Quality and staffing issues dominate the ANA agenda.
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Biomedical subjects
Publications and source records attributed to C Peterson.
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UNLABELLED: The purpose of this study was to develop a computer-based method for automatic detection and localization of coronary artery disease (CAD) in myocardial bull's-eye scintigrams. METHODS: A population of 135 patients who had undergone both myocardial 99mTc-sestamibi rest-stress scintigraphy and coronary angiography within 3 mo was studied. Different image data reduction methods, including pixel averaging and two-dimensional Fourier transform, were applied to the bull's-eye scintigrams. After a quantitative and qualitative evaluation of these methods, 30 Fourier components were chosen as inputs to multilayer perceptron artificial neural networks. The networks were trained to detect CAD in two vascular territories, using coronary angiography as gold standard. A "leave one out" procedure was used for training and evaluation. The performance of the networks was compared to those of two human experts. RESULTS: One of the human experts detected CAD in one of two vascular territories, with a sensitivity of 54.4% at a specificity of 70.5%. The sensitivity of the networks was significantly higher at that level of specificity (77.2%, p = 0.0022). The other expert had a sensitivity of 63.2% at a specificity of 61.5%. The networks had a sensitivity of 77.2% (p = 0.038) at this specificity level as well. The differences in sensitivity between human experts and networks for the other vascular territory were all less than 6% and were not statistically significant. CONCLUSION: Artificial neural networks can detect CAD in myocardial bull's-eye scintigrams with such a high accuracy that the application of neural networks as clinical decision support tools appears to have significant potential.
Intravenous methotrexate (MTX) therapy is widely used for treatment of various neoplastic diseases in children. The optimization of the MTX dose and/or the subsequent leucovorin rescue is based on pharmacokinetic data calculated from plasma concentrations collected after cessation of the MTX administration. The influence of the MTX assay method on the subsequent pharmacokinetic evaluation was studied in 13 children with acute lymphoblastic leukemia. Plasma samples were collected after administration of MTX (5-8 g/m2) as 24 h infusions. All samples were analyzed by five different analytical procedures, viz. liquid chromatography (LC), enzyme inhibition assay (EIA), two fluorescence polarization immunoassays (FPIA1 and FPIA2) and enzyme multiplied immunoassay (EMIT). Using measurements from the four non-chromatographic procedures, only about 50% of determined pharmacokinetic parameters (area under the plasma concentration time curve, calculated by the trapezoidal rule and from pharmacokinetic modelling, and the terminal half life time) were within the range 75-125% of the values obtained from LC data. We conclude that the clinical outcome of MTX therapy using estimated MTX pharmacokinetics as guidelines for proper dosing of MTX and/or leucovorin rescue might be affected by the lack of accuracy of non-chromatographic procedures for MTX analysis. There is still a need for improving the accuracy of the procedures aimed at therapeutic drug monitoring of MTX.
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The question of whether proteins originate from random sequences of amino acids is addressed. A statistical analysis is performed in terms of blocked and random walk values formed by binary hydrophobic assignments of the amino acids along the protein chains. Theoretical expectations of these variables from random distributions of hydrophobicities are compared with those obtained from functional proteins. The results, which are based upon proteins in the SWISS-PROT data base, convincingly show that the amino acid sequences in proteins differ from what is expected from random sequences in a statistically significant way. By performing Fourier transforms on the random walks, one obtains additional evidence for nonrandomness of the distributions. We have also analyzed results from a synthetic model containing only two amino acid types, hydrophobic and hydrophilic. With reasonable criteria on good folding properties in terms of thermodynamical and kinetic behavior, sequences that fold well are isolated. Performing the same statistical analysis on the sequences that fold well indicates similar deviations from randomness as for the functional proteins. The deviations from randomness can be interpreted as originating from anticorrelations in terms of an Ising spin model for the hydrophobicities. Our results, which differ from some previous investigations using other methods, might have impact on how permissive with respect to sequence specificity protein folding process is-only sequences with nonrandom hydrophobicity distributions fold well. Other distributions give rise to energy landscapes with poor folding properties and hence did not survive the evolution.
