Biomedical subjects

Jan A Kors

Publications and source records attributed to Jan A Kors.

At least 19 recordsLinked to original sources

PubMed2006

Evaluation of techniques for increasing recall in a dictionary approach to gene and protein name identification.

Gene and protein name identification in text requires a dictionary approach to relate synonyms to the same gene or protein, and to link names to external databases. However, existing dictionaries are incomplete. We investigate two complementary methods for automatic generation of a comprehensive dictionary: combination of information from existing gene and protein databases and rule-based generation of spelling variations. Both methods have been reported in literature before, but have hitherto not been combined and evaluated systematically. We combined gene and protein names from several existing databases of four different organisms. The combined dictionaries showed a substantial increase in recall on three different test sets, as compared to any single database. Application of 23 spelling variation rules to the combined dictionaries further increased recall. However, many rules appeared to have no effect and some appear to have a detrimental effect on precision.

Abstracting and Indexing↗

PubMed2006

The relation of thyroid function and ventricular repolarization: decreased serum thyrotropin levels are associated with short rate-adjusted QT intervals.

CONTEXT: The linkage of thyroid dysfunction with ventricular repolarization properties has not been investigated extensively, although alterations might be associated with an increased ventricular vulnerability. OBJECTIVE: The objective of the study was to investigate whether there is an association between functional thyroid status and rate-adjusted QT intervals (QTc). DESIGN, SETTING, AND PARTICIPANTS: The population-based Study of Health in Pomerania included 4310 subjects aged 20-79 yr. Data of 3610 subjects (1862 women and 1748 men) without branch bundle blocks or pacemaker were available for the present analyzes. MAIN OUTCOME MEASURES: QTc with respect to thyroid status. Short QTc was defined below the 25th percentile, and long QTc above the 75th percentile of the gender-specific distribution. RESULTS: TSH levels were positively associated with QTc independent from potential confounders in multivariable analyses (P for trend = 0.001). Subjects with decreased TSH levels had shorter QTc than those with normal TSH levels (426.4 +/- 8.2 vs. 430.2 +/- 8.2; P < 0.001). Adjusted odds ratios for short QTc in subjects with elevated, normal, and decreased TSH were 0.87 (95% confidence interval 0.58-1.31), 1.00 (reference), and 1.53 (95% confidence interval 1.16-2.03), respectively (P for trend = 0.008). CONCLUSION: TSH levels were positively related to QTc in a population-based sample. Subjects with decreased serum TSH levels had an increased risk for short QTc. Whether these findings are of clinical significance has to be investigated by further studies.

Adult↗

PubMed2006

Dispersion of repolarization, myocardial iso-source maps, and the electrocardiographic T and U waves.

The surface potential at any given electrode location is the net result of simultaneously acting and variously directed electrical forces in the myocardium. The degree to which the electrical forces in the heart are thus opposing each other has been defined as cancellation, and this mechanism plays a major role in the formation of the electrocardiogram (ECG). However, previous studies did not take into account the locations of the electrical sources. In this study, we used a computer model of the left ventricle to study the effect of source locations on cancellation during the T and U waves. The model represents an anatomically stylized cross-sectional slice of the left ventricle, containing 1961 hexagonal cells in a single layer. An action potential (AP) is assigned to each cell. The timing of the APs follows a simulated excitation sequence. The potential differences between the APs of adjacent cells produce time-varying electrical sources, each of which contributes to the potential in an arbitrary point P on the body proportionally to its own, location-dependent, transfer function (lead vector). The ECG at P is the sum of all potential contributions. For each time point in the ECG at P, the contribution of each cell is mapped back onto the slice. Adjacent cells with equal contributions form iso-source strings, together forming iso-source maps. The T-U wave as observed in P will be the sum of positive and negative contributions from the iso-source distributions as they change with time. The iso-source maps for an anteriorly located observation point P at 4.2 cm from the epicardial surface show a continuous interplay of positive and negative contributions. During the near-zero ST segment, cancellation varies between 80% and 100%. In the ascending limb of the T wave, positive contributions substantially increase, giving a decrease in cancellation to about 40%. At the end of the T wave (with almost zero amplitude), the positive contributions are only slightly reduced as compared with those at peak T, but greatly increased negative contributions cancel them out. This is contrary to the generally held view that the end of T signifies the end of the repolarization process. The manifest shape of the T and U waves is the result of complex interactions of varying and often largely canceling contributions. The iso-source maps are helpful to understand the genesis of the T and U waves.

