The association between platelet dysfunction and adverse outcomes in cardiac surgical patients.

Haemostatic activation during cardiopulmonary bypass is associated with prothrombotic complications. Although it is not possible to detect and quantify haemostatic activation directly, platelet dysfunction, as measured with point-of-care-assays, may be a useful surrogate. In this study, we assessed the association between cardiopulmonary bypass-associated platelet dysfunction and adverse outcomes in 3010 cardiac surgical patients. Platelet dysfunction, as measured near the end of the rewarming phase of cardiopulmonary bypass, was calculated as the proportion of non-functional platelets after activation with collagen. Logistic regression and multivariable analyses were applied to assess the relationship between platelet dysfunction and a composite of in-hospital death; myocardial infarction; stroke; deep vein thrombosis or pulmonary embolism; and acute kidney injury (greater than a two-fold increase in creatinine). The outcome occurred in 251 (8%) of 3010 patients. The median (IQR [range]) percentage platelet dysfunction was less for those without the outcome as compared with those with the outcome; 14% (8-28% [1-99%]) vs. 19% (11-45% [2-98%]), p < 0.001. After risk adjustment, platelet dysfunction was independently associated with the composite outcome (p < 0.001), such that for each 1% increase in platelet dysfunction there was an approximately 1% increase in the composite outcome (OR 1.012; 95%CI 1.006-1.018). This exploratory study suggests that cardiopulmonary bypass-associated platelet dysfunction has prognostic value and may be a useful clinical measure of haemostatic activation in cardiac surgery.

Gender difference in clinical and genetic characteristics of Brugada syndrome: SADS-TW BrS registry.

BACKGROUND: Brugada syndrome (BrS) is a heritable sudden cardiac death (SCD) disease with male predominance. Information on gender difference of BrS remains scarce. AIM: To investigate the gender difference of BrS in Han Chinese. DESIGN: We consecutively enrolled 169 BrS patients (153 males and 16 females) from Han Chinese in Taiwan from 1998 to 2017. METHODS: Clinical characteristics, electrocardiographic parameters and SCN5A mutation status were compared between genders. RESULTS: The percentage of family history of SCD in females was slightly higher (31.3% vs. 15%, P = 0.15). Females exhibited longer QTc (457.8 ± 33.0 vs. 429.5 ± 42.1 ms, P < 0.01). Regarding cumulative event occurrence by age, Mantel-Cox test showed females had earlier age of onset of first cardiac events (SCD or syncope) than males (P = 0.049), which was mainly attributed to syncope (P < 0.01). Males with SCD exhibited longer QRS duration (114.2 ± 26.8 vs. 104.8 ± 15.3 ms, P = 0.02) and QTc (442.5 ± 57.4 vs. 422.9 ± 28.8 ms, P = 0.02). Males with syncope exhibited longer PR interval (181.2 ± 33.7 vs. 165.7 ± 27.1 ms, P = 0.01), whereas females with SCD or syncope had a trend towards slower heart rates (69.1 ± 9.6 vs. 82.2 ± 16.3 bpm, P = 0.10) than female with no or mild symptoms. There was no difference in the percentage of SCN5A mutation between genders. CONCLUSION: Gender difference is present in BrS. Females have longer QTc and suffer from syncope earlier than males. Risk of SCD in males is associated with boarder QRS complex and longer QTc, whereas risk of syncope is associated with longer PR interval in males and slower heart rate in females.

Removal of single point diamond-turning marks by abrasive jet polishing.

Single point diamond turning (SPDT) is highly controllable and versatile in producing axially symmetric forms, non-axially-symmetric forms, microstructured surfaces, and free forms. However, the fine SPDT marks left in the surface limit its performance, and they are difficult to reduce or eliminate. It is unpractical for traditional methods to remove the fine marks without destroying their forms, especially for the aspheres and free forms. This paper introduces abrasive jet polishing (AJP) for the posttreatment of diamond-turned surfaces to remove the periodic microstructures. Samples of diamond-turned electroless nickel plated plano mirror were used in the experiments. One sample with an original surface roughness of more than 400 nm decreased to 4 nm after two iterations abrasive jet polishing; the surface roughness of another sample went from 3.7 nm to 1.4 nm after polishing. The periodic signatures on both of the samples were removed entirely after polishing. Contrastive experimental research was carried out on electroless nickel mirror with magnetorheological finishing, computer controlled optical surfacing, and AJP. The experimental results indicate that AJP is more appropriate in removing the periodic SPDT marks. Also, a figure maintaining experiment was carried out with the AJP process; the uniform polishing process shows that the AJP process can remove the periodic turning marks without destroying the original form.

