bluuebunny/crossref_metadata_2025_split huggingface dataset:
Replication in genetic studies of complex traits
Authors: Sillanpää Mikko J. , Auranen Kari 
Published: December 2004

SummaryDisappointments in replicating initial findings in gene mapping for complex traits are often attributed to small sample sizes and inadequate techniques to determine the threshold value. This is clearly not the whole truth. More fundamental reasons lie in the inherent heterogeneity related to disease, including genetic heterogeneity, differences in allele frequencies, and context‐dependency in genetic architecture. There are also other reasons related to the data collection and analysis. Replication may remain a source of frustration unless more emphasis is put on controlling these sources of heterogeneity between studies.
Power of Variance Component Linkage Analysis—II. Discrete Traits
Authors: WILLIAMS J. T. , BLANGERO J. 
Published: December 2004

SummaryWe determine the power of variance component linkage analysis in the case of discrete, dichotomous traits analyzed under a classical liability threshold model. For simplicity we consider randomly ascertained samples and an additive model of variation incorporating a qtl, residual additive genetic factors, and individual‐specific random environmental effects. We derive an expression for the power of variance component linkage analysis in arbitrary relative pairs, and compare the power of discrete and quantitative trait linkage analysis in the specific case of sibpairs. The predicted sample sizes required in linkage analysis of sibpairs are confirmed by analysis of simulated data. Unlike the affected‐sibpair method, the power of discrete trait variance component analysis increases with trait prevalence. The relative efficiency of a discrete trait for linkage analysis increases with population trait prevalence, but does not exceed about 40% and is typically much less.
Genetic Evidence Concerning the Origins of South and North Ossetians
Authors: Nasidze Ivan , Quinque Dominique , Dupanloup Isabelle , Rychkov Sergey , Naumova Oksana , Zhukova Olga , Stoneking Mark 
Published: December 2004

SummaryOssetians are a unique group in the Caucasus, in that they are the only ethnic group found on both the north and south slopes of the Caucasus, and moreover they speak an Indo‐European language in contrast to their Caucasian‐speaking neighbours. We analyzed mtDNA HV1 sequences, Y chromosome binary genetic markers, and Y chromosome short tandem repeat (Y‐STR) variability in three North Ossetian groups and compared these data to published data for two additional North Ossetian groups and for South Ossetians. The mtDNA data suggest a common origin for North and South Ossetians, whereas the Y‐haplogroup data indicate that North Ossetians are more similar to other North Caucasian groups, and South Ossetians are more similar to other South Caucasian groups, than to each other. Also, with respect to mtDNA, Ossetians are significantly more similar to Iranian groups than to Caucasian groups. We suggest that a common origin of Ossetians from Iran, followed by subsequent male‐mediated migrations from their Caucasian neighbours, is the most likely explanation for these results. Thus, genetic studies of such complex and multiple migrations as the Ossetians can provide additional insights into the circumstances surrounding such migrations.
Susceptibility to Basal Cell Carcinoma: Associations with PTCH Polymorphisms
Authors: Strange R. C. , El‐Genidy N. , Ramachandran S. , Lovatt T. J. , Fryer A. A. , Smith A. G. , Lear J. T. , Wong C. , Jones P. W. , Ichii‐Jones F. , Hoban P. R. 
Published: December 2004

SummaryLoss of function of the human patched gene (PTCH) is common and critical in basal cell carcinoma (BCC) development. Indirect evidence suggests polymorphism in PTCH mediates BCC risk. We studied 659 BCC cases and 300 controls to determine if exon 2318, 3429, 111552, 121665, 121686, 142199 and 233944 and intron 91336‐135 and 152560+9PTCH variants were sufficiently common for use in case‐control studies, and if selected markers were associated with risk. Intron 152560+9 and exon 233944 variants were studied further. Their genotype frequencies were not significantly different in controls and cases, though frequency of the G2560+9‐C3944 haplotype was lower in all cases (odds ratio = 0.44, p = 0.009) and those stratified by BCC site and rate of development of further tumours. This association was not mediated by the extent of UVR exposure. We confirmed the robustness of these findings by showing these associations demonstrated similar odds ratios in two groups of randomly selected cases and controls, and using the false positive report probability (FPRP) approach described by Wacholder et al. (2004). The FPRP value (0.168) was in the noteworthy category. These data, showing for the first time that PTCH polymorphism mediates susceptibility, are compatible with reports showing that PTCH haploinsufficiency influences development of BCC precursor lesions.
Correlation Between the Allelic Distribution of STRs in a Finnish Population and Phenotypically Different Gastrointestinal Tumours: A Study Using Four X‐Chromosomal Markers (DXS7423, DXS8377, ARA, DXS101)
Authors: Vauhkonen H. , Vauhkonen M. , Sipponen P. , Sajantila A. 
Published: December 2004

