Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement

The magnitude Of functional impairment that may indicate the threshold between MCI and incipient Alzheimer`s disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a University-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum. (JINS, 2010, 16, 297-305.)

Immunophenotyping and remodeling process in small airways of idiopathic interstitial pneumonias: functional and prognostic significance

Background and Aims: To test whether different degrees of immunologic and fibrotic airway remodeling processes occur in idiopathic interstitial pneumonias (IIPs), with impact on functional tests and survival, we studied the collagen/elastic system and immune cell density in the bronchiolar interstitium of lungs with the major types of IIPs. Materials and Methods: Histochemistry, immunohistochemistry and morphometric analysis were used to evaluate collagen/elastic fibers and immune cells in the bronchiolar interstitium of open lung biopsies of patients with cryptogenic organizing pneumonia [COP/organizing pneumonia (OP) = 10], acute interstitial pneumonia [AIP/diffuse alveolar damage (DAD) = 20], nonspecific interstitial pneumonia (NSIP/NSIP = 20) and idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) = 20. Results: OP lungs presented a significant increase in collagenous/elastic fibers and in the total density of immune cells in the bronchiolar interstitium compared to controls, DAD, NSIP and UIP. We observed a significant increase in CD4, CD8 and CD20 lymphocytes, as well as in neutrophils, macrophages and plasma cells in OP. The increased amount of elastic fibers in the bronchiolar interstitium from OP lungs has a direct association with forced vital capacity (FVC) (r(s) = 0.99, P = 0.03). The most important survival predictor was CD20+ lymphocytes in the bronchiolar interstitium. In decreasing order, patients with UIP [Odds Ratio (OR) = 35.01], high forced expiratory volume in 1 s (FEV1)/FVC FVC (OR = 7.01), increased CD20+ lymphocytes (OR = 4.44) and collagenous/elastic fiber densities (OR = 2.03 and OR = 1.49, respectively) in the bronchiolar interstitium were those who had the greatest risk of death, followed by those with AIP, NSIP and COP. Conclusion: Different degrees of immunologic and fibroelastotic airway remodeling processes occur in the major types of IIPs with impact on physiological tests and survival.

Particulate urban air pollution affects the functional morphology of mouse placenta

in humans, adverse pregnancy outcomes (low birth weight, prematurity, and intrauterine growth retardation) are associated with exposure to urban air pollution. Experimental data have also shown that such exposure elicits adverse reproductive outcomes. We hypothesized that the effects of urban air pollution on pregnancy outcomes could be related to changes in functional morphology of the placenta. To test this, future dams were exposed during pregestational and gestational periods to filtered or nonfiltered air in exposure chambers. Placentas were collected from near-term pregnancies and prepared for microscopical examination. Fields of view on vertical uniform random tissue slices were analyzed using stereological methods. Volumes of placental compartments were estimated, and the labyrinth was analyzed further in terms of its maternal vascular spaces, fetal capillaries, trophoblast, and exchange surface areas. From these primary data, secondary quantities were derived: vessel calibers (expressed as diameters), trophoblast thickness (arithmetic mean), and total and mass-specific morphometric diffusive conductances for oxygen of the intervascular barrier. Two-way analysis of variance showed that both periods of exposure led to significantly smaller fetal weights. Pregestational exposure to nonfiltered air led to significant increases in fetal capillary surface area and in total and mass-specific conductances. However, the calibers of maternal blood spaces were reduced. Gestational exposure to nonfiltered air was associated with reduced volumes, calibers, and surface areas of maternal blood spaces and with greater fetal capillary surfaces and diffusive conductances. The findings indicate that urban air pollution affects placental functional morphology. Fetal weights are compromised despite attempts to improve diffusive transport across the placenta.

Effect of Exercise Training on Plasma Levels and Functional Properties of High-Density Lipoprotein Cholesterol in the Metabolic Syndrome