Action Potentials↗

PubMed2006

Prevalence, incidence and lifetime risk of atrial fibrillation: the Rotterdam study.

AIMS: We aimed to investigate the prevalence and incidence of atrial fibrillation (AF) in a large European population-based study. METHODS AND RESULTS: The study is part of the Rotterdam study, a population-based prospective cohort study among subjects aged 55 years and above. The prevalence at baseline was assessed in 6808 participants. Incidence of AF was investigated during a mean follow-up period of 6.9 years in 6432 persons. We identified 376 prevalent and 437 incident cases. Overall prevalence was 5.5%, rising from 0.7% in the age group 55-59 years to 17.8% in those aged 85 years and above. The overall incidence rate was 9.9/1000 person-years. The incidence rate in the age group 55-59 years was 1.1/1000 person-years, rose to 20.7/1000 person-years in the age group 80-84 years and stabilized in those aged 85 years and above. Prevalence and incidence were higher in men than in women. The lifetime risk to develop AF at the age of 55 years was 23.8% in men and 22.2% in women. CONCLUSION: In this prospective study in a European population, the prevalence and incidence of AF increased with age and were higher in men than in women. The high lifetime risk to develop AF was similar to North American epidemiological data.

Age Distribution↗

PubMed2006

Incidence of recognized and unrecognized myocardial infarction in men and women aged 55 and older: the Rotterdam Study.

AIMS: Contemporary data on the incidence of unrecognized myocardial infarction (MI) among subjects aged 55 and older are limited. METHODS AND RESULTS: We studied the incidence of recognized and unrecognized MI in the Rotterdam Study, a population-based cohort of men and women aged 55 and older. The baseline examination was performed during 1990-93, with follow-up examinations during 1994-95, and 1997-2000. Baseline and follow-up 12-lead ECGs were analysed by the Modular ECG Analysis System. The 5148 participants who had no evidence of prevalent infarction were the subjects for analysis. Incident recognized infarction was defined as the occurrence of a fatal or non-fatal event coded as I21 according to the International Classification of Diseases, 10th edition. A repeat ECG was available in 4187 subjects. An unrecognized infarction was considered to have occurred if there was electrocardiographic evidence in the absence of a clinically recognized event. During a median follow-up of 6.4 years, 141 incident recognized infarctions occurred and the incidence rate of this event was 5.0 per 1000 person years. The incidence was higher in men (8.4) than in women (3.1). The incidence rate of unrecognized infarction was 3.8 per 1000 person years. Men (4.2) and women (3.6) had approximately similar incidence. Hence, the proportion of unrecognized infarction was lower in men (33%) than in women (54%). This difference in proportion of unrecognized infarctions was independent of age. CONCLUSION: A high proportion of incident MIs remains clinically unrecognized. As a history of MI is associated with an increased risk of repeat cardiovascular complications, our data suggest a need for periodical electrocardiographic screening to recognize (prevalent) infarctions and to install effective preventive treatment in those aged 55 and older.

Aged↗

PubMed2006

Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.

OBJECTIVES: This study sought to investigate whether prolongation of the heart rate-corrected QT (QTc) interval is a risk factor for sudden cardiac death in the general population. BACKGROUND: In developed countries, sudden cardiac death is a major cause of cardiovascular mortality. Prolongation of the QTc interval has been associated with ventricular arrhythmias, but in most population-based studies no consistent association was found between QTc prolongation and total or cardiovascular mortality. Only very few of these studies specifically addressed sudden cardiac death. METHODS: This study was conducted as part of the Rotterdam Study, a prospective population-based cohort study that comprises 3,105 men and 4,878 women aged 55 years and older. The QTc interval on the electrocardiogram was determined during the baseline visit (1990 to 1993) and the first follow-up examination (1993 to 1995). The association between a prolonged QTc interval and sudden cardiac death was estimated using Cox proportional hazards analysis. RESULTS: During an average follow-up period of 6.7 years (standard deviation, 2.3 years) 125 patients died of sudden cardiac death. An abnormally prolonged QTc interval (>450 ms in men, >470 ms in women) was associated with a three-fold increased risk of sudden cardiac death (hazard ratio, 2.5; 95% confidence interval, 1.3 to 4.7), after adjustment for age, gender, body mass index, hypertension, cholesterol/high-density lipoprotein ratio, diabetes mellitus, myocardial infarction, heart failure, and heart rate. In patients with an age below the median of 68 years, the corresponding relative risk was 8.0 (95% confidence interval 2.1 to 31.3). CONCLUSIONS: Abnormal QTc prolongation on the electrocardiogram should be viewed as an independent risk factor for sudden cardiac death.

