Why Are Women With Cervical Cancer Not Being Diagnosed in Preinvasive Phase? An Analysis of Risk Factors Using a Hierarchical Model

Objective: To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods: This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low-or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals' care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results: The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3-48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3-4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3-13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5-35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1-0.8) for delayed diagnosis. Conclusions: Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

Analysis of the NMDA in Focal Cerebral Ischemia in Rats

NMDAR (N-methyl-D-aspartate receptor) is one subtype of ionotrophic glutamate receptor which is extensively distributed in the central nervous system (CNS). In the mammalian CNS, NMDAR serves prominent roles in the pathophysiologic process of cerebral ischemia. This study aimed to investigate the pattern of expression of protein and gene of the excitatory neurotransmitter NMDAR in experimental focal cerebral ischemia and the hole of neuroprotection with hypothermia and ketoprofen. 120 rats were randomly divided into 6 groups (20 animals each): control - no surgery; sham - simulation of surgery; ischemic - focal ischemia for 1 hour, without reperfusion; ischemic + intraischemic hypothermia; ischemic + previous intravenous ketoprofen, and ischemic + hypothermia and ketoprofen. Ten animals from each experimental group were used to establish the volume of infarct. Transient focal cerebral ischemia was obtained in rats by occlusion of the middle cerebral artery with an intraluminal suture. The infarct volume was measured using morphometric analysis of infarct areas defined by triphenyl tetrazolium chloride and the patterns of expression of the protein and gene NMDA were evaluated by immunohistochemistry and quantitative real-time PCR, respectively. Increases in the protein and gene NMDA receptor in the ischemics areas were observed and these increases were reduced by hypothermia and ketoprofen. The increase in the NMDA receptor protein and gene expression observed in the ischemic animals was reduced by neuroprotection (hypothermia and ketoprofen). The NMDA receptor increases in the ischemic area suggests that the NMDA mediated neuroexcitotoxicity plays an important role in cell death and that the neuroprotective effect of both, hypothermia and ketoprofen is directly involved with the NMDA.

X-ray densitometry to assess internal seed morphology and quality

Non-destructive procedures are desirable for a precise internal seed morphology assessment. In this research the efficiency of X-ray densitometry for internal seed morphology analysis and physical quality of squash, melon and watermelon was evaluated. Seeds were submitted to X-ray densitometry and a typical density profile for each seed was generated. Based on the detailed densitometry profiles it was possible indicate density values for specific seed regions of the seeds and identify causes of poor germination. X-ray densitometry was considered as a promising non-destructive procedure to evaluate internal seed morphology of squash, melon and watermelon and demonstrated a strong potential for further research in seed testing.

Analysis of nonlinear dynamics of vocal folds using high-speed video observation and biomechanical modeling

Primary voice production occurs in the larynx through vibrational movements carried out by vocal folds. However, many problems can affect this complex system resulting in voice disorders. In this context, time-frequency-shape analysis based on embedding phase space plots and nonlinear dynamics methods have been used to evaluate the vocal fold dynamics during phonation. For this purpose, the present work used high-speed video to record the vocal fold movements of three subjects and extract the glottal area time series using an image segmentation algorithm. This signal is used for an optimization method which combines genetic algorithms and a quasi-Newton method to optimize the parameters of a biomechanical model of vocal folds based on lumped elements (masses, springs and dampers). After optimization, this model is capable of simulating the dynamics of recorded vocal folds and their glottal pulse. Bifurcation diagrams and phase space analysis were used to evaluate the behavior of this deterministic system in different circumstances. The results showed that this methodology can be used to extract some physiological parameters of vocal folds and reproduce some complex behaviors of these structures contributing to the scientific and clinical evaluation of voice production. (C) 2010 Elsevier Inc. All rights reserved.

Utilization of fringe projection technique for evaluation of wound dimensions and of healing progress.

