Burden of depressive symptoms and non-alcohol substance abuse; and their association with alcohol use and partner violence: a cross-sectional study in four sub-Saharan Africa countries.

In sub-Saharan Africa, there are limited data on burden of non-alcohol substance abuse (NAS) and depressive symptoms (DS), yet potential risk factors such as alcohol and intimate partner violence (IPV) are common and NAS abuse may be the rise. The aim of this study was to measure the burden of DS and NAS abuse, and determine whether alcohol use and IPV are associated with DS and/or NAS abuse. We conducted a cross-sectional study at five sites in four countries: Nigeria (nurses), South Africa (teachers), Tanzania (teachers) and two sites in Uganda (rural and peri-urban residents). Participants were selected by simple random sampling from a sampling frame at each of the study sites. We used a standardized tool to collect data on demographics, alcohol use and NAS use, IPV and DS and calculated prevalence ratios (PR). We enrolled 1415 respondents and of these 34.6% were male. DS occurred among 383 (32.3%) and NAS use among 52 (4.3%). In the multivariable analysis, being female (PR  =  1.49, p  =  0.008), NAS abuse (PR  =  2.06, p  =  0.02) and IPV (PR  =  2.93, p < 0.001) were significantly associated with DS. Older age [odds ratio (OR) = 0.31, p < 0.001)], female (OR = 0.48, p  =  0.036) were protective of NAS but current smokers (OR = 2.98, p < 0.001) and those reporting IPV (OR  =  2.16, p  =  0.024) were more likely to use NAS. Longitudinal studies should be done to establish temporal relationships with these risk factors to provide basis for interventions.

Risk of cardiovascular disease among teachers in Cape Town: Findings of the South African PaCT pilot study.

BACKGROUND: The accelerating epidemic of cardiovascular disease (CVD) and other non-communicable diseases (NCDs) highlights the need to establish long-term cohort studies in Africa. OBJECTIVE: The Partnership for Cohort Research and Training (PaCT) seeks to study NCDs in South Africa (SA), Uganda, Tanzania and Nigeria on a long-term basis. Pilot studies at each site have tested feasibility. The SA site additionally studied the prevalence of CVD risk factors and categorised participants' 10-year predicted risk of a cardiovascular event. METHODS: We enrolled teachers from 111 public schools in the Metro South Education District in Cape Town, SA, between January 2011 and May 2012. Participants completed a self-administered questionnaire and biological measurements, and chose post or email for 6-month follow-up. RESULTS: The participation of schools was permitted by 53.2% of principals, and 489 of 1 779 teachers agreed to participate. Of teachers willing to participate in the follow-up, 52% were retained, three-quarters by post and a quarter by email. Their mean age was 46.3 years and 70.3% were female. The prevalence of CVD risk factors was high and featured hypertension (48.5%), hypercholesterolaemia (20.5%), smoking (18.0%), diabetes (10.1%) and chronic kidney disease (10.4%), while 84.7% were overweight or obese. Of the participants, 18.7% were at high risk of a heart attack or stroke within 10 years. CONCLUSION: Establishing a cohort study among teachers has challenges but also opportunities for addressing CVD, which will soon impose a substantial burden on Cape Town's education system.

Targeted gene delivery of BMPR2 attenuates pulmonary hypertension.

Pulmonary arterial hypertension (PAH) remains a fatal disease despite modern pharmacotherapy. Mutations in the gene for bone morphogenetic protein receptor type II (BMPR2) lead to reduced BMPR2 expression, which is causally linked to PAH. BMPR2 is predominantly expressed on pulmonary endothelium and has complex interactions with transforming growth factor (TGF)-ß signalling mechanisms. Our objectives were to assess the effect on PAH of upregulating BMPR2 by targeted adenoviral BMPR2 gene delivery to the pulmonary vascular endothelium. We used two established rat models of PAH: chronic hypoxia and monocrotaline (MCT). In both hypertensive models, those receiving BMPR2 had less right ventricular hypertrophy, less pulmonary vascular resistance, improved cardiac function and reduced vascular remodelling. In the MCT model, there was an increase in TGF-ß, which was prevented by BMPR2 treatment. In vitro, TGF-ß1-induced endothelial-mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cells, which was associated with reduced BMPR2 expression. EndMT was partially ameliorated by stimulating BMPR2 signalling with appropriate ligands even in the ongoing presence of TGF-ß1. Collectively, these results indicate therapeutic potential for upregulation of the BMPR2 axis in PAH, which may be, in part, mediated by countering the remodelling effects of TGF-ß.