SummaryMicrosatellite instability in tumours has been suggested as a model to study the process of short tandem repeat (STR) mutations. In the present study we have determined the allelic variation of four X‐STRs (DXS7423, DXS8377, DXS101 and ARA) in a Finnish population of 103 individuals, and assessed whether a comparable allelic distribution could be found in a series of gastrointestinal cancers differing by the level of microsatellite instability. Fifty‐seven gastric and colorectal cancers were stratified by autosomal STRs, and the mononucleotide marker BAT‐26 into stable, low‐level unstable and high‐level unstable microsatellite (MSI‐H) cancers, of which the last produced the majority of X‐STR alleles. For the four markers analysed, a significant correlation of allele distribution between our Finnish population sample and MSI‐H tumours was noted. Together, the eight MSI‐H tumours found represented 80%, 66–80% and 100% of the DXS101 alleles in the Finnish, and in previously described Caucasian and Korean population samples, respectively. Of the ARA, DXS7423 and DXS8377 alleles in the Finnish population, 42%, 75% and 79% were found in the MSI‐H cancers, respectively. The results suggest that analysis of STR variation in a relatively small number of MSI‐H cancers may aid in pre‐evaluation of their allelic distribution in a population.
White Blood Cell Count and the Occurrence of Silent Ischemia after Myocardial Infarction
Authors: Kurpesa Małgorzata , Trzos Ewa , Krzemińska‐Pakuła Maria 
Published: December 2004

Background: Inflammation plays a role in the pathogenesis of atherosclerosis. Attempts are made to use markers of inflammation as prognostic factors in coronary artery disease and acute coronary syndromes. The correlation between inflammation and silent postinfarction ischemia is unknown. Methods: The study population consists of 104 asymptomatic patients who had uncomplicated Q‐wave myocardial infarction within 6 months prior to the enrollment. After the white blood cell (WBC) count was assessed, the population was divided into two groups: group I comprising 48 patients with WBC ≤ 7.0 × 103/μl and group II comprising 56 patients with WBC > 7.0 × 103/μl. Twenty‐four‐hour Holter monitoring was performed to detect the presence of silent ischemia. Results: Eighty‐eight silent ischemic episodes were recorded. Ischemia on Holter monitoring was detected in 47 patients (84%) from group II and in five patients (9%) in group I (P < 0.01). We have found a significant positive correlation between WBC count and the number of ischemic episodes (r = 0.25), their maximal amplitude (r = 0.39), duration (r = 0.34), and total ischemic burden (r = 0.36). In multivariate analysis leucocytosis proved to be the only parameter independently correlated with the presence of silent ischemia. Conclusion: Postinfarction asymptomatic patients with increased WBC count are more likely to have residual ischemia.
Seasonal Variability of QT Dispersion in Healthy Young Males
Authors: Kose Sedat , Aytemir Kudret , Can Ilknur , Iyisoy Atilla , Kursaklioglu Hurkan , Amasyali Basri , Kilic Ayhan , Isik Ersoy , Oto Ali , Demirtas Ertan 
Published: December 2004

Background: There are few data related to the seasonal influences on the QT dispersion. Methods: We analyzed the effects of seasons on QT dispersion in a large group of healthy young males. We studied the seasonal variability of QT dispersion in 523 healthy male subjects aged 22 ± 4 years (ranging from 20 to 26). Four seasonal 12‐lead resting electrocardiograms (ECGs) recorded at double amplitude were performed at 25 mm/s at intervals of 3 months. Subsequent ECGs were recorded within 1 hour of the reference winter recording. QT dispersion was defined as the difference between the longest and the shortest mean QT intervals. Results: There was a significant seasonal variation in QT dispersion (P = 0.001), with the largest QT dispersion in winter (71 ± 18 ms) and the smallest one in spring (43 ± 19). Conclusion: There exists a significant seasonal variation in QT dispersion of healthy subjects and such variability should be taken into consideration in the evaluation process of QT dispersion.
Sildenafil Citrate Does Not Affect QT Intervals and QT Dispersion: An Important Observation for Drug Safety
Authors: Alpaslan Mete , Onrat Ersel , Samli Murat , Dincel Cetin 
Published: December 2004

