The quality of life of patients on the lung transplantation waiting list

Introduction. Lung transplantation (LTx) candidates present incapacitating symptoms related to their mobility and activities of daily living, thereby affecting their work, social and emotional relations, and quality of life (QoL). Objective. To study the QoL of LTx candidates, seeking to identify domains that suffer the greatest impact and verify if there are differences among these impairments according to the original lung disease. Methods. We applied the Short Form-36 questionnaires and St George`s Respiratory Questionnaire (SGRQ). All data were analyzed by one-way analysis of variance and the Kruskal Wallis test for the probability with significance at P < 0.05. Results. Fifty patients were divided into groups of emphysema (n = 16), bronchiectasis (n = 12), idiopathic pulmonary fibrosis (n = 7), and cystic fibrosis (n = 15). The functional capacity, physical aspects, general status, and vitality domains showed average values below 50 points. The cystic fibrosis group showed higher functional capacity scores (46 +/- 23) than the emphysema (12 +/- 13) or idiopathic pulmonary fibrosis cohort (7 5). The limitation caused by pain affected the bronchiectasis more than the cystic fibrosis group (52 +/- 28 vs 81 +/- 25, respectively). The SGRQ scores showed impairment among all groups in all domains with average values over 50. The activities domain shows the highest score value; the emphysema (92 +/- 10) and idiopathic pulmonary fibrosis cohorts (91 +/- 9) were extremely affected compared with the cystic fibrosis (69 +/- 21) and bronchiectasis subjects (79 +/- 16). The impact domain show that subjects with cystic fibrosis were less emotionally affected by the disease. Conclusion. LTx candidates showed great impairment of their QoL due to their health problems, above all in the physical-functional aspects; the cystic fibrosis patients were the least affected by their health status.

Prognostic value of left atrial volume in patients who underwent dobutamine stress echocardiography for known or suspected coronary artery disease

Background Left atrial volume indexed (LAVI) has been reported as a predictor of cardiovascular events. We sought to determine the prognostic value of LAVI for predicting the outcome of patients who underwent dobutamine stress echocardiography (DSE) for known or suspected coronary artery disease (CAD). Methods From January 2000 to July 2005, we studied 981 patients who underwent DSE and off-line measurements of LAVI. The value of DSE over clinical and LAVI data was examined using a stepwise log-rank test. Results During a median follow-up of 24 months, 56 (6%) events occurred. By univariate analysis, predictors of events were male sex, diabetes mellitus, previous myocardial infarction, left ventricular ejection fraction (LVEF), left atrial diameter indexed, LAVI, and abnormal DSE. By multivariate analysis, independent predictors were LVEF (relative risk [RR] = 0.98, 95% CI 0.95-1.00), LAVI (RR = 1.04, 95% CI 1.02-1.05), and abnormal DSE (RR = 2.70, 95% CI 1.28-5.69). In an incremental multivariate model, LAVI was additional to clinical data for predicting events (chi(2) 36.8, P < .001). The addition of DSE to clinical and LAVI yielded incremental information (chi(2) 55.3, P < .001). The 3-year event-free survival in patients with normal DSE and LAVI <= 33 mL/m(2) was 96%; with abnormal DSE and LAVI <= 33 mL/m(2), 91%; with normal DSE and LAVI >34 mL/m(2), 83%; and with abnormal DSE and LAVI >34 mL/m(2) 51%. Conclusion Left atrial volume indexed provides independent prognostic information in patients who underwent DSE for known or suspected CAD. Among patients with normal DSE, those with larger LAVI had worse outcome, and among patients with abnormal DSE, LAVI was still predictive. (Am Heart J 2008; 156:1110-6.)

In vitro study of CD133 human stem cells labeled with superparamagnetic iron oxide nanoparticles

Superparamagnetic iron oxide nanoparticles (SPIONs) are applied in stem cell labeling because of their high magnetic susceptibility as compared with ordinary paramagnetic species, their low toxicity, and their ease of magnetic manipulation. The present work is the study of CD133(+) stem cell labeling by SPIONs coupled to a specific antibody (AC133), resulting in the antigenic labeling of the CD133+ stem cell, and a method was developed for the quantification of the SPION content per cell, necessary for molecular imaging optimization. Flow cytometry analysis established the efficiency of the selection process and helped determine that the CD133 cells selected by chromatographic affinity express the transmembrane glycoprotein CD133. The presence of antibodies coupled to the SPION, expressed in the cell membrane, was observed by transmission electron microscopy. Quantification of the SPION concentration in the marked cells using the ferromagnetic resonance technique resulted in a value of 1.70 x 10 (13) mol iron (9.5 pg) or 7.0 x 10 (6) nanoparticles per cell ( the measurement was carried out in a volume of 2 mu L containing about 6.16 x 10 5 pg iron, equivalent to 4.5 x 10 (11) SPIONs). (c) 2008 Elsevier Inc. All rights reserved.

