Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Musculoskeletal disorders (MSDs) in dancers and former dancers participating in the largest dance festival in the world

Objective: To verify the presence of musculoskeletal disorders (MSD) in dancers and former dancers participating in the 27th Joinville Dance FestivalMaterial and methods: The research was conducted at the 27th Joinville Dance Festival in Santa Catarina, Brazil, with 173 participants in the competition, where 139 were dancers and 34 were former dancers with at least ten years of practiceIn order to obtain information related to MSDs, dancers answered a specific questionnaireResults: The study group consisted of adults (28±9 years) with body mass index within the normal range (21.3±2.3) with high weekly training time (955.7±837.2) and featuring long-time experience in dancing (18±7years)The lumbar spine and knees were the most affected by MSDsThe pain of high intensity was the symptom that most often appeared in reports among survey participantsConclusion: It is important to have deeper knowledge of the prevalence of pain among professional dancers, the factors associated with pain conditions and its impact on everyday life in order to plan new forms of prevention and plan new forms of prevention and treatment within a multidisciplinary approach© 2012 Elsevier Masson SAS.

Potentially inappropriate medications used by the elderly: Prevalence and risk factors in Brazilian care homes

Abstract. Background: The use of potentially inappropriate medications (PIM) among the elderly is a serious public health problem because it is intrinsically linked to increased morbidity and mortality, causing high costs to public health systems. This study's objective was to verify the prevalence of and the factors associated with the use of PIMs by elderly Brazilians in institutional settings. Methods. We performed a transversal study, by consulting the case files of elderly people living in Long Term Care for the Elderly (LTC) in towns in the State of São Paulo, Brazil, as well as structured interviews with the nurses responsible for them.We identified PIMs using the list of recently updated Beers criteria developed by a group of specialists from the American Geriatrics Society (AGS), who reviewed the criteria based on studies with high scientific evidence levels. We defined the factors studied to evaluate the association with PIM use prior to the statistical analyses, which were the chi-square test and multiple logistic regression. Results: Among the elderly who used drugs daily, 82.6% were taking at least one PIM, with antipsychotics (26.5%) and analgesics (15.1%) being the most commonly used. Out of all the medications used, 32.4% were PIMs, with 29.7% of these being PIMs that the elderly should avoid independent of their condition, 1.1% being inappropriate medication for older adults with certain illnesses or syndromes, and 1.6% being medications that older adults should use with caution. In the multivariate analysis, the factors associated with PIM use were: polypharmacy (p = 0.0187), cerebrovascular disease (p = 0.0036), psychiatric disorders (p < 0.0001) and dependency (p = 0.0404). Conclusions: The results of this study showed a high prevalence of PIM use in institutionalized elderly Brazilian patients. and the associated factors were polypharmacy, psychiatric disorders, cerebrovascular diseases and dependency. © 2013 Lima et al.; licensee BioMed Central Ltd.

Carotid artery atherosclerotic profile as a predictor of the aorta atherosclerotic profile in patients with cerebrovascular events

