title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Signal enhancement techniques for chromatography detection systems. | The Environmental Protection Act has created a growing need for the measurement and assessment of trace emissions to the environment. This encompasses three main areas of ground, water and the atmosphere. The need to achieve lower emissions has placed a large burden on analytical techniques, particularly in the areas of trace analysis to ppb and ppt levels. Chromatographic techniques are widely used for assessment and measurement of emissions in all three areas. Enhanced detectors using mass spectrometry principles are available to lower detection limits, but these are expensive. Standard chromatography detectors can be used for trace analysis, but this often leads to extensive sample preparation stages to achieve low detection limits. This paper describes the techniques developed by Thomas Swan & Company to introduce a cost effective way of lowering detection limits. The approach taken meets both BATNEEC and BPEO constraints. | 18,924,800 |
Single standard calibration and data processing in flow injection titration based on concentration gradients. | This paper describes use of gradients of concentration generated in flow injection (FI) systems to perform determinations based on points where the concentration of titrant and analyte are at stoichiometric ratio. Two procedures were developed. In one procedure the titrant is injected in a FI manifold and merges with the sample which is continuously pumped towards the detector. In the other procedure the sample is injected and merged with the titrant which is continuously pumped. Both techniques make use of concentration gradients of the sample or titrant generated in FI manifolds that contain a mixing chamber. This gradient is calibrated employing only one standard solution (usually the titrant) in order to convert any detector signal, obtained in the elapsed time after injection, to instantaneous concentration values. The flow system is microcomputer controlled and data are treated to locate points where the concentration of titrant and analyte are at the stoichiometric ratio. These points are found in abrupt changes of the signal x concentration curves obtained in the presence of the reaction. The method has been evaluated for determination of Fe(II) and acetic acid by spectrophotometric and conductimetric detection, respectively. Results show a mean relative standard deviation lower than 1%, an average accuracy of 1% and a high sampling processing capability (40 to 60 samples per hour). | 18,924,802 |
Application of hand-held mobility spectrometers as sensors in manufacturing industries. | Ion mobility spectrometers (IMS) are small, lightweight, extremely robust devices with low power requirements, no moving parts, no absolute requirement for gases or vacuums, that can be operated at ambient temperatures and pressures, and yet are capable of measuring vapour phase concentrations of organic chemicals at very low levels (sub-mug/l). IMS are capable of analysing complex mixtures and producing a simple spectral output. Volatile components produce measurable negative and positive product ions in the spectrometer through chemical ionization. The spectra produced are essentially the vapour phase fingerprints of the target molecules/mixture. Quantitative data can be obtained provided instrument response is within the linear dynamic range of these instruments, but most practical applications of IMS have used the technology in a qualitative manner in situations which require just an above/below threshold or positive/ negative response.In the manufacturing industry there are many examples where the aroma/odour of raw materials has safety or product quality implications. IMS was not developed to replace traditional methods of analysis, e.g. GC/MS or sensory panels, but rather to provide a rapid, qualitative response complementary to more established methods. This paper reports on the use of a hand-held ion mobility spectrometer to characterize the vapours produced by volatile organic compounds,fresh herbs and retail spice mixtures at ambient temperature and pressure. The results show that by monitoring in both ion acquisition modes, ion mobility spectrometers are capable of discriminating between a wide range of products. | 18,924,815 |
Laboratory automation -some perspectives on the challenges in the implementation of the technology in pharmaceutical development. | The intensifying pressure on reducing the development time for new pharmaceutical products is resulting in an increasing need for laboratory automation. A key element for the successful implementation of robotics for drug product analysis is the establishment of a reliable process for interaction of the automation team with its various customers, for example development product team and manufacturing group. The reduction of cycle time for product development appears to be resulting in more stability studies to support NDA/MAA filings for several reasons. Key clinical information may not be available before initiation of the stability studies and simultaneous world-wide development may result in an increase in the number of product strength and pack options. | 18,924,828 |
The importance of the laboratory to the pharmaceutical business. | Understanding the contributions that the laboratory can make in product/process development, process improvement, market surveillance and general business is key to the pharmaceutical business today. Poor laboratory practice yields compliance issues, increased cost, increased cycle time and delayed product introductions. This paper covers key areas of customer satisfaction, the role of quality control and quality assurance laboratories, measures of account ability and progress, and an example of how laboratory robotics can help meet important goals. | 18,924,858 |
IFCC recommendation: The theory of reference values. Part 4. Control of analytical variation in the production, transfer and application of reference values. | This paper is the fourth in a series of Recommendations on the Theory of Reference Values. The others cover:Part 1. The Concept of Reference Values [1].Part 2. Selection of Individuals for the Production of Reference Values [2].Part 3. Preparation of Individuals and Collection of Specimens for the Production of Reference Values [3].Part 5. Statistical Treatment of Collected Reference Values. Determination of Reference Limits [4].Part 6. Presentation of Observed Values Related to Reference Values [5].A Guide to the Documents is currently in preparation.The Expert Panel of Theory of Reference Values (EPTRV) was created in 1970 by the Committee on Standards (at present: Scientific Division) of the International Federation of Clinical Chemistry (IFCC). Its task was to develop a nomenclature and recommend procedures for the production of reference values and their treatment, and presentation of observed values in relation to reference data.The first document in the above-mentioned series describes the subject of reference values and defines various terms. It would be best to read it for a thorough understanding of the present document. | 18,924,909 |
On-line analyte preconcentration with atomic spectrometric detection. | Pre-concentration of analytes, or matrix removal to overcome interferences using mini- or micro-columns of exchange media prior to atomic spectrometric detection is becoming increasingly more common. This paper is a review of some of the more recent applications of chelating, ion exchange and other resins and gels that have been used to accomplish this. | 18,924,915 |
Application of a computer-controlled flow analyser to the determination of glucose and to the study of beta -galactosidase activity. | Glucose was determined using an automated flow analyser and a commercial reagent preparation based on the glucose oxidaseperoxidase reaction. The coupling system for the hydrogen peroxide liberated consisted of 4-aminophenazone and 2,4-dichlorophenol. The analyser demonstrated linearity of>0.9997 for five consecutive sets of standards. The average RSD for individual standards is 0.76%, and a sample throughput rate of >80 h(-1) was achieved. The study of beta-galactosidase, using a novel substrate, was carried out in a simple single-line manifold. The enzyme-substrate reaction mixture was injected into a pH 10 buffer carrier to stop the reaction, and at the same time, propel the reaction zone to the flow cell. K(m) and V(max) values were calculated. | 18,924,935 |
Sequential automatic on-line determination of aquiculture nutrients: phosphate and nitrate. | A continuous-flow method for the determination of nitrate and phosphate in water is proposed. The method is based on insertion of reagents and sample solutions into a single channel through a programmable switching valve. The method depends upon heteropolyacid with phosphate and on the modified Griess reaction for nitrate, and permits the determination of PO(-3) (4) in the range 1-20 mug/ml and NO(-) (3) between 5 and 100 mug/ml, the achievable sampling frequency being 45/hour. The two analytes can be determined in N/P ratios between 0.25 and 100. The method has been applied to the determination of nitrate and phosphate in the sea-water used in fish farms. | 18,924,949 |
Analytical performance of the selective multianalyser Olympus AU 5200. | The analytical performance of a selective, automatic multianalyser- the Olympus A U5200 - was tested and assessed for practicability, following ECCLSguidelines. Twenty-two analytes were tested and compared with the Olympus A U5000 analyser. A Hitachi 747 analyser was also included in this survey in order to obtain correlation data for ISE measurements.The imprecision data, expressed as median CV values, were found to be below 2% in series for 21 parameters, and below 3% for 19 paramaters from day to day. Creatinine measured with the kinetic Jaffe method obtained a median CV value of 4% in series, creatine phosphokinase showed the worst imprecision from day to day with a CV of 9%. Slightly better precision values for the majority ofall tests were found on the Olympus AU5200 than on the AU 5000 analyser.The recovery of the assigned values in 32 commercial control sera was between 95% and 105% for 14 tests. Five of the remaining tests yielded recoveries with deviations between 5% and 10%, deviations above 10% showed albumine, alanine aminotransferase, aspartate aminotransferase and creatine phosphokinase. The accuracy of most test parameters was slightly better on the AU5200 analyser than on the comparison instrument.The range of linearity ofthe tested methods covered the range stated by the manufacturers; and no sample carry-over was detected. Most parameters tested yielded close correlation to those on the comparison instrument. Amylase measurements on both analysers correlate well but are not comparable without data correction due to different test methods. In addition, no drift effects were observed over a period of 9 hours.The ion-selective-electrode unit performed well in terms of throughput, precision and stability over time. The whole system showed good practicability with respect to patient sample and reagent handling, a short training period of technicians, ease of system software, maintenence, a robust barcode reader and a flexible host communication procedure. | 18,924,961 |
An automated method for the determination of deoxyribonuclease activity as exemplified by fractionation of the components of the medicament Varidase. | The activity of most deoxyribonuclease enzymes can be monitored by measuring the change in absorbance at 260 nm which accompanies the breakdown of the double-stranded structure of native DNA. An automated method for determining deoxyribonuclease activity, based on such an absorbance change, which can overcome problems of inhibition arising from the presence of inorganic cations, is described. Variations in inorganic cation concentration is a particular problem when measuring the activity of chromatographic fractions eluted via a salt gradient. A comparison is made between the automated and a manual method for the assay of deoxyribonuclease active constituents, of the medicament 'Varidase', eluted from a Cellex-D (Bio-Rad Laboratories Ltd) anionic exchange resin using a 0.05-1.0 M sodium chloride gradient. | 18,924,962 |
Automatic simultaneous determination of copper and lead in biological samples by flow injection/stripping voltammetric analysis. | An automatic-continuous method for the simultaneous determination of copper and lead based on flow injection analysis (FIA) and stripping voltammetry (SV) is proposed. The method affords the determination of the analytes at the ng/ml level (linear ranges 0.64 to 64.0 ng/ml and 2.1 to 62.2 ng/ml for copper and lead, respectively) with good precision (r.s.d. values smaller than 4%). The selectivity of SV allows the method to be applied to the determination of these analytes in bovine liver fresh samples and certified reference materials from the National Institute for Standards and Technology and the Community Bureau of Reference. The performance of the method was assessed by repeatability and validation statistical studies. | 18,924,966 |
Flow injection analysis of water. Part 1: Automatic preconcentration determination of sulphate, ammonia and iron(II)/iron(III). | This paper describes a simple flow-injection (FI) manifold for the determination of a variety of species in industrial water. The chemical systems involved in the determination of ammonia (formation of Indophenol Blue), sulfate (precipitation with Ba(II)), and iron (complexation with 1,10-phenanthroline with the help of a prior redox reaction for speciation) were selected so that a common manifold could be used for the sequential determination of batches of each analyte. A microcolumn of a suitable ion exchange material was used for on-line preconcentration of each analyte prior to injection; linear ranges for the determination of the analytes at the ng/ml levels were obtained with good reproducibility. The manifold and methods are ready for full automation. | 18,924,969 |
Use of a robotic station for full automation of the determination of organic matter in soil and fertilizers. | A fully automatic method for the determination of organic matter has been implemented using a robotic station. The overall process involves weighing, dilution, oxidation in very harsh working conditions (K(2)Cr(2)O(7) + concentrated H(2)SO(4)) dilution, centrifugation and photometric monitoring of the Cr(III) formed. Batches of six samples are manipulated by the robot, which also calibrates and delivers the results of the sample determination, both in soil and fertilizers, as percentages of organic matter which require slightly different sample treatment. The precision and validation of the method have been established using both types of samples and the results obtained compare well with those of the method used for routine analysis in official agricultural laboratories. | 18,924,989 |
Automation of a fixed-bed continuous-flow reactor. | This paper describes the design and operation of a laboratory plant with a fixed-bed continuous-flow reactor, fully automated and controlled from a personal computer. The automated variables include two gas flows, one liquid flow, six temperatures, two pressures, one circulation of a cooling liquid, and 10 electrovalves. An adaptive-predictive control system was used. The chemical process chosen to run the automated reactor was the conversion of methanol to gasoline over a ZSM-5 catalyst. This is a highly exothermal process, so a cascade control system had to be used to control the reactor internal temperature. Pressure and weight hourly space velocity (WHSV) were fixed at 1 arm and 1.5h(-1) respectively. Accurate control (+/-0.2( degrees )C) of the reactor's internal temperature was achieved and repeatability for the conversion of methanol to gasoline was good. | 18,924,990 |
Prejudice, segregation and immigration laws -integration of the robot into the laboratory society. | This paper addresses some serious issues about personnel morale, fears and hopes associated with and attributed to the laboratory robot. The introduction of the laboratory robot into the laboratory is examined from a managerial perspective. Human-rights and robot-rights issues are identified and addressed. Real world examples of how the integration of two high through-put robots affected the routine of a major industrial food laboratory are discussed. | 18,925,001 |
