Biomedical subjects

Attila Frigyesi

Publications and source records attributed to Attila Frigyesi.

8 recordsLinked to original sources

PubMed2006

Estimating the parameters of the operational model of pharmacological agonism.

The aim of this work is practical. We show that the parameters of the widely used operational model of pharmacological agonism are difficult to estimate from single dose-response curves. The parameters can be estimated using pairs of dose-response curves (usually treatment and control) sharing some parameters. Confidence bands for the estimators are developed. In the case of multiple dose-response curve pairs one can employ a non-linear mixed effects model to allow for inter-individual variation. The point estimates and the confidence intervals thus obtained are similar to the more naive construction based on mean and standard errors of parameter estimates. To test for difference of certain parameters between treatment and control we employ a permutation test and Wald's test.

Animals↗

PubMed2006

Independent component analysis reveals new and biologically significant structures in micro array data.

BACKGROUND: An alternative to standard approaches to uncover biologically meaningful structures in micro array data is to treat the data as a blind source separation (BSS) problem. BSS attempts to separate a mixture of signals into their different sources and refers to the problem of recovering signals from several observed linear mixtures. In the context of micro array data, "sources" may correspond to specific cellular responses or to co-regulated genes. RESULTS: We applied independent component analysis (ICA) to three different microarray data sets; two tumor data sets and one time series experiment. To obtain reliable components we used iterated ICA to estimate component centrotypes. We found that many of the low ranking components indeed may show a strong biological coherence and hence be of biological significance. Generally ICA achieved a higher resolution when compared with results based on correlated expression and a larger number of gene clusters with significantly enriched for gene ontology (GO) categories. In addition, components characteristic for molecular subtypes and for tumors with specific chromosomal translocations were identified. ICA also identified more than one gene clusters significant for the same GO categories and hence disclosed a higher level of biological heterogeneity, even within coherent groups of genes. CONCLUSION: Although the ICA approach primarily detects hidden variables, these surfaced as highly correlated genes in time series data and in one instance in the tumor data. This further strengthens the biological relevance of latent variables detected by ICA.

Algorithms↗

PubMed2006

What is the impact of resistance to activated protein C (Leiden mutation to factor V) in inflammatory bowel disease?

BACKGROUND AND AIMS: Resistance to activated protein C (APCR) caused by the Leiden mutation to factor V is the most common cause of inherited thrombosis. Patients with inflammatory bowel disease (IBD) are considered to have an increased risk of thromboembolic complications, and the role of APCR as a cause has previously been investigated. In this study, we investigated if APCR was associated with non-thrombotic morbidities in IBD. PATIENTS/METHODS: Of 951 patients asked to participate, 389 agreed by returning a signed informed consent and filled questionnaire and took the blood test for APCR. Self-reported IBD-related surgery was used as a rough indicator for increased morbidity. RESULTS: APCR was present in 6.6% of patients with Crohn's disease (CD; 10/152) and in 12.7% of ulcerative colitis (UC) patients (30/237). The difference of 6.1% is significant (p=0.039). Among patients with CD and APCR, 9 out of 10 had had surgery, significantly more than among those without APCR (81/142). In patients with UC and APCR, 10 out of 30 had had surgery, still significantly more than in those without APCR (36/207). For the whole group of IBD patients, APCR is associated with a significantly increased risk for thrombosis (p=0.0018), and for the UC group (8/28) p=0.0029, but not for the CD patients alone (2/9), p=0.2323. No other significant differences could be shown for parameters normally related to increased morbidity. CONCLUSIONS: APCR in IBD was associated with an increased frequency of IBD-related surgery, which may warrant screening for APCR in therapy-resistant IBD. In patients with APCR, it may be more difficult and/or important to control inflammation.

Activated Protein C Resistance↗

PubMed2005

Statistical behavior of complex cancer karyotypes.

Epithelial tumors commonly show complex and variable karyotypes that obscure the identification of general patterns of the karyotypic evolution. To overcome some of these problems, we previously systematically analyzed the accumulated cytogenetic data from individual tumor types by using various statistical means. In the present study, we compare previous results obtained for nine tumor types and perform several meta-analyses of data obtained from a number of epithelial tumors, including head and neck, kidney, bladder, breast, colorectal, ovarian, and lung cancer, as well as from malignant melanoma and Wilms tumor, with the specific aim of discovering common patterns of karyotypic evolution. We show that these tumors frequently develop through a hypo- or a hyperdiploid pathway and progress by an increasing number of alternative imbalances through at least two karyotypic phases, Phases I and II, and possibly through a third, Phase III. During Phase I, the karyotypes exhibited a power law distribution of both the number of changes per tumor and the frequency distribution at which bands were involved in breaks. At the transition from Phase I to Phase II/III, the observed power law distributions were lost, indicating a transition from an ordered and highly structured process to a disordered and chaotic pattern. The change in karyotypic orderliness at the transition from Phase I to Phase II/III was also shown by a drastic difference in karyotypic entropy.

