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Biomedical Technology↗
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Phenytoin and phenobarbital assayed by the ACCULEVEL method compared with EMIT in an outpatient clinic setting.
The ACCULEVEL (Syntex) therapeutic drug assay technique was evaluated for phenytoin and phenobarbital in 30 patients with epilepsy who attended a neurology outpatient clinic. This finger-prick whole blood method is calibrated by the manufacturer to give assay results equivalent to plasma drug concentration. The results were compared with EMIT (Syva) technique measurements on the plasma from venous blood drawn simultaneously. The results presented show regression lines of y = 0.91x + 10.8, (r2 = 0.92) and y = 0.97x + 5.01, (r2 = 0.77) for phenytoin and phenobarbital (microM), respectively, when the ACCULEVEL finger-prick blood assay was compared with the EMIT venous plasma assay. Acceptable precision and accuracy data are presented for replicated ACCULEVEL assays. The ACCULEVEL method was found to be reliable when performed by a laboratory technician and provides a very convenient quantitative drug assay that could easily be performed by a variety of individuals at a site remote from laboratory facilities.
Humans↗
Improved liquid chromatographic fluorescence method for estimation of plasma sotalol concentrations.
This article reports a modified liquid chromatographic fluorescence assay that has proved in our laboratory to give robust performance for the purposes of therapeutic drug monitoring. The sample preparation involves extraction of alkalinized plasma into 1-pentanol/chloroform and back extraction into HCl. Acceptable reproducibility and accuracy data are presented over the concentration range normally encountered in patient samples. The detection limit (25 ng/ml) is approximately one-tenth the lowest calibration standard used in our laboratory for quantitating patient pre-dose specimens, making the method applicable to pharmacokinetic studies.
Chromatography, Liquid↗
Disembedding performance and recognition memory in autism/PDD.
This study explored the claim that superior disembedding performance in autism reflects "less capture by meaning" and/or reduced "central coherence" [Shah & Frith, Journal of Child Psychology & Psychiatry, 24, 613-620 (1983); Shah & Frith, Journal of Child Psychology & Psychiatry, 34, 1351-1364 (1993)]. Meaningless as well as meaningful disembedding contexts were used, and memory for contextual information was examined. Neither qualitative (search strategy) nor quantitative (RT or accuracy) data indicated that high-functioning individuals with autism/PDD were superior to younger, developmentally matched controls. For both groups, disembedding was slowest from meaningful contexts, which generally were remembered best. No evidence was provided for "less capture by meaning" or reduced "central coherence" in autism/PDD, raising the possibility that earlier findings reflect a developmental, rather than a stable autism-specific, phenomenon.
Adolescent↗
Diagnostic value of anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease.
OBJECTIVES: Correct diagnosis of inflammatory bowel disease (IBD), especially the differentiation between Crohn's disease (CD) and ulcerative colitis (UC), is highly important toward treatment and prognosis. Serological markers are noninvasive diagnostic tools that could be of value in differentiating CD from UC, in cases of indeterminate colitis, and in the identification of subgroups in IBD. The aim of this study was to evaluate the diagnostic accuracy of perinuclear antineutrophil cytoplasmic (pANCA) and anti-Saccharomyces cerevisiae antibodies (ASCA) for IBD. METHODS: ASCA and pANCA were studied in a large cohort of consecutive IBD patients (n = 582: 407 CD, 147 UC, and 28 indeterminate colitis), patients with non-IBD diarrheal illnesses (n = 74), and healthy controls (n = 157). An indirect immunofluorescence technique and a standardized ELISA were performed for detection of pANCA and ASCA, respectively. RESULTS: Prevalence of ASCA and pANCA was high in CD patients (59.7%) and UC (49.7%) patients, respectively. Positivity for both markers was significantly lower in healthy and non-IBD controls. Accuracy data (sensitivity, specificity, PPV, and NPV, respectively) for differentiating IBD from controls are as follows: ASCA+: 60% (243/407), 91% (345/378), 88% (243/276), and 68% (345/509); pANCA+: 50% (73/147), 95% (605/638), 69% (73/106), and 89% (605/679); ASCA+/pANCA-: 56% (229/407), 94% (355/378), 91% (229/252), and 67% (355/533); and pANCA+/ASCA-: 44% (65/147), 97% (620/638), 78% (65/83), and 88% (620/702). CONCLUSIONS: Specificity of serological markers for IBD is high, but low sensitivity makes them less useful as diagnostic tests. The combination of tests is probably more powerful, although, clinical subgroups still need to be defined. The usefulness of these markers in indeterminate colitis needs to be studied prospectively.