Ultrastructural characterization of CD133(+) stem cells bound to superparamagnetic nanoparticles: possible biotechnological applications

CD133 antigen is an integral membrane glycoprotein that can bind with different cells. Originally, however. this cellular surface antigen was expressed in human stem cells and in various cellular progenitors of the haematopoietic system. Human cord blood has been described as an excellent source of CD133(+) haematopoietic progenitor cells with a large application potential. One of the main objectives of the present study is to describe for the first time the ultrastructural characteristics of CD133(+) stem cells using transmission electronic microscopy. Another objective of the manuscript is to demonstrate through transmission electronic microscopy the molecular image of magnetic nanoparticles connected to the stein cells of great biotechnological importance, as well as demonstrating the value of this finding for electronic paramagnetic resonance and its related nanobioscientific value. Ultrastructural results showed the monoclonal antibody anti-CD133 bound to the superparamagnetic nanoparticles by the presence of electrondense granules in cell membrane, as well as in the cytoplasm, revealing the ultrastructural characteristics of CD133(+) cells, exhibiting a round morphology with discrete cytoplasmic projections, having an active nucleus that follows this morphology. The cellular cytoplasm was filled up with mitochondrias, as well as microtubules and vesicles pinocitic. characterizing the process as being related to internalization of the magnetic nanoparticles that were endocyted by the cells in question. Electronic paramagnetic resonance analysis of the CD133(+) stem cells detected that the small (spectrum) generated by the labelled cells comes from the superparamagnetic nanoparticles that are bound to them. These results strongly suggest that these CD133(+) cells can be used in nanobiotechnology applications, with benefits in different biomedical areas.

Clinicopathological evaluation of in vivo epidermal nuclear fluorescence

Nuclear fluorescence in keratinocytes is an occasional phenomenon, often present in autoimmune diseases, especially in connective-tissue disease (CTD); however, its clinical significance remains unclear. To investigate the profile of patients with positive nuclear staining on direct immunofluorescence (DIF) of skin samples. A retrospective analysis of 28 patient records from our immunodermatology laboratory was performed between May 2003 and June 2006. Inclusion criteria were the presence of autoantibodies (IgG, IgA or IgM) or complement (C3) binding keratinocyte nuclei on DIF. The most prevalent diseases related to the nuclear keratinocyte DIF staining were systemic lupus erythematosus (n = 9), mixed CTD (n = 3), overlap syndrome (n = 3), Sjogren`s syndrome (n = 1), and CREST (calcinosis, Raynaud`s phenomenon, oesophageal dysmotility, sclerodactyly and telangiectasia) syndrome (n = 1). Serum antinuclear antibody (ANA) was positive in 20 of 28 patients, with titres varying from 1 : 160 to 1 : 1280. Of the 20 patients with positive anti-nuclear antibodies (ANA), 17 were positive for anti-extractable nuclear antigen antibodies, 12 had anti-SSA/Ro, 11 had anti-SSB/La and 8 had anti-ribonucleoprotein. Eight patients were negative for ANA. Positive predictive value of in vivo ANA for systemic CTDs was 75%. The present data suggest that in vivo ANA evaluation is an additional and feasible auxiliary tool for diagnosing CTDs.

