The association between air pollution and blood pressure in traffic controllers in Santo Andre, Sao Paulo, Brazil

Background: Urban air pollutants are associated with cardiovascular events. Traffic controllers are at high risk for pollution exposure during outdoor work shifts. Objective: The purpose of this study was to evaluate the relationship between air pollution and systemic blood pressure in traffic controllers during their work shifts. Methods: This cross-sectional study enrolled 19 male traffic controllers from Santo Andre city (Sao Paulo, Brazil) who were 30-60 years old and exposed to ambient air during outdoor work shifts. Systolic and diastolic blood pressure readings were measured every 15 min by an Ambulatory Arterial Blood Pressure Monitoring device. Hourly measurements (lags of 0-5 h) and the moving averages (2-5 h) of particulate matter (PM(10)), ozone (O(3)) ambient concentrations and the acquired daily minimum temperature and humidity means from the Sao Paulo State Environmental Agency were correlated with both systolic and diastolic blood pressures. Statistical methods included descriptive analysis and linear mixed effect models adjusted for temperature, humidity, work periods and time of day. Results: Interquartile increases of PM(10) (33 mu g/m(3)) and O(3) (49 mu g/m(3)) levels were associated with increases in all arterial pressure parameters, ranging from 1.06 to 2.53 mmHg. PM(10) concentration was associated with early effects (lag 0), mainly on systolic blood pressure. However, O(3) was weakly associated most consistently with diastolic blood pressure and with late cumulative effects. Conclusions: Santo Andre traffic controllers presented higher blood pressure readings while working their outdoor shifts during periods of exposure to ambient pollutant fluctuations. However, PM(10) and O(3) induced cardiovascular effects demonstrated different time courses and end-point behaviors and probably acted through different mechanisms. (C) 2011 Elsevier Inc. All rights reserved.

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

Early Increase in Myocardial Perfusion After Stem Cell Therapy in Patients Undergoing Incomplete Coronary Artery Bypass Surgery

Incomplete revascularization is associated with worse long-term outcomes. Autologous bone marrow cells (BMC) have recently been tested in patients with severe coronary artery disease. We tested the hypothesis that intramyocardial injection of autologous BMC increases myocardial perfusion in patients undergoing incomplete coronary artery bypass grafting (CABG). Twenty-one patients (19 men), 59 +/- 7 years old, with limiting angina and multivessel coronary artery disease (CAD), not amenable to complete CABG were enrolled. BMC were obtained prior to surgery, and the lymphomonocytic fraction separated by density gradient centrifugation. During surgery, 5 mL containing 2.1 +/- 1.3 x 10(8) BMC (CD34+ = 0.8 +/- 0.3%) were injected in the ischemic non-revascularized myocardium. Myocardial perfusion was assessed by magnetic resonance imaging (MRI) at baseline and 1 month after surgery. The increase in myocardial perfusion was compared between patients with < 50% (group A, n = 11) with that of patients with > 50% (group B, n = 10) of target vessels (stenosis a parts per thousand yenaEuro parts per thousand 70%) successfully bypassed. Injected myocardial segments included the inferior (n = 12), anterior (n = 7), and lateral (n = 2) walls. The number of treated vessels (2.3 +/- 0.8) was significantly smaller than the number of target vessels (4.2 +/- 1.0; P < 0.0001). One month after surgery, cardiac MRI showed a similar reduction (%) in the ischemic score of patients in group A (72.5 +/- 3.2), compared to patients in group B (78.1 +/- 3.2; P = .80). Intramyocardial injection of autologous BMC may help increase myocardial perfusion in patients undergoing incomplete CABG, even in those with fewer target vessels successfully treated. This strategy may be an adjunctive therapy for patients suffering from a more advanced (diffuse) CAD not amenable for complete direct revascularization.

The chemistry of 5-oxodihydroisoxazoles .19. The synthesis and photolysis of N-thioacylisoxazol-5(2H)-ones

5-Oxodihydroisoxazoles react with thiocarbonyl chlorides to afford N-thioacylisoxazol-5(2H)-ones which lose carbon dioxide under photochemical conditions and undergo intramolecular cyclisation of the iminocarbene to afford thiazoles, However, in some cases loss of carbon dioxide is accompanied by loss of sulfur, giving 1,3-oxazin-6-ones.

