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Biomedical subjects

U Koehler

Publications and source records attributed to U Koehler.

At least 55 records · Page 3Linked to original sources
PubMed1996

Chromosome painting defines genomic rearrangements between red howler monkey subspecies.

We hybridized whole human chromosome-specific DNA libraries to chromosomes of two supposed subspecies of Alouatta seniculus: Alouatta seniculus sara and Alouatta seniculus arctoides. The number of hybridization signals per haploid set is 42 in A. s. sara and 43 in A. s. arctoidea; the two karyotypes differ by at least 16 chromosomal rearrangements, including numerous translocations. An unusual sex chromosome system is shared by both taxa. The sex chromosome system results from a Y translocation with a chromosome homologous to parts of human chromosome 3/15 and can be described as X1X2Y1Y2/X1X1X2X2 (male/female). Both red howlers also have microchromosomes, a highly unusual karyological trait not found in other higher primates. These microchromosomes are not hybridized by any human chromosome paint and therefore are probably composed of repetitive DNA. It is well known that New World monkeys have high karyological variability. It is probable that molecular cytogenetic analyses including chromosome painting will permit an accurate reconstruction of the phylogeny of these monkeys and help establish the ancestral karyotype for higher primates.

Alouatta↗
PubMed1996

Analysis of the organisation and localisation of the FSHD-associated tandem array in primates: implications for the origin and evolution of the 3.3 kb repeat family.

The D4Z4 locus is a polymorphic tandem repeat sequence on human chromosome 4q35. This locus is implicated in the neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD). The majority of sporadic cases of FSHD are associated with de novo DNA deletions within D4Z4. However, it is still not known how this rearrangement causes FSHD. Although the repeat contains homeobox sequences, despite exhaustive searching, no transcript from this locus has been identified. Therefore, it has been proposed that the deletion may invoke a position effect on a nearby gene. In order to try to understand the role of the D4Z4 repeat in this disease, we decided to investigate its conservation in other species. In this study, the long-range organisation and localisation of loci homologous to D4Z4 were investigated in primates using Southern blot analysis, pulsed field gel electrophoresis and fluorescence in situ hybridisation. In humans, probes to D4Z4 identify, in addition to the 4q35 locus, a closely related tandem repeat at 10qter and many related repeat loci mapping to the acrocentric chromosomes; a similar pattern was seen in all the great apes. In Old World monkeys, however, only one locus was detected in addition to that on the homologue of human chromosome 4, suggesting that the D4Z4 locus may have originated directly from the progenitor locus. The finding that tandem arrays closely related to D4Z4 have been maintained at loci homologous to human chromosome 4q35-qter in apes and Old World monkeys suggests a functionally important role for these sequences.

Animals↗
PubMed1996

Is obstructive sleep apnea (OSA) a risk factor for myocardial infarction and cardiac arrhythmias in patients with coronary heart disease (CHD)?

We prospectively studied 74 men 39-78 years of age, with significant (> or = 70%) stenosis of one or more coronary arteries. The investigation included coronary arteriography, ventriculography and ambulatory monitoring of cardio-respiratory variables during sleep using the MESAM-IV. We found 48 subjects with a respiratory disturbance index (RDI) > or = 10 events per hour. Our analyses failed to establish a relationship between RDI, myocardial infarction and known risk factors for coronary heart disease. Similarly, there was no relationship between RDI, number of coronary vessels involved, or left ventricular ejection fraction. Compared to general population studies, however, our group of coronary heart disease patients had a high incidence of obstructive sleep apnea syndrome (35%).

Adult↗
PubMed1996

[Sleep apnea as a risk marker in coronary heart disease].

UNLABELLED: Obstructive sleep apnea (OSA) and coronary heart disease (CHD) are both frequent in the middle ages. Both disease share a similar spectrum or risk factors and attendant diseases. The aim of the study was to determine the prevalence of obstructive sleep apnea in patients with coronary heart disease diagnosed by coronary angiography. Furthermore, influence of sleep apnea and attendant diseases and risk factors for coronary heart disease, especially the risk for myocardial infarction and reduced left ventricular ejection fraction, was investigated. We included in this study 143 patients (121 men, 22 women mean age 60 +/- 8 years (35-81) who underwent coronary angiography because of angina pectoris or were suspicious for CHD due to noninvasive investigations. These patients has symptoms of OSA based on a standardized questionnaire. They underwent a four-channel screening with a non-laboratory-monitoring-system (NLMS) for detection of sleep-related breathing disorders. In addition, spectrum of risk factors and concomitant diseases were considered. Sleep apnea was more frequent in patients with CHD (30.6%) in comparison to patients without CHD (21.8%), but did not reach statistical significance. Patients with CHD and OSA had a significantly higher frequency of a history of myocardial infarction and had a significantly lower left ventricular ejection fraction than patients without OSA. IN CONCLUSION: Patients with the combination of OSA and CHD are at higher risk for myocardial infarction and reduced left ventricular ejection fraction. Patients with CHD should be screened for OSA in case of secondary prevention.

