Decreased liver-to-spleen ratio in low-dose computed tomography as a biomarker of fatty liver disease reflects risk for myocardial ischaemia.

Aims: A strong association between fatty liver disease (FLD) and coronary artery disease is consistently reported. Our aim was to evaluate whether FLD diagnosed using low-dose non-contrast computed tomography (LDCT), as a by-product of myocardial perfusion imaging (MPI), is associated with myocardial ischaemia or left ventricular function parameters. Methods and results: We analysed 742 patients who had undergone MPI using single photon emission computed tomography (SPECT) and LDCT. A liver-to-spleen ratio (in Hounsfield units) of <1 was defined as FLD. Myocardial ischaemia was defined as a summed difference score (SDS) ≥3. Left ventricular size and systolic function were assessed from the electrocardiogram-gated SPECT. FLD patients were younger (63 vs. 68 years) and had a higher body mass index (34.6 vs. 29.0 kg/m2) and a higher SDS (2.65 vs. 1.63), P < 0.001 for all. Independently of several possible confounding factors including traditional risk factors, patients with FLD had a 1.70-fold risk of ischaemia (95% confidence interval 1.11-2.58, P = 0.014). Left ventricular end-diastolic volume (109 vs. 109 mL) and ejection fraction (61 vs. 61%) were comparable in those with and without FLD (non-significant for both). Conclusions: With the help of LDCT, it is possible to identify FLD, which is associated with an increased risk of myocardial ischaemia. Therefore, evaluation of FLD from LDCT is recommended along with MPI.

Fatty liver disease is the most common liver disease, affecting a quarter of the population worldwide. It is connected to diabetes and high blood pressure as well as to overweight and obesity. Computed tomography is a common diagnostic method. Its downside is that it exposes patients to radiation. Images can be taken with lower doses of radiation, but these images are less clear and often cannot be used for diagnosis. Low-dose computed tomography is often used with other methods of medical imaging, especially for the heart and lungs. This study shows that fatty liver disease can be diagnosed as a free by-product of low-dose computed tomography images gathered as part of other diagnostic imaging. We also show that fatty liver disease diagnosed from these images is connected to reduced blood flow of heart muscle. Based on the findings, we recommend that these images be scanned for fatty liver disease to identify patients who are at higher risk of heart disease.

Long-lasting TMS motor threshold elevation in mild traumatic brain injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is very common, and part of the patients experience persistent symptoms. These may be caused by diffuse neuronal damage and could therefore affect cortical excitability. The motor threshold (MT), measured by transcranial magnetic stimulation (TMS), is a measure of cortical excitability and cortico-spinal tract integrity. MATERIALS AND METHODS: We used navigated TMS (nTMS) and electromyography to determine subjects' left hemisphere MTs. Nineteen subjects with mTBI (11 with persistent symptoms and eight fully recovered) and nine healthy controls were tested. The injuries had occurred on average 5 years earlier. All participants had normal brain MRIs, that is, no signs of injury. None used centrally acting medication. RESULTS: The mean MT in controls was 43.0% (SD 2.5) of maximum stimulator output. The mTBI subjects mean MT was 53.4% (SD 9.7), being higher than the controls' threshold. Subjective recovery did not correlate with MT. CONCLUSIONS: The results show chronic MT elevation in a sample of subjects with symptomatic or recovered mTBI. This suggests that mTBI may be compensated, although not fully recovered, years after the injury. While the cause for MT elevation cannot be concluded from these preliminary observations, possible explanations include decreased cortical excitability and impaired subcortical conduction.

The effects of rivastigmine on processing speed and brain activation in patients with multiple sclerosis and subjective cognitive fatigue.