Intense lifestyle modifications can change the high-density lipoprotein (HDL) cholesterol concentration. The aim of the present study was to analyze the early effects of short-term exercise training, without any specific diet, on the HDL cholesterol plasma levels and HDL functional characteristics in patients with the metabolic syndrome (MS). We studied 30 sedentary subjects, 20 with and 10 without the MS. The patients with the MS underwent moderate intensity exercise training for 3 months on bicycle ergometers. Blood was sampled before and after training for biochemical analysis, paraoxonase-1 activity, and HDL subfraction composition and antioxidative capacity. Lipid transfer to HDL was assayed in vitro using a labeled nanoemulsion as the lipid donor. At baseline, the MS group had greater triglyceride levels and a lower HDL cholesterol concentration and lower paraoxonase-1 activity than did the controls. Training decreased the plasma triglycerides but did not change the low-density lipoprotein or HDL cholesterol levels. Nonetheless, exercise training increased the HDL subfractions` antioxidative capacity and paraoxonase-1 activity. After training, the MS group had compositional changes in the smallest HDL subfractions associated with increased free cholesterol and cholesterol ester transfers to HDL, reaching normal values. In conclusion, the present investigation has added relevant information about the dissociation between the quantitative and qualitative aspects of HDL after short-term exercise training without any specific diet in those with the MS, highlighting the importance of evaluating the functional aspects of the lipoproteins, in addition to their plasma levels. (C) 2011 Elsevier Inc. All rights reserved. (Am J Cardiol 2011;107:1168-1172)

Comparison of language impairment in late-onset depression and Alzheimer`s disease

Objectives: Depression and dementia are highly prevalent in the elderly. Language impairment is an inherent component of Alzheimer`s disease (AD), which can also be encountered in depressed patients. The aim of this study wasto compare the profiles of language abilities in late-onset depression and mild AD groups. Methods: We studied 25 patients with late-onset depression (mean age 73.6 +/- 6.6 years; schooling 9.1 +/- 5.7 years) and 30 patients with mild AD (77.6 +/- 5.4 years; 7.5 +/- 7.1 years) using the Arizona Battery for Communication Disorders of Dementia (ABCD), compared to a group of 30 controls (73.8 +/- 5.8 years; 9.1 +/- 5.4 years). Cut-off scores to discriminate between Controls x Depression and Depression x AD were determined. Results: Depressed patients` scores were similar to AD in confrontation naming, concept definition, following commands, repetition and reading comprehension (sentence). Episodic memory and mental status subtests were useful in differentiating depressed patients from AD, a result that was reproduced when using analysis of covariance to control for the effect of age in the same subtests (p = 0.01 and 0.04, respectively). Conclusion: Language impairment resembling AD was found in the aforementioned language subtests of the ABCD in elderly depressed patients; the mental status and episodic memory subtests were useful to discriminate between AD and depression. The ABCD has proven to be a suitable tool for language evaluation in this population and should aid in the differentiation of AD and pseudodementia (as that of depression).

EVALUATION OF FUNCTIONAL GAIN OF THE ELBOW FOLLOWING STEINDLER SURGERY FOR BRACHIAL PLEXUS INJURY

Objective: To evaluate the gain in strength and range of motion after modified Steindler surgery of the elbow in patients with lesions of the upper trunk of the brachial plexus. Method: From 1998 to 2007, eleven patients with traumatic closed upper trunk lesion of the brachial plexus were studied. All the patients had development of at least 1 year of injury and degree of strength of elbow flexion ranging from M1 to M3. The patients underwent Steindler surgery with at least 6 months of follow-up. Pre- and post-operative assessments were carried out to determine gain in muscle strength, range of motion of the elbow, and DASH scale score. Results: Of the eleven patients studied, nine (82%) achieved a level of strength equal to or greater than M3 (MRC) with good functional recovery. Two (18%) reached strength level M2 (MRC). We observed that the patients had an average postoperative gain in range of motion of the elbow of 43.45 degrees. The average elbow flexion after surgery was 88 degrees. There was an improvement in elbow function, as demonstrated in the DASH Scale, in 81% of the patients studied. Conclusion: Modified Steindler surgery was effective in the treatment of patients with injuries of the upper trunk of the brachial plexus, with statistically significant gains in range of motion. In all the cases studied, there was some degree of gain in strength and range of elbow flexion, the gain being correlated with the initial muscle strength. Level of Evidence: Level II, prospective clinical trial.

Pain Relief and Functional Recovery in Patients with Complex Regional Pain Syndrome after Motor Cortex Stimulation

In addition to pain and neurovegetative symptoms, patients with severe forms of complex regional pain syndrome (CRPS) develop a broad range of symptoms, including sensory disturbances, motor impairment and dystonic posturing. While most patients respond to medical therapy, some are considered refractory and become surgical candidates. To date, the most commonly used surgical procedure for CRPS has been spinal cord stimulation. This therapy often leads to important analgesic effects, but no sensory or motor improvements. We report on 2 patients with pain related to CRPS and severe functional deficits treated with motor cortex stimulation (MCS) who not only had significant analgesic effects, but also improvements in sensory and motor symptoms. In the long term (27 and 36 months after surgery), visual analog scale pain scores were improved by 60-70% as compared to baseline. There was also a significant increase in the range of motion in the joints of the affected limbs and an improvement in allodynia, hyperpathia and hypoesthesia. Positron emission tomography scan in both subjects revealed that MCS influenced regions involved in the circuitry of pain. Copyright (C) 2011 S. Karger AG, Basel

