF) studies. The findings in NES were compared with the known findings in juvenile NCL (JNCL, CLN3) and Finnish variant late infantile NCL (vLINCLFIN, CLN5) that manifest around the same age as NES. Also postmortem MRI was performed on one brain. On the MRIs, slight to moderate cerebellar atrophy was seen in all patients, whereas only two patients had slightly enlarged cerebral sulci. None of the MRIs demonstrated signal intensity abnormalities that are commonly seen in JNCL and vLINCLFIN and are considered to reflect the Wallerian degeneration after neuronal death. Generally SEFs in NES were within normal limits, indicating that the disease had not impaired the function of the neurons on the somatosensory pathway. In conclusion, MRI imaging and SEF findings suggest that the cerebral neuronal death and dysfunction in NES are minimal compared with JNCL and vLINCLFIN.

No evidence for dependence of early cortical auditory processing on dopamine D(2)-receptor modulation: a whole-head magnetoencephalographic study.

Magnetoencephalography (MEG) was used to determine the effect of neuroleptic challenge on brain responses in healthy subjects. In a double-blind, randomized, placebo-controlled, cross-over design study, the dopamine D(2) receptor antagonist haloperidol (2 mg) was given orally to 12 healthy volunteers. The middle-latency auditory evoked magnetic fields (MAEF) were recorded 3 h after administration of haloperidol or placebo with a whole-head 122-channel MEG. Haloperidol did not significantly affect MAEF responses. The dipole moments and source locations of the responses were not significantly influenced by haloperidol. These results suggest that dopamine D(2) receptors are not involved in the early phases of auditory cortical processing.

Effects of haloperidol on selective attention: a combined whole-head MEG and high-resolution EEG study.

We used 122-channel magnetoencephalography (MEG) and 64-channel electroencephalogrphy (EEG) simultaneously to study the effects of dopaminergic transmission on human selective attention in a randomized, double-blind placebo-controlled cross-over design. A single dose of dopamine D2 receptor antagonist haloperidol (2 mg) or placebo was given orally to 12 right-handed healthy volunteers 3 hours before measurement. In a dichotic selective attention task, subjects were presented with two trains of standard (700 Hz to the left ear, 1,100 Hz to the right ear) and deviant (770 and 1,210 Hz, respectively) tones. Subjects were instructed to count the tones presented to one ear; whereas, the tones presented to the other ear were to be ignored. Haloperidol significantly attenuated processing negativity (PN), an event-related potential (ERP) component elicited by selectively attended standard tones at 300-500 ms after stimulus presentation. These results, indicating impaired selective attention by a blockade of dopamine D2 receptors, were further accompanied with increased mismatch negativity (MMN), elicited by involuntary detection of task-irrelevant deviants. Taken together, haloperidol seemed to induce functional changes in neural networks accounting for both selective and involuntary attention, suggesting modulation of these functions by dopamine D2 receptors.

Interhemispheric phase synchrony and amplitude correlation of spontaneous beta oscillations in human subjects: a magnetoencephalographic study.

Interhemispheric phase synchrony and amplitude correlation of beta oscillations were studied with MEG in a resting condition. The left and right hemisphere beta oscillations exhibited phase-locking with a phase-lag near zero degrees. The index of synchronization was strongest when these oscillations had large amplitude. Functionally, we interpret the phase synchrony on the basis of bilaterality of movement organization. A positive interhemispheric correlation was also found for the amplitude of spontaneous beta oscillations over long time intervals (> 1 s). The low-frequency correlation of spontaneous rhythmic activity may be the source of the low-frequency correlations of the hemodynamic responses in homologous areas that have been reported previously and have been interpreted as functional connectivity between these areas.

Auditory sensory memory and the cholinergic system: implications for Alzheimer's disease.

Auditory sensory memory represents one of the simplest types of short-term memory that can be studied electrophysiologically with mismatch negativity (MMN); a specific auditory event-related potential indexing automatic comparison of incoming stimuli to an existing memory trace. Previous results suggest that auditory sensory memory deteriorates in aging and especially in Alzheimer's disease (AD). It has remained unsettled, however, whether MMN is regulated by the cholinergic system, which is deteriorated in AD contributing to cognitive impairments. We recorded cortical auditory responses with a magnetometer from 13 healthy subjects after intravenous injection of scopolamine, centrally acting cholinergic antagonist, or glycopyrrolate, a drug with a peripheral anticholinergic properties without penetrating the blood-brain barrier, using a double-blind protocol. Scopolamine reduced MMNm amplitude in response to frequency, but not duration, change, increased P50m amplitude, and delayed N100m latency. These findings suggest that the cholinergic system regulates the frequency-specific comparison of incoming stimuli to existing memory trace and modulates the preattentive processing related to stimulus detection. Further, neural mechanisms responsible for cortical frequency- and duration-specific discrimination appear to have different sensitivities to cholinergic modulation. Auditory evoked potentials might be suitable to monitor cholinergic activity in AD.

Alpha-tocopherol (vitamin E) and beta-carotene supplementation does not affect the risk for large abdominal aortic aneurysm in a controlled trial.

Antioxidants may retard atherogenesis and limit inflammatory processes involved in aneurysm formation. We evaluated effects of alpha-tocopherol and beta-carotene supplementation on incidence of large abdominal aortic aneurysm (AAA) in a randomised, double-blind, placebo-controlled trial. Subjects (n=29133) were 50-69-years-old male smokers, participants in the Finnish alpha-Tocopherol, beta-Carotene Cancer Prevention (ATBC) Study. They were randomised to receive either 50 mg/day of alpha-tocopherol, or 20 mg/day of beta-carotene, or both, or placebo in a 2x2 design. Incidence of AAA was evaluated from mortality and hospital registers. During 5.8 years of follow-up, 181 men were diagnosed with either ruptured AAA (n=77) or nonruptured large AAA treated with aneurysmectomy (n=104). Relative risk (RR) for AAA was 0.83 (95% confidence interval [CI] 0.62-1.11) among men receiving alpha-tocopherol compared with those who did not, and 0.93 (95% CI 0.69-1.24) among men receiving beta-carotene compared with those who did not. A modest though nonsignificant decrease in risk for nonruptured AAA was observed among alpha-tocopherol supplemented men (RR 0.71, 95% CI 0.48-1.04) compared with men not receiving alpha-tocopherol. For beta-carotene, RR for nonruptured AAA was 0.86 (95% CI 0.59-1.27) compared with men not receiving beta-carotene. Neither antioxidant affected risk for ruptured AAA. In conclusion, long-term supplementation with alpha-tocopherol or beta-carotene had no preventive effect on large AAA among male smokers.