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Prognostic factors of clinical interest in poorly differentiated carcinomas of the thyroid.

Poorly differentiated (PD) carcinomas of the thyroid represent an heterogeneous but distinct group of tumors, clinically and histopathogenetically intermediate between follicular-derived well-differentiated and anaplastic carcinomas. Although the diagnostic criteria for inclusion in the PD tumor group are far from well established, and despite controversies on nomenclature, the identification of PD carcinomas as tumors with trabecular/insular/solid (TIS) growth patterns and high-grade histopathological parameters is generally accepted. Recent data on large tumor series were focused on the recognition of clinicopathological features able to predict aggressive behavior. Patient age >45 yr, the presence of necrosis (either focal or extensive), and mitotic count >3 per 10 HPF have been found to be the most influent prognostic parameters. Therefore, as also proposed for other thyroid carcinomas (e.g., papillary carcinoma) grading of PD carcinomas on the basis of these latter parameters is encouraged to select those cases with a high risk of poor outcome.

Adenocarcinoma, Follicular↗

Differences in survivability among F344 rats.

Important parameters to identify and develop appropriate animal models for longevity science include survivability, age-related disorders, and easy handling of aged individuals. It is found that F334/Du and F344/N have distinctive strain difference in these parameters. The finding suggests F334/Du and F344/N, even though they are historically siblings, need clearly separate identification when used as animal models for aging science, in particular, longevity science.

Aging↗

Periodontitis in humans and non-human primates: oral-systemic linkage inducing acute phase proteins.

BACKGROUND: The acute phase response (APR) represents a systemic counterpart to the localized inflammatory response. This report describes patient-oriented and non-human primate model studies to determine the effect of periodontal disease on systemic acute phase proteins (APP). METHODS: Patient-oriented studies included comparison of the levels of APP, using enzyme-linked immunosorbent assay (ELISA), with the presence and severity of periodontitis in localized chronic periodontitis (LCP), generalized aggressive periodontitis (GAP), and Sjogren's syndrome (SS) patients. The non-human primate experiments evaluated the serum level of APPs under natural conditions, following mechanical hygiene, experimental gingivitis, and during ligature-induced periodontitis. RESULTS: Analysis of the LCP population showed what appeared to be a threshold of periodontal disease severity required for elevating the C-reactive protein (CRP) and haptoglobin (HG). The results demonstrated a significant elevation in CRP in the GAP versus the control groups, as well as lower levels of all mediators in healthy non-smokers (HNS) versus smokers (HS), suggesting that these systemic inflammatory markers were altered in response to challenge by noxious materials from smoking. Significantly different levels of CRP, HG, and alpha1-antiproteinase were noted in the SS patients suggesting that the autoimmune aspects of Sjögren's syndrome may impact upon oral health and systemic responses. Parallel evidence was also obtained from the primate studies. Providing mechanical oral hygiene, which significantly lowered clinical inflammation and bleeding of the gingiva, decreased the serum APP levels. Both CRP and fibrinogen were significantly elevated during progressing periodontitis, which also appeared to have an impact on serum lipids and lipoproteins. CONCLUSIONS: These findings supported results relating chronic oral infections and the inflammation of periodontitis as contributors to and/or triggers for systemic inflammatory responses. Finally, similarities in the clinical and microbiological parameters of gingival inflammation and periodontitis between humans and non-human primates was extended to identification of changes in serum APP in the non-human primates that appeared to be in direct response to the induction of progressing periodontitis. These systemic changes provide additional evidence for the biological plausibility of periodontal infections contributing to various systemic diseases.

Acute-Phase Proteins↗

Plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in greyhounds.

