Biomedical subjects

C Lauer

Publications and source records attributed to C Lauer.

At least 19 recordsLinked to original sources

PubMed2004

Experimental limb transplantation, part II: excellent return of function and indefinite survival after withdrawal of immunosuppression.

In this study the three components of an immunosuppressive combination therapy were gradually withdrawn in a rat limb transplantation model to evaluate the effects on long-term survival of the grafted limbs, rejection rate, and functional recovery. The procedure was performed in 16 rats across a strong Brown Norway to Fischer 344 histocompatibility barrier. Eight animals served as a control group that was not given any antirejection therapy and rejected their limb within a few days. The remaining eight animals were administered a 2-week course of immunosuppressive therapy including tacrolimus (TRL; 2 mg/kg/d), mycophenolate mofetil (MMF; 15 mg/kg/d), and prednisolone (Pred; 0.5 mg/kg/d). At 2 weeks, Pred and MMF were simultaneously tapered by 20% of the dosage every week; by week 7 the animals were on TRL only. TRL was then tapered at the same rate (20% every week) to a maintenance dose of 0.6 mg/kg/d at week 12. After 6 months the immunosuppression was stopped. Four of 8 animals did not reject throughout the study up, to the 1-year endpoint. At this stage they show excellent functional outcomes, evaluated by clinical tests and walking tract analysis. The remaining four rats developed a rejection at an average of 267 days postoperatively (range 224 to 302 days), corresponding to an average of 87 days (range 44 to 122 days) without any immunosuppression. They were sacrificed as soon as rejection was confirmed for histological examination of the various tissues. This study showed that a triple combination therapy provides excellent long-term functional outcomes of the transplanted limbs, with no rejection episodes, no side effects, or complications, even 6 months after withdrawal of all immunosuppressive components, suggesting the possible emergence of tolerance.

Animals↗

PubMed1999

Impairment of peroxisomal biogenesis in human colon carcinoma.

Peroxisomes and the activities of their enzymes have been reported to be significantly reduced in various types of tumors including the colon carcinoma. Therefore, the present study was designed to investigate the gene expression of several peroxisomal proteins in human colon carcinoma and additionally those of the peroxisome proliferator activated receptor alpha (PPARalpha) and PEX5, a receptor protein involved in the import of most peroxisomal matrix proteins. Samples from adenocarcinomas and adjacent normal colon were analyzed by immunohistochemistry and western blotting. The mRNA content was assessed by a novel sensitive dot blot RNase protection assay and northern blotting. By immunohistochemistry, peroxisomes were distinctly visualized in normal colonocytes but were not detected in colon carcinoma cells. The protein levels of catalase (CAT), acyl-CoA oxidase as well as the 22 and 70 kDa peroxisomal membrane proteins (PMP22 and PMP70) were all significantly decreased in carcinomas. The corresponding mRNAs for CAT and PMP70, however, were unchanged. In contrast, the mRNA of PEX5 was significantly increased. The expression of PPARalpha was not altered in tumors, neither at protein nor mRNA levels. These observations show that the reduction of peroxisomes and their proteins in colon carcinoma is not due to a generalized reduction of transcription of their genes. It seems more likely that this phenomenon is regulated at a post-transcriptional or translational level. Alternatively, and more likely, an impairment of the biogenesis of the organelle could account for the paucity of peroxisomes in colon carcinoma.

ATP-Binding Cassette Transporters↗

PubMed1997

[Psychological, psychotherapeutic and other non-pharmacologic forms of therapy in treatment of insomnia. Position of the "Insomnia" Study Group of the German Society of Sleep Research and Sleep Medicine].

Psychological and psychotherapeutic techniques are an essential part of the treatment of insomnia. Mainly two facts stress the importance of psychological/psychotherapeutical strategies for insomnia: (1) Concepts for non-drug treatment aim at improvement of the symptoms and the underlying cause of the disease and (2) disadvantages of hypnotic therapy such as substance abuse or addiction are avoided. Effective treatment techniques such as patients education and counseling, sleep hygiene, stimulus control and relaxation techniques should be known to every therapist, especially general practitioners who treat the majority of patients haring difficulties in initiating or maintaining sleep. Several other effective behavioural techniques, e.g. sleep restriction, or cognitive therapy, and psychotherapy should be used only by skilled and trained experts. Insomniacs with chronic and severe complaints should be treated by therapists with experience in sleep medicine. Multimodal treatment strategies are provided for by sleep disorder centres and combine effective treatment elements in structured therapeutic concepts. There is absolute consensus of opinion that every hypnotic treatment of an insomniac patient should be combined with basal elements of non-drug treatment strategies.

Behavior Therapy↗

PubMed1996

Comparison of an enzyme-linked immunosorbent assay vs radioimmunoassay for measuring serum progesterone at low levels.