Role of serum- and glucocorticoid-inducible kinase-1 in regulating torsion-induced apoptosis in rats.

Serum- and glucocorticoid-inducible kinase-1 (SGK1) is a serine/threonine protein kinase that responds to various stimuli and mediates cell survival. Although it is known that testicular torsion leads to testicular damage and male infertility, the role of SGK1 in torsion remains unclear. This study investigated whether torsion-induced apoptosis is associated with changes in phosphoinositide-dependent protein kinase-1 (PDK1), SGK1 and forkhead transcription factor FOXO3a expression and/or phosphorylation in rats. Sprague-Dawley rats were divided into four groups: sham (control), 1, 2 and 4 h of unilateral torsion. Bilateral testes, testicular interstitial fluid (TIF) and blood samples were collected immediately after torsion. Our results revealed that SGK1 protein and mRNA were abundantly present in testes and were induced by 2 h of torsion, but that phosphorylation of SGK1, PDK1 and FOXO3a decreased simultaneously. After 2 h of torsion, the testosterone secretion capacity of the primary Leydig cells and testicular interstitial cells (TICs) was impaired and apoptotic spermatogonia and TICs were observed; in addition, the mean seminiferous tubular diameter was decreased. Torsion increased plasma corticosterone levels, but decreased plasma luteinizing hormone and testosterone levels. However, the testosterone levels of the TIF in the ipsilateral testes were significantly enhanced after 2 h of torsion, but suppressed in the contralateral testes. This animal study suggests that PDK1, SGK1 and FOXO3a are involved in torsion-induced apoptosis and that medical therapy should be performed as early as 2 h after the occurrence of torsion to prevent further damage.

Islet isolation from human pancreas with extended cold ischemia time.

The general consensus among transplant centers is that a cold ischemia time (CIT) beyond 8 hours results in reduced yields and quality of human islets. We sought to optimize the isolation process and enzymes for pancreata with extended CIT. We processed 16 extended CIT pancreata (13.2 +/- 0.7 hours). Donors averaged 50.8 +/- 2.6 (standard error of the mean) years old with a body mass index of 28.6 +/- 1.5. Glands were shipped in cold organ preservation solution without oxygenated perfluorocarbon. Isolations were performed under a protocol optimized for digestion with the new cGMP collagenase from Roche. Purification used continuous Euroficoll/University of Wisconsin gradients. Islets were cultured in two types of Prodo cGMP islet culture media and/or in Miami 1A media. Glucose-stimulated insulin secretion assays were performed after 8 to 16 days of culture. Prepurification yield averaged 415 +/- 41 KIEQ postpurification, 359 +/- 29 KIEQ (purification loss 13.5%); and postculture 317 +/- 27 KIEQ (culture loss 11.7%). Our process liberated an average of 4278 IEQ/g of pancreas (97 +/- 5 g). Most islets were recovered in the purest fraction (purity 79.7% +/- 1.9%). Culture loss in our enhanced culture media was 11.7%. After 2 to 3 days in culture, viability was 92% +/- 1%. Islets exhibited compactness and dithizone staining. Glucose-stimulated insulin secretion assays performed after 3 to 23 days in our PIM(R) media resulted in a stimulation index of 6.8 +/- 1.7 (G50 to G350). We concluded that our human islet isolation process permitted the recovery of large numbers of high-quality human islets from extended CIT pancreata and that our cGMP islet culture media was superior to the current standard CMRL-based media.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study.

AIM: To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan. METHODS: A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999-2004. Adult patients aged > or = 20 years old with prevalent and incident Type 2 diabetes were identified using ICD-9-CM diagnostic codes. Age-specific and age-direct-standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression. RESULTS: During the study years, the age-standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and > or = 80 years. The age-standardized incidence rates of Type 2 diabetes per 1000 person-years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20-1.42) for men and 1.04 (1.01-1.08) for women. The incidence trends for people aged > or = 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001). CONCLUSIONS: This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999-2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20-40 years were most susceptible to higher incidence of Type 2 diabetes.

Prevalence of albuminuria and cardiovascular risk profile in a referred cohort of patients with type 2 diabetes: an Asian perspective.