OBJECTIVE: To determine the plasma pharmacokinetics and synovial fluid concentrations after oral administration of single and multiple doses of celecoxib in Greyhounds. ANIMALS: 7 adult Greyhounds. PROCEDURES: Dogs received celecoxib (median dose, 11.8 mg/kg [range, 11.5 to 13.6 mg/kg], PO, q 24 h) for 10 days. Blood samples were collected prior to administration of celecoxib and serially for 24 hours after the 1st and 10th doses were administered. A synovial joint catheter was placed into a stifle joint in each dog for collection of synovial fluid samples. Concentrations of celecoxib in plasma and synovial fluid were quantified by use of a validated liquid chromatography/mass spectrometry method. Identification of hydroxy- and carboxyl-celecoxib in plasma and synovial fluid was also performed. Pharmacokinetic parameters were determined by use of noncompartmental analysis. RESULTS: Administration of multiple doses of celecoxib resulted in a significant decrease (40%) in median area under the curve (AUC) values and a corresponding decrease in median maximum concentrations (Cmax; 2,620 to 2,032 ng/mL) between the 1st and 10th doses. Synovial fluid concentrations were less than the corresponding plasma concentrations at all times except 24 hours after administration of the 10th dose of celecoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Celecoxib distributes into the synovial fluid of Greyhounds. Although the exact mechanism for the decreases in AUC and Cmax is not known, results suggested that the plasma pharmacokinetics of celecoxib are different after administration of multiple doses in Greyhounds. These findings warrant further investigation on the absorption, distribution, metabolism, and elimination of celecoxib in Greyhounds and other breeds of dogs.

Animals↗

Functional Annotation Routines Used by ABRF Bioinformatics Core Facilities - Observations, Comparisons, and Considerations.

The functional annotation of gene lists is a common analysis routine required for most genomics experiments, and bioinformatics core facilities must support these analyses. In contrast to methods such as the quantitation of RNA-Seq reads or differential expression analysis, our research group noted a lack of consensus in our preferred approaches to functional annotation. To investigate this observation, we selected 4 experiments that represent a range of experimental designs encountered by our cores and analyzed those data with 6 tools used by members of the Association of Biomolecular Resource Facilities (ABRF) Genomic Bioinformatics Research Group (GBIRG). To facilitate comparisons between tools, we focused on a single biological result for each experiment. These results were represented by a gene set, and we analyzed these gene sets with each tool considered in our study to map the result to the annotation categories presented by each tool. In most cases, each tool produces data that would facilitate identification of the selected biological result for each experiment. For the exceptions, Fisher's exact test parameters could be adjusted to detect the result. Because Fisher's exact test is used by many functional annotation tools, we investigated input parameters and demonstrate that, while background set size is unlikely to have a significant impact on the results, the numbers of differentially expressed genes in an annotation category and the total number of differentially expressed genes under consideration are both critical parameters that may need to be modified during analyses. In addition, we note that differences in the annotation categories tested by each tool, as well as the composition of those categories, can have a significant impact on results.

Computational Biology↗

Elastic registration of medical images through multiquadric method.

OBJECTIVE: To improve the precision and reliability of elastic registration of the medical images and to simplify the registration process. METHODS: Previous study concerning elastic registration mostly focused on manual selection of the landmarks and then use of adequate interpolating for elastic transformation. The landmarks extraction, however, was prone to error that often showed impact on the registration results, besides the difficulty and time consumption of manual identification of the landmarks. On the basis of Multiquadric method that allowed smooth adjustment of the parameters, we utilized a semi-automatic method to extract the landmarks by combining these 2 steps, and proposed a novel registration method. RESULTS: Using this method for medical image elastic registration, rapid and accurate registration between standard and deformed images was achieved. CONCLUSION: The method proposed presently is accurate, convenient and reliable.

Automation↗

[The benign chronic pain syndrome. Diagnostic subgroups, screening parameters, biographical disposition].

