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The reliability of plain radiography in experimental fracture healing.

OBJECTIVE: To investigate the reliability of radiographs in the evaluation of healing of closed fractures. DESIGN: A closed midshaft tibial fracture was created in 40 goats and stabilized with an external fixator. The animals were assigned to four groups: no injection, injection of 1 mg osteogenic protein-1 (OP-1), 1 mg OP-1 with collagenous carrier, or carrier alone. Radiographs were performed weekly until the animals were killed after 2 and 4 weeks. Healing was evaluated using radiographs, biomechanical testing, and histological examination. All radiographs were examined by two independent observers. Interobserver agreement was calculated and radiographic scores were compared with mechanical and histological scores using regression analysis. RESULTS: Regression analysis showed poor correlation between radiographic scores and biomechanical and histological data. Correlation coefficients varied between 0.39 and 0.63. Good agreement between the observers was seen in only three parameters: visibility of the fracture line, weightbearing ability, and a combined healing parameter. CONCLUSION: Plain radiography provides poor parameters for monitoring the fracture healing process.

Animals↗

Diagnostic value of multifocal VEP using cross-validation and noise reduction in glaucoma research.

BACKGROUND: The diagnostic value of multifocal visual evoked potentials (mf VEP) in glaucoma research is still under debate. Several previous studies proclaim it to be a useful tool for clinical applications, but according to other studies, different problems (low specificity, poor records, and interindividual variation) still retard its clinical use. The aim of the present study was to examine whether the mf VEP data obtained with the RETIscan system are appropriate for formulating a classification rule for glaucoma. METHOD: We examined and evaluated 65 eyes in 38 advanced glaucoma patients and 27 normal subjects, using four occipital gold cup electrodes (cross layout) for bipolar recording and a CRT monitor (display diameter 60 degrees, chequerboard pattern reversal, 60 segments in dartboard layout) for stimulation. In each case, eight cumulative measurements (77 s each) were made. The data of the 60 segments were cross-correlated with a RETIscan-internal VEP norm ("VEP finder"), combined in 16 sectors, and evaluated via the classification technique "double-bagging" and the Wilcoxon U-test. RESULTS: In three out of the 16 sectors, the VEP amplitudes of the patients were significantly reduced (Wilcoxon U-test). Applying double-bagging on the cross-correlated data (with VEP finder) resulted in a sensitivity of 75% and a specificity of 71%, and the estimated misclassification rate was 27%. For uncorrelated data (without VEP finder), the same analysis achieved a sensitivity of about 60% and a specificity of 40%. CONCLUSIONS: Estimated sensitivity and specificity suggest that by using the RETIscan system for recording, a classification of the VEP data--i.e. a separation between normal and glaucoma subjects--is possible.

Biomedical Research↗

1,3-Butanediol-induced increases in ketone bodies and potentiation of CCl4 hepatotoxicity.

Evidence previously reported suggest that 1,3-butanediol (BD) enhances the hepatotoxic effect of a single small dose of carbon tetrachloride (CCl4) in a dose-related manner. The present study provides additional information concerning the quantitative relationship between the severity of the ketotic state produced by BD and the magnitude of the potentiation observed and emphasizes the use of ketone bodies (KB) to predict the potential hazard of the BD-CCl4 interaction. Liver damage was modulated in male Sprague-Dawley rats by varying the concentration of the BD solutions ingested prior to a CCl4 challenge (0.1 ml/kg, i.p.). These data were compared to ketone bodies in plasma, hepatic tissue and urine. BD produced a dose-dependent metabolic ketosis observable at dosages between 1.1 and 9.9 g/kg per day given for 7 days. Plasma and liver data correlated well together. Concomitantly, potentiation of the CCl4-induced liver injury was also dose-related for the same dosage range; the minimum effective dosage of BD for potentiation was estimated as 1.1 g/kg per day. The linear correlations between hepatic or plasma KB values and the indices of hepatic dysfunction (ALT, OCT) were highly significant. Using a semiquantitative method, a correlation was also found for the urinary KB data. These results suggest that plasma KB concentrations might be useful for predicting possible potentiation of the hepatonecrotic effect of CCl4 by BD.

Acidosis↗

The immunobiology of cancer immunosurveillance and immunoediting.

The last fifteen years have seen a reemergence of interest in cancer immunosurveillance and a broadening of this concept into one termed cancer immunoediting. The latter, supported by strong experimental data derived from murine tumor models and provocative correlative data obtained by studying human cancer, holds that the immune system not only protects the host against development of primary nonviral cancers but also sculpts tumor immunogenicity. Cancer immunoediting is a process consisting of three phases: elimination (i.e., cancer immunosurveillance), equilibrium, and escape. Herein, we summarize the data supporting the existence of each of the three cancer immunoediting phases. The full understanding of the immunobiology of cancer immunosurveillance and immunoediting will hopefully stimulate development of more effective immunotherapeutic approaches to control and/or eliminate human cancers.

