SINGLE MEASUREMENTS OF C-REACTIVE PROTEIN AND DISEASE ACTIVITY SCORES ARE NOT PREDICTORS OF CAROTID ATHEROSCLEROSIS IN RHEUMATOID ARTHRITIS PATIENTS

Background: Although inflammation has a defined role in the pathogenesis of atherosclerosis, the link between rheumatoid arthritis (RA) parameters of disease activity and atherosclerotic findings are not defined. Objective: To investigate the association between subclinical carotid atherosclerosis and clinical/laboratorial parameters of RA systemic inflammatory activity. Methods: Seventy-one RA patients were consecutively selected and compared to 53 healthy controls. Smoking, diabetes and hypertension were excluded, as well as the use of statins or fibrates. B-mode carotid ultrasound was performed in all subjects. CRP, ESR and fibrinogen were determined in both groups. Clinical assessment of RA activity included DAS 28 and SDAI. Correlation between plaques and intima-media thickness (IMT) of common carotid arteries and inflammatory parameters was evaluated. Results: Carotid plaques were more prevalent in RA patients than in controls (14.1% vs. 1.9 %, p=0.02) and marginally increased IMT was observed (0.72 +/- 0.17 vs. 0.67 +/- 0.15mm, p=0.07). RA patients with plaques had older age (p=0.001) and increased IMT (p<0.001), but low SDAI (p=0.025) compared to those without plaques. RA patients with plaques had also longer disease duration, although this difference did not reach statistical significance (p=0.06). No significant correlations were found between IMT and ESR (p=0.80), CRP (p=0.75), fibrinogen (p=0.94), HAQ (p=0.89) and DAS 28 (p=0.13). Conclusions: Carotid atherosclerosis is more frequently detected in RA but its prevalence was not correlated with isolated inflammatory markers measurement or noncumulative activity scores. These findings reinforce the need to evaluate subclinical atherosclerosis in RA patients, and to find predictors of atherosclerotic lesions.

Use of SVM Methods with Surface-Based Cortical and Volumetric Subcortical Measurements to Detect Alzheimer`s Disease

Here, we examine morphological changes in cortical thickness of patients with Alzheimer`s disease (AD) using image analysis algorithms for brain structure segmentation and study automatic classification of AD patients using cortical and volumetric data. Cortical thickness of AD patients (n = 14) was measured using MRI cortical surface-based analysis and compared with healthy subjects (n = 20). Data was analyzed using an automated algorithm for tissue segmentation and classification. A Support Vector Machine (SVM) was applied over the volumetric measurements of subcortical and cortical structures to separate AD patients from controls. The group analysis showed cortical thickness reduction in the superior temporal lobe, parahippocampal gyrus, and enthorhinal cortex in both hemispheres. We also found cortical thinning in the isthmus of cingulate gyrus and middle temporal gyrus at the right hemisphere, as well as a reduction of the cortical mantle in areas previously shown to be associated with AD. We also confirmed that automatic classification algorithms (SVM) could be helpful to distinguish AD patients from healthy controls. Moreover, the same areas implicated in the pathogenesis of AD were the main parameters driving the classification algorithm. While the patient sample used in this study was relatively small, we expect that using a database of regional volumes derived from MRI scans of a large number of subjects will increase the SVM power of AD patient identification.

Evaluation of retinal nerve fiber layer thickness measurements using optical coherence tomography in patients with tobacco-alcohol-induced toxic optic neuropathy

Three patients with progressive visual loss, chronic alcoholism and tabagism were submitted to a complete neuro-ophthalmic examination and to retinal nerve fiber layer (RNFL) measurements using optical coherence tomography (OCT) scanning. Two patients showed marked RNFL loss in the temporal sector of the optic disc. However, a third patient presented RNFL measurements within or above normal limits, based on the Stratus-OCT normative database. Such findings may be due to possible RNFL edema similar to the one that may occur in the acute phase of toxic optic neuropathies. Stratus-OCT was able to detect RNFL loss in the papillomacular bundle of patients with tobacco-alcohol-induced toxic optic neuropathy. However, interpretation must be careful when OCT does not show abnormality in order to prevent diagnostic confusion, since overestimation of RNFL thickness measurements is possible in such cases.

