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Biomedical subjects

C Peterson

Publications and source records attributed to C Peterson.

At least 73 records · Page 4Linked to original sources

A confident decision support system for interpreting electrocardiograms.

Computer-aided interpretation of electrocardiograms (ECGs) is widespread but many physicians hesitate to rely on the computer, because the advice is presented without information about the confidence of the advice. The purpose of this work was to develop a method to validate the advice of a computer by estimating the error of an artificial neural network output. A total of 1249 ECGs, recorded with computerized electrocardiographs, on patients who had undergone diagnostic cardiac catheterization were studied. The material consisted of two groups, 414 patients with and 835 without anterior myocardial infarction. The material was randomly divided into three data sets. The first set was used to train an artificial neural network for the diagnosis of anterior infarction. The second data set was used to calculate the error of the network outputs. The last data set was used to test the network performance and to estimate the error of the network outputs. The performance of the neural network, measured as the area under the receiver operating characteristic (ROC) curve, was 0.887 (0.845-0.922). The 25% test ECGs with the lowest error estimates had an area under the ROC curve as high as 0.995 (0.982-1.000), i.e. almost all of these ECGs were correctly classified. Neural networks can therefore be trained to diagnose myocardial infarction and to signal when the advice is given with great confidence or when it should be considered more carefully. This method increases the possibility that artificial neural networks will be accepted as reliable decision support systems in clinical practice.

Bayes Theorem↗

Factors associated with success or failure in radiological interpretation: diagnostic thinking approaches.

RATIONALE AND OBJECTIVES: To identify those radiological diagnostic thinking approaches associated with success or failure in film interpretation. METHODS: A questionnaire was designed, piloted and tested for validity and reliability prior to use. This questionnaire was adapted and modified from the 'diagnostic thinking inventory' by Bordage et al. 21 One hundred and eighty students anonymously answered the questionnaire prior to their 15-case comprehensive film interpretation examination. Oral film-reading sessions were performed on a stratified random sample (n = 48) of students with complete transcripts of each session recorded. Spearman's correlation coefficient and multiple regression analysis statistics were applied to the questionnaire data. The unpaired t-test, ANOVA and correlation statistics were used to analyse the oral film-reading sessions. RESULTS: The most successful students were those who could easily see the integration of radiology with other subjects (P = 0.0042), students who could easily link the clinical information to the radiographic signs (P = 0.0354), and students who could easily identify the 'key' abnormal radiographic findings (P = 0.047). Students who used a flexible but complete search pattern performed significantly better (P = 0.0235) than students using any other search pattern approach. CONCLUSIONS: Radiology is a classic example of clinical problem solving and thus should be taught in that format. Those same factors which differentiate expert from novice diagnosticians are also evident in more successful vs. less successful students in radiology.

Chiropractic↗

Polyethylene particle morphology in synovial fluid of failed knee arthroplasty.

Synovial fluid from the knees of 16 patients undergoing revision knee arthroplasty for aseptic failure was subjected to base digestion and ultrafiltration. Filtered particles were scanned using scanning electron microscopy and analyzed with an image program. Polyethylene particles were identified visually and confirmed with the use of electron diffraction spectroscopy. Averaging more than 1500 particles per patient sample, 25,148 particles were analyzed. This corresponded to a concentration of 3000 polyethylene particles per milliliter of synovial fluid. Three populations of wear debris were identified in the fluid. Small globular particles with a mean area of 75 mu 2 represented 94% of all particles observed. The particles averaged 10 mu in diameter and often were seen in clumps. Long fibrous particles with a mean area of 1164 mu 2 made up 4% of the particle population. Large rhomboidal particles with an area of 557 mu 2 were observed least commonly and comprised the remainder of the particles visualized. All three particle types were observed in each fluid sample regardless of the wear pattern of the retrieved polyethylene liner. There were no differences in absolute particle counts, particle morphologic characteristics, or particle size between patients with and without gross polyethylene wear.

Aged↗

Posttraumatic stress disorder after injury: impact on general health outcome and early risk assessment.

