Spirometric values in elderly asthmatic patients are not influenced by obesity

Background Studies have suggested that asthma in obese individuals differs from the classic asthma phenotype, presenting as a disease that is more difficult to control. Objective The objective of the present study was to determine whether obesity, age or a combination of the two are associated with worse spirometry parameters in patients with asthma. Methods This was an observational cross-sectional study involving patients over 18 years of age who had been diagnosed with asthma (allergic or nonallergic). We evaluated the results of their spirometric tests. The patients were classified in accordance with two criteria: body mass index (BMI) and age. Based on their BMIs, the patients were divided into three groups: normal weight, overweight and obese. Patients were also separated into two categories by age: 18-59 years of age; and >= 60 years of age. Results We evaluated 451 patients with asthma and their spirometry tests. In the present study, the pulmonary function parameters were negatively correlated with BMI and age (P < 0.05). We found that there was a statistically significant correlation between spirometric values and BMI among patients 18-59 years of age (P < 0.001), however, among patients over 60, we did not observe this negative association. Conclusions and Clinical Relevance The spirometric values decreased significantly in proportion to the increase of BMI and age in patients with asthma, especially among young adults. There was no negative correlation between BMI and FEV1 in the group >= 60 years of age, suggesting that perhaps the time of disease is a major factor in the loss of lung function than weight gain in the elderly.

Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus

Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.

Searching for chronic hepatitis B patients in a low prevalence area – role of racial origin

Abstract Background Clinical studies for testing new drugs against hepatitis B ought to be carried out in low prevalence areas despite difficulties on patient recruitment. In such areas, relatives of chronic hepatitis B patients are considered to be at risk of acquiring the hepatitis B virus (HBV). The aim of this study was to evaluate the prevalence of HBV markers (anti-HBc, HBsAg and anti-HBs) in familial members of chronic hepatitis B (CHB) patients according to their origin (Asian or Western) in a low prevalence area, the city of São Paulo, Brazil. Methods Twenty three Asian CHB probands and their 313 relatives plus 31 CHB probands of Western origin and their 211 relatives were screened for HBV serological markers; the study was carried out in the outpatient clinic of the University of São Paulo School of Medicine. Results Mother to child transmission was greater in the Asian group whereas sexual transmission was more frequent in the Western group (p < 0.0001). Anti-HBc was positive in 90% and 57% of the Asian and Western parents (p = 0.0432) and in 97% and 33% of the Asian and Western brothers (p = 0.0001), respectively. HBsAg was more frequent among the Asian (66%) than the Western (15%) mothers (p = 0.0260) as well as among the Asian (81%) than the Western (19%) brothers (p = 0.0001). We could detect 110 new HBsAg-positive subjects related to the 54 index patients, being the majority (81%) of Asian origin. Conclusion In low prevalence area of hepatitis B, family members and household contacts of chronic HBV carriers are at high risk for acquiring hepatitis B.

Heritability of physical activity traits in Brazilian families: the Baependi Heart Study

Background It is commonly recognized that physical activity has familial aggregation; however, the genetic influences on physical activity phenotypes are not well characterized. This study aimed to (1) estimate the heritability of physical activity traits in Brazilian families; and (2) investigate whether genetic and environmental variance components contribute differently to the expression of these phenotypes in males and females. Methods The sample that constitutes the Baependi Heart Study is comprised of 1,693 individuals in 95 Brazilian families. The phenotypes were self-reported in a questionnaire based on the WHO-MONICA instrument. Variance component approaches, implemented in the SOLAR (Sequential Oligogenic Linkage Analysis Routines) computer package, were applied to estimate the heritability and to evaluate the heterogeneity of variance components by gender on the studied phenotypes. Results The heritability estimates were intermediate (35%) for weekly physical activity among non-sedentary subjects (weekly PA_NS), and low (9-14%) for sedentarism, weekly physical activity (weekly PA), and level of daily physical activity (daily PA). Significant evidence for heterogeneity in variance components by gender was observed for the sedentarism and weekly PA phenotypes. No significant gender differences in genetic or environmental variance components were observed for the weekly PA_NS trait. The daily PA phenotype was predominantly influenced by environmental factors, with larger effects in males than in females. Conclusions Heritability estimates for physical activity phenotypes in this sample of the Brazilian population were significant in both males and females, and varied from low to intermediate magnitude. Significant evidence for heterogeneity in variance components by gender was observed. These data add to the knowledge of the physical activity traits in the Brazilian study population, and are concordant with the notion of significant biological determination in active behavior.