Background: The methods used for evaluating wound dimensions, especially the chronic ones, are invasive and inaccurate. The fringe projection technique with phase shift is a non-invasive, accurate and low-cost optical method. Objective: The aim is to validate the technique through the determination of dimensions of objects of known topography and with different geometries and colors to simulate the wounds and tones of skin color. Taking into account the influence of skin wound optical factors, the technique will be used to evaluate actual patients’ wound dimensions and to study its limitations in this application. Methods: Four sinusoidal fringe patterns, displaced ¼ of period each, were projected onto the objects surface. The object dimensions were obtained from the unwrapped phase map through the observation of the fringe deformations caused by the object topography and using phase shift analysis. An object with simple geometry was used for dimensional calibration and the topographic dimensions of the others were determined from it. After observing the compatibility with the data and validating the method, it was used for measuring the dimensions of real patients’ wounds. Results and Conclusions: The discrepancies between actual topography and dimensions determined with Fringe Projection Technique and for the known object were lower than 0.50 cm. The method was successful in obtaining the topography of real patient’s wounds. Objects and wounds with sharp topographies or causing shadow or reflection are difficult to be evaluated with this technique.

Characterization of nanostructured material images using fractal descriptors

This work presents a methodology to the morphology analysis and characterization of nanostructured material images acquired from FEG-SEM (Field Emission Gun-Scanning Electron Microscopy) technique. The metrics were extracted from the image texture (mathematical surface) by the volumetric fractal descriptors, a methodology based on the Bouligand-Minkowski fractal dimension, which considers the properties of the Minkowski dilation of the surface points. An experiment with galvanostatic anodic titanium oxide samples prepared in oxalyc acid solution using different conditions of applied current, oxalyc acid concentration and solution temperature was performed. The results demonstrate that the approach is capable of characterizing complex morphology characteristics such as those present in the anodic titanium oxide.

LIQUID-PHASE MICROEXTRACTION FOR SIMULTANEOUS CHROMATOGRAPHIC ANALYSIS OF THREE ANTIDEPRESSANT DRUGS IN PLASMA

A method using Liquid Phase Microextraction for simultaneous detection of citalopram (CIT), paroxetine (PAR) and fluoxetine (FLU), using venlafaxine as internal standard, in plasma by high performance liquid chromatography with fluorescence detection was developed. The linearity was evaluated between 5.0 and 500 ng mL(-1) (r > 0.99) and the limit of quantification was 2.0, 3.0 and 5.0 ng mL-1 for CIT. PAR and FLU, respectively. Therefore, it can be applied to therapeutic drug monitoring, pharmacokinetics or bioavailability studies and its advantages are that it necessary relatively inexpensive equipment and sample preparation techniques.

In Vitro Analysis of Bacterial Morphology by Atomic Force Microscopy of Low Level Laser Therapy 660, 830 and 904 nm

Objective: The objective of this study was to analyze the bacterial morphology by atomic force microscopy (AFM) after the application of low-level laser therapy (LLLT) in in vitro culture of Staphylococcus aureus ATCC 29213. Background data: Infections caused by S. aureus are among the highest occurring in hospitals and can often colonize pressure ulcers. LLLT is among the methods used to accelerate the healing of ulcers. However, there is no consensus on its effect on bacteria. Materials and methods: After being cultivated and seeded, the cultures were irradiated using wavelengths of 660, 830, and 904 nm at fluences of 0, 1, 2, 3, 4, 5, and 16 J/cm(2). Viable cells of S. aureus strain were counted after 24 h incubation. To analyze the occurrence of morphological changes, the topographical measurement of bacterial cells was analyzed using the AFM. Results: The overall assessment revealed that the laser irradiation reduced the S. aureus growth using 830 and 904 nm wavelengths; the latter with the greatest inhibition of the colony-forming units (CFU/mL) (331.1 +/- 38.19 and 137.38 +/- 21.72). Specifically with 660 nm, the statistical difference occurred only at a fluence of 3 J/cm(2). Topographical analysis showed small changes in morphological conformity of the samples tested. Conclusions: LLLT reduced the growth of S. aureus with 830 and 904 nm wavelengths, particularly with 904 nm at a fluence of 3 J/cm(2), where the greatest topographical changes of the cell structure occurred.