Reports have suggested a correlation between low serum progesterone (P) levels prior to human chorionic gonadotropin (hCG) administration and increased pregnancy rates in patients undergoing in vitro fertilization (IVF) patients. We have published two opposite conclusions, dependent upon the methodology used. Pregnancy rates were higher when P by radioimmunoassay (RIA) was < 1 ng/mL, but no increase in pregnancy rates were found when P was measured by the same company's non-isotopic assay. To test if the lack of correlation was attributable to the P method, sera from IVF patients were assayed by two methods, RIA and enzyme linked immunosorbent assay (ELISA). There was 81.8% agreement between methods. Further studies are needed to determine the importance of low P; however, if non-isotopic methods are used, the IVF center should carefully determine the accuracy of their assay in the low range.

Chorionic Gonadotropin↗

PubMed1996

Relationship of early follicular phase sera follicle stimulating hormone and luteinizing hormone levels as measured by a radioimmunoassay and an enzyme-linked immunosorbent assay to number of oocytes retrieved.

A study was performed to see if the level of serum follicle stimulating hormone (FSH) or luteinizing hormone (LH) obtained in the early follicular phase could predict the number of oocytes retrieved following in vitro fertilization (IVF). For each patient the sera FSH and LH were measured by both an enzyme-linked immunosorbent assay (ELISA) and a radioimmunoassay (RIA) method. With the ELISA method when early follicular phase serum FSH was < or = to the group median (9.0 mIU/mL) 16.5 oocytes were retrieved vs 6.7 when FSH was greater than the median. Comparable values using the median of the RIA assay were 17.5 vs 8.1 oocytes. Similar analysis for serum LH failed to show any relationship between baseline LH and the number of oocytes retrieved. This study thus demonstrates that at least one non-isotopic method is equal to a specific RIA method in distinguishing good from average or poor responders.

Adult↗

PubMed1995

A randomized study comparing the efficacy of reducing the spontaneous abortion rate following lymphocyte immunotherapy and progesterone treatment versus progesterone alone in primary habitual aborters.

Presented herein is a randomized prospective study performed to evaluate the efficacy of the addition of lymphocyte immunotherapy (LI) to progesterone (P) therapy (LI/P) for the prevention of spontaneous abortion (SAB) in primary aborters with a history of three SABs. The incidence of intrauterine pregnancies in four cycles was 23 of 35 (65.7%) patients for LI/P vs. 14 of 31 (45.1%) patients treated with progesterone alone. SABs occurred in 6 of 23 (26.0%) LI/P-treated patients compared to 8 of 14 (57.1%) given progesterone alone. The mean number of previous abortions in both groups was 3.9. The mean age of the LI/P group was 34.1 vs. 33.6 years for the group treated with progesterone alone. These data could be interpreted to show that progesterone therapy and LI independently inhibit SAB or that LI/P acts synergistically to inhibit immune destruction. LI/P therapy was found to be more effective than progesterone therapy alone.

Abortion, Habitual↗

PubMed1994

Sleep endocrine effects of antigluco- and antimineralocorticoids in healthy males.

In several mammalian species the responsiveness of brain neurons to corticosteroids is mediated by mineralo- (MR) and glucocorticoid (GR) receptors. These receptors play a key role not only in the endocrine adaptation to stress but also in corticosteroid-induced changes of behavior, including sleep. We further explored the specific physiological role of this binary receptor system in the human brain by studying electroencephalogram (EEG) sleep and changes in plasma concentrations of adrenocorticotropic hormone (ACTH), cortisol, and growth hormone from 1800 to 0700 h in a series of investigations in healthy men pretreated the previous evening with the nonselective GR agonist dexamethasone (Dex) and then receiving at 1400 h either placebo, spironolactone (Spi), an MR antagonist, or mifepristone (Mif), a GR antagonist. The Dex-induced suppression of ACTH and cortisol was unaltered after Spi (200 mg) but attenuated by Mif treatment (400 mg). The sleep-associated plasma growth hormone surge was increased by Dex, an effect that remained unchanged by Spi but was reduced by Mif treatment. Pretreatment with Dex did not by itself induce recognizable effects on EEG sleep, but the Dex combination with Spi reduced the amount of rapid-eye-movement (REM) sleep. With Dex plus Mif, both REM sleep and slow wave sleep (SWS) were reduced compared with placebo. The Dex-induced endocrine effects on plasma ACTH, cortisol, and growth hormone concentrations could not be antagonized by Spi, which acts via MRs mainly located in the hippocampus, but were compensated for in part by Mif, which antagonizes GR at the pituitary and in the central nervous system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1993

The range of subtle rise in serum progesterone levels following controlled ovarian hyperstimulation associated with lower in vitro fertilization pregnancy rates is determined by the source of manufacturer.