Biological Evolution↗

PubMed2004

A model for karyotypic evolution in testicular germ cell tumors.

Testicular germ cell tumor karyotypes are characterized by near-triploidy, with chromosome numbers ranging from 50 to 70, and by the frequent appearance of i(12p). The high chromosome number has been attributed to the formation of tetraploid carcinoma in situ cells followed by chromosomal losses that ultimately lead to tumor forms that are more advanced. In the present investigation, we show by analysis of the accumulated cytogenetic data on testicular germ cell tumors and computer simulations that two distinct processes are operating in the karyotypic evolution of these tumors. The results suggest that whole-chromosome changes originate from a multipolar cell division of a tetraploid cell, whereas imbalances caused by structural changes accumulate in a stepwise manner.

Cell Division↗

PubMed2003

Power law distribution of chromosome aberrations in cancer.

Cancer cells are characterized by having aberrant chromosomes. The number of aberrations and the specific chromosomes affected are correlated with tumor progression. We show that for breast, colorectal, and renal cell carcinomas the distribution of the number of such aberrations per tumor follow a power law distribution with an exponent close to unity. We present two stochastic models that in simulation experiments result in power law distributions of the number of changes per tumor. The first model is based on a multiplicative fluctuation process and the second on a preferential attachment principle linked to an observation process, i.e., a tumor detection and treatment process. Because almost identical power law distributions are seen in breast, colorectal, and renal cell carcinomas we suggest that the obtained distributions are consequences of a common mechanism operating in malignant epithelial tumors.

Breast Neoplasms↗

PubMed2003

An automated method for the detection of pulmonary embolism in V/Q-scans.

In this paper, a fully automatic method for the diagnosis of pulmonary embolism (PE) from V/Q-scans is presented. Image analysis is applied to the ventilation and the perfusion images obtained in the V/Q-scan. The difference of the ventilation and the perfusion is calculated after transformation and hot-spot reduction of the images. From this difference image the integral of the underperfused areas are used as features. With the aid of these features a simple test for PE is devised. The method is evaluated on two sets of patients. One set comprises 102 patients who have undergone both V/Q-scanning and angiography. The performance given as the area under the Receiver Operating Characteristic (ROC) curve is 0.85. Another set is made up by the 507 consecutive patients examined with V/Q-scanning at Lund University Hospital in Sweden. In this case, the reference was the consensus opinion of two radiologists, the ROC-area is 0.67. A fully automatic and reasonably robust expert system is developed to aid the radiologist in the interpretation of V/Q-scans for PE.

Algorithms↗

PubMed2002

Patients with suspected acute coronary syndrome in a university hospital emergency department: an observational study.

BACKGROUND: Improved diagnostics in suspected acute coronary syndrome (ACS) are considered to be needed. To help clarify the current situation and the improvement potential, judged risk in the emergency department (ED) and outcome were analyzed among patients with suspected ACS at a university hospital. METHODS: 157 consecutive patients with symptoms of ACS were included at the ED during 10 days. Risk of ACS was estimated in the ED for each patient based on history, physical examination and ECG by assigning them to one of four risk categories; I (obvious myocardial infarction, MI), II (strong suspicion of ACS), III (vague suspicion of ACS), and IV (no suspicion of ACS). RESULTS: 4, 17, 29 and 50% of the patients were allocated to risk categories I-IV respectively. 74 patients (47%) were hospitalized but only 19 (26%) had ACS as the discharge diagnose. In risk categories I-IV, ACS rates were 100, 37, 12 and 0%, respectively. Of those admitted without ACS, at least 37% could probably, given perfect ED diagnostics, have been immediately discharged. 83 patients were discharged from the ED, and among them there were no hospitalizations for ACS or cardiac mortality at 6 months. Only about three patients per 24 h were considered eligible for a potential ED chest pain unit. CONCLUSIONS: Almost 75% of the patients hospitalized with suspected ACS did not have it, and some 40% of these patients could probably, given perfect immediate diagnostics, have been managed as outpatients. The potential for diagnostic improvement in the ED seems large.

Journal Article↗