BACKGROUND: Microalbuminuria (MA) is a risk marker for diabetic nephropathy and cardiovascular (CV) disease (CVD) in patients with diabetes. This study aimed to describe the prevalence of albuminuria, CV risk factors, and treatments for renal and CV protection in an Asian population with type 2 diabetes. METHODS: This cross-sectional study conducted in eight Asian countries enrolled normotensive/hypertensive adults with type 2 diabetes without known proteinuria and/or non-diabetic kidney disease. Exclusion criteria were type 1 diabetes, menstruation, pregnancy, and acute fever. A single random urinary albumin/creatinine test was carried out in all patients. RESULTS: Of 8,561 patients, 14% had diabetic retinopathy, and 17% and 21% had history of CV disease and smoking, respectively. Normoalbuminuria was seen in 44%, MA in 44%, and macroalbuminuria in 12%. Target glycosylated hemoglobin (HbA1c) (<7%) was reached in only 37% of 3,834 patients with available values. Diabetes was managed by diet alone in 6%, while others received oral hypoglycemic drugs and/or insulin. In total, 75% did not reach target blood pressure (BP) of

Iron-generated hydroxyl radicals kill retinal cells in vivo: effect of ferulic acid.

Siderosis bulbi is vision threatening. An investigation into its mechanisms and management is crucial. Experimental siderosis was established by intravitreous administration of an iron particle (chronic) or FeSO(4) (acute). After siderosis, there was a significant dose-responsive reduction in eletroretinogram (a/b-wave) amplitude, and an increase in OH level, greater when caused by 24 mM FeSO(4) than that by 8 mM FeSO(4). Furthermore, the FeSO(4)-induced oxidative stress was significantly blunted by 100 microM ferulic acid (FA). Siderosis also resulted in an excessive glutamate release, increased [Ca(++)](i), and enhanced superoxide dismutase immunoreactivity. The latter finding was consistent with the Western blot result. Obvious disorganization including loss of photoreceptor outer segments and cholinergic amacrines together with a wide-spreading ferric distribution across the retina was present, which were related to the eletro-retinographic and pathologic dysfunctions. Furthermore, b-wave reduction and amacrine damage were respectively, significantly, dose-dependently, and clearly ameliorated by FA. Thus, siderosis stimulates oxidative stress, and possibly, subsequent excitotoxicity, and calcium influx, which explains why the retina is impaired electro-physiologically and pathologically. Importantly, FA protects iron toxicity perhaps by acting as a free radical scavenger. This provides an approach to the study and treatment of the iron-related disorders such as retained intraocular iron and Alzheimer disease.

Bivariate genome-wide scan for metabolic phenotypes in non-diabetic Chinese individuals from the Stanford, Asia and Pacific Program of Hypertension and Insulin Resistance Family Study.

AIMS/HYPOTHESIS: Hypertension, obesity, impaired glucose tolerance and dyslipidaemia are metabolic abnormalities that often cluster together more often than expected by chance alone. Since these metabolic variables are highly heritable and are at least partially genetically determined, the clustering of defects in these traits implies that pleiotropic effects, where a common set of genes influences more than one trait simultaneously, are likely. METHODS: We conducted bivariate linkage analyses for highly correlated traits, aiming to dissect the genetic architecture affecting these traits, in 411 Chinese families participating in the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Study. RESULTS: We confirmed the pleiotropic effects of the locus at 37 cM on chromosome 20 on the following pairs: (1) fasting insulin and insulin AUC (empirical p = 0.0006); (2) fasting insulin and homeostasis model assessment of beta cell function (HOMA-beta) (empirical p = 0.0051); and (3) HOMA of insulin resistance (IR) and HOMA-beta (empirical p = 0.0044). In addition, the peak logarithm of the odds (LOD) scores of linkage between a chromosomal locus and a trait for the pair fasting insulin and HOMA-IR rose to 5.10 (equivalent LOD score in univariate analysis, LOD([1]) = 4.01, empirical p = 8.0 x 10(-5)) from 3.67 and 3.42 respectively for these two traits in univariate analysis. Additional significant linkage evidence, not shown in single-trait analysis, was identified at 45 cM on chromosome 16 for the pair 1 h insulin and the AUC for insulin, with a LOD score of 4.29 (or LOD([1]) = 3.27, empirical p = 2.0 x 10(-4)). This new locus is also likely to harbour the common genes regulating these two traits (p = 1.73 x 10(-6)). CONCLUSIONS/INTERPRETATION: These data help provide a better understanding of the genomic structure underlying the metabolic syndrome.