Advancing public health genomics in Africa through prospective cohort studies.

Human genomic studies have revolutionised science in high-income countries through large cohort studies (on the order of 100,000+ participants) which examine a multitude of risk factors. Yet Africa, with the most genetically diverse population in the world, large burdens of communicable and non-communicable diseases, and unique environments and risk factors, has no such large studies which comprehensively examine multiple interacting risk factors for disease. We argue that establishing such studies is overdue. Scientific discoveries from large cohort studies can drive innovation, foster training and local capacity building, and provide vital evidence for public health decision making. Furthermore, evidence from studies in Africa could provide insights to disease processes relevant to other populations around the globe. The enormous potential for genetic and epidemiologic discovery in Africa should not continue to go untapped. Combining powerful genomic tools with epidemiology through large cohort studies could dramatically advance public health in Africa.

Choline and betaine intake and risk of breast cancer among post-menopausal women.

BACKGROUND: Choline and betaine, similar to folate, are nutrients involved in one-carbon metabolism and hypothesised to reduce breast cancer risk. No prospective study among post-menopausal women has examined choline and betaine intakes in relation to breast cancer risk. METHODS: We examined the intake of choline and betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses' Health Study. Nutrient intake was assessed using a validated food-frequency questionnaire six times since 1984. During 20 years of follow-up from 1984 until 2004, we documented 3990 incident cases of invasive breast cancer. RESULTS: Overall, choline (mean+/-s.d.; 326+/-61 mg per day) and betaine (104+/-33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer. Participants in the highest quintile of intakes had multivariate relative risks of 1.10 (95% confidence interval (95% CI): 0.99-1.22; P-value, test for trend=0.14) for choline and 0.98 (95% CI: 0.89-1.09; P-value, test for trend=0.96) for betaine, compared with those in the lowest quintiles of intakes. The results were similar in breast cancer stratified by hormone receptor (oestrogen receptor/progesterone receptor) status. The association between choline intake and breast cancer risk did not differ appreciably by alcohol intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk factors, including family history of breast cancer, history of benign breast disease, body mass index, post-menopausal hormone use, and folate intake. CONCLUSION: We found no evidence that higher intakes of choline and betaine reduce risk of breast cancer among post-menopausal women.

Validation of a food frequency questionnaire measurement of selected nutrients using biological markers in African-American men.

OBJECTIVE: To validate selected nutrients assessed by the food frequency questionnaire (FFQ) used in the Harvard cohort studies in an African-American group. DESIGN: Blood aliquots were pooled for each decile of intake of two carotenoids and alpha tocopherol as measured by FFQ. These pooled samples were analyzed for nutrient content, and the resultant blood levels were plotted against the median for each decile of intake. In addition, adipose tissue samples taken from each man were analyzed for content of specific fatty acids. We calculated the Spearman correlations comparing intakes of specific fatty acids as percent of total fat intake, adjusted for energy intake, as measured by FFQ, with the percentage of the corresponding fatty acid in adipose tissue. SUBJECTS AND SETTINGS: African-American men (N=104) with prostate cancer were recruited from a Detroit physician's practice and completed a detailed FFQ. RESULTS: Comparing decile 10 with decile 1 intake of nutrients as measured by FFQ, there was a 32% higher blood level of lycopene, a 288% higher blood level of beta carotene and a 100% higher blood level of alpha tocopherol. The Spearman correlation coefficients between intakes of linoleic acid, alpha linolenic acid, long-chain n-3 fatty acids and trans fatty acid measured by FFQ and the corresponding adipose tissue levels were between 0.10 and 0.47. CONCLUSION: The FFQ was able to distinguish meaningful differences in biochemical measurements of selected nutrients and presumably corresponding differences in the extremes of intake in African-American men with prostate cancer who were likely to be motivated to report accurately. However, the results found are similar to those found in other populations.