Background: It is well known that the presence of atheroma of the thoracic aorta is a risk factor for cerebrovascular events. We sought to evaluate whether the presence and the morphology of atherosclerotic plaque in the carotid artery detected by duplex ultrasonography is associated with disease in the proximal aorta visualized by transesophageal echocardiogram in patients with a cerebrovascular event. Methods: We carried out a cross-sectional prospective study including 147 consecutive patients with prior stroke or transient ischemic attack (TIA). Neurological evaluations were performed by an expert neurologist using clinical and tomographic diagnostic criteria including the definition of etiology and whether the patient suffered from stroke or TIA. Transthoracic and transesophageal echocardiograms and carotid artery duplex ultrasonography were performed by the same examiner. Patients with and without plaque in the carotid artery were compared using Student's t test or the χ2 test. Regression analysis was used to determine whether the presence of plaque in the carotid artery was predictive of the presence of plaque in the proximal aorta and to analyze the relationship between the echogenicity of carotid and aortic plaques. The significance level was set at p < 0.05. Results: All 147 patients (95 men) were included in the analysis. Patients' ages ranged from 23 to 85 years (65 ± 12.4 years). Most of the patients (58.5%) were Caucasian, while 41.5% were African-Brazilian. Arterial hypertension, diabetes and tobacco use were more frequent among patients with atherosclerotic plaque in the aorta. A normal carotid intima-media thickness halved the risk of atherosclerotic plaque in the aorta [odds ratio (OR) 0.46, 95% confidence interval (CI) 0.23-0.91; p = 0.026]. The presence of carotid plaque increased the risk of aortic plaque by 70-fold (OR 73.2, 95% CI 25.6-2,018.6; p < 0.001) in univariate analysis. The absence of atherosclerotic plaque in the carotid artery reduced the risk of plaque in the aorta to almost 0 (OR 0.014, 95% CI 0.004-0.041; p < 0.001). Considering the 86 patients with both aortic and carotid plaques, the presence of hypoechoic plaque in the carotid artery was a predictor of hypoechoic plaque in the aorta (OR 10.1, 95% CI 3.3-31.2; p < 0.001). Conclusions: The carotid artery atherosclerotic profile defined by ultrasonography is a strong predictor of the atherosclerotic profile of the proximal aorta. This should be taken into consideration before referring patients with acute cerebrovascular events for transesophageal echocardiogram. © 2013 S. Karger AG, Basel.

Time-course morphological and functional disorders of the kidney induced by long-term high-fat diet intake in female rats

BackgroundEvidence is emerging that highlights the far-reaching consequences of a high-fat diet (HFD) on kidney morphology and function disorders.MethodsThe present study was performed on 3-, 5-, 7- and 9-week-old HFD female rats compared with the appropriate gender and age-matched animals. We evaluated the kidney expression of angiotensin type II receptor and fibrotic and epithelial-to-mesenchymal transition (EMT) markers, by immunoblotting and immunohistochemical and histological techniques, in parallel with kidney function.ResultsIn the current study, the time-course HFD-treated group showed, by immunoblotting and immunohistochemical analysis, an early time-course increase in the expression of transforming growth factor β-1 (TGFβ-1) in the entire kidney of HFD-treated rats, compared with that observed in the control group. Simultaneously, the study shows a transient increase in the expression of ZEB2 in the HFD whole kidney accompanied by a fall in the E-cadherin expression and increased collagen and fibronectin deposition. A pronounced decrease in fractional urinary sodium excretion was also demonstrated in the long-term HFD-treated rats. The decreased FENa + was accompanied by a fall in FEPNa + and FEPP Na +, which occurred in association with significantly decreased CCr and, certainly on the sodium-filtered load. The reduction in the glomerular filtration rate (GFR) occurred in parallel to proteinuria and glomerular desmin overexpression.ConclusionsThe results of the current study suggest that podocyte injury in parallel with observed proteinuria and evidence of EMT transformation are associated with long-term loss of kidney function and renal sodium and water retention. © 2013 The Author. All rights reserved.

Temporomandibular disorders, sleep bruxism, and primary headaches are mutually associated.