Background: Sildenafil is an effective and widely used therapeutic agent for erectile dysfunction. Deaths have been reported due to sildenafil use and most of them are attributed to concurrent use of nitrates. However, the effects of sildenafil on QT intervals, QT dispersion, and the possible risk of ventricular arrhythmia have not been studied before. Our aim in this study was to evaluate the effect of sildenafil citrate on QT intervals and QT dispersion. Methods: Thirty‐six patients with erectile dysfunction were included in this study. Twenty‐one patients had coronary artery disease whereas 12 of them also had accompanying diabetes mellitus. Standard 12‐lead electrocardiograms (ECG) were recorded three times: before, and at the first and fourth hours of 50 mg sildenafil citrate ingestion. All QT parameters were corrected for heart rate. Results: Mean age of the patients was 54 ± 12 years. The mean heart rate did not differ significantly between the three ECG examinations. The corrected and uncorrected maximum and minimum QT intervals were not significantly different between the three ECG examinations. The QT dispersion and corrected QT dispersion before and 1 hour and 4 hours after sildenafil ingestion were 31 ± 9 ms, 36 ± 10 ms; 32 ± 11 ms, 37 ± 14 ms; 27 ± 8 ms, 32 ± 9 ms, respectively (P > 0.05). Conclusions: Sildenafil does not prolong QT intervals or increase QT dispersion in patients with erectile dysfunction. Our results suggest that the risk of ventricular arrhythmia does not increase with ingestion of 50 mg sildenafil.
Increased P‐Wave Duration and P‐Wave Dispersion in Patients with Aortic Stenosis
Authors: Turhan Hasan , Yetkin Ertan , Atak Ramazan , Altinok Tayfun , Senen Kubilay , Ileri Mehmet , Sasmaz Hatice , Cehreli Sengul , Kutuk Emine 
Published: December 2004

Background: P‐wave dispersion (PWD), defined as the difference between the maximum and minimum P‐wave duration, has been proposed as being useful for the prediction of paroxysmal atrial fibrillation (AF). AF is the most common arrhythmia and an important prognostic indicator for clinical deterioration in patients with aortic stenosis (AS). The aim of the present study was to evaluate PWD in patients with AS. Methods: The study population consisted of two groups: Group I consisted of 98 patients with AS (76 men, 22 women; aged 63 ± 8 years) and group II consisted of 98 healthy subjects (same age and sex) without any cardiovascular disease. A 12‐lead electrocardiogram was recorded for each subject. The P‐wave duration was calculated in all leads of the surface electrocardiogram. The difference between the maximum and minimum P‐wave duration was calculated and was defined as the PWD. All patients and control subjects were also evaluated by echocardiography to measure the left atrial diameter, left ventricular ejection fraction, left ventricular wall thicknesses, and the maximum and mean aortic gradients. Patients were also evaluated for the presence of paroxysmal AF. Results: Maximum P‐wave duration and PWD of group I were found to be significantly higher than those of group II. In addition, patients with paroxysmal AF had significantly higher PWD than those without paroxysmal AF. There was no significant difference between the two groups regarding minimum P‐wave duration. In addition, there was no significant correlation between echocardiographic variables and PWD. Conclusion: PWD, indicating increased risk for paroxysmal AF, was found to be significantly higher in patients with AS than in those without it. Further assessment of the clinical utility of PWD for the prediction of paroxysmal AF in patients with severe AS will require longer prospective studies.
The Relation of QT Dispersion and Localized QT Difference to Coronary Pathology in a Population with Unstable Coronary Artery Disease
Authors: Kesek Milos , Englund Anders , Jernberg Tomas , Lagerqvist Bo , Lindahl Bertil 
Published: December 2004

