Biomedical subjects

R Bürger

Publications and source records attributed to R Bürger.

At least 19 recordsLinked to original sources

PubMed2006

Does competitive divergence occur if assortative mating is costly?

Most models of sympatric speciation have assumed that assortative mating has no costs. A few studies, however, have shown that the costs for being choosy can prevent such speciation. Here, we investigate the role of the strength of assortment and of the costs for being choosy for a simple genetic model of a single ('magic') trait that mediates both intraspecific competition for a continuum of resources and assortative mating, which is induced by choosy females who preferentially mate with males of similar phenotype. Choosiness may be costly if it is difficult to find a mating partner. Such magic trait models are considered to be most conducive of sympatric speciation. We consider a sexually reproducing population of haploid individuals that is density regulated. The trait is determined by a single locus with multiple alleles. The strength of stabilizing selection (caused by a unimodal resource distribution), the strength of competition, the degree of assortment and the costs for being choosy are independent parameters. We investigate analytically and numerically how these parameters determine the equilibrium and stability structure. In particular, we identify conditions under which no polymorphism at all is maintained as well as conditions under which strong competitive divergence occurs, or the population even splits into two reproductively isolated classes of highly diverse phenotypes. If costs are absent or moderate, genetic variability tends to be minimized at intermediate strengths of assortment, and reproductively isolated classes of phenotypes are a likely result of evolution only for intermediate or strong competition and for very strong assortment. The likelihood of divergence depends relatively weakly on the costs as long as they are not high. With high costs, however, increasingly strong assortment rapidly depletes all genetic variation, and strong competitive divergence is prevented.

Evolution, Molecular↗

PubMed2000

Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy.

BACKGROUND: The prevalence of coronary vessel wall alterations in the general population is not known. Therefore, the aim of our study was to determine the prevalence of coronary artery disease in persons in whom the underlying disease was not related to coronary artery disease and could therefore be regarded as a near normal population. METHODS: We included 331 consecutive patients (173 men, 158 women, aged between 40 and 70 years) who were referred for catheter ablation of an accessory pathway (67.4% ) or atrioventricular-node modification (32.6%) and who underwent coronary angiography as part of their routine baseline evaluation before radiofrequency current application. Most of the patients (79%) of this cohort were free of symptoms of coronary artery disease. Based on visual inspection of coronary angiograms in multiple projections, patients were classified to have one-, two- or three-vessel disease if stenoses greater than 50% of lumen diameter were present. In addition, diffuse vessel wall alterations were assessed using two different score systems. RESULTS: The prevalence of coronary artery disease in this near normal population was 7.3%, with a significant difference in coronary asymptomatic (3.8%) vs symptomatic patients (17.1%). Mean levels of total cholesterol and other risk factors were not significantly different in patients with coronary artery disease compared to those without. But levels of low-density lipoprotein (LDL) cholesterol and lipoprotein(a) were significantly higher and high-density (HDL) cholesterol lower in patients with a stenosis or extent score higher than zero compared to a score of zero. The values of all vessel scores evaluating the extent of critical and diffuse coronary vessel alterations were very low in patients affected with coronary artery disease, indicating a low degree of diffuse alteration of the vessel wall. CONCLUSIONS: The prevalence of coronary artery disease with at least one critical stenosis in subjects aged 40-70 years with an average cholesterol level of 238+/-42 mg. dl(-1)is 7.3%.

Arrhythmias, Cardiac↗

PubMed2000

Fixation of clonal lineages under Muller's ratchet.

For clonal lineages of finite size that differ in their deleterious mutational effects, the probability of fixation is investigated by mathematical theory and Monte Carlo simulations. If these fitness effects are sufficiently small in one or both lineages, then the lineage with the less deleterious effects will become fixed with high probability. If, however, in both lineages the deleterious effects are larger than a threshold s(c), then the probability of fixation is independent of the fitness effects and depends only on the initial frequencies of the lineages. This threshold decreases with decreasing genomic mutation rate U and increases with population size N. (For N = 10(5), we have s(c) approximately = 0.1 if U = 1, and s(c) approximately = 0.015 if U = 0.1). Above the threshold, the competition is not driven by the ratio of mean fitnesses of the lineages, but by the relative sizes of the zero-mutation classes, which are independent of the fitness effects of the mutations. After the loss of the zero-mutation class of a lineage, the other lineage will spread to fixation with high probability and within a short time span. If the mutation rates of the lineages differ substantially, the lineage with the lower mutation rate is fixed with very high probability unless the lineage with the larger mutation rate has very slightly deleterious mutational effects. If the mutation rates differ by not more than a few percent, then the lineage with the higher mutation rate and the more deleterious effects can become fixed with appreciable probability for a certain range of parameters. The independence of the fixation probability on the fitness effects in a single population leads to dramatic effects in metapopulations: lineages with more deleterious effects have a much higher fixation probability. The critical value s(c), above which this phenomenon occurs, decreases as the migration rate between the subpopulations decreases.