Adolescent↗
Antisaccades and task switching: studies of control processes in saccadic function in normal subjects and schizophrenic patients.
Executive functions allow us to respond flexibly rather than stereotypically to the environment. We examined two such functions, task switching and inhibition in the antisaccade paradigm, in two studies. One study involved 18 normal subjects; the other, 21 schizophrenic patients and 16 age-matched controls. Subjects performed blocks of randomly mixed prosaccades and antisaccades. Repeated trials were preceded by the same type of trial (i.e., an antisaccade following an antisaccade), and switched trials were preceded by a trial of the opposite type. We measured accuracy rate and latency as indices of processing costs. Whereas schizophrenic patients had a threefold increase in error rate for antisaccades compared to normals, the effect of task switching on their accuracy did not differ from that in normal subjects. Moreover, the accuracy rate of trials combining antisaccade and task switching was equivalent to a multiplication of the accuracy rates from trials in which each was done alone. Schizophrenic latencies were disproportionately increased for antisaccades, but again they were no different from normal subjects in the effect of task switching. In both groups the effect of task switching on antisaccades was a paradoxical latency reduction. We conclude that the executive dysfunction in schizophrenia is not generalized but selective, sparing task switching from exogenous cues, in which the switch is limited to a stimulus-response remapping. The accuracy data in both groups support independence of antisaccade and task-switching functions. The paradoxical task-switching benefit in antisaccadic latency effects challenges current models of task switching. It suggests either carryover inhibition by antisaccadic performance in the prior trial or facilitation of antisaccades by simultaneous performance of other cognitive operations.
Attention↗
Kinetics of renin-antirenin reaction: micromethods for the assay of renin and antirenin.
Indirect micromethods were designed for the assay of human renin (lower limit 0.25 times 10-4 U and of antirenin to human renin (lower limit 3 times 10-4 U), with the rat used for the bioassay of the angiotensin produced by the action of renin on renin substrate. This made possible the assay of unusually small amounts (0.01 mu1) of serum for antirenin. The Michaelis-Menten concept of a dissociating complex can be applied to the antireninrenin reaction: the rate constants for the formation and for the breakdown of the complex were k1 equal to 1.65 (ml/U antirenin per min) and k3 equal to 1.97 times 10-3 (U inactivated renin/U antirenin per min), respectively; the apparent Michaelis constant was 12 times 10-4 (U renin/ml). A second method of analysis was also applied by assuming the formation of a rather tight complex, with antirenin functioning as an irreversible inactivator of renin. Both methods of analysis yielded practically the same rate constant (k1 equal to 1.65 and k1 equal to 1.71), but the treatment according to the Michaelis-Menten equation affords a slightly better fit of the experimental data (accuracy equal to plus or minus 15.5 percent) than the second method of calculation (accuracy equal to plus or minus 21.6 percent).
Angiotensin II↗
Interactive neural-network-assisted screening. An economic assessment.