Artificial neural networks can be used to recognize lead reversals in the 12-lead electrocardiogram at very high specificity, and the sensitivity is much higher than that of a conventional interpretation program. The neural networks developed in this and an earlier study for detection of lead reversals, in combination with an algorithm for the right arm/right foot lead reversal, would recognize approximately 75% of lead reversals encountered in clinical practice.
Etoposide is extensively (approximately 94%) bound to plasma proteins and the free non-protein-bound levels have been shown to correlate more closely to toxicity than total drug concentrations. A rapid and easily performed method, compared to the time consuming equilibrium dialysis, to obtain the free fraction is needed. The aim of this study was to evaluate ultrafiltration and subsequent high performance liquid chromatography (HPLC) for the determination of protein binding of etoposide. Spiked plasma from healthy, drug-free volunteers was used to compare ultrafiltration, using Amicon Centrifree filters, with equilibrium dialysis at 37 degrees C. The variability (CV) of the ultrafiltration method was 6.1 and 13.5% (n = 6) at 37 degrees C and room temperature (RT), respectively. The relative size of the free fraction obtained by ultrafiltration at 37 degrees C and RT was 1.22 (P = 0.0005) and 0.37 (P = 0.0001), respectively, compared with equilibrium dialysis at 37 degrees C. The chromatographic separation of metabolites from the mother compound when free etoposide is analyzed is crucial. It is shown that a hydroxy-acid metabolite of etoposide is quite dominant in a protein-free plasma fraction. The free concentrations were determined throughout a dose interval of 24 h in a patient receiving etoposide 100 mg/m2 daily. Ultrafiltration and subsequent HPLC is considered convenient and suitable for in vivo pharmacokinetic investigations.
Etoposide is bound to plasma albumin (94%). Previous studies have revealed altered protein binding of etoposide in cancer patients. This has clinical implications since only the free fraction is considered pharmacologically active. We have studied the etoposide protein binding in 11 children (eight acute lymphocytic leukemia, two malignant histiocytosis, and one oligodendroglioma; age 1-17 years) and 46 adult patients (28 acute myelocytic leukemia, eight lymphoma, one multiple myeloma, and nine small cell lung cancer; age 38-81 years). All patients were treated with etoposide 50-200 mg/m2 i.v. or orally. Plasma from ten healthy volunteers, 26-50 years of age, was spiked with etoposide, 10 micrograms/ml, and the protein binding was compared with that in patient samples. The free etoposide concentration was determined by high performance liquid chromatography (HPLC) after ultrafiltration at room temperature. The free etoposide fraction was lower, 2.5 +/- 0.6% (mean +/- SD), in the children compared with 5.0 +/- 3.6% in adult cancer patients. In plasma from healthy adults it was 3.2 +/- 0.3%. It is concluded that children have significantly lower levels of free etoposide compared with adult patients (P = 0.03) as well as with healthy subjects (P = 0.001), which is likely to affect metabolism and renal clearance as well as cellular uptake of the drug.
The full length-mouse XPC cDNA contains a 2703 bp orf which encodes a polypeptide containing 900 amino acids. Overall, there is 75% identity in nucleotide sequence and 73% identity in amino acid sequence between mouse and human genes. The C-terminal half is more conserved (80%) than the N-terminal half (65%). Northern analysis has revealed a constitutive expression pattern for both human and mouse transcripts in various tissues examined. However, high level expression was observed in liver, testis and kidney in both species. The human XPC gene was cloned from a cosmid library and the full-length gene was found to span -24 kb. Analysis of the genomic structure indicated that the transcribed sequence is divided into 15 exons.
