Spectrum and Prevalence of FP/TMEM127 Gene Mutations in Pheochromocytomas and Paragangliomas

Context Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. Objectives To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. Design, Setting, and Participants We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. Main Outcome Measures The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. Results We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P=2.7 x 10(-4)) and/or with familial disease (5 of 20 samples; P=.005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P=.54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. Conclusions Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occured in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein. JAMA. 2010;304(23):2611-2619 www.jama.com

Incidence of stroke subtypes, prognosis and prevalence of risk factors in Joinville, Brazil: a 2 year community based study

Background: There have been few population based studies on stroke risk factors and prognosis conducted in Brazil. The objective of this study was to evaluate, over a 2 year period, the incidence of the subtypes of first ever stroke, the prevalence of cardiovascular risk factors and functional prognosis in a city located in the south of Brazil. Methods: The period from January 2005 to December 2006 was evaluated prospectively by compiling data on first ever stroke cases, medications used prior to the morbidity and the incidence of traditional risk factors. The annual incidence was adjusted for age using the direct method. Patients were monitored for at least 6 months following the event. Results: Of 1323 stroke cases, 759 were first ever stroke cases. Of these, 610 were classified as infarctions, 94 as intracerebral haemorrhage and 55 as subarachnoid haemorrhage. The crude incidence rate per 100 000 inhabitants was 61.8 for infarction (95% CI 57.0 to 66.9), 9.5 for intracerebral haemorrhage (95% CI 7.7 to 11.6) and 5.6 for subarachnoid haemorrhage (95% CI 4.2 to 7.3). The 30 day case fatality was 19.1%. The most prevalent cardiovascular risk factor was arterial hypertension. By post-stroke month 6, 25% had died (95% CI 21.4 to 29.1) whereas 61.5% had regained their independence (95% CI 56.2 to 68.3). Conclusions: Case fatality rate, prognosis and incidence adjusted for stroke subtypes were similar to those found in other population based studies. The prevalence rates of ischaemic heart disease, dyslipidaemia, arterial hypertension and diabetes suggest that Joinville presents a mixed pattern of cardiovascular risk, a pattern seen in developed and developing countries alike.

High prevalence of dementia among older adults from poor socioeconomic backgrounds in Sao Paulo, Brazil

Background: The aim of this study was to determine the prevalence of dementia in a socioeconomically disadvantaged population of older adults living in the city of Sao Paulo, Brazil. Methods: A cross-sectional one-phase population-based study was carried out among all residents aged >= 65 in defined census sectors of an economically disadvantaged area of Sao Paulo. Identification of cases of dementia followed the protocol developed by the 10/66 Dementia Research Group. Results: Of 2072 individuals in the study, 105 met the criteria for a diagnosis of dementia, yielding a prevalence of 5.1%. Prevalence increased with age for both men and women after age 75 years, but was stable from 65 to 74 years. Low education and income were associated with increased risk of dementia. Conclusions: The prevalence of dementia among older adults from low socioeconomic backgrounds is high. This may be partly due to adverse socioeconomic conditions and consequent failure to compress morbidity into the latter stages of life. The increasing survival of poorer older adults with dementia living in developing countries may lead to a rapid increase in the prevalence of dementia worldwide.

Fabry Disease in Hemodialysis Patients in Southern Brazil: Prevalence Study and Clinical Report

Background. Fabry disease (FD) is a lysosomal storage disorder caused by a deficiency of -Galactosidase A (-Gal A). Fabry nephropathy typically progresses throughout the fifth decade to end-stage renal disease (ESRD), requiring hemodialysis and/or kidney transplantation. Objective. To estimate the prevalence of FD among ESRD males on hemodialysis treatment in Rio Grande do Sul, the southernmost state of Brazil. Methods. Screening for -Gal A activity was performed by a dried blood spot (normal reference value: 1.5 nmoles/hour/mL). Positive screening results were confirmed by plasma -Gal A activity assay (reference value: 3.3 nmoles/hour/mL). Results. Five hundred fifty-eight male patients on hemodialysis were evaluated. Of these, only two had low -Gal A activity and were diagnosed with Fabry disease (0.36%). One of these, age 42, had left ventricular hypertrophy and renal manifestations of Fabry disease without the classic symptoms. The other, age 46, had the classical manifestations of angiokeratomas, acroparesthesias, hypohidrosis, and ocular opacities. Conclusions. Although the prevalence of Fabry disease was very low in our study (0.36%), routine screening of male hemodialysis patients would enable earlier identification of many other affected relatives in their families who might benefit from specific clinical treatment.