OBJECTIVE: To evaluate prospectively components of general health outcome after trauma and to report on the further validation of the Michigan Critical Events Perception Scale (MCEPS), an instrument that predicts increased risk for posttraumatic stress disorder (PTSD). METHODS: Adults without neurologic injury admitted to a Level I trauma center in 1997 were interviewed during hospitalization. Baseline data included demographics, injury mechanism, Injury Severity Score, the Short Form 36 (SF36), and the MCEPS, which measures peri-traumatic dissociation (the sense of depersonalization or derealization during an injury event). Surveys sent by mail and completed 6 months later included the SF36 and civilian Mississippi Scale for PTSD. RESULTS: A total of 140 patients were interviewed; the 70% (n = 100 patients) who completed the 6-month assessment form the study group. Injuries were categorized as 71% blunt, 13% penetrating, and 16% burn. Mean Injury Severity Score was 13.7+/-0.52. PTSD at 6 months occurred in 42% of the patients and was directly related to MCEPS dissociation (p = 0.001; odds ratio = 3.1; 95% confidence interval, 1.6, 5.9). A stepwise linear regression explains 40% of the variance in 6-month SF36 general health outcome (adjusted R2 = 0.402). The model controls for individual factors related to dissociation, PTSD, and general health outcome. Development of PTSD was independently and inversely related to general health outcome as measured by the SF36 at 6 months (p < 0.001, beta = -0.404). The R2 change of 0.132 for PTSD (vs. 0.082 for 6-month physical function) illustrates that PTSD contributes more to the patient's perceived general health at 6 months than the degree of physical function or injury severity. CONCLUSIONS: Within hours of injury, the MCEPS identifies patients who are three times more likely to develop PTSD. PTSD compromises self-reported general health outcome in injured adults independent of baseline status, Injury Severity Score, or degree of physical recovery. These data suggest that psychological morbidity is an important part of the patient's perceived general health.

Adult↗

Posttraumatic stress disorder in injured adults: etiology by path analysis.

OBJECTIVE: Posttraumatic Stress Disorder (PTSD) impairs outcome from injury. We present a path analysis of factors related to the development of PTSD in injured adults. METHODS: A prospective cohort of 250 patients without severe neurotrauma was evaluated by interview during admission and by mailed self-report 6 months later. Data were gathered from the trauma registry (age, injury mechanism, and Injury Severity Score), social history (gender, income, education, and social support), and survey instruments. Baseline assessment used the Michigan Critical Events Perception Scale (peritraumatic dissociation and subjective threat to life), the Life Experience Survey (stressful exposure history), and the SF36 (general and mental health). PTSD at 6 months was identified with the civilian Mississippi Scale for PTSD. Data are listed as mean +/- SEM or percent (%). Path analysis was conducted by linear regression and significant (p<0.05) variables are shown. Factors are listed with the standardized beta. A negative beta suggests a protective effect. RESULTS: The 176 patients (72%) who completed the 6-month follow-up were 37.7+/-0.88 years old; 75% were men; and blunt (70%), penetrating (13.5%), and burn (16.4%) mechanisms caused the injuries. Assault was involved in 14.5% of the cases. Average income was $44,300+/-2,700/yr, education was 13.0+/-0.15 years, and Injury Severity Score was 13.9+/-0.50. A total of 42.3% of the patients developed PTSD. The 39.7% of the variance in PTSD explained by the model was due to intentional injury (beta = 0.27), male gender (beta = -0.21), age (beta = -0.20), peritraumatic dissociation (beta = 0.174), baseline mental health (beta = -0.21), and prior life-threatening illness (beta = -0.29). Peritraumatic dissociation was due to the patient's sense of threat to life (beta = -0.47), and threat was related to Injury Severity Score (beta = 0.2), assault(beta = 0.14), education (beta = -0.15), and age (beta = -0.19). Baseline SF36 mental health was related to social support (beta = 0.27) and income (beta = 0.21). Income was contingent on education (beta = 0.21). CONCLUSION: PTSD occurred in 42.3% of injured adults 6 months after trauma and was related to assault, dissociation, female gender, youth, poor mental health, and prior illness. By modeling PTSD, we may learn more of the etiology, risk stratification, and potentials for the treatment of this common and important morbidity of injury.

