A synergistic relationship of elevated low-density lipoprotein cholesterol levels and systolic blood pressure with coronary artery calcification

We sought to evaluate this ""response-to-injury"" hypothesis of atherosclerosis by studying the interaction between systolic blood pressure (SBP) and LDL-cholesterol (LDL-C) in predicting the presence of coronary artery calcification (CAC) in asymptomatic men. We Studied 526 men (46 +/- 7 years of age) referred for electron-beam tomography (EBT) exam. The prevalence of CAC was determined across LDL-C tertiles (low: <115 mg/dl; middle: 115-139 mg/dl high: >= 140 mg/dl) within tertiles of SBP (low: <121 mmHg; middle: 121-130 mmHg; high: >= 131 mmHg). CAC was found in 220 (42%) men. There was no linear trend in the presence of CAC across LDL-C tertiles in the low (p = 0.6 for trend) and middle (p = 0.3 for trend) SBP tertile groups, respectively. In contrast, there was a significant trend for increasing CAC with increasing LDL-C (1st: 44%; 2nd: 49%; 3rd: 83%; p < 0.0001 for trend) in the high SBP tertile group. In multivariate logistic analyses (adjusting for age, smoking, triglyceride levels, HDL-cholesterol levels, body mass index, and fasting glucose levels), the odds ratio for any CAC associated with increasing LDL-C was significantly higher in those with highest SBP levels, whereas no such relationship was observed among men with SBP in the lower two tertiles. An interaction term (LDL-C x SBP) incorporated in the multivariate analyses was statistically significant (p = 0.038). The finding of an interaction between SBP and LDL-C relation to CAC in asymptomatic men support the response-to-injury model of atherogenesis. (C) 2007 Elsevier Ireland Ltd. All rights reserved.

Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock

Background: Calcium is one of the triggers involved in ischemic neuronal death. Because hypotension is a strong predictor of outcome in traumatic brain injury (TBI), we tested the hypothesis that early fluid resuscitation blunts calcium influx in hemorrhagic shock associated to TBI. Methods: Fifteen ketamine-halothane anesthetized mongrel dogs (18.7 kg +/- 1.4 kg) underwent unilateral cryogenic brain injury. Blood was shed in 5 minutes to a target mean arterial pressure of 40 mm Hg to 45 mm Hg and maintained at these levels for 20 minutes (shed blood volume = 26 mL/kg +/- 7 mL/kg). Animals were then randomized into three groups: CT (controls, no fluid resuscitation), HS (7.5% NaCl, 4 mL/kg, in 5 minutes), and LR (lactate Ringer`s, 33 mL/kg, in 15 minutes). Twenty minutes later, a craniotomy was performed and cerebral biopsies were obtained next to the lesion (""clinical penumbra"") and from the corresponding contralateral side (""lesion`s mirror"") to determine intracellular calcium by fluorescence signals of Fura-2-loaded cells. Results: Controls remained hypotensive and in a low-flow state, whereas fluid resuscitation improved hemodynamic profile. There was a significant increase in intracellular calcium in the injured hemisphere in CT (1035 nM +/- 782 nM), compared with both HS (457 nM +/- 149 nM, p = 0.028) and LR (392 nM +/- 178 nM, p = 0.017), with no differences between HS and LR (p = 0.38). Intracellular calcium at the contralateral, uninjured hemisphere was 438 nM +/- 192 nM in CT, 510 nM +/- 196 nM in HS, and 311 nM +/- 51 nM in LR, with no significant differences between them. Conclusion: Both small volume hypertonic saline and large volume lactated Ringer`s blunts calcium influx in early stages of TBI associated to hemorrhagic shock. No fluid resuscitation strategy promotes calcium influx and further neural damage.