Prevalence of cognitive and functional impairment in a community sample from Sao Paulo, Brazil

Aims: To present the prevalence of cognitive and functional impairment (CFI) in community-dwelling elderly subjects from the city of Sao Paulo. Methods: The population was aged 60 years and older (n = 1,563; 68.7% women and 31.3% men) and lived in different socioeconomic areas. The following instruments were administered to the elderly: the Mini Mental State Examination and the Fuld Object Memory Evaluation. The Informant Questionnaire on Cognitive Decline in the Elderly and the Bayer-Activities of Daily Living scale were administered to an informant. Results: The prevalence of CFI (n = 250) was 16% (95% confidence interval, CI: 14.2-17.8%) or 15.8% (95% CI: 13.8-17.8%). In regression models, the increase in the odds ratio (OR) of CFI was associated with age, for elderly individuals aged 75 years or older, illiterates or with 1-4 years of schooling, and with a history of stroke and diabetes mellitus. On the other hand, for subjects with a tumor history, the OR of CFI was significantly reduced. Conclusion: CFI was high and increased at older ages and in subjects with low education. Potentially changeable factors were identified (stroke and diabetes), and the possible `protective effect` of tumor/cancer against CFI should be further investigated by longitudinal studies. Copyright (C) 2007 S. Karger AG, Basel.

Anti-nucleosome and anti-chromatin antibodies are present in active systemic lupus erythematosus but not in the cutaneous form of the disease

The objective of this study is to investigate the presence of anti-nucleosome (anti-NCS) and anti-chromatin (anti-CRT) antibodies in patients with cutaneous lupus erythematosus (CLE) compared with active and inactive systemic lupus erythematosus (SLE). A total of 154 subjects were evaluated: 54 patients presenting CLE, 66 patients with active SLE and 34 with inactive SLE. Lupus activity was assessed using the disease activity index (SLEDAI). Anti-NCS and anti-CRT antibodies were detected by enzyme-linked immunosorbent assay ( ELISA). Only one of 54 patients with CLE tested positive for both anti-NCS and anti-CRT antibodies. The prevalence of anti-CRT antibodies was significantly higher in active SLE (84.8%) when compared with inactive SLE (26.4%) and CLE (1.8%) ( P < 0.001). Anti-NCS antibodies were also more prevalent in active SLE patients (74.2%) than inactive SLE (11.7%) and CLE patients ( 1.8%) ( P < 0.001). The presence of anti-CRT and anti-NCS antibodies was correlated to disease activity in patients with SLE (r = 0.4937, r = 0.5621, respectively). Furthermore, the detection of both antibodies was correlated with disease activity in patients with SLE who tested negative for anti-dsDNA antibodies ( r = 0.4754 for anti-NCS and r = 0.4281 for anti-CRT). The presence of these two auto-antibodies was strongly associated with renal damage in patients with SLE ( OR = 13.1, for anti-CRT antibodies and OR = 25.83, for anti-NCS antibodies). The anti-NCS and anti-CRT antibodies were not found in CLE. In patients with SLE, there is a correlation of these antibodies with disease activity and active nephritis. When compared with anti-dsDNA antibodies, anti-NCS and anti-CRT antibodies were more sensitive in detecting disease activity and kidney damage in lupus patients. Lupus (2009) 18, 223-229.

Prevalence of Toxoplasma gondii and Neospora caninum infections in sheep from Federal District, central region of Brazil

Serum samples from 1028 sheep were collected from 32 herds within Federal District, in the central region of Brazil. The samples were examined by indirect fluorescent antibody test (IFAT) using sera diluted 1:64 and 1:50 as cut-off values for the detection of antibodies against Toxoplasma gondii and Neospora caninum, respectively. The observed prevalence for T. gondii infection was 38.22% (26.81%< CI 0.95 < 49.62%), and the titers ranged from 64 to 65536. The observed prevalence for N. caninum infection was 8.81% (7.08%< CI 0.95 < 10.53%). The titers ranged from 50 to 51200. The reactant sera to both pathogens corresponded to 4.67% of the samples. The risk factors were not determined because of the absence of negative herds for T. gondii and the high proportion of positive herds for N. caninum (87.50%). The prevalence for T. gondii infection was significantly higher among males than in females. The present work is the first report on seroprevalence of T. gondii and N. caninum in sheep from Federal District and shows that infection by both parasites is widespread in the ovine population from this region.