Adaptation, Psychological↗

Increased intraluminal release of eosinophil granule proteins EPO, ECP, EPX, and cytokines in ulcerative colitis and proctitis in segmental perfusion.

OBJECTIVE: The role of the eosinophil granulocyte in bowel mucosa in inflammatory bowel disease still remains obscure. The present study was performed in order to elucidate the local eosinophil activity and activating cytokines in the inflamed lesions of colon and rectum in patients with ulcerative colitis and proctitis. METHODS: The activity of intestinal eosinophils with respect to the release of granule proteins was studied in 18 patients (10 with colitis and 8 with isolated proctitis) and 18 healthy controls, using intraluminal segmental perfusion of the sigmoid colon and rectum. The released amounts of eosinophil granule proteins: eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil protein X (EPX) to perfusion fluid were determined by radioimmunoassays. The intraluminal release of possible eosinophil priming cytokines granulocyte/macrophage-colony stimulating factor (GM-CSF) and interleukin 8 (IL-8), were analyzed by immunoassays. RESULTS: The mucosal release of ECP, EPO, and EPX was increased 10- to 20-fold in patients with colitis and proctitis compared with controls. The intraluminal release of GM-CSF and IL-8, was several-fold enhanced in patients with colitis and proctitis. We also found a correlation between all three eosinophil granule proteins and the levels of IL-8/GM-CSF in the sigmoidal segments of patients with colitis. CONCLUSIONS: We conclude that the increased release of ECP, EPO, and EPX to colorectal perfusion fluid indicate eosinophil involvement in the local disease in patients with colitis and proctitis. IL-8 and GM-CSF may play a role in eosinophil accumulation and priming in colitis.

Adult↗

Varicella outbreaks after vaccine licensure: should they make you chicken?

In 1998, 3 years after vaccine licensure, child care centers (CCC) in Los Angeles County continued to report varicella outbreaks. We investigated outbreaks at 2 CCCs to determine the cause for them, such as low vaccination coverage levels or unexpected low vaccine effectiveness. We collected information on past history of varicella, illness during the outbreak, and prior varicella vaccination among CCC attendees. We found that CCC "H" had a vaccination coverage of 87% (34/39) compared with 30% (6/20) in CCC "L." The overall attack rate was lower in CCC "H" (31%) than in "L" (61%; P value =.03). Vaccine effectiveness for any varicella was 71% in "H" and 100% in "L." Vaccinated children with varicella had milder disease than unvaccinated. In conclusion, we found varicella outbreaks in CCCs with both high and low vaccination coverage. Vaccine effectiveness was within the range predicted by the literature. Vaccination led to a lower attack rate in the highly vaccinated CCC and appeared to protect from severe disease.

Chickenpox↗

Intraclonal heterogeneity in the in vitro daunorubicin-induced apoptosis in acute myeloid leukemia.

Leukemic cells from ten patients with acute myeloid leukemia (AML) were sorted on the basis of in vitro daunorubicin (DNR) uptake. The obtained subpopulations with high and low DNR accumulation were compared with regard to induction of apoptosis, expression of bcl-2 and p53. Heterogeneous induction of apoptosis, confined to subpopulations with high DNR uptake, was observed. The size of the DNR-induced apoptotic fraction (4% to 16%) within a given AML blast population was determined by intracellular drug accumulation and was not related to the level of bcl-2 expression. All tested leukemic samples displayed expression of p53 in a growth promoter orientation, i.e. PAb1620-/PAb240+. In two samples, however, subpopulations expressing a growth suppressor orientation of p53, i.e. PAb 1620+/PAb240-, were also present. These subpopulations were confined to high-DNR-uptake fractions and associated with the induction of apoptosis. We conclude that intraclonal heterogeneity in the intracellular drug accumulation and subsequently in DNR-induced apoptosis might allow the selection of inherently drug-resistant AML clones thus contributing to relapse of leukemia.

Acute Disease↗

Biochemical pharmacology and resistance to 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine, a novel analogue of cladribine in human leukemic cells.