Animals↗

PubMed1999

Genetic variation maintained in multilocus models of additive quantitative traits under stabilizing selection.

Stabilizing selection for an intermediate optimum is generally considered to deplete genetic variation in quantitative traits. However, conflicting results from various types of models have been obtained. While classical analyses assuming a large number of independent additive loci with individually small effects indicated that no genetic variation is preserved under stabilizing selection, several analyses of two-locus models showed the contrary. We perform a complete analysis of a generalization of Wright's two-locus quadratic-optimum model and investigate numerically the ability of quadratic stabilizing selection to maintain genetic variation in additive quantitative traits controlled by up to five loci. A statistical approach is employed by choosing randomly 4000 parameter sets (allelic effects, recombination rates, and strength of selection) for a given number of loci. For each parameter set we iterate the recursion equations that describe the dynamics of gamete frequencies starting from 20 randomly chosen initial conditions until an equilibrium is reached, record the quantities of interest, and calculate their corresponding mean values. As the number of loci increases from two to five, the fraction of the genome expected to be polymorphic declines surprisingly rapidly, and the loci that are polymorphic increasingly are those with small effects on the trait. As a result, the genetic variance expected to be maintained under stabilizing selection decreases very rapidly with increased number of loci. The equilibrium structure expected under stabilizing selection on an additive trait differs markedly from that expected under selection with no constraints on genotypic fitness values. The expected genetic variance, the expected polymorphic fraction of the genome, as well as other quantities of interest, are only weakly dependent on the selection intensity and the level of recombination.

Alleles↗

PubMed1999

Evolution of genetic variability and the advantage of sex and recombination in changing environments.

The role of recombination and sexual reproduction in enhancing adaptation and population persistence in temporally varying environments is investigated on the basis of a quantitative-genetic multilocus model. Populations are finite, subject to density-dependent regulation with a finite growth rate, diploid, and either asexual or randomly mating and sexual with or without recombination. A quantitative trait is determined by a finite number of loci at which mutation generates genetic variability. The trait is under stabilizing selection with an optimum that either changes at a constant rate in one direction, exhibits periodic cycling, or fluctuates randomly. It is shown by Monte Carlo simulations that if the directional-selection component prevails, then freely recombining populations gain a substantial evolutionary advantage over nonrecombining and asexual populations that goes far beyond that recognized in previous studies. The reason is that in such populations, the genetic variance can increase substantially and thus enhance the rate of adaptation. In nonrecombining and asexual populations, no or much less increase of variance occurs. It is explored by simulation and mathematical analysis when, why, and by how much genetic variance increases in response to environmental change. In particular, it is elucidated how this change in genetic variance depends on the reproductive system, the population size, and the selective regime, and what the consequences for population persistence are.

Animals↗

PubMed1997

[Extracorporeal shockwave therapy in orthopedics. Positive results in tennis elbow and tendinosis calcarea of the shoulder].

Since the beginning of the 1990s scientific investigations on the use of extracorporeal shock wave therapy (ESWT) in the field of orthopedics have been carried out at the Orthopedic Department of the University of Mainz. Prospective studies demonstrated beneficial effects in chronic lateral humeral epicondylitis (tennis elbow), and in calcifying tendinitis of the shoulder in more than 50% of the cases. Additional indications for which positive results of prospective studies have been published during the past 2 years are plantar calcaneodynea and pseudoarthrosis. On the basis of the results achieved, it may be concluded that, for specific indications, extracorporeal shock wave therapy may now be taken out of the clinical testing stage and introduced into routine practice.

Calcinosis↗

PubMed1997

Adaptation and extinction in changing environments.

The extinction risk of a population is determined by its demographic properties, the environmental conditions to which it is exposed, and its genetic potential to cope with and adapt to its environment. All these factors may have stochastic as well as directional components. The present chapter reviews several types of models concerned with the vulnerability of small populations to demographic stochasticity and to random and directional changes of the environment. In particular, the influence of mutation and genetic variability on the persistence time of a population is explored, critical rates for environmental change are estimated beyond which extinction on time scales of tens to a few thousand generations is virtually certain, and the extinction risks caused by the above mentioned factors are compared.

Adaptation, Physiological↗

PubMed1997

[Testicular loss due to hemorrhagic infarct in Tauber antegrade scrotal varicocele sclerotherapy].