Canine visceral leishmaniasis: Performance of a rapid diagnostic test (Kalazar Detect (TM)) in dogs with and without signs of the disease

Current visceral leishmaniasis (VL) control programs in Brazil include the infected dog elimination but, despite this strategy, the incidence of human VL is still increasing. One of the reasons is the long delay between sample collection, analysis, control implementation and the low sensitivity of diagnostic tests. Due to the high prevalence of asymptomatic dogs, the diagnosis of these animals is important considering their vector infection capacity. Hence, a rapid and accurate diagnosis of canine visceral leishmaniasis is essential for an efficient surveillance program. In this study we evaluated the performance of rK39 antigen in an immunochromatographic format to detect symptomatic and asymptomatic Leishmania chagasi infection in dogs and compared the results with those using a crude antigen ELISA. The sensitivity of rK39 dipstick and ELISA were 83% vs. 95%, respectively, while the specificity was both 100%. Our results also demonstrated that the dipstick test was able to detect infected dogs presenting different clinical forms. (C) 2008 Elsevier B.V. All rights reserved.

Celiac disease detection using a transglutaminase electrochemical immunosensor fabricated on nanohybrid screen-printed carbon electrodes

Celiac disease is a gluten-induced autoimmune enteropathy characterized by the presence of tissue tranglutaminase (tTG) autoantibodies. A disposable electrochemical immunosensor (EI) for the detection of IgA and IgG type anti-tTG autoantibodies in real patient’s samples is presented. Screen-printed carbon electrodes (SPCE) nanostructurized with carbon nanotubes and gold nanoparticles were used as the transducer surface. This transducer exhibits the excellent characteristics of carbon–metal nanoparticle hybrid conjugation and led to the amplification of the immunological interaction. The immunosensing strategy consisted of the immobilization of tTG on the nanostructured electrode surface followed by the electrochemical detection of the autoantibodies present in the samples using an alkaline phosphatase (AP) labelled anti-human IgA or IgG antibody. The analytical signal was based on the anodic redissolution of enzymatically generated silver by cyclic voltammetry. The results obtained were corroborated with a commercial ELISA kit indicating that the electrochemical immunosensor is a trustful analytical screening tool.

An electrochemical deamidated gliadin antibody immunosensor for celiac disease clinical diagnosis

The first electrochemical immunosensor (EI) for the detection of antibodies against deamidated gliadin peptides (DGP) is described here. A disposable nanohybrid screen-printed carbon electrode modified with DGP was employed as the transducer's sensing surface. Real serumsampleswere successfully assayed and the results were corroborated with an ELISA kit. The presented EI is a promising analytical tool for celiac disease diagnosis.

Low prevalence of hypertension with pharmacological treatments and associated factors

OBJECTIVE: To assess the determinants of the lack of pharmacological treatment for hypertension. METHODS: In 2005, 3,323 Mozambicans aged 25-64 years old were evaluated. Blood pressure, weight, height and smoking status were assessed following the Stepwise Approach to Chronic Disease Risk Factor Surveillance. Hypertensives (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg and/or antihypertensive drug therapy) were evaluated for awareness of their condition, pharmacological and non-pharmacological management, as well as use of herbal or traditional remedies. Prevalence ratios (PR) were calculated, adjusted for sociodemographic characteristics, cardiovascular risk factors and non-pharmacological treatment. RESULTS: Most of the hypertensive subjects (92.3%), and nearly half of those aware of their condition were not treated pharmacologically. Among the aware, the prevalence of untreated hypertension was higher in men {PR = 1.61; 95% confidence interval (95%CI 1.10;2.36)} and was lower in subjects under non-pharmacological treatment (PR = 0.58; 95%CI 0.42;0.79); there was no significant association with traditional treatments (PR = 0.75; 95%CI 0.44;1.26). CONCLUSIONS: The lack of pharmacological treatment for hypertension was more frequent in men, and was not influenced by the presence of other cardiovascular risk factors; it could not be explained by the use of alternative treatments as herbal/traditional medicines or non-pharmacological management. It is important to understand the reasons behind the lack of management of diagnosed hypertension and to implement appropriate corrective actions to reduce the gap in the access to healthcare between developed and developing countries.