To investigate the association among temporomandibular disorders (TMD), sleep bruxism, and primary headaches, assessing the risk of occurrence of primary headaches in patients with or without painful TMD and sleep bruxism. The sample consisted of 301 individuals (253 women and 48 men) with ages varying from 18 to 76 years old (average age of 37.5 years). The Research Diagnostic Criteria for Temporomandibular Disorders were used to classify TMD. Sleep bruxism was diagnosed by clinical criteria proposed by the American Academy of Sleep Medicine, and primary headaches were diagnosed according to the International Classification of Headache Disorders-II. Data were analyzed by chi-square and odds ratio tests with a 95% confidence interval, and the significance level adopted was .05. An association was found among painful TMD, migraine, and tension-type headache (P < .01). The magnitude of association was higher for chronic migraine (odds ratio = 95.9; 95% confidence intervals = 12.51-734.64), followed by episodic migraine (7.0; 3.45-14.22) and episodic tension-type headache (3.7; 1.59-8.75). With regard to sleep bruxism, the association was significant only for chronic migraine (3.8; 1.83-7.84). When the sample was stratified by the presence of sleep bruxism and painful TMD, only the presence of sleep bruxism did not increase the risk for any type of headache. The presence of painful TMD without sleep bruxism significantly increased the risk in particular for chronic migraine (30.1; 3.58-252.81), followed by episodic migraine (3.7; 1.46-9.16). The association between painful TMD and sleep bruxism significantly increased the risk for chronic migraine (87.1; 10.79-702.18), followed by episodic migraine (6.7; 2.79-15.98) and episodic tension-type headache (3.8; 1.38-10.69). The association of sleep bruxism and painful TMD greatly increased the risk for episodic migraine, episodic tension-type headache, and especially for chronic migraine.

Inherited hemoglobin disorders in an Afro-Amazonian community: Saracura

ABSTRACT: The most common hemoglobinopathies, viz, hemoglobins S and C, and α-and β-thalassemias, were investigated through the molecular screening of 116 subjects from the community of Saracura, comprising fugitive African slaves from farms of the municipality of Santarém, in the west of Pará State, Brazilian Amazon. The observed frequency of the HBB*S gene (0.9%) was significantly lower than that encountered in other Afro-derived communities in the region. Concomitantly, the absence of the HBB*C allele has been reported for most of the Afro-Amazonian communities thus far studied. As remnant populations of quilombos are generally small, the heterogeneous distribution of HBB*S and HBB*C alleles among them is probably due to genetic drift and/or founder effect. The observed frequency of 3.7 kb deletion in Saracura (8.5%) was consistent with the African origin of the population, with a certain degree of local differentiation and admixture with individuals of Caucasian ancestry, placed in evidence by the occurrence of - -(MED) deletion (1.2%), a common mutation in Mediterranean regions. As regards f-thalassemia, among the seven different mutations found in Saracura, three βºand two β+ mutations were of Mediterranean origin, and two β+ of African. Thus, only 28% of the local β-thalassemia mutations found in Saracura were of African origin.

Radiographic study of dental anomalies in brazilian patients with neuropsychomotor disorders

The purposes of this study were to investigate radiographically the dental and maxillomandibular in patients with neuropsychomotor disorders and determine the role of panoramic radiographs for quantitative and qualitative analyses of dental alterations. A total of 322 panoramic radiographs from 190 males and 132 females aged 4 to 57 years were obtained from the files of the Center for Care to Patients with Special Needs (CAPE; Dental School, University of São Paulo) and subdivided into syndromes, special needs, neurological, neuromuscular or cerebral disorders, and sequels of diseases. 32% of dental alterations were in tooth position, with 69% of this group associated with tooth rotation. The mandible accounted for 54.62% of alterations. The male gender (55.85%) and the permanent dentition (78.7%) were most affected. Panoramic radiographs were proved to be well suited for quantitative evaluation of dental anomalies of epidemiological nature. Panoramic radiographs are important diagnostic resources when applied to patients with special needs because of the difficulty to place intraoral films and held them correctly positioned during the radiographic technique.

