Predictive value of hyperglycosylated human chorionic gonadotropin for pregnancy outcomes in threatened abortion in first-trimester viable pregnancies.

BACKGROUND: To investigate the value of a single determination of hyperglycosylated hCG (hCG-H) for predicting the clinical outcome of patients with threatened abortion in the first trimester of pregnancy. METHODS: Prospective study performed on 86 consecutively selected women with a diagnosis of threatened abortion and viable intrauterine pregnancy in the first trimester of pregnancy, conducted in two tertiary care hospitals. All patients underwent a single blood sample to determine hCG-H and total hCG serum levels and a transvaginal ultrasound 12-24 hours after diagnosis. Patients were monitored to determine whether the outcome was a miscarriage before the 20th week of pregnancy. RESULTS: Forty-three women (50%) had a miscarriage during the follow-up. We observed a very high correlation between hCG-H and total hCG (r?=?0.91, p?

Predictive value of hyperglycosylated human chorionic gonadotropin for pregnancy outcomes in threatened abortion in first-trimester viable pregnancies / Valor predictivo de la hCG hiperglosilada para predecir resultado de la gestación en amenaza de aborto de primer trimestre en gestación viable

BACKGROUND: To investigate the value of a single determination of hyperglycosylated hCG (hCG-H) for predicting the clinical outcome of patients with threatened abortion in the first trimester of pregnancy. METHODS: Prospective study performed on 86 consecutively selected women with a diagnosis of threatened abortion and viable intrauterine pregnancy in the first trimester of pregnancy, conducted in two tertiary care hospitals. All patients underwent a single blood sample to determine hCG-H and total hCG serum levels and a transvaginal ultra-sound 12-24 hours after diagnosis. Patients were monitored to determine whether the outcome was a miscarriage before the 20th week of pregnancy. RESULTS: Forty-three women (50%) had a miscarriage during the follow-up. We observed a very high correlation between hCG-H and total hCG (r = 0.91, p < 0.001). Median hCG-H and total hCG from pregnancies with normal outcome was significantly higher than those ending in abortion. hCG-H and total hCG were very similar predictors of pregnancy outcomes (AUC: 0.90 and 0.89, respectively). The ratio hCG-H / total hCG was a poor predictor (AUC: 0.64). CONCLUSION: A single hCG-H assay is helpful for predicting pregnancy outcomes in women with first trimester threatened abortion and viable or potentially viable pregnancy at the time of presentation. However, hCG-H is not a better predictor than total hCG

FUNDAMENTO: Investigar el valor de una única determinación de hCG hiperglicosilada (hCG-H) para predecir el resultado clínico de pacientes con amenaza de aborto en el primer trimestre del embarazo. MÉTODOS: Estudio prospectivo realizado en 86 mujeres, seleccionadas consecutivamente, con diagnóstico de amenaza de aborto y embarazo intrauterino viable en el primer trimestre de embarazo, realizado en dos hospitales de tercer nivel. A todas las pacientes se les realizó una única extracción sanguínea para determinar los niveles séricos de hCG-H y hCG total, y una ecografía transvaginal 12-24 horas después del episodio de sangrado. Se realizó seguimiento de las pacientes para determinar si el resultado fue un aborto espontáneo antes de la semana 20 de embarazo. RESULTADOS: Cuarenta y tres mujeres (50%) sufrieron un aborto espontáneo durante el seguimiento. Se observó una correlación muy alta entre hCG-H y hCG total (r = 0,91, p < 0,001). La mediana de hCG-H y hCG total de los embarazos con resultado normal fue significativamente mayor que la de aquellos que terminaron en aborto. La hCG-H y la hCG total fueron predictores muy similares del resultado del embarazo (AUC: 0,90 y 0,89, respectivamente). La relación hCG-H / hCG total fue un mal predictor (AUC: 0,64). CONCLUSIÓN: La determinación única de hCG-H es útil para predecir el resultado del embarazo en mujeres con amenaza de aborto en el primer trimestre y embarazo viable en el momento de la presentación clínica. Sin embargo, la hCG-H no es mejor predictor que la hCG total

