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Biomedical subjects

C Lauer

Publications and source records attributed to C Lauer.

At least 19 recordsLinked to original sources
PubMed1992

Antiglucocorticoid treatment disrupts endocrine cycle and nocturnal sleep pattern.

Mifepriston (RU 486) is a steroid antagonist which binds with high affinity to glucocorticoid receptors (GR), and also to progesterone receptors. The antiglucocorticoid action of Mifepriston in man has been demonstrated by blockade of the negative feedback action of endogenous cortisol and by antagonism of the effects of exogenously administered dexamethasone. In the present study Mifepriston was administered to a normal male volunteer at 14.00 h and its effects on pituitary-adrenal activity and nocturnal sleep pattern were recorded. Mifepriston caused a large rise in plasma ACTH levels during the morning hours in comparison to untreated male control subjects. Plasma ACTH levels in the Mifepriston treated subject at 7.00 h were threefold greater than in the control subjects (104.4 pg/ml vs. 37.6 +/- 13.9 pg/ml; mean +/- SD). Subsequently the cortisol secretion was enhanced and the rise was advanced by about 60 minutes compared to controls. The main effects of Mifepriston on EEG sleep pattern were a dramatic disruption of sleep quality with a prolonged sleep onset latency, increased nocturnal awakenings and a considerable reduction of both slow wave sleep (SWS) and REM sleep. After Mifepriston, SWS was reduced by about 80% in comparison to placebo, and REM sleep was reduced by more than 50%. While the present data were collected from only a single subject the effects observed were so pronounced that tentative conclusions seem to be justified: The well-established pharmacological properties of Mifepriston as a glucocorticoid antagonist are reflected by its action on sleep physiology since it influences sleep in a direction opposite to that produced by cortisol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1992

Increased number of alveolar macrophages expressing adhesion molecules of the leukocyte adhesion molecule family in smoking subjects. Association with cell-binding ability and superoxide anion production.

This study was designed to investigate whether the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18) are altered in human alveolar macrophages (AM) from smokers. Cells were obtained from 38 smokers (S) and 27 nonsmokers (NS) by bronchoalveolar lavage (BAL). Expression of LeuCAM on freshly isolated cells was studied using a sensitive peroxidase-antiperoxidase method with monoclonal antibodies (mAB) against CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring in vitro the binding of AM to the intracellular adhesion molecule-1 (ICAM-1) on human umbilical-vein endothelial cells (HUVEC). The influence of LeuCAM on the increased superoxide anion production (O2-) of smoker AM was quantified after blocking the CD18 molecule by a mAB. Compared with nonsmoker AM, significantly more AM from smokers expressed CD11b (p < 0.001), CD11c (p < 0.001), CD18 (p < 0.001), and CD11a (p < 0.004), whereas there was no difference in the expression of other common epitopes of human macrophages such as CD68, CD71, CD45, HLA-DQ, and HLA-DR. The number of AM expressing CD11a, CD11c, and CD18 showed a correlation to the total number of AM obtained by BAL (p < 0.001). Adherence of AM to HUVEC was higher for smoker than for nonsmoker AM (p < 0.05). The increased binding of smoker AM to endothelial cells could be inhibited by treating the HUVEC with a mAB against ICAM-1. The mAB anti-CD18 reduced O2- release from smoker AM by 42 +/- 5% after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

The effect of follicle-maturing drugs on mid-cycle androgen levels in women with normal baseline levels.

Theoretically, clomiphene citrate or human menopausal gonadotropins might have a higher chance of inducing pregnancy per cycle were it not for the concomitant rise in androgens induced by these follicle-maturing drugs. In the present study, mid-cycle androgen levels were evaluated in anovulatory women with normal baseline early follicular levels who were treated with either clomiphene citrate or human menopausal gonadotropins. The only mid-cycle androgen to rise above the normal range was androstenedione. However, no negative effects of elevated androstenedione levels on pregnancy rates were apparent. Thus, at least in women with normal baseline androgen levels, the use of follicle-maturing drugs does not appear to cause a rise in androgen levels except for androstenedione, and the rise in androstenedione at mid-cycle appears to have no adverse effect on conception.

Androgens↗
PubMed1991

Brain morphology and sleep EEG in patients with Huntington's disease.

