Polymorphism C1420T of Serine hydroxymethyltransferase gene on maternal risk for Down syndrome

Recent researches have investigated the factors that determine the maternal risk for Down syndrome (DS) in young woman. In this context, some studies have demonstrated the association between polymorphisms in genes involved on folate metabolism and the maternal risk for DS. These polymorphisms may result in abnormal folate metabolism and methyl deficiency, which is associated with aberrant chromosome segregation leading to trisomy 21. In this study, we analyzed the influence of the polymorphism C1420T in Serine hydroxymethyltransferase (SHMT) gene on maternal risk for DS and on metabolites concentrations of the folate pathway (serum folate and plasma homocysteine and methylmalonic acid). The study group was composed by 105 mothers with DS children (case group) and 185 mothers who had no children with DS (control group). The genotype distribution did not show significant statistical difference between case and control mothers (P = 0.24) however a protective effect between genotypes CC (P = 0.0002) and CT (P < 0.0001) and maternal risk for DS was observed. Furthermore, the SHMT C1420T polymorphism (rs1979277) does not affect the concentration of metabolites of folate pathway in our DS mothers. In conclusion, our data showed a protective role for the genotypes SHMT CC and CT on maternal risk for DS. The concentrations of metabolites of folate pathway did not differ significantly between the genotypes SHMT.

A Randomized Trial of Noninvasive Positive End Expiratory Pressure in Patients With Acquired Immune Deficiency Syndrome and Hypoxemic Respiratory Failure

BACKGROUND: Acquired immunodeficiency syndrome (AIDS) is a pandemic disease commonly associated with respiratory infections, hypoxemia, and death. Noninvasive PEEP has been shown to improve hypoxemia. In this study, we evaluated the physiologic effects of different levels of noninvasive PEEP in hypoxemic AIDS patients. METHODS: Thirty AIDS patients with acute hypoxemic respiratory failure received a randomized sequence of noninvasive PEEP (5, 10, or 15 cm H2O) for 20 min. PEEP was provided through a facial mask with pressure-support ventilation (PSV) of 5 cm H2O and an F-IO2, of 1. Patients were allowed to breathe spontaneously for a 20-min washout period in between each PEEP trial. Arterial blood gases and clinical variables were recorded after each PEEP treatment. RESULTS: The results indicate that oxygenation improves linearly with increasing levels of PEEP. However, oxygenation levels were similar regardless of the first PEEP level administered (5, 10, or 15 cm H2O), and only the subgroup that received an initial treatment of the lowest level of PEEP (ie, 5 cm H2O) showed further improvements in oxygenation when higher PEEP levels were subsequently applied. The P-aCO2, also increased in response to PEEP elevation, especially with the highest level of PEEP (ie, 15 cm H2O). PSV of 5 cm H2O use was associated with significant and consistent improvements in the subjective sensations of dyspnea and respiratory rate reported by patients treated with any level of PEEP (from 0 to 15 cm H2O). CONCLUSIONS: AIDS patients with hypoxemic respiratory failure improve oxygenation in response to a progressive sequential elevation of PEEP (up to 15 cm H2O). However, corresponding elevations in P-aCO2, limit the recommended level of PEEP to 10 cm H2O. At a level of 5 cm H2O, PSV promotes an improvement in the subjective sensation of dyspnea regardless of the PEEP level employed.

Analysis of MLL2 gene in the first Brazilian family with Kabuki syndrome

Most patients with Kabuki syndrome (KS) are the only person in their family with the condition. However, familial cases of KS have been described showing evidence that this syndrome can be inherited as a dominant trait with variable expressivity. We report on two related individuals with facial findings characteristic of KS. The proposita had arched eyebrows, long and upward slanting palpebral fissures, cleft lip and palate, retromicrognathia, brachydactyly of hands and feet, stubby fingers, nail hypoplasia, and prominent finger pads. Her mother had eyebrows with dispersed lateral half, long and upward slanting palpebral fissures, retrognathia, abnormal and posteriorly rotated ears, prominent finger pads, brachydactyly of feet, learning difficulties, and psychomotor development delay. DNA sequencing revealed a novel missense mutation in the MLL2 gene in both the proposita and her mother. The mutation (p.R5432Q) was found in the exon 51, within the SET domain of the gene, which confers methyltransferase activity on the protein. Therefore, the epigenetic and transcriptional regulatory properties of this protein may be altered and this suggests that the mutation is the cause of phenotype observed in both the patient and her mother. The clinical signs and the molecular evidence in this family further support the notion that KS is an autosomal dominant condition with variable expressivity. To our knowledge this is the first report of a Brazilian family with recurrence of this syndrome. (C) 2012 Wiley Periodicals, Inc.