Adult↗
PubMed1995

Genomic reorganization in the concolor gibbon (Hylobates concolor) revealed by chromosome painting.

We employed fluorescence in situ hybridization (FISH) of specific DNA libraries of all human chromosomes to establish homologies between the human karyotype and the karyotype of Hylobates concolor (2n = 52). Numerous intra- and interchromosomal rearrangements have led to a massive reorganization in the karyotype of H. concolor. There have been a minimum of 31 translocations. The 25 H. concolor autosomes are composed of 63-67 recognizable segments that show DNA homology to regions of the 22 human autosomes. Only 1 autosome, homologous to human chromosome 21, has not been involved in translocations. We compared the gene mapping data for H. concolor with our in situ hybridization and found that in most cases these data are confirmed by our results. H. concolor presents a case in a primate closely related to humans, in which chromosome morphology and synteny are highly disturbed in a manner similar to that encountered in rodents.

Animals↗
PubMed1995

Genomic reorganization and disrupted chromosomal synteny in the siamang (Hylobates syndactylus) revealed by fluorescence in situ hybridization.

We employed in situ hybridization ("chromosome painting") of chromosome-specific DNA libraries of all human chromosomes to establish homologies between the human and siamang karyotypes (Hylobates syndactylus, 2n = 50). Numerous intra- and interchromosomal rearrangements have led to a massive reorganization of the siamang karyotype. There have been a minimum of 33 translocations. The 24 siamang autosomes are composed of 60 recognizable segments that show DNA homology to regions of the 22 human autosomes. Only two autosomes have not been involved in translocations. The siamang presents a case, in a primate closely related to humans, in which chromosome morphology and synteny are highly disturbed in a manner similar to that encountered among rodents.

Animals↗
PubMed1995

A novel type of unstable homogeneously staining region with a head-to-tail arrangement: spontaneous decay and reintegration of DNA elements into a plethora of new chromosomal sites.

After transfection of amplification-promoting DNA elements into mammalian cells, homogeneously staining regions (HSRs) are formed by high copy numbers of transfected DNA arranged in head-to-tail polymers. Here, we wanted to evaluate the stability of this type of HSR during prolonged cultivation of transfected cells in selective medium. Thymidine kinase-deficient mouse L cells were transfected with pAPR4tk DNA harboring the amplification-promoting element 4 (APR4) linked to the gene for thymidine kinase (TK) or, alternatively, transfected with a DNA construct (pARP4t-PA) carrying, in addition, the expression cassette for human tissue-type plasminogen activator (t-PA). After transfection, one or two HSRs per cell were formed that disintegrated spontaneously after 25-40 wk of continuous cultivation in the presence of selective HAT (hypoxanthine-aminopterin-thymidine) medium. Unexpectedly, plasmid DNA reinserted into a plethora of new chromosomal sites, as revealed by in situ hybridization and Southern blot analysis. Coincidently, secretion of t-PA decreased to 10-20% of its original level. After transfection of pAPR4tk DNA lacking the t-PA expression cassette, HSR decay and reintegration of plasmid constructs into multiple chromosomal sites were also observed, whereas the ptk vector without an amplification-promoting DNA element did not form an HSR after transfection. We conclude that, in contrast to the pattern of known structures with head-to-tail arrangements, the HSR formed by amplification-promoting DNA elements represents a novel type of HSR that disintegrates by transposition into a plethora of new chromosomal integration sites. This process is mediated by the amplification-promoting DNA element itself and can be observed even when selective pressure is maintained.

Animals↗
PubMed1995

Chromosomal painting shows that "marked chromosomes" in lesser apes and Old World monkeys are not homologous and evolved by convergence.