Introduction: Laboratory automation at Schering-Plough-increased productivity today and foundation for the future. | The following is the introductory presentation to the 1994 ISLAR meeting held in Boston from 16 to 19 October 1994. The Editor is again grateful to the organizer, the Zymark Corporation, for permission to publish the papers in the Managing Laboratory Automation Session read at ISLAR. | 18,925,010 |
Evaluation of the Coulter Counter S-Plus VI. | This article reports an evaluation of the Coulter Counter model S-Plus VI automatic analyser for haematology, and data are presented on linearity, carry-over, precision, accuracy and stability of the instrument, when compared with a model S-Plus IV/D.The three-part differential count provided by Coulter S-Plus VI has been compared with manual eye counting. The results show a good agreement with only 2.5% of discrepancies in 2271 routine samples.ADVANTAGES OF THE NEW INSTRUMENT INCLUDE: reduction of running costs, largely due to manpower saving; simple and easy use, and improved operator safety, there being no need for human contact with blood. | 18,925,186 |
Automation in urinalysis: evaluation of three urine test strip analysers. | A clinical laboratory evaluation was conducted on the Clinitek Auto 2000, the Super Aution Analyzer and the Urotron RL9 for the determination of glucose, protein, pH, blood, ketone-bodies and bilirubin.Precision of the systems was tested using three commercial control urine materials, and reported as the percentage of times the instrument repeats a certain value. Good repeatability was obtained with all the instruments.Accuracy of the systems was evaluated by comparison with quantitative procedures, and to check agreement between methods yielding semi-quantitative and quantitative results, ranges of acceptability were defined, based on the criteria reported in a previous paper [2]. It was then found that 87.5 to 98.9% of results from the Urotron RL9 and the Clinitek Auto 2000 were acceptable. With the Super Aution Analyzer the level of agreement was apparently lower because of the higher number of concentration steps used by this instrument. | 18,925,198 |
Adaptation of a cold vapour mercury analyser to flow injection analysis. | Minor modifications to a Coleman MAS-50A Mercury Analyser System allowed the determination of mercury by flow injection analysis. Using sample volumes of 600 mul it was possible to analyse up to 120 samples per hour, with a detection limit of 0.2 mug. l(-1) (120 pg) of mercury. The authors also report on a simple digestion procedure which replaces the time- and reagent-consuming EPA procedure, when the sample content permits. | 18,925,214 |
A novel approach to non-segmented flow analysis: Part 3. Nitrate, nitrite and ammonium in waters. | A high-performance continuous-flow analyser is used for the analysis of nitrate, nitrite and ammonium ion in potable waters. The results demonstrate that (1) the analyser allows the sequential determination of a number of analytes without requiring modification to the manifold; (2) the use of programmed slicing of the reaction mixture allows a wide range of analyte concentrations to be handled; and (3) that the sensitivity achieved compares favourably with the best available from conventional flow-injection analysis. The limits of detection were found to be 5 ppb for NH(4) (+), 30 ppb for NO(3) (-), and 4 ppb for NO(2) (-). | 18,925,215 |
Patterns in clinical chemistry requests. | For each patient sample that is presented to the clinical chemistry laboratory a combination of various tests can be requested. This combination or profile will depend on the condition of the patient, and hence also on the requesting hospital department. Several techniques were applied to detect and describe patterns in tests requested by the cardiology, hepatology and nephrology sections of the out-patient's Department for Internal Medicine. Comparison of the frequencies of ordering the tests showed significant differences between these sections. Cluster analysis and multidimensional scaling were used to show similarities and differences in the test profiles that were used by the sections. These techniques are useful for generating hypotheses, but the statistical significance of the clustering found is difficult to assess. | 18,925,235 |
Generation of selenium hydride from alkaline solutions: a new concept of the hydride generation-atomic absorption technique. | The use of hydride generation is often useful in environmental analysis. The normal acid sodium tetrahydroborate reaction provides exceptional sensitivity with continuous flow hydride generators. In some situations there are interferences which will mask the sensitivity. An alternative chemistry system is described here and is shown to offer similar sensitivity to that normally used. A commercial continuous flow analyser is used in this work. | 18,925,246 |
An evaluation of the Diamat HPLC analyser for simultaneous determination of haemoglobins A(2) and F. | The authors describe a modification of the instrumental parameters of the Diamat fully automated HPLC system for Hb A(2) assay (Bio-Rad Laboratories, Milan, Italy) in order to obtain simultaneous determination of Hb A(2) and Hb F.Hb A(2) and Hb F measurements are reproducible (within-run CV 2.6%, with Hb A(2)2.7%; 5.1%, with Hb F 1.3%) and accurate (from a comparison with two microchromatographic techniques for Hb A(2): r = 0.9639 and 0.9755; with two alkali denaturation procedures for Hb F: r = 0.9990 and 0.9952; with radial immunodiffusion, r = 0.9877). Assay linearity has been confirmed for Hb A(2) concentrations between 0 and 6.0%, and for Hb F between 0 and 60%. The data obtained from the analysis of some pathological samples for Hb Bart's, Hb H, Hb J Sardegna, Hb Lepore and Hb S are in agreement with cellulose acetate electrophoresis analysis.The Hb A(2) reference intervals for normals (N = 597) and Beta-thalassemia carriers (N = 200) are respectively (95% limits) 2.02-3.27 and 3.92-5.90 in % units. Hb F values measured in normals (N = 968), in beta-thal carriers (N = 302) and in deltabeta-thal carriers (N =3) have been found to be consistent with the usual diagnostic parameters.SOME MINOR LIMITATIONS EMERGED: the most relevant concerns Hb A(1c), which is overestimated with respect to a reference method (y = 1.217x + 0.16; N = 79; r = 0.9235). A probable interference from labile fractions is responsible for this Hb A(1c) inaccuracy. | 18,925,255 |
Automatic continuous on-line monitoring of salicylic acid and acetylsalicylic acid in pharmaceuticals. | An asymmetrical FIA merging-zones manifold based on the dual injection of two sample microvolumes was developed for the simultaneous determination of salicylic acid and acetylsalicylic acid in pharmaceutical preparations at a sampling frequency of 30/h. The complex formed between the Fe(III) reagent continuously introduced in the system and salicylic acid was monitored photometrically at 520 nm. One of the sample plugs was prehydrolysed on injection into an NaOH stream and was circulated through a longer channel than the other plug. This yielded two FIA peaks corresponding to salicylic acid and the overall content, respectively. The proposed manifold was successfully used to control the dissolution test of a pharmaceutical preparation. | 18,925,284 |
Social disadvantage, stress, and alcohol use among black, Hispanic, and white Americans: findings from the 2005 U.S. National Alcohol Survey. | Despite growing evidence of the adverse health effects of social disadvantage on minority populations, few studies have investigated whether such effects extend to alcohol problems. This study examines social disadvantage as a source of stress and analyzes its association with alcohol use and problems in the three largest racial/ethnic groups in the United States. Data on white, black, and Hispanic Americans (n = 6,631) were obtained from the 2005 U.S. National Alcohol Survey, a nationally representative telephone-based survey of adults ages 18 and older. Social disadvantage was measured by poverty level, frequency of unfair treatment, racial/ethnic stigma consciousness, and cumulative disadvantage. Outcomes included drinking status, at-risk drinking, and problem drinking. Blacks and Hispanics reported greater exposure to social disadvantage than whites, including greater poverty, unfair treatment, racial/ethnic stigma, and cumulative disadvantage. In all three racial/ethnic groups, exposure to disadvantage was associated with problem drinking. Frequent unfair treatment, high racial stigma (among minorities), and multiple sources of extreme disadvantage corresponded to a twofold to sixfold greater risk of alcohol problems, partially explained by psychological distress. These results are consistent with other studies of stress and adverse health consequences associated with social disadvantage. Although there is a clear disparity in exposure to such hardship, experiences of disadvantage appear to have similar effects on problem drinking among both racial/ethnic minorities and whites. Future research should attempt to assess causal directions in the relationships among social and economic hardship, stress, and alcohol problems. | 18,925,340 |
Do patients with alcohol dependence respond to placebo? Results from the COMBINE Study. | The purpose of this study was to examine the nature of the effect of placebo medication plus accompanying medical management in the treatment of alcohol dependence. The National Institute on Alcohol Abuse and Alcoholism COMBINE (Combining Medications and Behavioral Interventions) study, a randomized controlled double-blind trial of 1,383 alcohol-dependent patients, compared combinations of medications (acamprosate [Campral] and naltrexone [ReVia]) and behavioral therapy (medical management and specialist-delivered behavioral therapy) for alcohol dependence. This report focuses on a subset of that study population (n = 466) receiving (1) specialized behavioral therapy alone (without pills), (2) specialized behavioral therapy + placebo medication + medical management, or (3) placebo + medical management. During 16 weeks of treatment, participants receiving behavioral therapy alone had a lower percentage of days abstinent (66.6%) than did the participants receiving placebo and medical management (73.1%) or those receiving specialized behavioral therapy + placebo + medical management (79.4%). The group receiving behavioral therapy alone relapsed to heavy drinking more often (79.0%) than those receiving behavioral therapy + placebo + medical management (71.2%). This report focuses on potential explanations for this finding. The two groups of participants receiving placebo + medical management were more likely to attend Alcoholics Anonymous meetings during treatment (32.7% and 32.0% vs 20.4%) and were less likely to withdraw from treatment (14.1% and 22.9% vs 29.3%). There appeared to be a significant "placebo effect" in the COMBINE Study, consisting of pill taking and seeing a health care professional. Contributing factors to the placebo response may have included pill taking itself, the benefits of meeting with a medical professional, repeated advice to attend Alcoholics Anonymous, and optimism about a medication effect. | 18,925,346 |
The therapeutic modulation of atherogenic dyslipidemia and inflammatory markers in the metabolic syndrome: what is the clinical relevance? | The metabolic syndrome consists of a constellation of clinical and biochemical risk factors that cluster together and heighten the risk for atherogenesis, cardiovascular diseases, and diabetes. Established risk cardiovascular factors like hypertension, atherogenic dyslipidaemia, and glucose intolerance occur in the setting of insulin resistance and central adiposity, with genetic and environmental influences modulating the ultimate risk. Chronic insults to the endothelium take its toll in the form of silent as well as clinically evident cardiovascular events. The cellular and vascular accompaniments have shed some light into the underlying pathophysiology. Heightened, low-grade inflammatory processes as well as a continuum of vascular insults ranging from early endothelial derangements to advanced atherosclerosis have been examined. In recent years there has been an explosion of basic and clinical knowledge related to the metabolic syndrome. Although dyslipidaemia is considered a traditional risk component for the syndrome, its qualitative aspects, genetically determined subfractions, and variation in proatherogenic tendency have generated renewed interest and debate. New targets within the dyslipidaemic spectrum that have differing clinical relevance are being evaluated. The effect of heredity, lifestyle changes, pharmacotherapeutic agents, and supplements is being investigated. Further research into the impact of dyslipidemia and inflammation as both pathophysiologic risk factors and objects for targeted therapy in the metabolic syndrome should deepen our understanding and unravel answers to the underlying dynamics in this global epidemic. | 18,925,358 |
Phylogenetic, structural and functional relationships between WD- and Kelch-repeat proteins. | The beta-propeller domain is a widespread protein organizational motif. Typically, beta-propeller proteins are encoded by repeated sequences where each repeat unit corresponds to a twisted beta-sheet structural motif; these beta-sheets are arranged in a circle around a central axis to generate the beta-propeller structure. Two superfamilies of beta-propeller proteins, the WD-repeat and Kelch-repeat families, exhibit similarities not only in structure, but, remarkably, also in the types of molecular functions they perform. While it is unlikely that WD and Kelch repeats evolved from a common ancestor, their evolution into diverse families of similar function may reflect the evolutionary advantages of the stable core beta-propeller fold. In this chapter, we examine the relationships between these two widespread protein families, emphasizing recently published work relating to the structure and function of both Kelch and WD-repeat proteins. | 18,925,367 |
Predictive CT findings of malignancy in ground-glass nodules on thin-section chest CT: the effects on radiologist performance. | Our purpose was to identify thin-section chest computed tomography (CT) findings of malignancy other than the presence of a solid portion within ground-glass nodules (GGNs) and to evaluate whether the radiologists' performance in determining malignancy can be enhanced with this information. The predictive CT findings of malignancy extracted from the CT findings of 80 GGNs (47 malignant, 33 benign) were a size of >8 mm [odds ratio (OR), 10.930; P = 0.045] and a lobulated border (OR, 13.769; P = 0.016) for pure GGNs and a lobulated border (OR, 10.200; P = 0.024) for mixed GGNs. Four chest radiologists and five radiology residents participated in the observer performance study with CT of 130 GGNs (67 malignant, 63 benign). Receiver-operating characteristic (ROC) analysis was used to compare radiologists' performances before and after providing these predictive findings. For pure GGNs, mean areas under the curve (A(z)) of all readers without and with CT predictive information were significantly different (0.621 +/- 0.052 and 0.766 +/- 0.055, P < 0.05). For mixed GGNs, the A(z) values achieved without and with predictive information were not significantly different (0.727 +/- 0.064 and 0.764 +/- 0.056, P > 0.05). Information about lesion size and morphological characteristics can enhance radiologists' performance in determining malignancy of pure GGNs. | 18,925,404 |