Long-Term Nutritional Outcome After Gastric Bypass

Weight loss and nutritional status 5 or more years after Roux-en-Y gastric bypass was prospectively documented. The hypothesis was that even after clinical adaptation, imbalances might still occur. Seventy-five consecutive patients (age 49.3 +/- 10.6 years, 89.3% females) were recruited 83.4 +/- 14.3 months after the intervention. Weight loss and nutritional abnormalities were registered. Body mass index (BMI) was 56.5 +/- 10.0 preoperatively, 29.4 +/- 6. 2 by 24 months and 34.4 +/- 14.6 when last seen. Major current deficit occurred for magnesium (32.1% of the patients), hemoglobin (50.8%), iron (29.8%), ferritin (36.0%), zinc (40.5%), vitamin B(12) (61.8%), vitamin D(3) (60.5%), and beta-carotene (56.8%). Low preoperative measurements had already been unveiled for iron, transferrin, zinc, and vitamin B(12). Total drug consumption tended to decrease after operation, and present findings correlated with excess weight loss (EWL). Also presence of diabetes and BMI value were predictors of long-term EWL, along with biochemical profile by 2 years. Multivitamin supplementation and gastrointestinal complaints partially correlated with nutritional results. (1) Good initial weight loss with moderate late regain, anemia, and multiple nutrient deficits was the common pattern. (2) Massive weight loss, frequent vomiting, dumping syndrome, and women in reproductive age were risk factors for hemoglobin or vitamin deficits, whereas superobesity, diabetes, and use of multiple drugs were associated with EWL result. (3) Most laboratory tests became stable by 2 years and along with BMI correlated with late EWL. (4) Two-year nutritional investigation is especially recommended because of its long-term predictive value.

Increased Immunoglobulin G Anti-Paracoccidioides brasiliensis Serum Antibody Avidity as a Predictor of Favorable Posttherapeutic Evolution in Paracoccidioidomycosis

Paracoccidioidomycosis is endemic in Latin America, and ca. 80% of all cases occur in Brazil. Little is known about antibody avidity or the evolution of such avidity in the posttherapeutic period for the different clinical presentations of the disease. In the present study, we evaluated 53 patients with paracoccidioidomycosis and calculated the avidity index. Medium-and high-avidity antibodies were found in 79.5% of patients with chronic presentation (n = 39). Among patients with the acute form (n = 14), 57.1% of the antibodies presented low avidity. In the posttherapeutic period, there was a significant increase in antibody avidity in patients presenting with the chronic multifocal form. In our preliminary study, which needs to be confirmed using a larger number of samples, the optimized method for studying antibody avidity detected differences among the clinical presentations of the mycosis and indicated the value of the avidity index as a marker of posttherapeutic evolution of patients with a multifocal chronic form of the disease.

The impact of gender, age and hearing loss on tinnitus severity

Tinnitus is a symptom present in approximately 15% of the world population. Most patients are between 40 and 80 years of age; the prevalence above 60 reaches 33%. About 20% have moderate to severe impact in the quality of life but the factors associated with the tinnitus annoyance are not completely known. Aim: The objective of this study is to evaluate the relationship between age, gender and hearing loss on tinnitus annoyance. Materials and methods: 68 patients were evaluated at the tinnitus center at our hospital, from March 2007 to march 2008, with a detailed interview, complete otolaryngological examination, the Portuguese version of the Tinnitus Handicap Inventory and pure tone audiometry. Results: Age varied from 24 to 83 (mean=59); the mean THI value was 39 (females: 36; males: 44). THI grades were: slight: 32.3%; mild: 19.1%; moderate: 20.6%; severe: 13.2% and catastrophic: 14.7%. No significant correlation was found between gender (p=0.30), age (p=0.77) hearing loss (p>0.05 for all averages analyzed) and tinnitus severity. Conclusion: Gender, age and hearing loss do not influence tinnitus annoyance, using the THI.

Characterization of bovine transcripts preferentially expressed in testis and with a putative role in spermatogenesis

Although the number of genes known to be associated with bovine spermatogenesis has increased in the past few years, regulation of this biological process remains poorly understood. Therefore, discovery of new male fertility genetic markers is of great value for assisted selection in commercially important cattle breeds, e.g., Nelore, that have delayed reproductive maturation and low fertility rates. The objective of the present study was to identify sequences associated with spermatogenesis that could be used as fertility markers. With RT-PCR, the following five transcripts preferentially expressed in adult testis were detected: TET(656) detected only in adult testis; TET(868) and TET(515) expressed preferentially in adult testis but also detected in fetal gonads of both sexes; and TET(456) and TET(262). expressed primarily in the testis, but also present in very low amounts in somatic tissues. Based on their homologies and expression profiles, we inferred that they had putative roles in spermatogenesis. Detection of sequences differentially expressed in testis, ovary, or both, was a useful approach for identifying new genes related to bovine spermatogenesis. The data reported here contributed to discovery of gene pathways involved in bovine spermatogenesis, with potential for prediction of fertility. (C) 2011 Elsevier Inc. All rights reserved.

