Biomedical subjects

B Thiel

Publications and source records attributed to B Thiel.

At least 19 recordsLinked to original sources

PubMed2005

Joint multi-population analysis for genetic linkage of bipolar disorder or "wellness" to chromosome 4p.

To test the hypothesis that the same genetic loci confer susceptibility to, or protection from, disease in different populations, and that a combined analysis would improve the map resolution of a common susceptibility locus, we analyzed data from three studies that had reported linkage to bipolar disorder in a small region on chromosome 4p. Data sets comprised phenotypic information and genetic marker data on Scottish, Danish, and USA extended pedigrees. Across the three data sets, 913 individuals appeared in the pedigrees, 462 were classified, either as unaffected (323) or affected (139) with unipolar or bipolar disorder. A consensus linkage map was created from 14 microsatellite markers in a 33 cM region. Phenotypic and genetic data were analyzed using a variance component (VC) and allele sharing method. All previously reported elevated test statistics in the region were confirmed with one or both analysis methods, indicating the presence of one or more susceptibility genes to bipolar disorder in the three populations in the studied chromosome segment. When the results from both the VC and allele sharing method were considered, there was strong evidence for a susceptibility locus in the data from Scotland, some evidence in the data from Denmark and relatively less evidence in the data from the USA. The test statistics from the Scottish data set dominated the test statistics from the other studies, and no improved map resolution for a putative genetic locus underlying susceptibility in all three studies was obtained. Studies reporting linkage to the same region require careful scrutiny and preferably joint or meta analysis on the same basis in order to ensure that the results are truly comparable.

Bipolar Disorder↗

PubMed2004

[New systems of mapping and navigation in electrophysiology].

The indications of radiofrequency ablation of arrhythmias have considerably increased since the introduction of the technique in the early 1990s. Interventional rhythmologists now treat arrhythmias which are more and more complex by their mechanism. This requires accurate representation of the ablation catheter position and the integration of spatial and temporal data to identify the arrhythmogenic substrate. The systems of mapping and navigation developed over the last ten years are important tools for interventional rhythmologists. They are very useful for the identification of complex arrhythmogenic substrates which require "individualised" ablations in specific cases. The aim of this article is to review different systems of mapping, and/or navigation currently on the market and their principal characteristics without entering into the details of their use in interventional electrophysiology.

Arrhythmias, Cardiac↗

PubMed2003

Correlation between electrogram morphology and standard criteria to validate bidirectional cavotricuspid block in common atrial flutter ablation.

AIM: Assessment of a bidirectional conduction block within the cavotricuspid isthmus (CTI) is critical during radiofrequency (RF) atrial flutter (AF) ablation. We investigated the use of bipolar atrial electrogram (BAE) morphology as an additional criterion identifying CTI block and tested it against two recognized criteria: differential pacing and reversal of the right atrial depolarization sequence during coronary sinus (CS) pacing. METHODS AND RESULTS: An RF ablation procedure was performed during 600 ms CS pacing in 100 consecutive patients with a common AF. BAE recorded along the CTI were continuously monitored. CTI conduction block was achieved by RF ablation in all patients and a clear change in BAE polarity in the Electrogram recorded by the dipoles located on the CTI and immediately lateral to the intended line of block (RS to QR pattern) associated with a confirmed CTI conduction block was observed in all cases. BAE morphology changes predicted bidirectional CTI conduction blocks with a 100% positive and a 100% negative predictive value. At a mean follow-up of 33 +/- 11 months, there was a 5% AF recurrence rate. CONCLUSIONS: Our study suggests that morphological changes in BAE recorded at sites lateral and adjacent to the target line of block may be used as a unique and robust criterion to validate CTI conduction block during AF ablation procedure.

Atrial Flutter↗

PubMed2002

Quantitative trait loci on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18 control variation in levels of T and B lymphocyte subpopulations.

