eNOS haplotype associated with hypertension in obese children and adolescents

Objective: The aim of our study is to investigate whether genetic polymorphisms in the endothelial nitric oxide synthase (eNOS) gene (in the promoter region T(-786)C, in exon 7 (Glu298Asp) and in intron 4 (4b/4a)) or eNOS haplotypes are associated with hypertension in obese children and adolescents. Methods: We genotyped 175 healthy (controls), 110 normotensive obese and 73 hypertensive obese children and adolescents. Genotypes were determined by Taqman allele discrimination assay and real-time PCR, and by PCR followed by fragment separation by electrophoresis. We compared the distribution of eNOS genotypes, alleles and haplotypes in the three study groups of subjects. We have also measured whole-blood nitrite concentrations. Results: The 4a4a genotype for the intron 4 polymorphism was more common in normotensive obese and hypertensive obese (P < 0.01). The AspAsp genotype for Glu298Asp polymorphism was less common in normotensive obese (P < 0.02). No significant differences were found in allele distributions for the three eNOS polymorphisms. However, the haplotype combining the C, 4b and Glu variants for the three polymorphisms was more common in hypertensive obese than in normotensive obese or control children and adolescents (odds ratio = 2.28 and 2.79, respectively; 95% confidence interval: 1.31-4.31 and 1.39-5.64, respectively; both P < 0.00625). This haplotype was not associated with significantly different nitrite concentrations (P > 0.05). Conclusions: Our findings suggest that the eNOS haplotype, C b Glu, is associated with hypertension in obese children and adolescents. Further studies examining the possible interactions of eNOS haplotypes with environmental factors and other genetic markers involved in the development of obesity and its complications are warranted. International Journal of Obesity (2011) 35, 387-392; doi:10.1038/ijo.2010.146; published online 27 July 2010

Tuberculosis among health care workers in a Brazilian tertiary hospital emergency unit

The Brazilian emergency system is being reorganized as a hierarchy in the region of Ribeirao Preto, state of Sao Paulo. We found increased occupational risk for tuberculosis in this region tertiary reference center-a nurse technician (Incidence rate [IR] 526.3/100000 inhabitants) had a risk of tuberculosis 12.6 (95% confidence interval [CI], 2.57-37.23) greater than the city population (41.8/100000 inhabitants). The system reorganization will have to make the centers adequate to deal with this problem. (C) 2008 Elsevier Inc. All rights reserved.

A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.

Symptoms of Temporomandibular Disorders in the Population: An Epidemiological Study

Aims: To estimate the prevalence of symptoms of temporomandibular disorders (TMD) as a function of age and gender, in a representative urban sample from the Brazilian population. Methods: A total of 1,230 inhabitants (51.5% women) aged 15 to 65 years were interviewed by a validated phone survey. Sample size had been previously calculated. TMD symptoms were assessed through five questions, as recommended by the American Academy of Orofacial Pain, in an attempt to identify possible TMD. Data were derived by age and gender. Prevalence of each TMD symptom, and of combination of symptoms, was calculated. Results: At least one TMD symptom was reported by 39.2% of the individuals. Pain related to TMD was noted by 25.6% of the population. Temporomandibular joint (TMJ) sound was the most common symptom of TMD, followed by TMJ pain and masticatory muscle pain. All symptoms were more prevalent in women than in men. With men used as the reference, a relative risk (RR) of at least one TMD symptom in women was 1.31 (95% confidence interval [CI] = 1.14 to 1.52). When at least two symptoms were present, the RR was 1.93 (95% CI = 1.49 to 2.51). For three or more TMD symptoms, the RR was 2.49 (95% CI = 1.67 to 3.71). Women were also more likely than men to have TMD pain (RR = 1.78; 9% CI = 1.45 to 2.18). Conclusion: Individual symptoms, as well as a combination of TMD symptoms, are prevalent in the Brazilian urban population and are more frequent in women than in men. Additional studies should focus on risk factors for and relevance of TMD for the sufferers. J OROFAC PAIN 2010;24:270-278

Nocturnal awakening with headache and its relationship with sleep disorders in a population-based sample of adult inhabitants of Sao Paulo City, Brazil