The concept that all pain must have an organic cause if not the pain is not real, is still very common in medical practice. For chronic pain this leads to big costs by repeated technical examinations and often even to iatrogenic injury to the patient as a result of diagnostic or therapeutic interventions. Psychogenic pain patients are particularly afflicted by this process of chronification. The results of a study investigating 151 chronic patients show, that psychogenic pain patients (PP, n = 75) are significantly different from those whose pain was caused by organic factors (OP, n = 35) regarding their development in childhood and adolescence (in the sense of a marked emotional deprivation). Including additional parameters raised by a structured interview (SBAS) and the trait-score of the STAI an identification of PS is possible with high sensitivity and specificity (about 95 percent). By the aid of the maturity of defence mechanisms three taxonomic subgroups in PP can be differentiated (type A, B, C). Between these types there are significant differences regarding illness behaviour (e.g. medication abuse, "doctor shopping") and responsiveness to a psychological pain interpretation. The results confirm the necessity of a differentiation of chronic pain patients as to the etiology and pathogenesis and furnish even the physician without psychosomatic education with diagnostic criteria relatively simple to raise. By these criteria a prevention of chronification in a lot of pain patients is possible. Derived from the results a pathogenic model for psychogenic pain is developed.

Adaptation, Psychological↗

Nutritional management of patients with kidney stones.

The nutritional management of individuals with recurrent calcium urolithiasis requires an individualized approach to the establishment of long-term goals. Diet therapy should be instituted only after careful consideration of serial metabolic evaluation of blood and urine parameters, along with stone analysis data. Interval monitoring of patient progress provides an opportunity for the identification and correction of clinical problems associated with the establishment of long-term goals.

Calcium↗

NAD kinase interaction with the activator--glutamate dehydrogenase.

An electrophoretically homogeneous preparation of the NAD kinase activating factor was isolated from rabbit liver and its physico-chemical properties were investigated. The similarity of molecular weights of the activator subunit and hexamer, pI values, the number of SH-groups to the corresponding parameters for glutamate dehydrogenase and the glutamate dehydrogenase activity demonstrated by this factor allowed for the identification of the NAD kinase activating factor as glutamate dehydrogenase. Using three independent methods, the formation of the NAD kinase--glutamate dehydrogenase complex was shown. Both the oligomeric and monomeric (subunit) forms of NAD kinase were found to be able to form complexes with glutamate dehydrogenase.

Animals↗

Three-dimensional manometric imaging of the lower esophageal sphincter.

The lower esophageal sphincter provides a pressure barrier between the negative intrathoracic and positive intra-abdominal pressure environment. The resistance of the lower esophageal sphincter to reflux of gastric juice is determined by the integrated effects of radial pressures exerted over the entire length of the sphincter. This can be best quantitated by manometry with radially oriented pressure transducers and calculation of the SPVV (ie, the volume of the 3D sphincter pressure image). Validation studies have shown that the SPVV is superior to standard parameters of sphincter strength (ie, sphincter resting pressure, overall length, and abdominal length) and improves the identification of patients that will benefit from an anti-reflux procedure. This is particularly so in patients with subtle sphincter defects and patients with increased esophageal acid exposure and no mucosal injury on endoscopy. In addition, asymmetry of the sphincter that may contribute to incompetence of the cardia can only be detected by 3D manometric sphincter imaging. The effect of an anti-reflux procedure in controlling reflux is dependent on restoration of the defective 3D sphincter pressure image. Failure to do so is associated with recurrent or persistent reflux. 3D sphincter imaging can also illustrate the severely asymmetric and hypertensive sphincter in patients with achalasia and the effect of myotomy with or without a concomitant anti-reflux procedure on the sphincter pressure profile.

Diagnostic Imaging↗

[Correlations between left atrial size and parameters of averaged atrial signal in patients with paroxysmal atrial fibrillation in the course of ischemic heart diseases].