In 12 patients with Huntington's disease, the relationship between brain morphology, nocturnal sleep EEG, and clinical variables was studied. Global cerebral atrophy did not significantly correlate with sleep parameters, whereas atrophy of the caudate nuclei was associated with reduced slow wave sleep and increased time spent awake. Several clinical parameters (e.g., anergia and thought disturbance scores of the Brief Psychiatric Rating Scale, illness duration and global clinical assessment) showed significant correlations with global cerebral atrophy. Similar studies in other neuropsychiatric disorders demonstrate associations between sleep alterations and brain morphological changes of different localizations, thus pointing to a complex relationship between both. It can be hypothesized that the caudate nuclei may be involved in sleep regulation; indirect evidence from studies with positron emission tomography (PET) point in the same direction.

Adult↗
PubMed1991

The action of clenbuterol on sleep and symptomatology in depressives.

Five female inpatients with major depression (melancholic type, DMS-III-R) were treated with the beta-adrenergic agonist clenbuterol for three weeks, with doses ranging from 100 micrograms to 150 micrograms. Remission of depressive symptomatology during treatment was observed in only one patient. All patients complained of side effects, especially tremor, agitation and restlessness. The sleep EEG showed no consistent effects on sleep parameters, including REM latency and percentage of REM sleep. Thus, the impact of clenbuterol on sleep clearly differs from that of most classical antidepressants. Regarding the lack of therapeutic efficacy, the data are compatible with the hypothesis of a relationship between REM sleep suppression and an antidepressant drug effect. Despite the small sample size, it can be concluded that clenbuterol is not likely to be a promising alternative to proven antidepressants in the treatment of major depression.

Adult↗
PubMed1990

Myocardial adaptation to creatine deficiency in rats fed with beta-guanidinopropionic acid, a creatine analogue.

A creatine analogue, beta-guanidinopropionic acid (GPA), was fed to 12 young rats for several weeks. Another 12 animals were kept in the same conditions and age matched. Six pairs of animals were used to measure some energetic and mechanical parameters of the isovolumic perfused heart and to measure the accumulation of the phosphorylated form of GPA (GPAP) by 31P-nuclear magnetic resonance (NMR) spectroscopy. As a result of GPAP accumulation, phosphocreatine and ATP content decreased by 90 and 40%, respectively, and mechanical performance was impaired. Six other pairs of animals were used to assess the mechanical performances of Triton X-100-skinned fibers and the myosin isoenzyme distribution. It was found that the maximal force, Ca and ATP sensitivities, and myofibrillar creatine kinase efficacy of creatine-depleted hearts were similar to control values. There was, however, a decrease in the rate of cross-bridge cycling, and the isoenzymic expression of myosin was changed from the fast myosin V1 to the slower forms V2 and V3. In all animals, hypertrophy was observed in both right and left ventricles. We conclude that rat hearts subjected to a slow and persistent decrease in creatine and phosphocreatine respond with both quantitative and qualitative changes. These alterations, which most probably lead to an improvement in the economy of cardiac contraction, are nonetheless not sufficient to maintain maximal force.

Adaptation, Physiological↗
PubMed1989

Brain morphology and regional cerebral blood flow in anorexia nervosa.

Cranial computed tomography (CT) was performed in 12 patients with anorexia nervosa, revealing that the majority of the patients displayed ventricular dilatation and/or sulcal widening. In addition, regional cerebral blood flow (rCBF) was measured at admission and once again after weight gain, using xenon-133 dynamic single-photon emission tomography (dSPECT). The mean flow rates assessed at the first examination did not significantly differ from those assessed at the second examination and from those of a control group. There was a significant inverse relationship between the size of the cerebrospinal fluid spaces and the cerebral blood flow in the anorectics; a decrease in ventricular size after weight gain was associated with an increase in cerebral blood flow in this area. This finding, however, has to be interpreted with caution, as partial volume effects render the flow rates ambiguous in brain areas, which, in addition to neuronal tissue, also include ventricular and sulcal structures.

Adolescent↗
PubMed1989

The effect of neuroendocrine secretion on brain morphology and EEG sleep in patients with eating disorders.

Neuroendocrine disturbances [low plasma levels of triiodothyronine (T3), high plasma concentrations of cortisol], morphological brain alterations [enlarged external cerebrospinal fluid (CSF) spaces, dilatation of the ventricles] and altered sleep patterns [fragmented sleep continuity, a reduction of slow wave sleep (SWS) or REM sleep] have been described in patients with anorexia nervosa and bulimia nervosa. The present study investigates to what degree these disturbances interact with each other. In ten anorexic and five bulimic patients cranial computed tomography (CT) to estimate the size of the CSF spaces, blood sampling to measure cortisol and T3 plasma concentrations, and all-night polysomnography were performed. In comparison with patients with normal CT scans, the patients displaying enlarged CSF spaces spent more time in SWS, and the duration of REM sleep was reduced. In the whole sample, a negative correlation was found between the amount of REM sleep and cortisol, whereas a positive association was found between the amount of REM sleep and the T3 level. In addition, the degree of brain shrinkage correlated positively with cortisol and negatively with T3. On the basis of these results, it can be assumed that in patients with eating disorders the disease process with its neuroendocrine alterations affects brain morphology as well as EEG sleep.