Animals↗

An analysis of least restrictive environment placement variables in physical education.

The purpose of this study was to determine the variables related to the successful least restrictive placement of students with disabilities into physical education classes. Subjects were 470 school building representatives and 62 adapted physical education professors throughout the nation. Confidence interval estimates (95%) of school building data correlated highest on relative importance with university census data on 8 of 37 total variables: motor ability test scores, developmental scale scores, reaching individualized education program instructional objectives, special education teacher recommendation, regular physical educator recommendation, activity offerings, classroom physical accessibility, and safety considerations. These represent those variables that should be used in some "best practices" combination by school personnel in making decisions regarding relevant students' class placement within physical education least restrictive environment alternatives. In addition, staff recommendation category variables were considered more important than test score, student related, class related, and administrative category variables.

Persons with Disabilities↗

An integrated approach utilizing artificial neural networks and SELDI mass spectrometry for the classification of human tumours and rapid identification of potential biomarkers.

MOTIVATION: MALDI mass spectrometry is able to elicit macromolecular expression data from cellular material and when used in conjunction with Ciphergen protein chip technology (also referred to as SELDI-Surface Enhanced Laser Desorption/Ionization), it permits a semi-high throughput approach to be taken with respect to sample processing and data acquisition. Due to the large array of data that is generated from a single analysis (8-10000 variables using a mass range of 2-15 kDa-this paper) it is essential to implement the use of algorithms that can detect expression patterns from such large volumes of data correlating to a given biological/pathological phenotype from multiple samples. If successful, the methodology could be extrapolated to larger data sets to enable the identification of validated biomarkers correlating strongly to disease progression. This would not only serve to enable tumours to be classified according to their molecular expression profile but could also focus attention upon a relatively small number of molecules that might warrant further biochemical/molecular characterization to assess their suitability as potential therapeutic targets. RESULTS: Using a multi-layer perceptron Artificial Neural Network (ANN) (Neuroshell 2) with a back propagation algorithm we have developed a prototype approach that uses a model system (comprising five low and seven high-grade human astrocytomas) to identify mass spectral peaks whose relative intensity values correlate strongly to tumour grade. Analyzing data derived from MALDI mass spectrometry in conjunction with Ciphergen protein chip technology we have used relative importance values, determined from the weights of trained ANNs (Balls et al., Water, Air Soil Pollut., 85, 1467-1472, 1996), to identify masses that accurately predict tumour grade. Implementing a three-stage procedure, we have screened a population of approximately 100000-120000 variables and identified two ions (m/z values of 13454 and 13457) whose relative intensity pattern was significantly reduced in high-grade astrocytoma. The data from this initial study suggests that application of ANN-based approaches can identify molecular ion patterns which strongly associate with disease grade and that its application to larger cohorts of patient material could potentially facilitate the rapid identification of validated biomarkers having significant clinical (i.e. diagnostic/prognostic) potential for the field of cancer biology. AVAILIBILITY: Neuroshell 2 is commercially available from ward systems.

Astrocytoma↗

Implications of follicular neoplasms, atypia, and lesions suspicious for malignancy diagnosed by fine-needle aspiration of thyroid nodules.