Surrogate estimates of insulin sensitivity in subjects with hypertension.

The purpose of the study is to compare surrogate estimates of insulin sensitivity with a directly measured insulin sensitivity index, steady-state plasma glucose (SSPG) from insulin suppression test (IST), in subjects with hypertension. Two hundred and twenty-eight hypertensive patients who received IST for SSPG were included for analysis. Estimates from fasting measurements alone, homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)), and indices from fasting and/or 2 h samples (ISI(0,120) and ISI(TX)) were calculated. In addition to Pearson and partial correlations, variance-component models were used to test the relationship between surrogate estimates of insulin sensitivity and SSPG. A large proportion of variance owing to covariates in the variance-component models indicated the goodness of model fit, irrespective of the independence among variables. SSPG was positively correlated with logarithmic transformation (Log) (HOMA-IR) and negatively correlated with QUICKI, Log (ISI(0,120)) and ISI(TX) (all P<0.0001). Log (ISI(0,120)) seemed to have a better correlation with SSPG (r=-0.72) than other measures in partial correlation. The proportion of variance owing to all covariates of Log (ISI(0,120)) and ISI(TX) were larger than those of Log (HOMA-IR) and QUICKI in the variance-component models. After adjustments for demographic and obesity covariates, the proportion of variance explained by Log (ISI(0,120)) were largest among the surrogate measures in the variance-component models. Our results showed that ISI(0,120) and ISI(TX) correlated better with SSPG than those used fasting measures alone (HOMA-IR and QUICKI). Log (ISI(0,120)) currently showing the strongest association with SSPG than other estimates is adaptable for use in large studies of hypertension.

Insulin sensitivity and resistin expression in nitric oxide-deficient rats.

AIMS/HYPOTHESIS: The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. METHODS: Male Sprague-Dawley rats received [Formula: see text]-nitro-L: -arginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. RESULTS: Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.

Hypoxic preconditioning attenuated in kainic acid-induced neurotoxicity in rat hippocampus.

The neuroprotective effect of hypoxic preconditioning on kainate (KA)-induced neurotoxicity, including apoptosis and necrosis, was investigated in rat hippocampus. Female Wistar-Kyoto rats were subjected to 380 mm Hg in an altitude chamber for 15 h/day for 28 days. Intrahippocampal infusion of KA was performed in chloral hydrate anesthetized rats, which acutely elevated 2,3-dihydroxybenzoic acid levels in normoxic rats. Seven days after the infusion, KA increased lipid peroxidation in the infused hippocampus and resulted in hippocampal CA3 neuronal loss. A 4-week hypoxic preconditioning attenuated KA-induced elevation in hydroxyl radical formation and lipid peroxidation as well as KA-induced neuronal loss. The effects of hypoxic preconditioning on KA-induced apoptosis and necrosis were investigated further. Two hours after KA infusion, cytosolic cytochrome c content was increased in the infused hippocampus. Twenty-four hours after KA infusion, pyknotic nuclei, cellular shrinkage, and cytoplasmic disintegration, but not TUNEL-positive staining, were observed in the CA3 region of hippocampus. Forty-eight hours after KA infusion, both DNA smear and DNA fragmentation were demonstrated in the infused hippocampus. Furthermore, TUNEL-positive cells, indicative of apoptosis, in the infused hippocampus were detected 72 h after KA infusion. Hypoxic pretreatment significantly reduced necrotic-like events in the KA-infused hippocampus. Moreover, hypoxic preconditioning attenuated apoptosis induced by KA infusion, including elevation in cytosolic cytochrome c content, TUNEL-positive cells, and DNA fragmentation. Our data suggest that hypoxic preconditioning may exert its neuroprotection of KA-induced oxidative injuries via attenuating both apoptosis and necrosis in rat hippocampus.

Neuronal correlates of gastric pain induced by fundus distension: a 3T-fMRI study.