Marfan syndrome: clinical consequences resulting from a medicolegal autopsy of a case of sudden death due to aortic rupture. | To investigate the sudden death of a 31-year-old man, a medicolegal autopsy was performed. Major findings were a dilated aortic root with a longitudinal rupture of the intima and dissection of aorta and right coronary artery and consequent tamponade of the pericardial sac. Moreover, arachnodactyly and other skeletal deformities in combination with the histological finding of a pseudocystic medionecrosis of the aortic wall were noted. By sequencing of the FBN1 gene, a mutation (1622G>A) leading to the diagnosis of Marfan syndrome was found. Genetic counseling was recommended to the relatives who reported that the father of the deceased had died at the same age from aortic rupture. While fortunately the child of the deceased lacked this mutation, it was found in his younger sister. The results of the autopsy thus enabled early diagnosis and beginning of treatment in the sister and thus a considerable statistical increase in lifespan. With this report, we want to show that medicolegal autopsies can also have medical consequences for relatives. We argue that in all sudden and unexpected deaths in young persons up to 35 years an autopsy should be performed, not only to detect unnatural causes of death but also to identify heritable diseases and thus aid the relatives. | 18,925,407 |
Identification and characterization of a serine protease inhibitor of Paragonimus westermani. | Paragonimus westermani is a trematode parasite that causes pulmonary and/or extrapulmonary granulomatous disease in humans. In this study, we identified a full-length gene encoding a novel serine protease inhibitor of P. westermani (PwSERPIN) and characterized the biochemical properties of the recombinant protein. PwSERPIN had an open reading frame of 1,164 bp, which encoded 387 amino acid residues. Sequence analysis of the primary structure of PwSERPIN revealed that it had the essential structural motifs which were well conserved among the serine protease inhibitor (serpin) superfamily and had shown 16.5-29.6% sequence identities with previously reported serpins from other helminthic parasites. No signal peptide or N-glycosylation site was found in the sequence. Genomic DNA structure analysis showed that PwSERPIN comprised six exons separated by five introns. The bacterially expressed recombinant PwSERPIN effectively inhibited the activities of trypsin, thrombin, and chymotrypsin in a dose-dependent manner, but showed lower inhibitory capacity on cathepsin G and elastases. Expression of PwSERPIN was detected throughout various developmental stages of the parasite, from metacercariae to adult worms, and the transcription level gradually increased with the maturation of the parasite. PwSERPIN was identified in the soluble extract of the parasite, but not in the excretory and secretory products (ESP) and in the insoluble extract of the parasite. These results collectively suggest that the PwSERPIN is an intracellular serpin of P. westermani and that might play primary roles in regulating the activities of intracellular serine proteases of the parasite. | 18,925,417 |
Comparing patients' and clinicians' assessment of outcomes in a randomised trial of sentinel node biopsy for breast cancer (the RACS SNAC trial). | The RACS sentinel node biopsy versus axillary clearance (SNAC) trial compared sentinel-node-based management (SNBM) and axillary lymph-node dissection (ALND) for breast cancer. In this sub study, we sought to determine whether patient ratings of arm swelling, symptoms, function and disability or clinicians' measurements were most efficient at detecting differences between randomized groups, and therefore, which of these outcome measures would minimise the required sample sizes in future clinical trials. 324 women randomised to SNBM and 319 randomised to ALND were included. The primary endpoint of the trial was percentage increase in arm volume calculated from clinicians' measurements of arm circumference at 10 cm intervals. Secondary endpoints included reductions in range of motion and sensation (both measured by clinicians); and, patients' ratings of arm swelling, symptoms and quality of life, using the European Organisation for Research and Treatment of Cancer Breast Cancer Module (EORTC QLM-BR23), the body image after breast cancer questionnaire (BIBC) and the SNAC study specific scales (SSSS). The relative efficiency (RE, the squared ratio of the test statistics, with 95% confidence intervals calculated by bootstrapping) was used to compare these measures in detecting differences between the treatment groups. Patients' self-ratings of arm swelling were generally more efficient than clinicians' measurements of arm volume in detecting differences between treatment groups. The SSSS arm symptoms scale was the most efficient (RE = 7.1) The entire SSSS was slightly less so (RE = 4.6). Patients' ratings on single items were 3-5 times more efficient than clinicians' measurements. Primary endpoints based on patient-rated outcome measures could reduce the required sample size in future surgical trials. | 18,925,434 |
Sister Mary Joseph's nodule as the sole presenting feature of disseminated squamous cell cancer of the esophagus: a rare case. | Umbilical nodule due to tumor metastasis is a rare presentation which is known as Sister Joseph's nodule. This is usually due to disseminated intra abdominal malignancies which are mostly adenocarcinomas. Esophageal squamous cell cancer commonly presents with progressive dysphagia, and it usually metastasizes to liver, lungs, bones, and regional lymph nodes; however, spreading to the umbilicus is an extremely rare occurrence. In this paper, we report a 77-year-old man presenting with a painful umbilical nodule as the only presenting feature of disseminated, poorly differentiated squamous cell carcinoma of the esophagus. | 18,925,437 |
Size and morphology of toxic oligomers of amyloidogenic proteins: a case study of human stefin B. | Amyloid-induced toxicity is a well-known phenomenon but the molecular background remains unclear. One hypothesis relates toxicity to amyloid-membrane interactions, predicting that amyloid oligomers make pores into membranes. Therefore, the toxicity and membrane interaction of prefibrillar aggregates and individual oligomers of a non-pathological yet highly amyloidogenic protein human stefin B (cystatin B) was examined. By monitoring caspase-3 activity and by testing cell viability, we showed that the lag phase aggregates obtained at pH 5 and 3 were toxic to neuroblastoma cells. Of equal toxicity were the higher-order oligomers prepared at pH 7 by freeze-thaw cycles. The higher-order oligomers eluted on size-exclusion chromatography (SEC) as a broad peak comprising hexamers, octamers, 12- and 16-mers, well separated from monomers, dimers and tetramers. Only oligomers higher than the tetramers (Rh >3.5 nm) proved toxic, in contrast to dimers and tetramers. In accordance with data from SEC, dynamic light scattering and atomic force microscopy data indicate that the toxic oligomers have diameters larger than 4 nm. Critical pressure measurements showed that the toxic higher-order oligomers inserted more effectively into model lipid monolayers than dimers and tetramers. They also bound, similarly to prefibrillar aggregates, to the plasma membrane and became internalized. Taken together, our results confirm the importance of membrane interaction and perforation in the phenomenon of cytotoxicity. | 18,925,453 |
Changes in quality attributes of intermediate-moisture raisins during storage. | The aim of this research was to determine the changes in chemical and microbiological qualities of ready-to-eat intermediate-moisture raisins during storage. Raisins were immersed into hot (98+/-1 degrees C) glucose solutions (10% w/v and 20% w/v) containing 1% (w/v) potassium sorbate to inhibit mould and yeast growth. Raisins were kept in glucose solutions until the moisture content became 20%, 25% and 30%, respectively. The reconstituted raisins were then stored at ambient temperature (23+/-3 degrees C) and 50-60% relative humidity for 8 months in polyethylene/polyamide (PE/PA) packaging material. The changes of moisture content, water activity, pH values, total titratable acidity, total sugar contents, Hunter L, a and b color values, total mesophylic aerobic bacteria counts, and mould and yeast counts were determined during storage at 2-month intervals. The results of chemical analysis showed that changes in the total titratable acidity, total mesophylic aerobic bacteria, and mould and yeast counts of the products were increased significantly (P<0.05). However, the pH values, total sugar contents, and Hunter L, a, and b color values were decreased during the storage period (P<0.05). | 18,925,480 |
A Rorschach journey with Bruno Klopfer: clinical application and teaching. | This article is a draft of a speech given as the recipient of the 2008 Bruno Klopfer Memorial award. I review some important details of the life of Bruno Klopfer, his contributions to the scoring and interpretation of the Rorschach (Exner, 2003), and his emphasis on the use of phenomenology in the process. I then focused on Klopfer's flexible scoring method and his use of Testing of the Limits techniques on the Rorschach, emphasizing their application to therapeutic and collaborative assessment. I illustrate my own application of Testing of the Limits using case vignettes. Finally, I present selected parts of two 1959 radio interviews of Bruno Klopfer. | 18,925,493 |
Behavioral correlates of selected MMPI-2 clinical, content, and restructured clinical scales. | In this study, we evaluated the validity of the Restructured Clinical (RC; Tellegen et al., 2003) scales by identifying and comparing behavioral correlates of selected RC scales (RCd, RC2, RC4), their original Clinical scale counterparts (Scale 2, Scale 4), and conceptually related Content scales (DEP, ASP, CYN) in an outpatient clinical sample (N = 150). The results of this study indicate that RC4 is a stronger predictor of several antisocial behaviors than Clinical Scale 4 or the Content Scales ASP and CYN. In contrast, RC2 demonstrated significantly lower correlations with several behaviors conceptually related to depression than its Clinical scale counterpart or DEP. DEP was highly correlated with RCd (r = .91, p < .0001), suggesting that the 2 scales may be measuring similar constructs. Overall, the results of this study demonstrate relatively few differences among the scales selected in their ability to predict extratest behaviors. | 18,925,503 |
Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation. | Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P < 0.05). Using one way ANOVA, high PCOs levels were found in DSS in comparison to DF and DHF cases on all the three days tested (P < 0.001). TAS levels were found to be low among DSS on days 5 and 7 and day 7 in DHF when compared with DF cases. Correlation analysis between MDA and hematocrit revealed a significant positive association between them in DHF and DSS on day 5 (DHF r = 0.372; p = 0.024 and DSS r = 0.535; p = 0.0-01) and day 7 (DHF r = 0.412; p = 0.003 and DSS r = 0.765; p < 0.0001). There was an important negative correlation between platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p < 0.001 and DSS r = -0.581; p < 0.001) and day 7 (DHF r = -0.418; p = 0.001 and DSS r = -0.515; p = 0.002)]. This study concludes that an increase in oxidative stress was found in dengue viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection. | 18,925,513 |
Effect of fluid therapy on prevention of acute renal failure in Bam earthquake crush victims. | At 5:28 a.m. (local time) on December 26, 2003, an earthquake measuring 6.51 on the Richter scale struck the city of Bam in the Kerman Province in southeastern Iran. Among the most important morbid events in survivors were acute renal problems. Clinical findings, laboratory data, and management of the renal victims, all of whom were transferred to Shiraz Hospitals, have been the subject of this analysis. Medical records of twenty patients with acute renal failure admitted to three university hospitals and one community hospital were reviewed. Overall, 801 patients were transferred to Shiraz hospitals, of whom 20 (mean age 36.2 +/- 14.8 years, 15 males) developed acute renal failure with mean duration of 14.5 +/- 9.6 days. Total mortality was 21 (2.6%) and acute renal failure mortality was 3 (15%). Seven patients received standard fluid therapy and 13 patients received variable volume treatment. In total, 79 dialysis sessions were performed in 15 patients (mean 5.2, 3.3 +/- 1 sessions per patients). There was a positive correlation between time spent under rubble and peak serum CK (creatine phosphokinase) level (p = 0.035), acute renal failure duration (p = 0.047), and admission potassium levels (p = 0.033). Serum CK level was positively correlated with acute renal failure duration (p = 0.008). Patients who had received standard treatment had significantly shorter duration of acute renal failure (7.1 versus 9.4 days, p = 0.008) and less need for dialysis (1 versus 6, p = 0.007) than patients who were treated variably. In victims of earthquake, time spent under rubble and peak serum CK level can serve to estimate morbidity, and early standard treatment may decrease renal morbidity. | 18,925,519 |
Chemiluminescent analysis of plasma antioxidant capacity in uremic patients undergoing hemodialysis. | Hemodialysis is a common therapeutic strategy for patients with end stage renal failure. During the hemodialytic process, the neutrophils are activated (neutrophil burst) due to the hemoincompatibility induced by hemodialysis. As a result, the activated neutrophils release reactive oxygen species (ROS), such as hydrogen peroxide, singlet oxygen, and hypochlorite, into the bloodstream and cause oxidative damage. This study investigated the antioxidant alteration of plasma in uremic patients undergoing hemodialysis by chemiluminescent analysis. The antioxidant capacities of plasma in scavenging hydrogen peroxide, singlet oxygen, and hypochlorite were investigated in this experiment. In addition, investigation of the ferric-reducing ability of plasma (FRAP) would be covered in this study as well. This study found that after hemodialysis, the antioxidant capacities of plasma in scavenging hydrogen peroxide, singlet oxygen, and hypochlorite decreases 7.9%, 18.8%, and 18.9%, respectively. Moreover, the FRAP is reduced by 56%. We speculate that the loss of dialyzable solutes (such as uremic solutes and antioxidants with small molecular weight) in plasma resulted in its decrease in antioxidant capacity. We therefore suggest that the supplement of antioxidants with small molecular weight is capable of regaining antioxidant defense in plasma and preventing oxidative damage induced by hemodialysis. | 18,925,521 |
AST-120 treatment in pre-dialysis period affects the prognosis in patients on hemodialysis. | An oral adsorbent, AST-120, has been shown to retard the deterioration of renal function in patients with chronic kidney disease (CKD) by decreasing serum nephrotoxic substances such as indoxyl sulfate. Recent studies have suggested that a high level of serum indoxyl sulfate may be one of the mechanisms underlying the progression of atherosclerotic lesion, which is the leading cause of cardiovascular event or death in dialysis patients. In this study, we examined retrospectively whether AST-120 given to patients in the pre-dialysis period influences the prognosis after the initiation of dialysis. One hundred and ninety-two CKD patients on dialysis were studied. The survival and causes of death after the initiation of dialysis were compared between patients who were administrated AST-120 (AST-120 group, n = 101) and those not administrated AST-120 (non-AST-120 group, n = 91) prior to the initiation of dialysis. The five-year survival rate was 72.6% in the AST-120 group and 52.6% in the non-AST-120 group, and was significantly higher in the AST-120 group (p = 0.018). The risk of death was increased 1.91-fold in the non-AST-120 group. However, no difference in the causes of death was observed between two groups. This study suggests that AST-120 given prior to the initiation of dialysis improves the prognosis of CKD patients under dialysis, although there is no association between AST-120 treatment and death caused by cardiovascular diseases such as heart failure, myocardial infarction, and cerebral hemorrhage. Further studies are needed to elucidate the effect of AST-120 on cardiovascular events and the prognosis in dialysis patients. | 18,925,523 |