Association Between Integrin Expression and Prognosis in Localized Prostate Cancer

BACKGROUND. Integrins and other adhesion molecules are essential for maintaining the epithelial phenotype. Some studies have reported correlations between abnormalities in their expression and carcinogenesis, but their role in prostate cancer is unclear. Our aim was to study the expression profile of integrins in surgical specimens of prostate cancer and associate their expression patterns with patient outcomes. METHODS. We selected 111 patients with localized prostate cancer who had undergone radical prostatectomy. Of these patients, 60 had no tumor recurrence after a median follow-up of 123 months. Integrin expression was evaluated by immunohistochemistry in a tissue microarray containing two tumor samples per patient. A semiquantitative analysis was employed. We measured the association between the expression of eight integrins and tumor recurrence. RESULTS. Multivariate analysis showed that expression of alpha 3 and alpha 3 beta 1 was related to worse outcome. When alpha 3 expression was strong and alpha 3 beta 1 expression was positive, the odds of recurrence were 3.0- and 2.5-fold higher, respectively. Only 19% and 28% of patients were recurrence-free in a mean period of 123 months of follow up when their tumors showed strong alpha 3 or positive alpha 3 beta 1 immuno-expression, respectively. CONCLUSIONS. We have shown that the expression of integrin alpha 3 beta 1 was independently associated with tumor recurrence after radical prostatectomy, suggesting that this integrin is a potential prognostic marker. Prostate 70: 1189-1195, 2010. (C) 2010 Wiley-Liss, Inc.

A randomized, comparative study of formoterol and terbutaline dry powder inhalers in the treatment of mild to moderate asthma exacerbations in the pediatric acute care setting

Background: Formoterol is a fast-acting, long-acting beta-agonist. Its on-demand use by outpatients has been beneficial in controlling asthma. Objective: To evaluate the efficacy of formoterol as rescue medication for pediatric asthma exacerbation. Methods: A randomized, double-blind study was conducted on parallel groups involving 79 pediatric patients (mean [SD] age, 9.92 [2.5] years) with mild to moderate asthma exacerbations. They were treated with up to 3 doses of formoterol aerolizer, 12 mu g, or terbutaline Turbuhaler, 0.5 mg (dry powder inhalers). Respiratory rate, clinical score, pulse oximetry, and spirometry were analyzed at baseline and 15 minutes after administration of each bronchodilator dose. All the patients received oral prednisolone, 1 mg/kg, at study entry, followed by a single daily dose for 4 days. Forty-one patients were treated with formoterol and 38 with terbutaline. The groups were comparable in age and in severity of asthma exacerbation. Results: Both treatments resulted in similar clinical and functional improvement; 37 patients (47%) required 1 bronchodilator dose. Increases of 19.5% and 1.5.3% occurred in forced expiratory volume in 1 second in the formoterol and terbutaline groups, respectively. Therapeutic failures occurred in 2 patients. No adverse effects were observed. At 1-week follow-up, patients were stable, with pulmonary function close to normal. Conclusion: Formoterol therapy was at least as effective as terbutaline therapy in children and adolescents with mild and moderate asthma exacerbations. Ann Allergy Asthma Immunol. 2009; 103:248-253.

Nomograms of fetal thyroid measurements estimated by 2-dimensional sonography

Purpose. To build nomograms of fetal thyroid circumference (FTC), fetal thyroid area (FTA), and fetal thyroid transverse diameter (FTTD) throughout gestational age (GA). Method. Between January 2006 and July 2006, FTC, FTA, and FTTD were measured once in 196 normal fetuses examined at a GA of 22-35 weeks. Inclusion criteria were a healthy mother with normal maternal thyrotropin level during pregnancy, a singleton pregnancy with normal fetal morphology on sonography, and GA confirmed via first-trimester sonographic examination. Results. Mean FTC, FTA, and FTTD ranged from 3.21 cm, 0.58 cm(2), and 1.19 cm at 22 weeks to 5.11 cm, 1.69 cm(2), and 1.89 cm at 35 weeks, respectively. Linear regression analysis yielded the following formulas for FTC, FTA, and FTTD according to GA: FTC (cm) = 0.146 X GA (weeks); FTA (cm(2)) = -1.289 + 0.085 X GA (weeks); FTTD (cm) = 0.054 X GA (weeks). The following logarithmic formulas were obtained for the expected fetal thyroid measurements according to estimated fetal weight (FW): FTC (cm) = -4.791 + 1.265 X logN FW; FTA (cm(2)) = -1.676 + 0.455 X logN FW; and FTTD (cm) = 0.399 + 0.001 X logN FW. Conclusion. We describe new nomograms of fetal thyroid measurements throughout gestation that may be useful in case of thyroid dysfunction. (C) 2008 Wiley Periodicals, Inc.