Angioplasty and Stent Placement in Symptomatic Internal Carotid Occlusion

PURPOSE: To report a series of patients with symptomatic internal carotid artery (ICA) occlusion treated with angioplasty and stents. MATERIALS AND METHODS: From a consecutive series of 50 patients experiencing neurologic ischemic symptoms and shown by conventional ultrasonography (US) to have a total ICA occlusion, 16 patients (ages 45-79 years; mean, 63 y; 10 men) were selected between August 2006 to September 2008 to be treated with angioplasty based on discovery of an open ICA distal to the occlusion through contrast-enhanced echo Doppler imaging and/or multislice contrast computed tomography (CT). Angioplasty and stent placement were performed under cerebral protection. Follow-up duplex imaging was performed at 14 days and 3 months and every 6 months thereafter and CT follow-up was performed at 2-9 months; the mean follow-up period was 9.9 months. RESULTS: Lesion crossing and stent placement was successful in 13 of 16 patients. There were no deaths, conversions, cardiac complications, or major strokes. One patient had a transient mild hemiparesis in the upper limb, with total recovery in 3 months. At follow-up, all 13 patients with a good initial result remained with patent arterial lumens and resolution of neurologic ischemic symptoms. After 2-9 months, ICAs with a ""string sign"" had calibers close or equal to those of normal arteries. CONCLUSIONS: Angioplasty with stent placement is an effective treatment with a low morbidity rate for selected patients who continue to experience neurologic ischemic symptoms despite US findings of total occlusion of the ICA.

Asbestos-related Disease Progression of Parenchymal Abnormalities on High-resolution CT

Purpose: To evaluate the changes over time in the pattern and extent of parenchymal abnormalities in asbestos-exposed workers after cessation of exposure and to compare 3 proposed semiquantitative methods with a careful side-by-side comparison of the initial and the follow-Lip computed tomography (CT) images. Materials and Methods: The study included 52 male asbestos workers (mean age SD, 62.2y +/- 8.2) who had baseline high-resolution CT after cessation of exposure and follow-up CT 3 to 5 years later. Two independent thoracic radiologists quantified the findings according to the scoring systems proposed by Huuskonen, Gamsu, and Sette and then did a side-by-side comparison of the 2 sets of scans without awareness of the dates of the CT scans. Results: There was no difference in the prevalence of the 2 most common parenchymal abnormalities (centrilobular small dotlike or branching opacities and interstitial lines) between the initial and follow-up CT scans. Honeycombing (20%) and traction bronchiectasis and bronchiolectasis (50%) were seen more commonly on the follow-up CT than on the initial examination (10% and 33%, respectively) (P = 0.01). Increased extent of parenchymal abnormalities was evident on side-by-side comparison in 42 (81%) patients but resulted in an increase in score in at least 1 semiquantitative system in only 16 (31%) patients (all P > 0.01, signed test). Conclusions: The majority of patients with previous asbestos exposure show evidence of progression of disease on CT at 3 to 5 years follow-up but this progression is usually not detected by the 3 proposed semiquantitative scoring schemes.

Age-related gray matter volume changes in the brain during non-elderly adulthood

Previous magnetic resonance imaging (MRI) studies described consistent age-related gray matter (GM) reductions in the fronto-parietal neocortex, insula and cerebellum in elderly subjects, but not as frequently in limbic/paralimbic structures. However, it is unclear whether such features are already present during earlier stages of adulthood, and if age-related GM changes may follow non-linear patterns at such age range. This voxel-based morphometry study investigated the relationship between GM volumes and age specifically during non-elderly life (18-50 years) in 89 healthy individuals (48 males and 41 females). Voxelwise analyses showed significant (p < 0.05, corrected) negative correlations in the right prefrontal cortex and left cerebellum, and positive correlations (indicating lack of GM loss) in the medial temporal region, cingulate gyrus, insula and temporal neocortex. Analyses using ROI masks showed that age-related dorsolateral prefrontal volume decrements followed non-linear patterns, and were less prominent in females compared to males at this age range. These findings further support for the notion of a heterogeneous and asynchronous pattern of age-related brain morphometric changes, with region-specific non-linear features. (C) 2009 Elsevier Inc. All rights reserved.