Should extragonadal germ cell tumors be included in studies of families with testicular germ cell tumors?

Abstract Background Family history is among the few established risk factors for testicular germ cell tumor (TGCT). Approximately 1.4% of newly diagnosed TGCT patients report a positive family history of TGCT. Sons and siblings of TGCT patients have four- to six fold and eight- to tenfold increase in TGCT risk, respectively. In twins of men with TGCT the relative risk of testicular cancer is 37.5 (12.3-115.6). Nevertheless, information about the occurrence of TGCT in relatives of patients with extragonadal germ cell tumor is limited. Case report A 24 year-old male patient was diagnosed with a mediastinum tumor and was submitted to image-guided biopsy, which revealed a seminoma. Two months later, his non-identical asymptomatic twin brother was submitted to an elective ultrasound of the testes, which showed a left testicular mass of 4.2 cm. This patient underwent orchiectomy revealing a seminoma of the left testis. There are no other cases of seminoma or other types of cancers reported in first-degree relatives in this family. Conclusions Although familial aggregations of TGCT have been well described, to the best of our knowledge, no data concerning the association of gonadal and extragonadal germ cell tumor in relatives has been previously reported. Further investigation on this association is warranted and may help in improving our knowledge of familial pattern inheritance.

Prevalence of the BRCA1 founder mutation c.5266dupin Brazilian individuals at-risk for the hereditary breast and ovarian cancer syndrome

About 5-10% of breast and ovarian carcinomas are hereditary and most of these result from germline mutations in the BRCA1 and BRCA2 genes. In women of Ashkenazi Jewish ascendance, up to 30% of breast and ovarian carcinomas may be attributable to mutations in these genes, where 3 founder mutations, c.68_69del (185delAG) and c.5266dup (5382insC) in BRCA1 and c.5946del (6174delT) in BRCA2, are commonly encountered. It has been suggested by some authors that screening for founder mutations should be undertaken in all Brazilian women with breast cancer. Thus, the goal of this study was to determine the prevalence of three founder mutations, commonly identified in Ashkenazi individuals in a sample of non-Ashkenazi cancer-affected Brazilian women with clearly defined risk factors for hereditary breast and ovarian cancer (HBOC) syndrome. Among 137 unrelated Brazilian women from HBOC families, the BRCA1c.5266dup mutation was identified in seven individuals (5%). This prevalence is similar to that encountered in non-Ashkenazi HBOC families in other populations. However, among patients with bilateral breast cancer, the frequency of c.5266dup was significantly higher when compared to patients with unilateral breast tumors (12.1% vs 1.2%, p = 0.023). The BRCA1 c.68_69del and BRCA2 c.5946del mutations did not occur in this sample. We conclude that screening non-Ashkenazi breast cancer-affected women from the ethnically heterogeneous Brazilian populations for the BRCA1 c.68_69del and BRCA2 c.5946del is not justified, and that screening for BRCA1c.5266dup should be considered in high risk patients, given its prevalence as a single mutation. In high-risk patients, a negative screening result should always be followed by comprehensive BRCA gene testing. The finding of a significantly higher frequency of BRCA1 c.5266dup in women with bilateral breast cancer, as well as existence of other as yet unidentified founder mutations in this population, should be further assessed in a larger well characterized high-risk cohort.