Risk factors for computer visual syndrome (CVS) among operators of two call centers in Sao Paulo, Brazil

The aims of this study were to investigate work conditions, to estimate the prevalence and to describe risk factors associated with Computer Vision Syndrome among two call centers' operators in Sao Paulo (n = 476). The methods include a quantitative cross-sectional observational study and an ergonomic work analysis, using work observation, interviews and questionnaires. The case definition was the presence of one or more specific ocular symptoms answered as always, often or sometimes. The multiple logistic regression model, were created using the stepwise forward likelihood method and remained the variables with levels below 5% (p < 0.05). The operators were mainly female and young (from 15 to 24 years old). The call center was opened 24 hours and the operators weekly hours were 36 hours with break time from 21 to 35 minutes per day. The symptoms reported were eye fatigue (73.9%), "weight" in the eyes (68.2%), "burning" eyes (54.6%), tearing (43.9%) and weakening of vision (43.5%). The prevalence of Computer Vision Syndrome was 54.6%. Associations verified were: being female (OR 2.6, 95% CI 1.6 to 4.1), lack of recognition at work (OR 1.4, 95% CI 1.1 to 1.8), organization of work in call center (OR 1.4, 95% CI 1.1 to 1.7) and high demand at work (OR 1.1, 95% CI 1.0 to 1.3). The organization and psychosocial factors at work should be included in prevention programs of visual syndrome among call centers' operators.

Assessing the benefits of rosiglitazone in women with polycystic ovary syndrome through its effects on insulin-like growth factor 1, insulin-like growth factor-binding protein-3 and insulin resistance: a pilot study

Federal University of Sao Paulo

Ocular manifestations of Noonan syndrome

Purpose: To describe the ophthalmological characteristics in a group of Noonan syndrome patients with proven mutations in the PTPN11 gene. Methods: Thirty-five Noonan syndrome patients with PTPN11 gene mutations underwent ophthalmological exams, which consisted of external inspection, slit-lamp biomicroscopy examination and an ophthalmoscopic examination after instillation of 1.0% tropicamide or 1.0% cyclopentolate. Results: All 35 patients had at least one abnormality upon ophthalmological examination. The eyelid and external eye abnormalities were the prevailing features, followed by prominent corneal nerves on slit-lamp exam. Fundus changes were detected in 8% of the subjects, mainly associated with high myopia. No statistically significant differences were observed among the patients presenting specific mutations in the PTPN11 gene. Conclusions: The current study further supports the finding that ocular symptoms account for a large fraction of the clinical manifestations of NS. Additional characteristics are described here. The roles for the various mutations of PTPN11 in ocular development are yet to be established.

How large is the lung recruitability in early acute respiratory distress syndrome: a prospective case series of patients monitored by computed tomography