Cytogeneticists have long held that the single pair of metacentric, NOR-bearing "marked chromosomes" in lesser apes (Hylobatidae) and Old World monkeys (Cercopithecidae) are homologous. Hylobatids have sometimes been excluded from Hominoidea (great apes and humans) and phylogenetically allied with the lower primates, primarily on the basis of this shared "trait." However, in situ hybridization of human chromosome-specific DNA probes to chromosomes of Hylobates lar, H. syndactylus, H. concolor, Cercopithecus aethiops, Macaca fuscata, Colobus guereza, and Presbytis cristata showed that the so-called "marked chromosomes" in Hylobatidae and Cercopithecidae evolved by convergence. Therefore, "marked chromosomes" cannot be used to exclude gibbons from Hominoidea or to link Hylobatidae with monkeys. Chromosomal painting is a powerful tool to resolve problems of chromosomal homology and helps eliminate phylogenetic errors due to confusing convergence with homology. Chromosomal painting improves the confidence in using cytogenetic data for evolutionary studies, especially in phylogeny and taxonomy.

Animals↗
PubMed1995

[Sleep apnea and cardiovascular risk].

Obstructive sleep apnea syndrome (OSAS) is the most important form of sleep-related breathing disorders due to its high prevalence and its potential for developing cardiovascular diseases. The increased morbidity of these patients is explained by the coincidence with cardiovascular diseases, and the increased mortality of untreated patients is due to cardiovascular complications, which depend on the degree of the breathing disorder. Heavy snoring, as a partial obstruction of the upper airways, and OSAS are independent risk factors for the development of cardiovascular diseases and stroke. Causal associations exist between acute hemodynamic changes, pressure and volume load, changes in the humoral and the central nervous system, and blood gas alterations during the obstructive apnea and the long-term condition due to OSAS. Obstructive apnea can be divided into an early phase, a late phase, and a phase of the postapneic hyperventilation with respect to hemodynamic changes, blood gas alterations, and the autonomic nervous system. The most striking changes in these parameters are seen at the end of apnea and in the first resumption of breathing, with an increase in systemic and pulmonary blood pressure, decrease in stroke volume, and a distinct change in heart rate. Manifestation of systemic hypertension even in the awake state is promoted by changes in the volume system, with activation of neurohumoral changes and by a resetting of baro- and chemoreceptors. Similar mechanisms are discussed in the development of pulmonary hypertension. In this circumstance the role of hypoxemia as a causal factor for pulmonary hypertension or as a consequence due to structural changes of the pulmonary vessels is controversial. OSAS is frequent in patients with coronary heart disease and these patients must be classified as a particular risk group because of apnea-associated silent myocardial ischemia and electric instability of the myocardium. The occurrence of arrhythmia in patients with OSAS is closely related to the apnea and hyperventilation events and depends on the sympathovagal balance. Early diagnosis and suitable therapy of patients at risk not only abolishes the sleep-related breathing disorder but also improves long-term outcome.

Autonomic Nervous System↗
PubMed1995

Manifestations and consequences of obstructive sleep apnoea.

Over the last two decades the diagnostic tools used in sleep medicine have developed enormously, making it possible to study the interaction of sleep-related breathing disorders (SRBD) with cardiovascular function and the autonomic nervous system, as well as the effects of SRBD on a variety of physiological processes during wakefulness. Different modes of nasal ventilation are now available, allowing all forms of SRBD to be treated. If early diagnosis and treatment are provided, the acute and long-term sequelae of SRBD can be prevented. In addition to the care and treatment of patients with severe obstructive sleep apnoea syndrome (OSAS), future patient management will need to focus on patients with milder forms of obstructive sleep apnoea (OSA). In particular, the consequences of SRBD on cardiac arrhythmias, arterial hypertension and hypersomnolence are discussed, considering epidemiological, clinical, diagnostic and therapeutic aspects. Some economical issues arising from SRBD are also discussed, and the authors conclude that a Europewide programme for early detection, treatment and prevention of SRBD is required. This could make a large contribution to the reduction of cardiovascular morbidity and mortality and also reduce the incidence of "human error catastrophes" due to hypersomnolence.

Arrhythmias, Cardiac↗
PubMed1994

[Morbidity and mortality in sleep apnea and nocturnal bradyarrhythmia].