Diagnostic value of the aminopeptidase N, N-acetyl-beta-D-glucosaminidase and dipeptidylpeptidase IV in evaluating tubular dysfunction in patients with glomerulopathies. | The aim of the present study was to investigate the value of the urine cell glycoprotein 1 (PC-1), aminopeptidase N (APN), N-acetyl-beta-D-glucosaminidase (NAGA), and dipeptidylpeptidase IV (DPP IV) in the evaluation of tubular damage in patients with primary glomerulonephritis, diabetic nephropathy, and lupus nephritis. PC-1, APN, NAGA, and DPP IV activities were determined in serum, urine, and lymphocytes of 178 subjects, including 10 patients with membranous nephropathy, 38 with IgA nephropathy, 29 with lupus nephritis, 51 with diabetic nephropathy, and 50 control subjects. Urinary PC-1 excretion in IgA nephropathy group was significantly higher (p < 0.05) than in controls. Urinary NAGA excretion was markedly (p < 0.01) higher in membranous nephropathy group, and APN excretion in diabetic nephropathy group was significantly higher (p < 0.01) than in healthy controls. Urinary APN activity was significantly (p < 0.01) higher in both type 1 and type 2 diabetic patients with microalbuminuria, as well as urinary NAGA and DPP IV activities in type 2 diabetics with microalbuminuria (p < 0.01 and p < 0.05, respectively) compared to controls. Serum PC-1 and APN activities were significantly higher than the control level in membranous nephropathy group, as well as serum PC-1 and DPP IV activities in IgA nephropathy patients (p < 0.05). However, significantly lower serum DPP IV and APN activity was observed in type 2 diabetics with microalbuminuria compared to controls (p < 0.05). Damage of tubules in primary glomerulonephritis, lupus nephritis, and diabetic nephropathy is accompanied by a release of several tubular enzymes, with possible diagnostic and prognostic significance. Increased serum PC-1, APN, and DPP IV activities could be also of diagnostic significance. | 18,925,530 |
Nebivolol reduces experimentally induced warm renal ischemia reperfusion injury in rats. | Ischemia/reperfusion injury, which is commonly seen in the field of renal surgery or transplantation, is a major cause of acute renal failure. The objective of the present study was to examine the role of nebivolol in modulating peroxynitrite species-induced inflammation and apoptosis after renal warm ischemia/reperfusion injury in rats. The present study was designed to investigate the effects of nebivolol on the renal warm ischemia/reperfusion injury in rats treated with the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester. After right nephrectomy, nebivolol was administered for 15 days. On the 16(th) day, ischemia was induced in contra lateral kidney for 45 min, followed by reperfusion for 24 hr. Renal function, inflammation, and apoptosis were estimated at the end of 24 hr reperfusion. Nebivolol improved the renal dysfunction and reduced inflammation and apoptosis after renal ischemia/reperfusion injury. In conclusion, nebivolol shows potent anti-apoptotic and anti-inflammatory properties due to its NO-releasing property. These findings may have major implications in the treatment of human ischemic acute renal failure. | 18,925,533 |
Paraneoplastic polymyositis associated with crescentic glomerulonephritis. | A female concurrently developed polymyositis (PM), lung cancer, and nephrotic range proteinuria. Renal biopsy revealed crescentic glomerulonephritis. Pathology of lung cancer was proved to be adenocarcinoma. After surgical treatment of lung cancer, the symptoms of PM-associated crescentic glomerulonephritis disappeared. PM is associated with a higher risk of malignancy, though renal involvement in patients with PM is thought to be uncommon. In patients with PM, there have been few reports concerning the coexistence of glomerular disease, including crescent glomerulonephritis. Herein we report a case of crescentic glomerulonephritis-associated PM that was successfully treated after the surgical removal of lung cancer. We consider that such association of PM and crescent glomerulonephritis is rare in adults. Careful evaluation of underlying malignancy is important. The definite treatment is adequate management of underlying malignancy. | 18,925,535 |
A case of latissimus dorsi pedicle arising from the lateral thoracic vessels. | The thoracodorsal system represents a versatile, yet reliable system for the harvest of tissues for microsurgical transplantation. Also, the donor vessel anatomy is generally thought to be highly predictable in terms of topography and branching patterns. In this article we describe for the first time the occurrence of a branching pattern during a clinical harvest of the latissimus dorsi muscle flap, previously encountered only in cadaver dissections. We compare our intraoperative findings with published anatomical investigations and discuss the implications of this particular variation of the blood supply to the latissimus dorsi muscle for clinical practice. | 18,925,544 |
The utility of detailed first trimester ultrasound examination in abnormal fetal nuchal translucency. | To determine the value of a first trimester fetal ultrasound examination in cases of an increased nuchal translucency (NT). A detailed fetal ultrasound examination was performed within 4 days of a detection of a first trimester increased NT. As many as 23 fetuses were evaluated. Severe anomalies were detected in eight and mild anomalies were detected in six fetuses. Two fetuses had trisomy 13, one had trisomy 21, and 16 fetuses had a normal karyotype. A chromosomal analysis was not available in four fetuses with major anomalies due to parental decision. In one fetus, craniosynostosis was detected only at 24 weeks' gestation. The current study shows that a first trimester targeted scan of fetuses with an increased NT in an experienced center can shorten the parental decision-making process and spare parents a prolonged period of diagnostic uncertainty and anxiety, particularly when a structural anomaly is clearly diagnosed in the first trimester. | 18,925,580 |
Quantification of heterocyclic amines from thermally processed meats selected from a small-scale population-based study. | Heterocyclic amines (HAs) are potent mutagens that form at high temperatures in cooked, protein-rich food. Due to their frequent intake, these compounds are considered a risk factor for human cancer. Cooking conditions and eating habits strongly influence the level of HA exposure. Thus, it is difficult to assess the intake of HAs in a large population. Food-frequency questionnaires (FFQs), designed to provide data on parameters that affect HA formation, were used to survey a small population (459 persons) from Barcelona (NE Spain). Subsequently, the most-consumed food items named were cooked according to the preferences of the population surveyed and analyzed for HAs using SPE and LC-MS/MS. In the population studied, the estimated intake via consumption of 13 meat dishes was 285.6 ng of mutagenic HAs per capita and day. PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was the HA to which the population was most exposed, mainly from fried chicken and griddled beef. When the co-mutagens norharman and harman are included, the mean daily intake of HAs rises to 475.6 ng per capita and day. A novel putative DMIP regioisomer was detected in the cooked meats, which was analyzed in the present study by multistage MS. | 18,925,613 |
Empirical test of bullies' status goals: assessing direct goals, aggression, and prestige. | The literature suggests that status goals are one of the driving motivations behind bullying behavior, yet this conjecture has rarely if ever been examined empirically. This study assessed status goals in three ways, using dyadic network analysis to analyze the relations and goals among 10-11 and 14-15 year olds in 22 school classes (N boys=225; N girls=277). As a validation bullies were contrasted with victims. Bullies had direct status goals (measured with the Interpersonal Goal Inventory for Children) and showed dominance as measured with proactive aggression. Moreover, as predicted from a goal perspective, bullying behavior was related to prestige in terms of perceived popularity. In contrast, victims lacked status goals, were only reactively aggressive, and low on prestige. That being popular is not the same as being liked could be shown by the fact that bullies were just as rejected as victims by their classmates. Eighth-grade bullies had more direct status goals than fourth-grade bullies, possibly indicating that striving for the popularity component of status increases in early adolescence. | 18,925,635 |
Relationship between vascular endothelial growth factor and nuclear factor-kappaB in renal cell tumors. | To assess the relationship between protein and messenger RNA (mRNA) levels of vascular endothelial growth factor (VEGF) and subcellular localization of nuclear factor-kappa B (NF-kappaB), proliferation rate of tumor cells, and clinicopathological characteristics of renal cell tumors. We analyzed 31 one renal cell tumors - 22 clear cell renal cell carcinomas (CCRCC) and 9 other histologic types (non-CCRCC). VEGF expression and subcellular localization of p65 member of NF-kappaB and Ki67 were immunohistochemically evaluated for the proliferation rate of tumor cells. Expression of VEGF mRNA was assessed using quantitative real-time polymerase chain reaction after total RNA extraction from snap-frozen tumor tissue samples. Cytoplasmic localization of VEGF protein in renal cell tumors showed a perimembranous and diffuse pattern, the former being more evident in CCRCC (27.1 -/+ 18.9 vs 3.3 -/+ 10 % tumors, P<0.001) and the latter in non-CCRCC type (71.7 -/+ 23.2 vs 31.1 -/+ 22.1 % tumors, P<0.001). Heterogeneity in VEGF gene expression was more pronounced in CCRCC type than in non-CCRCC type (P=0.004). In addition, perimembranous VEGF pattern was associated with higher VEGF mRNA levels (P=0.006) and diffuse VEGF pattern with lower VEGF mRNA levels (P<0.001). Nuclear and cytoplasmic staining of NF-kappaB/p65 was observed in the majority of tumor cells. A significant association was recorded between cytoplasmic NK-kappaB/65 staining and VEGF staining of diffuse pattern (P=0.026). Association between NF-kappaB/65 and proliferation rate of tumor cells was significant for cytoplasmic staining (P=0.039) but not for nuclear NFkB/p65 staining (P=0.099). Higher but inhomogeneous expression of VEGF in tumor cells, especially in CCRCCs, is associated with NF-kappaB/65 activity. This indicates that both VEGF and NF-kappaB/65 may be important in renal carcinogenesis, representing a possible molecular target in the treatment of renal cell carcinoma. | 18,925,694 |
[Cortical neuron apoptosis induced by beta-amyloid peptide and protective effect of panoxadiol in mice]. | To investigate the apoptosis of cortical neurons induced by beta-amyloid peptide (Abeta(1-40)) and the protective effect of panoxadiol. The Abeta(1-40) induced damage of primarily cultured mouse cortical neurons was examined with morphological observation, MTT assay, DNA agarose gel electrophoresis and Western-blot. After 48 h treated with 12 mumol/L Abeta(1-40), the cortical neurons showed apoptotic characteristics: including decreased OD570 value in MTT assay, DNA cleavage fragment in electrophoresis and increased apoptotic cells. Western-blot showed that the expression of bcl-2 reduced significantly (P<0.05). Cell apoptosis was significantly attenuated in 40 mg/L panoxadiol treated group. Panoxadiol can protect cultured cortical neurons from apoptosis induced by Abeta(1-40) in mice. | 18,925,710 |
[5-Lipoxygenase/cysteinyl leukotriene pathway is not involved in injury of rat C6 glioma cells induced by oxygen-glucose deprivation]. | To determine whether oxygen-glucose deprivation (OGD) induces C6 cell injury, and whether 5-lipoxygenase (5-LOX)/cysteinyl leukotriene (CysLT) pathway is involved in OGD-induced injury. After OGD treatment and recovery for various durations, the viability of C6 cells was determined, and the effects of 5-LOX inhibitors and CysLT receptor antagonists were investigated. Intracellular distribution of 5-LOX protein was detected by immunocytochemistry, and the mRNA expressions of CysLT1 and CysLT2 receptors were detected by RT-PCR. The effect of leukotriene D(4) (LTD(4)) on C6 cells was also investigated. OGD for 4-8 h followed by recovery for 24-72 h significantly induced C6 cell injury. Neither 5-LOX inhibitors nor CysLT receptor antagonists inhibited OGD-induced injury. OGD did not induce 5-LOX translocation into the nuclear membrane. C6 cells highly expressed CysLT(2) receptor, but the expression of CysLT1receptor was much weaker; the expression was not affected by OGD. In addition, LTD(4) did not affect C6 cells significantly. OGD can induce C6 cell injury, but 5-LOX/CysLT pathway might be not involved in OGD-induced injury. | 18,925,711 |
Role of the geometry, restricted rotations and solvents on the computed 2,2'-diphenyl-1-picrylhydrazyl hyperfine tensors. | The nuclear hyperfine tensor (A) components of the 2,2'-diphenyl-1-picrylhydrazyl neutral radical are computed using the UB1LYP hybrid density functional method. Solvent interactions via hydrogen bonding are found to play a crucial role in the position of the two phenyl rings relative to the picryl moiety. Under these conditions, the calculated isotropic hyperfine tensor components of the N 1 and N 2 hydrazyl backbone are within approximately 1.3 Gauss (G) of the experimental values determined by EPR and ENDOR spectroscopy. Just as important are the effects of restricted rotations of the phenyl rings on these tensors. Rotational averaging using a Maxwell-Boltzmann type distribution improves the agreement between theory and experiment to less than 1.0 G. In addition, rotational averaging of the twelve isotropic proton coupling constants has also been performed. They come within 0.3 G of the experimental values. Thus, for the first time, all the nuclear hyperfine tensor components of this large class of molecules are accurately calculated without resorting to post Hartree-Fock techniques. | 18,925,726 |
Thermodynamics of heterogeneous crystal nucleation in contact and immersion modes. | One of the most intriguing problems of heterogeneous crystal nucleation in droplets is its strong enhancement in the contact mode (when the foreign particle is presumably in some kind of contact with the droplet surface) compared to the immersion mode (particle immersed in the droplet). Heterogeneous centers can have different nucleation thresholds when they act in contact or immersion modes. The underlying physical reasons for this enhancement have remained largely unclear. In this paper we present a model for the thermodynamic enhancement of heterogeneous crystal nucleation in the contact mode compared to the immersion one. To determine if and how the surface of a liquid droplet can thermodynamically stimulate its heterogeneous crystallization, we examine crystal nucleation in the immersion and contact modes by deriving and comparing with each other the reversible works of formation of crystal nuclei in these cases. The line tension of a three-phase contact gives rise to additional terms in the formation free energy of a crystal cluster and affects its Wulff (equilibrium) shape. As an illustration, the proposed model is applied to the heterogeneous nucleation of hexagonal ice crystals on generic macroscopic foreign particles in water droplets at T = 253 K. Our results show that the droplet surface does thermodynamically favor the contact mode over the immersion one. Surprisingly, the numerical evaluations suggest that the line tension contribution (from the contact of three water phases (vapor-liquid-crystal)) to this enhancement may be of the same order of magnitude as or even larger than the surface tension contribution. | 18,925,734 |
Structure-activity relationship studies of phenanthridine-based Bcl-XL inhibitors. | Despite their structural similarities, the natural products chelerythrine ( 5) and sanguinarine ( 6) target different binding sites on the pro-survival Bcl-X L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X L and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC 50 values. | 18,925,736 |