OBJECTIVE: To apply clinical effectiveness estimates of interactive, neural network-assisted (INNA) screening to economic cervical cancer screening models to assess the economic impact of using this technology. STUDY DESIGN: Estimates of the sensitivity of INNA screening were drawn from a recently completed comprehensive synthesis of the INNA literature and applied to the Computer Model for Designing CANcer ConTROL Programs-based Cervical Cancer Screen economic model. The economic analysis was conducted from a modified payer perspective using costs borne by payers combined with patient deductibles and copayments. Costs of treating cervical cancer were updated to 1997 values using the medical care component of the Consumer Price Index. The model was run for a cohort of women starting at age 20 and screened on a triennial schedule through age 75. RESULTS: In the primary analysis (sensitivity of unassisted manual examination assumed to be 85%), the ratios found in this investigation varied from approximately $35,000 to $80,000 per life year saved, with the preponderance of ratios < $50,000 per life year saved. These results were sensitive to estimates of sensitivity of unassisted manual screening but not to estimates of treatment costs. CONCLUSION: This investigation applied accuracy data on INNA rescreening to a model of the cost-effectiveness of cervical cancer screening. The results support the use of INNA rescreening as an appropriate expenditure of resources to identify missed cases of cervical epithelial abnormalities and potential cervical cancer.
Adult↗
Evaluation of a quantitative solid phase reagent system for determination of blood analytes. Experiences with the analytes: LDH, bilirubin, BUN, glucose, and uric acid.
In the first part of the Seralyzer system evaluation the precision and accuracy was studied with a total of 1245 clinical specimens, various commercial control sera, and pooled human sera. The calculated overall precision (between-run, and within-run) and day-to-day precision (% CV) was found to be within 3.0 to 5.4 for glucose, 2.8 to 7.1 for BUN, 1.5 to 6.2 for uric acid, 5.3 to 7.5 for bilirubin, and 3.2 to 8.6 for LDH. The clinical values are in agreement with values from respective comparative methods, as indicated by the regression statistics. The analysis of Seralyzer accuracy data using quality control sera showed in some cases a between-method difference. Supporting studies simulating additional important clinical situations showed that the clinical values for BUN, glucose, and uric acid of approximately 200 specimens from the emergency ward correlated with the respective comparative method values. In this phase of the study we verified that the instrument calibration was stable for a 24-hour period and that there is no effect of module (test) change on precision of Seralyzer determinations. The intra- and inter-laboratory performance in general practitioners' laboratories could be demonstrated using quality control sera.
Bilirubin↗
A rapid assay for 17 alpha OH-progesterone in plasma, saliva and amniotic fluid using a magnetisable solid-phase antiserum.
A radioimmunoassay suitable for measurement of 17 alpha OH-progesterone concentrations in small aliquots of plasma (20 microL), amniotic fluid (20 microL) and saliva (200 microL) is described. The assay features an antiserum raised against a 17 alpha OH-progesterone-3-(O-carboxymethyl)oxime/BSA conjugate coupled to a magnetisable, solid-phase support; the homologous radioligand is a 125I-iodohistamine conjugate. This combination of a gamma-emitting ligand and a magnetic-separation procedure has the advantage of reducing assay time and cost; it also allows processing of plasma and saliva samples in the same assay batch. The method has satisfactory sensitivity, precision and accuracy. Data derived from clinical studies of patients with congenital adrenal hyperplasia indicate the usefulness of this assay in routine practice.
17-alpha-Hydroxyprogesterone↗
Physician reactions to quantitative individual performance reports.
The purpose of this study was to learn how primary care physicians experienced the introduction and evolution of an individual physician pay-for-performance program. Thirty primary care physicians participated in audiotaped focus groups 13 and 26 months after beginning the program. Transcribed audiotapes were used to group comments into themes. Ten thematic groups were identified. Practitioners reviewed their profiles but found it difficult to use them to change behaviors. They were concerned about the data accuracy, the influence of specialists and patients on their "scores," and, less, the validity of quality measures. They described ways the program changed their practices and consideration of cost, quality, and satisfaction. There were important concerns about the influence of pay-for-performance programs on professionalism. Primary care physicians were skeptical of this pay-for-performance program. On the other hand, physicians described positive influences on making improvements in quality, satisfaction, and practice efficiency.
Employee Performance Appraisal↗
Diagnostic accuracy of canine scent detection in early- and late-stage lung and breast cancers.