Visceral hypersensitivity in gastric fundus is a possible pathogenesis for functional dyspepsia. The cortical representation of gastric fundus is still unclear. Growing evidence shows that the insula, but not the primary or secondary somatosensory region (SI or SII), may be the cortical target for visceral pain. Animal studies have also demonstrated that amygdala plays an important role in processing visceral pain. We used fMRI to study central projection of stomach pain from fundus balloon distension. We also tested the hypothesis that there will be neither S1 nor S2 activation, but amygdala activation with the fundus distension. A 3T-fMRI was performed on 10 healthy subjects during baseline, fullness (12.7 +/- 0.6 mmHg) and moderate gastric pain (17.0 +/- 0.8 mmHg). fMRI signal was modelled by convolving the predetermined psychophysical response. Statistical comparisons were performed between conditions on a group level. Gastric pain activated a wide range of cortical and subcortical structures, including thalamus and insula, anterior and posterior cingulate cortices, basal ganglia, caudate nuclei, amygdala, brain stem, cerebellum and prefrontal cortex (P < 0.001). A subset of these neuronal substrates was engaged in the central processing of fullness sensation. SI and SII were not activated during the fundus stimulation. In conclusion, the constellation of neuronal structures activated by fundus distension overlaps the pain matrices induced musculocutaneous pain, with the exception of the absence of SI or SII activation. This may account for the vague nature of visceral sensation/pain. Our data also confirms that the insula and amygdala may act as the central role in visceral sensation/pain, as well as in the proposed sensory-limbic model of learning and memory of pain.

Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores.

AIM: To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. METHODS: The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. RESULTS: The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, P<0.001; fasting insulin, 4.06+/-0.77 vs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). CONCLUSIONS: The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.

Differential effects of carboxyfullerene on MPP+/MPTP-induced neurotoxicity.

The effects of carboxyfullerene on a well-known neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenyl-pyridinium (MPP+) were investigated. In chloral hydrate-anesthetized rats, cytosolic cytochrome c was elevated in the infused substantia nigra 4 h after an intranigral infusion of MPP+. Five days after local application of MPP+, lipid peroxidation (LP) was elevated in the infused substantia nigra. Furthermore, dopamine content and tyrosine hydroxylase (TH)-positive axons were reduced in the ipsilateral striatum. Concomitant intranigral infusion of carboxyfullerene abolished the elevation in cytochrome c and oxidative injuries induced by MPP+. In contrast, systemic application of carboxyfullerene did not prevent neurotoxicity induced by intraperitoneal injection of MPTP. In mice, systemic administration of MPTP induced a dose-dependent depletion in striatal dopamine content. Simultaneous injection of carboxyfullerene (10 mg/kg) actually potentiated MPTP-induced reduction in striatal dopamine content. Furthermore, systemic administration of carboxyfullerene (30 mg/kg) caused death in the MPTP-treated mice. An increase in the striatal MPP+ level and reduction in hepatic P450 level were observed in the carboxyfullerene co-treated mice. These data showed that systemic application of carboxyfullerene appears to potentiate MPTP-induced neurotoxicity while local carboxyfullerene has been suggested as a neuroprotective agent. Furthermore, an increase in striatal MPP+ level may contribute to the potentiation by carboxyfullerene of MPTP-induced neurotoxicity.

MEG localization of rolandic spikes with respect to SI and SII cortices in benign rolandic epilepsy.

The purpose of this study was to study the relationship between interictal spike sources and somatosensory cortices in benign rolandic epilepsy of childhood (BREC) using a whole-scalp neuromagnetometer. We recorded spontaneous magnetoencephalography (MEG) and EEG signals and cortical somatosensory-evoked magnetic fields (SEFs) to electric stimulation of the median nerve in 9 children with BREC. Interictal rolandic discharges (RDs) and SEFs were analyzed by equivalent current dipole (ECD) modeling. Based on the orientation and locations of corresponding ECDs, we compared generators of RDs with primary (SI) and second somatosensory cortices (SII). Our results showed that RDs and SII responses had similar ECD orientation on the magnetic field maps. The ECDs of RDs were localized 15.3 +/- 1.9 and 12.2 +/- 2.8 mm anterior to SI and SII, respectively. The spatial distance on average from the location of RDs to SII (21.9 +/- 1.6 mm) cortex was significantly shorter than to SI cortex (29.7 +/- 1.7 mm) (P<0.01, Wilcoxon signed-rank test). In conclusion, the cortical generators for RDs in patients with BREC are localized in the precentral motor cortex, closer to hand SII than to SI cortex.

Magnetoencephalographic yield of interictal spikes in temporal lobe epilepsy. Comparison with scalp EEG recordings.