OBJECTIVE: To break out subcategories of atypical and suspicious cytologic interpretations of thyroid aspirations and correlate those with final histologic diagnosis. SUMMARY BACKGROUND DATA: Fine-needle aspiration (FNA) of thyroid nodules has become the primary diagnostic tool in the initial evaluation of thyroid nodules. Management of thyroid nodules is based on statistical data correlating a specific cytologic reading with the probability of malignancy. Two particular cytologic readings that frustrate both cytopathologists and surgeons are follicular neoplasms and cells that show atypia. In most reported series, follicular neoplasms and cells showing atypia are included in a broad "suspicious" category, with reported overall malignancy rates generally between 20% and 30%. However, there is interest in determining whether these suspicious lesions can be subcategorized, allowing a more accurate assessment of the risk of malignancy. In addition, there is recent evidence that the incidence of follicular cancer may be declining in this country, possibly decreasing the probability that a "follicular neoplasm" will prove to be a follicular cancer. METHODS: From January 1994 through December 2000, 709 thyroid FNAs were performed at a single institution. Those interpreted as suspicious and the subsequent histologic reports were reviewed. From this set, four specific categories were defined, and the clinical records for patients whose cytology matched these categories form the subject of this study. These four categories are follicular neoplasms without atypia, follicular neoplasms with atypia, atypia, and suspicious for malignancy. In addition, lesions with nondiagnostic cytology were reviewed. Only lesions for which there was histologic follow-up were considered. RESULTS: Ninety-eight aspirates were categorized as follicular neoplasms without atypia, follicular neoplasms with atypia, or atypia alone. Of 74 follicular neoplasms without atypia, only 5 (6.8%) were malignant, and none of these were follicular thyroid cancers. Nine of the lesions were follicular neoplasms with atypia, and four (44.4%) of these were malignant, including two that were invasive follicular cancers. Of 15 lesions showing atypia alone, 3 (20%) were malignant, all of which were papillary thyroid cancers. Twenty-five additional patients had lesions highly suspicious for malignancy. Twenty-one (84%) of these lesions were malignant, the majority being papillary thyroid cancers. Only one was a follicular cancer. Fifty patients with nondiagnostic cytology had subsequent action taken. Thirty-one of these lesions were resected, with five (16.1%) proving to be malignant. CONCLUSIONS: Thyroid nodules whose FNA is diagnosed as highly suspicious for malignancy should be resected unless there are significant contraindications to a surgical procedure. The extremely low rate (2%) of invasive follicular cancers among all follicular neoplasms may reflect changing histologic criteria for follicular carcinoma, a true change in the disease frequency, or both. For thyroid nodules whose cytology shows a follicular neoplasm without atypia, malignancy rates of 8% or less may allow nonsurgical options, including reevaluation in selected populations. Continued efforts to correlate malignancy rates to specific cytologic criteria will allow patients to make more informed decisions regarding their medical care.

Adenocarcinoma, Follicular↗

Application of an enzyme-linked immunosorbent assay for screening of T-2 toxin-producing Fusarium spp.

Culture filtrates of Fusarium species were subjected without clean-up procedures to an indirect competitive enzyme-linked immunosorbent assay with anti-T-2 toxin monoclonal antibody. Fusarium sporotrichioides, F. poae, F. tricinctum, and F. culmorum strains were positive for T-2 toxin, with a minimum detection limit of 5 pg per assay (100 pg/ml of culture filtrate), and the assay data correlated well with the gas-liquid chromatographic data.

Antibodies, Monoclonal↗

[The clinical study of multi-slice helical CT three-dimensional reconstruction in the sphenopalatine foramen].

OBJECTIVE: Used multi-slice helical CT to observe the reconstruction of the surface structure of nasal lateral wall "sphenopalatine foramen" and compared with anatomical specimens to verify the dependability of 3D data. METHOD: The position, shape, size and their correlational data of sphenopalatine foramen of 5 cadaver heads (10 sides) in adults fixed with formalin were dissected and measured. RESULT: Multi-slice helical CT has more rapid speed of 3D reconstruction and clearer imaging. The technique of Shade surface display and Volume rendering can give very clear structure of nasal lateral wall "sphenopalatine foramen". The 3D data makes no statistic difference with anatomical measurement. The 3D data can instruct the clinic directly. CONCLUSION: Multi-slice helical CT three-dimensional reconstruction can be used to orientation of surgery.

Adult↗

Biophysical methods to monitor lens aging and pre-cataractous changes in vivo.

When monitoring for drug induced lenticular side effects and/or anti-cataract drug efficacy, it would be advantageous to detect such effects prior to the onset of a cataract. Our MRI technique can detect precataractous changes in the lens water compartments (T2 values) months to years before opacities become manifest. The in vivo human and animal studies correlate well with in vitro NMR pulse relaxation data on such lenses. The MRI technique requires 2-4 minutes per eye and provides excellent pictures of the globe as well as T2 values. These data correlate well with our in vivo lens fluorescence technique thereby providing two parameters capable of evaluating potential drug induced changes in the lens well before the cataract becomes manifest.

Adult↗

Evaluation of the lung uptake of iodine-131 HIPDM by the single-pass multiple indicator dilution technique in a rabbit model.