Infraslow oscillations modulate excitability and interictal epileptic activity in the human cortex during sleep.

Human cortical activity has been intensively examined at frequencies ranging from 0.5 Hz to several hundred Hz. Recent studies have, however, reported also infraslow fluctuations in neuronal population activity, magnitude of electroencephalographic oscillations, discrete sleep events, as well as in the occurrence of interictal events. Here we use direct current electroencephalography to demonstrate large-scale infraslow oscillations in the human cortex at frequencies ranging from 0.02 to 0.2 Hz. These oscillations, which are not detectable in conventional electroencephalography because of its limited recording bandwidth (typical lower limit 0.5 Hz), were observed in widespread cortical regions. Notably, the infraslow oscillations were strongly synchronized with faster activities, as well as with the interictal epileptic events and K complexes. Our findings suggest that the infraslow oscillations represent a slow, cyclic modulation of cortical gross excitability, providing also a putative mechanism for the as yet enigmatic aggravation of epileptic activity during sleep.

Topography and elimination of slow EEG responses related to tongue movements.

This study aimed to characterize the topography and mechanism of slow EEG potentials related to tongue movement (TMP), and to devise a method for their elimination. Eight adult subjects were recorded with 8-channel direct current (DC) EEG (n = 5) or with a 256-channel, dense array EEG (n = 4). Subjects were requested to push their tongue toward the incisors in a closed mouth. We examined the time course and topography of the ensuing TMP. The underlying mechanism and elimination of TMP were studied by electrical isolation of the tongue with a latex sheet, and by short-circuiting of tongue to gingival pouch. Forward movement of the tongue caused global changes in scalp potentials, with frontal areas more positive, and the strongest gradients between the mastoid region and other scalp areas. Scalp current source density was highest near ear canals and orbital fossae. Electrical isolation of the tongue tip with a latex sheet resulted in a near-complete elimination of TMPs, while short-circuiting resulted in high amplitude responses, suggesting that TMPs are caused by a change in the geometry of conductive pathways. Our results indicate that significant scalp potentials are caused by even modest tongue movements, which may occur subconsciously during various cognitive tasks. The topography and small amplitude of TMPs make their off-line rejection difficult, while an isolation method of the kind used here may substantially diminish TMP artifacts in studies on slow cognitive potentials.

Scalp-recorded slow EEG responses generated in response to hemodynamic changes in the human brain.

OBJECTIVE: To study whether hemodynamic changes in human brain generate scalp-EEG responses. METHODS: Direct current EEG (DC-EEG) was recorded from 12 subjects during 5 non-invasive manipulations that affect intracranial hemodynamics by different mechanisms: bilateral jugular vein compression (JVC), head-up tilt (HUT), head-down tilt (HDT), Valsalva maneuver (VM), and Mueller maneuver (MM). DC shifts were compared to changes in cerebral blood volume (CBV) measured by near-infrared spectroscopy (NIRS). RESULTS: DC shifts were observed during all manipulations with highest amplitudes (up to 250 microV) at the midline electrodes, and the most pronounced changes (up to 15 microV/cm) in the DC voltage gradient around vertex. In spite of inter-individual variation in both amplitude and polarity, the DC shifts were consistent and reproducible for each subject and they showed a clear temporal correlation with changes in CBV. CONCLUSIONS: Our results indicate that hemodynamic changes in human brain are associated with marked DC shifts that cannot be accounted for by intracortical neuronal or glial currents. Instead, the data are consistent with a non-neuronal generator mechanism that is associated with the blood-brain barrier. SIGNIFICANCE: These findings have direct implications for mechanistic interpretation of slow EEG responses in various experimental paradigms.

Age at focal epilepsy onset varies by sex and hemispheric lateralization.