Prevalence of syphilis in pregnancy and prenatal syphilis testing in Brazil: Birth in Brazil study

OBJECTIVE Determine the coverage rate of syphilis testing during prenatal care and the prevalence of syphilis in pregnant women in Brazil. METHODS This is a national hospital-based cohort study conducted in Brazil with 23,894 postpartum women between 2011 and 2012. Data were obtained using interviews with postpartum women, hospital records, and prenatal care cards. All postpartum women with a reactive serological test result recorded in the prenatal care card or syphilis diagnosis during hospitalization for childbirth were considered cases of syphilis in pregnancy. The Chi-square test was used for determining the disease prevalence and testing coverage rate by region of residence, self-reported skin color, maternal age, and type of prenatal and child delivery care units. RESULTS Prenatal care covered 98.7% postpartum women. Syphilis testing coverage rate was 89.1% (one test) and 41.2% (two tests), and syphilis prevalence in pregnancy was 1.02% (95%CI 0.84;1.25). A lower prenatal coverage rate was observed among women in the North region, indigenous women, those with less education, and those who received prenatal care in public health care units. A lower testing coverage rate was observed among residents in the North, Northeast, and Midwest regions, among younger and non-white skin-color women, among those with lower education, and those who received prenatal care in public health care units. An increased prevalence of syphilis was observed among women with < 8 years of education (1.74%), who self-reported as black (1.8%) or mixed (1.2%), those who did not receive prenatal care (2.5%), and those attending public (1.37%) or mixed (0.93%) health care units. CONCLUSIONS The estimated prevalence of syphilis in pregnancy was similar to that reported in the last sentinel surveillance study conducted in 2006. There was an improvement in prenatal care and testing coverage rate, and the goals suggested by the World Health Organization were achieved in two regions. Regional and social inequalities in access to health care units, coupled with other gaps in health assistance, have led to the persistence of congenital syphilis as a major public health problem in Brazil.

Prevalence of antibody to hepatitis B virus in an urban population of northeast Brazil

A sample of 1,288 inhabitants of Salvador, Bahia, Brazil, were submitted to the determination of anti-HBs using radioimmunoassay procedure, and analysed according to age, sex and income. Overall prevalence of anti-HBs was 11,8%. ranging from 6,7% among children aged less than three years old to 26,1% among those aged 30 years and older. Males presented prevalence of anti-HBs similar to female individuals, and those with a higher income showed frequencies of anti-HBs greater than those with a lower income level. The following conclusions were drawn: The high prevalence of anti-HBs observed among children suggests early contact with hepatitis B virus, possibly due to vertical transmission and intrafamiliar dissemination of the disease; the frequency of anti-HBs increases with age; the lower prevalence of anti-HBs among those with low income suggests that this group may present higher prevalence of carriers of the hepatitis B virus surface antigen.

Seroepidemiological and clinical study of Chagas' disease in Nicaragua

With the aim of determining the prevalence, immunological profile, and knowing the electrocardiographic alterations, a clinical and Seroepidemiological study of Chagas' disease was performed in three rural settlements located at the North, East and West of Nicaragua. Anti T. cruzi antibodies were searched by indirect immunofluorescence (IFI) and hemagglutination (IHA) in a total of 803 subjects. Seropositives and the same number of seronegatives, matched by age and sex, were included in a case-control design for the electrocardiographic assessment. Antibody prevalence was 13.1, 4.3 and 3.2% in the respective settlements. In the first two the immunological profile corresponds to that of an endemic zone of long standing, were transmission has decreased, and in the third the pattern is of a zone under control. Electrocardiographic changes compatible with Chagas' disease were found in seropositive individuals, but difference with control group was not statistically significant. It is concluded that the disease is endemic in the three settlements and the clinical aspect requires further evaluation, including additional cardiologic techniques.