The objective of the present study was to investigate the biochemical pharmacology of 2-chloro-2'-arabino-fluoro-2'-deoxyadenosine (CAFdA)--a fluorinated analogue of cladribine [2-chloro-2'-deoxyadenosine, Leustatin (CdA)] with improved acid and metabolic stability--in human leukemic cell lines and in mononuclear cells isolated from patients with chronic lymphocytic leukemia (CLL) and acute myelocytic leukemia (AML). We have also made and characterized two cell lines that are not sensitive to the growth inhibitory and cytotoxic effects of CAFdA. Incubation of cells isolated from the blood of CLL and AML patients with various concentrations of CdA or of CAFdA accumulated CdA and CAFdA nucleotides in a dose-dependent manner. A significantly higher rate of phosphorylation to monophosphates was observed for CAFdA than for CdA in cells from CLL patients (n = 14; P = 0.04). The differences in the phosphorylation were even more pronounced for the respective triphosphates in both CLL (n = 14; P = 0.001) and AML (n = 4; P = 0.04) cells. Retention of CAFdA 5'-triphosphate (CAFdATP) was also longer than that for CdA 5'-triphosphate (CdATP) in cells from leukemic patients. The relative efficacy of CAFdA as a substrate for purified recombinant deoxycytidine kinase (dCK), the key enzyme in the activation of nucleoside analogues, was very high and exceeded that of CdA as well as the natural substrate, deoxycytidine, by a factor of 2 and 8, respectively. The Km for CAFdA with dCK was also lower than that for CdA, as measured in crude extracts from the human acute lymphoblastic leukemia cell line CCRF-CEM and the promyelocytic leukemia cell line HL60. Acquired resistance to CAFdA in HL60 and in CCRF-CEM cell lines was directly correlated to the decreased activity of the nucleoside phosphorylating enzyme, dCK. Resistant cells also showed a considerable degree of cross-resistance to analogues that were activated by dCK. These observations demonstrated that dCK phosphorylates CAFdA more efficiently than CdA. Furthermore, CAFdATP is apparently more stable than CdATP and the mechanisms of resistance to CAFdA are similar to those leading to CdA resistance. These results encourage studies on the clinical effect of CAFdA in lymphoproliferative diseases.

Adenine Nucleotides↗

Klippel-Trenaunay syndrome.

Patients with Klippel-Trenaunay (KT) syndrome have a complex constellation of anomalies that includes cutaneous capillary malformation (usually on an affected limb), abnormal development of the deep and superficial veins, and limb asymmetry, usually enlargement. Mixed vascular malformations may be present and include capillary, venous, arterial, and lymphatic systems. The records of 79 patients referred for vascular anomalies were reviewed and 49 were found to have the three "cardinal" anomalies of KT syndrome. Twenty-six females and 23 males had 46 affected legs (27 right legs), 23 affected arms (15 right), 21 affected trunks, and 10 affected heads. Thirty-six had only one affected quadrant, 8 had two, and 5 had three or more. Although 40 patients had increased limb girth, measurable length discrepancy was noted in only 17 individuals. Patients were evaluated using a noninvasive imaging strategy including color duplex ultrasonography, MRI, lymphoscintigraphy, and plain radiographs. Treatment included compression, pulsed-dye laser treatment, reduction of arteriovenous malformations, and orthopedic procedures for overgrowth. All KT cases in this series occurred sporadically. We speculate that KT syndromes may be due to a somatic mutation for a factor critical to vasculogenesis and angiogenesis in embryonic development.

Adolescent↗

A Potts Neuron Approach to Communication Routing.

A feedback neural network approach to communication routing problems is developed, with emphasis on multiple shortest path problems, with several requests for transmissions between distinct start and end nodes. The basic ingredients are a set of Potts neurons for each request, with interactions designed to minimize path lengths and prevent overloading of network arcs. The topological nature of the problem is conveniently handled using a propagator matrix approach. Although the constraints are global, the algorithmic steps are based entirely on local information, facilitating distributed implementations. In the polynomially solvable single-request case, the approach reduces to a fuzzy version of the Bellman-Ford algorithm. The method is evaluated for synthetic problems of varying sizes and load levels, by comparing to exact solutions from a branch-and-bound method, or to approximate solutions from a simple heuristic. With very few exceptions, the Potts approach gives high-quality legal solutions. The computational demand scales merely as the product of the numbers of requests, nodes, and arcs.