Fracturas de falanges tratadas con placas de osteosintesis: Resultados a corto plazo / Phalangeal fractures treated with osteosynthesis plates. Short-term results

Introducción: Se realizo un estudio de cohorte prospectivo para evaluar los resultados funcionales de pacientes laborales con fracturas de falange tratadas mediante placas y establecer factores de mal pronostico. Materiales y Métodos: Desde mayo de 2012 hasta mayo de 2014, 55 pacientes laborales con fracturas de falange fueron operados consecutivamente, mediante reduccion y osteosintesis con placa y tornillos. Cuarenta y dos (39 hombres, edad promedio 30.76 anos) fueron evaluados, con 68 falanges operadas (primera falange 15, segunda falange 53). El 28% de las fracturas fueron expuestas; el 38,24%, conminutas y el 11,76% tenia compromiso articular. El seguimiento promedio fue de 3.38 meses. Resultados: Se logro la consolidacion osea de todas las fracturas a los 1.8 meses. La movilidad para el pulgar (Gingrass) fue buena en dos casos y regular en uno. En los restantes dedos (Belsky), fue excelente (35%), buena (55%) y mala (9%). El puntaje DASH promedio fue de 18,53. Se observaron peores resultados en las fracturas de la primera falange respecto de la segunda falange y en pacientes con mas edad que en los mas jovenes, ambos con significancia estadistica. No hubo relacion entre el resultado y las demas variables estudiadas. Cuatro pacientes tuvieron complicaciones (9,5%). Conclusiones: Al comparar nuestra serie con otras publicadas, hubo menos complicaciones y los resultados fueron similares, pero a diferencia de otros autores, no acostumbramos a retirar el material ni a realizar tenolisis ni artrolisis. Se logro la consolidacion osea en todos los casos y los resultados fueron satisfactorios en el 90% de los pacientes. Nivel de Evidencia: IV

Introduction: A prospective cohort study was carried out to evaluate functional results in workers with phalangeal fractures treated with plates and to establish poor prognostic factors. Methods: From May 2012 to May 2014, 55 workers with phalangeal fractures were operated on consecutively by reduction and fixation with plate and screws. Forty-two patients (39 men; average age 30.76 years) were evaluated, with 68 operated phalanges (first phalanx 15, second phalanx 53). Twenty-eight percent of fractures were open, 38.24% comminuted and 11.76% had joint involvement. Average follow-up: 3.38 months. Results: Bone union was achieved in all fractures in 1.8 months. Gingrass score for the thumb was good in two cases and regular in one. In the remaining fingers, Belsky score was excellent (35%), good (55%), and poor (9%). Average DASH score was 18.53. Worse results were observed in the first phalanx fractures with respect to the second and in older patients than in the younger, both with statistical significance. No relationship was observed among the outcome and other variables studied. Four patients had complications (9.5%). Conclusions: When comparing our findings with other studies, the rate of complications was small, and similar results were obtained, but unlike other authors, we are not used to removing hardware with tenolysis or arthrolysis. Bone union was achieved in all cases and results were satisfactory in 90% of patients. Level of Evidence: IV

IOTA simple rules for discriminating between benign and malignant adnexal masses: prospective external validation.

OBJECTIVE: To determine the diagnostic performance of International Ovarian Tumor Analysis (IOTA) 'simple' rules for discriminating between benign and malignant adnexal masses. METHODS: A prospective study was performed between January 2011 and June 2012. Eligible patients were women diagnosed with a persistent adnexal mass who presented to the participating centers. Four trainees evaluated the adnexal mass by transvaginal ultrasound under the supervision of an expert examiner. The trainee analyzed the mass according to IOTA simple rules and provided a diagnosis of benign, malignant or inconclusive. All women included in the study underwent surgery and tumor removal in the center of recruitment. Diagnostic performance was assessed by calculating sensitivity, specificity and positive (LR+) and negative (LR-) likelihood ratios. RESULTS: A total of 340 women were included (mean patient age, 42.1 (range, 13-79) years). Of the tumors, 55 (16.2%) were malignant and 285 (83.8%) were benign. The IOTA simple rules could be applied in 270 (79.4%) cases. In these cases, sensitivity was 87.9% (95% CI, 72.4-95.2), specificity 97.5% (95% CI, 94.6-98.8), LR+ 34.7 (95% CI, 15.6-77.3) and LR- 0.12 (95% CI, 0.05-0.31). CONCLUSIONS: Application of the IOTA simple rules yielded acceptable results in terms of specificity in the hands of non-expert examiners. However, with non-expert examiners there was a 12% false-negative rate, which is relatively high.