Our aim was to estimate the prevalence of nocturnal awakening with headache (NAH) in the population of Sao Paulo City according to gender, age (20-80 years old) and socioeconomic classes and its relationship to sleep disorders, sleep parameters, anxiety, depression, fatigue, life quality and obesity. We used a population-based survey with a representative three-stage cluster sample. Questionnaires and scales were applied face-to-face, and polysomnography was performed in 1101 volunteers, aged 42 +/- 14 years, 55% women. The complaint of NAH occurring at least once a week had a prevalence of 8.4%, mostly in women, obese subjects and those aged 50-59 years-old. We observed associations of NAH with insomnia, restless leg syndrome (RLS), nightmares and bruxism, but not obstructive sleep apnea syndrome. In a logistics regression model, risk factors for NAH were female gender, odds ratio (OR) (95% confidence interval [CI]) 4.5 (2.8-7.3); obesity, OR 1.9 (1.1-3.3); age between 50 and 59 years, OR 2.4 (1.2-4.7); severe anxiety, OR 8.1 (3.6-18.1); RLS, 2.7 (1.2-5.6); and nightmares, 2.2 (1.3-3.7). Our study shows that NAH was highly prevalent in the population of Sao Paulo and suggests that this phenomenon has specific characteristics with specific risk factors: obesity, RLS and nightmares.

Signs of Temporomandibular Disorders in Migraine Patients: A Prospective, Controlled Study

Objectives: To identify signs of temporomandibular disorders and cervical pain in individuals with episodic and chronic (transformed) migraine (CM), relative to controls without headaches. Methods: In this prospective, controlled, double-blind study, we examined 93 individuals divided in 3 groups: episodic migraine EM, (n= 31), CM chronic migraine (n= 34), and controls without migraine (n= 28). We recorded signs of temporomandibular disorders, and of pain in the neck, after the protocol of Helkimo (1974). We calculated the odds ratio (OR) and confidence intervals (CI) of symptoms as a function of headache status. Data from all groups were paired and compared using the chi(2) test. The level of significance was 5% in 2-tailed tests. Results: Relative to controls, participants with EM and CM were significantly more likely to have tenderness in the masticatory muscles [controls = 28%, migraine = 54%, (OR = 3.0, 95% CI = 1.1-8.9), CM = 73% (OR = 6.9, 95% CI = 2.3-21.2)], and in the temporomandibular joint [controls = 25%, migraine = 61%, (OR = 4.7, 95% CI = 1.5-14.5), CM = 61% (OR = 4.8, 95% CI = 1.6-14.5)]. They were numerically (but nonsignificantly) more likely to have limited lateral jaw movements (CM = 34%; EM = 26%; NP = 18%), joint sounds (CM = 44%; EM = 29%; NP = 28%), and tenderness in neck muscles (CM = 64%; EM = 51%; NP = 35%). Conclusion: In a tertiary care population, individuals with EM and CM are more likely to have tenderness at the temporomandibular joint and on the masticatory muscles, relative to controls. Studies are needed to investigate whether treatment of 1 disorder will improve the other.

Multi-system neurological disease is common in patients with OPA1 mutations

Additional neurological features have recently been described in seven families transmitting pathogenic mutations in OPA1, the most common cause of autosomal dominant optic atrophy. However, the frequency of these syndromal `dominant optic atrophy plus` variants and the extent of neurological involvement have not been established. In this large multi-centre study of 104 patients from 45 independent families, including 60 new cases, we show that extra-ocular neurological complications are common in OPA1 disease, and affect up to 20% of all mutational carriers. Bilateral sensorineural deafness beginning in late childhood and early adulthood was a prominent manifestation, followed by a combination of ataxia, myopathy, peripheral neuropathy and progressive external ophthalmoplegia from the third decade of life onwards. We also identified novel clinical presentations with spastic paraparesis mimicking hereditary spastic paraplegia, and a multiple sclerosis-like illness. In contrast to initial reports, multi-system neurological disease was associated with all mutational subtypes, although there was an increased risk with missense mutations [odds ratio = 3.06, 95% confidence interval = 1.44-6.49; P = 0.0027], and mutations located within the guanosine triphosphate-ase region (odds ratio = 2.29, 95% confidence interval = 1.08-4.82; P = 0.0271). Histochemical and molecular characterization of skeletal muscle biopsies revealed the presence of cytochrome c oxidase-deficient fibres and multiple mitochondrial DNA deletions in the majority of patients harbouring OPA1 mutations, even in those with isolated optic nerve involvement. However, the cytochrome c oxidase-deficient load was over four times higher in the dominant optic atrophy + group compared to the pure optic neuropathy group, implicating a causal role for these secondary mitochondrial DNA defects in disease pathophysiology. Individuals with dominant optic atrophy plus phenotypes also had significantly worse visual outcomes, and careful surveillance is therefore mandatory to optimize the detection and management of neurological disability in a group of patients who already have significant visual impairment.