A 38-year-old patient with a grade 3 testicular varicocele was treated by antegrade scrotal sclerotherapy. Although performed technically accurate, antegrade sclerotherapy led to a haemorrhagic infarction of the testis by complete occlusion of venous drainage. The testis had to be removed. This complication has not been described yet and patients should be informed about this rare event.

Adult↗

PubMed1997

[Extracorporeal shock-wave therapy. Experimental basis, clinical application].

The purpose of our studies was to investigate experimentally the dose-dependent effects of extracorporeal shock waves on tendon and bone and to unveil therapeutic possibilities in tendinopathies and pseudarthroses. In animal experiments, both positive and negative influences were exerted by shock waves, depending on the initial situation and on the power of the applied shock waves. In prospective clinical trials positive effects were found in the treatment of persistent tennis elbow, plantar fasciitis, calcifying tendinitis, and pseudarthrosis. Our data show that extracorporeal shock waves may provide analgesic, resorptive and osteo-inductive reactions with nearly no side effects. However, the high cost of apparatus and staff prevents a routine application. Extracorporeal shock waves thus remain a last alternative before the indication is made for an operative procedure.

Achilles Tendon↗

PubMed1996

Low-energy extracorporal shock wave therapy for persistent tennis elbow.

Fifty patients who suffered from persistent tennis elbow for more than 12 months, and were referred for surgical treatment, were assigned at random to 2 groups of low-energy extracorporal shock wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm2; group II (controls) 30 impulses of 0.08 mJ/mm2. Follow up was after 3 and 12 weeks. We found no significant differences between the 2 groups before treatment, there was but significant relief of pain and improvement of function in group I with good or excellent outcome in 56% at the last evaluation.

Adult↗

PubMed1996

Analgesic effect of extracorporeal shock-wave therapy on chronic tennis elbow.

We report a controlled, prospective study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow. We assigned at random 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm2 and group II, the control group, 30 impulses. The patients were reviewed after 3, 6 and 24 weeks. There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48% and an acceptable result in 42% at the final review, compared with 6% and 24%, respectively, in group II.

Adult↗

PubMed1995

Surgery in rhabdomyosarcoma of the bladder, prostate and vagina.

The treatment of bladder and prostate rhabdomyosarcoma (RMS) is highly controversial. Aside from chemotherapy, treatment modalities include conservative surgery, radical surgery, and pre-, intra-, or postoperative irradiation. Between 1968 and 1993, 78 children with RMS were treated at our institution. In all, 22 tumors were located in the urogenital tract (bladder/prostate, 13; paratesticular, 5; vaginal, 2; others, 2). Altogether, 6 patients had stage II disease; 7, stage III disease; and 2, stage IV disease. All 15 patients with RMS of the bladder, prostate, or vagina received chemotherapy, and 4 had additional radiotherapy. Surgery was also done in 10 patients; parents refused an operation in 3 cases. In all, 3 patients in an advanced tumor stage died of their disease. All other children currently show no evidence of disease (mean follow-up, 6 years; range, from 2 months to 18 years). After chemotherapy, radical operative intervention with multiple biopsies (encircling the tumor)--in contrast to local tumor excision or partial resection--permits complete tumor resection followed by excellent long-term results. Following radiotherapy, often a consequence of organ-sparing therapy, many complications ensued (60%); therefore, irradiation should be restricted to highly selected cases.

Adolescent↗

PubMed1994

Mutation load and mutation-selection-balance in quantitative genetic traits.

Haldane (1937) showed that the reduction of equilibrium mean fitness in an infinite population due to recurrent deleterious mutations depends only on the mutation rate but not on the harmfulness of mutants. His analysis, as well as more recent ones (cf. Crow 1970), ignored back mutation. The purpose of the present paper is to extend these results to arbitrary mutation patterns among alleles and to quantitative genetic traits. We derive first-order approximations for the equilibrium mean fitness (and the mutation load) and determine the order of the error term. For a metric trait under mutation-stabilizing-selection balance our result differs qualitatively from that of Crow and Kimura (1964), whose analysis is based on a Gaussian assumption. Our general approach also yields a mathematical proof that the variance under the usual mutation-stabilizing-selection model is, to first order, micro/s (the house-of cards approximation) as micro/s tends to zero. This holds for arbitrary mutant distributions and does not require that the population mean coincide with the optimum. We show how the mutant distribution determines the order of the error term, and thus the accuracy of the house-of-cards approximation. Upper and lower bounds to the equilibrium variance are derived that deviate only to second order as micro/s tends to zero. The multilocus case is treated under the assumption of global linkage equilibrium.

Alleles↗

PubMed1994

On the distribution of the mean and variance of a quantitative trait under mutation-selection-drift balance.