Different strains of mice present distinct lung tissue mechanics and extracellular matrix composition in a model of chronic allergic asthma

The impact of genetic factors on asthma is well recognized but poorly understood. We tested the hypothesis that different mouse strains present different lung tissue strip mechanics in a model of chronic allergic asthma and that these mechanical differences may be potentially related to changes of extracellular matrix composition and/or contractile elements in lung parenchyma. Oscillatory mechanics were analysed before and after acetylcholine (ACh) in C57BL/10, BALB/c, and A/J mice, subjected or not to ovalbumin sensitization and challenge. In controls, tissue elastance (E) and resistance (R), collagen and elastic fibres` content, and alpha-actin were higher in A/J compared to BALB/c mice, which, in turn, were more elevated than in C57BL/10. A similar response pattern was observed in ovalbumin-challenged animals irrespective of mouse strain. E and R augmented more in ovalbumin-challenged A/J [E: 22%, R: 18%] than C57BL/10 mice [E: 9.4%, R: 11 %] after ACh In conclusion, lung parenchyma remodelled differently yielding distinct in vitro mechanics according to mouse strain. (C) 2008 Elsevier B.V. All rights reserved.

Prognostic value of NDRG1 and SPARC protein expression in breast cancer patients

An increasing number of studies have shown altered expression of secreted protein acidic and rich in cysteine (SPARC) and N-myc down-regulated gene (NDRG1) in several malignancies, including breast carcinoma; however, the role of these potential biomarkers in tumor development and progression is controversial. In this study, NDRG1 and SPARC protein expression was evaluated by immunohistochemistry on tissue microarrays containing breast tumor specimens from patients with 10 years of follow-up. NDRG1 and SPARC protein expression was determined in 596 patients along with other prognostic markers, such as ER, PR, and HER2. The status of NDRG1 and SPARC protein expression was correlated with prognostic variables and patient clinical outcome. Immunostaining revealed that 272 of the 596 cases (45.6%) were positive for NDRG1 and 431 (72.3%) were positive for SPARC. Statistically significant differences were found between the presence of SPARC and NDRG1 protein expression and standard clinicopathological variables. Kaplan-Meier analysis showed that NDRG1 positivity was directly associated with shorter disease-free survival (DFS, P < 0.001) and overall survival (OS, P < 0.001). In contrast, patients expressing low levels of SPARC protein had worse DFS (P = 0.001) and OS (P = 0.001) compared to those expressing high levels. Combined analysis of the two markers indicated that DFS (P < 0.001) and OS rates (P < 0.001) were lowest for patients with NDRG1-positive and SPARC-negative tumors. Furthermore, NDRG1 over-expression and SPARC down-regulation correlated with poor prognosis in patients with luminal A or triple-negative subtype breast cancer. On multivariate analysis using a Cox proportional hazards model, NDRG1 and SPARC protein expression were independent prognostic factors for both DFS and OS of breast cancer patients. These data indicate that NDRG1 over-expression and SPARC down-regulation could play important roles in breast cancer progression and serve as useful biomarkers to better define breast cancer prognosis.

Reticular angiomatoid ""malignant"" fibrous histiocytoma-a case report with cytogenetics and molecular genetic analyses

Angiomatoid ""malignant"" fibrous histiocytoma is a rare sarcoma of low malignant potential that occurs most commonly in the extremities of children and young adults. Herein, we present a case of angiomatoid malignant fibrous histiocytoma with unusual histologic features arising in the mediastinum of an 80-year-old man. The tumor exhibited a reticular growth pattern and myxoid stroma. The tumor cells expressed epithelial membrane antigen and desmin. Cytogenetic analysis revealed the translocation t(2;22)(q33;q12). Molecular genetic analysis confirmed the rearrangement of the EWSR1 locus and the presence of the EWSR1/CREB1 fusion. This report expands the clinicopathologic spectrum of angiomatoid malignant fibrous histiocytoma and underscores the value of integrating morphologic, immunophenotypic, and molecular findings in the identification of its unusual morphologic variants. (C) 2011 Elsevier Inc. All rights reserved.