Ni(II) and hs-Fe(II) complexes of a paramagnetic thiazyl ligand, and decomposition products of the iron complex, including an Fe(III) tetramer. | Synthesis and structural, magnetic and electrochemical characterization of the Ni(hfac) 2(pyDTDA) and the Fe(hfac) 2(pyDTDA) complexes are reported (hfac = 1,1,1,5,5,5-hexafluoroacetylacetonato-; pyDTDA = 4-(2'-pyridyl)-1,2,3,5-dithiadiazolyl). Unlike the previously reported Mn(II) and Cu(II) complexes, but similar to the Co(II) complex, the Ni(II) and Fe(II) complexes are not dimerized in the solid state, allowing for magnetic coupling between the metal ion and paramagnetic ligand to be readily obtained from solid state magnetic measurements: Ni complex, J/k B = +132(1) K, using H = -2 J{ S Ni. S Rad} and g Ni = 2.04(2) and g Rad = 1.99(2); Fe complex, J/k B = -60.3(3) K, using H = -2 J{ S Fe. S Rad} and g av = 2.11(2). The iron complex is unusually unstable. A thermal decomposition product is isolated wherein the coordinated pyDTDA ligand appears to have been transformed into a coordinated 2-(2'-pyridyl)-4,6-bis(trifluoromethyl)pyrimidine. The iron complex also yields a solution decomposition product in the presence of air that is best described as an oxygen bridged iron(III) tetramer with two hfac ligands on each of three iron atoms and two oxidized pyDTDA ligands chelated on the fourth. | 18,925,737 |
Investigation of non-nucleophilic additives for the reduction of morphological anomalies in protein arrays. | Uniform spot morphology is of critical importance in the fabrication and successful use of protein arrays, and solution additives are often needed to ensure good spot quality. Whereas hydroxyl-bearing molecules such as glycerol have found wide use, in our experience these reduce the efficiency of probe immobilization (particularly in the context of aldehyde-terminated surfaces). Here, we report a series of non-nucleophilic molecules that can be used as additives to improve spot homogeneity in protein arrays. Arrayed imaging reflectometry, a label-free optical biosensing technique, has been used along with spectroscopic ellipsometry to test the spot homogeneity, antibody immobilization efficiency, and activity of antihuman IgG arrays prepared with these non-nucleophilic additives on glutaraldehyde surfaces. It has been determined that 0.1% v/v 12-crown-4 performs optimally in MPBS buffer. | 18,925,757 |
Engineering inorganic hybrid nanoparticles: tuning combination fashions of gold, platinum, and iron oxide. | Multistep colloidal chemical routes were employed to synthesize Pt/Au, Pt/iron oxide (IO), and Au/Pt/IO hybrid nanoparticles (NPs). The starting templates, Pt NPs, were synthesized by controlling the decomposition kinetics of platinum acetylacetonate in oleylamine. The morphologies of binary metal Pt/Au hybrid NPs were modulated by controllable attachment of Au nanoscale domains to Pt templates. Similarly, Pt/IO and Au/Pt/IO hybrid NPs were fabricated by the controllable attachment of Fe to the Pt or Pt/Au template NPs. The noble metal domains of as-prepared hybrid NPs had face center cubic crystal structures and did not alloy, as verified by high resolution transmission electron microscopy and X-ray diffraction spectrometry. X-ray diffraction spectrometry study indicates that the IO domains in the as-prepared NPs have a spinel structure. UV-vis study of binary metal Pt/Au hybrid NPs revealed that they have a characteristic plasmon resonance around 525 nm, while dumbbell-like Au/Pt/IO NPs had a plasmon resonance around 600 nm. Furthermore, magnetism study of the binary Pt-IO NPs clearly indicated that the interfacial interactions between Pt and IO domains could result in a shift of the blocking temperature. | 18,925,758 |
Arraying heterotypic single cells on photoactivatable cell-culturing substrates. | This article describes a photochemical method for the site-selective assembly of heterotypic cells on a glass substrate modified with a silane coupling agent having a caged functional group. Silane coupling agents having a carboxyl (COOH), amino (NH 2), hydroxyl (OH), or thiol (SH) group protected by a photocleavable 2-nitrobenzyl group were synthesized to modify the surfaces of glass coverslips. The caged substrates were first coated by the adsorption of a blocking agent, bovine serum albumin (BSA), to make the entire surface non-cell-adhesive and then irradiated at 365 nm under a standard fluorescence microscope. The photocleavage reaction on the surface was followed by contact angle measurements and X-ray photoelectron spectroscopy. When COS7, NIH3T3, and HEK293 cells were seeded onto these substrates in a serum-free medium, the cells adhered selectively and efficiently to the irradiated regions on the caged NH 2 substrate, whereas the other caged COOH, SH, and OH substrates were nonphotoactivatable for cell adhesion. Qualitative and quantitative analysis of BSA adsorbed to the uncaged substrates revealed that this highly efficient photoactivation on the caged NH 2 substrate arose because of the following reasons: (i) upon photoactivation, BSA adsorbed in advance on the 2-nitrobenzyl groups was readsorbed onto the uncaged functional groups and (ii) BSA readsorbed onto the NH 2 groups became unable to passivate the surface against cell adhesion whereas BSA on the other groups still had normal passivating activity. It was also demonstrated that heterotypic single COS7, NIH3T3, and HEK293 cells were positioned at any desired arrangement on the caged NH 2 substrate by repeating the UV irradiation at optimized array spot sizes and cell seeding in optimized cell concentrations. The present method will be particularly useful in studying the dynamic processes of cell-cell interactions at a single-cell level. | 18,925,763 |
Peptide-mediated cellular uptake of cryptophane. | Cryptophane-A has generated considerable interest based on its high affinity for xenon and potential for creating biosensors for (129)Xe nuclear magnetic resonance (NMR) spectroscopy. Here, we report the cellular delivery of three peptide-functionalized cryptophane biosensors. Cryptophanes were delivered using two cationic cell penetrating peptides into several human cancer and normal cell lines. An RGD peptide targeting alpha(v)beta(3) integrin receptor was shown to increase specificity of cryptophane cell uptake. Labeling the peptides with Cy3 made it possible to monitor cellular delivery using confocal laser scanning microscopy. The peptido-cryptophanes were determined to be relatively nontoxic by MTT assay at the micromolar cryptophane concentrations that are required for (129)Xe NMR biosensing experiments. | 18,925,770 |
Papillary thyroid carcinoma tall cell variant. | The most common of the aggressive variant of papillary thyroid carcinoma (PTC) is the tall cell variant (TCV). Because there are serious prognostic and management implications to a diagnosis of TCV, we review the entity to inform clinicians about the many facets of TCV. The TCV of PTC is characterized by cells having the nuclear features of PTC and whose height is at least twice or thrice their width. There is disagreement regarding the proportion of tall cells and the cell height required to diagnose TCV. In view of its blurred definition and rarity, studies have shown that TCV is still underdiagnosed. We propose that PTC be diagnosed as TCV if it is composed of > or =50% tall cells. The latter should have a height that is at least twice their width, an eosinophilic cytoplasm, and the nuclear features of PTC. Whatever its definition, there is a consensus that TCV has a higher recurrence and death rate than classical PTC. Most authorities believe that TCV's worse prognosis is related to its older age at presentation, larger tumor size, and high frequency of extrathyroid extension (ETE). However, in a recent article, TCV without ETE was shown to have a more aggressive behavior than classical PTC without ETE independent of age, gender, and tumor size. The aggressive behavior of TCV could be related to the high expression of Muc1 and matrix metalloproteinase and to the higher prevalence of B-RAF mutations when compared to classical PTC. The importance of TCV is accentuated by the fact that it is overrepresented in those fluorodeoxyglucose positron-emission tomogram (FDG-PET)-positive thyroid carcinomas that are refractory to radioactive iodine (RAI) therapy constituting 20% of these incurable tumors. TCV is a biologically and clinically aggressive form of PTC that is still underdiagnosed. TCV is overrepresented in patients with RAI refractory disease. It has a high prevalence of B-RAF mutations making the latter an attractive target in RAI refractory cases. Imaging modalities that can detect RAI refractory disease such as FDG-PET scanning are needed in many patients and a requirement in those with extensive ETE. More studies are needed to identify those TCV that become RAI refractory and develop effective target therapies against these incurable carcinomas. | 18,925,842 |
Bevacizumab: direct anti-VEGF therapy in renal cell carcinoma. | Bevacizumab, in combination with IFN, is approved in the EU as first-line therapy for advanced and/or metastatic renal cell carcinoma (mRCC). Data from Avastin and Roferon in Renal Cell Carcinoma [BO17705] (AVOREN), a Phase III trial, demonstrated that bevacizumab plus IFN significantly improves progression-free survival and response rate in patients with previously untreated mRCC compared with IFN plus placebo. Furthermore, bevacizumab plus IFN is well tolerated and has a predictable and well-established tolerability profile; reducing the dose of IFN, when necessary, can effectively manage IFN-related side effects without compromising efficacy. The rapid evolution of options for RCC therapy means that the optimal use of available agents to maximize patient benefit is not currently well defined. Combination regimens and sequencing of agents are both being investigated to maximize future outcomes, with bevacizumab playing a key role in first-line regimens. Trials over the next 5 years will guide clinical practice, but bevacizumab plus IFN is currently a standard first-line option for mRCC. | 18,925,847 |
Management of reproductive needs in cancer patients: clinical perspectives. | Over the last few decades, a growing number of cancer survivors cured or in long-term remission following successful cancer treatment, have particular reproductive health needs. Achieving or preventing pregnancies, as well as replacement of sex hormone deficiency are three main reproductive issues. Managing such reproductive needs requires a close collaboration between specialists in oncology, reproductive endocrinology and andrology. Currently, there are few collaborative efforts to bridge the gaps between these three subspecialties. Patients are often lost between oncologists who lack the interest in addressing reproductive issues, and reproductive endocrinologists and andrologists, who do not have the clinical practice model to provide emergency consultations for cancer patients or adequate follow-up. On the other hand, there is severe deficiency in patients' education and knowledge regarding the consequences of cancer treatment on their reproductive life and the available modern technologies in reproductive medicine. Perhaps the time has come to build a new medical subspecialty that can address and manage the long-term health needs of cancer survivors, including reproductive needs. | 18,925,851 |
Molecular abnormalities in Ewing's sarcoma. | Ewing's sarcoma is one of the few solid tumors for which the underlying molecular genetic abnormality has been described: rearrangement of the EWS gene on chromosome 22q12 with an ETS gene family member. These translocations define the Ewing's sarcoma family of tumors (ESFT) and provide a valuable tool for their accurate and unequivocal diagnosis. They also represent ideal targets for the development of tumor-specific therapeutics. Although secondary abnormalities occur in over 80% of primary ESFT the clinical utility of these is currently unclear. However, abnormalities in genes that regulate the G(1)/S checkpoint are frequently described and may be important in predicting outcome and response. Increased understanding of the molecular events that arise in ESFT and their role in the development and maintenance of the malignant phenotype will inform the improved stratification of patients for therapy and identify targets and pathways for the design of more effective cancer therapeutics. | 18,925,858 |
mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1). | SGK1 (serum- and glucocorticoid-induced protein kinase 1) is a member of the AGC (protein kinase A/protein kinase G/protein kinase C) family of protein kinases and is activated by agonists including growth factors. SGK1 regulates diverse effects of extracellular agonists by phosphorylating regulatory proteins that control cellular processes such as ion transport and growth. Like other AGC family kinases, activation of SGK1 is triggered by phosphorylation of a threonine residue within the T-loop of the kinase domain and a serine residue lying within the C-terminal hydrophobic motif (Ser(422) in SGK1). PDK1 (phosphoinositide-dependent kinase 1) phosphorylates the T-loop of SGK1. The identity of the hydrophobic motif kinase is unclear. Recent work has established that mTORC1 [mTOR (mammalian target of rapamycin) complex 1] phosphorylates the hydrophobic motif of S6K (S6 kinase), whereas mTORC2 (mTOR complex 2) phosphorylates the hydrophobic motif of Akt (also known as protein kinase B). In the present study we demonstrate that SGK1 hydrophobic motif phosphorylation and activity is ablated in knockout fibroblasts possessing mTORC1 activity, but lacking the mTORC2 subunits rictor (rapamycin-insensitive companion of mTOR), Sin1 (stress-activated-protein-kinase-interacting protein 1) or mLST8 (mammalian lethal with SEC13 protein 8). Furthermore, phosphorylation of NDRG1 (N-myc downstream regulated gene 1), a physiological substrate of SGK1, was also abolished in rictor-, Sin1- or mLST8-deficient fibroblasts. mTORC2 immunoprecipitated from wild-type, but not from mLST8- or rictor-knockout cells, phosphorylated SGK1 at Ser(422). Consistent with mTORC1 not regulating SGK1, immunoprecipitated mTORC1 failed to phosphorylate SGK1 at Ser(422), under conditions which it phosphorylated the hydrophobic motif of S6K. Moreover, rapamycin treatment of HEK (human embryonic kidney)-293, MCF-7 or HeLa cells suppressed phosphorylation of S6K, without affecting SGK1 phosphorylation or activation. The findings of the present study indicate that mTORC2, but not mTORC1, plays a vital role in controlling the hydrophobic motif phosphorylation and activity of SGK1. Our findings may explain why in previous studies phosphorylation of substrates, such as FOXO (forkhead box O), that could be regulated by SGK, are reduced in mTORC2-deficient cells. The results of the present study indicate that NDRG1 phosphorylation represents an excellent biomarker for mTORC2 activity. | 18,925,875 |
IgE antibodies to omega-5 gliadin associate with immediate symptoms on oral wheat challenge in Japanese children. | Gliadins have been implicated in immunoglobulin E (IgE)-mediated allergy to ingested wheat and omega-5-gliadin is known to represent a major allergen in wheat-dependent exercise-induced anaphylaxis. Less known is whether omega-5-gliadin is a clinically relevant allergen in children with immediate allergy to ingested wheat. This study investigates whether specific IgE antibodies to omega-5-gliadin (sIgE-omega-5-gliadin-ab) could be used as a marker for oral wheat challenge outcome in wheat-sensitized children. A secondary objective was to study whether the level of sIgE-omega-5-gliadin was related to symptom severity in children with a positive challenge test. Serum samples from 88 children sensitized to wheat, of whom 35 underwent wheat challenge, were collected consecutively. sIgE-omega-5-gliadin-ab was related to a physician's diagnosis of wheat allergy and challenge symptoms. The mean concentration of sIgE-omega-5-gliadin-ab was 7.25 kU(A)/l in patients with wheat allergy and 1.08 kU(A)/l in patients with no wheat allergy (P < 0.01). sIgE-omega-5-gliadin-ab was only detected in 12 of the non-wheat allergic children and 11 of them had a specific IgE to wheat below 1.30 kU(A)/l. Children reacting with severe symptoms upon challenge (n = 8) had increased levels of sIgE-omega-5-gliadin-ab compared to children with moderate, mild or no symptoms (P < 0.001). The presence of sIgE-omega-5-gliadin-ab is related to the reaction level to wheat challenge outcome in wheat-sensitized children. The sIgE-omega-5-gliadin-ab was found to be associated with a strong convincing history of wheat allergy also in those cases when oral food challenge was avoided. The sIgE-omega-5-gliadin-ab level may serve as a marker for clinical reactivity in wheat-sensitized individuals. | 18,925,890 |