Aged↗

PubMed2006

Unrecognized myocardial infarction: the association with cardiopulmonary symptoms and mortality is mediated via echocardiographic abnormalities of global dysfunction instead of regional dysfunction: the Olmsted County Heart Function Study.

BACKGROUND: There are very few data describing the association of electrocardiogram-based unrecognized myocardial infarction (ECG-UMI) with nonanginal cardiopulmonary symptoms, echocardiographic abnormalities, and mortality in the community. METHODS: We studied 2042 Olmsted County residents, who were randomly selected and aged > or = 45 years, by a survey questionnaire for symptoms, echocardiogram for structural abnormalities, and a 5-year follow-up for all-cause mortality. Unrecognized myocardial infarctions (n = 81) were diagnosed if ECG-based myocardial infarction (MI) criteria were met without the history of a documented recognized MI. RESULTS: In UMI versus no MI controls, the prevalence (%) of dyspnea on exertion (49 vs 29), orthopnea (6 vs 4), palpitations (20 vs 15), and history of fluid overload (6 vs 1) was significantly higher (P < .05). The associations of exertional dyspnea and history of fluid overload with UMI were independent of age, sex, and pulmonary disease but had a significant reduction in their magnitude after adjusting for global dysfunction (diastolic or systolic dysfunction). All the 4 symptoms were associated with increased risk of mortality (hazard ratios ranging from 2.3 to 9.1, P < .0001), which was meaningfully attenuated by adjusting for ECG-UMI status. Global ventricular dysfunction had a more significant impact on this association than regional ventricular dysfunction (wall motion abnormalities). CONCLUSIONS: The increased risk of mortality associated with symptoms is at least in part mediated via ECG-UMI. Structural abnormalities of global dysfunction play a greater role in mediating this risk than regional dysfunction, challenging the current clinical practice of calling an ECG-based MI false positive in symptomatic adults in the absence of wall motion abnormalities.

Aged↗

PubMed2005

Cardiovascular disease, risk factors and heart rate variability in the elderly general population: design and objectives of the CARdiovascular disease, Living and Ageing in Halle (CARLA) Study.

BACKGROUND: The increasing burden of cardiovascular diseases (CVD) in the ageing population of industrialized nations requires an intensive search for means of reducing this epidemic. In order to improve prevention, detection, therapy and prognosis of cardiovascular diseases on the population level in Eastern Germany, it is necessary to examine reasons for the East-West gradient of CVD morbidity and mortality, potential causal mechanisms and prognostic factors in the elderly. Psychosocial and nutritional factors have previously been discussed as possible causes for the unexplained part of the East-West gradient. A reduced heart rate variability appears to be associated with cardiovascular disease as well as with psychosocial and other cardiovascular risk factors and decreases with age. Nevertheless, there is a lack of population-based data to examine the role of heart rate variability and its interaction with psychosocial and nutritional factors regarding the effect on cardiovascular disease in the ageing population. There also is a paucity of epidemiological data describing the health situation in Eastern Germany. Therefore, we conduct a population-based study to examine the distribution of CVD, heart rate variability and CVD risk factors and their associations in an elderly East German population. This paper describes the design and objectives of the CARLA Study. METHODS/DESIGN: For this study, a random sample of 45-80 year-old inhabitants of the city of Halle (Saale) in Eastern Germany was drawn from the population registry. By the end of the baseline examination (2002-2005), 1750 study participants will have been examined. A multi-step recruitment strategy aims at achieving a 70% response rate. Detailed information is collected on own and family medical history, socioeconomic, psychosocial, behavioural and biomedical factors. Medical examinations include anthropometric measures, blood pressure of arm and ankle, a 10-second and a 20-minute electrocardiogram, a general physical examination, an echocardiogram, and laboratory analyses of venous blood samples. On 200 participants, a 24-hour electrocardiogram is recorded. A detailed system of quality control ensures high data quality. A follow-up examination is planned. DISCUSSION: This study will help to elucidate pathways to CVD involving autonomic dysfunction and lifestyle factors which might be responsible for the CVD epidemic in some populations.