Effects of electrotactile vestibular substitution on rehabilitation of patients with bilateral vestibular loss

The present study evaluated the effectiveness of electrotactile tongue biofeedback (BrainPort (R)) as a sensory substitute for the vestibular apparatus in patients with bilateral vestibular loss (BVL) who did not have a good response to conventional vestibular rehabilitation (VR). Seven patients with BVL were trained to use the device. Stimulation on the surface of the tongue was created by a dynamic pattern of electrical pulses and the patient was able to adjust the intensity of stimulation and spatially centralize the stimulus on the electrode array. Patients were directed to continuously adjust head orientation and to maintain the stimulus pattern at the center of the array. Postural tasks that present progressive difficulties were given during the use of the device. Pre- and post-treatment distribution of the sensory organization test (SOT) composite score showed an average value of 38.3 +/- 8.7 and 59.9 +/- 11.3, respectively, indicating a statistically significant improvement (p = 0.01). Electrotactile tongue biofeedback significantly improved the postural control of the study group, even if they had not improved with conventional VR. The electrotactile tongue biofeedback system was able to supply additional information about head position with respect to gravitational vertical orientation in the absence of vestibular input, improving postural control. Patients with BVL can integrate electrotactile information in their postural control in order to improve stability after conventional VR. These results were obtained and verified not only by the subjective questionnaire but also by the SOT composite score. The limitations of the study are the small sample size and short duration of the follow-up. The current findings show that the sensory substitution mediated by electrotactile tongue biofeedback may contribute to the improved balance experienced by these patients compared to VR. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Validation of a Cutoff Value on Echo Doppler Analysis to Replace Right Heart Catheterization During Pulmonary Hypertension Evaluation in Heart Transplant Candidates

Background. Heart transplantation (OHT) has traditionally been contraindicated in the presence of severe pulmonary hypertension (PH), as detected by right heart catheterization. Noninvasive methods are still not reliably accurate to make this evaluation. Objectives. Determine the efficacy of echo Doppler analysis for the diagnosis of severe PH. Methods. One hundred thirty patients (mean age = 42 +/- 15 years, 82 men) showed severe left ventricular dysfunction (mean ejection fraction = 29 +/- 12%; functional class III-IV). We excluded patients with atrial fibrillation, heart failure secondary to congenital disease, and valvulopathy. The pulmonary parameters defined as severe PH were: systolic pulmonary artery pressure (sPAP) >= 60 mm Hg; a mean transpulmonary gradient >= 15; or pulmonary vascular resistance >= 5 Wood units. Patients underwent a right heart catheterization using a Swan-Ganz catheter to measure hemodynamic parameters and to noninvasively estimate right-sided pressures from spectral Doppler recordings of tricuspid regurgitation velocity (right ventricular systolic pressure [RVsP]). A Pearson correlation of sPAP was obtained with RVsP by; the sensitivity of RVsP for the diagnosis of PH was determined by a receiver operating characteristic (ROC) curve. Results. A good correlation between sPAP and RVsP was obtained by Pearson correlation analysis (r = 0.64; 95% confidence interval [CI] 0.50-0.75; P < .001). The ROC curve analysis showed a sensitivity of 100%, a specificity of 37.2%, (95% CI 0.69-0.83, P < .0001) of a RVsP < 45 mm Hg (cutoff) on the exclusion of severe PH. Conclusions. The cutoff of RVsP < 45 mm Hg, on noninvasive echo Doppler evaluation of PH is an efficient method to replace invasive heart catheterization in OHT candidates.

Effect of PaCO(2) variation on standard base excess value in critically ill patients

Purpose: The aim of this study was to investigate the impact of acute PaCO(2) temporal variation on the standard base excess (SBE) value in critically ill patients. Methods: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding PaCO(2) as a variable determinant of SBE), and both were tested in the validation group. Results: In the modeling group, the mathematical model including SIDai, SIG, L-lactate, albumin, phosphate, and PaCO(2) had a predictive superiority in comparison with the model without PaCO(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without PaCO(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. Conclusions: Acute PaCO(2), temporal variation is related to SBE changes in critically ill patients. (C) 2009 Elsevier Inc. All rights reserved.