The programmed death (PD)-1/PD-ligand 1 pathway regulates graft-versus-host-reactive CD8 T cells after liver transplantation. | Acute graft-versus-host disease (aGVHD) is a life-threatening complication after solid-organ transplantation, which is mediated by host-reactive donor T cells emigrating from the allograft. We report on two liver transplant recipients who developed an almost complete donor chimerism in peripheral blood and bone marrow-infiltrating T cells during aGVHD. By analyzing these T cells directly ex vivo, we found that they died by apoptosis over time without evidence of rejection by host T cells. The host-versus-donor reactivity was selectively impaired, as anti-third-party and antiviral T cells were still detectable in the host repertoire. These findings support the acquired donor-specific allotolerance concept previously established in animal transplantation studies. We also observed that the resolution of aGVHD was not accompanied by an expansion of circulating immunosuppressive CD4/CD25/FoxP3-positive T cells. In fact, graft-versus-host-reactive T cells were controlled by an alternative negative regulatory pathway, executed by the programmed death (PD)-1 receptor and its ligand PD-L1. We found high PD-1 expression on donor CD4 and CD8 T cells. In addition, blocking PD-L1 on host-derived cells significantly enhanced alloreactivity by CD8 T cells in vitro. We suggest the interference with the PD-1/PD-L1 pathway as a therapeutic strategy to control graft-versus-host-reactive T cells in allograft recipients. | 18,925,909 |
Gillies lecture: dissecting glaucoma: understanding the molecular risk factors. | WE Gillies was a major contributor to research in glaucoma, notably pseuodexfoliation (XFS), as well as strabismus, particularly in relation to axial length (AL). The latter work involved breaking down the geometry of the eye to its basic components and using the measured AL to tailor the amount of strabismus surgery required. Similarly, the search for glaucoma genes requires us to break down glaucoma into its component measures and associated risk factors. Over the last 14 years, our data from the Glaucoma Inheritance Study in Tasmania have shown the following: that a family history is present in 60% of glaucoma cases; that 27% of members of large glaucoma families were unaware of their family history of glaucoma; and that familial glaucoma is more severe than sporadic glaucoma. Myocilin mutations account for 3% of cases of primary open angle glaucoma. Some genotype-phenotype correlations have been identified. Notably, with respect to earlier age of onset, higher maximum recorded intraocular pressure and need for surgery, the Gln368Stop mutation confers mild risk, Thr377Met and Gly252Arg mutations intermediate risk, and the Pro370Leu mutation severe risk. To identify the other genes associated with glaucoma, we have examined normal twins in the Twins Eye Study to determine the heritability of parameters that are abnormal in glaucoma - intraocular pressure and cup-to-disc ratio and confounding factors for glaucoma such as central corneal thickness, disc area, refraction and AL. We have identified high heritabilities for all of these as well as a gene locus associated with AL on chromosome 5. Recently, the LOXL1 gene was associated with XFS. Identification of further genes will improve our understanding of glaucoma and allow cascade genetic screening. | 18,925,913 |
Osteolipoma of the eyelid. | A 50-year-old woman presented with a nodular swelling on her right upper eyelid. The tumour was diagnosed as osteolipoma histologically after resection. Osteolipoma is a very rare variant of lipoma and only a few cases affecting the head and neck are reported in literature. To the best of the author's knowledge this is the first reported case of osteolipoma of the eyelid. | 18,925,915 |
Whole blood assessment of antigen specific cellular immune response by real time quantitative PCR: a versatile monitoring and discovery tool. | Monitoring of cellular immune responses is indispensable in a number of clinical research areas, including microbiology, virology, oncology and autoimmunity. Purification and culture of peripheral blood mononuclear cells and rapid access to specialized equipment are usually required. We developed a whole blood (WB) technique monitoring antigen specific cellular immune response in vaccinated or naturally sensitized individuals. WB (300 microl) was incubated at 37 degrees C with specific antigens, in the form of peptides or commercial vaccines for 5-16 hours. Following RNAlater addition to stabilize RNA, the mixture could be stored over one week at room temperature or at 4 degrees C. Total RNA was then extracted, reverse transcribed and amplified in quantitative real-time PCR (qRT-PCR) assays with primers and probes specific for cytokine and/or chemokine genes. Spiking experiments demonstrated that this technique could detect antigen specific cytokine gene expression from 50 cytotoxic T lymphocytes (CTL) diluted in 300 microl WB. Furthermore, the high sensitivity of this method could be confirmed ex-vivo by the successful detection of CD8+ T cell responses against HCMV, EBV and influenza virus derived HLA-A0201 restricted epitopes, which was significantly correlated with specific multimer staining. Importantly, a highly significant (p = 0.000009) correlation between hepatitis B surface antigen (HBsAg) stimulated IL-2 gene expression, as detectable in WB, and specific antibody titers was observed in donors vaccinated against hepatitis B virus (HBV) between six months and twenty years before the tests. To identify additional markers of potential clinical relevance, expression of chemokine genes was also evaluated. Indeed, HBsAg stimulated expression of MIP-1beta (CCL4) gene was highly significantly (p = 0.0006) correlated with specific antibody titers. Moreover, a longitudinal study on response to influenza vaccine demonstrated a significant increase of antigen specific IFN-gamma gene expression two weeks after immunization, declining thereafter, whereas increased IL-2 gene expression was still detectable four months after vaccination. This method, easily amenable to automation, might qualify as technology of choice for high throughput screening of immune responses to large panels of antigens from cohorts of donors. Although analysis of cytokine gene expression requires adequate laboratory infrastructure, initial antigen stimulation and storage of test probes can be performed with minimal equipment and time requirements. This might prove important in "field" studies with difficult access to laboratory facilities. | 18,925,935 |
BioVenn - a web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. | In many genomics projects, numerous lists containing biological identifiers are produced. Often it is useful to see the overlap between different lists, enabling researchers to quickly observe similarities and differences between the data sets they are analyzing. One of the most popular methods to visualize the overlap and differences between data sets is the Venn diagram: a diagram consisting of two or more circles in which each circle corresponds to a data set, and the overlap between the circles corresponds to the overlap between the data sets. Venn diagrams are especially useful when they are 'area-proportional' i.e. the sizes of the circles and the overlaps correspond to the sizes of the data sets. Currently there are no programs available that can create area-proportional Venn diagrams connected to a wide range of biological databases. We designed a web application named BioVenn to summarize the overlap between two or three lists of identifiers, using area-proportional Venn diagrams. The user only needs to input these lists of identifiers in the textboxes and push the submit button. Parameters like colors and text size can be adjusted easily through the web interface. The position of the text can be adjusted by 'drag-and-drop' principle. The output Venn diagram can be shown as an SVG or PNG image embedded in the web application, or as a standalone SVG or PNG image. The latter option is useful for batch queries. Besides the Venn diagram, BioVenn outputs lists of identifiers for each of the resulting subsets. If an identifier is recognized as belonging to one of the supported biological databases, the output is linked to that database. Finally, BioVenn can map Affymetrix and EntrezGene identifiers to Ensembl genes. BioVenn is an easy-to-use web application to generate area-proportional Venn diagrams from lists of biological identifiers. It supports a wide range of identifiers from the most used biological databases currently available. Its implementation on the World Wide Web makes it available for use on any computer with internet connection, independent of operating system and without the need to install programs locally. BioVenn is freely accessible at http://www.cmbi.ru.nl/cdd/biovenn/. | 18,925,949 |
Attempts at in vitro fertilization and culture of in vitro matured oocytes in sei ( Balaenoptera borealis) and Bryde's ( B. edeni) whales. | The cumulus-oocyte-complexes (COCs) recovery rates with respect to reproductive status per sei (Balaenoptera borealis) and Bryde's (B. edeni) whales were determined in Experiment 1. The number of COCs recovered ranged from 16.0 to 30.6 and from 6.7 to 26.8 per sei and Bryde's whales, respectively. The effects of COCs grades and protein supplementation in embryo culture medium on development of in vitro fertilized (IVF) embryos were evaluated in sei and Bryde's whales in Experiment 2. The COCs were classified into either Grade A (COCs with five or more layers of compact cumulus cells) or Grade B (COCs with less than five layers of compact or expanded cumulus cells) before being cultured for IVM. The cleavage (12.0 to 19.5%), 4-cell (8.0 to 12.0%) and 8-cell (4.0 to 8.0%) formation rates in sei whales did not vary significantly between embryos derived from either grade A or B oocytes and between embryos cultured in either fetal whale serum (FWS)- or bovine serum albumin (BSA)-supplemented medium. The cleavage (4.0 to 14.8%), 4-cell (0.0 to 7.5%) and 8-cell (0.0 to 2.6%) formation rates in Bryde's whales did not vary significantly between embryos derived from either grade A or B oocytes and between embryos cultured in either FWS- or BSA-supplemented medium. The grade B oocytes cultured in FWS-supplemented medium developed to morula stage (1.1%) in sei whales. In conclusion, the present study indicates that IVF in sei whales is possible to achieve cleaved embryos developing to morula stage. This is the first in vitro embryo production attempt in sei and Bryde's whales. | 18,925,980 |
Why should disorders of the ear, nose and throat be treated by the same specialty? Can this situation persist? | The surgical specialty of otorhinolaryngology has its origins in the nineteenth century. Subsequently, the specialty also incorporated allied disciplines such as plastics and head and neck surgery. Following World War II, the survival of the specialty was threatened by the advent of antibiotics and the rise of the general surgeon. Despite this, the specialty of ENT was strengthened by strong post-war leadership and robust training.Today, with ENT knowledge ever increasing, the subspecialties have again begun to subdivide. Specialisation brings improved efficiency and outcomes; however, there remains a great need for the ENT generalist. Not all cases require subspecialist attention, and the generalist remains the basis of competent emergency cover. The natural development of otorhinolaryngology has brought the invaluable synergistic knowledge required to comprehensively treat disorders of the ear, nose and throat, knowledge that must not be overlooked when shaping the future of the specialty. | 18,925,994 |
Thyroid surgery: the sub-mental drain. | To propose an alternative site of thyroid drain placement. During thyroid surgery, post-operative drains are often placed. It is common practice to bring out the drain lateral to the wound, often creating an additional, unsightly scar. We have found excellent cosmesis is achieved by bringing out the drain in the midline in a sub-mental skin crease, with the scar hidden in the chin shadow. In our experience, such drain placement is a safe, straightforward method with an excellent cosmetic result. | 18,926,000 |
Spontaneous intracranial hypotension presenting to the ENT surgeon: case report. | To highlight a case of spontaneous intracranial hypotension presenting to the ENT surgeon. We present a case report and a review of the literature concerning spontaneous intracranial hypotension. Spontaneous intracranial hypotension is a rare diagnosis, particularly to the ENT surgeon. We report a patient with tinnitus, hearing loss and headache, symptoms suggestive of an ENT diagnosis such as Ménière's disease or vestibular schwannoma. However, magnetic resonance imaging revealed the characteristic findings of spontaneous intracranial hypotension. The patient's symptoms resolved, except for a mild residual tinnitus, with conservative management alone. This case highlights the importance of considering spontaneous intracranial hypotension as a differential diagnosis of certain ENT symptoms. | 18,926,003 |
Fully automated high-performance signal-to-noise ratio enhancement based on an iterative three-point zero-order Savitzky-Golay filter. | The automated processing of data from high-throughput and real-time collection procedures is becoming a pressing problem. Currently the focus is shifting to automated smoothing techniques where, unlike background subtraction techniques, very few methods exist. We have developed a filter based on the widely used and conceptually simple moving average method or zero-order Savitzky-Golay filter and its iterative relative, the Kolmogorov-Zurbenko filter. A crucial difference, however, between these filters and our implementation is that our fully automated smoothing filter requires no parameter specification or parameter optimization. Results are comparable to, or better than, Savitzky-Golay filters with optimized parameters and superior to the automated iterative median filter. Our approach, because it is based on the highly familiar moving average concept, is intuitive, fast, and straightforward to implement and should therefore be of immediate and considerable practical use in a wide variety of spectroscopy applications. | 18,926,027 |
The diagnosis and misdiagnosis of tuberculosis. | There are two worlds when it comes to the diagnosis of tuberculosis (TB). One world has only smear microscopy at its disposal. There may also be some radiological facilities, usually at the patients' expense. The other world has all modern techniques available, including culture, nucleic acid amplification, molecular diagnostics and sophisticated radiological techniques such as computed tomography and positron emission tomography scanning. The ability to diagnose or misdiagnose TB will vary across these two worlds. In this review, we provide an overview of clinical, radiological, molecular and immunological diagnosis of TB and highlight the common difficulties and pitfalls in TB diagnosis. | 18,926,032 |
Comparison of MAS-PCR and GenoType MTBDR assay for the detection of rifampicin-resistant Mycobacterium tuberculosis. | Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, the tertiary referral hospital for tuberculosis (TB) in Southern Vietnam. To develop and evaluate a simple, rapid and accurate multiplex allele specific polymerase chain reaction (MAS-PCR) test to detect rifampicin (RMP) resistance point mutations at codons 516, 526 or 531 in the rpoB gene of Mycobacterium tuberculosis. The novel MAS-PCR was compared with the commercial M. tuberculosis Drug Resistance (MTBDR) test in 104 RMP-resistant and 50 RMP-susceptible routine isolates, defined by conventional 1% phenotypic susceptibility testing. The sensitivity of the MAS-PCR and MTBDR tests was respectively 83.7% (95%CI 75.1-90.2) and 93.3% (95%CI 86.6-97.3). Both tests were 100% specific. The negative predictive value was 74.6% (95%CI 65.3-83.1) for the MAS-PCR and 87.7% (95%CI 80.0-93.6) for the MTBDR test. The MTBDR test, although more sensitive, is currently prohibitively expensive in resource-poor, high-burden settings. The MAS-PCR described here presents a less laborious economic alternative. A susceptible result returned by either test cannot be used to exclude multidrug-resistant TB. | 18,926,042 |