The first-pass lung uptake of [131I]HIPDM was studied in a rabbit model using a conventional single-pass multiple indicator dilution (SPMID) technique with [99mTc]HSA as the intravascular marker. Lung extraction of [131I]HIPDM determined by the SPMID method was saturable, decreasing from 89.5 +/- 5.8% (mean +/- s.d., n = 4) at 4 nmol kg-1 to 63.8 +/- 6.2% at 1.5 X 10(4) nmol kg-1 relative to the intravascular tracer. The first-pass extraction of [131I]HIPDM derived from gamma-camera emission imaging data correlated well (R = 0.834) with simultaneously derived SPMID data. The extraction efficiencies were 94.4 +/- 3.3 and 87.9 +/- 3.2 at 200 nmol kg-1 and 68.0 +/- 6.2 and 64.0 +/- 10.7 at 1 X 10(4) nmol kg-1 (n = 4) for the SPMID and gamma-camera methods, respectively. Analysis of the lung arterial effluent blood indicated that no appreciable de-iodination or metabolism of [131I]HIPDM, within the limits of detection, occurred during the first pulmonary transit.

Animals↗

Measurement of gastric emptying rate in humans. Simplified scanning method.

Simultaneous measurements of the gastric emptying rate of the solid and liquid phase of a dual-isotope-labeled test meal were made using a gamma camera and a simple scintillation detector, similar to that used in a hand-held probe. A simple scanning apparatus, similar to that used in a hand-held scintillation probe, was compared with simultaneous measurements made by a gamma camera in 16 healthy males. A dual-labeled test meal was utilized to measure liquid and solid emptying simultaneously. Anterior and posterior scans were taken at intervals up to 120 min using both a gamma camera and the scintillation probe. Good relative agreement between the methods was obtained both for solid-phase (correlation range 0.92-0.99, mean 0.97) and for liquid-phase data (correlation range 0.93-0.99, mean 0.97). For solid emptying data regression line slopes varied from 0.75 to 1.03 (mean 0.84). Liquid emptying data indicated that slopes ranged from 0.71 to 1.06 (mean 0.87). These results suggested that an estimate of the gamma measurement could be obtained by multiplying the scintillation measurement by a factor of 0.84 for the solid phase and 0.87 for the liquid phase. Correlation between repeat studies was 0.97 and 0.96 for solids and liquids, respectively. The application of a hand-held probe technique provides a noninvasive and inexpensive method for accurately assessing solid- and liquid-phase gastric emptying from the human stomach that correlates well with the use of a gamma camera, within the range of gastric emptying rate in the normal individuals in this study.

Adult↗

Nutritional status as a predictor of morbidity and mortality in maintenance dialysis patients.

Many epidemiologic studies indicate that protein-energy malnutrition is a strong predictor of morbidity and mortality in maintenance hemodialysis and chronic peritoneal dialysis patients. Those parameters of protein-energy malnutrition that have been most clearly associated with morbidity or mortality include serum albumin, dietary protein intake as indicated by the protein equivalent of total nitrogen appearance (PNA, also referred to as PCR), and the predialysis serum urea nitrogen. In large scale clinical surveys, low predialysis serum creatinine, cholesterol, potassium, phosphorus, calcium, and bicarbonate also correlate with increased mortality rates in maintenance hemodialysis patients. These correlations may reflect an association between dietary intake and mortality. The paucity of data correlating energy intake or body composition (e.g., total body protein or nitrogen, skeletal muscle mass, total body fat) with clinical outcome may reflect the difficulty of obtaining these data in large scale prospective or retrospective analyses. The correlation between protein-energy malnutrition and increased morbidity and mortality rates does not prove that a higher protein and/or energy intake or a more optimal body composition will improve the patient's outcome. Prospective, randomized studies will be necessary to examine this question. However, two retrospective analyses of the effect of intradialytic parenteral nutrition on mortality rates in maintenance hemodialysis patients are consistent with the thesis that increased nutrient intake will reduce mortality in maintenance hemodialysis patients. Methods for assessing protein-energy nutritional status are discussed. There are essentially no data indicating that the more complicated and expensive techniques for nutritional assessment have important advantages over the more simple methods for the clinical management of maintenance dialysis patients.

Creatinine↗

Comparisons of spontaneous pain and tenderness in patients with primary fibromyalgia.

Pain was assessed in 47 patients with fibromyalgia in the University Rheumatology Clinic in Basle with the aid of three different techniques. First, a simple visual analog scale was used, later a body diagram on which patients could indicate pain separately in different regions of the body (pain score) and, finally, dolorimetric measurements at 56 typical PFS tender points. After four weeks of therapy, pain was again scored by patients using these techniques. The changes in assessment were compared with the aid of Spearman correlation. Data recorded with the aid of the body diagram correlated better with dolorimetric findings than did the results obtained from a simple visual analog scale. The severity of the disease can be more objectively assessed using these three techniques than it can using only the visual analog scale. In particular, the pain score and dolorimetry make possible a clear assessment of the value of therapeutic regimens.

Female↗

Electrochemical Parametrization in Sandwich Complexes of the First Row Transition Metals.