From EEG to BOLD: Brain mapping and estimating transfer functions in simultaneous EEG-fMRI acquisitions

Simultaneous acquisition of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) aims to disentangle the description of brain processes by exploiting the advantages of each technique. Most studies in this field focus on exploring the relationships between fMRI signals and the power spectrum at some specific frequency bands (alpha, beta, etc.). On the other hand, brain mapping of EEG signals (e.g., interictal spikes in epileptic patients) usually assumes an haemodynamic response function for a parametric analysis applying the GLM, as a rough approximation. The integration of the information provided by the high spatial resolution of MR images and the high temporal resolution of EEG may be improved by referencing them by transfer functions, which allows the identification of neural driven areas without strong assumptions about haemodynamic response shapes or brain haemodynamic`s homogeneity. The difference on sampling rate is the first obstacle for a full integration of EEG and fMRI information. Moreover, a parametric specification of a function representing the commonalities of both signals is not established. In this study, we introduce a new data-driven method for estimating the transfer function from EEG signal to fMRI signal at EEG sampling rate. This approach avoids EEG subsampling to fMRI time resolution and naturally provides a test for EEG predictive power over BOLD signal fluctuations, in a well-established statistical framework. We illustrate this concept in resting state (eyes closed) and visual simultaneous fMRI-EEG experiments. The results point out that it is possible to predict the BOLD fluctuations in occipital cortex by using EEG measurements. (C) 2010 Elsevier Inc. All rights reserved.

Peritumoral brain edema in benign meningiomas: correlation with clinical, radiologic, and surgical factors and possible role on recurrence

Background: Approximately 60% of meningiomas are associated with peritumoral edema. Various causative factors have been discussed in the literature. The objective of this study was to investigate the correlation of PTBE with clinical, radiologic, and surgical aspects and recurrence of meningiomas. Methods: Sixty-one patients with benign meningiomas were chosen for surgical treatment by the Group of Brain Tumors and Metastasis of the Department of Neurosurgery. All patients underwent complete surgical resection (Simpson grades I and 2), and those with atypical and malignant histopathologic grades were excluded. Tumors located in the cavernous sinus, tuberculum sellae, foramen magnum, ventricles, and petroclival region were excluded. Results: Edema extension had a positive correlation with the higher recurrence rates (P=.042) and with the presence of irregular margins (P<.011) on bivariate analysis. Meningiomas with larger edema sizes also showed correlation with large meningiomas (P=.035), and the ones with smaller edema sizes correlated with the tentorial location (P=.032). Multivariate analysis showed an association between PTBE and the presence of seizures (odds ratio, 3.469), large meningiomas (odds ratio, 15.977), and for each cubic centimeter added to its size, the risk of edema increased 1.082 times (odds ratio). Conclusion: Peritumoral brain edema may be related to the invading potential of meningiomas and may play a role in the recurrence potential of the tumor. As a consequence, it is reasonable to consider the presence of edema as an additional factor to be taken into account when mapping out strategies for the treatment of meningiomas. (C) 2008 Elsevier Inc. All rights reserved.

Screening Anal Dysplasia in HIV-Infected Patients: Is There an Agreement Between Anal Pap Smear and High-Resolution Anoscopy-Guided Biopsy?

PURPOSE: The purpose of this study was to analyze the agreement between anal Pap smear and high-resolution anoscopy-guided biopsy in diagnosing anal dysplasia in HIV-infected patients. METHODS: We conducted cross-sectional analysis of HIV-infected patients receiving anal dysplasia screening as part of routine care. Agreement between measures was estimated by weighted kappa statistics, using a three-tiered cytologic and histologic grading system (normal, low-grade dysplasia, and high-grade dysplasia). Estimates of sensitivity, specificity, and predictive values were calculated using a two-tiered cytologic and histologic grading system (""without dysplasia"" and ""with dysplasia of any grade""). Estimates were also calculated for the detection of high-grade dysplasia. RESULTS: During a one-year period, 222 patients underwent 330 anal Pap smears followed by high-resolution anoscopy-guided biopsies. There were 311 satisfactory Pap smears with concurrent biopsies. Considering histology the standard, the frequency of anal dysplasia was 46%. Kappa agreement between anal Pap smear and biopsy was 0.20. For detection of anal dysplasia of any grade, anal Pap smear showed sensitivity of 61%, specificity of 60%, positive predictive value of 56%, and negative predictive value of 64%. For high-grade dysplasia, anal Pap smear showed sensitivity of 16% and specificity of 97%. CONCLUSION: Anal Pap smears alone were not sensitive enough to rule out anal dysplasia. We recommend that high-resolution anoscopy-guided biopsy be incorporated as a complementary screening test for anal dysplasia in high-risk patients. Following baseline high-resolution anoscopy, these individuals could be followed with serial anal cytology to dictate the need for future high-resolution anoscopy-guided biopsies.