Tracheal aspirate pH is alkaline in pre-term human infants.

The pH of sputum and exhaled breath condensate is abnormal in several pulmonary disorders. Though airway pH regulatory proteins may be abnormally expressed in human development, the tracheal aspirate pH of infants born prematurely has not been studied. Undiluted mid-tracheal aspirate samples were obtained on the first day of life from pre-term (23-30 weeks' gestation) and term (> or =37 weeks' gestation) infants for pH measurement; subsequently, pH was measured on days 7, 14 and 21 from the pre-term infants who remained intubated. Thirty-five pre-term infants and eight term infants had samples collected on the first day of life. The mean pH of the pre-term infant samples (8.31 +/- 0.35) was significantly higher than that of the term infants (7.83 +/- 0.39). The pH in pre-term infants' airways fell with prolonged endotracheal intubation; the maximal decrease was of -1.37 +/- 0.96 pH units to 6.89 +/- 0.77. Pre-term infants have a higher tracheal aspirate pH than full-term infants, and their airways tend to become more acidic with prolonged mechanical ventilation. The present data demonstrate for the first time that premature infants may have abnormal tracheal aspirate pH.

Exhaled breath condensate: methodological recommendations and unresolved questions.

Collection of exhaled breath condensate (EBC) is a noninvasive method for obtaining samples from the lungs. EBC contains large number of mediators including adenosine, ammonia, hydrogen peroxide, isoprostanes, leukotrienes, nitrogen oxides, peptides and cytokines. Concentrations of these mediators are influenced by lung diseases and modulated by therapeutic interventions. Similarly EBC pH also changes in respiratory diseases. The aim of the American Thoracic Society/European Respiratory Society Task Force on EBC was to identify the important methodological issues surrounding EBC collection and assay, to provide recommendations for the measurements and to highlight areas where further research is required. Based on the currently available evidence and the consensus of the expert panel for EBC collection, the following general recommendations were put together for oral sample collection: collect during tidal breathing using a noseclip and a saliva trap; define cooling temperature and collection time (10 min is generally sufficient to obtain 1-2 mL of sample and well tolerated by patients); use inert material for condenser; do not use resistor and do not use filter between the subject and the condenser. These are only general recommendations and certain circumstances may dictate variation from them. Important areas for future research involve: ascertaining mechanisms and site of exhaled breath condensate particle formation; determination of dilution markers; improving reproducibility; employment of EBC in longitudinal studies; and determining the utility of exhaled breath condensate measures for the management of individual patients. These studies are required before recommending this technique for use in clinical practice.

Acid-base equilibrium in exhaled breath condensate of allergic asthmatic children.

BACKGROUND: The dysregulation of airway pH control may have a role in asthma pathophysiology. The measurement of exhaled breath condensate (EBC) pH and ammonia levels may be used as a noninvasive method to study acid-base status in the airway of asthmatics. METHODS: Exhaled breath condensate from 29 allergic stable asthmatic children and 13 healthy controls was collected by cooling exhaled air during tidal breathing. Ammonia was measured by high-performance liquid chromatography with fluorescence detection. pH was measured after deaeration of EBC samples by bubbling with argon. The children also underwent FENO measurement. RESULTS: Both pH and ammonia values in EBC were significantly lower in the asthmatics than in the control group [pH: ICS-treated (median and interquartile range) 7.70 (7.62-7.74), steroid-naive 7.53 (7.41-7.68), controls 7.85 (7.80-7.90), P <0.01 and P <0.001, respectively; ammonia: ICS-treated 476.17 microM (282.50-594.80), steroid-naive 253.24 microM (173.43-416.08), controls 788.30 microM (587.29-1310.39), P < 0.05 and P <0.001, respectively]. Both pH and ammonia values were higher in ICS-treated than in steroid-naive asthmatic children. There was a significant correlation between EBC pH and ammonia concentrations. CONCLUSIONS: These data show that EBC pH values of stable asthmatic children are lower compared with those of healthy controls and positively correlated with ammonia concentrations, supporting the hypothesis that airway acidification may have a role in the pathobiology of allergic asthma.