Inequalities in smoking profiles in Morocco: the role of educational level. | Cigarette smoking is increasingly associated with lower socio-economic status, indicated by lower educational levels. This association has never been investigated in Morocco. The MARTA survey was undertaken to assess tobacco use in the Moroccan population according to level of education and other socio-demographic characteristics. A cross-sectional survey based on a representative sample of the Moroccan population was conducted in 2005-2006. The survey questionnaire gathered socio-demographic information, educational level and smoking status. chi(2) analyses were performed to determine whether the smoking outcome variables differed significantly between different educational levels in relation to demographic variables. Multiple logistic regression analysis was used to calculate the adjusted odds ratio for smoking status according to educational level. A total of 9195 subjects were included in the study; 52% were men and 17.9% illiterate. The overall prevalence of current smoking was 18.0% (95%CI 17.2-18.8): 31.5% (95%CI 30.2-32.9) in males and 3.3% (95%CI 2.8-3.8) in females. The prevalence of current smoking was inversely associated with level of education in men and increased with educational level in women. Illiterate males tended to have a higher probability of being current smokers than males with university-level education (OR 1.93, 95%CI 1.51-2.46). These results indicate a need for tobacco control to reach all sectors of society, and especially the illiterate population. | 18,926,045 |
Endothelial activation and systemic inflammation in obese asthmatic children. | Asthma and obesity are prevalent disorders, each with a significant impact on the public health. The causality relating obesity and asthma has not been established. The objective of this article is to investigate whether asthma could exacerbate the endothelial activation and to determine the relationship between systemic inflammation and endothelial activation in obese asthmatic children. Eighty-nine children (10-16 years old) were divided according to their diagnosis (asthma, obese nonasthmatic, and obese asthmatic children). Twenty healthy children formed the control group. Three adhesion molecules (E-selectin, sICAM-1, and sVCAM-1) and C-reactive protein (CRP) were measured in serum samples. The levels of sICAM-1 were significantly higher in obese nonasthmatic and obese asthmatic children versus control and lean asthmatic children (414.7+/-154.7, 434.9+/-181.1, 238.6+/-117.8, and 351.2+/-153.5 ng/mL, respectively). No difference was observed between obese nonasthmatic and obese asthmatic groups. No difference of the levels of CRP, E-selectin, and sVCAM-1 was found among the study groups. Correlation analysis showed that E-selectin associated significantly with body mass index (BMI), CRP and the other two adhesion molecules. CRP depended on BMI. sICAM-1 associated with CRP, BMI, and triglycerides. Correlations were verified in multiple regression analysis models in the whole study groups: CRP levels depended on sICAM-1, E-selectin, and sICAM-1 concentrations depended on BMI. Correlations were verified in asthmatic subjects: CRP depended on sICAM-1. These results confirmed the endothelial activation in obese children. Mild nonallergic asthma in our study did not exacerbate the endothelial activation in obese or lean asthmatic children. Significant association between systemic inflammation and endothelial activation was observed in asthmatic children. | 18,926,053 |
[A randomized controlled trial study of pulmonary rehabilitation with respiratory physiology as the guide on prognosis in patients with chronic obstructive pulmonary disease]. | To observe the effect of pulmonary rehabilitation with respiratory physiology as guide in patients with chronic obstructive pulmonary disease (COPD). Sixty patients of severe and very severe COPD as categorized by global proposed diagnostic criteria for COPD (GOLD, 2006) were enrolled for study. They were randomly divided into three groups, and with 20 patients in each group. The patients in group A were given pulmonary rehabilitation guided by respiratory physiology thrice a day, 15 minutes each time for 8 weeks. The patients in group B were given pulmonary rehabilitation with pursed lip respiration thrice a day, 15 minutes per time for 8 weeks. The patients in group C were given no pulmonary rehabilitation. Six minute-walk-distance (6MWD), medical research council (MRC) dyspnea scale, activities of daily living (ADL), maximal expiratory pressure (MEP), maximal inspiratory pressure (MIP), and quality of life (QOL) were determined before and after respective pulmonary rehabilitation course. (1) There were 3, 5, 5 patients in group A, group B, group C dropped off in the course of rehabilitation respectively. (2) The patients' MRC grade after pulmonary rehabilitation in group A and group B decreased compared with that before pulmonary rehabilitation (both P<0.01), but the difference was not significant between two groups (P>0.05). (3) 6MWD, ADL, MEP, MIP of patients in group A and group B increased after pulmonary rehabilitation compared with that before pulmonary rehabilitation, and 6MWD, ADL, MEP, MIP of patients in group A were increased after pulmonary rehabilitation more than those in group B (P<0.05 or P<0.01). (4)The patients' body status, shortness of breath, social activity, home chores in group A and group B, and uneasiness in group A after pulmonary rehabilitation were improved more than those before pulmonary rehabilitation (P<0.05 or P<0.01), but the difference in state of mind, headache, appetite was not markedly different before and after pulmonary rehabilitation in two groups (all P>0.05). The difference in QOL was not marked between group A and group B after pulmonary rehabilitation (all P>0.05). (1) The pulmonary rehabilitation with pursed lip respiration and the pulmonary rehabilitation with the guide of respiratory physiology ameliorates dyspnea, improves ADL, QOL, exercise tolerance, function of respiratory muscle in the severe and very severe COPD patients remarkably. (2) The effect of the pulmonary rehabilitation with the guide of respiratory physiology is better than that of the pulmonary rehabilitation with pursed lip respiration, and it can be considered as a more effective pulmonary rehabilitation method for the patients with severe and very severe COPD. | 18,926,073 |
Combined modality therapy of esophageal cancer. | Esophageal cancer is a deadly disease. Only one third of patients with localized disease experience long-term survival. Over the past 20 years, investigators have evaluated neoadjuvant strategies to improve the outcomes of surgical management. Chemotherapy and radiation have been evaluated individually and in combination for preoperative management of patients with localized esophageal cancer. This article provides a critical review of the data on multimodality approaches to the management of esophageal cancer. | 18,926,094 |
An update on biochemotherapy of advanced gastric and gastroesophageal adenocarcinoma. | Gastric and gastroesophageal adenocarcinoma (GGA) are significant worldwide health problems. With most patients presenting with advanced disease, palliative chemotherapy plays a significant role in treatment. Results from recent phase III studies of cytotoxic agents in combination therapy, such as docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1, have been encouraging and provide patients with additional therapeutic options. Although these forthcoming regimens have allowed for more flexible patient-tailored therapy, survival continues to be suboptimal. Although still in its infancy, targeted biotherapy, including inhibitors of the vascular endothelial and epidermal growth factor receptors, seems to be promising and its incorporation into the next generation of clinical trials will hopefully improve outcomes and help advance future treatments. This article reviews current active chemotherapeutic regimens and explores the role of novel targeted therapies in advanced GGA. | 18,926,099 |
Impact of age and comorbidity in myelodysplastic syndromes. | Myelodysplastic syndromes (MDS) represent a heterogeneous group of myeloid neoplasms that are preferentially diagnosed in the elderly. With the increase in older patients with MDS in the Western world and the availability of more therapeutic options, new strategies and algorithms for optimal management and treatment of these patients must be developed. Although age is recognized as an important adverse variable affecting survival, most scoring systems have not included age in score risk calculations. Comorbidity is of particular importance and a frequent covariable in elderly patients with MDS. However, although comorbidity scores have been established and used for risk assessment in younger high-risk patients scheduled to undergo intensive therapy, these scores are only just being applied to elderly patients, with relevant results. Advanced age should not exclude a patient with MDS from appropriate treatment, and age alone should not be considered a surrogate marker for functional decline or comorbidities. This article discusses the need to improve scoring systems, individualized risk-assessment, and treatment algorithms for elderly patients with MDS by including age and comorbidities. | 18,926,101 |
Dietary restraint and gestational weight gain. | To determine whether a history of preconceptional dieting and restrained eating was related to higher weight gains in pregnancy. Dieting practices were assessed among a prospective cohort of pregnant women using the Revised Restraint Scale. Women were classified on three separate subscales as restrained eaters, dieters, and weight cyclers. Participants included 1,223 women in the Pregnancy, Infection, and Nutrition Study. Total gestational weight gain and adequacy of weight gain (ratio of observed/expected weight gain based on Institute of Medicine recommendations). Multiple linear regression was used to model the two weight-gain outcomes, while controlling for potential confounders including physical activity and weight-gain attitudes. There was a positive association between each subscale and total weight gain, as well as adequacy of weight gain. Women classified as cyclers gained an average of 2 kg more than noncyclers and showed higher observed/expected ratios by 0.2 units. Among restrained eaters and dieters, there was a differential effect by body mass index. With the exception of underweight women, all other weight status women with a history of dieting or restrained eating gained more weight during pregnancy and had higher adequacy of weight gain ratios. In contrast, underweight women with a history of restrained eating behaviors gained less weight compared to underweight women without those behaviors. Restrained eating behaviors were associated with weight gains above the Institute of Medicine's recommendations for normal, overweight, and obese women, and weight gains below the recommendations for underweight women. Excessive gestational weight gain is of concern because of its association with postpartum weight retention. The dietary restraint tool is useful for identifying women who would benefit from nutritional counseling prior to or during pregnancy with regard to achieving targeted weight-gain recommendations. | 18,926,129 |
Determining the most appropriate components for a composite clinical trial outcome. | Because composite end points augment event rates, they are often thought to increase statistical power. This may not be true if the intervention has a lesser effect on some components of the composite. Consequently, treatment effect size may depend on the choice of composite. To explore this issue, we performed a meta-analysis to determine the effect of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers on individual cardiovascular (CV) outcomes. We then applied these treatment effects to 2 different composite CV outcomes generated using blinded data from the ongoing Nateglinide and Valsartan in Impaired Glucose Tolerance (IGT) Outcomes Research (NAVIGATOR) trial and analyzed them on a time-to-first-event basis. The composites were CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure and an "extended" composite that included hospitalization for angina and coronary revascularization. The odds reductions due to angiotensin-converting enzyme/angiotensin receptor blocker treatment estimated from the meta-analysis were as follows: CV death: 13%, P < .0001; nonfatal myocardial infarction: 16%, P < .00001; nonfatal stroke: 14%, P = .006; heart failure: 28%, P < .00001; hospitalization for angina: 7%, P = .02; and revascularization: 5%, P = .17. For the CV composites, the projected odds reduction was larger (17.8%, 95% CI 0.452-1.189) for the narrower composite compared with the extended CV composite (11.7%, 95% CI 0.623-1.136); that is, use of the extended composite reduced power to detect a difference between treatment groups. Although the use of CV composites augments event rates, it may not increase statistical power. Inclusion of events little influenced by an intervention may reduce the precision of the composite end point and mask treatment effects. | 18,926,145 |
Long-term economic outcomes associated with intensive versus moderate lipid-lowering therapy in coronary artery disease: results from the Treating to New Targets (TNT) Trial. | In 10,001 patients with stable coronary artery disease (CAD) enrolled in the Treating to New Targets (TNT) trial, 80 mg/d of atorvastatin (high-dose regimen) reduced the composite primary end point of death from CAD, nonfatal myocardial infarction, resuscitation from cardiac arrest, or stroke by 22% relative to 10 mg/d (low-dose regimen). We performed an economic analysis of this trial from the US perspective using hospital bills and Medicare physician fees to estimate costs for cardiovascular hospitalizations in all US patients (n = 5,308). Atorvastatin costs were assigned using a discounted average wholesale price. Cost-effectiveness was calculated as the within-trial incremental cost required to prevent one primary end point event with high-dose atorvastatin. During a mean 4.9-year follow-up, the high-dose arm had fewer potential end point cardiovascular hospitalizations (35% vs 41%, P < .001) and revascularization procedures (16% vs 22%, P < .001). The high-dose regimen was $1 per day more expensive. At the end of 5 years, cumulative incremental cost for the high-dose arm was $252 (95% CI-$722 to +$1,276). With an absolute reduction in the primary end point of 2.8 per 100 treated with the high-dose regimen, the cost to prevent one additional primary end point event was $8,964. High-dose atorvastatin treatment of 5 years had only a small net incremental cost because of reduced complications and procedures. The cost to prevent one additional primary end point event with high-dose therapy was similar to that for drug-eluting stents versus bare metal stents in stable CAD and for early invasive versus early conservative therapy in acute coronary syndromes. | 18,926,150 |
Decreased heart rate variability is associated with higher levels of inflammation in middle-aged men. | Many traditional risk factors for coronary artery disease (CAD) are associated with altered autonomic function. Inflammation may provide a link between risk factors, autonomic dysfunction, and CAD. We examined the association between heart rate variability (HRV), a measure of autonomic function, and inflammation, measured by C-reactive protein (CRP) and interleukin-6 (IL-6). We examined 264 middle-aged male twins free of symptomatic CAD. All underwent ambulatory electrocardiogram monitoring and 24-hour ultra low, very low, low, and high-frequency power were calculated using power spectral analysis. C-reactive protein and IL-6 were measured, and risk factors including age, smoking, hypertension, lipids, diabetes, body mass index (BMI), depression, and physical activity were assessed. Physical activity, BMI, high-density lipoprotein cholesterol, smoking, depression, and hypertension were directly associated with CRP and IL-6 and inversely associated with one or more HRV variables. There was a graded inverse relationship between all HRV parameters (except high frequency) and CRP and IL-6. After adjustment for age, BMI, activity, high-density lipoprotein, smoking, hypertension, depression, and diabetes, ultra low frequency and very low frequency remained significant predictors of CRP (P < .01). C-reactive protein is associated with decreased HRV, even after controlling for traditional CAD risk factors. Autonomic dysregulation leading to inflammation may represent one pathway through which traditional risk factors promote development of CAD. | 18,926,158 |