The as yet unanswered question, whether patients with sleep apnoea and apnoea-associated bradyarrhythmias have a higher morbidity and mortality rate, was retrospectively investigated in 132 men with sleep apnoea (apnoea index > 10/h). Sleep-associated bradycardic arrhythmias were recorded in 71 (mean age 50.1 years; group 1). For comparison served 61 men with sleep apnoea but no bradyarrhythmias (mean age 51.4 years; group 2), matched for age and weight. There was no significant difference between the two groups as to diagnosis and initial findings on ergometry, lung function tests and blood gas analysis. The apnoea index of 48.1 +/- 23.9/h in group 1 was significantly higher than that of 31.9 +/- 20.1/h in group 2 (P < 0.001). During a follow-up period of a mean of 41.1 (19-66) months, two patients in group 1 died (of myocardial infarction), while one died (of bronchial carcinoma) in group 2 (follow-up period of 29.6 [18-54] months). The two deaths in group 1 were in a subgroup of 16 patients who had declined treatment or had used it irregularly. There was no death among those who had been treated (n = 54), by nasal continuous positive airway pressure, operation or pacemaker implantation. However, no causal relationship could be established from these data between increased mortality rate and apnoea-associated arrhythmias.

Adult↗
PubMed1993

[Nocturnal ventricular arrhythmia in patients with sleep apnea and suspected coronary heart disease].

BACKGROUND: Patients with sleep apnea and nocturnal brady- and tachyarrhythmia are considered to be patients at especially high risk within the group of all apnea patients. PATIENTS AND METHODS: 13 patients with sleep apnea (apnea-index > 10 events/h), suspected coronary heart disease and known increased frequency of nocturnal premature ventricular contractions (PVC) were studied. Polysomnography, long-term ECG and six-lead ECG were performed. RESULTS: Within the period studied (1.00 to 6.00 o'clock), an average of 47 PVC per hour was recorded (range 4 to 337/h). In two patients 24 episodes of nocturnal myocardial ischemia were observed, but were not accompanied by PVC. Interestingly only 387 of 1371 premature ventricular contractions (28.2%) were associated to apnea/hyperventilation episodes. Arrhythmia occurred mainly during sleep stages I/II and REM (n.s.). There was a tendency towards more frequent PVC with more pronounced oxygen desaturations. CONCLUSION: Patients with coronary heart disease, obstructive sleep apnea and severe hyoxemia are at higher risk of developing nocturnal PVC because reduced hypoxic tolerance of the heart may lead to electrical instability.

Bradycardia↗
PubMed1993

[Long-term theophylline therapy in sleep apnea--follow-up over a period of 12 months].

Among all the sleep-related respiratory disorders, sleep apnoea is clinically the most important one because of its high incidence and potential cardiovascular sequelae. Treatment depends upon the risk profile of the individual patient; in severe cases or in risk patients nasal continuous superpressure ventilation is employed, whereas in milder cases theophylline has been successfully used alongside general measures. 103 patients were followed up during treatment on an outpatient basis for 2 to maximum 12 months. Initially a significant reduction of the apnoea index by a 50% average was achieved. This therapeutical effect remained largely constant with a slight average deterioration at the end of the observation period, whereas the subjective feeling tone also improved in most patients. The treatment course was prematurely discontinued in 34 patients. Good to very good success was achieved in a total of 43 patients, whereas 26 patients were non-responders either initially or as the treatment proceeded. Even though theophylline treatment is now well-tried in mild forms of sleep apnoea, predictors for its use in certain groups of patients must be determined before treatment is initiated.

Adult↗
PubMed1993

[Nocturnal hypoxia--its relevance with reference to sleep structure in patients with coronary heart disease].

A disorder in the physiological structure of the sleep cycles (macrostructure) is known to occur both in patients with sleep apnoea (SA) and coronary heart disease (CHD). The study presented here was concerned with the problem whether the sleep structure in patients suffering from CHD and apnoea-conditioned hypoxia is greatly disturbed e.g. by myocardial ischaemia. Polysomnographic recordings including EEG, EOG, EMG and 6-channel ECG were performed for 6 nights in 30 patients suffering from sleep apnoea (AI > 10/h) and/without CHD. The average age of the patients was 57.9 years (range 47-68 yrs). The 2nd, 4th and 6th nights were subjected to fine analysis. In 6 patients it was possible to detect a total of 144 episodes with nocturnal myocardial ischaemia, 123 of these during cumulative apnoea and oxygen desaturation. The 30 patients spent on the average 67.1% in sleep stages I and II, 14.9% in deep sleep (stages III and IV) and 18% in REM sleep. 77.8% of the ischemie, episodes occurred during REM sleep and only 1.4% during the deep sleep stages. Sleep during myocardial ischaemia showed significantly more arousals than to control periods without ischaemia. There was furthermore a dependence of the degree of arousal on the degree of oxygen desakivations during apnoea. I. Patients suffering from CHD and sleep apnoea are endangered by nocturnal hypoxia-conditioned myocardial ischaemia which in turn can lead to increased electrical instability. II. The macrostructure of the sleep of patients suffering from CHD and sleep apnoea is comparatively as disturbed as that of patients with apnoea without CHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