Two previous studies found a correlation of higher pregnancy rates (PRs) with lower serum progesterone (P) levels at the time of human chorionic gonadotropin (hCG) injection in in vitro fertilization (IVF) cycles when luteal phase leuprolide acetate (LA)-human menopausal gonadotropin (hMG) was used for the controlled ovarian hyperstimulation (COH) regimen. In these two studies the radioimmunoassay (RIA) by Diagnostic Products Corporation (DPC) was used to measure P levels. This study attempted to corroborate these findings using a different RIA for P (Amersham) when the same COH regime was administered. The PR was significantly higher in the group where P was < or = 1 ng/ml at the time of hCG (43.2%) versus the groups where the P level ranged from 1.1 to 2 ng/ml (15.8%). Viable PRs were also significantly higher in the lower P group. In contrast to the previous data with the DPC assay, no differences were seen with P < 0.5 ng/ml (36.4%) versus 0.5-1 ng/ml (44.6%). Nevertheless, using the Amersham RIA, the data does suggest decreasing PRs with higher serum P levels at time of hCG when using luteal phase LA-hMG COH regimen.

Chorionic Gonadotropin↗

PubMed1993

The sleep EEG and nocturnal hormonal secretion studies on changes during the course of depression and on effects of CNS-active drugs.

1. The sleep EEG and nocturnal hormone secretion were studied simultaneously in normal male controls and in male patients with major endogenous depression before treatment with tricyclics and after recovery and drug cessation. 2. Several studies were performed in normal male controls to investigate the effect of antidepressants (brofaromine, moclobemide, amitriptyline, clomipramine and trimipramine) and of neuropeptides (CRH and the ACTH (4-9) fragment analog ebiratide) on the sleep EEG and sleep-associated hormone secretion. 3. Elevated cortisol and blunted testosterone secretion are state markers of acute depression, whereas sleep EEG, GH and prolactin variables do not show marked differences between acute depression and recovery. Except for trimipramine, all antidepressants investigated suppress REM sleep. No systematic relationship between the sleep EEG and endocrine effects of antidepressants is detectable. Pulsatile application of CRH in controls mimicks some of the neurobiological symptoms of acute depression. More shallow sleep occurs under ebiratide, whereas hormonal secretion remains unchanged. 4. Our data demonstrate that antidepressants exert distinct effects on sleep. However, these substances do not induce changes in sleep structure which persist after their withdrawal in remitted patients. Pulsatile application of neuropeptides leads to specific effects on CNS activity which are not mediated by changes of peripheral hormone secretion. The view that CRH plays a key role in the pathophysiology of affective disorders is corroborated.

Adult↗

PubMed1993

Origin of first trimester 17-hydroxyprogesterone levels as determined in pregnancies by donor oocyte fertilization.

The study presented herein measured 17-hydroxyprogesterone (17-OHP) levels in women with ovarian failure who conceived by transfer of embryos which resulted from donor oocytes fertilization. A significant increase in 17-OHP during the first trimester was seen compared to baseline nonpregnant levels. The 17-OHP levels increased from a baseline average of 47.7 +/- 9.7 ng/dl to a first-trimester average of 175.8 +/- 80.6 ng/dl in the donor oocytes recipients vs. 63.0 +/- 38.0 ng/dl baseline to 295.0 +/- 83.9 ng/dl first-trimester in the control group. Initially these data may appear to contradict previous findings demonstrating a lack of 17-OHP secretion by the first-trimester placenta. However, by comparing the first-trimester progesterone (P) levels of normal pregnant women, and also measuring 17-OHP in patients with natural menopause and surgical menopause given exogenous P we concluded the following about the origin of first-trimester sera 17-OHP levels: hydroxylation of P to 17-OHP by the ovaries, some secretion by the first trimester placenta; and also increased adrenal conversion of P to 17-OHP. Contributing to the total serum 17-OHP level is the fact that there is cross-reactivity with P to 17-OHP.

17-alpha-Hydroxyprogesterone↗

PubMed1993

A conservative treatment protocol with human menopausal gonadotropins aimed at reducing multiple births.

In multicenter studies involving 3002 courses of human menopausal gonadotropins (hMG) therapy in 1286 patients, 20% of the patients who delivered had multiple gestations; 75% of these were twins and 25% were triplets or higher parity. Our stimulation regimen is very conservative in that we 1) try to allow a female with LPD and regular cycles but not reaching a mature follicle to first select her dominant follicle and wait until the serum E2 reaches approximately 100 pg/mL then add the hMG. With anovulatory women we frequently begin with only 75 IU hMG and gradually increase the hMG dosage. Using this approach we have usually attained at least a 70% pregnancy rate in six months. A study was performed to see if this conservative approach resulted in a decreased multiple birth rate percentage especially with triplets or more. The study was to evaluate the outcome of 241 consecutive pregnancies in which hMG was the sole therapy. There were 203 with one gestation and 38 with multiples. Twins--32; triplets--6. Thus 15% (38/241) had multiple births; six of 38 (15%) of the multiples had triplets or more. Though our multiple birth rate and especially higher parity rate appears to be lower than average no statistical difference was found. Thus even with conservative use of hMG multiple births cannot be easily avoided.

Estradiol↗

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↗