Change in expression of miR-let7c, miR-100, and miR-218 from high grade localized prostate cancer to metastasis

Objective: MicroRNAs (miRNAs) are small noncoding regulatory RNAs (19-25 nucleotides) that play a major role in regulation of gene expression. They are responsible for the control of fundamental cellular processes that has been reported to be involved in human tumorigenesis. The characterization of miRNA profiles in human tumors is crucial for the understanding of carcinogenesis processes, finding of new tumor markers, and discovering of specific targets for the development of innovative therapies. The aim of this study is to find miRNAs involved in prostate cancer progression comparing the profile of miRNA expressed by localized high grade carcinoma and bone metastasis. Material and methods: Two groups of tumors where submitted to analyses. The first is characterized by 18 patients who underwent radical prostatectomy for treatment of localized high grade prostate carcinoma (PC) with mean Gleason score 8.6, all staged pT3. The second group is composed of 4 patients with metastatic, androgen-independent prostate carcinoma, and 2 PC cell lines. LNCaP derived from a metastatic PC to a lymph node, and another derived from an obstructive, androgen-independent PC (PcBRA1). Expression analysis of 14 miRNAs was carried out using quantitative RT-PCR. Results: miR-let7c, miR-100, and miR-218 were significantly overexpressed by all localized high GS, pT3 PC in comparison with metastatic carcinoma. (35.065 vs. 0.996 P < 0.001), (55.550 vs. 8.314, P = 0.010), and (33.549 vs. 2.748, P = 0.001), respectively. Conclusion: We hypothesize that miR-let7c, miR-100, and miR-218 may be involved in the process of metastasization of PC, and their role as controllers of the expression of RAS, c-myc, Laminin 5 beta 3, THAP2, SMARCA5, and BAZ2A should be matter of additional studies. (C) 2011 Elsevier Inc. All rights reserved.

Mucoepidermoid Carcinoma of the Lung Arising at the Primary Site of A Bronchogenic Cyst: Clinical, Cytogenetic, and Molecular Findings

Primary lung tumors are rare in children, and mucoepidermoid carcinoma (MEC) represents less than 10% of them. Additionally, MEC arising from bronchogenic cysts (BC) is particularly unusual. We describe the clinical and genetic findings on a MEC occurring within a previous location of a BC in an adolescent. This particular association has not been previously reported. The lesion revealed normal karyotype without the typical t(11;19)(q21;p13) translocation. Cyclin D1 overexpression (165-fold increase) was demonstrated by real-time PCR although FISH assessment showed normal hybridization at 11q13. Information on these unusual clinical presentations may present relevant insight on tumorigenesis of infrequent pediatric pulmonary tumors. Pediatr Blood Cancer 2011;56:311-313. (C) 2010 Wiley-Liss, Inc.

Meningiomas and schwannomas: Molecular subgroup classification found by expression arrays

Microarray gene expression profiling is a high-throughput system used to identify differentially expressed genes and regulation patterns, and to discover new tumor markers. As the molecular pathogenesis of meningiomas and schwannomas, characterized by NF2 gene alterations, remains unclear and suitable molecular targets need to be identified, we used low density cDNA microarrays to establish expression patterns of 96 cancer-related genes on 23 schwannomas, 42 meningiomas and 3 normal cerebral meninges. We also performed a mutational analysis of the NF2 gene (PCR, dHPLC, Sequencing and MLPA), a search for 22q LOH and an analysis of gene silencing by promoter hypermethylation (MS-MLPA). Results showed a high frequency of NF2 gene mutations (40%), increased 22q LOH as aggressiveness increased, frequent losses and gains by MLPA in benign meningiomas, and gene expression silencing by hypermethylation. Array analysis showed decreased expression of 7 genes in meningiomas. Unsupervised analyses identified 2 molecular subgroups for both meningiomas and schwannomas showing 38 and 20 differentially expressed genes, respectively, and 19 genes differentially expressed between the two tumor types. These findings provide a molecular subgroup classification for meningiomas and schwannomas with possible implications for clinical practice.

Increased arterial stiffness in nonobese women with polycystic ovary syndrome (PCOS) without comorbidities: one more characteristic inherent to the syndrome?