Aged↗

PubMed2005

Databases for knowledge discovery. Examples from biomedicine and health care.

Examples are given of the use of large research databases for knowledge discovery. Such databases are not only increasingly used for research in the 'hard' mathematics-based disciplines such as physics and engineering but also in more 'soft' disciplines, such as sociology, psychology and, in general, the humanities. In between the 'hard' and the 'soft' disciplines lie disciplines such as biomedicine and health care, from which we have selected our illustrations. This latter area can be subdivided into: (1) fundamental biomedical research, related to the 'hard' scientific approach; (2) clinical research, using both 'hard' and 'soft' data and (3) population-based research, which can be subdivided into prospective and retrospective research. The examples that we shall offer are representative for using computers in scientific research in general, but in medical and health informatics in particular.

Biomedical Research↗

PubMed2005

Echocardiographic characteristics of electrocardiographically unrecognized myocardial infarctions in a community population.

Unrecognized myocardial infarction (UMI) as diagnosed by surveillance electrocardiography has been shown to carry the same poor prognosis as recognized myocardial infarction (RMI). The echocardiographic characteristics of UMI have never been studied before. Due to a similar prognosis, we hypothesized that UMI and RMI would exhibit similar degrees of echocardiographic ventricular dysfunction. We studied a random community cohort of 2,042 adults who were > or =45 years of age in a cross-sectional setting in Olmsted County, Minnesota. RMI was diagnosed by review of medical records and UMI was diagnosed if the electrocardiogram met MI criteria without a previous MI recorded in the medical record. All subjects underwent transthoracic echocardiography. We identified 80 patients who had UMI and 101 who had RMI. In bivariate analyses, a stepwise increase in echocardiographic abnormalities was observed from participants who had no MI to UMI to RMI: respective mean ejection fractions were 63%, 61%, and 55; prevalences in left ventricular enlargement were 13%, 22%, and 52%; mean left ventricular mass indexes were 98, 103, and 118 g/m(2); prevalences in regional wall motion abnormality were 2%, 13%, and 42%; and prevalences in diastolic dysfunction were 25%, 56%, and 65% (p for trend <0.0001 for all comparisons). After adjusting for standard coronary risk factors, patients who had UMI continued to exhibit significant abnormalities in systolic dysfunction, diastolic dysfunction, and regional wall motion abnormality, although to a lesser extent than patients who had RMI. In conclusion, patients who have UMI manifest structural abnormalities more commonly than do patients who have no MI but less commonly than do those who have RMI. The similar prognosis after UMI and RMI cannot be explained by comparable degrees of ventricular damage.

Aged↗

PubMed2005

The U wave in the electrocardiogram: a solution for a 100-year-old riddle.

OBJECTIVE: In the electrocardiogram (ECG) the U wave follows the T, which is considered to reflect the repolarization of the cardiac ventricles. Despite the U wave's well-known clinical relevance, a satisfactory explanation of its origin is still outstanding. We have undertaken to explain the formation of the U wave by means of a simple digital model of the left ventricle. METHODS: The model employs a multi-layered segment of the myocardium. To each layer an action potential (AP) is assigned with shape and duration according to published data. The potential differences between the APs produce time-varying electrical sources. Each source contributes to the potentials in an arbitrary point P of the body. The strength of this contribution is determined by a specific coefficient, the "lead vector", linking P to the source. The ECG recorded at P is calculated as the sum of all potential contributions. RESULTS: The repolarization waves constructed in this way reproduce the natural aspects of a T wave followed by a U wave. The creation of a U wave is conditional on small voltage differences between the tail ends of the APs. No fundamental demarcation exists between U wave and preceding T wave. The morphology of the T-U wave is dependent on the geometrical position of P with respect to the myocardium. CONCLUSION: T and U form a continuum. Together they are the resultant of one and the same process of repolarization of the ventricular myocardium. This has implications for the measurement of QT duration and for safety testing of drug-induced QT prolongation.