Endometriosis lesions that compromise the rectum deeper than the inner muscularis layer have more than 40% of the circumference of the rectum affected by the disease

Study Objective: To estimate the relationship between the depth of lesions of rectal endometriosis and the percentage of the circumference of the bowel segment affected by the disease. Design: A prospective pathologic analysis of 45 surgical specimens of bowel endometriosis obtained by laparoscopic segmental resection of the rectosigmoid (Canadian Task Force classification II-1). Setting: Tertiary referral hospital. Patients: forty-five patients were submitted to a segmental resection of the rectum due to endometriosis between July 2004 and September 2006. Interventions: Morphometric aspects of endometriotic lesions were analyzed, such as size and thickness of the lesion, deepest layer of bowel affected by lesion, and percentage of circumference of bowel affected by endometriosis. Measurements and Main Results: Results showed that in lesions that reached the submucous layer of the bowel, the circumference affected was 31.6% greater than in lesions that reached only the outer muscular layer, whereas in lesions that reached the mucous layer, the circumference affected was 52.5% greater than in those that reached the outer muscular layer of the bowel. In addition, 89.3% of lesions with an affected circumference greater than 40% were those affecting the submucous or mucous layers of the bowel. These results suggest that when a lesion reaches these 2 deepest layers of the rectosiamoid, risk increases that the circumference affected will be greater than 40% (relative risk = 1.5; 95% CI: 1.0-2.3; p =.03). Conclusion: In endometriotic lesions affecting the rectosigmoid beyond the inner muscular layer of the bowel wall, more than 40% of the circumference of the rectosigmoid is affected by the disease, confirming the recommendation of segmental resection of the bowel for this form of the disease.

A population-based morphometric MRI study in patients with first-episode psychotic bipolar disorder: comparison with geographically matched healthy controls and major depressive disorder subjects

Objectives: Many morphometric magnetic resonance imaging (MRI) studies that have investigated the presence of gray matter (GM) volume abnormalities associated with the diagnosis of bipolar disorder (BD) have reported conflicting findings. None of these studies has compared patients with recent-onset psychotic BD with asymptomatic controls selected from exactly the same environment using epidemiological methods, or has directly contrasted BD patients against subjects with first-onset psychotic major depressive disorder (MDD). We examined structural brain differences between (i) BD (type I) subjects and MDD subjects with psychotic features in their first contact with the healthcare system in Brazil, and (ii) these two mood disorder groups relative to a sample of geographically matched asymptomatic controls. Methods: A total of 26 BD subjects, 20 subjects with MDD, and 94 healthy controls were examined using either of two identical MRI scanners and acquisition protocols. Diagnoses were based on DSM-IV criteria and confirmed one year after brain scanning. Image processing was conducted using voxel-based morphometry. Results: The BD group showed increased volume of the right dorsal anterior cingulate cortex relative to controls, while the MDD subjects exhibited bilateral foci GM deficits in the dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons). Direct comparison between BD and MDD patients showed a focus of GM reduction in the right-sided dorsolateral prefrontal cortex (p < 0.05, corrected for multiple comparisons) and a trend (p < 0.10, corrected) toward left-sided GM deficits in the dorsolateral prefrontal cortex of MDD patients. When analyses were repeated with scanner site as a confounding covariate the finding of increased right anterior cingulate volumes in BD patients relative to controls remained statistically significant (p = 0.01, corrected for multiple comparisons). Conclusions: These findings reinforce the view that there are important pathophysiological distinctions between BD and MDD, and indicate that subtle dorsal anterior cingulate abnormalities may be relevant to the pathophysiology of BD.

Lateral ventricle differences between first-episode schizophrenia and first-episode psychotic bipolar disorder: A population-based morphometric MRI study

Objectives. The extent to which psychotic disorders fall into distinct diagnostic categories or can be regarded as lying on a single continuum is controversial. We compared lateral ventricle volumes between a large sample of patients with first-episode schizophrenia or bipolar disorder and a healthy control group from the same neighbourhood. Methods. Population-based MRI study with 88 first-episode psychosis (FEP) patients, grouped into those with schizophrenia/schizophreniform disorder (N = 62), bipolar disorder (N = 26) and 94 controls. Results. Right and left lateral ventricular and right temporal horn volumes were larger in FEP subjects than controls. Within the FEP sample, post-hoc tests revealed larger left lateral ventricles and larger right and left temporal horns in schizophrenia subjects relative to controls, while there was no difference between patients with bipolar disorder and controls. None of the findings was attributable to effects of antipsychotics. Conclusions. This large-sample population-based MRI study showed that neuroanatomical abnormalities in subjects with schizophrenia relative to controls from the same neighbourhood are evident at the first episode of illness, but are not detectable in bipolar disorder patients. These data are consistent with a model of psychosis in which early brain insults of neurodevelopmental origin are more relevant to schizophrenia than to bipolar disorder.