Lymphocyte subpopulation levels are used for prognosis and monitoring of a variety of human diseases, especially those with an infectious etiology. As a primary step to defining the major gene variation underlying these phenotypes, we conducted the first whole-genome screen for quantitative variation in lymphocyte count, CD4 T cell, CD8 T cell, B cell, and natural killer cell numbers, as well as CD4:CD8 ratio. The screen was performed in 15 of the CEPH families that form the main human genome genetic project mapping resource. Quantitative-trait loci (QTLs) that account for significant proportions of the phenotypic variance of lymphocyte subpopulations were detected on chromosomes 1, 2, 3, 4, 8, 9, 11, 12, and 18. The most significant QTL found was for CD4 levels on chromosome 8 (empirical P=.00005). Two regions of chromosome 4 showed significant linkage to CD4:CD8 ratio (empirical P=.00007 and P=.003). A QTL for the highly correlated measures of CD4 and CD19 levels colocalized at 18q21 (both P=.003). Similarly, a shared region of chromosome 1 was linked to CD8 and CD19 levels (P=.0001 and P=.002, respectively). Several of the identified chromosome regions are likely to harbor polymorphic candidate genes responsible for these important human phenotypes. Their discovery has important implications for understanding the generation of the immune repertoire and understanding immune-system homeostasis. More generally, these data show the power of an integrated human gene-mapping approach for heritable molecular phenotypes, using large pedigrees that have been extensively genotyped.

Alleles↗

PubMed2001

Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish.

Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity.

Bipolar Disorder↗

PubMed2001

The future of genetic case-control studies.

The case-control study design has been a veritable workhorse in epidemiological research since its inception and acceptance as a valid and valued field of inquiry. The reasons for this owe to the simplicity of the required sampling and the (potential) ease of analysis and interpretation of results. Unfortunately, there are a number of problems that plague the use of the case-control design in assessing relationships between genetic variation and disease susceptibility in the population at large. Many of these problems are entirely analogous to problems that inhere in applications of the case-control design in nongenetic settings. These problems include stratification, the assessment of statistical significance, heterogeneity, and the interpretation of multiple outcomes or phenotypic information. In this chapter we describe 10 problems thought to plague genetic case-control studies and offer potential solutions to each. Many of our proposed solutions require the use of multiple DNA markers to accommodate the genetic background of the individuals sampled as cases and controls. It is hoped that our discussions and proposals will spark further debate about the analysis and ultimate utility of the case-control study in genetic epidemiology research.

Case-Control Studies↗

PubMed2000

Laparoscopic fundoplication for gastro-oesophageal reflux disease - a consensus development conference and the evidence-based benefit.

The aim of this paper is to demonstrate an example of evidence-based medicine for a clinically relevant and frequent disease - gastro-oesophageal reflux disease - for which an increasing number of laparoscopic operations is performed. A consensus development conference was performed on this topic in 1996. During the following 3-year period, increase of knowledge shown by the number of publications was monitored and the consecutive changes of the consensus as well as its consequences and impact were analysed. The six published randomised clinical trials revealed important information about the technique of the laparoscopic operation focussing on the gastric fundic mobilisation and the modification of the anti-reflux wrap. Five consecutive consensus conferences were performed and published. Citations of the 1996 consensus conference could not be found in the major surgical journals - not even by participants of the conference. The responsibility of societies to run such conferences continues.

Consensus Statements as Topic↗

PubMed2000

Lack of association between a biallelic polymorphism in the adducin gene and blood pressure in whites and African Americans.

Population-based candidate gene association analyses are becoming increasingly popular as a result of a greater number of genes and gene polymorphisms having been identified for which some functional information is available. Because many biochemical and physiologic systems impact blood pressure regulation and hypertension susceptibility, many of these identified genes and polymorphisms are candidates for population-level association studies involving blood pressure levels or hypertension status. Recent studies have suggested that the alpha-adducin gene may harbor polymorphisms that influence blood pressure level. Therefore, we embarked on a study to test one such polymorphism in two large US samples: one from an urban African American population (Maywood, IL) and another from a rural white population (Tecumseh, MI). We used both family-based association tests and tests that consider the impact of additional measured factors beyond adducin gene variation on blood pressure levels. We found no evidence for a significant effect of the chosen adducin polymorphism on blood pressure variation in either sample. We also found no association between Adducin genotypes and antihypertensive use. These facts, together with similar findings in companion studies, suggest that the alpha-adducin gene polymorphism does not have a pronounced effect on blood pressure variation in the populations studied. This does not suggest, however, that the alpha-adducin gene does not have a role in blood pressure regulation and hypertension susceptibility.