Computer Simulation↗

PubMed2005

Storing, linking, and mining microarray databases using SRS.

BACKGROUND: SRS (Sequence Retrieval System) has proven to be a valuable platform for storing, linking, and querying biological databases. Due to the availability of a broad range of different scientific databases in SRS, it has become a useful platform to incorporate and mine microarray data to facilitate the analyses of biological questions and non-hypothesis driven quests. Here we report various solutions and tools for integrating and mining annotated expression data in SRS. RESULTS: We devised an Auto-Upload Tool by which microarray data can be automatically imported into SRS. The dataset can be linked to other databases and user access can be set. The linkage comprehensiveness of microarray platforms to other platforms and biological databases was examined in a network of scientific databases. The stored microarray data can also be made accessible to external programs for further processing. For example, we built an interface to a program called Venn Mapper, which collects its microarray data from SRS, processes the data by creating Venn diagrams, and saves the data for interpretation. CONCLUSION: SRS is a useful database system to store, link and query various scientific datasets, including microarray data. The user-friendly Auto-Upload Tool makes SRS accessible to biologists for linking and mining user-owned databases.

Computational Biology↗

PubMed2005

Thesaurus-based disambiguation of gene symbols.

BACKGROUND: Massive text mining of the biological literature holds great promise of relating disparate information and discovering new knowledge. However, disambiguation of gene symbols is a major bottleneck. RESULTS: We developed a simple thesaurus-based disambiguation algorithm that can operate with very little training data. The thesaurus comprises the information from five human genetic databases and MeSH. The extent of the homonym problem for human gene symbols is shown to be substantial (33% of the genes in our combined thesaurus had one or more ambiguous symbols), not only because one symbol can refer to multiple genes, but also because a gene symbol can have many non-gene meanings. A test set of 52,529 Medline abstracts, containing 690 ambiguous human gene symbols taken from OMIM, was automatically generated. Overall accuracy of the disambiguation algorithm was up to 92.7% on the test set. CONCLUSION: The ambiguity of human gene symbols is substantial, not only because one symbol may denote multiple genes but particularly because many symbols have other, non-gene meanings. The proposed disambiguation approach resolves most ambiguities in our test set with high accuracy, including the important gene/not a gene decisions. The algorithm is fast and scalable, enabling gene-symbol disambiguation in massive text mining applications.

Algorithms↗

PubMed2005

Mild renal dysfunction is associated with electrocardiographic left ventricular hypertrophy.

BACKGROUND: Both renal dysfunction and left ventricular hypertrophy (LVH) are signs of end-organ damage, risk markers of cardiovascular (CV) disease and chronic heart failure. In selected populations such as those with diabetes or hypertension, renal dysfunction was found to be related to LVH. We studied the relation between renal dysfunction and LVH in a cross-sectional study in 8592 inhabitants from Groningen, The Netherlands. METHODS: Standard 12-lead electrocardiograms were recorded, and LVH was classified using the Cornell voltage duration product. Renal dysfunction was defined as creatinine clearance <60 mL/min/1.73 m(2) or microalbuminuria (30 to 300 mg/24 h). RESULTS: Electrocardiographic signs of LVH were present in 396 of subjects (5.3%). Subjects with LVH were older and had a more extensive CV risk profile. We found that LVH was more prevalent in subjects with renal dysfunction than in those without (8% v 4%, P < .001). Multivariate regression analysis demonstrated that renal dysfunction was independently related to a 1.47-fold increased risk of the presence of LVH (95% CI = 1.15 to 1.88, P = .009). In addition, both creatinine clearance (OR = 1.56, 95% CI = 1.07 to 2.2, P = .044) and microalbuminuria (OR = 1.37, 95% CI = 1.04 to 1.80, P = .024) were independently associated with the presence of LVH. CONCLUSION: Subjects with mild renal dysfunction have a substantially higher risk of LVH on electrocardiography than those without renal dysfunction.