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The introduction of serotonin receptor (5-HT3) antagonists has improved the control of acute nausea and vomiting induced by cancer chemotherapy, but they seem to have little or no effect on delayed symptoms. Corticosteroids are known to reduce both acute and delayed nausea and vomiting. The aim of the present study was to test the hypothesis that a single high dose of dexamethasone (20 mg), a long-acting corticosteroid, given after cisplatin and in addition to ondansetron (8 mg three times a day), would enhance the control of both acute and delayed nausea and vomiting. A group of 104 chemotherapy-naive ovarian cancer patients, scheduled for at least three cycles of combination chemotherapy including cisplatin (50 mg/m2), were randomly allocated to receive either dexamethasone or placebo in addition to ondansetron. Two-thirds of the patients received doxorubin and melphalan on the day before cisplatin and 1/3 received doxorubicin immediately before cisplatin. Unexpectedly we found, in all three chemotherapy cycles, that patients receiving dexamethasone suffered from more delayed nausea and vomiting than patients receiving placebo. In patients with no acute nausea or vomiting, the boomerang effect of dexamethasone could be seen on the first day after chemotherapy. In a follow-up study on 5 patients not included in the randomized trial, dexamethasone induced a pronounced reduction in urinary cortisol excretion on the day after chemotherapy with a return to normal excretion on day 2. It is concluded that a single high dose of dexamethasone does not seem appropriate for controlling delayed nausea and vomiting.
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BACKGROUND: Bronchial asthma is associated with elevated serum levels of eosinophil products, such as eosinophil protein X (EPX), but the occurrence in urine of this substance in patients with asthma has not previously been studied. OBJECTIVE: This study was performed to clarify whether increased amounts of eosinophil granulocyte proteins in urine and serum reflect ongoing asthmatic inflammation and whether decreasing values reflect successful treatment. METHODS: Twelve children with a median age of 12.5 years who had mild or moderate atopic asthma were studied for 3 months. At the time of inclusion in the study, treatment with inhaled budesonide was initiated. Nine children of the same age without atopic disease served as control subjects. Levels of EPX, eosinophil cationic protein (ECP), and myeloperoxidase in serum and in urine (urinary EPX) were determined at inclusion and then after 3 months of treatment. Spirometry was performed on the same occasions. RESULTS: At the time of inclusion, urinary EPX and serum ECP were significantly higher in children with atopic asthma than in the control subjects (mean, 116.4 vs 43.0 micrograms/mmol creatinine [p = 0.004] and 37.0 vs 14.8 micrograms/L [p = 0.004]). In the asthma group urinary EPX, as well as serum ECP, decreased significantly after 3 months of treatment with budesonide (116.4 to 68.4 micrograms/mmol creatinine [p = 0.005] and 37.0 to 24.0 micrograms/L [p = 0.04]). At the same time, peak expiratory flow values increased significantly in the children with asthma (76.0% to 87.8% of predicted value [p = 0.005]) but not in the control subjects (87.0% to 90.1%). In the asthma group the levels of myeloperoxidase were similar to those in the control group, both at inclusion and after 3 months. CONCLUSION: Increased urinary EPX and serum ECP levels seem to reflect active atopic asthma, whereas decreased levels after antiinflammatory treatment probably reflect normalization of airway inflammation, and indirectly, improved lung function.
OBJECTIVES: The purpose of this study was to compare the diagnoses of healed myocardial infarction made from the 12-lead electrocardiogram (ECG) by artificial neural networks and an experienced electrocardiographer. BACKGROUND: Artificial neural networks have proved of value in pattern recognition tasks. Studies of their utility in ECG interpretation have shown performance exceeding that of conventional ECG interpretation programs. The latter present verbal statements, often with an indication of the likelihood for a certain diagnosis, such as "possible left ventricular hypertrophy." A neural network presents its output as a numeric value between 0 and 1; however, these values can be interpreted as Bayesian probabilities. METHODS: The study was based on 351 healthy volunteers and 1,313 patients with a history of chest pain who had undergone diagnostic cardiac catheterization. A 12-lead ECG was recorded in each subject. An expert electrocardiographer classified the ECGs in five different groups by estimating the probability of anterior myocardial infarction. Artificial neural networks were trained and tested to diagnose anterior myocardial infarction. The network outputs were divided into five groups by using the output values and four thresholds between 0 and 1. RESULTS: The neural networks diagnosed healed anterior myocardial infarctions at high levels of sensitivity and specificity. The network outputs were transformed to verbal statements, and the agreement between these probability estimates and those of an expert electrocardiographer was high. CONCLUSIONS: Artificial neural networks can be of value in automated interpretation of ECGs in the near future.