To compare magnetoencephalography (MEG) with scalp electroencephalography (EEG) in the detection of interictal spikes in temporal lobe epilepsy (TLE), we simultaneously recorded MEG and scalp EEG with a whole-scalp neuromagnetometer in 46 TLE patients. We visually searched interictal spikes on MEG and EEG channels and classified them into three types according to their presentation on MEG alone (M-spikes), EEG alone (E-spikes), or concomitantly on both modalities (M/E-spikes). The M-spikes and M/E-spikes were localized with MEG equivalent current dipole modeling. We analyzed the relative contribution of MEG and EEG in the overall yield of spike detection and also compared M-spikes with M/E-spikes in terms of dipole locations and strengths. During the 30- to 40-min MEG recordings, interictal spikes were obtained in 36 (78.3%) of the 46 patients. Among the 36 patients, most spikes were M/E-spikes (68.3%), some were M-spikes (22.1%), and some were E-spikes (9.7%). In comparison with EEG, MEG gave better spike yield in patients with lateral TLE. Sources of M/E- and M-spikes were situated in the same anatomical regions, whereas the average dipole strength was larger for M/E- than M-spikes. In conclusion, some interictal spikes appeared selectively on either MEG or EEG channels in TLE patients although more spikes were simultaneously identified on both modalities. Thus, simultaneous MEG and EEG recordings help to enhance spike detection. Identification of M-spikes would offer important localization of irritative foci, especially in patients with lateral TLE.

Genetic epistasis of adiponectin and PPARgamma2 genotypes in modulation of insulin sensitivity: a family-based association study.

AIMS/HYPOTHESIS: Genetic interactions in modulating the phenotypes of a complex trait, such as insulin sensitivity, were usually taken for granted. However, this has not been commonly shown. Previous studies have suggested that both PPARgamma2 and adiponectin genes could influence insulin sensitivity. Therefore it is likely that they could modulate insulin sensitivity through gene to gene interactions. METHODS: We genotyped 1793 subjects of Chinese and Japanese descendents from 601 hypertensive families recruited in Sapphire study for a T94G in the adiponectin gene exon 2 and the PPARgamma2 Pro12Ala polymorphisms. Serum insulin concentrations and insulin resistance index (HOMA(IR)) were used as the markers of insulin sensitivity. RESULTS: We found that the T allele of adiponectin gene was associated with a higher Ins60 and higher area under curve of insulin (AUCi) in OGTT utilizing all subjects in a mixed model that corrected for family effects. Important interactions between adiponectin and PPARgamma2 genotypes were found in fasting insulin concentrations (Ins0), insulin concentrations at 2-h (Ins120) in OGTT and insulin resistance index (HOMA(IR)). The main effects of the PPARgamma2 genotypes were in the plasma glucose concentrations in OGTT. In contrast, the main effects of adiponectin genotypes were in every insulin variable, including Ins0, Ins60, Ins120, AUCi and HOMA(IR). The subjects carrying the adiponectin G allele and the PPARgamma2 Ala12 allele seemed to be more insulin sensitive. CONCLUSION/INTERPRETATION: These results showed that adiponectin is a genetic factor associated with insulin sensitivity. Interactions with PPARgamma2 genotypes modified this association.

Magnetoencephalographic study of rhythmic mid-temporal discharges in non-epileptic and epileptic patients.

To evaluate the source location and clinical significance of rhythmic mid-temporal theta discharges (RMTD) by MEG in non-epileptic and epileptic patients, we conducted simultaneous MEG and EEG recordings with a whole-scalp 306-channel neuromagnetometer in three patients: one with right temporal lobe epilepsy (TLE), one with right frontal lobe epilepsy (FLE), and one with tension headache. We visually detected the RMTD activity and interictal spikes, and then localised their generators by MEG source modelling. We repeated MEG measurement 3 months after right anterior temporal lobectomy (ATL) in the TLE patient; 3 months after anticonvulsant medication in the FLE patient. In epileptic patients, RMTD activities were found during drowsiness over the left temporal channels of both MEG and EEG recordings, and their generators were localised to the left posterior inferior temporal region. In the patient with tension headache, RMTD was localised in the right inferior temporal area. When the epileptic patients became seizure free with disappearance of epileptic spikes, RMTD was still found over the left temporal channels. Besides, some bursts of RMTD appeared also in the right temporal channels in our TLE patient after ATL. Our results indicate that the source of RMTD activity is located in the fissural cortex of the posterior inferior temporal region. As a physiologic rhythm related to dampened vigilance, RMTD has no direct relation to epileptogenic activity.