Overall Survival Improvement in Patients with Lung Cancer and Bone Metastases Treated with Denosumab Versus Zoledronic Acid Subgroup Analysis from a Randomized Phase 3 Study

Introduction: Denosumab, a fully human anti-RANKL monoclonal antibody, reduces the incidence of skeletal-related events in patients with bone metastases from solid tumors. We present survival data for the subset of patients with lung cancer, participating in the phase 3 trial of denosumab versus zoledronic acid (ZA) in the treatment of bone metastases from solid tumors (except breast or prostate) or multiple myeloma. Methods: Patients were randomized 1:1 to receive monthly subcutaneous denosumab 120 mg or intravenous ZA 4 mg. An exploratory analysis, using Kaplan-Meier estimates and proportional hazards models, was performed for overall survival among patients with non-small-cell lung cancer (NSCLC) and SCLC. Results: Denosumab was associated with improved median overall survival versus ZA in 811 patients with any lung cancer (8.9 versus 7.7 months; hazard ratio [HR] 0.80) and in 702 patients with NSCLC (9.5 versus 8.0 months; HR 0.78) (p = 0.01, each comparison). Further analysis of NSCLC by histological type showed a median survival of 8.6 months for denosumab versus 6.4 months for ZA in patients with squamous cell carcinoma (HR 0.68; p = 0.035). Incidence of overall adverse events was balanced between treatment groups; serious adverse events occurred in 66.0% of denosumab-treated patients and 72.9% of ZA-treated patients. Cumulative incidence of osteonecrosis of the jaw was similar between groups (0.7% denosumab versus 0.8% ZA). Hypocalcemia rates were 8.6% with denosumab and 3.8% with ZA. Conclusion: In this exploratory analysis, denosumab was associated with improved overall survival compared with ZA, in patients with metastatic lung cancer.

Automated analysis of lidocaine and its metabolite in plasma by in-tube solid-phase microextraction coupled with LC-UV for pharmacokinetic study

A sensitive, selective, and reproducible in-tube solid-phase microextraction and liquid chromatographic (in-tube SPME/LC-UV) method for determination of lidocaine and its metabolite monoethylglycinexylidide (MEGX) in human plasma has been developed, validated, and further applied to pharmacokinetic study in pregnant women with gestational diabetes mellitus (GDM) subjected to epidural anesthesia. Important factors in the optimization of in-tube SPME performance are discussed, including the draw/eject sample volume, draw/eject cycle number, draw/eject flow rate, sample pH, and influence of plasma proteins. The limits of quantification of the in-tube SPME/LC method were 50 ng/mL for both metabolite and lidocaine. The interday and intraday precision had coefficients of variation lower than 8%, and accuracy ranged from 95 to 117%. The response of the in-tube SPME/LC method for analytes was linear over a dynamic range from 50 to 5000 ng/mL, with correlation coefficients higher than 0.9976. The developed in-tube SPME/LC method was successfully used to analyze lidocaine and its metabolite in plasma samples from pregnant women with GDM subjected to epidural anesthesia for pharmacokinetic study.

Analysis of carvedilol enantiomers in human plasma using chiral stationary phase column and liquid chromatography with tandem mass spectrometry