Depersonalization and personality in panic disorder

Background: Prevalence and clinical correlates of depersonalization symptoms have been associated with panic disorder. Personality traits might increase the likelihood of experiencing depersonalization symptoms or depersonalization disorder in panic patients. Aims: The objectives of this study are to establish the prevalence of depersonalization symptoms during the panic attack and in depersonalization disorder and to examine the personality factors associated with the presence of depersonalization in patients with panic disorder. Methods: The sample comprised 104 consecutive adult outpatients with panic disorder, diagnosed according to the Semistructured Clinical Interview for DSM-IV (Axis I/II disorders). Participants were assessed with the Cambridge Depersonalization Scales, the Temperament and Character Inventory, and the Panic and Agoraphobia Scale. Results: Forty-eight percent of the sample had depersonalization symptoms during the panic attack, whereas 20% of patients had a depersonalization disorder. Women presented more depersonalization disorders than did men (P = .036). Patients with panic disorder with depersonalization disorder had a more severe panic disorder (P = .002). Logistic regression analysis showed that self-transcendence trait (odds ratio, 1.089; 95% confidence interval, 1.021-1.162; P = .010) and severity of panic (odds ratio, 1.056; 95% confidence interval, 1.005-1.110; P = .032) were independently associated with depersonalization disorder. Conclusions: A high prevalence of depersonalization symptoms and depersonalization disorder was confirmed in patients with panic disorder, supporting a dosage effect model for understanding depersonalization pathology. Self-transcendence trait and severity of panic disorder were reported as risk factors for depersonalization disorder. (C) 2011 Elsevier Inc. All rights reserved.

Orbital Involvement in Craniofacial Brown Tumors

Purpose: To describe the clinical and radiologic features of orbital involvement in craniofacial brown tumors and to compare the rate of brown tumors in primary and secondary hyperparathyroidism. Methods: A retrospective hospital-based study of 115 patients with chronic kidney disease and secondary hyperparathyroidism and 34 with primary hyperparathyroidism was conducted. Laboratory results such as serum levels of alkaline phosphatase, calcium, phosphorus, and parathyroid hormone were recorded. Demographic data (age, sex, duration of disease) and image findings (bone scan scintigraphy, skull and long bone x-rays, CT) were also obtained. The main outcome measures were analysis of clinical, biochemical, and radiologic findings of all patients. Results: Of the 115 patients with chronic kidney disease, 10 (8.7%) had brown tumors in different bones of the skeleton. Five patients had lesions in the craniofacial bones. The maxilla, mandible, maxillary sinus, and nasal cavity were the most affected sites. The orbit was involved in 2 patients with lesions arising in the maxillary and ethmoid sinuses. One patient had facial leontiasis. All patients with brown tumors had extremely high levels of parathyroid hormone (>1,000 pg/ml, normal values 10-69 pg/ml) and alkaline phosphatase (>400 U/l, normal values 65-300 U/l). The mean serum levels of phosphorus and calcium were not abnormal among the patients with brown tumors. Age and time of renal failure were similar for patients with and without brown tumors. Among the patients with primary hyperparathyroidism, only 2 (5.8%) had brown tumors, and in just 1, the lesion was localized in the craniofacial skeleton. A 2-tailed Z test applied to compare the proportion of occurrence of brown tumors in the 2 groups revealed that the difference at the 90% of confidence level was not significant. Conclusions: Brown tumors are equally found in secondary and primary hyperparathyroidism. Craniofacial brown tumors involve the orbit, usually because of the osteodystrophy process that involves the maxilla and paranasal sinuses. The lesions do not necessarily need to be excised and may regress spontaneously after the control of hyperparathyroidism.