Exhaled breath condensate pH is a robust and reproducible assay of airway acidity.

Exhaled breath condensate (EBC) pH is low in several lung diseases and it normalises with therapy. The current study examined factors relevant to EBC pH monitoring. Intraday and intraweek variability were studied in 76 subjects. The pH of EBC collected orally and from isolated lower airways was compared in an additional 32 subjects. Effects of ventilatory pattern (hyperventilation/hypoventilation), airway obstruction after methacholine, temperature (-44 to +13 degrees C) and duration of collection (2-7 min), and duration of sample storage (up to 2 yrs) were examined. All samples were collected with a disposable condensing device, and de-aerated with argon until pH measurement stabilised. Mean EBC pH (n=76 subjects, total samples=741) was 7.7+/-0.49 (mean+/-SD). Mean intraweek and intraday coefficients of variation were 4.5% and 3.5%. Control of EBC pH appears to be at the level of the lower airway. Temperature of collection, duration of collection and storage, acute airway obstruction, subject age, saliva pH, and profound hyperventilation and hypoventilation had no effect on EBC pH. The current authors conclude that in health, exhaled breath condensate pH is slightly alkaline, held in a narrow range, and is controlled by lower airway source fluid. Measurement of exhaled breath condensate pH is a simple, robust, reproducible and relevant marker of disease.

S-Nitrosylation of mitochondrial caspases.

Caspase-3 is a cysteine protease located in both the cytoplasm and mitochondrial intermembrane space that is a central effector of many apoptotic pathways. In resting cells, a subset of caspase-3 zymogens is S-nitrosylated at the active site cysteine, inhibiting enzyme activity. During Fas-induced apoptosis, caspases are denitrosylated, allowing the catalytic site to function. In the current studies, we sought to identify the subpopulation of caspases that is regulated by S-nitrosylation. We report that the majority of mitochondrial, but not cytoplasmic, caspase-3 zymogens contain this inhibitory modification. In addition, the majority of mitochondrial caspase-9 is S-nitrosylated. These studies suggest that S-nitrosylation plays an important role in regulating mitochondrial caspase function and that the S-nitrosylation state of a given protein depends on its subcellular localization.

S-nitrosothiols signal the ventilatory response to hypoxia.

Increased ventilation in response to hypoxia has been appreciated for over a century, but the biochemistry underlying this response remains poorly understood. Here we define a pathway in which increased minute ventilation (&Vdot;E ) is signalled by deoxyhaemoglobin-derived S-nitrosothiols (SNOs). Specifically, we demonstrate that S-nitrosocysteinyl glycine (CGSNO) and S-nitroso-l-cysteine (l-CSNO)-but not S-nitroso-d-cysteine (d-CSNO)-reproduce the ventilatory effects of hypoxia at the level of the nucleus tractus solitarius (NTS). We show that plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia. Further, this activity is mediated by S-nitrosoglutathione (GSNO), and GSNO activation by gamma-glutamyl transpeptidase (gamma-GT) is required. The normal response to hypoxia is impaired in a knockout mouse lacking gamma-GT. These observations suggest that S-nitrosothiol biochemistry is of central importance to the regulation of breathing.

Evaluation of regional bond strength of resin cement to endodontic surfaces.

The purpose of this study was to test the feasibility of adapting a new microtensile testing technique to measure resin cement bond strengths to the cervical, middle, and apical thirds of root canals. Post spaces were created in extracted human teeth, and the roots were ground flat on one side to expose the canal and permit ideal placement of one of two resin cements (Panavia 21 or C&B Metabond). After 48 h of storage, serial 1-mm-thick cross-sections were cut to create 6-10 specimens per root. The first three specimens were from the cervical third, the next three were from the middle third, and the last three were from the apical third of the root. Each 1 x 1 x 8 mm specimen was pulled to failure in a miniature testing machine. The results indicated that both resin cements produced high bond strengths (12-23 MPa), and that bond strengths to the apical third were significantly higher (p < 0.05) than to the cervical or middle third with either cement. This new method shows promise for evaluating resin bond strengths within root canals.