Background: QT dispersion (QTd) contains prognostic information in several patient groups. The variable increases in several conditions with ischemia. Originally, it was thought to reflect the local repolarization inhomogeneity. Even though this explanation has been questioned lately, it continues to be put forward. In order to elucidate a possible local mechanism, we investigated the relation between QT dispersion, an ECG parameter reflecting the local dispersion, and angiographical measures in a population with unstable coronary artery disease. Methods: The 276 patients were recruited from the FRISC II trial. As the QTd parameter we used the mean value of automatically measured QTd during 27 hours after admission (QTdMean). As a local repolarization measure we used the maximal difference in QT between two adjacent ECG leads (QTdiffMean). The computations were performed on all available ECG leads and on a restricted set without the V1–V2 combination. Previously published angiographic scoring tools were adapted for rating and localizing the coronary pathology by two approaches and applied on 174 patients undergoing angiography. Results: QTdMean was significantly higher than that reported in previous material with unselected chest pain patients (55 vs 40 ms). QTdiffMean correlated strongly with QTdMean. No differences in QTdMean were detected between patients with different angiographical scores. No relation could be shown between the region with dominating coronary pathology as expressed by the scoring tools and the localization of QTdiffMean. Conclusions: QTd in ischemia seems to be increased by a mechanism unrelated to localization and severity of coronary disease.
Relationship Between ST‐Segment Morphology and Conduction Disturbances Detected by Signal‐Averaged Electrocardiography in Brugada Syndrome
Authors: Takami Mitsuaki , Ikeda Takanori , Enjoji Yoshihisa , Sugi Kaoru 
Published: December 2004

Background: Although arrhythmogenesis of Brugada syndrome is still unknown, it has been reported to be associated with conduction disturbances. Two ST‐segment morphologies (coved and saddle‐back patterns) have been described in this syndrome. No study has sought to determine which morphology has stronger conduction disturbances, thereby associating with life‐threatening events. Methods: Forty‐six patients who presented the Brugada‐type ECG with either of a characteristic coved (n = 25) or saddle‐back (n = 21) pattern of ST‐segment morphology underwent signal‐averaged ECG (SAECG). SAECG parameters, and the history of life‐threatening events defined as syncope or aborted sudden death, were compared between groups. Results: Although filtered QRS duration did not differ between groups, the incidence of late potentials in the coved group was higher than in the saddle‐back group (22 patients (88%) versus 4 patients (19%); P < 0.01), showing lower RMS40 and longer LAS40. Life‐threatening events occurred in 17 patients (68%) in the coved group and 7 patients (33%) in the saddle‐back group (P = 0.02). Conclusion: The coved pattern of ST segment was more closely related to conduction disturbances than the saddle‐back pattern in patients with Brugada‐type ECG. Life‐threatening events were more common in patients with the coved ST‐segment elevation. Conduction disturbances in the coved pattern of ST segment may reflect a substrate of arrhythmogenesis in Brugada syndrome.
Prevalence of Potential Noninvasive Arrhythmia Risk Predictors in Healthy, Middle‐Aged Persons
Authors: Grimm Wolfram , Liedtke Julia , Müller Hans‐Helge 
Published: December 2004

Background: To date, prevalence and clinical significance of noninvasive arrhythmia risk predictors in apparently healthy, middle‐aged persons are largely unknown. Methods: A total of 110 apparently healthy persons 20–75 years old were enrolled in this prospective observational monocenter study and followed up for 32 ± 15 months. Baseline investigations included symptom‐limited bicycle ergometry, echocardiography, time‐domain analysis, and spectral turbulence analysis of the signal‐averaged electrocardiogram (ECG), ventricular arrhythmias, and heart rate variability on 24‐hour Holter ECG, baroreflex sensitivity, and t‐wave alternans in all persons. Results: The prevalence of an abnormal signal‐averaged ECG was 1% for spectral turbulence analysis and varied between 1% and 37% for time‐domain analysis depending upon the definition used for an abnormal time‐domain analysis. A reduced heart rate variability defined as a standard deviation of normal‐to‐normal intervals ≤105 ms, <100 ms and <70 ms was found in 12%, 9%, and 1% of persons. A baroreflex sensitivity <6 ms/mmHg and <3 ms/mmHg was present in 15% and 2% of persons. Microvolt t‐wave alternans was found to be positive in 5%, negative in 88%, and indeterminate in 7% of persons, respectively. During the 32 ± 15 months follow‐up, no arrhythmic events and no cardiovascular mortality were observed in this population. Conclusions: Abnormal findings of noninvasive arrhythmia risk stratification can be found in 1–37% of healthy, middle‐aged persons when previously reported cut‐off values are used.
Long‐Term Improvement of QT Dispersion is Unaffected by Short‐Term Changes in Blood Pressure During Treatment of Systemic Hypertension with Enalapril
Authors: Seara Francisco Javier García , Juanatey José Ramón González , Sande José Luis Martínez , Veloso Pedro Rigueiro , Reino Antonio Pose , Román Alfonso Varela , Cerrato José Cabezas , Peña Miguel Gil de la 
Published: December 2004