BACKGROUND: Cognitive decline and fatigue are typical in multiple sclerosis (MS). However, there is no official medication for either of these symptoms. OBJECTIVE: The purpose of this study was to estimate the effects of a single dose of rivastigmine on processing speed and associated brain activity in patients with MS and subjective cognitive fatigue. METHODS: Fifteen patients with MS and subjective cognitive fatigue and 13 healthy controls (HCs) matched for age, gender and education performed a neuropsychological assessment and functional (f)MRI. A modified version of the Paced Visual Serial Addition Test (mPVSAT) was used as the behavioural task during fMRIs. After the first scanning session, both groups were randomly divided into two subgroups receiving either rivastigmine or placebo. A single dose of rivastigmine or placebo was administrated double-blindly and 2.5 hours later the scanning was repeated. RESULTS: At baseline, the patients with MS showed slower processing speed in mPVSAT compared with the HCs. They also demonstrated stronger bilateral frontal activation after sustained cognitive effort than the HCs. Performance improvement and a further activation increase in the left anterior frontal cortex and additional activation in the right cerebellum were observed in patients who received rivastigmine but not in patients on placebo, or in HCs with placebo or rivastigmine. CONCLUSION: These preliminary findings suggest that rivastigmine may improve cognitive processing speed by enhancing compensatory brain activation in patients with MS.

Right visual field advantage for perceived contrast: correlation with an auditory bias and handedness.

Studies have suggested that supramodal attentional resources are biased rightward due to asymmetric spatial fields of the two hemispheres. This bias has been observed especially in right-handed subjects. We presented left and right-handed subjects with brief uniform grey visual stimuli in either the left or right visual hemifield. Consistent with the proposed asymmetry in attentional resources, right-handed subjects estimated right hemifield targets as having a higher contrast than physically identical stimuli presented in the left hemifield. Left-handed participants did not show a systematic rightward or leftward bias. However, the group of left-handed participants also took part in a dichotic listening experiment whose results showed that visual bias score correlated positively with ear-advantage in dichotic listening. Our results are consistent with the view that supramodal processing resources are biased towards the right hemispace, and that this bias is influenced by handedness.

Comparison of the Behavioural Inattention Test and the Catherine Bergego Scale in assessment of hemispatial neglect.

The objective of the study was to correlate visual and behavioural assessments of hemispatial neglect caused by cerebrovascular accident. We assessed 17 consecutive right-hemisphere stroke patients with hemispatial neglect: the Catherine Bergego Scale (CBS) was used to evaluate neglect in spontaneous behaviour and the conventional subtests of the Behavioural Inattention Test (BIT C) were used to assess visual neglect. The proportional severity of both visual and behavioural neglect was calculated in each individual patient. Dissociations were found between mild neglect in visual screening tasks and moderate or severe neglect in behaviour, although in most patients, neglect was equally evident in both tests. Only the line bisection subtest from the BIT correlated significantly with the CBS, yet both tests showed good internal consistency. The line bisection test and several items of the CBS were especially sensitive in detecting the combination of visual field deficit and hemispatial neglect. In conclusion, we propose that visual fields should always be assessed in patients with neglect because neglect may be exacerbated by a visual field deficit and this can cause prolonged functional disability in everyday life situations. Specific rehabilitation methods might also be needed in neglect with or without hemianopia.

Bone mineral content in young adults with active or inactive juvenile idiopathic arthritis and in controls.

OBJECTIVE: To obtain information on bone mineral content (BMC) in juvenile idiopathic arthritis (JIA) in young adulthood. METHODS: BMC measurements of 116 young adults with JIA and controls were performed at the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry (DXA). RESULTS: Patients were divided into the JIA-active group (n = 73) and the JIA-inactive group (n = 43). Fifty-five per cent of men and 30% of women had their disease in remission. Forty-eight per cent in the JIA-active group and 16% in the JIA-inactive group had used glucocorticoids (p < 0.001). Mean BMC in the femoral neck was 5.76 (SD 0.21) g for men and 4.74 (SD 0.10) g for women in the JIA-active group; 5.84 (SD 0.23) g for men and 4.59 (SD 0.06) g for women in the JIA-inactive group; and 6.65 (SD 0.20) g for men and 4.78 (SD 0.07) g for women in the controls. Both JIA groups had lower BMC values in the femoral neck than the controls (p < 0.001), but a statistically significant difference was found among men (p = 0.006). There was no significant difference in mean BMC in the lumbar spine between the JIA groups and the controls, nor between men and women. Glucocorticoid use, weight and also height among women were associated statistically significantly with BMC in the femoral neck. CONCLUSIONS: Young adults, especially men, with JIA have reduced BMC values in the femoral neck. Glucocorticoid use and weight, but not disease activity, seem to be associated with lower BMC. However, osteoporosis is rare.

Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes.

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.

Biological responses of midge (Chironomus riparius) and lamprey (Lampetra fluviatilis) larvae in ecotoxicity assessment of PCDD/F-, PCB- and Hg-contaminated river sediments.

We evaluated the utility of chironomid and lamprey larval responses in ecotoxicity assessment of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F)-, polychlorinated biphenyls (PCB)- and mercury (Hg)-contaminated river sediments. Sediment samples were collected from the River Kymijoki with a known industrial pollution gradient. Sediment for the controls and lamprey larvae were obtained from an uncontaminated river nearby. Contamination levels were verified with sediment and tissue PCDD/F, PCB and Hg analyses. Behaviour of sediment-exposed chironomid and lamprey larvae were measured with Multispecies Freshwater Biomonitor© utilizing quadrupole impedance conversion technique. In addition, mortality, growth and head capsule deformity incidence of chironomids were used as ecotoxicity indicators. WHOPCDD/F+PCB-TEQ in the R. Kymijoki sediments ranged from the highest upstream 22.36 ng g(-1) dw to the lowest 1.50 ng g(-1) near the river mouth. The sum of PCDD/Fs and PCBs correlated strongly with Hg sediment concentrations, which ranged from <0.01 to 1.15 µg g(-1). Lamprey tissue concentrations of PCDD/Fs were two orders and PCBs one order of magnitude higher in the R. Kymijoki compared to the reference. Chironomid growth decreased in contaminated sediments and was negatively related to sediment ∑PCDD/Fs, WHOPCDD/F+PCB-TEQ and Hg. There were no significant differences in larval mortality or chironomid mentum deformity incidence between the sediment exposures. The distinct behavioural patterns of both species indicate overall applicability of behavioural MFB measurements of these species in sediment toxicity bioassays. Chironomids spent less and lampreys more time in locomotion in the most contaminated sediment compared to the reference, albeit statistically significant differences were not detected. Lamprey larvae had also a greater activity range in some of the contaminated sediments than in the reference. High pollutant levels in lamprey indicate risks for biomagnification in the food webs, with potential health risks to humans consuming fish.

Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

Free fatty acids (FFAs) are an important substrate for myocardial and skeletal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertaken to assess whether myocardial or muscle uptake of FFA is altered in patients with impaired glucose tolerance (IGT). Eight healthy men (control group; age 48+/-1 years, BMI 25+/-1 kg/m2, mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49+/-1 years, BMI 29+/-1 kg/m2) were studied in the fasting state. Myocardial oxygen consumption and blood flow and myocardial and femoral muscle FFA uptake rates were measured with positron emission tomography (PET) and [15O]O2, [15O]H2O, [15O]CO, and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA), a fatty acid tracer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intolerant group during the PET study, but FFA concentrations were comparable between the groups. No differences between the groups were observed in the myocardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FFA uptake indices (5.6+/-0.4 vs. 5.2+/-0.4 pmol x 100 g(-1) x min(-1), glucose-intolerant versus control, NS). In the femoral muscle, fractional FTHA uptake (0.0062+/-0.0003 vs. 0.0072+/-0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30+/-0.02 vs. 0.43+/-0.04 min(-1), P = 0.020) were significantly lower in the glucose-intolerant group than in the control group. In conclusion, when studied at the fasting state and normal serum FFA concentrations, subjects with IGT have similar myocardial but lowered femoral muscle FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired peripheral glucose utilization and insulin resistance commonly observed in IGT.

The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis.

OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.