Accelerated s-nitrosothiol breakdown by amyotrophic lateral sclerosis mutant copper,zinc-superoxide dismutase.

Mutations in copper,zinc-superoxide dismutase (SOD) have been implicated in familial amyotrophic lateral sclerosis (FALS). We have investigated the breakdown of S-nitrosothiols by wild-type (WT) SOD and two common FALS mutants, alanine-4 valine (A4V) SOD and glycine-37 arginine (G37R) SOD. In the presence of glutathione, A4V SOD and G37R SOD catalyzed S-nitrosoglutathione breakdown three times more efficiently than WT SOD. Indeed, A4V SOD catabolized GSNO more efficiently than WT SOD throughout the physiological range of GSH concentrations. Moreover, a variety of additional S-nitrosothiols were catabolized more readily by A4V SOD than by WT SOD. Initial rate data for fully reduced WT SOD and A4V SOD, and data using ascorbic acid as the reductant, suggest that FALS mutations in SOD may influence the efficiency of reduction of the copper center by glutathione. We have identified a potentially toxic gain of function of two common FALS mutations that may contribute to neurodegeneration in FALS.

S-nitrosoglutathione increases cystic fibrosis transmembrane regulator maturation.

Endogenous S-nitrosoglutathione (GSNO) is known to increase the expression of certain proteins at concentrations present in the normal human airway. We hypothesized that GSNO would increase expression and maturation of the cystic fibrosis transmembrane conductance regulator (CFTR). Cells expressing DeltaF508 and wild type CFTR were exposed to GSNO and analyzed for expression and maturation by Western blot analysis. Physiologically relevant concentrations of GSNO resulted in dose- and time-dependent increases in expression. The GSNO-induced increases were eliminated by cycloheximide, suggesting a posttranscriptional effect. Unlike proteasome inhibitors, GSNO resulted in an increase CFTR maturation. The GSNO effect could be reversed by dithiothreitol and inhibited by acivicin, a gamma glutamyl transpeptidase inhibitor. These observations suggest that GSNO leads to maturation of mutated DeltaF508 CFTR, a process associated with restoration of CFTR function. Because endogenous levels of GSNO are low in the cystic fibrosis (CF) airway, these results raise the possibility that GSNO replacement therapy could be an effective treatment for CF.

NO chemical events in the human airway during the immediate and late antigen-induced asthmatic response.

A wealth of evidence supports increased NO (NO.) in asthma, but its roles are unknown. To investigate how NO participates in inflammatory airway events in asthma, we measured NO. and NO. chemical reaction products [nitrite, nitrate, S-nitrosothiols (SNO), and nitrotyrosine] before, immediately and 48 h after bronchoscopic antigen (Ag) challenge of the peripheral airways in atopic asthmatic individuals and nonatopic healthy controls. Strikingly, NO(3)(-) was the only NO. derivative to increase during the immediate Ag-induced asthmatic response and continued to increase over 2-fold at 48 h after Ag challenge in contrast to controls [P < 0.05]. NO(2)(-) was not affected by Ag challenge at 10 min or 48 h after Ag challenge. Although SNO was not detectable in asthmatic airways at baseline or immediately after Ag, SNO increased during the late response to levels found in healthy controls. A model of NO. dynamics derived from the current findings predicts that NO. may have harmful effects through formation of peroxynitrite, but also subserves an antioxidant role by consuming reactive oxygen species during the immediate asthmatic response, whereas nitrosylation during the late asthmatic response generates SNO, safe reservoirs for removal of toxic NO. derivatives.

Normoxic stabilization of hypoxia-inducible factor-1 expression and activity: redox-dependent effect of nitrogen oxides.