BACKGROUND: Previous studies have shown that interictal epileptiform discharges favor the left hemisphere in adults but the right side in children up until age 5. This may be due to sex-influenced asymmetric brain maturation. To clarify this relationship, the authors analyzed age at epilepsy onset by sex and by lateralization of epileptiform activity. METHODS: An adult epilepsy center long-term monitoring database was used to define patients with exclusively unilateral epileptiform findings. Three groups were studied: any epileptiform activity (n = 404), ictal activity (n = 287), and interictal activity (n = 265). The second and third groups were drawn from the first group and the second and third groups overlapped with each other. Side of lateralized finding and sex were analyzed via factorial two-way analysis of variance with the outcome variable being age at epilepsy onset. Comparison analysis included patients with generalized epilepsy (n = 114), nonepileptic seizures (NES, n = 232), and surgical mesial temporal sclerosis (MTS, n = 116). RESULTS: Patients with unilateral epileptiform activity displayed bimodal epilepsy onset ages with infant and adolescent peaks. For patients with a right-sided focus, epilepsy onset was earlier in men (14.4 years) than women (20.7 years). In contrast, among patients with a left-sided focus, epilepsy began earlier in women (18.2 years) than men (19.9 years, p < 0.01). Parallel results were found in unilateral ictal (p < 0.01) and unilateral interictal activity (p = 0.01). Patients with surgical MTS, NES, or generalized seizure showed no similar patterns. CONCLUSIONS: In adult patients with focal epilepsy, sex and lateralized epileptiform abnormalities may be related to age at epilepsy onset.

Very slow EEG responses lateralize temporal lobe seizures: an evaluation of non-invasive DC-EEG.

BACKGROUND: This study tested the idea that very slow EEG responses (direct current [DC] potential shifts) could be detected noninvasively during temporal lobe (TL) seizures, and that these shifts give lateralizing information consistent with that obtained by other methods. METHODS: Seven patients with TL epilepsy (TLE) were recorded with scalp DC-EEG technique at bedside. All recordings were performed simultaneously with conventional EEG (scalp in five, and intracranially in two; two patients with scalp recordings were recorded intracranially later). Seizures in five patients originated in the mesial TL. Ictal DC shifts were evaluated by comparing them to the temporal evolution of ictal discharges, and by comparing the laterality of these shifts to the side of seizure onset defined by routine EEG and other presurgical diagnostic tests. RESULTS: All seizures (35/35) were associated with negative DC shifts at temporal derivations (30 to 150 micro V relative to vertex), beginning at the electrical seizure onset, and lasting for the whole seizure. In eight seizures (five patients) with documented mesial TL onset, the polarity of the DC shift was initially positive followed by a negative one after lateral spread of seizure activity. In all cases, the side of the EEG shift agreed with other diagnostic tests, and, at times, was more clearly lateralized than the conventional scalp EEG. CONCLUSIONS: DC-EEG recordings are practical and achievable at the bedside. Ictal DC shifts are consistently observed in scalp recordings in TL seizures, and reliably lateralize them. This method may hold promise in reducing the need for invasive monitoring in patients with TLE where other noninvasive tests are equivocal.

Singing seizures.

Automatisms are commonly seen in epilepsy, either ictally or postictally. However, most automatisms are simple, with hand movements, mouth smacking, nose-rubbing, repetition of a single word, or coughing, grunting, or screeching. Complex automatisms are less common and striking. The authors report two cases of seizure-associated singing where song expression may be recognizable.

Dietary fat, fat subtypes, and breast cancer risk: lack of an association among postmenopausal women with no history of benign breast disease.