Adult↗

PubMed2005

Effect of n-3 fatty acids from fish on electrocardiographic characteristics in patients with frequent premature ventricular complexes.

n-3 Fatty acids may protect against heart disease mortality by preventing fatal arrhythmias. Underlying effects on cardiac electrophysiology may be demonstrable in the standard electrocardiogram (ECG) and provide insight into the mechanism. Therefore, we investigated the effect of dietary n-3 fatty acids on heart-rate-corrected QT interval, T-loop width, spatial QRS-T angle and spatial U-wave amplitude in patients with frequent premature ventricular complexes. Seventy-four patients received either capsules providing 1.5 g n-3 fatty acids daily or placebo for approximately 14 weeks. ECG were recorded before and after intervention. None of the ECG characteristics was significantly affected by treatment. The present results do not provide additional support for the hypothesis that n-3 fatty acids prevent cardiac arrhythmia through generic electrophysiologic effects on heart cell membranes. However, we cannot exclude effects of n-3 fatty acids on clinical relevant endpoints that are not easily detected by prior changes in the ECG.

Aged↗

PubMed2005

Word sense disambiguation in the biomedical domain: an overview.

There is a trend towards automatic analysis of large amounts of literature in the biomedical domain. However, this can be effective only if the ambiguity in natural language is resolved. In this paper, the current state of research in word sense disambiguation (WSD) is reviewed. Several methods for WSD have already been proposed, but many systems have been tested only on evaluation sets of limited size. There are currently only very few applications of WSD in the biomedical domain. The current direction of research points towards statistically based algorithms that use existing curated data and can be applied to large sets of biomedical literature. There is a need for manually tagged evaluation sets to test WSD algorithms in the biomedical domain. WSD algorithms should preferably be able to take into account both known and unknown senses of a word. Without WSD, automatic metaanalysis of large corpora of text will be error prone.

Algorithms↗

PubMed2005

Online tools to support literature-based discovery in the life sciences.

In biomedical research, the amount of experimental data and published scientific information is overwhelming and ever increasing, which may inhibit rather than stimulate scientific progress. Not only are text-mining and information extraction tools needed to render the biomedical literature accessible but the results of these tools can also assist researchers in the formulation and evaluation of novel hypotheses. This requires an additional set of technological approaches that are defined here as literature-based discovery (LBD) tools. Recently, several LBD tools have been developed for this purpose and a few well-motivated, specific and directly testable hypotheses have been published, some of which have even been validated experimentally. This paper presents an overview of recent LBD research and discusses methodology, results and online tools that are available to the scientific community.

Abstracting and Indexing↗

PubMed2005

Identification of optimal electrocardiographic criteria for the diagnosis of unrecognized myocardial infarction: a population-based study.

BACKGROUND: Despite using the same tool (ECG), the proportion of myocardial infarctions that goes unrecognized varies from 20% to 60% in population-based studies. The reasons for such wide variations have not been studied. We sought to evaluate the effect of ECG-MI criteria and study methodology on the prevalence of unrecognized myocardial infarction (UMI) and to identify the optimal ECG-MI criteria for UMI detection in epidemiologic studies. METHODS: A random population-based sample of 2042 adults, age > or = 45 years, underwent history, medical record abstraction and ECG. Six different ECG-MI criteria and two subjective recognized myocardial infarction (RMI) identification criteria, from different published studies, were applied to the same survey ECG. The operating test characteristics of different criteria were compared with the objective criterion standard of a RMI by Gillum criteria. RESULTS: The UMI proportion estimates varied from 32% to 61% due to variation in ECG-MI criteria, while keeping the study population, MI recognition criteria, and ECG constant. Subjective criteria for MI recognition had limited value (positive predictive value of 44-93%) in picking up RMI. Depending on the ECG abnormality used to define MI, ECG reading had widely varying sensitivity (21-37%; P < 0.0001) with consistently high specificity (92-97%) for detection of RMI. CONCLUSIONS: The prevalence estimates of UMI vary widely and are strongly dependent on the ECG-MI and MI recognition criteria. Future studies of UMI should explicitly recognize this variation and select the ECG-MI criteria that match their study aims.

Cross-Sectional Studies↗