Brain↗
PubMed1989

Structural brain abnormalities in patients with bulimia nervosa.

Computed tomographic (CT) brain scans were performed in 50 inpatients with bulimia nervosa, 50 anorectic inpatients, and 50 age-matched control subjects. A number of patients with bulimia nervosa had enlarged ventricles and/or sulcal widening, but the degree and frequency of ventricular dilatation and sulcal widening were not so pronounced as in patients with anorexia nervosa. As the bulimic patients were of normal body weight, the CT abnormalities cannot be attributed to emaciation, which has often been suggested as the cause of abnormalities found in anorectic patients. Since many bulimic patients repeatedly attempt to lose weight by going on restrictive diets, the morphological brain alterations may reflect the endocrine and metabolic reactions to starvation--regardless of whether starvation has led to emaciation, as in the case of anorexia nervosa, or only counterbalanced the binges of high-caloric food. This assumption is supported by the finding that in both bulimic and anorectic patients ventricular size is inversely correlated with the plasma levels of triiodothyronine, a low concentration of which is an indicator for starvation.

3-Hydroxybutyric Acid↗
PubMed1989

Afferent arteriolar C3 disease--a distinct pathological entity.

Afferent arteriolar C3 deposition was the sole histological abnormality in 79 and the major histological abnormality in an additional 39 of 959 renal biopsies performed over a 10-year period. Of these 79 patients, hematuria was the presenting symptom in 90%, with coincident loin pain in 49%. Urine microscopy of asymptomatic first-degree relatives revealed hematuria in 44% of children and siblings and 54% of parents, suggesting autosomal dominant inheritance. Arteriolar C3 deposition was confirmed by biopsy in four asymptomatic relatives with hematuria. Generalized thinning of glomerular basement membrane (less than 200 nm) was observed in five patients and focal thinning was observed in six patients with coincident afferent arteriolar C3 deposition. Seven other patients were identified as having generalized thinning of glomerular basement membrane in the absence of afferent arteriolar C3 deposition. Renal function was stable and similar in all groups studied over 37.9 +/- 23.7 months. No difference in clinical presentation or urinary abnormalities was evident between the groups. No arteriolar C3 deposition was evident in eight autopsy specimens with no known renal disease. It was concluded that afferent arteriolar C3 deposition is a marker of a distinct hereditary pathological entity, with differentiation from thin basement membrane disease not possible on clinical grounds. The medium- and long-term prognoses with respect to renal function are excellent.

Adolescent↗
PubMed1989

[Sleep in anorexia nervosa, bulimia nervosa and depressive diseases: a polysomnographic comparative study].

All-night EEG sleep in 20 anorexics, 10 bulimics, 10 endogenous depressives, and in 10 healthy subjects (all age matched) was compared. In addition, the REM sleep-induction-test was performed in 12 patients with an eating disorder, 7 depressives, and 12 controls by application of the cholinergic agent RS 86. During baseline night, EEG-sleep parameters, especially REM latency, did not differ between the patients and the controls, except for the phasic components of REM sleep (REM density) that were increased in the depressive patients. The frequency of shortened REM latencies, however, was significantly higher in the depressed patients. These observations indicate that in some of the young depressives the disturbance of the REM sleep regulating transmitter system is already present to a similar degree as it is assumed in elderly depressives. After the application of RS 86, REM latency was shortened in all groups under investigation. However, the REM sleep inducing effect of RS 86 was significantly more pronounced in the depressives when compared with both the eating disorder patients and the controls. In the latter two samples, the shortening of REM latency was similar. Furthermore, the eating disorder patients with a concomitant major depression reacted similar to RS 86 as the non-depressed eating disorder patients and the control subjects. Whereas baseline EEG-sleep did not differ significantly among eating disorder patients, young depressives, and healthy subjects, the REM sleep inducing effect of the cholinergic agent RS 86 clearly distinguished between the depressives and both the patients suffering from eating disorders and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Brain structure and brain function in anorexia nervosa: a computerized tomography study].