The aim of this study was to assess the correlation between left atrial size and atrial signal-averaged electrocardiogram (ALP) in time-domain and frequency analysis in patients with paroxysmal atrial fibrillation (PAF) during ischaemic heart disease (IHD). The study population consisted of 75 patients with PAF during IHD who were divided into two groups; gr. I (left atrial dimension 40 mm) and gr. II (left atrial dimension 40 mm). The control group (gr. III) consisted of 50 healthy subjects. Recording of ALP was carried out by HIPEC-200HA. The high gain ECG was recorded during basic rhythm with orthogonal Frank leads X,Y,Z. These signals were amplified, averaged and filters. The filtered signals were combined into a vector magnitude and time-domain and frequency analysis was done. These findings suggest that the size of the left atrium does not change time-domain and frequency parameters of ALP in patients with PAF and IHD. We noticed significant influence of IHD on these parameters. On the other hand frequency analysis of ALP did not show any uselessness in diagnostic identification of patients with PAF during IHD and healthy subjects.

Adult↗

Speech discrimination via cochlear implants with two different digital speech processing strategies: preliminary results for 7 patients.

The following processing strategies have been implemented on an experimental laboratory system of a cochlear implant digital speech processor (CIDSP) for the Nucleus 22-channel cochlear prosthesis. The first approach (PES, Pitch Excited Sampler) is based on the classical channel vocoder concept whereby the time-averaged spectral energy of a number of logarithmically spaced frequency bands is transformed into appropriate electrical stimulation parameters for up to 22 electrodes. The pulse rate at any electrode is controlled by the voice pitch of the input speech signal. The pitch extraction algorithm calculates the autocorrelation function of a lowpass-filtered segment of the speech signal and searches for a peak within a specified time window. A random pulse rate of about 150 to 250 Hz is used for unvoiced speech portions. The second approach (CIS, Continuous Interleaved Sampler) uses a stimulation pulse rate which is independent of the input signal. The algorithm scans continuously all specified frequency bands (typically between 4 and 22) and samples their energy levels. Evaluation experiments with 7 experienced cochlear implant users showed significantly better performance in consonant identification tests with the new processing strategies than with the subjects' own wearable speech processors whereas improvements in vowel identification tasks were rarely observed. Modifications of the basic PES- and CIS-strategies resulted in large variations of identification scores. Information transmission analysis of confusion matrices revealed a rather complex pattern across conditions and speech features. No final conclusions can yet be drawn. Optimization and fine-tuning of processing parameters for these coding strategies require more data both from speech identification and discrimination as well as psychophysical experiments.

Acoustic Stimulation↗

Duplex ultrasound criteria for the identification of carotid stenosis should be laboratory specific.

BACKGROUND AND PURPOSE: Published criteria for the determination of carotid stenosis have been widely applied by vascular laboratories. We compared two vascular laboratories and their duplex ultrasound (DU) machines in terms of their overall diagnostic performance and the optimal criteria to identify patients who have a 70% to 99% stenosis of the internal carotid artery. METHODS: Measurements of stenosis by DU and angiography were compared for 123 carotid arteries (60 arteries, laboratory A; 63 arteries, laboratory B). Receiver operating characteristic (ROC) curves were created, and the areas under the ROC curves and the optimal criteria for determining a 70% to 99% stenosis were compared. Multiple regression analysis was used to measure the effect of laboratory on the relationship between angiographic stenosis and DU velocity parameters. RESULTS: Areas under the ROC curves were similar for both laboratories (0.89 to 0.90, laboratory A; 0.90 to 0.92, laboratory B). However, the optimal criterion for the identification of a 70% to 99% carotid stenosis was different for each laboratory. For most velocity parameters, based on regression analyses, the predicted percent angiographic stenosis for laboratory A was significantly greater than that for laboratory B. In addition, performance differed between the laboratories when established criteria from the literature were applied. CONCLUSIONS: Two vascular laboratories with similar diagnostic accuracy by ROC analysis have markedly different "optimal" DU criteria. For a given angiographic stenosis, velocities in one laboratory were consistently greater than those in the other laboratory. Laboratory-specific criteria rather than published criteria should be used to identify patients with internal carotid artery stenoses.