Methylprednisolone improves lung mechanics and reduces the inflammatory response in pulmonary but not in extrapulmonary mild acute lung injury in mice

Objective: Gorticosteroids have been proposed to be effective in modulating the inflammatory response and pulmonary tissue remodeling in acute lung injury (ALI). We hypothesized that steroid treatment might act differently in models of pulmonary (p) or extrapulmonary (exp) ALI with similar mechanical compromise. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: One hundred twenty-eight BALB/c mice (20-25 g). Interventions: Mice were divided into six groups. In control animals sterile saline solution was intratracheally (0.05 mL, Cp) or intraperitoneally (0.5 mL, Gexp) injected, whereas ALI animals received Escherichia coli lipopolysaccharide intratracheally (10 mu g, ALIp) or intraperitoneally (125 mu g, ALIexp). Six hours after lipopolysaccharide administration, ALIp and ALlexp animals were further randomized into subgroups receiving saline (0.1 mL intravenously) or methylprednisolone (2 mg/kg intravenously, Mp and Mexp, respectively). Measurements and Main Results: At 24 hrs, lung state elastance, resistive and viscoelastic pressures, lung morphometry, and collagen fiber content were similar in both ALI groups. KC, interieukin-6, and transforming growth factor (TGF)-beta levels in bronchoatveolar lavage fluid, as well as tumor necrosis factor (TNF)-alpha, migration inhibitory factor (MIF), interferon (IFN)-gamma, TGF-beta 1 and TGF-beta 2 messenger RNA expression in lung tissue were higher in ALIp than in ALIexp animals. Methylprednisolone attenuated mechanical and morphometric changes, cytokine levels, and TNF-alpha, MIF, IFN gamma, and TGF-beta 2 messenger RNA expression only in ALIp animals, but prevented any changes in collagen fiber content in both ALI groups. Conclusions. Methylprednisolone is effective to inhibit fibrogenesis independent of the etiology of ALI, but its ability to attenuate inflammatory responses and lung mechanical changes varies according to the cause of ALI.

Lack of Circadian Variation of Pulse Wave Velocity Measurements in Healthy Volunteers

Arterial stiffness is an independent marker of cardiovascular events. Pulse wave velocity (PWV) is a validated method to detect arterial stiffness that can be influenced by several factors including age and blood pressure. However, it is not clear whether PWV could be influenced by circadian variations. In the present study, the authors measured blood pressure and carotid-femoral PWV measurements in 15 young healthy volunteers in 4 distinct periods: 8 am, noon, 4 pm, and 8 pm. No significant variations of systolic (P=.92), mean (P=.77), and diastolic (P=.66) blood pressure among 8 am (113 +/- 15, 84 +/- 8, 69 +/- 6 mm Hg), noon (114 +/- 13, 83 +/- 8, 68 +/- 6 mm Hg), 4 pm (114 +/- 13, 85 +/- 8, 70 +/- 7 mm Hg), and 8 pm (113 +/- 7, 83 +/- 10, 68 +/- 7 mm Hg), respectively, were observed. Similarly, carotid-femoral PWV did not change among the periods (8 am: 7.6 +/- 1.4 m/s, noon: 7.4 +/- 1.1 m/s, 4 pm: 7.6 +/- 1.0 m/s, 8 pm, 7.6 +/- 1.3 m/s; P=.85). Considering all measurements, mean blood pressure significantly correlated with PWV (r=.31; P=.016). In young healthy volunteers, there is no significant circadian variation of carotid-femoral PWV. These findings support the concept that it does not appear mandatory to perform PWV measurements at exactly the same period of the day. J Clin Hypertens (Greenwich). 2011;13:19-22. (c) 2010 Wiley Periodicals, Inc.

Static Knee Alignment Measurements among Caucasians and African Americans: The Johnston County Osteoarthritis Project

Objective. To determine if knee alignment measures differ between African Americans and Caucasians without radiographic knee osteoarthritis (rOA). Methods. A single knee was randomly selected from 175 participants in the Johnston County Osteoarthritis Project without rOA in either knee. Anatomic axis, condylar, tibia] plateau, and condylar plateau angles were measured by I radiologist; means were compared and adjusted for age and body mass index (BMI). Results. There were no significant differences in knee alignment measurements between Caucasians and African Americans among men or women. Conclusion. Observed differences in knee rOA occurrence between African Americans and Caucasians are not explained by differences in static knee alignment. (First Release July 15 2009; J Rheumatol 2009;36:1987-90; doi: 10.3899/jrheum.081294)

Neuronal Correlates of Brain-derived Neurotrophic Factor Val66Met Polymorphism and Morphometric Abnormalities in Bipolar Disorder