Hypoxia-inducible factor-1 (HIF-1) is an essential transcription factor involved in the oxygen-dependent regulation of gene expression. Thiol groups in HIF-1 or in proteins that modify HIF-1 are conventional targets for regulation by nitric oxide (NO). Moreover, NO delivery to tissue by hemoglobin appears to be oxygen dependent. Therefore, the role NO plays in regulating HIF-1 activity and expression was examined. The 1-substituted diazen-1-ium-1, 2-diolate NOC-18 induced HIF-1 DNA-binding activity in normoxic bovine pulmonary artery endothelial cells and rat aortic smooth muscle cells in a time- and dose-dependent manner. Induction of HIF-1-binding activity was consistent with an increased expression of HIF-1 subunit proteins HIF-1alpha and HIF-1beta. The effect of NOC-18 on HIF-1 activity was blocked by cycloheximide, consistent with a post-transcriptional effect. NOC-18 induction of HIF-1 DNA-binding activity was not blocked with oxyhemoglobin, nor was it related to the rate of NO evolution, arguing against NO-mediation of the effect. Additionally, the effect of NOC-18 could not be mimicked by Angeli's salt, arguing against nitroxyl mediation. However, the NOC-18 effect could be reproduced by S-nitrosoglutathione (GSNO), an endogenous nitrosonium donor formed in the presence of deoxyhemoglobin. Furthermore, the GSNO effect could be reversed by dithiothreitol as well as acivicin, an inhibitor of GSNO bioactivation. Taken together, these results suggest that an S-nitrosylation reaction stabilizes HIF-1 protein expression and activity. We speculate that one signaling mechanism by which deoxyhemoglobin may activate HIF-1 involves NO.

Elevated nitric oxide metabolite levels in chronic sinusitis.

Decreased exhaled nitric oxide (NO) is found in chronic sinusitis. NO metabolites (nitrates, nitrites, and S-nitrosothiols) were measured in sinus lavages with a rabbit model of chronic sinusitis. NO metabolite levels (mean +/- SD) were 3.0+/-1.6 micromol/L in uninfected rabbits, 10.7+/-11.4 micromol/L in infected animals, and 7.6+/-5.4 micromol/L in postantrostomy recovering animals. Infected sinuses had elevated levels of NO metabolites that were statistically significant (P<0.01) when compared with uninfected sinuses. Mucociliary transport velocity was measured in uninfected (16.0+/-5.7 mm/minute), infected (5.2+/-1.3 mm/minute), and recovery phases (3.0 mm/minute). Endoscopic appearance, light and electron microscopy, and bacterial cultures improved during recovery. Elevated levels of NO metabolites were found during chronic sinusitis and began to return to normal levels during recovery. The possible link between NO in epithelial autotoxicity and host defense mechanisms warrants further investigation.

S-nitrosoglutathione breakdown prevents airway smooth muscle relaxation in the guinea pig.

Airway levels of the endogenous bronchodilator S-nitrosoglutathione (GSNO) are low in children with near-fatal asthma. We hypothesized that GSNO could be broken down in the lung and that this catabolism could inhibit airway smooth muscle relaxation. In our experiments, GSNO was broken down by guinea pig lung homogenates, particularly after ovalbumin sensitization (OS). Two lung protein fractions had catabolic activity. One was NADPH dependent and was more active after OS. The other was NADPH independent and was partially inhibited by aurothioglucose. Guinea pig lung tissue protein fractions with GSNO catabolic activity inhibited GSNO-mediated guinea pig tracheal ring relaxation. The relaxant effect of GSNO was partially restored by aurothioglucose. These observations suggest that catabolism of GSNO in the guinea pig 1) is mediated by lung proteins, 2) is partially upregulated after OS, and 3) may contribute to increased airway smooth muscle tone. We speculate that enzymatic breakdown of GSNO in the lung could contribute to asthma pathophysiology by inhibiting the beneficial effects of GSNO, including its effect on airway smooth muscle tone.

Airway nitrogen oxide measurements in asthma and other pediatric respiratory diseases.

Markers for airway inflammation that can be measured noninvasively in expired air may be helpful in treating patients with asthma. For example, levels of nitric oxide are high in the breath of children with asthma exacerbations and decrease with anti-inflammatory therapy. Expired nitric oxide testing has now been standardized and may be useful for children with recurring wheezing that is diagnostically or therapeutically challenging. However, the results may be influenced by several biochemical and anatomic variables and must therefore be interpreted with caution.