Aged↗

Identification of relevant prognostic histopathologic features in 69 intracranial ependymomas, excluding myxopapillary ependymomas and subependymomas.

BACKGROUND: The results of attempts to identify histopathologic parameters that contribute to the clinical outcome of patients with ependymomas have been controversial. This may be due to the relative rareness of ependymomas. Furthermore, in many investigations, myxopapillary ependymomas and subependymomas were included and may have confounded results, because those tumors should be considered clinicopathologic entities distinct from the other ependymomas. METHODS: In this retrospective study, the influence of the histologic subtype of ependymoma and of individual histologic features on the outcome of 69 patients with ependymomas was investigated. Myxopapillary ependymomas, subependymomas, and ependymomas with spinal localizations were excluded from the analysis. The ependymomas were subdivided into cellular, papillary, clear cell, and tanycytic subtypes. The study extended over a period of 30 years. RESULTS: No differences in clinical outcome between the four histologic subtypes of ependymomas were revealed. Neither tumor localization (either infratentorial or supratentorial), patient age, nor gender affected survival. The survival of patients who underwent complete tumor resection differed significantly from that of patients who underwent partial resection. In univariate analysis, the features of nuclear atypia, the mitotic index, and the MIB-1 labeling index (LI) significantly influenced survival. With regard to survival, the presence of microcysts, blood vessel density, and the feature of vascular hyalinization demonstrated a trend but did not reach significance. In multivariate analysis, only the mitotic index and the MIB-1 LI were identified as factors with independent prognostic significance (P = 0.027 and P = 0.023, respectively). Both proliferation indices were correlated strongly with each other. CONCLUSIONS: The results of the univariate analysis indicated that, for patients with intracranial ependymoma, nuclear atypia, the mitotic index, and the MIB-1 LI significantly influenced survival. In the multivariate analysis, the mitotic index and the MIB-1 LI were the only features that had independent prognostic significance. Because both showed strong correlations, only one of them should be included in a grading scheme for intracranial ependymomas.

Adolescent↗

In vivo measurement of ANP overall turnover and identification of its main metabolic pathways under steady state conditions in humans.

Using a tracer method, we evaluated, in vivo, the main turnover parameters and the main metabolic pathways of ANP in 10 normal subjects. HPLC was used to purify the labeled hormone and the principal labeled metabolites present in venous plasma samples collected at determined times after tracer injection. The main ANP kinetic parameters were derived from the disappearance curves of [125I] ANP, which were satisfactorily fitted by a biexponential function in all subjects. Newly produced ANP initially distributes in a large, plasma equivalent space (10.9 +/- 3.6 l/m2 body surface); the hormone rapidly leaves this space due to both degradation and to distribution in peripheral spaces. The mean residence time in the body (19.4 +/- 19.8 min) and the plasma equivalent total distribution volume (28.2 +/- 11.5 l/m2) indicate that ANP is also widely distributed outside the initial space in humans (circulating ANP is no more than 1/15 of the body pool). Metabolic clearance rate values were distributed across a wide range (from 740 ml/min/m2 to 2581 ml/min/m2, mean 1849 ml/min/m2), and were shown to strongly correlate (R = 0.962) with the daily urinary excretion of sodium. A complete separation of labeled ANP from its labeled metabolites was achieved by the HPLC technique; at least 3 different peaks due to labeled metabolites in vivo produced from the injected [125I]ANP1-28 were found. The first chromatographic peak eluted showed an identical elution time to monoiodotyrosine. At least two other peaks due to in vivo generated labeled metabolites were well identified in the chromatograms: one peak (coeluting with labeled COOH-terminal tripeptide, H-Phe-Arg-Tyr-OH) was eluted ahead and one (coeluting with labeled peptide fragments ANP7-28, ANP13-28, and ANP18-28) behind the elution peak of the labeled ANP. The peak of labeled tyrosine appearing in the plasma ranged between 3 and 5 min after tracer injection; the other two peaks of radioiodinated metabolites showed their highest activity in the first sample (1.5 min), suggesting an earlier occurrence of their peaks. These labeled metabolites seem to be intermediate peptides, between the intact circulating form of the hormone and the final labeled metabolite (tyrosine), which is the last amino acid of the peptide hormone, produced in vivo after injection of the tracer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Identification and measurement of genomic biomarkers of nephrotoxicity.