Evaluation of the impact of podiatrist care in the primary prevention of foot problems in diabetic subjects.

OBJECTIVE: To evaluate the influence of podiatrist activities on the outpatient care of diabetic patients in terms of knowledge of diabetic foot care, self-care, and minor foot problems. RESEARCH DESIGN AND METHODS: There were 733 patients, aged 10-79 years, identified from the national diabetes register. Patients without recent visits to a podiatrist and without an obvious need for foot care were randomized into a podiatric care group (education and primary prevention measures, n = 267) and a control group (written instructions only, n = 263). The patients were examined by an independent study podiatrist at baseline and after 1 year. RESULTS: Patients in the podiatrist group had greater improvement in knowledge of diabetic foot care (P = 0.004) and self-care (P < 0.001) scores compared with control subjects. The prevalence of callosities in regions other than the calcaneal region decreased more (P = 0.009) in the podiatrist group (from 54.5 to 39.5%) than in the control group (from 51.3 to 48.2%), and the size of the callosities decreased more (P < 0.001) in the podiatrist group than in the control group. Reduction in the prevalence of callosities was associated with younger age (< 50 years). CONCLUSIONS: Education and primary preventive measures provided individually by a podiatrist result in significant improvements in knowledge and foot self-care scores and in improvements in the prevalence of some minor foot problems. Long-term studies are needed to evaluate whether the intervention of podiatrists starting at an early phase would lead to a reduction in major foot problems.

Signaling lymphocytic activation molecule (SLAM) is differentially expressed in human Th1 and Th2 cells.

We have used a real-time quantitative RT-PCR technique (TaqMan, PE Biosystems) to identify genes that are differentially expressed by human polarised CD4(+) T cell subsets (Th1 or Th2). The goal was to test the feasibility of the detection method in profiling the expression of a set of marker genes important for Th1 and Th2 differentiation. We demonstrate that in polarised human Th1 cells signaling lymphocytic activation molecule (SLAM), a member of the immunoglobulin superfamily, is expressed at 7-25-fold higher levels than in Th2 cells. Along with SLAM, expression of the IL-12 receptor chain beta 2 (IL-12R beta 2) and the IFN-gamma receptor chain beta (IFN-gamma R beta) proved to be useful molecular markers indicating the state of T cell polarisation, as previously reported. Treatment with IL-12 increased SLAM mRNA expression in T cells by 3-4-fold, whereas a number of other cytokines including PDGF-BB, IFN-alpha A, IFN-alpha A/D, IFN-beta, IFN-gamma or IL-9 had no effect. Stimulating T cells by co-ligating CD3 and CD28 increased SLAM protein surface expression in both Th1 and Th2 cells. In conclusion, real-time RT-PCR detection was found to be an accurate, sensitive and highly reproducible method for fast profiling of mRNA expression in Th1 and Th2 cell subsets.

Separate finger representations at the human second somatosensory cortex.

We recorded neuromagnetic responses of the second somatosensory cortex in healthy humans. Cutaneous electrical stimulation of fingers elicited a response around 100 ms, with a field pattern agreeing with activation of the second somatosensory cortex in the upper bank of the Sylvian fissure. In an oddball paradigm, with standards presented to the thumb and deviants (10%) to the middle finger, or vice versa, the second somatosensory cortex responses to deviants were almost three times as high in amplitude as those to standards. A similar amplitude enhancement was obtained when the deviants were presented in the absence of the intervening standards but with the same interstimulus interval. The results indicate that an accurate functional representation of different body areas is maintained at the human second somatosensory cortex.

Effects of five years of cardiac rehabilitation after coronary artery bypass grafting on coronary risk factors.

Coronary risk factors were studied in 119 patients randomly assigned to cardiac rehabilitation and compared with 109 patients receiving standard care alone after coronary artery bypass grafting. The long-term impact of rehabilitation on risk factors was modest in patients undergoing elective coronary surgery.

fMRI activations of SI and SII cortices during tactile stimulation depend on attention.