Adult↗

PubMed1998

A genome-wide search for chromosomal loci linked to mental health wellness in relatives at high risk for bipolar affective disorder among the Old Order Amish.

Bipolar affective disorder (BPAD; manic-depressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5. 22 x 10(-4); SIBPAL Pempirical value <3 x 10(-5)) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 10(-3); SIBPAL Pempirical value <1 x 10(-3)) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.

Adult↗

PubMed1998

Genetic regulation of commitment to interleukin 4 production by a CD4(+) T cell-intrinsic mechanism.

The dysregulated expression of interleukin 4 (IL-4) can have deleterious effects on the outcome of infectious and allergic diseases. Despite this, the mechanisms by which naive T cells commit to IL-4 expression during differentiation into mature effector cells remain incompletely defined. As compared to cells from most strains of mice, activated CD4(+) T cells from BALB mice show a bias towards IL-4 production and T helper 2 commitment in vitro and in vivo. Here, we show that this bias arises not from an increase in the amount of IL-4 produced per cell, but rather from an increase in the proportion of CD4(+) T cells that commit to IL-4 expression. This strain-specific difference in commitment was independent of signals mediated via the IL-4 receptor and hence occurred upstream of potential autoregulatory effects of IL-4. Segregation analysis of the phenotype in an experimental backcross cohort implicated a polymorphic locus on chromosome 16. Consistent with a role in differentiation, expression of the phenotype was CD4(+) T cell intrinsic and was evident as early as 16 h after the activation of naive T cells. Probabilistic gene activation is proposed as a T cell-intrinsic mechanism capable of modulating the proportion of naive T cells that commit to IL-4 production.

Animals↗

PubMed1998

Impact of experimentally induced serotonin deficiency by tryptophan depletion on sleep EEG in healthy subjects.

The tryptophan depletion test is a research strategy to investigate the functional consequences of decreasing the brain serotonin metabolism. Because serotonin is involved in sleep regulation and the regulation of affective states, we studied the acute polysomnographic effects of tryptophan depletion and expected to induce similar changes of sleep EEG as observed in depressed patients. A total of 12 healthy subjects (mean age 34 +/- 3 years) had eight polysomnograms, divided in two blocks of 4 consecutive nights. After one adaptation and 1 baseline night, subjects received a low-protein diet on day 3 and 4 until midday. On day 4 at 18.00 h, they drank an amino acid mixture either devoid of tryptophan or containing 2.3 g of tryptophan (placebo control) in randomized and double-blind order, resulting in an 85% decrease (tryptophan depletion) and a 144% increase (placebo control) of serum tryptophan at 22.00 h. After tryptophan depletion but not placebo, significant effects on sleep EEG were observed in terms of decreased non-rapid eye movement (non-REM) stage 2, increase of wake %, and of rapid eye movement (REM) density compared with baseline. REM latency was not altered, however the first and second REM period interval were significantly shorter after tryptophan depletion. This study underlines the impact of the serotonergic system on sleep maintenance and on REM sleep.

Adult↗

PubMed1998

Multiple phenotype modeling in gene-mapping studies of quantitative traits: power advantages.