Comparison of Fourier-Domain and Time-Domain Optical Coherence Tomography in the Detection of Band Atrophy of the Optic Nerve

PURPOSE: To compare the ability of Fourier-domain (FD) optical coherence tomography (3D OCT-1000; Top, con, Tokyo, Japan) and time domain (TD) OCT (Stratus; Carl Zeiss Meditec Inc, Dublin, California, USA) to detect axonal loss in eyes with band atrophy (BA) of the optic nerve. DESIGN: Cross-sectional study. METHODS: Thirty-six eyes from 36 patients with BA and temporal visual field (VF) defect from chiasmal compression and 36 normal eyes were studied. Subjects were submitted to standard automated perimetry and macular and retinal nerve fiber layer (RNFL) measurements were taken using 3D OCT-1000 and Stratus OCT. Receiver operating characteristic (ROC) curves were calculated for each parameter. Spearman correlation coefficients were obtained to evaluate the relationship between RNFL and macular thickness parameters and severity of VF loss. Measurements from the two devices were compared. RESULTS: Regardless of OCT device, all RNFL and macular thickness parameters were significantly lower in eyes with BA compared with normal eyes, but no statistically significant difference was found with regard to the area under the ROC curve. Structure-function relationships were also similar for the two devices. In both groups, RNFL and macular thickness measurements were generally and in some cases significantly smaller with 3D OCT-1000 than with Stratus OCT. CONCLUSIONS: The introduction of FD technology did not lead to better discrimination ability for detecting BA of the optic nerve compared with TD technology when using the software currently provided by the manufacturer. 3D OCT-1000 FD OCT RNFL and macular measurements were generally smaller than TD Stratus OCT measurements. Investigators should be aware of this fact when comparing measurements obtained with these two devices. (Am J Oplathalmol 2009;147: 56-63. (c) 2009 by Elsevier Inc. All rights reserved.)

Pulmonary lesion induced by low and high positive end-expiratory pressure levels during protective ventilation in experimental acute lung injury

Objective: To investigate the effects of low and high levels of positive end-expiratory pressure (PEEP), without recruitment maneuvers, during lung protective ventilation in an experimental model of acute lung injury (ALI). Design: Prospective, randomized, and controlled experimental study. Setting: University research laboratory. Subjects: Wistar rats were randomly assigned to control (C) [saline (0.1 ml), intraperitoneally] and ALI [paraquat (15 mg/kg), intra peritoneally] groups. Measurements and Main Results: After 24 hours, each group was further randomized into four groups (six rats each) at different PEEP levels = 1.5, 3, 4.5, or 6 cm H(2)O and ventilated with a constant tidal volume (6 mL/kg) and open thorax. Lung mechanics [static elastance (Est, L) and viscoelastic pressure (Delta P2, L)] and arterial blood gases were measured before (Pre) and at the end of 1-hour mechanical ventilation (Post). Pulmonary histology (light and electron microscopy) and type III procollagen (PCIII) messenger RNA (mRNA) expression were measured after 1 hour of mechanical ventilation. In ALI group, low and high PEEP levels induced a greater percentage of increase in Est, L (44% and 50%) and Delta P2, L (56% and 36%) in Post values related to Pre. Low PEEP yielded alveolar collapse whereas high PEEP caused overdistension and atelectasis, with both levels worsening oxygenation and increasing PCIII mRNA expression. Conclusions: In the present nonrecruited ALI model, protective mechanical ventilation with lower and higher PEEP levels than required for better oxygenation increased Est, L and Delta P2, L, the amount of atelectasis, and PCIII mRNA expression. PEEP selection titrated for a minimum elastance and maximum oxygenation may prevent lung injury while deviation from these settings may be harmful. (Crit Care Med 2009; 37:1011-1017)

Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally (i.t.) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 mu g i.t.). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v.) or methylprednisolone (2 mg center dot kg(-1) i.v.) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.