Introduction: The benefits of higher positive end expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS) have been modest, but few studies have fully tested the "open-lung hypothesis". This hypothesis states that most of the collapsed lung tissue observed in ARDS can be reversed at an acceptable clinical cost, potentially resulting in better lung protection, but requiring more intensive maneuvers. The short-/middle-term efficacy of a maximum recruitment strategy (MRS) was recently described in a small physiological study. The present study extends those results, describing a case-series of non-selected patients with early, severe ARDS submitted to MRS and followed until hospital discharge or death. Methods: MRS guided by thoracic computed tomography (CT) included two parts: a recruitment phase to calculate opening pressures (incremental steps under pressure-controlled ventilation up to maximum inspiratory pressures of 60 cmH(2)O, at constant driving-pressures of 15 cmH(2)O); and a PEEP titration phase (decremental PEEP steps from 25 to 10 cmH2O) used to estimate the minimum PEEP to keep lungs open. During all steps, we calculated the size of the non-aerated (-100 to +100 HU) compartment and the recruitability of the lungs (the percent mass of collapsed tissue re-aerated from baseline to maximum PEEP). Results: A total of 51 severe ARDS patients, with a mean age of 50.7 years (84% primary ARDS) was studied. The opening plateau-pressure was 59.6 (+/- 5.9 cmH(2)O), and the mean PEEP titrated after MRS was 24.6 (+/- 2.9 cmH(2)O). Mean PaO2/FiO(2) ratio increased from 125 (+/- 43) to 300 (+/- 103; P < 0.0001) after MRS and was sustained above 300 throughout seven days. Non-aerated parenchyma decreased significantly from 53.6% (interquartile range (IQR): 42.5 to 62.4) to 12.7% (IQR: 4.9 to 24.2) (P < 0.0001) after MRS. The potentially recruitable lung was estimated at 45% (IQR: 25 to 53). We did not observe major barotrauma or significant clinical complications associated with the maneuver. Conclusions: MRS could efficiently reverse hypoxemia and most of the collapsed lung tissue during the course of ARDS, compatible with a high lung recruitability in non-selected patients with early, severe ARDS. This strategy should be tested in a prospective randomized clinical trial.

KRAS gene mutations in Noonan syndrome familial cases cluster in the vicinity of the switch II region of the G-domain: Report of another family with metopic craniosynostosis

Noonan syndrome (NS) and Noonan-related disorders [cardio-facio-cutaneous (CFC), Costello, Noonan syndrome with multiple lentigines (NS-ML), and neurofibromatosis-Noonan syndromes (NFNS)] are a group of developmental disorders caused by mutations in genes of the RAS/MAPK pathway. Mutations in the KRAS gene account for only a small proportion of affected Noonan and CFC syndrome patients that present an intermediate phenotype between these two syndromes, with more frequent and severe intellectual disability in NS and less ectodermal involvement in CFC syndrome, as well as atypical clinical findings such as craniosynostosis. Recently, the first familial case with a novel KRAS mutation was described. We report on a second vertical transmission (a mother and two siblings) with a novel mutation (p.M72L), in which the proband has trigonocephaly and the affected mother and sister, prominent ectodermal involvement. Metopic suture involvement has not been described before, expanding the main different cranial sutures which can be affected in NS and KRAS gene mutations. The gene alteration found in the studied family is in close proximity to the one reported in the other familial case (close to the switch II region of the G-domain), suggesting that this specific region of the gene could have less severe effects on intellectual ability than the other KRAS gene mutations found in NS patients and be less likely to hamper reproductive fitness. (c) 2012 Wiley Periodicals, Inc.

The Effects of Oxybutynin on Urinary Symptoms in Children with Williams-Beuren Syndrome

Purpose: Williams-Beuren syndrome is a genomic disorder caused by a hemizygous contiguous gene deletion on chromosome 7q11.23. Lower urinary tract symptoms are common in children with Williams-Beuren syndrome. However, there are few data on the management of voiding symptoms in this population. We report our experience using oxybutynin to treat urinary symptoms in children with Williams-Beuren syndrome. Materials and Methods: We prospectively analyzed 42 patients with Williams-Beuren syndrome and significant lower urinary tract symptoms due to detrusor overactivity diagnosed on urodynamics in a 12-week, open-label study. Urological assessment included symptomatic evaluation, the impact of lower urinary tract symptoms on quality of life, frequency-volume chart, urodynamics and urinary tract sonography. After 12 weeks of treatment with 0.6 mg/kg oxybutynin per day given in 3 daily doses, patients were assessed for treatment efficacy and side effects. Results: A total of 17 girls and 19 boys completed medical therapy and were assessed at 12 weeks. Mean +/- SD patient age was 9.2 +/- 4.3 years (range 3 to 18). The most common urinary complaint was urgency, which occurred in 31 patients (86.1%), followed by urge incontinence, which was seen in 29 (80.5%). Compared to baseline, urinary symptoms were substantially improved. The negative impact of storage symptoms on quality of life was significantly decreased from a mean +/- SD of 3.3 +/- 1.7 to 0.5 +/- 0.9 (p <0.001). Mean +/- SD maximum urinary flow improved from 14.2 +/- 15.0 to 20.5 +/- 6.4 ml per second (p <0.001). Conclusions: A total of 12 weeks of therapy with 0.6 mg/kg oxybutynin daily resulted in improvement of lower urinary tract symptoms, quality of life and maximum flow rate in most patients with Williams-Beuren syndrome.