[Lipomatous hypertrophy of the atrial septum. Cardiac-induced syncope in hamartoma of the right heart atrium].

A previously well 40-year-old woman suddenly collapsed and had to be resuscitated by an emergency physician. Admitted to hospital she remained unconscious and needed artificial respiration. Diagnostic tests failed to find evidence for pulmonary embolism, myocardial infarction or myocarditis. ECG monitoring in the intensive care unit merely revealed occasional unifocal ventricular premature systoles. Echocardiography was within normal limits. She remained in coma without spontaneous respiration. Cranial computed tomography and serial electroencephalograms indicated brain death. Autopsy revealed lipomatous hypertrophy (hamartoma) of the atrial septum with extensive bleeding into it as the most likely cause of (unrecorded) malignant cardiac arrhythmias.

Adult↗
PubMed1991

Nocturnal myocardial ischemia and cardiac arrhythmia in patients with sleep apnea with and without coronary heart disease.

To study the effect of apnea and hypoventilation-induced hypoxemia on the heart, we carried out polysomnographic recordings over 4 nights with electrocardiographic tracings in 30 patients with and without coronary heart disease. Evaluations of the data were based on the 2nd and 4th nights. In six subjects, five with coronary heart disease, we found 85 episodes of nocturnal ischemia, mainly during REM sleep (83.5%), high apnea activity, and sustained and progressive hypoxemia. Complex ventricular ectopy was observed in 14/13 patients (nights 2/4) and repetitive ventricular ectopy in 5/3. There was no significant difference in the quality and quantity of ventricular ectopy during wake and sleep states between the CHD group and the control group. In one patient ventricular bigeminy was observed only at a threshold of SaO2 below 60%. Bradyarrhythmia was made evident in four subjects from the CHD group and correlated mainly with apnea activity. We suppose that patients with sleep apnea and CHD are at cardiac risk because coronary heart disease can be aggravated by insufficient arterial oxygen supply due to cumulative phase of apnea and hypoventilation. The reduced hypoxic tolerance of the heart may lead to myocardial ischemia and increased electrical instability.

Aged↗
PubMed1991

[Sleep-related respiratory disorders and coronary heart disease].

A review of the literature shows that more than 50% of examined patients suffering from coronary heart disease were also suffering from sleep-related apnea. We were able to diagnose a pathological sleep apnea in 9 out of 25 patients (36%) suffering from an angiographically confirmed coronary 2-vessel and 3-vessel disorder. Patients with this combination--this is the hypothesis derived from our study--are at risk due to nocturnal apnea-induced myocardial ischaemia and rhythmic disorders. In 15 patients with sleep apnea and coronary heart disease or small vessel disease, nocturnal polysomnography was conducted, in parallel a 6-channel ECG was recorded. The apnea index (second night) was on the average 33 phases/h, the maximal duration of an apnea phases being 120 seconds. The minimal blood gas saturation recorded during sleep was between 46 and 89% (median 76.0%). In 4 of the 15 patients it was possible to confirm myocardial ischaemia (correlated via REM and also via NREM) with a maximum duration of 60 seconds, mainly during the phases of maximal apnea activity and blood gas desaturation. On comparing the ventricular arrhythmias waking/sleep, the Lown class did not change in 12 patients; there was deterioration in 2 patients and in one patient a qualitative improvement during the sleep phase. Patients suffering from sleep-related respiratory disorders and coronary heart disease are at cardiac risk, the more so since long-lasting apneas can lead to conditions of hypoxia at the heart in pre-existing changes in the coronary arteries, restricted coronary reserves and reduced tolerance to hypoxia. Such hypoxia can in turn induce enhanced electrical instability and a disturbance of the contractile function.

Arrhythmias, Cardiac↗