Significance of topoisomerase III beta expression in breast ductal carcinomas: strong associations with disease-specific survival and metastasis

Topoisomerases are ubiquitous nuclear enzymes that regulate DNA structure in eukaryotic cells. The role of topoisomerase III beta, the newest member of the topoisomerase family, in the clinical outcome of breast cancer is still poorly understood. This study aims to investigate the immunoexpression of topoisomerase III beta in breast cancer and its relationships with clinicopathologic features and immunohistochemical markers of prognostic significance in breast pathology. Using tissue microarrays containing 171 cases of primary invasive breast cancer, we analyzed the immunoexpression of topoisomerase III beta, estrogen receptor, progesterone receptor, HER-2, BRCA-1, p53, and Ki67. Immunostaining for topoisomerase III beta was found in 33.9% of breast carcinomas, and immunopositivity was correlated with distant metastasis (P = .036) and death (P = .006). Decreased expression of topoisomerase III beta correlated with low expression of Ki67 (P < .001) and negativity for HER-2 (P < .001), BRCA-1 (P = .001), and p53 (P < .001). In the multivariate analysis, topoisomerase Hip expression was a significant predictor of survival (hazard ratio, 3.006 [95% confidence interval, 1.582-5.715]; P = .001). In conclusion, topoisomerase III beta expression can be a useful marker in assessing the prognosis of patients with breast cancer and is an independent predictor of survival. (C) 2010 Elsevier Inc. All rights reserved.

Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Objective: To assess whether the -11391G > A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ -11391G > A genotype-phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years (catch-down growth), and at 23-25 years of age (cardiometabolic profile). Results: The -11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the -11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7 +/- 6.2 versus GA: 12.2 +/- 6.5 versus AA: 14.2 +/- 6.8 mu g/ml; P < 0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P < 0.001) at 23-25 years. Conclusions: The -11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

Vitamin A deficiency among Brazilian school-aged children in a healthy child service

Background/Objectives: Vitamin A deficiency (VAD) is a world public health problem contributing to the increase in childhood morbidity and mortality in developing countries and severe deficiency of vitamin A may lead to xerophthalmia and blindness. The objective of this study was to determine the prevalence of VAD among Brazilian school-aged children attended at a primary health unit and to verify if some considered risk factor was associated with VAD in this group. Subjects/Methods: A descriptive prospective transverse study was conducted on 103 randomly selected children. A total of 54 boys and 49 girls aged 5.5-11 years had the relative dose-response (RDR) test performed on. Possible ocular alterations related to vitamin A and the status of anemia, serum zinc, some acute-phase proteins, and anthropometric situation were determinate by an analytic design. Results: No child presented xerophthalmia. Serum retinol values lower than 1.05 and 0.7 mu moll(-1), respectively were found in 26.2 and 5.8% of the children. The prevalence of hypovitaminosis detected by RDR test was 20.4%. The following variables and their relationship with VAD were evaluated: sex (P = 0.33; 95% confidence interval 0.61-4.34), weight and height (P >= 0.5), hemoglobin (P = 0.15), C-reactive protein (P = 0.56; 95% confidence interval 0.75-18.26), alpha-1-acid-glycoprotein (P = 0.56; 95% confidence interval 0.15-15.42) and serum zinc (P = 0.31). None of these variables was related to VAD. Conclusions: In this population, the prevalence of VAD detected could be considered a public health problem. School-aged children can be considered at risk for VAD mainly of a subclinical level, even without some associated risk factors.

Impact of specific sensitization on asthma and rhinitis in young Brazilian and Chilean adults

Background The pattern of associations and the attributable fractions (AF) of atopic conditions due to specific sensitizations vary between countries. Objective To assess the level of associations and AF between sensitization to five allergens and atopic conditions in two settings. Methods We studied 2063 Brazilians and 1231 Chileans of both sexes using representative samples selected at birth in the 1970s. Information on asthma and rhinitis was based on the European Community Respiratory Health Survey questionnaire. We assessed bronchial hyperresponsiveness (BHR) to methacholine and sensitization to Dermatophagoides pteronyssinus, cat, dog, grass blend and Alternaria alternata. Results The prevalence of sensitization to one or more allergens was 50% in Brazilians and 22% in Chileans. The level of associations varied according to the outcome used. Strong associations between sensitization and asthma, defined as wheeze or awakening with breathlessness at night and positive BHR, were found for each of the five allergens in Chileans [varying from odds ratio (OR) 3.24, 95% confidence interval (CI) 1.47, 7.15 for D. pteronyssinus to 8.44, 95% CI 3.82, 18.66 for cat], whereas the level of associations was restricted to D. pteronyssinus, cat and dog in Brazilians and was somewhat weaker (highest OR 3.90, 95% CI 2.80-5.44). The AF of sensitization on asthma was 54% in Brazil and 44% in Chile. D. pteronyssinus and cat made an independent contribution to asthma in the two samples. The patterns of associations between sensitization and rhino-conjunctivitis were similar to those for asthma. Conclusion The associations between sensitization, and asthma and rhinitis were high in Chile and moderately high in Brazil, but the AF were higher in Brazil, reflecting a higher prevalence of sensitization. In Brazil, dust mite had the greatest impact on atopic conditions while in Chile several allergens had an impact. Sensitization is as serious a problem in Chile and Brazil as in developed countries.