Cranial computed tomography (CT) was performed in 12 patients with anorexia nervosa revealing that the majority of the patients displayed ventricular dilatation and/or sulcal widening. In six patients re-examined these structural brain alterations showed a strong trendency towards normalization after weight gain. With the intention of finding a functional correlate of the CT abnormalities, the regional cerebral blood flow (rCBF) was measured at admission and once again after weight gain and compared with the flow rates of a healthy control group. The mean flow rates assessed at the first examination did not significantly differ from those assessed at the second examination and from those of a control group. Thus, despite the CT findings of structural brain abnormalities, the measurement of the regional cerebral blood flow gave no hint of a reduced functioning of certain brain areas in anorexia nervosa.

Adolescent↗
PubMed1988

Endocrine, metabolic, and cranial computed tomographic findings in anorexia nervosa.

Computerized tomographic brain scans were completed in 50 inpatients with anorexia nervosa and were compared with an age- and sex-matched control group. Seventy percent of the anorectic patients displayed enlarged lateral ventricles. There was a close link between ventricular size and low weight, but not between ventricular size and duration of the eating disorder. In addition, sulcal widening was observed more frequently in patients with enlarged ventricles than in patients without these structural changes. After weight gain, a statistically significant decrease in ventricular dilatation could be observed even when mean ventricular size still far exceeded that of the control subjects. The analysis of the endocrine and metabolic parameters, known to be indicators for the process of starvation, revealed a significant inverse correlation between triiodothyronine and ventricular size. Various possible pathogenetic mechanisms for the morphological brain alterations in patients with eating disorders are discussed.

3-Hydroxybutyric Acid↗
PubMed1988

Influence of the cholinergic agonist RS 86 on normal sleep: sex and age effects.

In 36 healthy control subjects (21 females, 15 males; age range 18-65 years; mean age 41.8 years, SD 15.6 years), a bedtime dose of 1.5 mg RS 86, an orally acting cholinergic agonist, shortened rapid eye movement (REM) latency, increased REM sleep, and decreased slow-wave sleep. Six of the subjects (greater than 40 years old) even displayed sleep-onset REM periods after the drug. Results of the present study agree well with those of studies using other cholinomimetics (i.e., physostigmine, arecholine) and confirm the importance of the cholinergic system for REM sleep regulation. Since RS 86 mimicked some of the REM sleep abnormalities specific for patients with depressive disorders, the cholinergic system may play a role in the pathogenesis and pathophysiology of depressive diseases.

Adolescent↗
PubMed1988

EEG sleep and the cholinergic REM induction test in anorexic and bulimic patients.

The electroencephalographic (EEG) sleep of 20 anorexic patients, 10 bulimic patients, and 10 age-matched healthy controls was studied. In addition, six anorexic patients and six bulimic patients had a cholinergic rapid eye movement (REM) sleep induction test (RIT) performed with the cholinergic agent RS 86. The three samples showed no major differences in sleep patterns. The same held true when attention was focused on patients who additionally met DSM-III criteria for major depression. The RIT results were similar in the patients with eating disorders and in controls, but differed from those reported in depressives. Therefore, the present study found no hints of depression-like sleep patterns in patients with eating disorders.

Adult↗
PubMed1988

Sustained function of normoxic hearts depleted in ATP and phosphocreatine: a 31P-NMR study.

A model of high-energy phosphate depletion was developed in the normoxic isovolumic rat heart perfused with acetate, 2-deoxy-D-glucose (2DG), and insulin. Intracellular phosphorylation of 2DG abstracts phosphorus from its normal pathways. This results in a decrease of high-energy phosphates without any increase in Pi. During the first 15 min of 2DG phosphorylation, the changes in ATP, Pi, and intracellular pH (pHi) were slight, and work was unaltered, although phosphocreatine (PCr) concentration dropped by 50%. After 45 min, the heart reached a new steady state characterized by a drastic reduction in both PCr and ATP: PCr was 15% of control, and in most hearts ATP became invisible on the nuclear magnetic resonance (NMR) spectra. Nevertheless, the heart still developed 65% of its original systolic pressure, whereas diastolic pressure was unchanged. Oxygen consumption per unit work remained constant during 2DG perfusion. This is, to our knowledge, the first experimental model of sustained cardiac contractility at such low contents of both ATP and PCr. However, our results are compatible with present knowledge of the cytosolic energy transfer by PCr and of the control of force in myofilaments.

Adenine Nucleotides↗