Genomewide searches for loci influencing complex human traits and diseases such as diabetes, hypertension, and obesity are often plagued by low power and interpretive difficulties. Attempts to remedy these difficulties have typically relied on, and have promoted the use of, novel subject-ascertainment schemes, larger sample sizes, a greater density of DNA markers, and more-sophisticated statistical modeling and analysis strategies. Many of these remedies can be costly to implement. We investigate the utility of a simple statistical model for the mapping of quantitative-trait loci that incorporates multiple phenotypic or diagnostic endpoints into a gene-mapping analysis. The approach considers finding a linear combination of multiple phenotypic values that maximizes the evidence for linkage to a locus. Our results suggest that substantial increases in the power to map loci can be obtained with the proposed technique, although the increase in power obtained is a function of the size and direction of the residual correlation among the phenotypes used in the analysis. Extensive simulation studies are described that justify these claims, for cases in which two phenotypic measures are analyzed. This approach can be easily extended to cover more-complex situations and may provide a basis for more insightful genetic-analysis paradigms.

Chromosome Mapping↗

PubMed1998

The Polycomb-group gene eed is required for normal morphogenetic movements during gastrulation in the mouse embryo.

We have characterized an induced mutation, called embryonic ectoderm development or eed, that disrupts A-P patterning of the mouse embryo during gastrulation. Positional cloning of this gene revealed it to be the highly conserved homologue of the Drosophila gene extra sex combs, which is required for maintenance of long-term transcriptional repression of homeotic gene expression. Mouse embryos homozygous for loss-of-function alleles of eed initiate gastrulation but display abnormal mesoderm production. Very little embryonic mesoderm is produced; in contrast, extraembryonic mesoderm is relatively abundant. These observations, along with mRNA in situ hybridization analyses, suggested a defect in the anterior primitive streak, from which much of the embryonic mesoderm of the wild-type embryo is derived. To analyse this defect, we initiated clonal analysis of the pre-streak epiblast in eed mutant embryos, using the lineage tracer horseradish peroxidase (HRP). The results of these studies indicate that epiblast cells ingress through the anterior streak, but the newly formed mesoderm does not migrate anteriorly and is mislocalized to the extraembryonic compartment. Abnormal localization of mesoderm to the extraembryonic region did not appear to be due to a restriction and alteration of distal epiblast cell fate, since the majority of clones produced from regions fated to ingress through the anterior streak were mixed, displaying descendants in both embryonic and extraembryonic derivatives. eed mutant embryos also fail to display proper epiblast expansion, particularly with respect to the A-P axis. Based on patterns of clonal spread and calculated clone doubling times for the epiblast, this does not appear to be due to decreased epiblast growth. Rather, epiblast, which is normally fated to make a substantial contribution to the axial midline, appears to make mesoderm preferentially. The data are discussed in terms of global morphogenetic movements in the mouse gastrula and a disruption of signalling activity in the anterior primitive streak.

Animals↗

PubMed1998

[Is the laryngeal mask a viable alternative to endotracheal intubation in adenoidectomies in children?].

Based on our results and experiences, we consider the laryngeal mask anaesthesia a recommendable alternative to endotracheal intubation anaesthesia for adenotomies in children. Prerequisites with regard to the highest possible safety for the patient are specialist's knowledge, close anaesthesiological-otolaryngological cooperation and continuous clinical and apparative monitoring in order to detect possible accidental dislocations of the laryngeal mask without any delay. Using the laryngeal mask, disadvantages of endotracheal intubation, such as lesions of the vocal cords and damages to the tracheal mucous membrane can be avoided and the total time of narcosis can be reduced on average by about five minutes, particularly by shortening the recovery time of anaesthesia.

Adenoidectomy↗

PubMed1998

[Polymorphous ventricular tachycardia occurring three months following radiofrequency ablation of the bundle of His].

The authors report the case of a 73-year-old patient presenting with polymorphous ventricular tachycardias one to 3 months after radiofrequency His bundle resection, as soon as the pacing frequency was reduced to 70 bpm. The clinical history revealed the existence of a possible clinical predisposition, as this patient had experienced an episode of torsade de pointe induced by hydroquinidine, one year previously. This case illustrates the importance of selecting a sufficiently high minimal stimulation frequency after His bundle resection.

Bundle of His↗

PubMed1998

[Evaluation of high amplification ECG and the study of sinus variability in the detection of patients at risk of sudden death].