BACKGROUND: Lung and breast cancers are leading causes of cancer death worldwide. Prior exploratory work has shown that patterns of biochemical markers have been found in the exhaled breath of patients with lung and breast cancers that are distinguishable from those of controls. However, chemical analysis of exhaled breath has not shown suitability for individual clinical diagnosis. METHODS: The authors used a food reward-based method of training 5 ordinary household dogs to distinguish, by scent alone, exhaled breath samples of 55 lung and 31 breast cancer patients from those of 83 healthy controls. A correct indication of cancer samples by the dogs was sitting/lying in front of the sample. A correct response to control samples was to ignore the sample. The authors first trained the dogs in a 3-phase sequential process with gradually increasing levels of challenge. Once trained, the dogs' ability to distinguish cancer patients from controls was then tested using breath samples from subjects not previously encountered by the dogs. The researchers blinded both dog handlers and experimental observers to the identity of breath samples. The diagnostic accuracy data reported were obtained solely from the dogs' sniffing, in double-blinded conditions, of these breath samples obtained from subjects not previously encountered by the dogs during the training period. RESULTS: Among lung cancer patients and controls, overall sensitivity of canine scent detection compared to biopsy-confirmed conventional diagnosis was 0.99 (95% confidence interval [CI], 0.99, 1.00) and overall specificity 0.99 (95% CI, 0.96, 1.00). Among breast cancer patients and controls, sensitivity was 0.88 (95% CI, 0.75, 1.00) and specificity 0.98 (95% CI, 0.90, 0.99). Sensitivity and specificity were remarkably similar across all 4 stages of both diseases. CONCLUSION: Training was efficient and cancer identification was accurate; in a matter of weeks, ordinary household dogs with only basic behavioral "puppy training" were trained to accurately distinguish breath samples of lung and breast cancer patients from those of controls. This pilot work using canine scent detection demonstrates the validity of using a biological system to examine exhaled breath in the diagnostic identification of lung and breast cancers. Future work should closely examine the chemistry of exhaled breath to identify which chemical compounds can most accurately identify the presence of cancer.
Animals↗
Method development and subsequent survey analysis of biological tissues for platinum, lead, and manganese content.
An emission spectrochemical method is described for the determination of trace quantities of platinum, lead, and manganese in biological tissues. Total energy burns in an argon-oxygen atmosphere are employed. Sample preparation, conditions of analysis, and preparation of standards are discussed. The precision of the method is consistently better than +/- 15%, and comparative analyses indicate comparable accuracies. Data obtained for experimental rat tissues and for selected autopsy tissues are presented.
Animals↗
TOXMAP: a GIS-based gateway to environmental health resources.
The National Library of Medicine (NLM) has an extensive collection of environmental health information, including bibliographic and technical data on hazardous chemical substances, in its TOXNET databases. TOXNET also provides access to the United States Environment Protection Agency (EPA)'s Toxics Release Inventory (TRI) data, which covers release of specific chemicals via air, water, and land, and by underground injection, as reported by industrial facilities around the United States. NLM has developed a Web-based geographic information system (GIS), TOXMAP , which allows users to create dynamic maps that show where TRI chemicals are released and that provides direct links to information about the chemicals in TOXNET. By extracting the associated regional geographic text terms from the displayed map (e.g., rivers, towns, county, state), TOXMAP also provides customized chemical and/or region-specific searches of NLM's bibliographic biomedical resources. This paper focuses on TOXMAP's features, data accuracy issues, challenges, user feedback techniques, and future directions.
Databases, Factual↗
Effect of water storage on tooth displacement in maxillary complete dentures.