A recent study among 13,707 postmenopausal women without benign breast disease (BBD) from the Breast Cancer Detection Demonstration Project (BCDDP) cohort found breast cancer risk associated with greater total fat, unsaturated fat, and oleic acid intake. We assessed the associations between cumulative averaged dietary intake from 1980, 1984, 1986, and 1990 with breast cancer risk through 1994 among 44,697 postmenopausal participants without BBD in the Nurses' Health Study (NHS). Multivariate Cox proportional hazard models, with age as the time variable, provided the estimated rate ratios (RRs) with 95% confidence intervals (CIs) from the 14 years of follow-up and the 1,071 breast cancer cases. In the Nurses' Health Study, breast cancer rates over the time period from 1980 to 1994 did not increase significantly with greater total fat [quintile (Q) 5 versus Q1 RR, 0.94; 95% CI, 0.77-1.15], saturated fat (RR(Q5 to Q1), 0.88; 95% CI, 0.70-1.12), unsaturated fat (RR(Q5 to Q1), 1.16; 95% CI, 0.92-1.46), oleic acid (RR(Q5 to Q1), 1.13; 95% CI, 0.81-1.57), linoleic acid (RR(Q5 to Q1), 0.93; 95% CI, 0.74-1.16), trans fatty acid (RR(Q5 to Q1), 0.9184; 95% CI, 0.73-1.13), or energy intake (RR(Q5 to Q1), 0.81; 95% CI, 0.67-0.99). A parallel analysis restricted to the same time period as the BCDDP study did not differ substantially. We found no increase in the rate of breast cancer with greater intake of dietary fat and fat subtypes among postmenopausal women without a history of BBD.

Is the left cerebral hemisphere more prone to epileptogenesis than the right?

PURPOSE: To determine if there is evidence that the left cerebral hemisphere is more prone to epileptogenesis than the right hemisphere. METHODS: We examined 532 patients with localization-related epilepsy, as documented by long-term EEG-video monitor studies. We identified those with interictal epileptiform patterns on EEG confined to one hemisphere, those with clinical seizures that arose only from one side, and individuals with neuropsychological deficits lateralizing more to one cerebral hemisphere than the other. These data were then related to the handedness of the subjects. RESULTS: For left-handed patients, interictal discharges were significantly more likely to be confined to the left side, seizures more frequently arose from only the left hemisphere, and neuropsychological deficits lateralized more often to the left brain. In contrast, for right-handed subjects, there were no significant differences in unilateral localization of either interictal discharges or of seizure onsets, nor did neuropsychological deficits lateralize more often to one side or the other. Although, as a group, left-handers had an earlier age of onset of epilepsy than right-handers, the lateralizing EEG and neuropsychological patterns seen in left-handers were not related to age of onset of epilepsy, febrile seizures, family history of either epilepsy or left-handedness, or other risk factors. CONCLUSION: In localization-related epilepsy, there is a significant association of left-handedness with left hemispheric lateralization of epileptiform EEG patterns and neuropsychological deficits. These findings do not clearly reflect a greater left than right cerebral hemispheric vulnerability to epileptogenesis, except possibly in left-handers.

Pre-protachykinin-A mRNA is increased in the airway epithelium of smokers with chronic bronchitis.

OBJECTIVE: Tachykinins are neuropeptides present in sensory nerves in the lung. Aside from their role as neurotransmitters, these peptides exert pro-inflammatory and protective effects in the airways. Although tachykinins may be released from sensory nerves, there is increasing evidence that they are also produced by non-neuronal cells. The net effect of tachykinins will likely result from relative changes in the levels of tachykinins, tachykinin receptors and tachykinin degrading enzymes. We investigated whether tachykinins might be produced locally in human airway epithelium in vivo, and whether mRNA levels for either tachykinins, their receptors, or for the tachykinin degrading enzyme neutral endopeptidase (NEP) were altered in subjects with chronic bronchitis compared to normals. METHODOLOGY: We used reverse transcription polymerase chain reaction analysis of brush biopsy samples to detect mRNAs of interest. We then developed a semi-quantitative approach to compare subject groups. RESULTS: We detected a signal for preprotachykinin A (PPT-A) mRNA as well as for tachykinin receptors and NEP in patients with airways disease and normal subjects. We found a relative 10-fold increase in PPT-A mRNA in smokers with chronic bronchitis, along with similar increases in mRNA for the inflammatory markers intercellular adhesion molecule-1 and interleukin-8. In contrast, NEP and NK1 tachykinin receptor mRNA levels were not different between the groups. CONCLUSION: These findings imply that up-regulation of tachykinin production by cells present in the airway epithelium contributes to the pathophysiology of chronic bronchitis.