The distributions of the mean phenotype and of the genetic variance of a polygenic trait under a balance between mutation, stabilizing selection and genetic drift are investigated. This is done by stochastic simulations in which each individual and each gene are represented. The results are compared with theoretical predictions. Some aspects of the existing theories for the evolution of quantitative traits are discussed. The maintenance of genetic variance and the average dynamics of phenotypic evolution in finite populations (with Ne < 1000) are generally simpler than those suggested by some recent deterministic theories for infinite populations.

Chromosome Mapping↗

PubMed1993

Predictions of the dynamics of a polygenic character under directional selection.

A quantitative genetic model for the response of the distribution of a single metric trait to directional selection is investigated. Particular attention is paid to the performance of approximations that use only limited information on the initial state of the population, such as the mean, the variance, the skewness and the kurtosis. Selection is imposed according to an exponentially increasing fitness function, populations mate at random, have discrete generations, and all genetic effects are supposed to be additive. Neglecting random drift, qualitatively different predictions for the initial response of a large population that has previously been at a mutation-stabilizing selection balance are derived. These depend on different assumptions about the initial distribution and are compared to the exact dynamics of that model. Linkage disequilibrium can be ignored as long as linkage is not too tight. The mathematical analysis rests on the method of cumulants and of cumulant-generating functions and produces exact equations for the evolution of cumulants in this model. Small populations subject to random drift are shown to respond in a qualitatively different way. The case of small populations is treated, primarily, by Monte Carlo simulations. The consequences of qualitatively different assumptions about maintenance of variation through mutation for the initial response to exponential directional selection are discussed. It is concluded that a significant initial increase in variance is unlikely to be observed in selection experiments if the effective population size is not larger than 500 and if response is caused by additive genes. The present results also apply to weak truncation selection.

Mathematics↗

PubMed1993

Reservoir characteristics of Mainz pouch studied in animal model. Osmolality of filling solution and effect of oxybutynin.

In a canine model of the Mainz pouch, intracavitary pressure and compliance were measured during instillation of isosmotic and hyperosmotic (900 mmol/kg water) solutions of saline. Wall properties of small- and large-bowel segments of the pouch were assessed individually by sonomicrometry. Intraluminal pressures increased more steeply during filling with hyperosmotic solution, resulting in reduced distensibility of small- and large-bowel segments. Additionally, instillation of the hyperosmotic solution resulted in increased amplitudes and frequency of intracavitary pressure waves. The results indicate that this was the result of a combination of intensified bowel contractions and an increased mural tension. Topical application of oxybutynin abolished these effects. These findings are reviewed in light of the nocturnal increase in urine osmolality, its correlation with nocturnal incontinence in patients with enterocystoplasty, and possible treatment choices.

Animals↗

PubMed1993

[Kinetic studies of the lumbar vertebrae and the lumbosacral transition in the German shepherd dog. 2. Our personal investigations].

The range and type of ventrodorsal motion between two adjacent vertebra (L3-S1) was analyzed on isolated vertebral columns of 13 German Shepherd Dogs. All except one were neurologically normal dogs. The movement from maximal flexion to maximal extension was divided into 5 degree steps. For each step, the center of motion was determined on laterolateral radiographs. It could be shown that mobility between two adjacent vertebra within the lumbar spine increases towards the lumbosacral region with the highest mobility in this joint. In the cranial portion of the lumbar spine, rotation and ventrodorsal (parallel) displacement between two adjacent vertebra was seen. Rotation dominated in the lumbosacral joint in 11 dogs, whereas parallel displacement was mainly seen in 2 dogs. Further studies on pathologic and surgically modified vertebral columns are necessary to clarify the significance of these findings in the pathogenesis of lumbosacral instability and cauda equina compression in the German Shepherd Dog.

Animals↗

PubMed1992

Survival of small populations under demographic stochasticity.

We estimate the mean time to extinction of small populations in an environment with constant carrying capacity but under stochastic demography. In particular, we investigate the interaction of stochastic variation in fecundity and sex ratio under several different schemes of density dependent population growth regimes. The methods used include Markov chain theory, Monte Carlo simulations, and numerical simulations based on Markov chain theory. We find a strongly enhanced extinction risk if stochasticity in sex ratio and fluctuating population size act simultaneously as compared to the case where each mechanism acts alone. The distribution of extinction times deviates slightly from a geometric one, in particular for short extinction times. We also find that whether maximization of intrinsic growth rate decreases the risk of extinction or not depends strongly on the population regulation mechanism. If the population growth regime reduces populations above the carrying capacity to a size below the carrying capacity for large r (overshooting) then the extinction risk increases if the growth rate deviates from an optimal r-value.

Animals↗