Painful temporomandibular disorders, self reported tinnitus, and depression are highly associated

Objetivo Investigar a associação entre disfunção temporomandibular (DTM) dolorosa, auto-relato de zumbido e níveis de depressão. Método A amostra foi composta por 224 indivíduos com idades de 18 a 76 anos. O Research Diagnostic Criteria for Temporomandibular Disorders , eixo I, foi usado para classificar a DTM e o eixo II para obtenção do auto-relato de zumbido e dos níveis de depressão. Para a análise dos dados, foi aplicado o teste odds ratio (OR) com intervalo de confiança (IC) de 95%. Resultado Somente a presença de DTM dolorosa estava significativamente associada aos níveis de depressão moderado/severo (OR=9,3, 95%; IC: 3,44-25,11). A presença concomitante de DTM dolorosa e auto-relato de zumbido aumentaram a magnitude da associação com os níveis de depressão moderado/severo (OR=16,3; 95% IC: 6,58-40,51). Conclusão Disfunção temporomandibular dolorosa, altos níveis de depressão e auto-relato de zumbido estão fortemente associados. Entretanto, o desenho do estudo não permite estabelecer uma relação causal entre essas três entidades.

uPAR expression in canine normal prostate and with proliferative disorders

Prostatic lesions such as prostatic intraepithelial neoplasia (PIN) and proliferative inflammatory atrophy (PIA) are studied in human and canine species due to their malignance potential. The plasminogen activator (PA) system has been suggested to play a central role in cell adhesion, angiogenesis, inflammation, and tumor invasion. The urokinase-type plasminogen activator receptor (uPAR) is a component of the PA, with a range of expression in tumor and stromal cells. In this study, uPAR expression in both canine normal prostates and with proliferative disorders (benign prostatic hyperplasia-BPH, proliferative inflammatory atrophy-PIA, prostatic intraepithelial neoplasia-PIN, and carcinoma-PC) was evaluated by immunohistochemistry in a tissue microarray (TMA) slide to establish the role of this enzyme in extracellular matrix (ECM) remodeling and in the processes of tissue invasion. A total of 298 cores and 355 diagnoses were obtained, with 36 (10.1%) normal prostates, 46 (13.0%) with BPH, 128 (36.1%) with PIA, 74 (20.8%) with PIN and 71 (20.0%) with PC. There is variation in the expression of uPAR in canine prostate according to the lesion, with lower expression in normal tissue and with BPH, and higher expression in tissue with PIA, PIN and PC. The high expression of uPAR in inflammatory and neoplastic microenvironment indicates increased proteolytic activity in canine prostates with PIA, PIN, and PC.

Severity of temporomandibular disorders in women: validity and reliability of the Fonseca Anamnestic Index

The aim of this study was to assess the validity and reliability of the Fonseca Anamnestic Index (IAF), used to assess the severity of temporomandibular disorders, applied to Brazilian women. We used a probabilistic sampling design. The participants were 700 women over 18 years of age, living in the city of Araraquara (SP). The IAF questionnaire was applied by telephone interviews. We conducted Confirmatory Factor Analysis (CFA) using Chi-Square Over Degrees of Freedom (χ2/df), Comparative Fit Index (CFI), Tucker-Lewis Index (TLI), and Root Mean Square Error of Approximation (RMSEA) as goodness of fit indices. We calculated the convergent validity, the average variance extracted (AVE) and the composite reliability (CR). Internal consistency was assessed by Cronbach's alpha coefficient (α).The factorial weights of questions 8 and 10 were below the adequate values. Thus, we refined the original model and these questions were excluded. The resulting factorial model showed appropriate goodness of fit to the sample (χ2/df = 3.319, CFI = 0.978, TLI = 0.967, RMSEA = 0.058). The convergent validity (AVE = 0.513, CR = 0.878) and internal consistency (α = 0.745) were adequate. The reduced IAF version showed adequate validity and reliability in a sample of Brazilian women.