In order to define the best strategy of prognostic evaluation in relation to patients in heart failure, 415 patients with impaired left ventricular function (ejection fraction < 40%) were prospectively included, between June 1993 and 1996, in a study comparing the respective value of high amplification ECG and Holter analysis of sinus variability, 308 patients in sinus rhythm and narrow QRS complexes were included. The patients were distributed into 4 groups according to the presence or absence of late potentials and altered sinus variability (group I with 2 normal examinations, group II with late potentials and normal variability, group III without late potentials, but with altered variability and group IV with 2 abnormal examinations). The sudden and overall mortality was significantly greater in groups III (28 and 11%) and IV (28 and 9%) than in group I (7 and 3%) and II (11 and 2%). The presence of potential was unable to identify patients at risk of ventricular tachycardia and sudden death. In another 60 patients with complete branch block, the prognosis was also correlated with the alteration of sinus variability. In conclusion, high amplification ECG correctly evaluated the prognosis of subjects in heart failure. However, analysis of sinus variability should be systematically proposed to detect subjects at high risk of mortality, whether the subject has large or narrow QRS complexes.

Adult↗

PubMed1996

Significance and prevalence of inducible atrial tachyarrhythmias in patients undergoing electrophysiologic study for presyncope or syncope.

The purpose of the study was to report the prevalence of inducible supraventricular tachyarrhythmias (SVTA) in 827 consecutive patients aged 17 to 90 years who did not have spontaneous documented SVTA and who had unexplained presyncope and/or syncope. The electrophysiologic study (EPS) included programmed atrial and ventricular stimulation up to two extrastimuli at three cycle lengths, and the study of sino-atrial and AV conduction. The results were as follows. EPS was normal in 386 patients. Inducible junctional tachycardia or atrial flutter and fibrillation was the only finding in 187 patients (23%). In the remaining patients we found ventricular tachycardia in 103 (12%), heart block in 67 (8%), sick sinus syndrome in 56 (7%) and increased vagal tone in 28 (3%). The presence of an underlying heart disease (47%) and salvos of atrial premature beats on Holter monitoring (39%) were significantly correlated with the induction of SVTA. However, the comparison with similar groups without syncope indicates that only the induction of SVTA in patients with hypertrophic cardiomyopathy and mitral valve prolapse was significantly correlated with the history of syncope. In patients without heart disease or with prior myocardial infarction or decreased left ventricular function, the induction of SVTA, which is not associated with hypotension in the supine position, could require an induction after head-up tilting, because of the lack of specificity of programmed stimulation in these patients. Programmed atrial stimulation should be systematically performed in patients with unexplained syncope, in particular in those with hypertropic cardiomyopathy and mitral valve prolapse, who require a specific treatment, if a SVTA is induced. In other patients the results of programmed atrial stimulation should be interpreted cautiously.

Adolescent↗

PubMed1996

Mixture distributions in human genetics research.

The use of mixture distributions in genetics research dates back to at least the late 1800s when Karl Pearson applied them in an analysis of crab morphometry. Pearson's use of normal mixture distributions to model the mixing of different species of crab (or 'families' of crab as he referred to them) within a defined geographic area motivated further use of mixture distributions in genetics research settings, and ultimately led to their development and recognition as intuitive modelling devices for the effects of underlying genes on quantitative phenotypic (i.e. trait) expression. In addition, mixture distributions are now used routinely to model or accommodate the genetic heterogeneity thought to underlie many human diseases. Specific applications of mixture distribution models in contemporary human genetics research are, in fact, too numerous to count. Despite this long, consistent and arguably illustrious history of use, little mention of mixture distributions in genetics research is made in many recent reviews on mixture models. This review attempts to rectify this by providing insight into the role that mixture distributions play in contemporary human genetics research. Tables providing examples from the literature that describe applications of mixture models in human genetics research are offered as a way of acquainting the interested reader with relevant studies. In addition, some of the more problematic aspects of the use of mixture models in genetics research are outlined and addressed.

Genetic Heterogeneity↗