Background: We report the reduction of QT and QTc dispersion in patients treated for 7 years with enalapril for systemic hypertension with left ventricular (LV) hypertrophy. We assess the correlation between QT dispersion and LV mass during this period and at the end of an 8‐week period of suspension of enalapril treatment after 5 years. Methods: Twenty‐four previously untreated patients with this condition took enalapril (20 mg twice daily) for 7 years, except during an 8‐week period following 5‐year follow‐up. Cardiovascular parameters were determined by two‐dimensional guided M‐mode echocardiography, and QT interval was measured, in a pretreatment placebo phase, 8 weeks and 1, 3, 5, and 7 years after the start of the therapy, at the end of the 8‐week suspension effected after 5 years, and 8 weeks after the end of the suspension. Results: Therapy rapidly reduced blood pressure (BP) from 156/105 mmHg to normal values: 134/84 mmHg after 8 weeks’ treatment, 130–84 mmHg at 7‐year follow‐up (P < 0.001 with respect to the placebo phase). LV mass index decreased progressively until at 5‐year follow‐up the reduction had reached 39% (P < 0.001), after which neither LV mass nor any other structural parameter underwent any further significant change. During this time, QT dispersion (ΔQT) and the dispersion of “corrected” QT (ΔQTc) decreased significantly: ΔQT (from 61 ± 21 to 37 ± 13 ms) and ΔQTc (from 67 ± 27 to 41 ± 16 ms). After suspension of treatment for 8 weeks following 5‐year follow‐up, ΔQT was 40 ± 14 ms and ΔQTc was 44 ± 17 ms; there were no significant changes either in ΔQT and ΔQTc or LV hypertrophy although BP had returned to pretreatment values (BP: 150 ± 16; 101 ± 10 mmHg). Conclusions: Long‐term enalapril treatment of hypertensive patients with LV hypertrophy induces marked regression of LV mass and improvement of QT dispersion. These improvements occur on a longer timescale than improvement in BP, and are not affected by transient changes in BP values.
Testing of a New T‐Wave Subtraction Algorithm as an Aid to Localizing Ectopic Atrial Beats
Authors: Marenco John P. , Nakagawa Hiroshi , Yang Shawn , MacAdam David , Xu Lucien , He Ding S. , Link Mark S. , Homoud Munther K. , Estes III N.A. Mark , Wang Paul J. 
Published: December 2004

Background: Identifying the timing and morphology of an ectopic P wave from the surface electrogram can aid in the diagnosis and localization of atrial arrhythmias. Given the relatively short coupling interval of atrial ectopic beats, the P wave is often obscured by the larger amplitude QRS‐T wave complex. A method to uncover such “buried” P waves using a standard 12‐lead surface ECG would be clinically useful and could potentially be a noninvasive guide to catheter ablation of focal atrial tachycardia. Methods: We developed an automated computerized program (BARD DUO LAB SYSTEM™) designed to subtract the QRS‐T wave complex from the surface electrogram and uncover a previously obscured P wave. The purpose of the present study was to validate this program. The surface ECG from 21 patients undergoing atrial pacing during electrophysiologic study (group I) and 10 patients with atrial tachycardia (group II) were analyzed and the derived P‐wave morphology assessed using correlation waveform analysis (CWA) and visual grading by three reviewers. Results: The algorithm successfully uncovered the P wave in each surface ECG. For the 21 patients in group I, average CWA comparing the derived P wave with the previous paced P wave was 83%. Average CWA for group II was 82%. Visual grading of the match between derived P waves and paced P waves revealed a 21/21 match in group I patients and a 12/12 match in 9/10 of group II patients. Conclusions: An ectopic atrial P wave obscured by a coincident QRS‐T wave complex can be accurately uncovered using this new algorithm. Addition of this technique to existing methods may improve the diagnosis of atrial arrhythmias and aid in the localization and ablation of ectopic atrial foci.