The purpose of this study was to investigate the effect of water storage at 37 degrees C (1 week, 1 month and 3 months) on tooth displacement in maxillary complete dentures. Ten maxillary dentures were constructed with Clássico acrylic resin using the conventional method of packing in metallic flasks. Metallic reference pins were placed in the incisal border of the central incisors (I), labial cusp of the first premolars (PM), and mesiolabial cusp of the second molars (M). Twelve hours after final flask closure, the acrylic resin was cured in water at 74 degrees C for 9 h. The flasks were removed from the thermo-polymerizing unit after water-cooling and the dentures were deflasked, finished and stored in water at a temperature of 37 degrees C for 1 week, 1 month and 3 months. At deflasking and at the water storage intervals, the I-I (incisor to incisor), PM-PM (pre-molar to pre-molar), and M-M (molar to molar) transversal distances, and LI-LM (left incisor to left molar) and RI-RM (right incisor to right molar) anteroposterior distances were measured using an optical microscope with 0.0005 mm accuracy. Data were submitted to ANOVA and Tukey's test (5%). Comparing the evaluation periods for each individual transversal and anteroposterior reference point, no statistically significant differences were observed among deflasking and the water storage intervals for I-I, PM-PM, M-M and RI-RM distances (p>0.05). For LI-LM, however, deflasking values were statistically different from those of 1-week, 1-month and 3-month water storage intervals (p<0.05), which, in turn, did not differ statistically to each other (p>0.05). These results confirm the complexity of tooth displacement in complete dentures. From a clinical standpoint, the difference observed in LI-LM distance after water storage would not be detected by the patients during clinical use.
Dentures↗
Dynamic reasoning to solve complex problems in activated sludge processes: a step further in decision support systems.
Decision support systems (DSS) have generated high expectations as a tool to support activated sludge operation because of their ability to represent heuristic reasoning and to handle large amounts of qualitative, uncertain and low-accuracy data. Previous applications have been satisfactory to control simple problems, when static reasoning and literature-based solutions were enough. However to face complex operational problems with biological origin and slow dynamics (e.g. solids separation problems), it is necessary to use dynamic reasoning and apply long-term control strategies, monitoring the evolution of the process and adjusting the action plan according to the feed back of the process. This paper presents a dynamic reasoning DSS to face solids separation problems in the activated sludge system. The DSS is capable of identifying the complex problem affecting the process, determining if the current situation is new or a continuation from the previous one, assessing what is the specific cause of the situation, and recommending a long-term control strategy, which is daily adjusted according to the evolution of the process.
Artificial Intelligence↗
A method for repeated high-fidelity micromanometer measurement of intracardiac pressures.
Dial-tipped, high-fidelity micromanometers were inserted through polyurethane catheters to acutely measure blood pressures within the chambers of the heart and the great vessels of baboons, rhesus monkeys, and goats. Repeated measurements of atrial, ventricular, aortic, and pulmonary artery pressure were possible with this method, with calibration of micromanometers accomplished immediately prior to and after pressure recordings to assure data accuracy. All attempts to pass micromanometers into the atria in all species were successful. Passage of micromanometers from the left ventricle across the aortic valve and into the aorta was successful in 97% of the attempts in baboons, 100% for rhesus monkeys, and 75% for goats; while insertions into the pulmonary artery from the right ventricle were successful in 64% of the baboons, 40% of the rhesus monkeys, and 75% of the goats. Advantages of this technique are that a permanent conduit for cardiac vascular access is available and that high-fidelity pressure signals may be acquired.
Animals↗
A computational model of anterior cingulate function in speeded response tasks: effects of frequency, sequence, and conflict.
A growing body of evidence from functional neuroimaging and computational modeling studies indicates that the anterior cingulate cortex (ACC) detects the presence of response conflict and conveys this information to other brain regions, enabling subsequent adjustments in cognitive control. The present study examined previous empirical findings of increased ACC for low-frequency stimuli across three distinct speeded response tasks (two-alternative forced choice, go/no-go, and oddball). Simulations conducted in a neural network model incorporating sequential priming mechanisms (developed in Cho et al., 2002) confirmed that a computational measure of response conflict was higher on low-frequency trials across all three tasks. In addition, the model captured detailed aspects of behavioral reaction time and accuracy data, predicted the dynamics of ACC activity related to trial sequence effects, and provided evidence for the functional role of conflict information in performance monitoring and optimization. The results indicate that the conflict-monitoring hypothesis, augmented by mechanisms for encoding stimulus history, can explain key phenomena associated with performance in sequential speeded response tasks.
Adolescent↗