A novel system for mitigation of ectopic transgene expression induced by adenoviral vectors.

Adenoviral (Ad) vectors are good candidates for gene therapy in view of their high in vivo gene delivery efficiency. However, greater control over the tissue distribution of transgene expression is required to avoid potentially deleterious effects in non-target organs. In this regard, the liver is particularly at risk due to the high natural tropism of Ad for this organ, where dose limiting toxicity has been seen due to toxic transgene expression. We hypothesized that the cre/loxP system could be utilized to reduce unintended transgene expression at this site. This concept was tested using an Ad vector (AdLCLLL) carrying a reporter gene cassette in which the promoter and luciferase gene were flanked by LoxP sequences. Co-administration of this vector with a second vector carrying the cre recombinase gene in vitro and in vivo resulted in specific down-regulation of transgene expression. This novel approach thus has the potential to improve the safety of gene therapy strategies that rely upon the delivery of genes which may be hepatotoxic.

The absence of interictal spikes with documented seizures suggests extratemporal epilepsy.

PURPOSE: To determine the demographic and clinical characteristics of patients who have documented epileptic seizures on long-term video-EEG monitoring who do not have interictal spikes. METHODS: The records of 1,223 monitoring studies from 919 patients who underwent noninvasive long-term video-EEG monitoring were reviewed. In 28 patients (3.0% of monitored patients, 4.4% of patients with electrographic evidence of epilepsy), no interictal spikes were found despite the occurrence of at least one recorded electrographic seizure. The demographic, medical, neuropsychological, and EEG data of these patients were compared with those of 28 matched control patients with documented interictal spikes. RESULTS: Extratemporal seizures were significantly more frequent in the patients with at least one recorded epileptic seizure but without interictal spikes compared with patients with epileptic seizures and interictal spikes (p = 0.031). The only other significant difference between the groups (p = 0.016) was a later age at seizure onset (18.3 vs. 10.7 years) for the patients without interictal spikes. Age at evaluation, gender, handedness, clinical seizure type, family history of epilepsy, history of febrile seizures, neuropsychological testing, and neurologic and psychiatric history did not differ between the two groups. CONCLUSIONS: In patients with documented epilepsy without interictal spikes on EEG monitoring, the possibility of an extratemporal focus should be considered.

Tachykinin-induced bronchoconstriction in sheep is NK-1 receptor mediated and exhibits tachyphylaxis.

OBJECTIVE: Tachykinins are mediators of airway hyper-reactivity and inflammation. There is in vitro evidence that ovine responses to tachykinins correlate closely to human responses. This study was designed to characterize the effect of intravenously administered tachykinins on sheep lung resistance in vivo to determine the effect of dose timing on reproducibility of responses and the induction of tachyphylaxis. We then used this information to help further characterize the response with several pharmacological agents. METHODOLOGY: Substance P (SP) was administered by infusion to conscious merino ewes and lung resistance (RL) was measured. Infusions were given at 30, 60, 120 min and 24 h intervals. The effect of various agents on the response to SP was then assessed. RESULTS: Substance P led to a transient increase in RL, mean (+/- SEM) 754.8 (+/- 139)% of baseline, with marked tachyphylaxis at 30, 60 and 120 min. Phosphoramidon increased the peak response to 1151.5 +/- 196%. Atropine and CP 96 345 abolished the response to SP, while indomethacin, sodium cromoglycate and pyrilamine had no significant effect. Substance P had a greater effect on RL than did neurokinin A. CONCLUSIONS: Substance P increases RL in sheep via a cholinergic mechanism which is mediated by NK-1 receptors, and is subject to tachyphylaxis. These findings have implications for the design of studies using the ovine model in the evaluation of tachykinin antagonists as potential therapeutic agents.