Journal Article↗

Determinants of Clara cell protein (CC16) concentration in serum: a reassessment with two different immunoassays.

Clara cell protein (CC16) is a 16 kiloDalton protein secreted by Clara cells in the lining fluid of bronchiolar and bronchial epithelium. Recently, Nomori et al., using a nephelometric latex immunoassay, reported a strong correlation between serum CC16 (sCC16) and serum lipids as well as the body mass index (BMI) [Nomori H, Horio H, Takagi M Kobayashi Y, Hirabayashi Y. Clara cell protein correlation with hyperlipidemia. Chest 1996;110:680-4]. The same authors found higher values of sCC16 in males compared to females and did not detect any significant influence of tobacco smoking. Since these results are in disagreement with previous observations showing consistently a decrease of sCC16 in smokers and no influence of sex, we have reassessed in healthy subjects the determinants of sCC16 using two different assays: a particle counting-based latex immunoassay (LIA) using polyclonal antibodies and a fluorescence enzyme immunoassay (FEIA) using monoclonal antibodies. sCC16 was determined in a group of 52 female and 44 male healthy subjects (age 18 to 66 years), including 35 smokers and 61 nonsmokers. sCC16 measured by LIA and FEIA were well correlated (r = 0.92, n = 96, P < 0.0001) with values (geometric mean and range) of 13.3 (5.2-34.5) and 14.7 (4.1-53.1) microg/l, respectively. The determinants of sCC16 measured by both techniques were traced by stepwise regression analysis using as independent variables age, sex, smoking status, BMI or serum lipids (total cholesterol and triglycerides) and the glomerular filtration rate (GFR) estimated on the basis of serum creatinine or beta2-microglobulin. Only two significant determinants emerged: tobacco smoking which correlated negatively and the GFR which correlated positively with sCC16. No influence of serum lipids, BMI, age and sex on sCC16 was detected. We think that an analytical interference with serum lipids explains the results by Nomori et al. which are not confirmed here by two independent techniques and are inconsistent with the current understanding of the physiopathology of the Clara cell and its main secretory product, CC16.

Adolescent↗

Memory for medical emergencies experienced by 1- and 2-year-olds.

Children (13-18 months, 20-25 months, and 26-34 months) who had experienced trauma injuries were recruited in a hospital Emergency Room and subsequently interviewed about them within days (if verbal) and after 6, 12, and 18 or 24 months. The youngest children demonstrated little long-term verbal recall, whereas a few children in the intermediate group, who could not narrate about past events at time of injury, could verbally recall the target events 18 months later. Most of the oldest children, who had narrative skills at time of injury, demonstrated good verbal recall 2 years later. Illustrative case histories were described. Accuracy of recall was low for the youngest children, and although the majority of older children's recalled information was accurate, there were still many errors.

Child, Preschool↗

Telomerase activity and the expression of telomerase components in acute myelogenous leukaemia.

In 95 leukaemic cell samples from 66 patients with acute myelogenous leukaemia (AML) (47 de novo and 19 secondary AML) telomerase activity was determined and the expression of the telomerase components: telomerase reverse transcriptase (hTERT), telomerase RNA template (hTR) and telomerase-associated protein (TP1) evaluated by RT-PCR. Compared to peripheral blood mononuclear cells (PBMC) from normal adult 87% (82/95) of patient samples exhibited elevated telomerase activity hTERT, but not hTR and TP1 expression strongly correlated with the levels of telomerase activity (r=0.47, P<0.0001). The levels of telomerase activity were significantly higher at time of relapse or progression than at time of diagnosis (P=0.003), and correlated to CD34 expression and chromosomal abnormalities of leukaemic cells (P=0.01 and P=0.001 respectively). The rate and duration of complete remission (CR) did not correlate with the levels of telomerase activity at diagnosis. Among eight patients in first relapse, however, two of three with low levels of telomerase activity re-entered CR. whereas none of five patients with high telomerase activity achieved a second CR. Taken together, telomerase activation/up-regulation in AML is a disease progression-associated event. Undifferentiated status and chromosomal aberration also lead to the up-regulation of telomerase activity in AML.