Age-Related Metabolic Profiles in Cognitively Healthy Elders: Results from a Voxel-Based [(18)F]Fluorodeoxyglucose-Positron-Emission Tomography Study with Partial Volume Effects Correction

BACKGROUND AND PURPOSE: Functional brain variability has been scarcely investigated in cognitively healthy elderly subjects, and it is currently debated whether previous findings of regional metabolic variability are artifacts associated with brain atrophy. The primary purpose of this study was to test whether there is regional cerebral age-related hypometabolism specifically in later stages of life. MATERIALS AND METHODS: MR imaging and FDG-PET data were acquired from 55 cognitively healthy elderly subjects, and voxel-based linear correlations between age and GM volume or regional cerebral metabolism were conducted by using SPM5 in images with and without correction for PVE. To investigate sex-specific differences in the pattern of brain aging, we repeated the above voxelwise calculations after dividing our sample by sex. RESULTS: Our analysis revealed 2 large clusters of age-related metabolic decrease in the overall sample, 1 in the left orbitofrontal cortex and the other in the right temporolimbic region, encompassing the hippocampus, the parahippocampal gyrus, and the amygdala. The division of our sample by sex revealed significant sex-specific age-related metabolic decrease in the left temporolimbic region of men and in the left dorsolateral frontal cortex of women. When we applied atrophy correction to our PET data, none of the above-mentioned correlations remained significant. CONCLUSIONS: Our findings suggest that age-related functional brain variability in cognitively healthy elderly individuals is largely secondary to the degree of regional brain atrophy, and the findings provide support to the notion that appropriate PVE correction is a key tool in neuroimaging investigations.

Comparison of Different Spectral Domain Optical Coherence Tomography Scanning Areas for Glaucoma Diagnosis

Purpose: To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. Design: Diagnostic, case-control study. Participants: One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). Methods: All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. Main Outcome Measures: Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. Results: The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). Conclusions: The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

Individual vulnerability to escalated aggressive behavior by a low dose of alcohol: decreased serotonin receptor mRNA in the prefrontal cortex of male mice

Low to moderate doses of alcohol consumption induce heightened aggressive behavior in some, but not all individuals. Individual vulnerability for this nonadaptive behavior may be determined by an interaction of genetic and environmental factors with the sensitivity of alcohol`s effects on brain and behavior. We used a previously established protocol for alcohol oral self-administration and characterized alcohol-heightened aggressive (AHA) mice as compared with alcohol non-heightened (ANA) counterparts. A week later, we quantified mRNA steady state levels of several candidate genes in the serotonin [5-hydroxytryptamine (5-HT)] system in different brain areas. We report a regionally selective and significant reduction of all 5-HT receptor subtype transcripts, except for 5-HT(3), in the prefrontal cortex of AHA mice. Comparable gene expression profile was previously observed in aggressive mice induced by social isolation or by an anabolic androgenic steroid. Additional change in the 5-HT(1B) receptor transcripts was seen in the amygdala and hypothalamus of AHA mice. In both these areas, 5-HT(1B) mRNA was elevated when compared with ANA mice. In the hypothalamus, AHA mice also showed increased transcripts for 5-HT(2A) receptor. In the midbrain, 5-HT synthetic enzyme, 5-HT transporter and 5-HT receptors mRNA levels were similar between groups. Our results emphasize a role for postsynaptic over presynaptic 5-HT receptors in mice which showed escalated aggression after the consumption of a moderate dose of alcohol. This gene expression profile of 5-HT neurotransmission components in the brain of mice may suggest a vulnerability trait for alcohol-heightened aggression.

Brain abscess due to viridans streptococci in a severely immunosuppressed HIV-infected patient

We report a case of viriclans streptococcus brain abscess in a severely immunosuppressed HIV-infected patient with a history of chronic sinusitis. A 39-year-old homosexual man showed mental confusion and worsening of a frontal brain lesion after two weeks with antitoxoplasma therapy. Empiric treatment for central nervous system tuberculosis and pyogenic brain abscess was started. He underwent surgical drainage and the diagnosis of brain abscess due to viriclans streptococci was confirmed. All empiric treatments were stopped and ceftriaxone was used for eight weeks, showing complete clinical and radiological resolution. Although infrequent, viriclans streptococci, a common pyogenic aetiology of brain abscess in immunocompetent patients, should be considered in the differential diagnosis of brain lesions in AIDS patients.