We investigated how residual tumour burden after cytoreductive surgery was related to the occurrence of acute and delayed nausea and vomiting in 101 ovarian cancer patients receiving their first chemotherapy course. The anti-emetic treatment included ondansetron combined with dexamethasone or placebo. After chemotherapy all patients received ondansetron only for 5 days. Two categories of tumour burden (TB) were formed according to the diameter of the greatest residual tumour (< 2 cm = minimal TB and > or = 2 cm = large TB). Self-reports of nausea and vomiting were obtained for 15 days. Other potential predictor variables were assessed and included in multivariate analyses. Patients with large compared with minimal TB had more delayed emesis, especially on days 2-7. They also had more acute nausea. The aggravating effect associated with large residual TB was more evident in patients > or = 55 years. During the second week after the chemotherapy the occurrence of nausea was higher in patients > or = 55 years than in those < 55 years. This was seen primarily in patients with large residual TB. Predictors for no delayed emesis at all were anti-emetic treatment with dexamethasone, minimal tumour burden, low neuroticism and no history of motion sickness. The increased risk of "persistent' delayed nausea and vomiting seen in older patients with large tumour burden may have important clinical implications and warrants further attention.
Multidrug resistance gene (mdrl) expression is associated with a poor prognosis in acute myelocytic leukaemia (AML). Whether expression of the recently described multidrug resistance-associated gene (mrp) has any prognostic importance in AML is still unclear. The aim of the present study was to investigate the functional role of the mdr1 and mrp mRNA levels in peripheral leukaemic cell populations from patients with AML. Peripheral leukaemic cells from 10 patients with AML were incubated with daunorubicin (DNR). Cellular DNR content was analysed with a fluorescence-activated cell sorter (FACS). From each cell population the 20-25% cells with the lowest and highest DNR content were sorted out, and mdr1 and mrp RNA were quantified in these subpopulations with competitive polymerase chain reaction. The ratio between the mean DNR content in the cell populations with high and low DNR content varied between 1.9 and 6.6. the cell fraction with low DNR content had higher (3.8-40 times)mdr1 mRNA levels in 10/10 patients and higher (1.4-26 times) mrp mRNA levels in 8/10, as compared to the cell fraction with high DNR accumulation. In conclusion, mdr1 and mrp mRNA expressions are heterogenous in leukaemic cell populations from patients with AML. The mdr1 expression, and to some extent mrp expression, is inversely correlated to DNR accumulation in vitro.
BACKGROUND: The University of Texas Medical Branch (UTMB) and Texas Tech Health Science Center (TTHSC) are responsible for providing health care for approximately 130,000 inmates of the Texas Department of Criminal Justice through a health maintenance organization (HMO). Telemedicine was considered a way to solve some of the problems presented. OBJECTIVES: To develop approaches to patient care, technology, support systems, evaluation, and uses of the system for applications other than patient care as part of the first stage of implementation. METHODS: Four prison delivery unit models were utilized. After a pilot study, the first patients were seen from October 1994 to November 1995, when 1715 consults were conducted in 18 scheduled specialty telemedicine clinics. Patients and providers were surveyed by interviews and questionnaires for their views on this form of providing care. RESULTS: Ninety-five per cent of the telemedicine consults saved one or more trips to UTMB for outpatient specialty appointments. User surveys indicated a high degree of satisfaction on the part of patients, presenters, and specialty consultants. CONCLUSIONS: Preliminary review of the data indicated favorable care outcomes, and initial economic analyses suggested that telemedicine is likely to be cost-effective in this environment. The project will be continued.
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