Carvedilol is an antihypertensive drug available as a racemic mixture. (-)-(S)-carvedilol is responsible for the nonselective beta-blocker activity but both enantiomers present similar activity on a1-adrenergic receptor. To our knowledge, this is the first study of carvedilol enantiomers in human plasma using a chiral stationary phase column and liquid chromatography with tandem mass spectrometry. The method involves plasma extraction with diisopropyl ether using metoprolol as internal standard and direct separation of the carvedilol enantiomers on a Chirobiotic T (R) (Teicoplanin) column. Protonated ions [M + H]+ and their respective ion products were monitored at transitions of 407 > 100 for the carvedilol enantiomers and 268 > 116 for the internal standard. The quantification limit was 0.2 ng ml-1 for both enantiomers in plasma. The method was applied to study enantioselectivity in the pharmacokinetics of carvedilol administered as a single dose of 25 mg to a hypertensive patient. The results showed a higher plasma concentration of (+)-(R)-carvedilol (AUC08 205.52 vs. 82.61 (ng h) ml-1), with an enantiomer ratio of 2.48. Chirality, 2012. (C) 2012 Wiley Periodicals, Inc.

Analysis of phase transition and dehydration processes of nevirapine

Solid-state characterization of crystalline drugs is an important pre-formulation step for the development and design of solid dosage forms, such as pellets and tablets. In this study, phase transition and dehydration processes of nevirapine have been studied by differential scanning calorimetry and thermogravimetry differential thermal analysis to overcome the problems of drug formulation, namely poor solubility and poor content uniformity. Phase solubility studies elucidated the mechanism of enhanced nevirapine solubility.

A LED Based Photometer for Solid Phase Photometry: Zinc Determination in Pharmaceutical Preparation Employing a Multicommuted Flow Analysis Approach

In this work, a LED (light emitting diode) based photometer for solid phase photometry is described. The photometer was designed to permit direct coupling of a light source (LED) and a photodiode to a flow cell with an optical pathlength of 4 mm. The flow cell was filled with adsorbing solid phase material (C-18), which was used to immobilize the chromogenic reagent 1-(2-thiazolylazo)-2-naphthol (TAN). Aiming to allow accuracy assessment, samples were also analyzed employing ICP OES (inductively coupled plasma optical emission spectrometry) methodology. Applying the paired t-test at the 95% confidence level, no significant difference was observed. Other useful features were also achieved: linear response ranging from 0.05 to 0.85 mg L-1 Zn, limit of detection of 9 mu g L-1 Zn (3 sigma criterion), standard deviation of 1.4% (n = 10), sampling throughput of 36 determinations per h, and a waste generation and reagent consumption of 1.7 mL and of 0.03 mu g per determination, respectively.

Morphology and topography analysis of mesoporous titania templated by micrometric latex sphere arrays

In this work, mesoporous titania is prepared by templating latex sphere arrays with four different sphere diameters at the micrometric scale (phi > 1 mu m). The mesoporous titania homogeneously covers the latex spheres and substrate, forming a thin coating characterized by N-2 adsorption isotherm, small angle X-rays scattering, atomic force, field emission and transmission electronic microscopies. Mesoporous titania has been templated into different shapes such as hollow particles and monoliths according to the amount of sol used to fill the voids of the close packed latex spheres. Titania topography strongly depends on the adsorption of polymeric segments over latex spheres surface, which could be decreased by changing the dimensions of latex spheres (phi = 9.5 mu m) generating a lamellar architecture. Thus, micrometric latex sphere arrays can be used to achieve new surface patterns for mesoporous materials via a fast and inexpensive chemical route for construction of functional devices in different technological fields such as energy conversion, inclusion chemistry and biomaterials. (C) 2011 Elsevier Inc. All rights reserved.

Analysis of Insect Cuticular Compounds by Non-lethal Solid Phase Micro Extraction with Styrene-Divinylbenzene Copolymers

Insect cuticular hydrocarbons including relatively non-volatile chemicals play important roles in cuticle protection and chemical communication. The conventional procedures for extracting cuticular compounds from insects require toxic solvents, or non-destructive techniques that do not allow storage of subsequent samples, such as the use of SPME fibers. In this study, we describe and tested a non-lethal process for extracting cuticular hydrocarbons with styrene-divinylbenzene copolymers, and illustrate the method with two species of bees and one species of beetle. The results demonstrate that these compounds can be efficiently trapped by ChromosorbA (R) (SUPELCO) and that this method can be used as an alternative to existing methods.