Applying the ligand electrochemical parameter approach to sandwich complexes and standardizing to the Fe(III)/Fe(II) couple, we obtained E(L)(L) values for over 200 pi-ligands. Linear correlations exist between formal potential (E degrees ) and the summation operatorE(L)(L) for each metal couple. In this fashion, we report correlation data for many first row transition metal couples. The correlations between the E(L)(L) of the substituted pi-ligand and the Hammett substituent constants (sigma(p)) are also explored.

Journal Article↗

Reconstruction of gene networks using Bayesian learning and manipulation experiments.

MOTIVATION: The analysis of high-throughput experimental data, for example from microarray experiments, is currently seen as a promising way of finding regulatory relationships between genes. Bayesian networks have been suggested for learning gene regulatory networks from observational data. Not all causal relationships can be inferred from correlation data alone. Often several equivalent but different directed graphs explain the data equally well. Intervention experiments where genes are manipulated can help to narrow down the range of possible networks. RESULTS: We describe an active learning algorithm that suggests an optimized sequence of intervention experiments. Simulation experiments show that our selection scheme is better than an unguided choice of interventions in learning the correct network and compares favorably in running time and results with methods based on value of information calculations.

Algorithms↗

Familial risk of pancreatic cancer.

BACKGROUND: Pancreatic cancer is the fifth leading cause of cancer-related mortality in the United STATES: Although smoking and age are known risk factors for pancreatic cancer, several case reports and case-control studies have suggested that there is also a familial risk. We evaluated whether a family history of pancreatic cancer increases the risk of pancreatic cancer in first-degree relatives and whether smoking and younger age at cancer diagnosis further increase this risk. METHODS: We conducted in-person interviews with 247 patients ("case probands") with pancreatic cancer and 420 population-based control probands to collect risk factor data and pancreatic cancer family history for 1816 first-degree relatives of the case probands and 3157 first-degree relatives of the control probands. We analyzed the data by unconditional logistic regression models, with adjustment for correlated data by use of generalized estimating equations. All statistical tests were two-sided. RESULTS: A positive family history of pancreatic cancer (i.e., being related to a case proband) or ever-smoking cigarettes approximately doubled the risk of pancreatic cancer (relative risk [RR] = 2.49; 95% confidence interval [CI] = 1.32 to 4.69; RR = 2.04; 95% CI = 1.09 to 3.83, respectively). The RR increased to 8.23 (95% CI = 2.18 to 31.07) for relatives who ever smoked and were related to a case proband who was diagnosed before age 60 years. CONCLUSION: Routine questioning of patients about a family history of pancreatic cancer, the age of onset of this cancer in their relatives, and the patient's smoking status may identify individuals at high risk of pancreatic cancer. Future research exploring the genetic and environmental interactions associated with the risk of pancreatic cancer is critically important.

Adenocarcinoma↗

Taxonomy of Australian clinical isolates of the genus Photorhabdus and proposal of Photorhabdus asymbiotica subsp. asymbiotica subsp. nov. and P. asymbiotica subsp. australis subsp. nov.

The relationship of Photorhabdus isolates that were cultured from human clinical specimens in Australia to Photorhabdus asymbiotica isolates from human clinical specimens in the USA and to species of the genus Photorhabdus that are associated symbiotically with entomopathogenic nematodes was evaluated. A polyphasic approach that involved DNA-DNA hybridization, phylogenetic analyses of 16S rRNA and gyrB gene sequences and phenotypic characterization was adopted. These investigations showed that gyrB gene sequence data correlated well with DNA-DNA hybridization and phenotypic data, but that 16S rRNA gene sequence data were not suitable for defining species within the genus Photorhabdus. Australian clinical isolates proved to be related most closely to clinical isolates from the USA, but the two groups were distinct. A novel subspecies, Photorhabdus asymbiotica subsp. australis subsp. nov. (type strain, 9802892T=CIP 108025T=ACM 5210T), is proposed, with the concomitant creation of Photorhabdus asymbiotica subsp. asymbiotica subsp. nov. Analysis of gyrB sequences, coupled with previously published data on DNA-DNA hybridization and PCR-RFLP analysis of the 16S rRNA gene, indicated that there are more than the three subspecies of Photorhabdus luminescens that have been described and confirmed the validity of the previously proposed subdivision of Photorhabdus temperata. Although a non-luminescent, symbiotic isolate clustered consistently with P. asymbiotica in gyrB phylogenetic analyses, DNA-DNA hybridization indicated that this isolate does not belong to the species P. asymbiotica and that there is a clear distinction between symbiotic and clinical species of Photorhabdus.

Adult↗