Treatment of Comorbid Migraine and Temporomandibular Disorders: A Factorial, Double-Blind, Randomized, Placebo-Controlled Study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Incidence of Dysphagia in Patients Receiving Cerebral Reperfusion Therapy Poststroke

Background: The high prevalence of dysphagia after stroke leads to increased mortality, and cerebral reperfusion therapy has been effective in reducing neurologic deficits. The aim of this study was to investigate the severity and evolution of dysphagia and the occurrence of pneumonia in patients submitted to cerebral reperfusion therapy. Methods: Seventy ischemic stroke patients were evaluated. Of these, 35 patients (group 1) were submitted to cerebral reperfusion therapy and 35 (group 2) did not receive thrombolytic treatment. The following were evaluated: severity of dysphagia by means of videofluoroscopy, evolution of oral intake rate by means of the Functional Oral Intake Scale, and the occurrence of pneumonia by international protocol. The relation between the severity of dysphagia and the occurrence of pneumonia with the treatment was evaluated through the chi-square test; the daily oral intake rate and its relation to the treatment were assessed by the Mann-Whitney test and considered significant if P is less than .05. Results: The moderate and severe degrees of dysphagia were more frequent (P = .013) among the patients who were not submitted to cerebral reperfusion therapy. The daily oral intake evolved independently of the treatment type, without statistical significance when compared between the groups, whereas pneumonia occurred more frequently in group 2 (28%) in relation to group 1 (11%) and was associated with the worst degrees of dysphagia (P = .045). Conclusions: We can conclude that there is improvement in the oral intake rate in both groups, with lower severity of dysphagia and occurrence of pneumonia in ischemic stroke patients submitted to cerebral reperfusion therapy. (C) 2014 by National Stroke Association

Enteral nutrition feeding alters antioxidant activity in unstimulated whole saliva composition of patients with neurological disorders

Patients with neurological disorders have an increased risk of oral and systemic diseases due to compromised oral hygiene. If patients lose the ability to swallow and chew food as a result of their disorder, enteral nutrition is often utilized. However, this type of feeding may modify salivary antioxidant defenses, resulting in increased oxidative damage and the emergence of various diseases. The aim of this study was to evaluate the effects of enteral nutrition on biochemical parameters in the unstimulated whole saliva composition of patients with neurological disorders. For this, enzymatic (superoxide dismutase - SOD; glutathione peroxidase - GPx) and non-enzymatic (uric acid; ferric ion reducing antioxidant power - FRAP) antioxidant activity, as well as a marker for oxidative damage (thiobarbituric acid reactive substances - TBARS) were analyzed. Unstimulated whole saliva was collected from 12 patients with neurological disorders and tube-feeding (tube-fed group - TFG), 15 patients with neurological disorders and normal feeding via the mouth (non-tube-fed group - NTFG), and 12 volunteers without neurological disorders (control group - CG). The daily oral hygiene procedures of TFG and NTFG patients were similar and dental care was provided monthly by the same institution's dentist. All patients exhibited adequate oral health conditions. The salivary levels of FRAP, uric acid, SOD, GPx, TBARS, and total protein were compared between studied groups. FRAP was increased (p < 0.05) in the NTFG (4651 +/- 192.5 mmol/mL) and the TFG (4743 +/- 116.7 mmol/mL) when compared with the CG (1844 +/- 343.8 mmol/mL). GPx values were lower (p < 0.05) in the NTGF (8.24 +/- 1.09 mmol/min/mg) and the TFG (8.37 +/- 1.60 mmol/min/mg) than in the CG (15.30 +/- 2.61 mmol/min/mg). Uric acid in the TFG (1.57 +/- 0.23 mg/dL) was significantly lower than in the NTFG (2.34 +/- 0.20 mg/dL) and the CG (3.49 +/- 0.21 mg/dL). Protein was significantly lower in the TFG (5.35 +/- 0.27 g/dL) than in the NTFG (7.22 +/- 0.57 g/dL) and the CG (7.86 +/- 0.54 g/dL). There was no difference in the salivary flow rate and SOD between groups. Enteral nutrition in patients with neurological disorders was associated with lower oxidative damage, resulting in increased salivary. antioxidant capacity. These results emphasize the importance of oral care for this population to prevent oral and systemic diseases. (C) 2014 Elsevier Ltd. All rights reserved.