Background Polycystic ovary syndrome (PCOS) is associated with adverse metabolic effects. Some cardiovascular disease (CVD) risk markers are increased in women with PCOS. However, early markers of atherosclerosis are also associated with obesity and insulin resistance, which are related to PCOS. These markers may result either directly from PCOS or indirectly as a consequence of the comorbidities associated with the syndrome. Context To assess the presence of early CVD markers in young, nonobese women with PCOS. Patients Forty women with PCOS and 50 healthy women with regular menstrual cycles, matched for age and body mass index (BMI). Measurements The following CVD markers were assessed by ultrasonography: common carotid artery (CCA) stiffness index (beta), distensibility and intima-media thickness (IMT), and brachial artery flow-mediated dilatation (FMD). Inflammatory markers, including interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, homocysteine, C-reactive protein (CRP), glycaemia, lipid profile and insulin, were also assessed. Results CCA beta was higher in PCOS than in control women (3 center dot 72 +/- 0 center dot 96 vs. 3 center dot 36 +/- 0 center dot 96, P = 0 center dot 04) and CCA distensibility was lower (0 center dot 31 +/- 0 center dot 08 vs. 0 center dot 35 +/- 0 center dot 09 mmHg(-1), P = 0 center dot 02). Waist circumference, total testosterone and the Free Androgen Index (FAI) were higher in PCOS patients than in controls (78 center dot 2 +/- 10 center dot 0 vs. 71 center dot 5 +/- 7 center dot 2 cm, P = 0 center dot 001; 88 center dot 1 +/- 32 center dot 4 vs. 57 center dot 1 +/- 21 center dot 2 ng/dl, P < 0 center dot 01; 12 center dot 7 +/- 15 center dot 7%vs. 4 center dot 7 +/- 2 center dot 3%, P < 0 center dot 01, respectively), while SHBG was reduced (37 center dot 9 +/- 19 center dot 1 vs. 47 center dot 8 +/- 18 center dot 3 nmol/l, P = 0 center dot 01). The remaining variables did not differ between the groups. Conclusions Young women with PCOS exhibit changes in vascular elasticity even in the absence of classical risk factors for CVD, such as hypertension and obesity.

Lipid peroxidation and vitamin E in serum and follicular fluid of infertile women with peritoneal endometriosis submitted to controlled ovarian hyperstimulation: a pilot study

Objective: To assess the level of lipid peroxidation (LP) and vitamin E in the follicular fluid and serum of infertile patients, with or without endometriosis. who were submitted to ovulation induction for assisted reproduction procedures. Design: Prospective study. Setting: Assisted conception unit, university hospital. Patient(s): Infertile patients 20 to 38 years of age were selected prospectively and consecutively and were divided into the endometriosis group (17 patients with pelvic endometriosis) and the control group (19 patients with previous tubal ligation or male factor and without endometriosis). Intervention(s): Peripheral blood samples were collected on D1 (before the beginning of the use of gonadotropins), D2 (day of hCG administration), and D3 (day of oocyte retrieval). On D3, follicular-fluid samples free from blood contamination also were collected and stored. Main Outcome Measure(S): Lipid peroxidation was assessed by malondialdehyde quantification by spectrophotometry, and measurement of vitamin E was performed by HLPC. Result(s): On D1, no significant difference in LP was observed between groups. However, vitamin E levels were significantly higher in the control group. On D2, LP levels were significantly higher in the endometriosis group compared with in the control group, and vitamin E levels continued to be significantly higher in the control group. On D3, there was no significant difference in serum and follicular-fluid levels of LP and vitamin E between groups. However, on D3, vitamin E levels were found to be significantly higher in serum than in follicular fluid in both groups, whereas malondialdchyde levels were significantly lower in follicular fluid than in serum only in the control group. Conclusion(s): Before the beginning of ovulation induction, a significant decrease in vitamin E was observed in patients with endometriosis, perhaps because antioxidants are consumed during oxidation reactions. After ovulation induction with exogenous gonadotropins, the group of patients with endometriosis not only presented increased lipid peroxidation but also maintained lower vitamin E levels than the control group, a fact that hypothetically could compromise oocyte quality in endometriotic patients. However, on the day of oocyte retrieval, both serum LP potential and vitamin E levels were found to be similar in the two groups. (Fertil Steril(R) 2008; 90:2080-5. (C) 2008 by American Society for Reproductive Medicine.)

Pitfalls in the Differential Diagnosis of Renal Tumor in an Adolescent

The differential diagnosis of renal tumors, particularly in adolescents, may be challenging. We describe an 11-year-old female with a primary intra-renal mass. Initial differential diagnoses included primitive neuroectodermal tumor (PNET), desmoplastic small round cell tumor (DSRCT), and Wilms Turner (WT). Extensive pathologic and molecular analysis on initial and relapsed tumor samples confirmed WT. The EWS-WTI and EWS-FL11 rearrange-merits, distinctive of DSRCT and PNET were negative. The differential diagnosis on monophasic blastemal WT may be complex. Primary renal DSRCT and MET have been rarely described. Nevertheless, molecular confirmation for these rare conditions may be necessary in selected cases. Pediatr Blood Cancer 2010;54:3 19-321. (C) 2009 Wiley-Liss, Inc.