The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism has been proposed as a possible candidate for involvement in the pathophysiology of bipolar disorder ( BD). To determine whether an association exists between the BDNF Val66Met genotype and morphometric abnormalities of the brain regions involved in memory and learning in BD and healthy subjects. Forty-two BD patients and 42 healthy subjects were studied. Interactions between BDNF Val66Met genotype and diagnosis in gray ( GM) volumes were analyzed using an optimized voxel-based morphometry technique. Declarative memory function was assessed with the California Verbal Learning Test II. Left and right anterior cingulate GM volumes showed a significant interaction between genotype and diagnosis such that anterior cingulate GM volumes were significantly smaller in the Val/Met BD patients compared with the Val/Val BD patients (left P = 0.01, right P = 0.01). Within-group comparisons revealed that the Val/Met carriers showed smaller GM volumes of the dorsolateral prefrontal cortex compared with the Val/Val subjects within the BD patient (P = 0.01) and healthy groups (left P = 0.03, right P = 0.03). The Val/Met healthy subjects had smaller GM volumes of the left hippocampus compared with the Val/Val healthy subjects (P<0.01). There was a significant main effect of diagnosis on memory function (P = 0.04), but no interaction between diagnosis and genotype was found (P = 0.48). The findings support an association between the BDNF Val66Met genotype and differential gray matter content in brain structures, and suggest that the variation in this gene may play a more prominent role in brain structure differences in subjects affected with BD. Neuropsychopharmacology (2009) 34, 1904-1913; doi: 10.1038/npp.2009.23; published online 18 March 2009

Agreement between stress intraocular pressure and long-term intraocular pressure measurements in primary open angle glaucoma

The aim of this paper is to study the correlation between the intraocular pressure peaks and fluctuation detected during the water drinking test and the same parameters observed during long-term follow up. This prospective cohort study enrolled 22 eyes of 22 newly diagnosed primary open angle glaucoma patients. After an initial complete ophthalmological examination, patients were started on antiglaucoma medication and returned 4 weeks later to perform the water drinking test. Thereafter, patients were evaluated at least eight times within a period of 6-12 months. The intraocular pressure peaks and fluctuation detected during the water drinking stress test were compared with those observed during regular office visits. Spearman`s correlation coefficient and Bland-Altman Plots were used for statistical analysis. The mean age of participants was 54.3 +/- 8.2 years (+/- SD), 59% were women, and average mean deviation -10.2 +/- 4.5 dB. The mean follow-up period was 8.2 +/- 2.0 months. The average intraocular pressure peaks and fluctuation during the water drinking test were 20.0 +/- 2.9 mmHg and 40 +/- 10%, respectively, and 18.1 +/- 2.8 mmHg and 30 +/- 10% during follow up. Spearman`s correlation coefficients were significant and strong between the intraocular pressure peaks and fluctuation detected during the water drinking test and during the follow-up period (P < 0.001, rho = 0.76 and 0.82, respectively). There was good agreement between the variables. The intraocular pressure peaks and fluctuation detected during the water drinking test showed significant correlation and agreement with the pressures observed during follow-up visits. Stress tests could be used to estimate long-term intraocular pressure variation.

Comparative study of Botox (R) injection treatment for upper eyelid retraction with 6-month follow-up in patients with thyroid eye disease in the congestive or fibrotic stage

Aim To compare morphometric data of the eyelid fissure and the levator muscle function (LF) before and up to 6 months after transcutaneous injection with five units of Botox (R) in patients with upper lid retraction (ULR) from congestive or fibrotic thyroid eye disease (TED). Methods Twenty-four patients with ULR from TED were submitted to transcutaneous injection of 5 units (0.1 ml) of Botox in one eye only. Patients were divided into two groups: 12 with congestive-stage TED (CG), and 12 with fibrotic-stage TED (FG). Bilateral lid fissure measurements using digital imaging and computer-aided analysis were taken at baseline and at regular intervals 2 weeks, 1 month, 3 months and 6 months after unilateral Botox injection. Mean values taken at different follow-up points were compared for the two groups. Results Most patients experienced marked improvement in ULR, with a mean reduction of 3.81 mm in FG and 3.05 mm in CG. The upper eyelid margin reflex distance, fissure height and total area of exposed interpalpebral fissure were significantly smaller during 1 month in CG and during 3 months in FG. Reduction in LF and in the difference between lateral and medial lid fissure measurements was observed in both groups. The treatment lasted significantly longer in FG than in CG. Conclusions A single 5-unit Botox injection improved ULR, reduced LF and produced an adequate lid contour in patients with congestive or fibrotic TED. The effect lasts longer in patients with fibrotic orbitopathy than in patients with congestive orbitopathy.