Dietary glycemic load assessed by food-frequency questionnaire in relation to plasma high-density-lipoprotein cholesterol and fasting plasma triacylglycerols in postmenopausal women.

BACKGROUND: In metabolic studies, both greater carbohydrate intakes and higher glycemic indexes (GIs) raise fasting triacylglycerol concentrations. In epidemiologic studies, dietary glycemic load (GL) is positively associated with risk of coronary artery disease and type 2 diabetes. OBJECTIVE: We examined both the physiologic relevance of GI and GL and the ability of dietary questionnaires to measure these variables. DESIGN: In the Nurses' Health Study, we measured plasma triacylglycerol concentrations in fasting blood samples from 185 healthy postmenopausal women and HDL-cholesterol concentrations in an additional 95 nonfasting samples. Dietary carbohydrate, GI, and GL were assessed by use of semiquantitative food-frequency questionnaires. The cross-sectional associations between these 3 variables and plasma triacylglycerol and HDL were assessed, with adjustment for potential confounding factors. RESULTS: For the lowest and highest quintiles of GL, the multivariate-adjusted geometric mean triacylglycerol concentrations were 0.98 and 1.75 mmol/L (87 and 155 mg/dL; P for trend < 0.001). Both overall GI (P for trend = 0.03) and carbohydrate (P for trend < 0.01) contributed independently to the strong positive association between GL and fasting triacylglycerol concentrations. GL was also inversely associated with HDL-cholesterol concentrations. For the lowest and highest quintiles of GL, the mean HDL-cholesterol concentrations were 1.50 and 1.34 micromol/L (58 and 52 mg/dL; P for trend = 0.03). The relation between GL and fasting triacylglycerol concentrations differed significantly by body mass index (BMI; in kg/m(2)) categories (P < 0.001 for interaction). For the lowest to the highest quintiles of GL, the mean triacylglycerol concentrations were 0.92 and 2.24 mmol/L (81 and 198 mg/dL) in women with BMIs > 25 (P for trend < 0.001) and 1.02 and 1.42 mmol/L (90 and 126 mg/dL) in women with BMIs < or = 25 (P for trend < 0.001). CONCLUSION: These data support the physiologic relevance of the GL as a potential risk factor for coronary artery disease in free-living women, particularly those prone to insulin resistance. These findings also document the ability of a semiquantitative food-frequency questionnaire to assess dietary GIs and GLs.

Interictal, unifocal spikes in refractory extratemporal epilepsy predict ictal origin and postsurgical outcome.

OBJECTIVES: To evaluate the significance of exclusively unifocal, unilateral, interictal epileptiform patterns on scalp electroencephalography (EEG) in surgical candidates with medically intractable extratemporal epilepsy. METHODS: We reviewed 126 patients with refractory extratemporal partial seizures who underwent epilepsy surgery at our center. All were followed for at least 2 years after resections. Surgery was based on ictal EEG recordings. We examined ictal onsets and surgical outcome in subjects whose preoperative, interictal scalp EEGs during long-term monitoring (LTM) demonstrated only unilateral, well-defined focal discharges, and outcome in patients whose interictal EEGs during LTM showed bilateral, non-localized, or multifocal epileptiform patterns. RESULTS: We found that 26 subjects exhibited only unilateral, unifocal, interictal epileptiform patterns. In all 26 cases (100%) clinical seizures arose from the regions expected by the interictal findings (P<0.0001, Sign test). At last follow-up 77% (20/26) of these patients were seizure-free, while 23% (6/26) had >75% reduction in seizures. This compares to the remaining patients, of whom 34% (34/100) were seizure-free, 41% (41/100) had >75% reduction in seizures, and 25% (25/100) had <75% reduction in seizures (P=0.0001, Fisher's Exact test). CONCLUSIONS: Strictly unifocal, interictal epileptiform patterns on scalp EEG, though seen in a minority of subjects, may be an important, independent factor in evaluating subjects with intractable extratemporal, localization-related epilepsy for surgical therapy. This finding is highly predictive of both ictal onsets and successful postsurgical outcome.