Adult↗

Intelligent computer reporting 'lack of experience': a confidence measure for decision support systems.

The purpose of this study was to explore the feasibility of developing artificial neural networks that are able to provide confidence measures for their diagnostic advice. Computer-aided decision making can improve physician performance, but many physicians hesitate to use these 'black boxes'. If we are to rely upon decision support systems for such tasks as medical diagnosis it is essential that the computers indicate when the advice given is based on experience, i.e. give a confidence measure. An artificial neural network was trained to diagnose healed anterior myocardial infarction and to indicate 'lack of experience' when test electrocardiograms were different from the electrocardiograms of the training set. A database of 1249 electrocardiograms from patients who had undergone cardiac catheterization was used to train and test the neural network. Thereafter, the ability of the network to indicate 'lack of experience' was assessed using 100 left bundle branch block electrocardiograms, an electrocardiographic pattern that was excluded from the training set. The network indicated that 83% of the left bundle branch block electrocardiograms and 1% of the test electrocardiograms from catheterized patients were different from the electrocardiograms of the training set. All but one of the left bundle branch block electrocardiograms would otherwise be falsely classified as anterior myocardial infarction by the network. Artificial neural networks can be trained to indicate 'lack of experience', and this ability increases the possibility for neural networks to be accepted as reliable decision support systems in clinical practice.

Bundle-Branch Block↗

Clinical and pharmacokinetic risk factors for high-dose methotrexate-induced toxicity in children with acute lymphoblastic leukemia--a logistic regression analysis.

The clinical and pharmacokinetic risk factors for toxicity after high-dose methotrexate (MTX) in children with acute lymphoblastic leukemia were evaluated using a multivariate statistical analysis. Plasma samples were collected after 44 24-h infusions of MTX (5 or 8 g/m2) in 13 children (age 3.3-12.9 years) and subsequently analyzed by HPLC to determine the MTX and 7-hydroxymethotrexate (7-OHMTX) concentrations. Toxicity was evaluated according to the WHO criteria. Severe toxicity was not observed. Oral mucositis (WHO grade > or = 1) was significantly related to a high plasma MTX concentration at 28 h after starting the infusion (p = 0.013), a low ratio of plasma 7-OHMTX/MTX at 66 h after starting the infusion (p = 0.049), and a slow clearance of MTX (p = 0.048). The risk of leukopenia (WHO grade > or = 2) increased significantly with the number of courses (p = 0.02). Increasing age and a long exposure to a high MTX concentration in plasma (AUC) were significant risk factors (p = 0.047 and p = 0.009, respectively) for developing elevated liver enzymes (ALAT) (WHO grade > or = 2). This study shows how a statistical model can be used to identify clinical and pharmacokinetic factors that may influence MTX-induced toxicity. The therapeutic ratio could thereby potentially be improved.

Bone Marrow↗

Challenging drug resistance in cancer therapy--review of the First Nordic Conference on Chemoresistance in Cancer Treatment, October 9th and 10th, 1997.

The First Nordic Conference on Chemoresistance in Cancer Treatment was held in the Danish town of Helsingør on October 9th and 10th, 1997, under the auspices of the Nordic Cancer Chemoresistance Group (NCCG). The meeting focused on biochemical chemoresistance in a multidisciplinary approach. There were 19 oral and 15 poster presentations documenting recent advances in experimental and clinical research of drug transport mechanisms, DNA repair systems, detoxifying enzymes, drug target regulation, in vitro sensitivity tests, apoptosis inhibition, and strategies to circumvent chemoresistance. In the present paper we review the main issues that were addressed and discuss the findings with reference to the current literature in the field. The meeting demonstrated the plurality and the complexity of chemoresistance, which is a major obstacle to successful chemotherapy in cancer patients. The new insights to mechanisms of drug resistance and sensitization represent a useful basis for further development of strategies to circumvent chemoresistance in clinical practice.

Alkylating Agents↗