Nomograms of fetal thyroid measurements estimated by 2-dimensional sonography

Purpose. To build nomograms of fetal thyroid circumference (FTC), fetal thyroid area (FTA), and fetal thyroid transverse diameter (FTTD) throughout gestational age (GA). Method. Between January 2006 and July 2006, FTC, FTA, and FTTD were measured once in 196 normal fetuses examined at a GA of 22-35 weeks. Inclusion criteria were a healthy mother with normal maternal thyrotropin level during pregnancy, a singleton pregnancy with normal fetal morphology on sonography, and GA confirmed via first-trimester sonographic examination. Results. Mean FTC, FTA, and FTTD ranged from 3.21 cm, 0.58 cm(2), and 1.19 cm at 22 weeks to 5.11 cm, 1.69 cm(2), and 1.89 cm at 35 weeks, respectively. Linear regression analysis yielded the following formulas for FTC, FTA, and FTTD according to GA: FTC (cm) = 0.146 X GA (weeks); FTA (cm(2)) = -1.289 + 0.085 X GA (weeks); FTTD (cm) = 0.054 X GA (weeks). The following logarithmic formulas were obtained for the expected fetal thyroid measurements according to estimated fetal weight (FW): FTC (cm) = -4.791 + 1.265 X logN FW; FTA (cm(2)) = -1.676 + 0.455 X logN FW; and FTTD (cm) = 0.399 + 0.001 X logN FW. Conclusion. We describe new nomograms of fetal thyroid measurements throughout gestation that may be useful in case of thyroid dysfunction. (C) 2008 Wiley Periodicals, Inc.

Reliability assessment of Cobb angle measurements using manual and digital methods

BACKGROUND CONTEXT: The vertebral spine angle in the frontal plane is an important parameter in the assessment of scoliosis and may be obtained from panoramic X-ray images. Technological advances have allowed for an increased use of digital X-ray images in clinical practice. PURPOSE: In this context, the objective of this study is to assess the reliability of computer-assisted Cobb angle measurements taken from digital X-ray images. STUDY DESIGN/SETTING: Clinical investigation quantifying scoliotic deformity with Cobb method to evaluate the intra- and interobserver variability using manual and digital techniques. PATIENT SAMPLE: Forty-nine patients diagnosed with idiopathic scoliosis were chosen based on convenience, without predilection for gender, age, type, location, or magnitude of the curvature. OUTCOME MEASURES: Images were examined to evaluate Cobb angle variability, end plate selection, as well as intra- and interobserver errors. METHODS: Specific software was developed to digitally reproduce the Cobb method and calculate semiautomatically the degree of scoliotic deformity. During the study, three observers estimated the Cobb angle using both the digital and the traditional manual methods. RESULTS: The results showed that Cobb angle measurements may be reproduced in the computer as reliably as with the traditional manual method, in similar conditions to those found in clinical practice. CONCLUSIONS: The computer-assisted method (digital method) is clinically advantageous and appropriate to assess the scoliotic curvature in the frontal plane using Cobb method. (C) 2010 Elsevier Inc. All rights reserved.

Morphologic and morphometric evaluation of experimental acute crush injuries of the sciatic nerve of rats

In order to qualify and quantify nerve fiber lesion following an acute crush injury, a morphologic and morphometric study was carried out in 25 Wistar rats divided into live groups of five animals each according to the crushing load applied, i.e., 500,1000, 5000, 10 000, and 15 000 g. The injury was produced under general anesthesia on a 5 mm-long intermediate segment of the right sciatic nerve for 10 min using a dead-weight machine. The animals were killed with an excessive dose of anesthetics 72 h later and submitted to perfusion with a fixing solution through the abdominal aorta immediately after death. Both the right and left sciatic nerves were removed and prepared for histologic and morphometric examinations: 5 mu m-thick sections stained with 1% Toluidine blue were examined under a light microscope equipped with a video camera linked to a computer loaded with a graphic program (KS 400). The morphometric studies included measuring total number of fibers, fiber density, fiber diameter, myelin fiber area, axon diameter, axon area and G ratio. The results showed that damage to the nerve fibers began to appear as early as with the 500g load and was similar in all groups despite the load applied, increasing with the 10000 and 15000g loads, although the external supporting tissues and small diameter fibers were preserved. The predominant type of lesion produced was axonotmesis. (c) 2008 Elsevier B.V. All rights reserved.