An accelerated pace for drug discovery and development requires the application of measurements of novel parameters for drug-induced toxicity. Genomic biomarkers can contribute to this process as indicators or predictors of toxicity. Transcript levels for genes such as the kidney injury molecule have been identified and evaluated as genomic biomarkers of nephrotoxicity.

Animals↗

Physiologic identification of eighth nerve subdivisions: direct recordings with bipolar and monopolar electrodes.

The purpose of this study was to determine stimulation and recording parameters that maximize differences in evoked responses recorded between the cochlear nerve and the surrounding tissues. Click-evoked potentials were obtained using monopolar and bipolar recording electrodes placed directly on the exposed eighth nerve of anesthetized cats. Responses were compared as stimulus intensity, electrode location, and bipolar electrode orientation and interelectrode spacing were systematically varied. Wave amplitudes increased monotonically with intensity for both monopolar and bipolar configurations, but bipolar configurations exhibited greater selectivity in differentiating cochlear from vestibular subdivisions. The optimal stimulus intensity was 70 to 80 dB peak sound pressure level (pSPL). Monopolar recordings were often confounded by activity originating at remote sites, typically the cochlear nucleus and (for recording sites on the vestibular nerve) the cochlear nerve. Bipolar response amplitudes increased with interelectrode spacing and were largest when electrodes were oriented parallel to the long axis of the nerve. Extrapolation of empirical data indicated that amplitudes of bipolar responses would be maximal at an electrode separation of 7.5 mm. Cochlear nerve conduction velocity, calculated from wave latencies at each of the two monopolar electrodes, was 11.6 +/- 1.6 m/sec.

Animals↗

Tidal breath analysis for infant pulmonary function testing. ERS/ATS Task Force on Standards for Infant Respiratory Function Testing. European Respiratory Society/American Thoracic Society.

The aim of this position paper is to provide recommendations pertaining to software and equipment requirements when analysing tidal breathing measurements in infants. These guidelines cover numerous aspects including terminology and definitions, equipment, data acquisition and analysis, and reporting of results, and highlight areas in which further research is needed before consensus can be reached. When collecting tidal breathing data in infants and children, equipment dead space and resistance must be minimized, all sources of leak eliminated, and a flowmeter with appropriate frequency response and linearity employed. Inspired gases should be corrected to body temperature, barometric pressure and saturated with water vapour conditions and efforts made to eliminate the various sources of drift in volume that can occur. In addition, the analogue-to-digital converter used to sample data must be capable of adequately resolving the highest and lowest flows required by the study. An adequate sampling rate must be used; 50-100 Hz may be sufficient for the determination of timing and volume parameters, especially in older infants, but rates of 200 Hz are recommended for analysis of the tidal breathing flow/volume loop and other sensitive parameters such as time to peak tidal expiratory flow/expiratory time. The potentially most troublesome aspect of tidal breath analysis from the computational point of view is the identification of the beginning and end of inspiration and expiration. Once methods and equipment for the measurement and analysis of tidal breathing in infants have been standardized, there is an urgent need to establish appropriate reference ranges for various key parameters so that they may be used more effectively in the clinical setting. Implementation of these recommendations should help to ensure that such measurements are as accurate as possible and that more meaningful comparisons can be made between data collected in different centres or with different equipment.

Child↗