Fatores causais e aplicação de provas complementares relacionadas à gravidade no transtorno fonológico

OBJETIVO: Verificar se o índice de gravidade, que mede a porcentagem de consoantes corretas, distingue as crianças com transtorno fonológico em relação às medidas de estimulabilidade e inconsistência de fala, bem como à presença dos históricos familial e de otite média. MÉTODOS: Participaram da pesquisa 15 sujeitos com idades entre 5 e 7 anos e 11meses, com diagnóstico de transtorno fonológico. O índice Porcentagem de Consoantes Corretas - Revisado (PCC-R) foi calculado para as provas de imitação de palavras e de nomeação de figuras, separadamente. A partir destas provas também foi computada a necessidade de aplicação da prova de estimulabilidade, de acordo com os critérios propostos em pesquisas anteriores. A prova de inconsistência de fala permitiu classificar os sujeitos como consistentes ou inconsistentes. Os dados foram submetidos à análise estatística. RESULTADOS: Na comparação entre os valores do PCC-R medido na prova de nomeação e de imitação foi observada diferença em relação à necessidade da aplicação da estimulabilidade. Em relação à prova de inconsistência de fala, não houve evidência desta relação. Não foi verificada diferença no PCC-R considerando-se a presença dos históricos de otite média e familial. CONCLUSÃO: O estudo indica que as crianças que precisaram da aplicação da prova de estimulabilidade apresentaram valores mais baixos de PCC-R. Entretanto, em relação à prova de inconsistência de fala e aos históricos de otite ou familial, o PCC-R não determinou diferenças entre as crianças.

Pituitary tumors in patients with MEN1 syndrome

We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

Surgical approach to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2

We briefly review the surgical approaches to medullary thyroid carcinoma associated with multiple endocrine neoplasia type 2 (medullary thyroid carcinoma/multiple endocrine neoplasia type 2). The recommended surgical approaches are usually based on the age of the affected carrier/patient, tumor staging and the specific rearranged during transfection codon mutation. We have focused mainly on young children with no apparent disease who are carrying a germline rearranged during transfection mutation. Successful management of medullary thyroid carcinoma in these cases depends on early diagnosis and treatment. Total thyroidectomy should be performed before 6 months of age in infants carrying the rearranged during transfection 918 codon mutation, by the age of 3 years in rearranged during transfection 634 mutation carriers, at 5 years of age in carriers with level 3 risk rearranged during transfection mutations, and by the age of 10 years in level 4 risk rearranged during transfection mutations. Patients with thyroid tumor >5 mm detected by ultrasound, and basal calcitonin levels >40 pg/ml, frequently have cervical and upper mediastinal lymph node metastasis. In the latter patients, total thyroidectomy should be complemented by extensive lymph node dissection. Also, we briefly review our data from a large familial medullary thyroid carcinoma genealogy harboring a germline rearranged during transfection Cys620Arg mutation. All 14 screened carriers of the rearranged during transfection Cys620Arg mutation who underwent total thyroidectomy before the age of 12 years presented persistently undetectable serum levels of calcitonin (<2 pg/ml) during the follow-up period of 2-6 years. Although it is recommended that preventive total thyroidectomy in rearranged during transfection codon 620 mutation carriers is performed before the age of 5 years, in this particular family the surgical intervention performed before the age of 12 years led to an apparent biochemical cure.

Anti-Toxocara spp. antibodies in an adult healthy population: serosurvey and risk factors in Southeast Brazil.

Objective: To evaluate the frequency of anti-Toxocara spp. antibodies in an adult healthy population. Methods: The study was performed by interviewing 253 blood donors, from 19 to 65 years of age, in a hematological centre in Presidente Prudente, São Paulo, southeast Brazil. A survey was applied to blood donors in order to evaluate the possible factors associated to the presence of antibodies, including individual (gender and age), socioeconomic (scholarship, familial income and sanitary facilities) and habit information (contact with soil, geophagy, onycophagy and intake of raw/undercooked meat) as well as the presence of dogs or cats in the household. ELISA test was run for detection of the anti-Toxocara spp. IgG antibodies. Bivariate analysis followed by logistic regression was performed to evaluate the potential risk factors associated to seropositivity. Results: The overall prevalence observed in this study was 8.7% (22/253). Contact with soil was the unique risk factor associated with the presence of antibodies (P=0.0178 ; OR=3.52; 95% CI=1.244-9.995) Conclusions. The results of this study reinforce the necessity in promoting preventive public health measures, even for healthy adult individual, particularly those related to the deworming of pets to avoid the soil contamination, and hygiene education of the population.