The use of body circumferences for the prediction of intra-abdominal fat in obese women with polycystic ovary syndrome

Introduction: Computerizd tomography (CT) is the gold standard for the evaluation of intra- (IAF) and total (TAF) abdominal fat; however, the high cost of the procedure and exposure to radiation limit its routine use. Objective: To develop equations that utilize anthropometric measures for the estimate of IAF and TAF in obese women with polycystic ovary syndrome (PCOS). Methods: The weight, height, BMI, and abdominal (AC), waist (WC), chest (CC), and neck (NC) circumferences of thirty obese women with PCOS were measured, and their IAF and TAF were analyzed by CT. Results: The anthropometric variables AC, CC, and NC were chosen for the TAF linear regression model because they were better correlated with the fat deposited in this region. The model proposed for TAF (predicted) was: 4.63725 + 0.01483 x AC - 0.00117 x NC - 0.00177 x CC (R-2 = 0.78); and the model proposed for IAF was: IAF (predicted) = 1.88541 + 0.01878 x WC + 0.05687 x NC - 0.01529 x CC (R-2 = 0.51). AC was the only independent predictor of TAF (p < 0.01). Conclusion: The equations proposed showed good correlation with the real value measured by CT, and can be used in clinical practice. (Nutr Hosp. 2012;27:1662-1666) DOI:10.3305/nh.2012.27.5.5933

Expanding the differential diagnosis of inherited neuropathies with non-uniform conduction: Andermann syndrome

Uniform conduction slowing has been considered a characteristic of inherited demyelinating neuropathies. We present an 18-year-old girl, born from first cousins, that presented a late motor and psychological development, cerebellar ataxia, facial diplegia, abnormal eye movement, scoliosis, and corpus callosum agenesis, whose compound muscle action potentials were slowed and dispersed. A mutation was found on KCC3 gene, confirming Andermann syndrome, a disease that must be included in the differential diagnosis of inherited neuropathies with non-uniform conduction slowing.

Cardiometabolic benefits of exercise training in an experimental model of metabolic syndrome and menopause

Objective: The aim of this study was to investigate the cardiometabolic effects of exercise training in ovariectomized hypertensive rats both submitted and not submitted to fructose overload. Methods: Spontaneously hypertensive ovariectomized rats were divided into sedentary and trained (THO) groups submitted to normal chow and sedentary and trained groups submitted to fructose overload (100 g/L in drinking water for 19 wk). Exercise training was performed on a treadmill (8 wk). Arterial pressure (AP) was directly recorded. Cardiovascular autonomic control was evaluated through pharmacological blockade (atropine and propranolol) and in the time and frequency domains by spectral analysis. Results: The THO group presented reduced AP (approximately 16 mm Hg) and enhanced cardiac vagal tonus (approximately 49%) and baroreflex sensitivity (approximately 43%) compared with the sedentary hypertensive ovariectomized group. Exercise training attenuated metabolic impairment, resting tachycardia, cardiac and vascular sympathetic increases, and baroreflex sensitivity decrease induced by fructose overload in hypertensive rats. However, the trained hypertensive ovariectomized group submitted to fructose overload presented higher AP (approximately 32 mm Hg), associated with baroreflex sensitivity (approximately 69%) and parasympathetic dysfunctions compared with the THO group. Conclusions: These data suggest that the metabolic disorders in hypertensive rats after ovarian hormone deprivation could blunt and/or attenuate some exercise training benefits.