Influence of the Fibroblast Growth Factor Receptor 4 Expression and the G388R Functional Polymorphism on Cushing`s Disease Outcome

Context: Abnormal FGFR4 expression has been detected in pituitary tumors, especially in larger and invasive adenomas. In addition, the FGFR4 functional polymorphism G388R has been associated with poor outcome in several human malignancies. Then, we hypothesized that FGFR4 expression and genotype could be markers of adverse outcome of Cushing`s disease after transsphenoidal surgery. Objectives: The objective was to investigate whether there is an association between the postoperative outcome of Cushing`s disease (remission/recurrence) and the FGFR4 G388R genotype or the FGFR4 expression in corticotrophinomas. Design and Patients: Clinical, hormonal, and pathological data of 76 patients who underwent the first transsphenoidal surgery were retrospectively reviewed. All patients were genotyped for G388R polymorphism. FGFR4 expression was assessed by real-time PCR in 18 corticotrophinomas. Main Outcome Measures: The outcome measures included the FGFR4 G388R genotype and FGFR4 expression in postoperative remission and recurrence of Cushing`s disease. Results: Homozygosis for FGFR4 glycine (Gly(388)) allele was associated with reduced disease-free survival, in the univariate analysis (hazard ratio of 6.91; 95% confidence interval of 1.14-11.26; P = 0.028). Male gender (P = 0.036), lack of pathology confirmation (P = 0.009), and cortisol levels more than 2 mu g/dl in the early postoperative period (P < 0.001) were also significant predictors of Cushing`s disease recurrence in the univariate analysis. FGFR4 overexpression was found in 44% of the corticotrophinomas, and it was associated with lower postoperative remission rate (P = 0.009). Conclusions: Our data suggest that homozygosis for FGFR4 Gly(388) allele and FGFR4 overexpression are associated with higher frequency of postoperative recurrence and persistence of Cushing`s disease, respectively. (J Clin Endocrinol Metab 95: E271-E279, 2010)

Translation and Cross-Cultural Adaptation of the Brazilian Version of the International Knee Documentation Committee Subjective Knee Form Validity and Reproducibility

Background: The perception of improvement by a patient has assumed a central role in functional evaluation after a variety of knee problems. One of the instruments most used in clinical research is the International Knee Documentation Committee (IKDC) Subjective Knee Form because its psychometric properties are considered to be excellent. Nonetheless, this questionnaire was originally developed for use in the English language. Therefore, to use this questionnaire in the Brazilian population, it is essential to translate and validate it. Purpose: The aim of this study was to translate the IKDC Subjective Knee Form into a Brazilian version and to test its validity and reproducibility. Study Design: Cohort study (diagnosis); Level of evidence, 2. Methods: The translation of the original IKDC Subjective Knee Form into a Brazilian version was accomplished in accordance with the American Orthopaedic Society for Sports Medicine guidelines and was tested in 32 patients with knee pathologic conditions to develop the first Brazilian version. To test validity and reproducibility, 117 patients with several knee complaints completed the Brazilian IKDC Subjective Knee Form, the Short Form 36 (SF-36), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and the Lysholm score. From these patients, 85 were retested within a week to achieve reproducibility. The validation was addressed by correlating the Brazilian IKDC Subjective Knee Form to the other outcome measures. The reproducibility was tested by measuring internal consistency, test-retest reliability, and agreement. Results: The Brazilian IKDC Subjective Knee Form was highly related to the physical component summary of the SF-36, the Lysholm score, and the WOMAC, and weakly related to the mental component summary of SF-36 (r=.79, .89, .85, and .51, respectively). The internal consistency was strong, with a Cronbach a value of .928 and .935 in the test and retest assessment, respectively. The test-retest reliability proved to be excellent, with a high value of the intraclass correlation coefficient (.988), as well as the agreement, demonstrated by the low differences between the means of the test and retest, and the short limit of agreement, observed in the Altman-Bland and survival-agreement plots. Conclusion: The results of this study provide evidence that the Brazilian IKDC Subjective Knee Form has psychometric properties similar to the original version. In addition, it was a reliable evaluation instrument for patients with knee-related problems.