Somatosensory cortical areas are widely studied with new functional imaging techniques, but usually with poor control over the attentional state of subjects. We applied fMRI to determine possible changes in activations of these areas due to modulations of attention. Attention induced large regional changes, mostly enlargements of activated areas, and more of those at SII than at SI. The number of instances where activation was only seen in attend conditions was also larger at SII than at SI. These results show the importance of controlling the attentional state of the subjects in imaging studies, and give evidence of the different roles of SI and SII cortices in the somatosensory system.

The effects of electromagnetic field emitted by GSM phones on working memory.

The influence of pulsed radiofrequency (RF) electromagnetic fields of digital GSM mobile phones on working memory in healthy subjects were studied. Memory load was varied from 0 to 3 items in an n-back task. Each subject was tested twice within a single session, with and without the RF exposure (902MHz, 217Hz). The RF field speeded up response times when the memory load was three items but no effects of RF were observed with lower loads. The results suggest that RF fields have a measurable effect on human cognitive performance and encourage further studies on the interactions of RF fields with brain function.

The MMN amplitude increases in hypnosis: a case study.

The neural mechanisms associated with hypnosis were investigated in a single highly hypnotizable subject by measuring the mismatch negativity (MMN) component of auditory ERP, reflecting the preattentive discrimination of change in stimulus flow, in normal baseline state and under hypnosis. It has been proposed that the frontal inhibition associated with hypnosis can be measured as a decrease in MMN. ERPs were elicited using the passive oddball paradigm with standard and deviant sine tone stimuli of 500 and 553Hz, respectively. The measurement was repeated in five separate sessions. In hypnosis the MMN was significantly larger compared to baseline. The results indicate that hypnosis can give rise to altered information processing in the brain even at a relatively early, i.e. preattentive level and that the larger MMN measured under hypnosis does not support frontal inhibition theory.

Effects of 902 MHz electromagnetic field emitted by cellular telephones on response times in humans.

The present study examined possible influences of a 902 MHz electromagnetic field emitted by cellular telephones on cognitive functioning in 48 healthy humans. A battery of 12 reaction time tasks was performed twice by each participant in a counterbalanced order: once with and once without the exposure to the field. The results showed that the exposure to the electromagnetic field speeded up response times in simple reaction time and vigilance tasks and that the cognitive time needed in a mental arithmetics task was decreased. The results suggest that exposure to the electromagnetic field emitted by cellular telephones may have a facilitatory effect on brain functioning, especially in tasks requiring attention and manipulation of information in working memory.

Visuospatial mnemonic load modulates event-related slow potentials.

Electroencephalographic slow wave potentials were recorded during the performance of visuospatial working memory tasks. The aim was to study the effects of varying mnemonic loads on slow potentials, and to dissociate the contribution of mnemonic and motor components. Subjects were tested with three spatial delayed matching-to-sample tasks in which the mnemonic load varied while the preparatory motor demands remained constant. The delay-related slow potential was more negative during the tasks in which the subjects had to memorize the locations of six or four stimuli than when only one location had to be memorized. Significant differences between the slow potentials in the tasks with different mnemonic loads were recorded at frontal and temporal recording sites. Since the preparatory motor requirements were similar in all tasks, the modulation of slow potentials reflects working memory processing rather than motor preparatory activity.

Effects of electromagnetic field emitted by cellular phones on the EEG during a memory task.

The effects of electromagnetic fields (EMF) emitted by cellular phones on the ERD/ERS of the 4-6 Hz, 6-8 Hz, 8-10 Hz and 10-12 Hz EEG frequency bands were studied in 16 normal subjects performing an auditory memory task. All subjects performed the memory task both with and without exposure to a digital 902 MHz EMF in counterbalanced order. The exposure to EMF significantly increased EEG power in the 8-10 Hz frequency band only. Nonetheless, the presence of EMF altered the ERD/ERS responses in all studied frequency bands as a function of time and memory task (encoding vs retrieval). Our results suggest that the exposure to EMF does not alter the resting EEG per se but modifies the brain responses significantly during a memory task.