Diagnosis of adrenocortical tumor in a neonate by detection of elevated blood 17-hydroxyprogesterone measured as a routine neonatal screening for congenital adrenal hyperplasia: a case report. | We report herein a case of prenatally detected neonatal adrenocortical tumor (ACT). The patient was an otherwise healthy newborn girl. No signs of Beckwith-Wiedemann syndrome were identified, and her family medical history did not suggest predisposition to cancer. Computed tomography and ultrasonography after birth revealed a round solid tumor 40 mm in diameter in the right suprarenal area. The precise diagnosis of ACT was unexpectedly obtained based on results from the Japanese neonatal mass screening program. Blood 17-hydroxyprogesterone is routinely measured as a part of this program for early detection of congenital adrenal hyperplasia in Japan. Abnormally elevated level of 17-hydroxyprogesterone was reported in the patient and, thus, led to the diagnosis of ACT. Surgical resection was safely performed with perioperative steroid replacement. Adrenocortical tumors are extremely rare in childhood, particularly in the neonatal period. Some of these tumors secrete abnormally high levels of cortisol, suppressing function of the contralateral adrenal gland and, thus, leading to life-threatening postoperative adrenal insufficiency. Scheduled steroid replacement enables safe perioperative management in such cases. Adrenocortical tumor should always be considered among the differential diagnoses for neonatal suprarenal mass because precise diagnosis will enable the physician to develop appropriate treatment strategies. | 18,926,198 |
Primary repair of a large incomplete sternal cleft in an asymptomatic infant with Prolene mesh. | A cleft of the sternum is a rare congenital anomaly, often diagnosed as an asymptomatic condition at birth. We present a case of a large incomplete sternal cleft in a full-term baby boy. Surgical repair of the sternum with the use of Prolene mesh was performed during the neonatal period without cardiac compression. | 18,926,203 |
Maternal tobacco smoking, obesity, and low socioeconomic status during early pregnancy in the etiology of esophageal atresia. | The etiology of the congenital malformation esophageal atresia (EA) is essentially unknown. We hypothesized that maternal tobacco smoking, obesity, and low socioeconomic status (SES) during early pregnancy might increase the risk of the fetus developing EA. A nationwide, population-based, case-control study was nested in a cohort of children born in Sweden in 1982 to 2004. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Matching, stratification, and multivariable regression were used to control for confounding. Among 2,305,858 newborn children constituting the study cohort, 722 cases of EA and 3610 controls were included. For women smoking 10 cigarettes or more daily, the adjusted OR was 0.88 (95% CI, 0.62-1.25) compared to nonsmokers. For obese women (body mass index, >30), OR was 0.99 (95% CI, 0.64-1.55) compared to lean women (body mass index, <20). Women with more than 12 years of formal education, representing SES, had an OR of 0.94 (95% CI, 0.69-1.29) compared to those with less than 10 years of education. The lack of association remained in stratified analyses of isolated EA and EA accompanied by associated malformations. This study provides evidence refuting the hypotheses of an increased risk of EA among children of women who smoke, are obese, or have a low SES during early pregnancy. | 18,926,209 |
Gastric outlet obstruction in children: an overview with report of Jodhpur disease and Sharma's classification. | Gastric outlet obstruction (GOO) is overwhelmingly described as infantile hypertrophic pyloric stenosis that overshadows other causes; thereby, there is a need to develop an elaborate and comprehensive classification. We present the same and establish a new disease called primary acquired gastric outlet obstruction during infancy and childhood that was reported for the first time by us in 1997, reviewing the literature published since then, with report of our new cases. Eight patients of this disease presented at our center from 1996 to May 2008, and these were analyzed epidemiologically and clinically. Other reports published in literature were compared, and all reported patients were compiled. All 8 cases presented at age ranging from 1 month to 6 years, with mean age of 2.9 years; there was predilection for male sex (male, 7; female, 1). Presenting symptoms and signs were nonbilious vomiting, weight loss, dehydration, dyselectrolytemia, abdominal pain, and visible gastric peristalsis. Upper gastrointestinal contrast study showed large stomach and increased gastric emptying time. Endoscopy displayed normal stomach without intraluminal lesion. Exploration revealed a dilated stomach, without any pyloric muscular hypertrophy, scarring, inflammation, or obstruction externally or intraluminally. Result of histopathologic examination was normal. All patients except 1 (died of unrelated cause) were cured by Heineke-Mikulicz pyloroplasty. These patients represent a new disease entity designated as primary acquired gastric outlet obstruction during infancy and childhood. Author's classification is complete and scientific, encompassing all rare causes of GOO. We nickname this idiopathic variety of GOO the Jodhpur disease, the place of the first cases. | 18,926,227 |
From expression to signaling: roles of TREM-1 and TREM-2 in innate immunity and bacterial infection. | Triggering receptor expressed on myeloid cells (TREM) proteins play important roles in innate and adaptive immunity. Since the discovery of TREM-1 and TREM-2 in 2000, the field has exploded over the past 8 years and currently TREM-1 is thought of as an amplifier of the immune response, while TREM-2 is believed to be a negative regulator. Here, we discuss the current state of the literature on TREMs, with a focus on TREM-1 and TREM-2 and their expression, signaling in mononuclear phagocytes and roles in innate immunity and bacterial infection. | 18,926,286 |
Cybr, CYTIP or CASP: an attempt to pinpoint a molecule's functions and names. | Over the last decade several groups, including ourself, have published a series of findings on a molecule expressed in leukocytes. The molecule was termed Cybr, CYTIP or CASP for its functions and PSCDBP for its binding properties. In this review we attempt to chronicle and combine the findings on the molecule to gain an overview of its features. | 18,926,288 |
Interferon-alpha controls IL-17 expression in vitro and in vivo. | The type I interferons interferon alpha (IFNalpha) and IFNbeta are the first line of defense potently induced upon viral infection, and at the same time are immunomodulatory cytokines bridging innate and adaptive immunity. T cells secreting interleukin-17 (IL-17) have recently been identified to regulate neutrophil-mediated inflammation, and have been implicated in the pathogenesis of experimental colitis and human inflammatory bowel disease, and are considered to regulate the inflammatory response in these models. We therefore hypothesized that type I IFNs as sentinels of viral infection might counteract the development of Th17 cells. We studied the effects of IFNalpha on IL-17 mRNA and protein expression in human peripheral blood mononuclear cells (PBMC) and during differentiation of human and murine naïve T cells into Th17 cells. In patients with ulcerative colitis (UC) treated systemically with IFNalpha, we studied colonic expression of IL-17 before and 4 weeks after therapy. IFNalpha potently suppressed IL-17 production in PBMC both at the mRNA and protein level. Th17 differentiation of human and murine naïve T cells was markedly suppressed in the presence of IFNalpha. UC patients exhibited increased IL-17 expression in colonic tissue biopsies compared to healthy controls, which was down-regulated during IFNalpha therapy. IL-17 expression in colonic tissue correlated with clinical remission in these patients. Our data suggest that IFNalpha down-regulates IL-17 expression and Th17 differentiation in vitro and in vivo. As a corollary, these effects might play a role in the mode of action of type I IFNs in the treatment of various diseases. | 18,926,293 |
Identification and characterization of human thymic cortical dendritic macrophages that may act as professional scavengers of apoptotic thymocytes. | We identify and characterize a special type of macrophage in the human thymic cortex that may act as professional scavengers of apoptotic thymocytes. These are large cells with clear cytoplasm, evenly distributed exclusively in the thymic cortex, and usually contain degraded nuclei in their cytoplasm. They are distinct from ordinary macrophages (OM) in the thymic cortex in expressing fascin, an actin-bundling protein specific for dendritic cells (DC), and in lacking lysozyme (LZM) and CD68. They are also different from DC in lacking major histocompatibility complex (MHC)-class II molecules. To distinguish them from OM and DC, we called them thymic cortical dendritic macrophages (TCDM). Both TCDM and OM are positive for DC-SIGN (CD209) and HAM56, whereas fascin(hi) MHC-class II(hi) medullary DC (mDC) are negative for these antigens. TCDM exhibit either dendritic or plump feature depending on cases examined. Plump TCDM usually contain several degraded nuclei, while dendritic TCDM contain one or two. These degraded nuclei are positive for active caspase-3 (aCasp-3), indicating that they are apoptotic thymocytes. In contrast to TCDM, LZM(hi) CD68(hi) OM are smaller round cells, distributed unevenly throughout the thymus, and do not contain apoptotic thymocytes at all. TCDM tend to adhere to capillaries with their dendrites or they make extensive contacts covering a large portion of the capillaries. Electron microscopic analysis confirmed the extensive contact between TCDM and capillaries and indicated that TCDM possess extremely electron-lucent, abundant cytoplasm with numerous tubulovesicular structures and secondary lysosomes. The finding of numerous condensed nuclei in most of the TCDM indicates that these cells represent a special type of fixed macrophages in the human thymic cortex, and that they play a central role in the clearance of apoptotic thymocytes. | 18,926,298 |
Monitoring of glucocorticoid therapy by assessment of CD14(+)CD16(+) monocytes: a case report. | Bronchiolitis obliterans with organizing pneumonia (BOOP) is a disease affecting small airways and alveoli. It is characterized by interstitial inflammation rich in foamy macrophages and by fibroblastic connective tissue expanding into the airway and alveolar lumen. We report herein on a 54-year-old male BOOP patient who was treated with glucocorticoids (GCs) and who over a 5-year period had three relapses. At diagnosis the patient showed elevated CD14(+)CD16(+) monocyte numbers (85 cells/microl) and increased serum C-reactive protein (CRP) levels (29.4 mg/l). With GC therapy both parameters decreased within a few days. Diagnosis of relapse was preceded by a rise in CD14(+)CD16(+) monocyte numbers and in CRP levels which again responded to GC treatment. We conclude that determination of CD14(+)CD16(+) monocytes is a useful marker for monitoring of BOOP diagnosis and GC therapy. | 18,926,305 |
Benzyl alcohol and ethanol can enhance the pathogenic potential of clinical Staphylococcus epidermidis strains. | Staphylococcus epidermidis is the most frequent cause of health care-associated infections, particularly in neonates and patients with indwelling catheters. The pathogenesis of infections caused by this organism is associated with its ability to form biofilms. We hypothesized that alcohol used in skin disinfectants, as well as preservative in solutions administered through catheters, can enhance biofilm formation by S epidermidis. We performed polymerase chain reaction (PCR) analysis to investigate the prevalence of ica locus in a collection of 169 commensal and clinical S epidermidis strains. Using a microtiter plate assay, we examined the effect of ethanol and benzyl alcohol on biofilm production. Quantitative real-time reverse transcriptase PCR analysis evaluated quantitative changes in gene expression. We found that ica-positive but biofilm-negative or low-grade biofilm-positive S epidermidis strains displayed induction or increase in biofilm production after incubation in media supplemented with both ethanol and benzyl alcohol. The expression of the icaADBC operon was up-regulated in the presence of alcohol. Our results suggest that biofilm production and, therefore, the pathogen potential of S epidermidis can be induced by alcohol. Considering the routine use of alcohol-based skin disinfectants and benzyl alcohol-containing solutions in hospitals, the alcohol-inducible biofilm phenotype of S epidermidis has potentially profound clinical ramifications. | 18,926,307 |
Nosocomial infections after pediatric cardiac surgery. | This study examined the rate of nosocomial infection (NI) in children who underwent cardiac surgery, and also investigated the impact of postdischarge infection surveillance. Risk factors for surgical site infections (SSIs) also were evaluated. All patients who underwent open-heart cardiac surgery in the Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland, between January 2000 and December 2002 were included. Data were collected retrospectively from hospital registries. A prospective postdischarge survey was conducted to detect SSIs arising within 30 days after surgery, as well as respiratory and gastrointestinal infections with onset within 3 days after discharge. The study included 614 procedures performed in 511 patients. A total of 80 NIs were found (overall NI rate, 6.3 per 1000 patient days), including 21 superficial and 6 deep SSIs. Multivariable analysis identified preoperative hospitalization > 48 hours and high American Society of Anesthesiologists (ASA) score as risk factors for SSI. The postdischarge study revealed 7 additional superficial SSIs, 29 respiratory infections, and 29 gastrointestinal infections; 12 patients required rehospitalization. Almost 25% of the patients had at least 1 NI. All severe NIs were detected during the postoperative hospital stay. Respiratory and gastrointestinal infections were common and often led to rehospitalization, thus increasing costs. | 18,926,309 |
Influenza vaccination coverage rate among high-risk children during the 2002-2003 influenza season. | Influenza vaccination is the primary method for preventing influenza and its complications. Characteristics of influenza vaccination coverage among high-risk children (HRC) during the 2002-2003 influenza season are described. Children aged 1 to 17 years continuously enrolled in private health insurance plans during the 2002-2003 influenza season and entered in MarketScan paid claims databases were included. Children were partitioned into 2 groups: high-risk children and nonhigh-risk children (non-HRC) based on their diagnosis history since 1998. The influenza vaccination coverage rates of both groups during the 2002-2003 influenza season were assessed by demographic, child, and provider-related variables. The influenza vaccination coverage rate was 4.63% among all sampled children. Overall, influenza vaccination coverage rates were higher among HRC (11.74%) than non-HRC (3.31%). Among children ages 12 to 23 months, HRC had lower coverage than non-HRC, but, from age 2 years onward, HRC consistently had higher coverage than non-HRC. Influenza vaccination coverage varied by geographic area, with higher coverage among children living within metropolitan areas and in the Western and the Northeast regions of the United States. Children receiving vaccination under a comprehensive insurance plan had significantly lower coverage than children served by all other plan types. Influenza vaccination coverage during the 2002-2003 influenza season was very low among all children, leaving many children at risk for influenza and influenza-related complications. Coverage was influenced by child age, insurance plan type, and area of residence. | 18,926,312 |
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