Birth Prevalence and Natural History of Congenital Cytomegalovirus Infection in a Highly Seroimmune Population

Background. The natural history of congenital cytomegalovirus (CMV) infection is scarcely known in populations with high maternal CMV seroprevalence. This study evaluated the birth prevalence, clinical findings at birth, and hearing outcome in CMV-infected children from such a population. Methods. Consecutively born infants were screened for the presence of CMV in urine and/or saliva specimens during the first 2 weeks after birth. Neonatal clinical findings were recorded, and CMV-infected children were tested to document hearing function during follow-up. A subset of mothers of CMV-infected infants were prenatally tested for the presence of anti-CMV immunoglobulin G antibodies. Results. Congenital CMV infection was confirmed in 87 (1.08%; 95% confidence interval [CI], 0.86%-1.33%) of 8047 infants. Seven infants (8.1%; 95% CI, 3.3%-15.9%) had at least 1 clinical finding suggestive of CMV infection, and 4 (4.6%; 95% CI, 1.3%-11.3%) had 13 findings of systemic disease. Sensorineural hearing loss was found in 5 (8.6%; 95% CI, 2.9%-19.0%) of 58 children tested at a median age of 21 months. Bilateral profound hearing loss was observed in 2 children, and the hearing threshold was 160 decibels in all 5 children with hearing loss, including 2 children born to mothers with probable nonprimary CMV infection. Conclusions. The results of this large newborn screening study in a population with high CMV seroimmunity provide additional evidence that congenital CMV disease occurs in populations with high seroprevalence rates, with a similar incidence of CMV-related hearing loss to that reported in the offspring of women from populations in developed countries with lower rates of seroimmunity to CMV.

Matrix metalloproteinase 9 gene haplotypes affect left ventricular hypertrophy in hypertensive patients

Background: Matrix metalloproteinases (MMPs) are involved in cardiac remodeling and are encoded by genes showing genetic polymorphisms that have functional implications. We examined whether MMP-9 genetic polymorphisms are associated with hypertension and with left ventricular (LV) remodeling in hypertensive patients. Methods: We studied 173 hypertensive patients and 137 age, race and gender matched healthy controls. Heart echocardiography was performed in all patients and the following MMP-9 genetic polymorphisms were analyzed: C-(1562)T (rs3918242). -90 (CA)(14-24) (rs2234681) and Q279R (rs17576). Haplo.stats analysis was used to assess whether MMP-9 haplotypes are associated with hypertension. Linear regression analysis was performed to assess whether MMP-9 haplotypes affect LV mass index (LVMI) and other echocardiography parameters. Results: MMP-9 90 (CA)14-24 ""HH"" genotype (H allele defined by number of CA repeats >= 21) was associated with hypertension (P = 0.0085; OR = 2.321, 95% confidence interval = 1.250 to 4.309). While one MMP-9 haplotype (""C. H, Q"") protects against LVMI and end-diastolic diameter increases due to remodeling (P = 0.0490 and P = 0.0367), another MMP-9 haplotype apparently has detrimental effects over both parameters in hypertensive patients (""T, H. Q"", P = 0.0015 and P = 0.0057. respectively). Conclusion: Genetic polymorphisms in MMP-9 gene may modify the susceptibility of hypertensive patients to LV remodeling. Further studies are necessary to examine whether these polymorphisms affect clinical events in hypertensive patients. (C) 2010 Elsevier B.V. All rights reserved.